High-grade dysplasia in IBD

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Background

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

Traditionally, the approach to managing HGDHigh grade dysplasia has been surgical resection. This recommendation stemmed from early studies that indicated a high prevalence of CRCColorectal cancer (42–67%) in the resected specimen in patients who underwent colectomy for HGDHigh grade dysplasia. However, the management approach in these patients has recently evolved and has moved away from routine colectomy due to several factors: improved lesion visualisation in the era of high-definition white light endoscopy (WLEWhite light endoscopy) 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 colectomy.

Three factors need to be considered to determine the best management protocol for IBDInflammatory bowel disease patients with HGDHigh grade dysplasia:

  • the natural history of HGDHigh grade dysplasia and the degree of risk that a given patient will develop cancer
  • comparative patient outcomes after colectomy 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 IBDInflammatory bowel disease? (MNG2)

Systematic review evidence

The systematic review identified only one publication that met the inclusion criteria: the SCENICSurveillance for colorectal endoscopic neoplasia detection and management in inflammatory bowel disease patients: International Consensus recommendations International Consensus Statement on Surveillance and Management of Dysplasia in Inflammatory Bowel Disease.[1] Dysplasia in IBDInflammatory bowel disease 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 SCENICSurveillance for colorectal endoscopic neoplasia detection and management in inflammatory bowel disease patients: International Consensus recommendations 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, SCENICSurveillance for colorectal endoscopic neoplasia detection and management in inflammatory bowel disease patients: International Consensus recommendations 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 HGDHigh grade dysplasia is indicative of a more aggressive lesion than low-grade dysplasia (LGDLow grade dysplasia). 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 HGDHigh grade dysplasia was considered separately in the SCENICSurveillance for colorectal endoscopic neoplasia detection and management in inflammatory bowel disease patients: International Consensus recommendations Statement, because the natural history of these lesions is likely to be different.[1]
Non-resectable high grade dysplasia
Patients with endoscopically non-resectable HGDHigh grade dysplasia should undergo colectomy.[1]
Resectable polypoid high grade dysplasia

Of the studies that reported outcomes for polypoid HGDHigh grade dysplasia, most studies were heterogeneous in that both LGDLow grade dysplasia and HGDHigh grade dysplasia were included.[1] Only one study reported on outcomes for patients with polypoid HGDHigh grade dysplasia alone. Of the six studies that reported on the incidence of CRCColorectal cancer in patients with LGDLow grade dysplasia and HGDHigh grade dysplasia, most patients had LGDLow grade dysplasia. Over a mean follow up period of 36–82 months, 19 of 311 patients developed a CRCColorectal cancer. The overall incidence of CRCColorectal cancer was 6% with a range of 2–13%. In the only study that focused on polypoid HGDHigh grade dysplasia, none of the nine patients developed CRCColorectal cancer 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 CRCColorectal cancer incidence of 0.5%, which was considered comparable to that of synchronous and metachronous CRCColorectal cancer.[1] This finding would favour surveillance over colectomy.

Resectable non-polypoid high grade dysplasia

In patients with resectable non-polypoid HGDHigh grade dysplasia, it remains acceptable to offer surveillance over colectomy as most dysplasia will be visible provided that careful, high-quality colonoscopic surveillance is performed by an IBDInflammatory bowel disease expert using high-definition colonoscopy. The use of chromoendoscopy is required to further exclude multi-focal dysplasia. However, the SCENICSurveillance for colorectal endoscopic neoplasia detection and management in inflammatory bowel disease patients: International Consensus recommendations suggestion to offer these patients surveillance colonoscopy rather than colectomy was conditional, given the higher risk of CRCColorectal cancer with non-polypoid HGDHigh grade dysplasia 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 IBDInflammatory bowel disease 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 IBDInflammatory bowel disease patients) reported on the incidence of CRCColorectal cancer after the diagnosis of invisible dysplasia.[1] Over a mean follow up period of 15–50 months, CRCColorectal cancer developed in 7 of 122 (6%, range 3–9%) patients. This contrasts with earlier studies which reported a much higher incidence of synchronous CRCColorectal cancer in the resected specimen when the colectomy was performed for invisible dysplasia. Notably, a systematic review comprising 20 studies, which included 477 patients with invisible LGDLow grade dysplasia reported a CRCColorectal cancer rate of 22% in the resected colectomy specimen.[1][4] An even earlier (1994) systematic review found CRCColorectal cancer in 42% (10 of 24 patients) of patients with invisible HGDHigh grade dysplasia.[5] Subsequent studies have echoed similar rates of CRCColorectal cancer ranging between 45% and 67%.[6][7][8][9] However, it is likely that these high rates of CRCColorectal cancer are related to technological issues in an era where high-definition WLEWhite light endoscopy 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 LGDLow grade dysplasia or colectomy for invisible HGDHigh grade dysplasia therefore no longer stands. Instead, the SCENICSurveillance for colorectal endoscopic neoplasia detection and management in inflammatory bowel disease patients: International Consensus recommendations statement recommended referral to an endoscopist skilled with IBDInflammatory bowel disease 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 colectomy.

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Treatment of high grade dysplasia

No studies were found that compared endoscopic management with colectomy after endoscopic resection of lesions with HGDHigh grade dysplasia, whether polypoid or non-polypoid HGDHigh grade dysplasia.[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 colectomy 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 SCENICSurveillance for colorectal endoscopic neoplasia detection and management in inflammatory bowel disease patients: International Consensus recommendations consensus statement, but the authors described one study in which 199 patients with UCUlcerative colitis were surveyed. The study found that patients preferred colonoscopic surveillance over colectomy unless the risk of synchronous CRCColorectal cancer 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 HGDHigh grade dysplasia, colonoscopic surveillance is preferable over colectomy.

Following complete endoscopic resection of non-polypoid HGDHigh grade dysplasia, colonoscopic surveillance is preferable to colectomy.

III-1 [11], [12], [13], [14], [15], [16], [17], [18]
In the presence of invisible HGDHigh grade dysplasia 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 recommendationA recommendation formulated after a systematic review of the evidence, indicating supporting references.Question mark transparent.png Grade
Patients with endoscopically non-resectable high-grade dysplasia should undergo colectomy.
C
Evidence-based recommendationA recommendation formulated after a systematic review of the evidence, indicating supporting references.Question 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 colectomy.
C
Consensus-based recommendationA recommendation formulated in the absence of quality evidence, after a systematic review of the evidence was conducted and failed to identify admissible evidence on the clinical question.Question 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 recommendationA recommendation formulated in the absence of quality evidence, after a systematic review of the evidence was conducted and failed to identify admissible evidence on the clinical question.Question mark transparent.png

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

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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 HGDHigh grade dysplasia 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-IBDInflammatory bowel disease patients, as published by various societies. The SCENICSurveillance for colorectal endoscopic neoplasia detection and management in inflammatory bowel disease patients: International Consensus recommendations consensus statement[1] recommended that patients with resected HGDHigh grade dysplasia should undergo further surveillance colonoscopy in 3–6 months. Patients with small (<10mm) resected HGDHigh grade dysplasia 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 MAMetachronous adenoma, 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 CAConventional adenoma, 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 SPSerrated polyp, 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 MAMetachronous adenoma, 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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