TP1.2.5Colonoscopic Surveillance Versus Surgical Resection After Polypectomy for Colorectal Polyp Cancers: Are We Overtreating Malignant Colorectal Polyps?

Aims Colorectal polyp cancers are increasingly detected in the era of screening. This raises the dilemma regarding management by colonoscopic surveillance or surgical segmental resection. The evidence base remains relatively limited and guidelines are still evolving to balance the risk of overtreatment and unnecessary surgical resection or undertreatment and cancer recurrence. In this study we investigate the management of polyp cancers in our centre. Methods This single centre retrospective study in a university teaching hospital included all patients with malignant colorectal polyps found endoscopically and over a 15-month period. All patients were discussed at the colorectal MDT. The threshold for incomplete endoscopic excision was 1mm. Data from endoscopy reports, histopathology reports and operation notes was collected to determine rate of surgical resection and of residual disease. Results 70 patients with colorectal polyps, classified as at least high-grade dysplasia, were included. 22/70 polyp cancers (31%) patients had surgical resection. Residual adenocarcinoma was identified in 1/22 (4%) and one further patient had lymph node metastases. Two individual patients developed post-operative ileus and pancreatitis resulting from surgery. Conclusions Of those patients undergoing surgical resection only 8% patients had malignancy in the postoperative specimen, raising the possibility of overtreatment under current guidelines. This highlights a need to update clinical guidelines to avoid overtreatment without compromising oncological outcomes.

Preoperative Endoscopic Activity Predicts the Occurrence of Pouchitis After Ileal Pouch–Anal Anastomosis in Ulcerative Colitis: A Multicenter Retrospective Study in China

Background: Pouchitis is the most common long-term complication after ileal pouch–anal anastomosis (IPAA) in patients with ulcerative colitis (UC). Ulcerative colitis endoscopic index of severity (UCEIS) and Mayo endoscopic score (MES) are widely used indices to evaluate endoscopic activity. This study aimed to clarify the predictive value of preoperative endoscopic activity on the occurrence of pouchitis after IPAA.Methods: Data of patients with UC who underwent IPAA from January 2008 to January 2020 were collected retrospectively. UCEIS and MES were based on the preoperative colonoscopy findings of two independent endoscopists.Results: A total of 102 patients with a median follow-up of 5 (interquartile range, 2–9) years were included in the study. Among them, 21.6% developed pouchitis. Compared with MES, UCEIS had a stronger correlation with pouchitis disease activity index. UCEIS ≥ 7 had the most significant receiver-operating characteristic (ROC) curve area of 0.747 with a sensitivity of 68.2% and specificity of 81.2% in predicting pouchitis, which outperformed MES of 3 with an ROC area of 0.679 with a sensitivity of 54.5% and specificity of 81.2%. Furthermore, we found that UCEIS ≥ 7 was an independent risk factor for post-IPAA pouchitis [odds ratio (OR), 8.860; 95% CI, 1.969–39.865, p < 0.001] with a higher risk than MES of 3 (OR, 5.200; 95% CI, 1.895–14.273; p = 0.001).Conclusion: Ulcerative colitis endoscopic index of severity performed better in predicting pouchitis after IPAA than MES. Earlier and more frequent postoperative colonoscopic surveillance should be considered in patients with preoperative UCEIS ≥ 7 to detect the occurrence of pouchitis earlier.

Colorectal Strictures in Patients With Inflammatory Bowel Disease Do Not Independently Predict Colorectal Neoplasia

Background Colorectal strictures have been considered independent risk factors for neoplasia in patients with inflammatory bowel disease (IBD). We examined the association between colorectal stricture and subsequent risk of colorectal neoplasia (CRN) in patients with IBD colitis undergoing colonoscopic surveillance. Methods We conducted a retrospective cohort analysis of patients with IBD colitis enrolled in colonoscopic surveillance for CRN at an academic medical center between 2005 and 2017. Inclusion criteria were IBD involving the colon for ≥8 years (or any duration with primary sclerosing cholangitis [PSC]) undergoing surveillance. Exclusion criteria were advanced CRN (ACRN; colorectal cancer [CRC] or high-grade dysplasia [HGD]) prior to or at enrollment, prior colectomy, or limited (<30%) disease extent or proctitis. Multivariable logistic and Cox regression analysis estimated the association between colorectal stricture on the index colonoscopy and ACRN, CRN (indefinite dysplasia, low-grade dysplasia, HGD, CRC), or colectomy. Results Among 789 patients with IBD undergoing CRC surveillance, 72 (9%; 70 with Crohn’s colitis) had a colorectal stricture on index colonoscopy. There was no significant difference in the frequency of ACRN or requirement for colectomy between patients with vs without a colorectal stricture (P > .05). Colorectal stricture was not associated with subsequent ACRN (adjusted odds ratio [aOR], 1.41; 95% CI, 0.49–4.07), CRN (aOR, 1.15; 95% CI, 0.51–2.58), or colectomy (aOR, 1.10; 95% CI, 0.65–1.84). Conclusions In this analysis of patients with IBD colitis undergoing CRN surveillance, the presence of a colorectal stricture was not independently associated with risk of ACRN or colectomy. Multicenter, prospective studies are needed to confirm these findings, particularly in patients with ulcerative colitis–associated colorectal stricture.

