Risk of Metachronous High-Risk Adenomas and Large Serrated Polyps in Individuals With Serrated Polyps on Index Colonoscopy: Data From the New Hampshire Colonoscopy Registry.
ABSTRACT: BACKGROUND & AIMS:Surveillance guidelines for serrated polyps (SPs) are based on limited data on longitudinal outcomes of patients. We used the New Hampshire Colonoscopy Registry to evaluate risk of clinically important metachronous lesions associated with SPs detected during index colonoscopies. METHODS:We collected data from a population-based colonoscopy registry that has been collecting and analyzing data on colonoscopies across the state of New Hampshire since 2004, including rates of adenoma and SP detection. Patients completed a questionnaire to determine demographic characteristics, health history, and risk factors for colorectal cancer, and were followed from index colonoscopy through all subsequent surveillance colonoscopies. Our analyses included 5433 participants (median age, 61 years; 49.7% male) with 2 colonoscopies (median time to surveillance, 4.9 years). We used multivariable logistic regression models to assess effects of index SPs (n = 1016), high-risk adenomas (HRA, n = 817), low-risk adenomas (n = 1418), and no adenomas (n = 3198) on subsequent HRA or large SPs (>1 cm) on surveillance colonoscopy (metachronous lesions). Synchronous SPs, within each index risk group, were assessed for size and by histology. SPs comprise hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas. In this study, SSA/Ps and traditional serrated adenomas are referred to collectively as STSAs. RESULTS:HRA and synchronous large SP (odds ratio [OR], 5.61; 95% confidence interval [CI], 1.72-18.28), HRA with synchronous STSA (OR, 16.04; 95% CI, 6.95-37.00), and HRA alone (OR, 3.86; 95% CI, 2.77-5.39) at index colonoscopy significantly increased the risk of metachronous HRA compared to the reference group (no index adenomas or SPs). Large index SPs alone (OR, 14.34; 95% CI, 5.03-40.86) or index STSA alone (OR, 9.70; 95% CI, 3.63-25.92) significantly increased the risk of a large metachronous SP. CONCLUSIONS:In an analysis of data from a population-based colonoscopy registry, we found index large SP or index STSA with no index HRA increased risk of metachronous large SPs but not metachronous HRA. HRA and synchronous SPs at index colonoscopy significantly increased risk of metachronous HRA. Individuals with HRA and synchronous large SP or any STSA could therefore benefit from close surveillance.
Project description:BACKGROUND:It is unknown whether narrow-band imaging (NBI) could be more effective than high-definition white-light endoscopy (HD-WLE) in detecting serrated lesions in patients with prior serrated lesions >?5?mm not completely fulfilling serrated polyposis syndrome (SPS) criteria. METHODS:We conducted a randomized, cross-over trial in consecutive patients with prior detection of at least one serrated polyp ?10?mm or???3 serrated polyps larger than 5?mm, both proximal to the sigmoid colon. Five experienced endoscopists performed same-day tandem colonoscopies, with the order being randomized 1:1 to NBI-HD-WLE or HD-WLE-NBI. All tandem colonoscopies were performed by the same endoscopist. RESULTS:We included 41 patients. Baseline characteristics were similar in the two cohorts: NBI-HD-WLE (n?=?21) and HD-WLE-NBI (n?=?20). No differences were observed in the serrated lesion detection rate of NBI versus HD-WLE: 47.4% versus 51.9% (OR 0.84, 95% CI: 0.37-1.91) for the first and second withdrawal, respectively. Equally, no differences were found in the polyp miss rate of NBI versus HD-WLE: 21.3% versus 26.1% (OR 0.77, 95% CI: 0.43-1.38). Follow-up colonoscopy in nine patients (22%) allowed them to be reclassified as having SPS. CONCLUSIONS:In patients with previous serrated lesions, the serrated lesion detection rate was similar with NBI and HD-WLE. A shorter surveillance colonoscopy interval increases the detection of missed serrated polyps and could change the diagnosis of SPS in approximately one in every five patients. TRIAL REGISTRATION:ClinicalTrials.gov NCT02406547, registered on April 2, 2015.
