Whereas colorectal cancer [CRC] risk among inflammatory bowel disease [IBD] patients appears to be declining in recent years, the risk in this group remains higher compared with the general population, particularly in patients with longer disease duration, extensive colonic involvement, family history of CRC, presence of pseudopolyps, and concomitant diagnosis of primary sclerosing cholangitis [PSC].1–3 Consequently, intensive CRC surveillance programmes tailored around these risk factors are recommended for all IBD patients with colonic involvement. In Europe, the European Crohn’s and Colitis Organisation [ECCO] consensus for endoscopy in IBD recommends initial screening 8 years after the onset of symptoms, with subsequent surveillance intervals ranging from 1–5 years depending on the individual risk stratification.4 In the USA, the American Gastroenterological Association [AGA] recommends first screening at 8–10 years after the onset of symptoms with subsequent surveillance at intervals of every 1–2 years regardless of the individual risk stratification—with one exception for patients with concomitant PSC diagnosis who should undergo annual surveillance starting from the time of diagnosis.5 There is still some debate on the best techniques to perform surveillance colonoscopies to detect subtle dysplastic lesions in IBD patients. Today the use of high definition equipment is recommended over standard definition equipment in all IBD surveillance colonoscopies, since it allows better visualisation and detection of dysplasia. The current recommendations by most gastrointestinal [GI] societies recommend chromoendoscopy over white light endoscopy [WLE]. WLE with random biopsies is accepted as an alternative when resources and expertise for performing chromoendoscopy are not available.4–6 However, the recommendations may soon be updated since two recent studies showed similar dysplasia detection rates and shorter withdrawal times for high definition endoscopy or narrow band imaging compared with chromoendoscopy.7,8 Box 1 summarises surveillance recommendations from ECCO, AGA, and the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in IBD patients: International Consensus [SCENIC], which was endorsed by AGA and several GI societies in North America, Europe and Asia. Box 1. CRC surveillance guidelines by ECCO, AGA, and SCENIC4-6 ECCO guidelines  AGA guidelines  SCENIC recommendations  Candidates: patients with left-sided and extensive UC, patients with CD involving more than one segment of the colon Method: Surveillance colonoscopy should take into account local expertise. Chromoendoscopy with targeted biopsies has been shown to increase dysplasia detection rate. Alternatively, random biopsies [quadrantic biopsies every 10 cm] and targeted biopsies of any visible lesion should be performed if white light endoscopy is used. High- definition endoscopy should be used if available Initial screening: 8 years after the onset of symptoms Surveillance intervals: based on risk stratification, annually for high-risk patients, every 2–3 years for intermediate-risk, and every 5 years for low-risk patients Candidates: patients with left-sided and extensive UC, patients with CD involving ≥1/3 of the colon Method: colonoscopy with representative biopsy specimens from each anatomical section. Chromoendoscopy with targeted biopsies is suggested as an alternative, based on available expertise Initial screening: 8–10 years after onset of symptoms. Patients with PSC should have first screening at the time of diagnosis Surveillance intervals: within 1–2 years after initial screening. After 2 negative surveillance colonoscopies, surveillance can be extended to every 1–3 years 1. When performing surveillance with WLE, high definition is recommended rather than standard definition 2. When performing surveillance with standard-definition colonoscopy, chromoendoscopy is recommended rather than WLE 3. When performing surveillance with high-definition colonoscopy, chromoendoscopy is suggested rather than WLE 4. When performing surveillance with standard-definition colonoscopy, narrow-band imaging is not suggested in place of white-light colonoscopy 5. When performing surveillance with high-definition colonoscopy, narrow-band imaging is not suggested in place of WLE ECCO guidelines  AGA guidelines  SCENIC recommendations  Candidates: