How to characterize dysplastic lesions in IBD?

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1 How to characterize dysplastic lesions in IBD? Name: Institution: Helmut Neumann, MD, PhD, FASGE University Medical Center Mainz

2 What do we know? Patients with IBD carry an increased risk of developing CRC CRC accounts for 10 15% of all death in IBD patients Increased lifetime risk of CRC up to 6 fold Risk factors Greater duration of disease Extent of disease Severity of disease Family history of CRC Presence of primary sclerosing cholangitis (PSC) Samadder NJ et al. Dig Dis Sci 2017 Bernstein CN et al. Cancer 2001

3 Why should we optimize? Low yield of random biopsies in colitis surveillance 466 surveillance colonoscopies in 167 patients 11,772 random biopsies (median 29) 24 detected neoplasia (0.2% per biopsy yield) ~ 1 in 500 random biopsies The yield of random biopsies is low whereas UC associated neoplasia is macroscopically visible in 94% of colonoscopies Van den Broek et al., Am J Gastroenterol 2014

4 How could we optimize? New Techniques Traditional Chromoendoscopy Indigo Carmine, Methylene Blue Optical chromoendoscopy NBI, CBI, i scan OE Digital chromoendoscopy FICE, i scan SPIES Laser Blue Laser Imaging, Endomicroscopy LED FUSE, Blue Light Imaging Spectroscopy WavSTAT CAD LUMOS

5 How could we optimize? THE adequate Technique? 3 randomized trials using first and second generation NBI compared to white-light endoscopy for dysplasia detection. 1. NBI did NOT increase detection rates 2. NBI did NOT allow for differentiation of neoplastic and non-neoplastic tissue. LGIEN Dekker E et al., Endoscopy 2007 Van den Broek FJ et al., Endoscopy 2011 Ignjatovic A et al., Am J Gastroenterol 2012

6 Challenge in IBD Lesions are often flat (non polypoid lesions) Often chronically inflamed mucosa Contrast enhancement

7 Dye-based Chromoendoscopy Indigo Carmine (0.1% 0.5%) 100 patients, rectum and sigmoid 48 patients no polyps BUT after staining 27 had polyps (3mm; 93% hyperplastic; 7% adenomas) Methylene blue (0.1% 1%) 263 patients with ulcerative colitis more intraepithelial neoplasias were found (32 vs. 10; P=.003) Better detection and characterisation of colorectal lesions Kiesslich R et al., Endoscopy 2001 Kiesslich R et al., Gastroenterology 2003

8 Performance of chromoendoscopy in IBD 1. Surveillance when disease is in remission (avoid misdiagnosis inflammation vs. dysplasia) 2. Clean bowel preparation (split dose; free of pus, mucus, blood, stool) 3. Reduce peristaltic waves (e.g. glucagon) 4. Washing of the mucosa during insertion 5. Careful suction to avoid tissue artefacts

9 Performance of chromoendoscopy in IBD Recommendation of the SCENIC consensus statement Remove air before spraying, consider gravity (dye drops down) Spray and evaluate per colonic segment (i.e. right colon, transverse colon,...) Consider dye used (methylene blue = absorptive staining agent) Laine L et al., Gastrointest Endosc 2015

10 Performance of chromoendoscopy in IBD Recommendation of the SCENIC consensus statement Laine L et al., Gastrointest Endosc 2015

11 Chromoendoscopy Meta-analysis including six studies (1277 patients) Difference in dysplasia yield between chromoendoscopy and white-light endoscopy was 7% Number needed to treat of 14.3 Difference of lesions detected was 44% Difference of flat lesions detected was 27% Chromoendoscopy is superior to white-light endoscopy Subramanian V et al., Aliment Pharmacol Ther 2011

12 Interpretation of findings 1. Appearance 2. Inflammation vs. Neoplasia 3. Biopsy vs. Resection

13 Appearance of lesion Endoscopicalresectable or unresectable

14 Appearance of lesion Paris IIa Neumann H and Pohl J., VJGIE 2014

15 Inflammation vs. Neoplasia What should be of concern? Slightly elevated or depressed lesion Friability Discoloration (uneven redness) Villous mucosa or nodularity Obscure vascular pattern Indistinctive borders Enhanced characterisation (more concentrated dye, magnification, CLE)

16 Biopsy vs. resection Biopsies should only taken from lesions which are unresectable Polypectomy/ EMR of endoscopically resectable lesions ESD or KAR in expert setting After resection biopsies from the area surrounding the lesion to rule out dysplasia Consider endoscopic tattooing of non resectable lesions and after endoscopic resection of suspicious dysplastic lesions

17 How good is the pathologist? Kappa Indices for Interobserver Agreement in the diagnosis of dysplasia in ulcerative colitis No dysplasia Indefinite LGD HGD Cancer K =0.51 Good K =0.18 Poor K =0.36 Fair K =0.54? Good 2nd opinion by expert GI pathologist is advised Odze RD et al., Mod Pathol 2002

18 What is the best surveillance strategy? ECCO 2008 BSG 2010 (and AGA 2010 ACG 2010 NICE) 1st screening 8 10 yr 10 yr Max 8 yr 8 10 yr Surveillance interval Extensive: 2 yearly to 20 yr then annually Left sided: 2 yearly starting at 15 yr PSC: 1 yearly Chromoendoscopy Biopsies Superior to white light 33+ if no chromo By risk: Low: 5 yr Intermediate: 3 yr High: 1 yr Recommended 1 3 yr More often at high risk, e.g., PSC Special cases 1 2 yr Not yet 33+ if no chromo East JE. Clin Endosc 2012

19 What is the best surveillance strategy? Dutch nationwide pathology database = diagnosis of CRC was delayed or missed in 17% to 35% of patients when screening was delayed until 8 to 10 or even 15 years. ASGE Guideline, Gastrointest Endosc 2015 Lutgens MW, et al., Gut 2008 Baars JE, et al., J Gastroenterol 2012

20 Conclusion Chromoendoscopy should be used for surveillance if possible. Lesions should be resected en bloc whenever possible. Biopsies should be performed of endoscopically not resectable lesions and from the surrounding mucosa after endoscopic resection. Second opinion of expert GI pathologist for dysplastic lesions in IBD. Regular surveillance starting no later than 8 years after symptom onset and sooner in patients with primary sclerosing cholangitis or strong family history of CRC.