Low-grade dysplasia in IBD

From Cancer Guidelines Wiki


Background

In light of the recent 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 (IBDInflammatory bowel disease),[1] flat mucosal dysplasia should be differentiated into visible and invisible. Invisible dysplasia cannot be visualised on high-definition white-light endoscopy (WLEWhite light endoscopy) even after chromoendoscopy enhancement, making resection impossible.

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

Evidence

What should be the protocol to manage low grade dysplasia in IBDInflammatory bowel disease? (MNG3)

Systematic review evidence

Data from tertiary referral centres have generally shown that LGDLow grade dysplasia is associated with progression to high-grade dysplasia (HGDHigh grade dysplasia) or cancer.[2][3] Of 47 patients who were diagnosed with LGDLow grade dysplasia at St Mark’s Hospital (London, UKUnited Kingdom), 20% eventually developed CRCColorectal cancer and 39% developed either HGDHigh grade dysplasia or cancer.[2] In a cohort treated at Mount Sinai Hospital (New York, USAUnited States of America), 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 LGDLow grade dysplasia to advanced neoplasia is slow and not inevitable.[4][5][6]

A meta-analysis of 20 surveillance studies involving 508 cases of LGDLow grade dysplasia 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 value of LGDLow grade dysplasia for concurrent cancer was 25% and for progression to cancer was 8%.[7] Of 159 patients with LGDLow grade dysplasia followed longitudinally, 10 were found to progress to advanced dysplasia on follow up (5 HGDHigh grade dysplasia, 5 cancer) with an overall incidence of 1.34 cases in 100 patient-years. Of 89 subjects with visible LGDLow grade dysplasia that was completely removed (52 identified with standard definition WLEWhite light endoscopy, 17 with high-definition WLEWhite light endoscopy 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 WLEWhite light endoscopy.[7] These data support the use of high-definition endoscopy and/or chromoendoscopy in surveillance following detection of LGDLow grade dysplasia.

Although more lesions can be detected by chromoendoscopy, the impact on CRCColorectal cancer risk remains less certain.[8] Patients in whom invisible dysplasia is detected should be referred to an endoscopist with expertise in chromoendoscopy surveillance for IBDInflammatory bowel disease. 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 colectomy in this setting.[1]

Due to the uncertainty about the predictive value of invisible LGDLow grade dysplasia, it is recommended that surgery be considered if it is multifocal. However, patients with LGDLow grade dysplasia 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 LGDLow grade dysplasia in flat mucosa is less likely to be associated with imminent cancer, and follow-up colonoscopy is reasonable within 6 months in these cases.

Back to top

Overview of additional evidence (non-systematic literature review)

Two retrospective studies, including a total of 223 patients with LGDLow grade dysplasia, reported that rates of progression to high grade dysplasia or colorectal cancer (CRCColorectal cancer) 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 LGDLow grade dysplasia to HGDHigh grade dysplasia and CRCColorectal cancer 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 LGDLow grade dysplasia 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]
LGDLow grade dysplasia arising from flat mucosa should be evaluated for multifocal dysplasia typically by an expert IBDInflammatory bowel disease endoscopist utilising chromoendoscopy with high-definition colonoscopy. III-3 [1], [8]
Following endoscopic resection of LGDLow grade dysplasia, close surveillance is recommended due to the increased risk of synchronous and metachronous dysplasia. III-3 [1], [8]
Evidence-based recommendationA recommendation formulated after a systematic review of the evidence, indicating supporting references.Question 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 recommendationA recommendation formulated after a systematic review of the evidence, indicating supporting references.Question 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 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

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 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

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

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

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

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Multifocal low-grade dysplasia is associated with a sufficiently high risk of future cancer that colectomy 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.

Back to top

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 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.
  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 ColonThe main part of the large bowel, which absorbs water and electrolytes from undigested food (solid waste). Its four parts are the ascending colon, transverse colon, descending colon and sigmoid colon. RectumThe final section of the large bowel, ending at the anus. 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 IDIndefinite dysplasia, 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.


Back to top

Appendices

Jutta's magnifying glass icon.pngPICO question MNG3 View Evidence statement form MNG3Evidence statement form MNG3 View Systematic review report MNG3Systematic review report MNG3
Back to top