Association Between Metabolic Syndrome and the Risk of Colorectal Cancer Diagnosed Before Age 50 Years According to Tumor Location.

BACKGROUND & AIMS: The increasing prevalence of obesity at younger ages is concurrent with an increased earlier-onset colorectal cancer (CRC) (before age 50 years) incidence, particularly left-sided colon cancer. We investigated whether obesity and metabolic syndrome (MetS) are associated with increased earlier-onset CRC risk according to tumor location. METHODS: Our nationwide population-based cohort study enrolled 9,774,081 individuals who underwent health checkups under the Korean National Health Insurance Service from 2009 to 2010, with follow-up until 2019. We collected data on age, sex, lifestyle factors, body mass index (BMI), waist circumference (WC), blood pressure, and laboratory findings. A multivariate Cox proportional hazards regression analysis was performed. RESULTS: A total of 8320 earlier-onset and 57,257 later-onset CRC cases developed during follow-up. MetS was associated with increased earlier-onset CRC (adjusted hazard ratio, 1.20; 95% CI, 1.14-1.27), similar to later-onset CRC (adjusted hazard ratio, 1.19; 95% CI, 1.17-1.21). The adjusted hazard ratios for earlier-onset CRC with 1, 2, 3, 4, and 5 MetS components were 1.07 (95% CI, 1.01-1.13), 1.13 (95% CI, 1.06-1.21), 1.25 (95% CI, 1.16-1.35), 1.27 (95% CI, 1.15-1.41), and 1.50 (95% CI, 1.26-1.79), respectively (P for trend < .0001). We found that higher body mass index and larger waist circumference were significantly associated with increased earlier-onset CRC (P for trend < .0001). These dose-response associations were significant in distal colon and rectal cancers, although not in proximal colon cancers. CONCLUSIONS: MetS and obesity are positively associated with CRC before age 50 years with a similar magnitude of association as people diagnosed after age 50 years. Thus, people younger than 50 years with MetS require effective preventive interventions to help reduce CRC risk.

Adolescent boys who participate in sports exhibit similar ramp torque control with young men despite differences in strength and tendon characteristics.

PURPOSE: The goal of this paper was to determine if sports participation influences torque control differently for adolescent boys and young men during a slow ramp task. METHODS: Twenty-one adolescent boys (11 athletes) and 31 young men (16 athletes) performed a slow ramp increase in plantar flexion torque from 0 to maximum. We quantified torque control as the coefficient of variation (CV) of torque during the ramp and quantified the Achilles tendon mechanical properties using ultrasonography. RESULTS: Relative to adolescent boys, young men were taller, heavier, stronger, and had a longer and stiffer Achilles tendon. However, these characteristics were not different between athletes and non-athletes in adolescent boys. For the CV of torque, there was a significant interaction with sports participation, indicating that only adolescent boys who were non-athletes had greater variability than young men. The CV of torque of all participants was predicted from the maximum torque and torque oscillations from 1 to 2 Hz, whereas the CV of torque for adolescent boys was predicted only from torque oscillations from 1 to 2 Hz. CONCLUSION: These findings suggested that adolescent boys who participate in sports exhibited lower torque variability during a slow ramp task, which was not explained by differences in Achilles tendon properties or strength.

Resolvin D1 suppresses inflammation-associated tumorigenesis in the colon by inhibiting IL-6-induced mitotic spindle abnormality.

While failure in resolution of inflammation is considered to increase the risk of tumorigenesis, there is paucity of experimental as well as clinical evidence supporting this association. Resolvin D1 (RvD1) is a representative pro-resolving lipid mediator that is endogenously generated from docosahexaenoic acid for the resolution of inflammation. Here, we report a decreased level of RvD1 in the blood from colorectal cancer patients and mice having inflammation-induced colon cancer, suggesting plasma RvD1 as a potential biomarker for monitoring colorectal cancer. Administration of RvD1 attenuated dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM) plus DSS-induced colorectal carcinogenesis by suppressing the production of interleukin-6 (IL-6) and IL-6-mediated chromosomal instability. The protective effect of RvD1 against chromosomal instability is associated with downregulation of IL-6-induced Cyclin D1 expression, which appears to be mediated by blocking the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) axis. RvD1 inhibited the STAT3 signaling pathway by interfering with the binding of IL-6 to its receptor (IL-6R), suggesting the novel function of RvD1 as a putative IL-6R antagonist. Together, our findings suggest that RvD1-mediated blockade of IL-6 signal transmission may contribute to inhibition of chromosomal instability and tumorigenesis.