patients with left-sided and extensive UC, patients with CD involving more than one segment of the colon Method: Surveillance colonoscopy should take into account local expertise. Chromoendoscopy with targeted biopsies has been shown to increase dysplasia detection rate. Alternatively, random biopsies [quadrantic biopsies every 10 cm] and targeted biopsies of any visible lesion should be performed if white light endoscopy is used. High- definition endoscopy should be used if available Initial screening: 8 years after the onset of symptoms Surveillance intervals: based on risk stratification, annually for high-risk patients, every 2–3 years for intermediate-risk, and every 5 years for low-risk patients Candidates: patients with left-sided and extensive UC, patients with CD involving ≥1/3 of the colon Method: colonoscopy with representative biopsy specimens from each anatomical section. Chromoendoscopy with targeted biopsies is suggested as an alternative, based on available expertise Initial screening: 8–10 years after onset of symptoms. Patients with PSC should have first screening at the time of diagnosis Surveillance intervals: within 1–2 years after initial screening. After 2 negative surveillance colonoscopies, surveillance can be extended to every 1–3 years 1. When performing surveillance with WLE, high definition is recommended rather than standard definition 2. When performing surveillance with standard-definition colonoscopy, chromoendoscopy is recommended rather than WLE 3. When performing surveillance with high-definition colonoscopy, chromoendoscopy is suggested rather than WLE 4. When performing surveillance with standard-definition colonoscopy, narrow-band imaging is not suggested in place of white-light colonoscopy 5. When performing surveillance with high-definition colonoscopy, narrow-band imaging is not suggested in place of WLE CD, Crohn’s disease; UC, ulcerative colitis; PSC, primary sclerosing cholangitis; WLE, white-light endoscopy. In this issue of the Journal of Crohn’s and Colitis, the paper titled ‘Incidence and classification of postcolonoscopy colorectal cancer in inflammatory bowel disease: A Dutch population-based cohort study’ by Wintjens et al. provides more insight into the problem of CRC in IBD patients, and raises important concerns about current surveillance guidelines.9 Using the IBD South Limburg [IBDSL] cohort, a longitudinal, population-based cohort of adult IBD patients who live in the region of South Limburg in The Netherlands and were diagnosed with IBD between 1991 and 2011, investigators aimed to evaluate the rate and potential aetiologies of postcolonoscopy CRC [PCCRC], defined as CRC diagnosed within 6–60 months of having a full colonoscopy. The previous surveillance colonoscopy aimed to prevent the development of CRC if a precancerous lesion was identified and appropriately managed at the time and hence, studying these patients may help in identifying potential opportunities to improve current surveillance programmes. In addition to evaluating PCCRCs, investigators also assessed the overall incidence of CRC and adherence to surveillance guidelines in this population. A total of 2801 patients were included with a median follow-up of 8.8 years and 8.1 years for UC and CD patients, respectively. Of the 2801 patients, a total of 20 CRC cases were identified with a relatively low overall incidence rate of 0.77/1000 patient-years. Among the reported CRC cases, nine were considered PCCRC [45.0%]. Of the nine cases, the majority [n = 5], were either diagnosed within 36 months of the index colonoscopy or had advanced CRC (> stage 1 rectal cancer [T1N0M0]) at the time of diagnosis and were classified as ‘missed lesions’. The remaining four cases were deemed to be secondary to: incomplete resection [n = 1]; inadequate bowel examination [n = 1]; inappropriate surveillance interval [n = 1]; and newly developed cancer [n = 1]. One potential explanation for the high rate of ‘missed lesions’ in this study is that most of the index colonoscopies were not performed for surveillance purposes but to assess disease activity; thus, surveillance techniques were not applied. For instance, random biopsies were obtained in only one index colonoscopy, which was done using standard WLE. In the remaining eight cases, one was performed using high definition endoscopy without random biopsies or