Project description:BACKGROUND & AIMS:Serrated polyps (SPs) and conventional adenomas are precursor lesions for colorectal cancer (CRC), but they are believed to arise via distinct pathways. We characterized risk factor profiles for SPs and conventional adenomas in a post hoc analysis of data from 3 large prospective studies. METHODS:We collected data from the Nurses' Health Study, the Nurses' Health Study 2, and the Health Professionals Follow-up Study on subjects who developed SPs or conventional adenomas. Our analysis comprised 141,143 participants who had undergone lower gastrointestinal endoscopy, provided updated diet and lifestyle data every 2-4 years, and were followed until diagnosis of a first polyp. We assessed 13 risk factors for CRC in patients with SPs or conventional adenomas and examined the associations according to histopathology features. RESULTS:We documented 7945 SPs, 9212 conventional adenomas, and 2382 synchronous SPs and conventional adenomas during 18-20 years of follow-up. Smoking, body mass index, alcohol intake, family history of CRC, and height were associated with higher risk of SPs and conventional adenomas, whereas higher intake of vitamin D and marine omega-3 fatty acid were associated with lower risk. The associations tended to be stronger for synchronous SPs and conventional adenomas. Smoking, body mass index, and alcohol intake were more strongly associated with SPs than conventional adenomas (P for heterogeneity <.05), whereas physical activity and intake of total folate and calcium were inversely associated with conventional adenomas but not SPs. For SPs and conventional adenomas, the associations tended to be stronger for polyps in the distal colon and rectum, of 10 mm or larger or with advanced histology. CONCLUSIONS:In an analysis of data from 3 large prospective studies, we found that although SPs and conventional adenomas share many risk factors, some factors are more strongly associated with one type of lesion than the other. These findings provide support for the etiologic heterogeneity of colorectal neoplasia.
Project description:BACKGROUND & AIMS:Endoscopists do not routinely follow guidelines to survey individuals with low-risk adenomas (LRAs; 1-2 small tubular adenomas, < 1 cm) every 5-10 years for colorectal cancer; many recommend shorter surveillance intervals for these individuals. We aimed to identify the reasons that endoscopists recommend shorter surveillance intervals for some individuals with LRAs and determine whether timing affects outcomes at follow-up examinations. METHODS:We collected data from 1560 individuals (45-75 years old) who participated in a prospective chemoprevention trial (of vitamin D and calcium) from 2004 through 2008. Participants in the trial had at least 1 adenoma, detected at their index colonoscopy, and were recommended to receive follow-up colonoscopy examinations at 3 or 5 years after adenoma identification, as recommended by the endoscopist. For this analysis we collected data from only participants with LRAs. These data included characteristics of participants and endoscopists and findings from index and follow-up colonoscopies. Primary endpoints were frequency of recommending shorter (3-year) vs longer (5-year) surveillance intervals, factors associated with these recommendations, and effect on outcome, determined at the follow-up colonoscopy. RESULTS:A 3-year surveillance interval was recommended for 594 of the subjects (38.1%). Factors most significantly associated with recommendation of 3-year vs a 5-year surveillance interval included African American race (relative risk [RR] to white, 1.41; 95% confidence interval [CI], 1.14-1.75), Asian/Pacific Islander ethnicity (RR to white, 1.7; 95% CI, 1.22-2.43), detection of 2 adenomas at the index examination (RR vs 1 adenoma, 1.47; 95% CI, 1.27-1.71), more than 3 serrated polyps at the index examination (RR=2.16, 95% CI, 1.59-2.93), or index examination with fair or poor quality bowel preparation (RR vs excellent quality, 2.16; 95% CI, 1.66-2.83). Other factors that had a significant association with recommendation for a 3-year surveillance interval included family history of colorectal cancer and detection of 1-2 serrated polyps at the index examination. In comparisons of outcomes, we found no significant differences between the 3-year vs 5-year recommendation groups in proportions of subjects found to have 1 or more adenomas (38.8% vs 41.7% respectively; P = .27), advanced adenomas (7.7% vs 8.2%; P = .73) or clinically significant serrated polyps (10.0% vs 10.3%; P = .82) at the follow-up colonoscopy. CONCLUSIONS:Possibly influenced by patients' family history, race, quality of bowel preparation, or number or size of polyps, endoscopists frequently recommend 3-year surveillance intervals instead of guideline-recommended intervals of 5 years or longer for individuals with LRAs. However, at the follow-up colonoscopy, similar proportions of participants have 1 or more adenomas, advanced adenomas, or serrated polyps. These findings support the current guideline recommendations of performing follow-up examinations of individuals with LRAs at least 5 years after the index colonoscopy.