Nationwide cohort study: cholesterol level is inversely related with the risk of gastric cancer among postmenopausal women.

BACKGROUND: Recent studies showed inverse relationship between hypercholesterolemia and the risk of gastric cancer, especially among male. However evidence among female is inconsistent. We aimed to investigate the relationship between cholesterol level and the risk of gastric cancer among female according to menopausal status. METHODS: We analyzed the data from a population-based prospective cohort of female ≥ 30 years old who underwent cancer screening and general health screening provided by the Korean National Health Insurance Corporation in 2009. Under quartile stratification of the level of cholesterol components, we calculated the hazard ratio (HR) for gastric cancer incidence until 2018 for each level group according to the menopausal status at 2009. RESULTS: Among total 2,722,614 individuals, 17,649 gastric cancer cases developed after mean 8.26 years of follow-up (premenopausal 3746/1180666; postmenopausal 13,903/1541948). Total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) showed inverse relationship with the risk of gastric cancer among postmenopausal women (adjusted HR (95% confidence interval) for the highest quartile vs. lowest quartile and p-for-trend: 0.88 (0.84-0.92) and < 0.001 for total cholesterol; 0.89 (0.85-0.92) and < 0.001 for HDL-C; 0.92 (0.89-0.97) and 0.001 for LDL-C), whereas none showed statistically significant risk relationship among premenopausal women. Triglyceride was not independently related with gastric cancer risk among both pre- and postmenopausal women. CONCLUSIONS: Cholesterol levels, including total cholesterol, HDL-C, and LDL-C, are inversely related with the risk of gastric cancer among postmenopausal women, but not among premenopausal women.

In-depth characterization of non-human sialic acid (Neu5Gc) in human serum using label-free ZIC-HILIC/MRM-MS.

Sialic acid Neu5Gc, a non-human glycan, is recognized as a new harmful substance that can cause vascular disease and cancer. Humans are unable to synthesize Neu5Gc due to a genetic defect that converts Neu5Ac to Neu5Gc, but Neu5Gc is often observed in human biological samples. Therefore, the demand for accurately measuring the amount of Neu5Gc present in human blood or tissues is rapidly increasing, but there is still no method to reliably quantify trace amounts of a non-human sugar. In particular, selective isolation and detection of Neu5Gc from human serum is analytically challenging due to the presence of excess sialic acid Neu5Ac, which has physicochemical properties very similar to Neu5Gc. Herein, we developed the label-free approach based on ZIC-HILIC/MRM-MS that can enrich sialic acids released from human serum and simultaneously monitor Neu5Ac and Neu5Gc. The combination of complete separation of Neu5Gc from abundant Neu5Ac by hydrophilic and electrostatic interactions with selective monitoring of structure-specific cross-ring cleavage ions generated by negative CID-MS/MS was remarkably effective for quantification of Neu5Ac and Neu5Gc at the femtomole level. Indeed, we were able to successfully determine the absolute quantitation of Neu5Gc from 30 healthy donors in the range of 3.336 ± 1.252 pg/µL (mean ± SD), 10,000 times lower than Neu5Ac. In particular, analysis of sialic acids in protein-free serum revealed that both Neu5Ac and Neu5G are mostly bound to proteins and/or lipids, but not in free form. In addition, the correlation between expression level of Neu5Gc and biological factors such as BMI, age, and sex was investigated. This method can be widely used in studies requiring sialic acid-related measurements such as disease diagnosis or prediction of immunogenicity in biopharmaceuticals as it is both fast and highly sensitive.

Association between obesity and the risk of gastric cancer in premenopausal and postmenopausal women: A nationwide cohort study.

