Early-onset colorectal cancer (EOCRC), defined as that diagnosed before the age of 50, accounts for 10–12% of all new colorectal cancer (CRC) diagnoses. Epidemiological data indicate that EOCRC incidence is increasing, despite the observed heterogeneity among countries. Although the cause for such increase remains obscure, ≈13% (range: 9–26%) of EOCRC patients carry pathogenic germline variants in known cancer predisposition genes, including 2.5% of patients with germline pathogenic variants in hereditary cancer genes traditionally not associated with CRC predisposition. Approximately 28% of EOCRC patients have family history of the disease. This article recapitulates current evidence on the inherited syndromes that predispose to EOCRC and its familial component. The evidence gathered support that all patients diagnosed with an EOCRC should be referred to a specialized genetic counseling service and offered somatic and germline pancancer multigene panel testing. The identification of a germline pathogenic variant in a known hereditary cancer gene has relevant implications for the clinical management of the patient and his/her relatives, and it may guide surgical and therapeutic decisions. The relative high prevalence of hereditary cancer syndromes and familial component among EOCRC patients supports further research that helps understand the genetic background, either monogenic or polygenic, behind this increasingly common disease.

Individuals with a non-syndromic family history of colorectal cancer are known to have an increased risk. There is an opportunity to prevent early-onset colorectal cancer (age less than 50 years) (EOCRC) in this population. The aim was to explore the proportion of EOCRC that is preventable due to family history of colorectal cancer. This was a retrospective multicentre European study of patients with non-hereditary EOCRC. The impact of the European Society of Gastrointestinal Endoscopy (ESGE), U.S. Multi-Society Task Force (USMSTF), and National Comprehensive Cancer Network (NCCN) guidelines on prevention and early diagnosis was compared. Colorectal cancer was defined as potentially preventable if surveillance colonoscopy would have been performed at least 5 years before the age of diagnosis of colorectal cancer, and diagnosed early if colonoscopy was undertaken between 1 and 4 years before the diagnosis. Some 903 patients with EOCRC were included. Criteria for familial colorectal cancer risk in ESGE, USMSTF, and NCCN guidelines were met in 6.3, 9.4, and 30.4 per cent of patients respectively. Based on ESGE, USMSTF, and NCCN guidelines, colorectal cancer could potentially have been prevented in 41, 55, and 30.3 per cent of patients, and diagnosed earlier in 11, 14, and 21.1 per cent respectively. In ESGE guidelines, if surveillance had started 10 years before the youngest relative, there would be a significant increase in prevention (41 versus 55 per cent; P = 0.010). ESGE, USMSTF, and NCCN criteria for familial colorectal cancer were met in 6.3, 9.4, and 30.4 per cent of patients with EOCRC respectively. In these patients, early detection and/or prevention could be achieved in 52, 70, and 51.4 per cent respectively. Early and accurate identification of familial colorectal cancer risk and increase in the uptake of early colonoscopy are key to decreasing familial EOCRC.

Backgrounds Cold snare EMR (CS-EMR) in large flat nonpedunculated colonic lesions (LFNPCLs) is an alternative to the standard EMR procedure with a better safety profile, but scientific evidence on its efficacy is unavailable. This study aimed to compare the recurrence rate between the two techniques at 6 months. Secondary aims were comparison of the safety profile and procedure-related outcomes. Methods This was a noninferiority, multicenter, open-label, randomized controlled trial of consecutive large (≥ 20 mm) LFNPCLs without suspicious features of submucosal invasion. Results 229 patients were randomized to receive CS-EMR (n = 115) or EMR (n = 114). The median lesion size was 25 mm and 74.6 % were adenomas. The trial was stopped early by clinical consensus according to a safety monitoring board. At first surveillance colonoscopy (n = 220) the recurrence rate was significantly greater in the CS-EMR group than in the EMR group: 33.0 % vs. 16.2 % (P = 0.004) and 34.7 % vs. 14.8 % (P = 0.001) in the intention-to-treat and per-protocol analyses, respectively. According to the subgroup analysis, the recurrence rate was significantly greater after CS-EMR for LFNPCLs ≥ 30 mm (43.1 % vs. 18.2 %). There was no difference in the rate of adverse events. The use of clips was more common in the EMR group (52.6 % vs. 27.8 %). Conclusions The recurrence rate of LFNPCLs after CS-EMR was significantly greater than after the standard hot technique. A similar safety profile was found between groups.