Project description:We aimed to evaluate whether obesity was associated with a certain clinicopathologic characteristics of metachronous CRA. This retrospective longitudinal cohort study included 2,904 subjects who had at least one resected CRA at index colonoscopy and who subsequently underwent one or more surveillance colonoscopies within 5 years. Of the 2,904 subjects, 60.9% (n?=?1,769) were normal, 35.8% (n?=?1,040) were overweight, and 3.3% (n?=?95) were obese. Patients with any metachronous CRA were 53.7% (n?=?1,559). In multivariate analyses, higher BMI at index colonoscopy was significantly associated with any metachronous CRA (overweight, OR?=?1.07; obese, OR?=?1.82; p for trend?=?0.049). Regarding the multiplicity, the ORs of???3,???4 and???5 metachronous CRAs significantly increased as index BMI increased (p for trend?<?0.001,?=?0.007 and?=?0.004, respectively). In negative binomial regression regarding the incidence for total number of metachronous CRA, the higher BMI the subject has at the time of index colonoscopy, the more metachronous CRAs the subject will have at the surveillance colonoscopy (p for trend?=?0.016). Higher index BMI was significantly associated with the risk of multiple metachronous CRAs on surveillance colonoscopy within 5 years.
Project description:Serum C-reactive protein (CRP) is a sensitive marker of systemic inflammation. Because there is a well-recognized relationship between local inflammation and colorectal cancer, we aimed to evaluate whether serum CRP levels were associated with the occurrence of colorectal adenomas and serrated polyps using data from a large adenoma prevention trial. A total of 930 participants with a history of colorectal adenomas were enrolled in a randomized trial of calcium supplementation (1,200 mg/day) for the prevention of colorectal adenomas. Outcomes in this analysis are metachronous adenomas (and advanced neoplasms specifically), and serrated polyps at follow-up colonoscopy. High-sensitivity CRP levels were measured 1 year following baseline colonoscopy. Multivariate analysis was performed to estimate risk ratios (RR) using Poisson regression, controlling for potential confounders. We measured serum CRP levels in 689 participants (mean CRP, 3.62 ± 5.72 mg/L). There was no difference in CRP levels with respect to calcium versus placebo treatment assignment (P = 0.99). After adjustment for potential confounders, we found no association between CRP level and risk of recurrent adenoma or advanced lesion [quartile 4 vs. quartile 1: RR, 95% confidence interval (CI) = 0.99 (0.73-1.34) and 0.92 (0.49-1.75), respectively]. Similarly, no association was seen between CRP levels and risk of serrated polyps or proximal serrated polyps [quartile 4 vs. quartile 1: RR (95% CI) = 1.32 (0.85-2.03) and 1.19 (0.54-2.58), respectively]. In conclusion, this large prospective colorectal adenoma chemoprevention study found no significant relationship between CRP levels and occurrence of adenomas, advanced neoplasms, or serrated polyps.