BACKGROUND AND AIM: Obesity was suggested to increase the incidence of gastric cancer (GC) in women, but results from previous studies were inconsistent. We investigated the relationship between obesity and the risk of GC according to menopausal status. METHODS: We enrolled 1 418 180 premenopausal and 4 854 187 postmenopausal women aged ≥ 40 years using the Korean National Health Insurance System Cohort (2009-2014). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for GC incidence according to body mass index (BMI) and waist circumference (WC) using the Cox proportional hazards models. RESULTS: During the mean follow-up period of 7.2 years, 42 441 women were newly diagnosed with GC. Compared with the group with BMI 18.5-22.9 kg/m2 , the adjusted HRs (95% CIs) for GC in the groups with BMI < 18.5, 23-24.9, 25-29.9, and ≥ 30 kg/m2 were 1.12 (0.95-1.33), 0.96 (0.89-1.04), 1.02 (0.94-1.11), and 0.99 (0.83-1.18), respectively, for premenopausal women and 1.07 (1.00-1.14), 1.01 (0.99-1.04), 1.03 (1.00-1.05), and 1.11 (1.10-1.16), respectively, for postmenopausal women. Compared with the group with WC 65-74.9 cm, the adjusted HRs (95% CIs) for GC for the groups with WC < 65, 75-84.9, 85-94.9, and ≥ 90 cm were 1.00 (0.88-1.15), 1.03 (0.96-1.11), 1.10 (0.99-1.22), and 1.02 (0.81-1.27), respectively, for premenopausal women and 1.01 (0.94-1.09), 1.01 (0.99-1.04), 1.09 (1.06-1.13), and 1.14 (1.09-1.19), respectively, for postmenopausal women. CONCLUSIONS: We found a positive association between the highest BMI and WC category and risk of GC in postmenopausal women; however, such an association was not evident in premenopausal women.

Effect of Helicobacter pylori eradication after subtotal gastrectomy on the survival rate of patients with gastric cancer: follow-up for up to 15 years.

OBJECTIVE: Helicobacter pylori (HP) is known to play an important role in the development of gastric cancer (GC). The aim of this study was to analyze the effect of HP eradication on the survival rate and cancer recurrence in patients who underwent subtotal gastrectomy for GC. DESIGN: Totally 1,031 patients diagnosed with gastric adenocarcinoma who received surgical treatment at the Seoul National University Bundang Hospital from 2003 to 2017 and positive for HP infection were analyzed. The overall and GC-related survival according to HP eradication were compared; risk factors for GC-specific death and cancer recurrence were analyzed, and propensity score matching (PSM) was performed. RESULTS: Statistically significant benefits of overall and GC-specific survival were observed in the eradicated group compared to the non-eradicated group (P < 0.001), and these benefits were maintained after PSM (P < 0.001) in both of early and advance stage. In Cox proportional hazards multivariate analyses, cancer stage (stage II, adjusted hazard ratio [aHR] = 9.33, P < 0.001; stage III or IV, aHR = 26.17, P < 0.001), and HP positivity (aHR = 3.41, P = 0.001) were independent risk factors for GC-specific death; cancer stage (cancer stage II, aHR = 7.08, P < 0.001; cancer stage III or IV, aHR = 19.64, P < 0.001) and HP positivity (aHR = 2.70; P = 0.005) were independent risk factors for cancer recurrence. CONCLUSION: Our results suggest that HP needed to be conducted more intensively in patients who are surgically treated for GC, regardless of cancer stage.

Adult height in relation to risk of cancer in a cohort of 22,809,722 Korean adults.

