Interval Colorectal Cancers: What and why

An increasing number of studies now indicate that colonoscopic examination is not perfect in preventing colorectal cancer (CRC), especially of the proximal colon. Several factors can be implicated in the occurrence of interval CRCs-further referred to as postcolonoscopy CRCs-, such as missed, incompletely resected lesions and newly developed cancers. Missed lesions represent by far the dominant cause of postcolonoscopy CRCs, with nonpolypoid (flat or depressed) neoplasms and sessile serrated polyps playing a significant role. Molecular events underlying progression of such lesions may further augment the cancer risk. In this article, we review the literature about postcolonoscopy CRC risk and the most common explanations. We discuss potential implications, paying special attention to improvements required in education and training

Metachronous neoplasms in patients with laterally spreading tumours during surveillance

BACKGROUND: Laterally spreading tumours represent a major challenge for endoscopic detection and resection. OBJECTIVE: To examine synchronous and metachronous neoplasms in patients with laterally spreading tumours. METHODS: We prospectively collected colonoscopy and histopathology data from patients who underwent colonoscopy in our centre at up to 6 years' follow‐up. Post‐resection surveillance outcomes between laterally spreading tumours, flat colorectal neoplasms 10 mm or greater, and large polypoid colorectal neoplasms, polypoid colorectal neoplasms 10 mm or greater, were compared. RESULTS: Between 2008 and 2012, 8120 patients underwent colonoscopy for symptoms (84.6%), screening (6.7%) or surveillance (8.7%). At baseline, 151 patients had adenomatous laterally spreading tumours and 566 patients had adenomatous large polypoid colorectal neoplasms. Laterally spreading tumour patients had more synchronous colorectal neoplasms than large polypoid colorectal neoplasm patients (mean 3.34 vs. 2.34, p < 0.001). Laterally spreading tumour patients significantly more often developed metachronous colorectal neoplasms (71.6% vs. 54.2%, p = 0.0498) and colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients (36.4% vs. 15.8%, p < 0.001). After correction for age and gender, laterally spreading tumour patients were more likely than large polypoid colorectal neoplasm patients to develop a colorectal neoplasm with high grade dysplasia or submucosal invasion (hazard ratio 2.9, 95% confidence interval 1.8–4.6). The risk of metachronous colorectal cancer was not significantly different in laterally spreading tumours compared to large polypoid colorectal neoplasm patients. CONCLUSION: Patients with laterally spreading tumours developed more metachronous colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients. Based on these findings endoscopic treatment and surveillance recommendations for patients with laterally spreading tumours should be optimised

Molecular pathways in post-colonoscopy versus detected colorectal cancers: results from a nested case–control study

Background: Post-colonoscopy colorectal cancers (PCCRCs) pose challenges in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. In a nested case–control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs). Methods: Whole-genome chromosomal copy number changes and mutation status of genes commonly affected in CRC were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status was also determined. Results: In total, 122 PCCRCs and 98 DCRCs with high-quality DNA were examined. PCCRCs were more often located proximally (P < 0.001), non-polypoid appearing (P = 0.004), early stage (P = 0.009) and poorly differentiated (P = 0.006). PCCRCs showed significantly less 18q loss (FDR < 0.2), compared to DCRCs. No significant differences in mutations were observed. PCCRCs were more commonly CIMP high (P = 0.014) and MSI (P = 0.029). After correction for tumour location, only less 18q loss remained significant (P = 0.005). Conclusion: Molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. These together with the clinical features observed support the hypothesis that SSLs and non-polypoid CRNs are contributors to the development of PCCRCs. The future focus should be directed at improving the detection and endoscopic removal of these non-polypoid CRN and SSLs. Clinical trial registration: NTR3093 in the Dutch trial register (www.trialregister.nl)