High-grade dysplasia in IBD

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Background

The management of high-grade dysplasia (HGD) in patients with IBD depends on whether or not the lesion is amenable to complete endoscopic resection and whether the dysplasia is visible.

Traditionally, the approach to managing HGD has been surgical resection. This recommendation stemmed from early studies that indicated a high prevalence of CRC (42–67%) in the resected specimen in patients who underwent colectomyThe surgical removal of all or part of the colon. for HGD. However, the management approach in these patients has recently evolved and has moved away from routine colectomyThe surgical removal of all or part of the colon. due to several factors: improved lesion visualisation in the era of high-definition white light endoscopy (WLE) and chromoendoscopy, better cancer risk stratification as a result of better understanding of the natural history of dysplasia, and patient preference for continued surveillance over colectomyThe surgical removal of all or part of the colon..

Three factors need to be considered to determine the best management protocol for IBD patients with HGD:

  • the natural history of HGD and the degree of risk that a given patient will develop cancer
  • comparative patient outcomes after colectomyThe surgical removal of all or part of the colon. and continued surveillance
  • patients' preferences for the different treatment options.

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Evidence

What should be the protocol to manage high grade dysplasia in IBD? (MNG2)

Systematic review evidence

The systematic review identified only one publication that met the inclusion criteria: the SCENIC International Consensus Statement on Surveillance and Management of Dysplasia in Inflammatory Bowel Disease.[1] Dysplasia in IBD was the focus of this consensus statement, which was based on a synthesis of existing literature and consensus expert opinion.

Although Australian experts were not involved in the development of these guidelines, the panel of experts from the SCENIC consensus statement development panel were all from developed countries where the healthcare system and patient demographics are likely to be comparable to that in Australia. For these reasons, SCENIC recommendations are likely to be applicable to Australia.

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Natural history of high-grade dysplasia

Confirmation of the grade of dysplasia is initially required, through consensus between expert gastrointestinal pathologists. The distinction is important, because HGD is indicative of a more aggressive lesion than low-grade dysplasia (LGD). Exclusion of invasion (intramucosal cancer) is required, and is often best done by en bloc resection.

The management of patients with non-resectable or resectable polypoid and non-polypoid HGD was considered separately in the SCENIC Statement, because the natural history of these lesions is likely to be different.[1]
Non-resectable high grade dysplasia
Patients with endoscopically non-resectable HGD should undergo colectomyThe surgical removal of all or part of the colon..[1]
Resectable polypoid high grade dysplasia

Of the studies that reported outcomes for polypoid HGD, most studies were heterogeneous in that both LGD and HGD were included.[1] Only one study reported on outcomes for patients with polypoid HGD alone. Of the six studies that reported on the incidence of CRC in patients with LGD and HGD, most patients had LGD. Over a mean follow up period of 36–82 months, 19 of 311 patients developed a CRC. The overall incidence of CRC was 6% with a range of 2–13%. In the only study that focused on polypoid HGD, none of the nine patients developed CRC after a mean follow up period of 76.5 months (range 52–99 months).[1]

A systematic review that included data from 376 patients with resected polypoid dysplasia in 10 studies reported an annualised CRC incidence of 0.5%, which was considered comparable to that of synchronous and metachronous CRC.[1] This finding would favour surveillance over colectomyThe surgical removal of all or part of the colon..

Resectable non-polypoid high grade dysplasia

In patients with resectable non-polypoid HGD, it remains acceptable to offer surveillance over colectomyThe surgical removal of all or part of the colon. as most dysplasia will be visible provided that careful, high-quality colonoscopic surveillance is performed by an IBD expert using high-definition colonoscopy. The use of chromoendoscopy is required to further exclude multi-focal dysplasia. However, the SCENIC suggestion to offer these patients surveillance colonoscopy rather than colectomyThe surgical removal of all or part of the colon. was conditional, given the higher risk of CRC with non-polypoid HGD and the greater difficulty in ensuring complete resection.

Invisible dysplasia

The term invisible dysplasia refers to lesions identified by random biopsies. Invisible dysplasia accounts for <10% of dysplasia.[1] Invisible dysplasia is uncommon in sporadic colorectal carcinogenesis and tends to be associated with IBD chronic colitis. The risk of invisible dysplasia is highest for patients with additional high-risk factors primary sclerosing cholangitis, prior colorectal dysplasia, and a tubular foreshortened colon. In the presence of one or more high risk factors, random colonic biopsies are required in order to identify invisible dysplasia that can be missed even with advanced imaging techniques. The yield of invisible dysplasia with random biopsies is low – approximately 0.2-0.3%.[2][3]