chromoendoscopy, and seven were performed using standard WLE also without random biopsies or chromoendoscopy. Furthermore, seven of nine patients had active disease at the time of the index colonoscopy, which may have further limited visualisation and contributed to the high proportion of missed lesions. Therefore, these findings do not reflect the performance of IBD-CRC surveillance programmes since recommended surveillance procedures were not applied. Nevertheless, it supports the premises that standard colonoscopies are not adequate for CRC screening and surveillance in IBD patients, and additional techniques to enhance visualisation and improve dysplasia detection are required. Another interesting finding in this study is that of the 20 reported CRC cases, a third [n = 6] were diagnosed before the 8-year mark recommended to initiate CRC surveillance in IBD patients. A similar observation was made before by Lutgens et al who used a pathology database from The Netherlands to assess CRCs in IBD patients, and reported a rate of 17–22% of CRC cases developing before the recommended starting points for surveillance at that time [8–10 years for extensive colitis, and 15–20 years for left-sided colitis].10 In line with the current guidelines, if only cases diagnosed within 8 years of IBD diagnosis are considered, the rate remains relatively high at 20.5%. This raises the question of whether earlier surveillance may be beneficial in some IBD patients other that those with concomitant PSC diagnosis. The very low absolute cumulative risk of CRC within the first 8–10 years of diagnosis, along with the clear trend of increasing risk with increased disease duration, is the reason for the current guidelines. The frequently quoted cumulative risks reported in the meta-analysis by Eaden et al. are 2% after 10 years, 8% at 20 years, and 18% at 30 years.1 A more recent meta-analysis using exclusively population-based data reported even lower risks of 1.15% after 15 years, 1.69% after 20 years, and 2.61% after 25 years.2 Hence, recommending earlier screening for all IBD patient may be difficult to justify from a cost-effectiveness standpoint, given the low absolute risk of CRC in such cases; however, an approach that incorporates risk factors, such as the extent of the disease or severity of inflammation, should be investigated. The authors suggested one-time screening after achieving remission, to confirm absence of any dysplasia before applying the current surveillance guidelines. This is not an unreasonable approach, but it requires further study to investigate feasibility and cost-effectiveness. Finally, it is worth noting that seven of the 20 reported cases of CRCs [35%] were diagnosed at age ≥75 years. This brings forward the question as to whether CRC surveillance should be stopped at certain age or continued indefinitely in IBD patients. For average-risk CRC screening, the United States Preventive Services Task Force [USPSTF] recommends against routine screening for patients older than 75.11 Likewise, the American College of Physicians recommends discontinuing screening in average-risk patients with a life expectancy of <10 years, which is the average life expectancy for a 75-year-old in the USA.12 In Europe, most screening programmes continue sending invitations for screening up to age 70–75.13 Conversely, there are no such recommendations or guidance as to when surveillance should or can be discontinued in patients with higher than average risk for CRC, including those with IBD, in any of the general CRC or even in the more specialised IBD guidelines. Continuing surveillance indefinitely is unlikely to be the answer, as even in high-risk patients for CRC, the potential risks from the bowel preparation, sedation, and the procedure itself would eventually outweigh any benefit that can be potentially gained from detecting dysplasia or even cancer. Thus, in this population, an individualised approach taking into consideration patient’s age, comorbidities, previous inflammatory burden, PSC, and other risk factors for CRC, is likely the way to go. Findings on earlier colonoscopies should also be taken into consideration when considering surveillance discontinuation. A recent study by Ten Hove Jr et al. showed that in IBD patients with no additional risk factors for CRC [i.e. PSC, colonic stricture, history of dysplasia