BACKGROUND: The present study examined whether adult height was associated with all site-combined or site-specific cancers. METHODS: We used a nationwide claim data of 22,809,722 Korean participants including both men and women (2009-2012). The deciles of height from different age and sex groups were merged into a new quintile. We used Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals. RESULTS: During a 5-year follow-up period, 765,651 patients were diagnosed with cancer. Height was positively associated with risk of all site-combined cancers and with malignancy in the oral cavity, larynx, lung, stomach, colorectum, liver, pancreas, biliary tract and gallbladder, breast, ovary, cervix and corpus uteri, prostate, testes, kidney, bladder, central nervous system, thyroid, skin, and lymphatic and haematopoietic systems. The HRs for all-site cancers per 5 cm increment in height was 1.09 and that of each site was the highest in thyroid, breast, lymphoma, testicular, and renal cancers. This association was more prominent in women and male non-smokers than in other counterparts. CONCLUSIONS: Taller adult height was significantly related to an increased risk of most cancers including neoplasm in the gallbladder or biliary tract and testes, but except for oesophagus.

Increased Risk of Osteoporotic Fracture in Postgastrectomy Gastric Cancer Survivors Compared With Matched Controls: A Nationwide Cohort Study in Korea.

OBJECTIVES: Gastrectomy can lead to bone loss. Previous studies have suggested that there is an increased risk of fracture in gastric cancer survivors. However, these studies were performed without proper control groups. Therefore, we used Korean national health insurance data to compare the fracture risk in gastric cancer survivors who received gastrectomy to that of the general population. METHODS: A total of 133,179 gastric cancer survivors were included and matched to noncancer controls using 1:1 propensity score matching. Cox proportional hazards regression analysis was used to determine the relative risk of fracture between the gastric cancer survivors and matched controls. We also examined the factors associated with fracture in gastric cancer survivors. RESULTS: Compared with the matched controls, gastric cancer survivors had an elevated risk of osteoporotic fracture (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.53-1.70), which was most prominent in patients who underwent total gastrectomy (HR 2.18, 95% CI 1.96-2.44) and adjuvant chemotherapy (HR 2.01, 95% CI 1.81-2.23). In multivariate analysis, anemia was significantly associated with increased fracture risk (aHR 1.34, 95% CI 1.13-1.59), while decrease in weight >5% was not (aHR 1.06, 95% CI 0.89-1.25). DISCUSSION: Gastric cancer survivors who underwent gastrectomy had an increased osteoporotic fracture risk than did matched controls. Total gastrectomy, adjuvant chemotherapy, and anemia were associated with an even higher risk in these patients. Additional studies are needed to establish optimal strategies, such as screening for osteoporosis and preventive interventions, that will reduce fracture risk in this population.

Risk of Dementia in Gastric Cancer Survivors Who Underwent Gastrectomy: A Nationwide Study in Korea.

PURPOSE: This study was designed to compare the risk of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD), between gastric cancer patients who underwent gastrectomy and the general population. METHODS: All patients (n = 63,998) aged ≥ 50 years who received a diagnosis of gastric cancer and underwent curative gastrectomy between 2007 and 2012 and a noncancer control population (n = 203,276), matched by age and sex, were identified from the Korean National Health Insurance Services and traced until 2017. Hazard ratios and 95% confidence intervals for dementia were calculated with a Cox regression analysis. RESULTS: Gastric cancer patients who received a gastrectomy showed an increased risk of AD [adjusted hazard ration (aHR) 1.08, 95% confidence interval (CI) 1.03-1.14], and the risk was especially marked for those who received a total gastrectomy (aHR 1.39, 95% CI 1.25-1.54). Gastric cancer survivors showed a decreased risk for VaD (aHR 0.85; 95% CI 0.73-0.98) regardless of operation type. Those who received continual vitamin B12 supplementation after a total gastrectomy were less likely than controls to develop AD (aHR 0.71; 95% CI 0.54-0.92). CONCLUSIONS: Compared with controls, gastric cancer patients who received a total gastrectomy had an increased incidence of AD and a decreased risk of VaD. Our results suggest that vitamin B12 deficiency might play a role in the development of AD and highlight the need for vitamin B12 supplementation after total gastrectomy.

Nationwide antibiotic resistance mapping of Helicobacter pylori in Korea: A prospective multicenter study.