Project description:<h4>Background</h4>Individuals with serrated polyps (SP) are at higher risk for synchronous colorectal advanced neoplasms (AN) and cancers. However, it remains unclear whether there is a unique involvement of the serrated pathway and/or the classical adenoma-carcinoma sequence in this setting.<h4>Methods</h4>Colorectal ANs, which include tubular adenomas ? 10 mm, adenomas with villous histology, high-grade intraepithelial neoplasms, and cancers, were collected retrospectively. The groups included ANs with (AN+SP) or without (AN-only) coexisting SPs. Clinicopathological findings were compared between groups. BRAF and KRAS mutations in ANs and SPs, and methylation levels at long interspersed element-1 (LINE-1) in adjacent mucosa were determined by pyrosequencing.<h4>Results</h4>Seventy-five ANs from 40 patients in the AN+SP group, and 179 ANs from 119 patients in the AN-only group were analyzed. There were no significant differences in clinicopathological findings between the two groups, except that intraepithelial neoplasia in the AN+SP group was more likely to be located in the right colon (P=0.018). BRAF mutations were significantly more frequent in the AN+SP group (P=0.003), while KRAS mutations showed no significant differences between groups (P=0.142). The majority of high-grade intraepithelial neoplasms in both groups showed a contiguous component of conventional adenoma. Individuals with large and right-sided SPs had significantly more conventional adenomas compared to those without such SPs (P=0.027 and P=0.031, respectively). Adjacent mucosa from individuals with multiple and large SPs showed significantly lower methylation levels at LINE-1 compared to individuals without such associated SPs (P=0.049 and P=0.015, respectively).<h4>Conclusion</h4>Our data suggest that both the adenoma-carcinoma sequence and the serrated pathway are operational in individuals with coexisting ANs and SPs. The reduced methylation levels at LINE-1 in the background mucosa suggest the possibility of an underlying 'field defect'.
Project description:BACKGROUND:Visceral adiposity is a risk factor for colorectal adenomas, and aspirin is an established chemopreventive agent. Evidence from clinical trials suggests the effectiveness of aspirin at preventing cardiovascular disease and cancer may require higher doses for higher body weight. METHODS:Body mass index, body surface area, fat-free mass, and fat mass were calculated from baseline height and weight in 1,121 participants of the Aspirin/Folate Polyp Prevention Study, a double-blind, placebo-controlled, 3 × 2 factorial randomized clinical trial of low-dose (81 mg/day) or high-dose (325 mg/day) aspirin and/or 1 mg/day folic acid to prevent metachronous colorectal adenomas. Participants were treated during a surveillance colonoscopy interval of approximately 3 years. Risk ratios (RR) with 95% confidence intervals (CI) for any colorectal neoplasia and high-risk adenoma (HRA, advanced or ?3 adenomas) were estimated from log-linear regression. RESULTS:We did not find evidence to suggest aspirin dose-response differed by body composition measurements, including weight alone. Among those weighing ? 80 kg, treatment effects for low-dose aspirin (RR for colorectal neoplasia, 0.75; 95% CI, 0.60-0.94; RR for HRA, 0.52; 95% CI, 0.31-0.86) and high-dose aspirin (RR for colorectal neoplasia, 0.88; 95% CI, 0.72-1.08; RR for HRA, 0.68; 95% CI, 0.43-1.09) were not meaningfully different than for those weighing 70-79 kg or <70 kg. CONCLUSIONS:Measurements of body composition calculated from height and weight did not modify aspirin treatment effects for colorectal adenoma prevention. IMPACT:Aspirin dosing strategies accounting for body weight suggested in previous trials of colorectal cancer may not apply to adenomas.