or CRC on previous colonoscopies, or first-degree relative with history of CRC], having two consecutive negative colonoscopies predicted very low risk of advanced colorectal neoplasia on follow-up.14 Hence, this represents a case scenario where discontinuing surveillance in an elderly patient is reasonable. In conclusion, in the era of individualised medicine, it is probably time to rethink the current ‘one size fits all’ approach applied for CRC surveillance, particularly with regard to time to initiate and and time to discontinue surveillance. Funding HH is supported by the National Institute of Diabetes and Digestive Kidney Diseases [U01DK092239, P30 DK034987]. Conflict of Interest HH has received consulting fees from Merck, Pfizer, Celltrion, Lycera, Boehringer-Ingelheim, Seres, AMAG, Finch, Alivio. Author Contributions MA and HH both conceptualised, wrote, and revised the manuscript. References 1. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001; 48: 526– 35. Google Scholar CrossRef Search ADS PubMed 2. Jess T, Rungoe C, Peyrin-Biroulet L. Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies. Clin Gastroenterol Hepatol 2012; 10: 639– 45. Google Scholar CrossRef Search ADS PubMed 3. Velayos FS, Loftus EVJr, Jess T, et al. Predictive and protective factors associated with colorectal cancer in ulcerative colitis: A case-control study. Gastroenterology 2006; 130: 1941– 9. Google Scholar CrossRef Search ADS PubMed 4. Magro F, Gionchetti P, Eliakim R, et al. ; European Crohn’s and Colitis Organisation [ECCO]. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohns Colitis 2017; 11: 649– 70. Google Scholar CrossRef Search ADS PubMed 5. Farraye FA, Odze RD, Eaden J, Itzkowitz SH. AGA technical review on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010; 138: 746– 74, 774.e1–4; quiz e12–3. Google Scholar CrossRef Search ADS PubMed 6. Laine L, Kaltenbach T, Barkun A, McQuaid KR, Subramanian V, Soetikno R; SCENIC Guideline Development Panel. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology 2015; 148: 639– 51.e28. Google Scholar CrossRef Search ADS PubMed 7. Bisschops R, Bessissow T, Joseph JA, et al. Chromoendoscopy versus narrow band imaging in UC: a prospective randomised controlled trial. Gut 2018;67:1087–94. 8. Iacucci M, Kaplan GG, Panaccione R, et al. A randomized trial comparing high definition colonoscopy alone with high definition dye spraying and electronic virtual chromoendoscopy for detection of colonic neoplastic lesions during IBD surveillance colonoscopy. Am J Gastroenterol 2018; 113: 225– 34. Google Scholar CrossRef Search ADS PubMed 9. Wintjens DSJ, Bogie RMM, van den Heuvel TRA, et al. Incidence and classification of postcolonoscopy colorectal cancers in inflammatory bowel disease: A Dutch population-based cohort study. J Crohns Colitis 2018 Apr 10. doi: 10.1093/ecco-jcc/jjy044. [Epub ahead of print.] 10. Lutgens MW, Vleggaar FP, Schipper ME, et al. High frequency of early colorectal cancer in inflammatory bowel disease. Gut 2008; 57: 1246– 51. Google Scholar CrossRef Search ADS PubMed 11. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for colorectal cancer: US preventive services task force recommendation statement. JAMA 2016; 315: 2564– 75. Google Scholar CrossRef Search ADS PubMed 12. Wilt TJ, Harris RP, Qaseem A; High Value Care Task Force of the American College of Physicians. Screening for cancer: advice for high-value care from the American College of Physicians. Ann Intern Med 2015; 162: 718– 25. Google Scholar CrossRef Search ADS PubMed 13. Armaroli P, Villain P, Suonio E, et al. European Code Against Cancer, 4th edition: cancer screening. Cancer Epidemiol 2015; 39[ Suppl 1]: S139– 52. Google Scholar CrossRef Search ADS PubMed 14. Ten Hove JR, Shah SC, Shaffer SR, et al. Consecutive negative findings on colonoscopy during surveillance predict a low risk of advanced neoplasia in patients with inflammatory bowel disease with long-standing colitis: results of a 15-year multicentre, multinational cohort study. Gut 2018. doi https://doi.org/10.1136/gutjnl-2017–315440. [Epub 2018/05/04.] Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: firstname.lastname@example.org This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)
Journal of Crohn's and Colitis – Oxford University Press
Published: May 26, 2018
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