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Background & Aims: The role of circulating 25-hydroxyvitamin D (25(OH)D) in the prevention of early-onset colorectal cancer (CRC) in young adults aged <50 years is uncertain. We evaluated the age-stratified associations (<50 vs ≥50 years) between circulating 25(OH)D levels and the risk of CRC in a large sample of Korean adults., Methods: Our cohort study included 236,382 participants (mean age, 38.0 [standard deviation, 9.0] years) who underwent a comprehensive health examination, including measurement of serum 25(OH)D levels. Serum 25(OH)D levels were categorized as <10, 10 to 20, and ≥20 ng/mL. CRC, along with the histologic subtype, site, and invasiveness, was ascertained through linkage with the national cancer registry. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRC according to the serum 25(OH)D status, with adjustment for potential confounders., Results: During the 1,393,741 person-years of follow-up (median, 6.5 years; interquartile range, 4.5-7.5 years), 341 participants developed CRC (incidence rate, 19.2 per 10 5 person-years). Among young individuals aged <50 years, serum 25(OH)D levels were inversely associated with the risk of incident CRC with HRs (95% CIs) of 0.61 (0.43-0.86) and 0.41 (0.27-0.63) for 25(OH)D 10 to 19 ng/mL and ≥20 ng/mL, respectively, with respect to the reference (<10 ng/mL) (P for trend <.001, time-dependent model). Significant associations were evident for adenocarcinoma, colon cancer, and invasive cancers. For those aged ≥50 years, associations were similar, although slightly attenuated compared with younger individuals., Conclusions: Serum 25(OH)D levels may have beneficial associations with the risk of developing CRC for both early-onset and late-onset disease., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Timosaponin A3 (TA3), extracted from the rhizome of Anemarrhena asphodeloides Bunge, has been reported to affect various diseases, such as cancer, Alzheimer's disease, and allergies. However, the underlying molecular mechanisms and impacts are largely unknown. In the present study, we hypothesized that TA3 induces apoptosis through the inhibition of c-Myc expression via CNOT2 or MID1IP1 in HCT116. An MTT assay and colony formation assay were used to measure cell viability and proliferation. The protein expression of apoptotic markers and oncogenes was measured using immunoblotting and immunofluorescence assays. The interaction between MID1IP1 and c-Myc was confirmed by performing an immunoprecipitation assay. TA3 markedly inhibited colon cancer cell proliferation. Consistently, TA3 regulated the apoptotic proteins pro-PARP and caspase 3. TA3 inhibited the half-life of c-Myc and suppressed its expression in response to serum stimulation. In addition, TA3 enhanced the apoptotic effects of doxorubicin and 5-FU in colon cancer cells. Altogether, our results reveal a mechanism by which TA3 induces apoptosis through inhibiting c-Myc expression via CNOT2 or MID1IP1 in HCT116, which may help in the development of new therapies for colon cancer based on TA3 in the future.

Objectives: Some neoplastic lesions remain undetected on colonoscopy. To date, no studies have investigated whether combining cap-assisted colonoscopy with chromoendoscopy increases the adenoma detection rate (ADR). This study aimed to compare cap-assisted chromoendoscopy (CAP/CHROMO) with standard colonoscopy (SC) with respect to their efficacy in detecting adenomas., Methods: This prospective, multicenter, randomized controlled trial included asymptomatic subjects aged 45-75 years who underwent colonoscopy for the first time at 14 university hospitals. Subjects were randomized to either the CAP/CHROMO group (with 0.09% indigo carmine spraying using a cap-mounted catheter at the tip of the colonoscope) or the SC group. All polyps were resected, but only histologically confirmed neoplastic lesions were considered for analysis. The primary outcome was ADR, defined as the proportion of subjects with at least 1 adenoma., Results: A total of 1,905 subjects were randomized to the CAP/CHROMO (n = 948) or SC (n = 957) group at 14 centers. Subjects' demographic characteristics were similar between both groups. The CAP/CHROMO group had significantly higher ADR than the SC group (54.4% vs 44.9%, P < 0.001). Significantly, more subjects with at least 1 proximal colon adenoma were identified by CAP/CHROMO (38.6%) than by SC (31.2%) (P = 0.001). The proximal serrated polyp detection rate by CAP/CHROMO was significantly higher in the female subgroup vs SC. However, advanced ADR was not different between the CAP/CHROMO and SC groups (9.3% vs 7.6%, P = 0.180)., Discussion: CAP/CHROMO markedly improved the ADR and enhanced the detection of proximal adenoma. CAP/CHROMO is feasible for routine application and will allow for a more effective surveillance program.

