11October2019

Y-ECCO Literature Review: Sailish Honap

Sailish Honap

No association between pseudopolyps and colorectal neoplasia in patients with inflammatory bowel diseases

Mahmoud R, Shah SC, Ten Hove JR, Torres J, Mooiweer E, Castaneda D, Glass J, Elman J, Kumar A, Axelrad J, Ullman T, Colombel JF, Oldenburg B, Itzkowitz SH; Dutch Initiative on Crohn and Colitis

Gastroenterology. 2019;156:1333–44.e3.

Introduction

Sailish Honap picture
Sailish Honap
© Sailish Honap

Patients with Inflammatory Bowel Disease (IBD) are at an increased risk of developing high-grade dysplasia and colorectal carcinoma [1, 2]. The risk of carcinogenesis, driven by chronic inflammation, increases with several factors, including duration and anatomic extent of colitis, family history and the presence of primary sclerosing cholangitis (PSC). European clinical guidelines for colonoscopy surveillance in this high-risk cancer population also suggest a shorter surveillance interval for those with post-inflammatory polyps (PIPs), also known as pseudopolyps [3–5]. PIPs are a common finding, more so in Ulcerative Colitis (UC) than in Crohn’s Disease, and are formed after alternating cycles of inflammation and regeneration of the epithelial mucosa. However, data are conflicting and evidence is lacking in this field as previous case control studies have reported up to a 2.5-fold increased risk [6, 7] whereas a more recent cohort study showed no significant association between PIPs and colorectal neoplasia (CRN) [8]. The authors of this study aimed to use a large cohort study to further define the risk of CRN and PIPs in patients with Inflammatory Bowel Disease.  

Methods

This was a large, multinational retrospective cohort study looking at patients with Inflammatory Bowel Disease who were enrolled in the dysplasia surveillance programme over a 20-year period between 1997 and 2017. Enrolled patients had a history of colitis spanning back at least 8 years and included any patient with PSC undergoing surveillance. Patients with a history of colorectal high-grade dysplasia (HGD) or CRN were excluded.

The study’s primary outcome was the rate of occurrence of HGD and CRN, according to PIP status. The occurrence rate of all grades of dysplasia and colectomy were secondary outcomes. Moreover, factors associated with the presence or absence of PIPs and factors predictive of or protective against neoplasia were also investigated.

Key Findings

In total, 1,582 eligible patients from both US and Dutch cohorts were followed up for a median of 4.8 years, accruing 8,182 patient-years of follow-up. Of these patients, 29% were found to have PIPs. There was no significant difference in the occurrence of advanced CRN between those with and those without PIPs [adjusted hazard ratio (aOR) 1.17; 95% confidence interval (95% CI) 0.59–2.31]. Although PSC, disease duration, prior dysplasia and mean histological inflammation were independent positive predictors of advanced CRN occurrence, the presence of PIPs was not.

PIPs were associated with more severe inflammation (aOR 1.32; 95% CI 1.13–1.55), greater disease extent (aOR 1.92; 95% CI 1.34–2.74) and lower likelihood of primary sclerosing cholangitis (aOR 0.38; 95% CI 0.26–0.55). Interestingly, the colectomy rate was significantly higher in patients with PIPs. This may be explained by the difficulty in distinguishing between large innumerable pseudopolyps and dysplasia/neoplasia.

Conclusion

This large retrospective cohort study covering a 20-year period reported that pseudopolyposis in Inflammatory Bowel Disease is not a predictor of risk for development of colorectal cancer. These findings challenge the prior notion of an increased cancer risk in this group of patients, which has become embedded in practice guidelines suggesting more frequent endoscopic surveillance. Reducing the burden of endoscopy would offer economic benefits and improve patients’ quality of life.

Strengths of the study included the large cohort size, which allowed capture of HGD and CRN cases and calculation of hazard ratios. This was further supported by statistically significant links between the already known predictive factors for HGD and CRN in IBD, including prior dysplasia and the severity and duration of inflammation. However, the study was not without its limitations. First, this was a retrospective study and was subject to the bias associated with such studies. Secondly, the reporting of PIPs was not standardised, and PIPs may not have been commented upon by endoscopists, particularly if there were other pathological findings. Finally, the study was underpowered to detect a link between density of PIPs and neoplasia, which is of importance as it is usually in this setting that mucosal visualisation is obscured.

References

    1. Ullman TA, Itzkowitz SH. Intestinal inflammation and cancer. Gastroenterology. 2011;140:1807–16. 2. Lutgens MWMD, van Oijen MGH, van der Heijden GJMG, Vleggaar FP, Siersema PD, Oldenburg B. Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies. Inflamm Bowel Dis. 2013;19:789–99.
    3. Cairns SR, Scholefield JH, Steele RJ, et al. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut. 2010;59:666–89.
    4. Annese V, Daperno M, Rutter MD, et al. European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohns Colitis. 2013;7:982–1018.
    5. Harbord M, Eliakim R, Bettenworth D, et al. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 2: Current management. J Crohns Colitis. 2017;11:769–84.
    6. Velayos FS, Loftus EV, Jess T, et al. Predictive and protective factors associated with colorectal cancer in ulcerative colitis: A case-control study. Gastroenterology. 2006;130:1941–9.
    7. Rutter MD, Saunders BP, Wilkinson KH, et al. Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk. Gut. 2004;53:1813–6.
    8. Choi C-HR, Al Bakir I, Ding N-SJ, et al. Cumulative burden of inflammation predicts colorectal neoplasia risk in ulcerative colitis: a large single-centre study. Gut. 2017 Nov 17; doi: 10.1136/gutjnl-2017-314190. [Epub ahead of print].

 

Sailish is a gastroenterology trainee in the South London rotation and a clinical research fellow in Inflammatory Bowel Disease at Guy’s and St. Thomas’ Hospital. His interests include therapeutic drug monitoring and emerging pharmacological agents in IBD and is working towards an MD at King’s College London.”

Posted in ECCO News, Committee News, Y-ECCO Literature Reviews, Volume 14, Issue 3, Y-ECCO

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