Genomic, Microbial and Immunological Microenvironment of Colorectal Polyps

Colorectal cancer (CRC) develops from pre-cancerous cellular lesions in the gut epithelium, known as polyps. Polyps themselves arise through the accumulation of mutations that disrupt the function of key tumour suppressor genes, activate proto-oncogenes and allow proliferation in an environment where immune control has been compromised. Consequently, colonoscopic surveillance and polypectomy are central pillars of cancer control strategies. Recent advances in genomic sequencing technologies have enhanced our knowledge of key driver mutations in polyp lesions that likely contribute to CRC. In accordance with the prognostic significance of Immunoscores for CRC survival, there is also a likely role for early immunological changes in polyps, including an increase in regulatory T cells and a decrease in mature dendritic cell numbers. Gut microbiotas are under increasing research interest for their potential contribution to CRC evolution, and changes in the gut microbiome have been reported from analyses of adenomas. Given that early changes to molecular components of bowel polyps may have a direct impact on cancer development and/or act as indicators of early disease, we review the molecular landscape of colorectal polyps, with an emphasis on immunological and microbial alterations occurring in the gut and propose the potential clinical utility of these data.

Malignant potential of colorectal neoplasms in Lynch syndrome: an analysis of 325 lesions endoscopically treated at a single institute

Background Patients with Lynch syndrome are at an increased risk of developing colorectal cancer, and the adenoma-carcinoma sequence is accelerated in these patients. However, the clinicopathological characteristics of colorectal neoplasms in Lynch syndrome patients are not well-known. Methods A total of 325 consecutive colorectal neoplasms were endoscopically removed from 68 patients with Lynch syndrome between June 2005 and May 2018 and retrospectively reviewed. Results Of the 325 lesions, 94 (29%), 220 (68%) and 11 (3%) were from patients with MLH1, MSH2 and MSH6 mutations, respectively. The median lesion size was 5 mm (range 2–40 mm), with 229 (71%) lesions having a non-polypoid morphology. The frequencies of advanced neoplasms, including high-grade adenomas, intramucosal carcinomas and submucosal invasive carcinomas were 14, 34, 97 and 93% for lesions with diameters of <5, ≥5 and <10, ≥10 and <20, and ≥20 mm, respectively. The frequencies of advanced neoplasms in the proximal colon, distal colon and rectum did not significantly differ (36, 35 and 41%, respectively). Conclusions Our results suggest that the malignant transformation interval from low-grade adenomas to advanced neoplasms is similar in all parts of the colon. Furthermore, since one-third of neoplastic lesions with diameters of ≥5 and <10 mm and most of those ≥10 mm were advanced neoplasms, we recommend that in Lynch syndrome patients, careful colonoscopic surveillance should be performed throughout the colon, and all neoplastic lesions, regardless of the size, should be subjected to detailed endoscopic examination, complete resection and detailed pathological examination.

Second primary cancers in patients with sporadic deficient mismatch repair (dMMR) colorectal cancer (CRC).

45 Background: Patients with hereditary non polyposis colorectal cancer (HNPCC) diagnosed with CRC have an elevated risk of a second primary CRC (SPCRC) and of rapid primary cancer development. This informs both initial surgical approach and endoscopic surveillance intervals. A feature of HNPCC is dMMR, also found in 15% of sporadic CRC, where the risk of SPCRC has yet to be defined. Methods: We examined a multi-site comprehensive CRC database (Melbourne, Australia), where prospectively collected data includes family history (including HNPCC), histology, surgery performed and incidence of second primary cancer. Sporadic dMMR included any case with a BRAF V600E mutation, confirmed hypermethylation, negative germline testing, or age over 60 years. We explored the incidence and timing of SPCRC in patients with early stage sporadic dMMR (or MSI-H) versus pMMR cancers. Results: From February 2004 to December 2019, 7442 patients diagnosed with stage I-III CRC were recorded. MMR status was known in 4079 (54.8%), including 714 with dMMR colorectal cancer (17.4%) of which 575 (14.6%) were deemed sporadic dMMR. Sporadic dMMR patients were older (mean 76.2 years vs 65.9 years, p = < 0.001), more likely to be female (65.2% vs 42%, p = < 0.001) and have a right sided primary (80.9% vs 32.8%, p = < 0.001), compared to patients with pMMR CRC. A SPCRC was diagnosed in 11/575 patients (1.91%) with sporadic dMMR CRC versus 27/3365 (0.83%) patients with pMMR CRC (HR = 2.57, 95% CI 1.28 - 5.17, p = 0.008). Median time to SPCRC was 1.13 years vs 2.38 years (p = 0.49). The SPCRC diagnosed in sporadic dMMR CRC vs pMMR CRC were more likely to be dMMR ((72.7%) vs (25.9%), p = 0.03), but a similar number were stage I or II ((81.8%) vs (81.5%)) and a similar number were surveillance detected ((72.7%) vs (77.8%). Conclusions: Patients with sporadic dMMR appear to have a significantly elevated risk of SPCRC compared to the pMMR population and were diagnosed at a shorter interval. The SPCRC is also more likely to also be dMMR. Increased colonoscopic surveillance of patients presenting with an initial sporadic dMMR cancer should be considered where clinically appropriate.