Background: Obesity and metabolic syndrome are risk factors for colorectal neoplasia (CRN). However, the association between metabolically healthy obese (MHO) or metabolically unhealthy non-obese (MUNO) status and the risk of CRN remains unclear., Aims: We aimed to elucidate the association between MHO or MUNO status and the risk of CRN., Methods: A total of 139,023 asymptomatic subjects who underwent a primary screening colonoscopy were categorized into 4 groups according to obesity and metabolic status: metabolically healthy non-obese (MHNO), MHO, MUNO, and metabolically unhealthy obese (MUO)., Results: Mean participant age was 41.0 years, and the proportion of men was 65.3%. Among men, the risk of overall CRN increased in MHO (adjusted odds ratio [AOR] 1.22, 95% confidence intervals [CI] 1.12-1.33), MUNO (AOR 1.25, 95% CI 1.18-1.31), and MUO groups (AOR 1.47, 95% CI 1.40-1.54) compared with the MHNO group, whereas the risk of advanced CRN (ACRN) increased in MUNO (AOR 1.16, 95% CI 1.002-1.33) and MUO groups (AOR 1.49, 95% CI 1.31-1.70), but not in the MHO group (AOR 0.92, 95% CI 0.70-1.21). Moreover, among non-obese men, the risk of overall CRN and ACRN linearly increased with an increasing number of metabolic abnormalities. However, among women, only the MUO group had an increased risk of overall CRN (AOR 1.34, 95% CI 1.21-1.47) and no other significant associations were observed., Conclusions: Poor metabolic health, regardless of obesity, is an independent risk factor for CRN in men. Our results suggest that men with metabolic abnormalities should be considered as a high-risk group for colorectal cancer, even if they are not obese.

Background/aims: Aberrant DNA methylation has a specific role in field cancerization. Certain molecular markers, including secreted frizzled-related protein 2 (SFRP2), tissue factor pathway inhibitor 2 (TFPI2 ), N-Myc downstream-regulated gene 4 (NDRG4) and bone morphogenic protein 3 (BMP3), have previously been shown to be hypermethylated in colorectal cancer (CRC). We aim to examine field cancerization in CRC based on the presence of aberrant DNA methylation in normal-appearing tissue from CRC patients., Methods: We investigated promoter methylation in 34 CRC patients and five individuals with normal colonoscopy results. CRC patients were divided into three tissue groups: tumor tissue, adjacent and nonadjacent normal-appearing tissue. The methylation status (positive: methylation level >20%) of SFRP2 , TFPI2 , NDRG4 , and BMP3 promoters was investigated using methylation-specific PCR., Results: The methylation frequencies of the SFRP2 , TFPI2 , NDRG4 and BMP3 promoters in tumor/adjacent/nonadjacent normal-appearing tissue were 79.4%/63.0%/70.4%, 82.4%/53.6%/60.7%, 76.5%/61.5%/69.2%, 41.2%/35.7%/50.0%, respectively. The methylation levels of the SFRP, TFPI2, NDRG4 and BMP3 promoters in tumor tissues were significantly higher than those in normal-appearing tissue (SFRP2, p=0.013; TFPI2, p<0.001; NDRG4, p=0.003; BMP3, p=0.001). No significant correlation was observed between the methylation levels of the promoters and the clinicopathological variables., Conclusions: The field effect is present in CRC and affects both the adjacent and nonadjacent normal-appearing mucosa.