Four studies (each with more than 15 IBD patients) reported on the incidence of CRC after the diagnosis of invisible dysplasia.[1] Over a mean follow up period of 15–50 months, CRC developed in 7 of 122 (6%, range 3–9%) patients. This contrasts with earlier studies which reported a much higher incidence of synchronous CRC in the resected specimen when the colectomyThe surgical removal of all or part of the colon. was performed for invisible dysplasia. Notably, a systematic review comprising 20 studies, which included 477 patients with invisible LGD reported a CRC rate of 22% in the resected colectomyThe surgical removal of all or part of the colon. specimen.[1][4] An even earlier (1994) systematic review found CRC in 42% (10 of 24 patients) of patients with invisible HGD.[5] Subsequent studies have echoed similar rates of CRC ranging between 45% and 67%.[6][7][8][9] However, it is likely that these high rates of CRC are related to technological issues in an era where high-definition WLE and chromoendoscopy were not yet available.[1] This is likely to account for the disparity between the rates of 'invisible' dysplasia reported in older studies (87%)[5] and more recent studies (10%).[1]

The rationale for recommending surveillance colonoscopy for invisible LGD or colectomyThe surgical removal of all or part of the colon. for invisible HGD therefore no longer stands. Instead, the SCENIC statement recommended referral to an endoscopist skilled with IBD surveillance using chromoendoscopy with high-definition colonoscopy when invisible dysplasia is diagnosed. A visible lesion should be managed according to its features (above) and, if no dysplasia is identified (i.e. true invisible dysplasia), patients should be counselled appropriately about the role of continued surveillance versus colectomyThe surgical removal of all or part of the colon..

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Treatment of high grade dysplasia

No studies were found that compared endoscopic management with colectomyThe surgical removal of all or part of the colon. after endoscopic resection of lesions with HGD, whether polypoid or non-polypoid HGD.[1] Hence, the management of these lesions relies heavily on the clinician’s assessment of cancer risk and the patient’s preference for surveillance versus colectomyThe surgical removal of all or part of the colon. following an informed discussion.

Exclusion of multi-focal dysplasia, indicative of a widespread field defect, is required. Close surveillance is required after complete endoscopic resection of solitary resectable high-grade dysplastic lesions, which have been confirmed as non-invasive by a pathologist.

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Patient preferences

Patient preference was not part of the review undertaken for the SCENIC consensus statement, but the authors described one study in which 199 patients with UC were surveyed. The study found that patients preferred colonoscopic surveillance over colectomyThe surgical removal of all or part of the colon. unless the risk of synchronous CRC was greater than 73%.[10] No other studies were described.

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Evidence summary and recommendations

Evidence summary Level References
Following complete endoscopic resection of polypoid HGD, colonoscopic surveillance is preferable over colectomyThe surgical removal of all or part of the colon..

Following complete endoscopic resection of non-polypoid HGD, colonoscopic surveillance is preferable to colectomyThe surgical removal of all or part of the colon..

III-1 [11], [12], [13], [14], [15], [16], [17], [18]
In the presence of invisible HGD that has been confirmed by a second expert gastrointestinal pathologist, chromoendoscopy with high-definition colonoscopy is recommended to help determine if there is multi-focal dysplasia. IV [6], [14], [16], [7], [9], [8], [4], [19], [20]
Evidence-based recommendationQuestion mark transparent.png Grade
Patients with endoscopically non-resectable high-grade dysplasia should undergo colectomyThe surgical removal of all or part of the colon..
C
Evidence-based recommendationQuestion mark transparent.png Grade
For patients with endoscopically resectable high grade dysplasia, whether polypoid or non-polypoid, continued colonoscopic surveillance after complete resection of the lesion is recommended rather than referral for colectomyThe surgical removal of all or part of the colon..
C
Consensus-based recommendationQuestion mark transparent.png

Patients with resected high-grade dysplasia should undergo further surveillance in 3–12 months. Subsequent surveillance intervals depend on the findings of each subsequent surveillance colonoscopy.

Consensus-based recommendationQuestion mark transparent.png

Patients with invisible high-grade dysplasia (HGD) should undergo more intensive colonoscopic surveillance than patients with visible HGD.

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Considerations in making these recommendations

Surveillance intervals after complete resection of high grade dysplasia

The optimal frequency of surveillance following complete endoscopic resection of HGD is unclear. More frequent surveillance for these patients would seem sensible but the appropriate interval is not well defined. Most recommendations are extrapolated from existing post-polypectomy surveillance guidelines for non-IBD patients, as published by various societies. The SCENIC consensus statement[1] recommended that patients with resected HGD should undergo further surveillance colonoscopy in 3–6 months. Patients with small (<10mm) resected HGD may return at 12 months for surveillance.

Intervals for subsequent surveillance colonoscopies depend on the findings at the initial repeat procedure. Where no further dysplasia is identified on the initial repeat colonoscopy, it would seem reasonable to perform a follow-up surveillance colonoscopy in 12 months.