INTRODUCTION: The eradication rates for Helicobacter pylori have decreased in Korea although the prevalence of this bacterium has also decreased. Antibiotic resistance is likely to be a crucial factor in H. pylori eradication success, and we therefore mapped these resistance patterns nationwide in Korea. MATERIALS AND METHODS: Five hundred and ninety adult subjects were prospectively enrolled from 2017 to 2018 from 15 centers across six geographic areas of Korea. A total of 580 biopsy tissues had been sampled from these patients during an upper endoscopy and were frozen at -80°C and delivered to a central laboratory. The agar dilution method was used to determine the minimum inhibitory concentration of amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin for each H. pylori isolate. RESULTS: The culture success rate was 60.2% (349/580). Resistance rates against clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and ciprofloxacin were 17.8%, 29.5%, 9.5%, 0%, 37.0%, and 37.0%, respectively. The geographic distribution of metronidazole and quinolone resistance was highly variable. Some subjects had multiple H. pylori strains in the antrum and body of the stomach and showed a heterogeneous resistance profile between these anatomic areas. The H. pylori multidrug resistance (MDR) rate was 25.2% (88/349) among amoxicillin, clarithromycin, metronidazole, tetracycline, and quinolone and 11.2% (39/349) among four of these major antibiotics except for quinolone. The Seoul and Chungcheong areas showed a relatively lower MDR rate. CONCLUSION: The antibiotic resistance of H. pylori differs by drug and geographic area in Korea. Detailed nationwide antibiotic resistance mapping is needed to develop an effective H. pylori eradication strategy.

Secondary Breast, Ovarian, and Uterine Cancers After Colorectal Cancer: A Nationwide Population-Based Cohort Study in Korea.

BACKGROUND: The risk of a second primary cancer has increased along with the increasing life expectancies of colorectal cancer survivors. OBJECTIVE: We aimed to evaluate the incidence rate and risk factors of breast and gynecological (ovarian, uterine cervix/corpus) cancers among female colorectal cancer survivors. DESIGN: This is a retrospective population-based cohort study. SETTINGS: This study used data from the National Health Insurance Corporation of Korea. PATIENTS: Each patient with colorectal cancer diagnosed from 2007 to 2012 was followed until 2015 and compared with age-matched women without colorectal cancer at a 1:5 ratio. MAIN OUTCOME MEASURES: The primary outcome was de novo breast/gynecological cancer. Patients with available medical checkup data were included in an additional analysis. RESULTS: We analyzed 56,682 patients with colorectal cancer and 288,119 age-matched noncolorectal cancer controls. The risk of breast/gynecological cancer was higher among patients with colorectal cancer than among controls (HR, 2.91; p < 0.001). The association with colorectal cancer was the highest for ovarian cancer (HR, 6.72), followed by uterine corpus cancer (HR, 3.99), cervical cancer (HR, 2.82), and breast cancer (HR, 1.85). This association remained consistent in the subgroup analysis of medical checkup data (14,190 patients with colorectal cancer, 71,933 controls). Among patients with colorectal cancer, those aged <55 years had a higher risk of breast/gynecological cancers than those aged >55 years (HR, 3.51 vs 2.59), and those with dyslipidemia had a higher risk of breast cancer than those without dyslipidemia (HR, 2.66 vs 2.06). LIMITATIONS: This was a retrospective, population-based study. A prospectively designed study is needed to validate our conclusions. CONCLUSIONS: Compared with the general population, patients with colorectal cancer carry a higher risk of developing secondary breast, ovarian, and uterine cancers. See Video Abstract at http://links.lww.com/DCR/A731.

Predictive factors of therapeutic intervention in on-call endoscopy for suspected gastrointestinal bleeding.