Background: The incidence of early-onset colorectal cancer is increasing, but in Europe this growth shows a heterogeneous pattern in different countries and regions. Methods: Patients from six countries who participated in the Global Early-Onset COlorectal Cancer DatabasE (GEOCODE)-Europe group were included. The inclusion criteria were patients with colorectal adenocarcinoma diagnosed between 18 and 49 years of age, between January 2010 and December 2017, with at least 3 years of follow-up. Patients with inherited colorectal cancer syndromes were excluded. Results: A total of 851 patients were included with almost equal sex distribution, most were diagnosed at age 39 years or older and 42% of patients were overweight or obese. Diagnoses were predominantly at later stages (62.5% stage III–IV) and tumours were predominantly located in the distal colon (76.9% left colon and rectum). Comparative analysis between countries demonstrated that the UK had a younger age at diagnosis and the Italian cohort had a higher prevalence of being overweight or obese. Patients from Luxembourg had more advanced stage diagnoses and those from The Netherlands had more polyps. Patients from the UK had a greater family history of colorectal cancer. Comparison of Mediterranean versus non-Mediterranean countries showed significant differences in the age at diagnosis and body mass index. The prevalence of early-onset colorectal cancer over the age of 40 years in Mediterranean versus non-Mediterranean countries was 71.4% versus 62.1% (P = 0.002), and early-onset colorectal cancer was diagnosed at a more advanced stage in Mediterranean countries versus non-Mediterranean countries (65.3% versus 54.7%; P = 0.033). Family history of colorectal cancer in a first-degree relative was more common in non-Mediterranean versus Mediterranean countries (19.1% versus 11.4%; P < 0.001). Conclusion: This study highlights significant geographical disparities in the clinical, pathological and familial features of early-onset colorectal cancer across European countries.

Implementation of population-based colorectal cancer screening programs has led to increases in the incidence of pT1 colorectal cancer. These incipient invasive cancers have a very good prognosis and can be treated locally, but more than half of these cases are treated with surgery due to the presence of histological high-risk criteria. These high-risk criteria are suboptimal, with no consensus among clinical guidelines, heterogeneity in definitions and assessment, and poor concordance in evaluation, and recent evidence suggests that some of these criteria considered high risk might not necessarily affect individual prognosis. Current criteria classify most patients as high risk with an indication for additional surgery, but only 2–10.5% have lymph node metastasis, and the residual tumor is present in less than 20%, leading to overtreatment. Patients with pT1 colorectal cancer have excellent disease-free survival, and recent evidence indicates that the type of treatment, whether endoscopic or surgical, does not significantly impact prognosis. As a result, the protective role of surgery is questionable. Moreover, surgery is a more aggressive treatment option, with the potential for higher morbidity and mortality rates. This article presents a comprehensive review of recent evidence on the clinical management of pT1 colorectal cancer. The review analyzes the limitations of histological evaluation, the prognostic implications of histological risk status and the treatment performed, the adverse effects associated with both endoscopic and surgical treatments, and new advances in endoscopic treatment.

Background and study aims In patients with familial adenomatous polyposis (FAP), endoscopic resection of duodenal adenomas is commonly performed to prevent cancer and prevent or defer duodenal surgery. However, based on studies using different resection techniques, adverse events (AEs) of polypectomy in the duodenum can be significant. We hypothesized that cold snare polypectomy (CSP) is a safe technique for duodenal adenomas in FAP and evaluated its outcomes in our centers. Patients and methods We performed a prospective international cohort study including FAP patients who underwent CSP for one or more superficial non-ampullary duodenal adenomas of any size between 2020 and 2022. At that time, this technique was common practice in our centers for superficial duodenal adenomas. The primary outcome was the occurrence of intraprocedural and post-procedural AEs. ResultsIn total, 133 CSPs were performed in 39 patients with FAP (1–18 per session). Median adenoma size was 10 mm (interquartile range 8–15 mm), ranging from 5 to 40 mm; 27 adenomas were ≥20 mm (20%). Of the 133 polypectomies, 109 (82%) were performed after submucosal injection. Sixty-one adenomas (46%) were resected en bloc and 72 (54%) piecemeal. Macroscopic radical resection was achieved for 129 polypectomies (97%). Deep mural injury type II occurred in three polyps (2%) with no delayed perforation after prophylactic clipping. There were no clinically significant bleeds, perforations or other post-procedural AEs. Histopathology showed low-grade dysplasia in all 133 adenomas. Conclusions CSP for (multiple) superficial non-ampullary duodenal adenomas in FAP seems feasible and safe. Long-term prospective research is needed to evaluate whether protocolized duodenal polypectomies prevent cancer and surgery.