Low-grade dysplasia in IBD

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Background

In light of the recent SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease (IBD),[1] flat mucosal dysplasia should be differentiated into visible and invisible. Invisible dysplasia cannot be visualised on high-definition white-light endoscopy (WLE) even after chromoendoscopy enhancement, making resection impossible.

The significance of low grade dysplasia (LGD) in flat mucosa is controversial.

Evidence

What should be the protocol to manage low grade dysplasia in IBD? (MNG3)

Systematic review evidence

Data from tertiary referral centres have generally shown that LGD is associated with progression to high-grade dysplasia (HGD) or cancer.[2][3] Of 47 patients who were diagnosed with LGD at St Mark’s Hospital (London, UK), 20% eventually developed CRC and 39% developed either HGD or cancer.[2] In a cohort treated at Mount Sinai Hospital (New York, USA), the rate of progression to higher grades of neoplasia was 53% at 5 years.[3] These results contrast with other data which show progression from LGD to advanced neoplasia is slow and not inevitable.[4][5][6]

A meta-analysis of 20 surveillance studies involving 508 cases of LGD in flat mucosa or dysplastic mass lesions found the cancer incidence to be 14 per 1000 person-years duration (PYD), and the incidence of any advanced lesion was 30 per 1000 PYD. The positive predictive valueA measure for the probability that a subject with a positive screening result truly has the disease for which they are being tested. of LGD for concurrent cancer was 25% and for progression to cancer was 8%.[7] Of 159 patients with LGD followed longitudinally, 10 were found to progress to advanced dysplasia on follow up (5 HGD, 5 cancer) with an overall incidence of 1.34 cases in 100 patient-years. Of 89 subjects with visible LGD that was completely removed (52 identified with standard definition WLE, 17 with high-definition WLE and 20 with chromoendoscopy), 5 patients developed advanced neoplasia (0.97 cases per 100 patient-years), all of whom had undergone surveillance with standard-definition WLE.[7] These data support the use of high-definition endoscopy and/or chromoendoscopy in surveillance following detection of LGD.

Although more lesions can be detected by chromoendoscopy, the impact on CRC risk remains less certain.[8] Patients in whom invisible dysplasia is detected should be referred to an endoscopist with expertise in chromoendoscopy surveillance for IBD. If visible dysplasia is identified, it should be resected endoscopically, if possible. After successful endoscopic resection, initial surveillance colonoscopy should be performed in 3–6 months. There are currently no studies comparing surveillance colonoscopy with colectomyThe surgical removal of all or part of the colon. in this setting.[1]

Due to the uncertainty about the predictive value of invisible LGD, it is recommended that surgery be considered if it is multifocal. However, patients with LGD in flat mucosa who wish to avoid an operation require repeat colonoscopy at 3–6 months, preferably with chromoendoscopy, and thereafter at yearly intervals. A finding of unifocal LGD in flat mucosa is less likely to be associated with imminent cancer, and follow-up colonoscopy is reasonable within 6 months in these cases.

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Overview of additional evidence (non-systematic literature review)

Two retrospective studies, including a total of 223 patients with LGD, reported that rates of progression to high grade dysplasia or colorectal cancer (CRC) were generally low (5–12%) over a median follow-up period of 3–5 years. Flat dysplasia located in the distal colon is associated with higher risk of progression.[9][10] In recent data from a Dutch nationwide study, the progression of LGD to HGD and CRC was 21.9% at an interval of 15 years.[11]Back to top

Evidence summary and recommendations

Evidence summary Level References
The predictive value of LGD in flat mucosa for future cancer is controversial, but probably higher if it is located in multiple synchronous sites. III-2 [2], [7], [3], [4], [5], [6]
LGD arising from flat mucosa should be evaluated for multifocal dysplasia typically by an expert IBD endoscopist utilising chromoendoscopy with high-definition colonoscopy. III-3 [1], [8]
Following endoscopic resection of LGD, close surveillance is recommended due to the increased risk of synchronous and metachronous dysplasia. III-3 [1], [8]
Evidence-based recommendationQuestion mark transparent.png Grade
Unifocal low-grade dysplasia should be followed by ongoing surveillance using high-definition white-light endoscopy and chromoendoscopy at 6 months. If 6-month surveillance colonoscopy is normal, surveillance should be repeated annually.
C
Evidence-based recommendationQuestion mark transparent.png Grade
Low-grade dysplasia in flat mucosa should be evaluated for multifocal dysplasia by an endoscopist with expertise in inflammatory bowel disease surveillance using high-definition white-light endoscopy and/or chromoendoscopy.
C
Consensus-based recommendationQuestion mark transparent.png

Visible dysplasia should be resected endoscopically and then followed up with surveillance colonoscopy with high-definition white-light endoscopy and chromoendoscopy within 3–12 months.

Consensus-based recommendationQuestion mark transparent.png

Consider shorter surveillance intervals for flat dysplasia located in the distal colon, as this is associated with higher risk of progression.

Practice pointQuestion mark transparent.png

When determining an individual’s appropriate surveillance frequency, the risk factors for progression of low-grade dysplasia (LGD) towards high-grade dysplasia (HGD) or colorectal cancer are: older age at diagnosis of LGD (age >55 years), male sex and inflammatory bowel disease duration of >8 years at diagnosis of LGD.

Practice pointQuestion mark transparent.png

Multifocal low-grade dysplasia is associated with a sufficiently high risk of future cancer that colectomyThe surgical removal of all or part of the colon. is usually recommended. Patients who elect to avoid surgery require follow-up surveillance at 3 months, preferably with chromoendoscopy and high-definition white-light endoscopy. If 3-month surveillance colonoscopy is normal, surveillance should be repeated annually.

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References

  1. 1.01.11.21.3 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. 2.02.12.2 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.
  3. 3.03.13.2 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.
  4. 4.04.1 Befrits R, Ljung T, Jaramillo E, Rubio C. Low-grade dysplasia in extensive, long-standing inflammatory bowel disease: a follow-up study. Dis Colon Rectum 2002 May;45(5):615-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12004210.
  5. 5.05.1 Jess T, Loftus EV Jr, Velayos FS, Harmsen WS, Zinsmeister AR, Smyrk TC, et al. Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota. Gastroenterology 2006 Apr;130(4):1039-46 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16618397.
  6. 6.06.1 Lim CH, Dixon MF, Vail A, Forman D, Lynch DA, Axon AT. Ten year follow up of ulcerative colitis patients with and without low grade dysplasia. Gut 2003 Aug;52(8):1127-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12865270.
  7. 7.07.17.2 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.
  8. 8.08.18.2 Ten Hove JR, Mooiweer E, van der Meulen de Jong AE, Dekker E, Ponsioen CY, Siersema PD, et al. Clinical implications of low grade dysplasia found during inflammatory bowel disease surveillance: a retrospective study comparing chromoendoscopy and white-light endoscopy. Endoscopy 2017 Feb;49(2):161-168 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27951611.
  9. 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.
  10. 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.
  11. de Jong ME, van Tilburg SB, Nissen LHC, Kievit W, Nagtegaal ID, Hoentjen F, Derikx LAAP. Long-term risk of high-grade dysplasia and colorectal cancer after low-grade dysplasia in Inflammatory Bowel Disease. A nationwide cohort study. 2018 Feb 14-17; Vienna, Austria. Inflammatory Bowel Diseases, 13th Congress of ECCO; 2018.


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Appendices

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