We investigated the risk factors for adenoma occurrence at surveillance colonoscopy, especially focusing on patient characteristics, including metabolic factors.Surveillance colonoscopy intervals depend on baseline adenoma characteristics. However, patients' characteristics may also influence the occurrence of adenomas.Of 62,171 asymptomatic subjects who underwent colonoscopy for a health check-up between 2010 and 2011, 4869 subjects who underwent follow-up colonoscopy between 2012 and 2013 were included in this longitudinal study. The risk of adenoma occurrence was assessed using Cox proportional hazards modeling.Of 4869 subjects, 2827 (58.1%), 1619 (33.3%), and 423 (8.7%) were assigned to the normal, low-risk, and high-risk groups, respectively, according to baseline adenoma characteristics. The mean interval between initial and follow-up colonoscopy was 2.2 ± 0.6 years. Certain patient factors, including older age (≥50 years; adjusted hazard ratio [aHR], 2.08; 95% CI, 1.73-2.49), male sex (aHR, 1.69; 95% CI, 1.30-2.19), metabolic syndrome (MetS) (aHR, 1.28; 95% CI, 1.09-1.51), obesity (aHR, 1.17; 95% CI, 1.02-1.34), elevated fasting blood glucose levels (aHR, 1.37; 95% CI, 1.19-1.58), and elevated triglyceride levels (aHR, 1.19; 95% CI, 1.03-1.37), as well as baseline adenoma characteristics, were associated with a higher risk of adenoma occurrence at follow-up colonoscopy. The cumulative incidence of adenoma occurrence in the high-risk group was higher than that in the low-risk group, whereas the incidence in the high-risk group without MetS was comparable with that in the low-risk group with MetS.Patient characteristics, such as MetS, obesity, older age, and male sex, in addition to adenoma characteristics, were independent risk factors for adenoma occurrence at surveillance colonoscopy. These patient characteristics may be considered in surveillance colonoscopy intervals.

Background: Although adenoma detection rate (ADR) has been proposed as a quality indicator of colonoscopies, adenomas per colonoscopy (APC) is a promising alternative to ADR, as it reflects inspection over the entire length of the colon. This study investigated the correlation between ADR and APC, and compared the efficacy of ADR and APC based on the correlation of each with the advanced adenoma detection rate (AADR)., Study: Two prospectively collected databases, including the 1142 subjects who underwent screening colonoscopies by 28 colonoscopists, were retrospectively reviewed. AADR1 were definded as the proportion of participants having advanced neoplasms, and AADR2 were definded as the proportion of participants having advanced neoplasms or three or more adenomas. Pearson correlation and Steiger's z-test was used to evaluate the relationship between ADR-APC, ADR-AADR and APC-AADR., Results: The ADRs ranged from 16.67 to 66.67% (mean, 37.29%) and APCs ranged from 0.22 to 1.28 (mean, 0.65). The ADR and APC showed a significant correlation (R = 0.82; p < 0.001). The screening ADR was significantly correlated with AADR1/AADR2 (R = 0.60; p = 0.001 and R = 0.64; p < 0.001, respectively). APC was also significantly correlated with AADR1/AADR2 (R = 0.65; p < 0.001 and R = 0.77; p < 0.001, respectively). The correlation coefficient for APC-AADR2 was higher than ADR-AADR2 (0.77 versus 0.64, p = 0.04)., Conclusions: Colonoscopists' ADRs and APC were significantly correlated. Moreover, as the correlation coefficient for AADR was higher with APC than it was with ADR, APC might be a better quality indicator of colonoscopy than ADR.