BACKGROUND AND AIMS: Performing an endoscopy out of hours confer significant burdens on limited health-care resources. However, not all on-call endoscopies lead to therapeutic interventions. The purpose of the present study was to analyze predictive factors for performing therapeutic intervention in patients with suspected gastrointestinal bleeding. METHODS: We reviewed and analyzed electronic medical records regarding on-call endoscopy that were prospectively collected for quality control. The subjects were patients with suspected gastrointestinal bleeding who underwent on-call endoscopies at night, on weekends and on holidays between April 2013 and January 2017 in Seoul National University Bundang Hospital. To determine predictive factors for performing therapeutic intervention, the following variables were analyzed: symptoms, patient status, coexisting disease, laboratory findings and medications. To clarify the association between the likelihood of therapeutic intervention in on-call endoscopy and AIMS65 score, the included variables were divided by cutoffs. RESULTS: A total of 270 patients (male: 72.6%, mean age: 62.6 years) with suspected gastrointestinal bleeding had on-call endoscopies and 153 (56.7%) patients had therapeutic intervention. Gastroscopy, colonoscopy and both endoscopic techniques were performed in 215, 42 and 13 patients, respectively. In the multivariate analysis, hematemesis (p < .001, odds ratio [OR], 2.484) and prolonged prothrombin time-international normalized ratio (PT-INR) (p = .033; OR, 1.958) were correlated with performing therapeutic intervention in on-call endoscopy. AIMS65 score with a cutoff of 2 was associated with the likelihood of intervention (p = .043). CONCLUSIONS: Hematemesis and prolonged PT-INR were predictive factors of therapeutic intervention when on-call endoscopy was performed in patients with suspected gastrointestinal bleeding.

Abdominal obesity, glucose intolerance and decreased high-density lipoprotein cholesterol as components of the metabolic syndrome are associated with the development of colorectal cancer.

Metabolic syndrome (MetS) and its components has been thought to be involved in the development of colorectal cancer (CRC). However, the results is often inconsistent according to gender or anatomical location of tumor. This study aimed to investigate the association between MetS and its components and CRC development by gender and tumor location. We evaluated the data of 22,809,722 Korean individuals of the National semi-compulsive cohort who underwent regular health check-ups between 2009 and 2012. Compared to subjects without MetS components, the hazard ratio for CRC development in patients with MetS was 1.22 (95% Confidence Interval [CI] 1.20-1.24) and this association was more prominent in men than in women (HR 1.41 95% CI 1.37-1.44 vs. HR 1.23 95% CI 1.20-1.27, P for interaction < 0.001). Left-sided colon cancers were more associated with MetS among men compared to women (HR 1.70, 95% CI 1.61-1.80 vs. HR 1.43, 95% CI 1.33-1.54), while right colon cancers showed a stronger association with MetS among women than men (HR 1.63, 95% CI 1.49-1.78 vs. HR 1.34, 95% CI 1.24-1.44) (all P for interaction < 0.001, respectively). Having two MetS components was still associated with CRC development and the association was the highest when two of glucose intolerance, abdominal obesity and low high-density lipoprotein cholesterol (HDL-C) combined. Individuals with glucose intolerance, abdominal obesity or low HDL-C levels, may need to undergo thorough screening for CRC even if they do not meet the diagnostic MetS criteria.

Association of ischemic stroke with ankylosing spondylitis: a nationwide longitudinal cohort study.

BACKGROUND: The purpose of this nationwide age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in ankylosing spondylitis (AS). METHODS: The data in this study, spanning from January 1, 2010 to December 31, 2014, was obtained from a database maintained by the Korean National Health Insurance Service. A total of 12,988 patients with a diagnosis of AS were enrolled. The control group consisted of 64,940 age-sex-stratified matching subjects without AS. The 6year ischemic stroke incidence rate for each group was calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke. RESULTS: During the follow-up period, 73 patients (0.56%) in the AS group and 250 patients (0.38%) in the control group developed ischemic stroke (p = 0.0041). The hazard ratio of ischemic stroke in the AS group was 1.46 (95% confidence interval [95% CI], 1.13-1.90) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the AS group was 1.35 (95% CI, 1.04-1.75) after controlling for demographics and comorbid medical disorders. According to subgroup analysis, in female and diabetes and non-hypertension and dyslipidemia subgroups, ischemic stroke incidence rates were significantly higher in AS patients than those in control group. CONCLUSION: Our nationwide longitudinal study suggests an increased risk of ischemic stroke in AS patients.

Correction to: Association of ischemic stroke with ankylosing spondylitis: a nationwide longitudinal cohort study.

The authors regret to state that an incorrect image was uploaded in Fig. 2. Please see a newly updated Fig. 2. All statements including Figure Legends are correct.