Project description:Background:The aim of this study was to evaluate the risk of development of colorectal adenomas in patients with colorectal cancer (CRC) with and without colonic diverticulosis. Methods:We performed a retrospective cohort study that included patients with CRC between 2008 and 2011. All patients underwent preoperative colonoscopic and barium enema examinations. Follow-up colonoscopic examinations were performed within 1 year and between 3 and 5 years postoperatively. The incidence of colorectal adenomas was compared based on the presence or absence of diverticulosis. Additionally, multivariate logistic regression analysis was performed to identify the factors independently associated with the development of synchronous and metachronous colorectal adenomas. Results:Of the 168 patients with CRC included in the study, 55 showed colonic diverticulosis. Synchronous colorectal adenomas were more common in CRC patients with diverticulosis than in those without diverticulosis (P > 0.001). Multivariate regression analysis showed that colonic diverticulosis (odds ratio (OR) 3.874, 95% confidence interval (CI) 1.843-8.144, P > 0.001) and obesity (body?mass?index > 25.0?kg/m2, OR 2.395, 95% CI 1.089-5.270, P = 0.030) were associated with an increased risk of synchronous colorectal adenomas. The presence of synchronous colorectal adenomas increased the risk of metachronous colorectal adenomas (OR 4.407, 95% CI 1.855-10.473, P > 0.001). Conclusions:Colonic diverticulosis was associated with synchronous colorectal adenomas in patients with CRC, which is eventually increasing the risk of metachronous adenomas.
Project description:Measures shown to improve the adenoma detection during colonoscopy (excellent bowel preparation, cecal intubation, cap fitted colonoscope to examine behind folds, patient position change to optimize colon distention, trained endoscopy team focusing on detection of subtle flat lesions, and incorporation of optimum endoscopic examination with adequate withdrawal time) are applicable to clinical practice and, if incorporated are projected to facilitate comprehensive colonoscopy screening program for colon cancer prevention. To determine adenoma and serrated polyp detection rate under conditions designed to optimize quality parameters for comprehensive screening colonoscopy. Retrospective analysis of data obtained from a comprehensive colon cancer screening program designed to optimize quality parameters. Academic medical center. Three hundred and forty-three patients between the ages of 50 years and 75 years who underwent first screening colonoscopy between 2009 and 2011 among 535 consecutive patients undergoing colonoscopy. Comprehensive colonoscopy screening program was utilized to screen all patients. Cecal intubation was successful in 98.8% of patients. The Boston Bowel Preparation Scale for quality of colonoscopy was 8.97 (95% confidence interval [CI]; 8.94, 9.00). The rate of adenoma detection was 60% and serrated lesion (defined as serrated adenomas or hyperplastic polyps proximal to the splenic flexure) detection was 23%. The rate of precancerous lesion detection (adenomas and serrated lesions) was 66%. The mean number of adenomas per screening procedure was 1.4 (1.2, 1.6) and the mean number of precancerous lesions (adenomas or serrated lesions) per screening procedure was 1.6 (1.4, 1.8). Retrospective study and single endoscopist experience. A comprehensive colonoscopy screening program results in high-quality screening with high detection of adenomas, advanced adenomas, serrated adenomas, and multiple adenomas.
Project description:Serrated pathway polyps are a relatively new area of interest in the field of colorectal cancer screening and prevention. Akin to conventional adenomas, some serrated polyps (SPs) have the potential to develop into malignant serrated neoplasms, yet little is known regarding risk factors for these lesions. Early epidemiological studies of hyperplastic polyps were performed without knowledge of the serrated pathway and likely included a mixture of SPs. More recently, studies have specifically evaluated premalignant SPs, such as the sessile serrated adenoma (SSA) or surrogates for these polyps such as large or proximally located SPs. SPs share some risk factors with conventional adenomas and have been associated with tobacco use, obesity, and age. Nonsteroidal anti-inflammatory drug (NSAID) use, fiber, folic acid, and calcium have been associated with reduced risk of SPs. Studies focused on SSAs specifically have reported associations with age, female sex, smoking, obesity, diabetes, and possibly diets high in fat, carbohydrates, and calories. Higher education has also been associated with risk of SSAs, while an inverse association between NSAID use and SSAs has been reported. Risk factors for traditional serrated adenomas are largely unknown. Studies are largely limited by varying inclusion criteria, as well as differences in pathological classification schemes. Further epidemiological studies of SPs are needed to aid in risk stratification and screening, and etiological research.