Background and Aims: Although the malignant progression of serrated polyps has been clearly documented, the malignant potential of the traditional serrated adenoma (TSA) subtype has not been established. We compared the prevalence of metachronous polyps in surveillance colonoscopies between patients with TSA and those with conventional adenomas (CAs)., Methods: Four hundred twenty patients were diagnosed with TSAs by current diagnostic criteria at 10 tertiary care university hospitals in Korea from January 2003 to December 2005; 186 patients who received surveillance colonoscopy after removal of initial polyps were enrolled. During the same time period, 372 age- and sex-matched patients diagnosed with CAs were used as a control group., Results: TSA patients had a significantly higher recurrence rate of colorectal polyps compared with CA patients (66.1% vs 43.5%, respectively). TSA patients had a greater number (3 vs 2) and larger size (8.6 ± 5.7 vs 6.3 ± 5.2 mm) of recurrent polyps compared with CA patients. TSA patients also had a higher rate of CA (54.8% vs 37.9%), serrated adenoma (14.0% vs. 0.8%), and hyperplastic polyp (33.3% vs. 13.7%) recurrence compared with CA patients. TSA patients had significantly greater odds of having a recurrent high-risk polyp than CA patients (odds ratio, 2.37; 95% confidence interval, 1.55-3.63)., Conclusions: In comparison with patients with CAs, patients with TSAs have a higher metachronous occurrence rate of all polyp subtypes including CAs, serrated adenomas, and hyperplastic polyps. Moreover, the presence of TSAs is an independent predictor of a high-risk polyp occurrence., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background/aims: For the possibility of regional lymph node metastasis (LNM), early colon cancer (ECC) is a boundary lesion between endoscopic resection and surgery. The aim of study is to clarify risk factors for LNM and to determine therapeutic strategy after endoscopic resection in patients with ECC., Methodology: The histopathology of patients with ECC underwent surgery with LN dissection in 8 university hospitals were reviewed by experienced pathologist blinded to LN status., Results: In total, 370 patients (107 with mucosal cancer, 263 with submucosal invasive colorectal carcinoma [SICC]) were enrolled. Excluding mucosal cancer, the LNM rate was 11.8% (31/263, including 15.4% [8/52] with pedunculated SICC [P-SICC] and 10.9% [23/211] with non-pedunculated SICC [NP-SICC]). Multivariate analysis showed that tumor sprouting (P < 0.001; odds ratio [OR], 8.83; 95% confidence interval [CI], 3.04-25.69), submucosal invasion depth (SM depth) > 2000 μm (P = 0.024; OR, 3.68; 95% CI, 1.19-11.37), and lymphatic invasion (P = 0.022; OR, 3.48; 95% CI, 1.19-10.13) were related to LNM. All LNMs with SM depth < 2000 μm showed tumor sprouting without lymphatic invasion., Conclusions: Significant risk factors for predicting LNM in patients with SICC were tumor sprouting, SM depth > 2000 μm, and lymphatic invasion.

Background/aims: The polyp detection rate (PDR) has been suggested as a surrogate for adenoma detection rate (ADR). The purpose of this study was to determine the level of agreement between PDR and ADR in the proximal and distal colon., Methods: A total of 1,937 consecutive, asymptomatic individuals aged 40 years and older who underwent colonoscopies at six academic teaching hospitals in Korea were included in this study. PDR and ADR were calculated for each colonic segment. PDR was compared with ADR in the proximal and distal colon., Results: During 1,937 colonoscopies, 1,862 polyps were removed; 1,421 (76%) were adenomas. The PDR and ADR in the proximal colon was 25.8% and 22.8%, respectively (kappa value=0.917, p=0.26), and that in the distal colon was 28.9% and 22.2%, respectively (p<0.001). There was a strong correlation between PDR and ADR in the proximal colon, but diverged in sigmoid colon and rectum., Conclusions: PDR and ADR correlate well in the proximal colon, but not in the distal colon, especially sigmoid and rectum. PDR should be measured for each colonic segment when using PDR as a surrogate for ADR. PDR is a valid proxy for ADR in the proximal colon.