Association Among Obesity, Metabolic Health, and the Risk for Colorectal Cancer in the General Population in Korea Using the National Health Insurance Service-National Sample Cohort.

BACKGROUND: In Korea, the incidence of colorectal cancer has increased and obesity is on a rising trend because of a Westernized lifestyle in men. OBJECTIVE: The purpose of this study was to evaluate the relationship between metabolic health status, as well as BMI, and the incidence of colorectal cancer. DESIGN: This was a prospective cohort study. SETTINGS: The study was conducted with the National Health Insurance Service-National Sample Cohort. PATIENTS: A total of 408,931 Korean adults without cancer at baseline were followed up until 2013 (mean follow-up, 9 y). MAIN OUTCOME MEASURES: Demographic, anthropometric, and laboratory data at baseline were collected and categorized. The presence of diabetes mellitus, hypertension, and dyslipidemia was defined using the criteria of previous studies. The incidence of colorectal cancer was also defined according to the International Classification of Disease, 10 Revision, codes and the claim data on endoscopy with biopsy. RESULTS: During the follow-up, 5108 new cases of colorectal cancer occurred. Being underweight (<18.5 kg/m) reduced the risk for colorectal cancer among women (adjusted HR = 0.646 (95% CI, 0.484-0.863)), whereas high BMI significantly increased the risk in men and in the elderly. Obesity (≥25 kg/m), diabetes mellitus, and hypertension were identified as risk factors for colorectal cancer in men but not for women. Although metabolically unhealthy nonobese men had a higher risk for colorectal cancer than metabolically healthy nonobese men (adjusted HR = 1.114 (95% CI, 1.004-1.236)), the risk was lower than that in the obese men. LIMITATIONS: The study population consisted of people who underwent health examinations, thus there could be selection bias. CONCLUSIONS: In Korean adults, obesity contributes to the incidence of colorectal cancer with a sex difference. Nonobese but metabolically unhealthy men are considered to be a high-risk group for colorectal cancer, but obesity itself is more important in colorectal carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A475.

Overlap between irritable bowel syndrome and functional dyspepsia including subtype analyses.

BACKGROUND AND AIM: Coexistent gastrointestinal symptom profiles and prevalence or associated factors for the overlap between each functional dyspepsia (FD) and irritable bowel syndrome (IBS) group remain unclear. Thus, the aim of the present study was to evaluate the clinicodemographic features of FD, IBS, and IBS-FD overlap and assess the risk factors thereof, including subtype and genetic polymorphisms for IBS-FD. METHODS: Consecutive patients were enrolled from the outpatient Gastroenterology clinics of Bundang Seoul National University Hospitals in Korea. All gastrointestinal symptoms occurring at least once per week in the previous 3 months were recorded. Diagnostic criteria of functional gastrointestinal disorders were based on the Rome III criteria. Risk factors including genetic polymorphisms of 5-HTTLPR and ADRA2A 1291 G alleles and CCK-1R intron 779T>C were assessed using a multivariate logistic regression model. RESULTS: A total of 632 subjects (278 control subjects, 308 FD, 156 IBS, and 110 who met the criteria for both FD and IBS) were included in this study. Patients with IBS-FD overlap had more severe symptoms (such as bloating, nausea, vomiting, hard or lumpy stools, defecation straining, and a feeling of incomplete bowel movement) and higher depression scores compared with non-overlap patients. Single/divorced or widowed marital status, nausea, bloating, and a feeling of incomplete emptying after bowel movements were independent risk factors for IBS-FD overlap among IBS patients. In contrast, young age, depression, bloating, and postprandial distress syndrome were positively associated with IBS-FD overlap among FD patients. 5-HTTLPR L/L was a risk factor for the co-occurrence of IBS-C among FD patients (OR: 12.47; 95% CI: 2.00-77.75; P = 0.007). CONCLUSIONS: Bloating was a risk factor for IBS-FD overlap. Patients with postprandial distress syndrome have a higher risk of coexisting IBS, particularly constipation-dominant IBS.

Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670).