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Clinical Features and Genomic Characterization of Post-Colonoscopy Colorectal Cancer.

ABSTRACT: INTRODUCTION:Some colorectal cancers (CRCs) may be missed during colonoscopies. We aimed to determine the clinicopathological, biological, and genomic characteristics of post-colonoscopy CRCs (PCCRCs). METHODS:Of the 1,619 consecutive patients with 1,765 CRCs detected between 2008 and 2016, 63 patients with 67 PCCRCs, when colonoscopies were performed 6-60 months before diagnosis, were recruited. After excluding patients with inflammatory bowel disease, familial polyposis syndrome, CRCs that developed from diminutive adenomatous polyps, and recurrent CRCs after endoscopic resection, 32 patients with 34 PCCRCs were enrolled. The lesions' clinicopathological features, mismatch repair proteins (MMRs), and genomic alterations were investigated. RESULTS:The overall PCCRC-5y rate, rate of intramucosal (Tis) lesions, and rate of T1 or more deeply invasive cancers were 3.7% (66/1,764), 3.9% (32/820), and 3.6% (34/944), respectively. Thirty-three patients' MMRs were investigated; 7 (21%) exhibited deficient MMRs (dMMRs), comprising 4 with T2 or more deeply invasive cancers and 5 whose lesions were in the proximal colon. Twenty-three tumors' genomic mutations were investigated; PIK3CA had mutated in 5 of 6 T2 or more deeply invasive cancers, of which, 4 were located in the proximal colon. Two patients with dMMRs and BRAF mutations had poor prognoses. Sixty-one percent (17/28) of the macroscopic type 0 lesions were superficial. All superficial Tis and T1 PCCRCs were detected <24 months after the negative colonoscopies. They were distributed throughout the colon and rectum. DISCUSSION:PCCRCs may be invasive cancers in the proximal colon that exhibit dMMRs and/or PIK3CA mutations or missed early CRCs especially superficial lesions.

SUBMITTER: Tanaka H

PROVIDER: S-EPMC7544176 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Clinical Features and Genomic Characterization of Post-Colonoscopy Colorectal Cancer.

Tanaka Hidenori H Urabe Yuji Y Oka Shiro S Shimohara Yasutsugu Y Nishimura Tomoyuki T Inagaki Katsuaki K Okamoto Yuki Y Matsumoto Kenta K Yamashita Ken K Sumimoto Kyoku K Ninomiya Yuki Y Yuge Ryo R Tanaka Shinji S Chayama Kazuaki K

Clinical and translational gastroenterology 20201001 10

<h4>Introduction</h4>Some colorectal cancers (CRCs) may be missed during colonoscopies. We aimed to determine the clinicopathological, biological, and genomic characteristics of post-colonoscopy CRCs (PCCRCs).<h4>Methods</h4>Of the 1,619 consecutive patients with 1,765 CRCs detected between 2008 and 2016, 63 patients with 67 PCCRCs, when colonoscopies were performed 6-60 months before diagnosis, were recruited. After excluding patients with inflammatory bowel disease, familial polyposis syndrome ...[more]

PMID: 33031197

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Project description:Background & aimsColonoscopy provides incomplete protection from colorectal cancer (CRC), but determinants of post-colonoscopy CRC are not well understood. We compared clinical features and molecular characteristics of CRCs diagnosed at different time intervals after a previous colonoscopy.MethodsWe performed a population-based, cross-sectional study of incident CRC cases in Denmark (2007-2011), categorized as post-colonoscopy or detected during diagnostic colonoscopy (in patients with no prior colonoscopy). We compared prevalence of proximal location and DNA mismatch repair deficiency (dMMR) in CRC tumors, relative to time since previous colonoscopy, using logistic regression and cubic splines to assess temporal variation.ResultsOf 10,365 incident CRCs, 725 occurred after colonoscopy examinations (7.0%). These were more often located in the proximal colon (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.90-2.89) and were more likely to have dMMR (OR, 1.26; 95% CI, 1.00-1.59), but were less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89) compared with CRCs diagnosed in patients with no prior colonoscopy. The highest proportions of proximal and/or dMMR tumors were observed in CRCs diagnosed 3-6 years after colonoscopy, but these features were still more frequent among cancers diagnosed up to 10 years after colonoscopy. The relative excess of dMMR tumors was most pronounced in distal cancers. In an analysis of 85 cases detected after colonoscopy, we found BRAF mutations in 23% of tumors and that 7% of cases had features of Lynch syndrome. Colonoscopy exams were incomplete in a higher proportion of cases diagnosed within <1 year (in 38%) than in those diagnosed within 1-10 years after colonoscopy (16%).ConclusionsIn a study of incident CRC cases in Denmark, we observed that tumors found in patients who have undergone colonoscopy are more often proximal and have dMMR compared to CRCs detected in patients without previous colonoscopies. The excess of right-sided tumors and the modest independent effects of dMMR reinforce the importance of proper colonoscopic examination of the proximal large bowel.

Project description:ImportanceAlthough some countries have implemented widespread colonoscopy screening, most European countries have not introduced it because of uncertainty regarding participation rates, procedure-related pain and discomfort, endoscopist performance, and effectiveness. To our knowledge, no randomized trials on colonoscopy screening currently exist.ObjectiveTo investigate participation rate, adenoma yield, performance, and adverse events of population-based colonoscopy screening in several European countries.Design, setting, and populationA population-based randomized clinical trial was conducted among 94 959 men and women aged 55 to 64 years of average risk for colon cancer in Poland, Norway, the Netherlands, and Sweden from June 8, 2009, to June 23, 2014.InterventionsColonoscopy screening or no screening.Main outcomes and measuresParticipation in colonoscopy screening, cancer and adenoma yield, and participant experience. Study outcomes were compared by country and endoscopist.ResultsOf 31 420 eligible participants randomized to the colonoscopy group, 12 574 (40.0%) underwent screening. Participation rates were 60.7% in Norway (5354 of 8816), 39.8% in Sweden (486 of 1222), 33.0% in Poland (6004 of 18 188), and 22.9% in the Netherlands (730 of 3194) (P < .001). The cecum intubation rate was 97.2% (12 217 of 12 574), with 9726 participants (77.4%) not receiving sedation. Of the 12 574 participants undergoing colonoscopy screening, we observed 1 perforation (0.01%), 2 postpolypectomy serosal burns (0.02%), and 18 cases of bleeding owing to polypectomy (0.14%). Sixty-two individuals (0.5%) were diagnosed with colorectal cancer and 3861 (30.7%) had adenomas, of which 1304 (10.4%) were high-risk adenomas. Detection rates were similar in the proximal and distal colon. Performance differed significantly between endoscopists; recommended benchmarks for cecal intubation (95%) and adenoma detection (25%) were not met by 6 (17.1%) and 10 of 35 endoscopists (28.6%), respectively. Moderate or severe abdominal pain after colonoscopy was reported by 601 of 3611 participants (16.7%) examined with standard air insufflation vs 214 of 5144 participants (4.2%) examined with carbon dioxide (CO2) insufflation (P < .001).Conclusions and relevanceColonoscopy screening entails high detection rates in the proximal and distal colon. Participation rates and endoscopist performance vary significantly. Postprocedure abdominal pain is common with standard air insufflation and can be significantly reduced by using CO2.Trial registrationclinicaltrials.gov Identifier: NCT00883792.

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Clinical Features and Genomic Characterization of Post-Colonoscopy Colorectal Cancer.

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Clinical Features and Genomic Characterization of Post-Colonoscopy Colorectal Cancer.

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