Background and Study Aims: Cold biopsy forceps polypectomy (CBP) is commonly used for the removal of diminutive polyps; however, evidence for the efficacy of CBP is lacking. The aim of this study was to evaluate the adequacy of resection of diminutive polyps and to identify predictors for complete resection using CBP., Patients and Methods: This was a prospective study from a tertiary referral hospital in Korea. A total of 196 patients were screened, and 65 patients with diminutive polyps were enrolled. CBP was used to resect diminutive polyps until no polyp was visible by chromoendoscopy using indigo carmine spray. Each polyp base was then resected using endoscopic mucosal resection (EMR) with a 1-3-mm free margin. CBP and EMR specimens were sent to the histopathology department for the evaluation of the completeness of the resection. Cross sections of the EMR specimens made at 1-mm intervals were examined by a pathologist., Results: A total of 86 diminutive polyps were available for assessment. Overall, 90.7% (78/86) of the diminutive polyps were completely resected using CBP (95%CI 84.6-96.8%). The complete resection rate for all diminutive adenomas was 92.3 % (60/65; 95%CI 85.8-98.8%) and for 1-3-mm adenomas 100% (95%CI 81.5-100%). Polyp size, histology, and location, and number of biopsies were not different between the complete and incomplete resection groups., Conclusions: In this small study approximately 90 % of all diminutive polyps and 100% of 1-3-mm adenomatous polyps were completely resected using CBP and chromoendoscopy. CBP appears to be adequate for the resection of the majority of diminutive polyps, especially small sized adenomas (≤ 3 mm) if no residual tissue is visible by chromoendoscopy., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background/aims: A dietary regimen consisting of a clear liquid diet (CLD) for at least 24 hours is recommended for colonoscopy preparation. However, this requirement results in problems in patient compliance with bowel preparation. The aim of this study was to evaluate the efficacy of a CLD compared with a regular diet (RD) for colonoscopy preparation using a polyethylene glycol (PEG) solution., Methods: This was a multicenter, randomized, investigator-blind prospective study. A total of 801 healthy outpatients undergoing afternoon colonoscopy were randomized to either a CLD or RD in addition to a 4 L PEG regimen., Results: The quality of bowel cleansing was not different between the CLD and RD groups in terms of the proportion with excellent or good preparation. In addition, no significant differences were observed between the two groups for polyp and adenoma detection rates and overall adverse events. Good compliance with bowel preparation was higher in the RD group than in the CLD group., Conclusions: A CLD for a full day prior to colonoscopy should not be mandatory for PEG-based bowel preparation. Dietary education concerning the avoidance of high-fiber foods for 3 days before colonoscopy is sufficient, at least for healthy outpatients.

Background/aims: Because colonoscopy can be a technically challenging procedure, endoscopist fatigue, which usually increases as day progresses, may impact procedural performance. The aim of this study was to determine the influence of colonoscopy scheduling on adenoma and polyp detection rates (ADR and PDR, respectively)., Methodology: This was a retrospective study of data prospectively collected on 1,293 consecutive, asymptomatic, average-risk patients. Three separate timing variables were assessed, as follows: morning vs. afternoon procedures; start times throughout the day; and four groups by matching each subsequent passing hour in the morning and afternoon sessions., Results: 420 (32%) were performed in the morning and 881 (68%) were performed in the afternoon. There was a significantly higher ADR and PDR in the morning colonoscopies compared to the afternoon colonoscopies (42.3% vs. 34.7% [po=0.008] and 52.5% vs. 46.3% [p=0.038], respectively). Based on multivariable analysis, afternoon colonoscopies and colonoscopies performed during 4th hour of session were significantly associated with a decreased ADR (OR, 0.739 [0.576-0.949], p=0.018; and OR, 0.651 [0.443-0.975], p=0.029)., Conclusions: Colonoscopies scheduled in the morning have a significantly higher ADR and PDR as compared to colonoscopies scheduled in the afternoon. Also,colonoscopies performed during 4th hour of the session were associated with decreased ADR.