References

  1. 1.001.011.021.031.041.051.061.071.081.091.101.111.12 Laine L, Kaltenbach T, Barkun A, McQuaid KR, Subramanian V, Soetikno R, et al. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology 2015 Mar;148(3):639-651.e28 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25702852.
  2. Leong RW, Ooi M, Corte C, Yau Y, Kermeen M, Katelaris PH, et al. Full-Spectrum Endoscopy Improves Surveillance for Dysplasia in Patients With Inflammatory Bowel Diseases. Gastroenterology 2017 May;152(6):1337-1344.e3 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28126349.
  3. Bisschops R, Bessissow T, Joseph JA, Baert F, Ferrante M, Ballet V, et al. Chromoendoscopy versus narrow band imaging in UC: a prospective randomised controlled trial. Gut 2017 Jul 11 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28698230.
  4. 4.04.1 Thomas T, Abrams KA, Robinson RJ, Mayberry JF. Meta-analysis: cancer risk of low-grade dysplasia in chronic ulcerative colitis. Aliment Pharmacol Ther 2007 Mar 15;25(6):657-68 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17311598.
  5. 5.05.1 Bernstein CN, Shanahan F, Weinstein WM. Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis? Lancet 1994 Jan 8;343(8889):71-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7903776.
  6. 6.06.1 Rutter MD, Saunders BP, Wilkinson KH, Rumbles S, Schofield G, Kamm MA, et al. Thirty-year analysis of a colonoscopic surveillance program for neoplasia in ulcerative colitis. Gastroenterology 2006 Apr;130(4):1030-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16618396.
  7. 7.07.1 Connell WR, Lennard-Jones JE, Williams CB, Talbot IC, Price AB, Wilkinson KH. Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis. Gastroenterology 1994 Oct;107(4):934-44 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7926483.
  8. 8.08.1 Hata K, Watanabe T, Kazama S, Suzuki K, Shinozaki M, Yokoyama T, et al. Earlier surveillance colonoscopy programme improves survival in patients with ulcerative colitis associated colorectal cancer: results of a 23-year surveillance programme in the Japanese population. Br J Cancer 2003 Oct 6;89(7):1232-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14520452.
  9. 9.09.1 Friedman S, Rubin PH, Bodian C, Goldstein E, Harpaz N, Present DH. Screening and surveillance colonoscopy in chronic Crohn's colitis. Gastroenterology 2001 Mar;120(4):820-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11231935.
  10. Siegel CA, Schwartz LM, Woloshin S, Cole EB, Rubin DT, Vay T, et al. When should ulcerative colitis patients undergo colectomy for dysplasia? Mismatch between patient preferences and physician recommendations. Inflamm Bowel Dis 2010 Oct;16(10):1658-62 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20186940.
  11. Odze RD, Farraye FA, Hecht JL, Hornick JL. Long-term follow-up after polypectomy treatment for adenoma-like dysplastic lesions in ulcerative colitis. Clin Gastroenterol Hepatol 2004 Jul;2(7):534-41 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15224277.
  12. Wanders LK, Dekker E, Pullens B, Bassett P, Travis SP, East JE. Cancer risk after resection of polypoid dysplasia in patients with longstanding ulcerative colitis: a meta-analysis. Clin Gastroenterol Hepatol 2014 May;12(5):756-64 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23920032.
  13. Blonski W, Kundu R, Furth EF, Lewis J, Aberra F, Lichtenstein GR. High-grade dysplastic adenoma-like mass lesions are not an indication for colectomy in patients with ulcerative colitis. Scand J Gastroenterol 2008;43(7):817-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18584520.
  14. 14.014.1 Goldstone R, Itzkowitz S, Harpaz N, Ullman T. Progression of low-grade dysplasia in ulcerative colitis: effect of colonic location. Gastrointest Endosc 2011 Nov;74(5):1087-93 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21907984.
  15. Kisiel JB, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Sandborn WJ. Outcome of sporadic adenomas and adenoma-like dysplasia in patients with ulcerative colitis undergoing polypectomy. Inflamm Bowel Dis 2012 Feb;18(2):226-35 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21416564.
  16. 16.016.1 Navaneethan U, Jegadeesan R, Gutierrez NG, Venkatesh PG, Hammel JP, Shen B, et al. Progression of low-grade dysplasia to advanced neoplasia based on the location and morphology of dysplasia in ulcerative colitis patients with extensive colitis under colonoscopic surveillance. J Crohns Colitis 2013 Dec;7(12):e684-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23916526.
  17. Rutter MD, Saunders BP, Wilkinson KH, Kamm MA, Williams CB, Forbes A. Most dysplasia in ulcerative colitis is visible at colonoscopy. Gastrointest Endosc 2004 Sep;60(3):334-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15332019.
  18. van Schaik FD, Mooiweer E, van der Have M, Belderbos TD, Ten Kate FJ, Offerhaus GJ, et al. Adenomas in patients with inflammatory bowel disease are associated with an increased risk of advanced neoplasia. Inflamm Bowel Dis 2013 Feb;19(2):342-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23340679.
  19. Ullman T, Croog V, Harpaz N, Sachar D, Itzkowitz S. Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis. Gastroenterology 2003 Nov;125(5):1311-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14598247.
  20. Ullman TA, Loftus EV Jr, Kakar S, Burgart LJ, Sandborn WJ, Tremaine WJ. The fate of low grade dysplasia in ulcerative colitis. Am J Gastroenterol 2002 Apr;97(4):922-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12008669.

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Appendices

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