Background: No reported prospective, randomized study has evaluated the impact of an endoscopy nurse participating as a second observer during colonoscopy., Objective: To determine whether the participation of an endoscopy nurse enhanced the polyp detection rate (PDR) and adenoma detection rate (ADR) during screening colonoscopy., Design: Multicenter, prospective, randomized study., Setting: Academic hospitals., Patients: A total of 844 consecutive patients undergoing screening colonoscopy., Interventions: Single observation by colonoscopist or dual observation by colonoscopist and endoscopy nurse during colonoscope withdrawal., Main Outcome Measurements: PDR and ADR., Results: No significant difference in patient demographic data, adequacy of bowel preparation, or mean withdrawal time was observed between the 2 groups. In total, 1153 polyps, including 762 adenomas, were detected in 791 patients. Seven nonpolypoid, depressed neoplastic lesions (0-IIc or combined types) were only detected in the dual observation group. A multivariate analysis revealed that experienced (≥ 2 years) endoscopy nurse participation significantly increased the PDR and ADR compared with those in the single observation group by a colonoscopist alone (adjusted odds ratio [OR] 1.58 [95% CI, 1.07-2.32]; adjusted OR 1.47 [95% CI, 1.01-2.12], respectively). Additionally, the PDR was significantly higher in the dual-observation group with fellows (<500 colonoscopies) and an experienced endoscopy nurse versus that in the single observation group (adjusted OR 2.07 [95% CI, 1.15-3.74]). There was no significant benefit of experienced nurse participation in the subgroup with experienced colonoscopists., Limitations: Absence of colonoscopist blinding., Conclusions: Experienced endoscopy nurse participation increased the PDR and ADR during screening colonoscopy. However, the benefit of participation by experienced nurses appears to be exclusively with inexperienced colonoscopists., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background/aims: The possibility of proximal lesion without distal polyps is a weak point of sigmoidoscopic colon cancer screening, but the clinical significance of distal findings for advanced proximal neoplasm (APN) is uncertain. The aim of this study was to assess the significance of a distal finding as a predictor of APN., Materials and Methods: Asymptomatic patients > or =50 years old were enrolled from among patients who underwent polypectomy at 11 tertiary medical centers during the Korean Association for the Study of Intestinal Disease prospective study conducted between July 2003 and March 2004. Polyps located distal to the splenic flexure were defined as distal polyps. An advanced neoplasm was defined as a polyp of > or =10 mm in size, and/or with villous features, and/or with high-grade dysplasia, or invasive cancer. Age, gender, and distal polyp size, appearance, and histology were analyzed as risk factors of APN. The sensitivity and positive predictive value of distal polyps for APN were calculated., Results: Data from 826 patients were analyzed. Mean patient age was 60.1 years (range 50-86), and 71.3% were men. APN was found in 98 patients, and 45 (45.9%) patients had no distal polyps. Risk factors of APN were a male gender, distal polyp size, and an advanced distal neoplasm. Sensitivities of a distal polyp of > or =10 mm and of an advanced distal neoplasm for APN were both 38.8% with positive predictive values of 13.3 and 14.4%, respectively., Conclusions: Although distal colon findings were found to be helpful for predicting APN in asymptomatic patients aged > or =50 years, APN without distal polyps requires careful consideration.

Background/aims: The HER-2/neu protein is involved in normal cell proliferation and tissue growth because it is extensively homologous and related to epidermal growth factor receptor. As a prognostic marker, HER-2/neu is used to forecast the clinical course and poor outcome in breast cancer. As a predictive marker, HER-2/neu is used to predict the therapeutic response to adjuvant chemotherapy and endocrine therapy in breast cancer. In this study, we investigated the relationships between clinical and pathologic characteristics of tumor and prognosis according to the HER-2/neu expression in colon cancer. This study was conducted for the future introduction of Herceptin therapy for colon cancer patients., Methods: Overexpression of HER-2/neu was examined by semiquantitative standardized immunohistochemical staining kit in 88 patients with colon cancer. The patients underwent curative surgery at the Kangbuk Samsung Hospital., Results: Overexpression of HER-2/neu was detected in 11 (12.5%) of 88 patients. Tumors with positive HER-2/neu staining showed a tendency for higher rates of nodal metastasis and poor mean survival (1,646 +/- 269 vs 2,631 +/- 141 days) and 5-year survival (65.5% vs 78.9%)., Conclusions: Tumors with positive HER-2/neu staining showed a tendency for higher rates for nodal metastasis and poor clinical survival rate.