Chromoendoscopy and Endomicroscopy for detecting colonic dysplasia

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1 Chromoendoscopy and Endomicroscopy for detecting colonic dysplasia Ralf Kiesslich I. Medical Department Johannes Gutenberg University Mainz, Germany Cumulative cancer risk in ulcerative colitis % /year after 10 years of disease duration Eaden et al., Gut

2 The incidence of colitis associated cancer is declining! Cumulative cancer risk Study Year Country 10 years 20 years 30 years Eaden Meta-Analyse 1.6% 8.3% 18.4% Winther Denmark 0.4% 1.1% 2.1% Rutter UK 0% 2.5% 7.6% Lakatos Hungary 0.6% 5.4% 7.5% Macroscopic classification of dysplasia Old: New: Flat and invisible Circumscribed after chromoendoscopy DALM: Raised within inflamed mucosa ALM = polypoid (new) Within inflamed or uninflamed mucosa 2

3 Three Essential Diagnostic Steps Confirmation Characterization Recognition Recognition 3

4 Chromoendoscopy Kiesslich et al., Gastroenterology 2003 Magnification & Chromoendoscopy Kiesslich et al., Gastroenterology

5 Circumscribed lesion Pit Pattern Classification Non-Neoplastic Neoplastic (targeted Bx) Kudo et al. Gastrointest Endosc

6 Proofed value of Chromoendoscopy White light imaging versus Pan-Chromoendoscopy in UC Total number of patients = 1544! Neurath, Kiesslich Nat Clin Pract Gastroenterol Hepatol ECCO Consensus 2008 Methylene blue or indigo carmine chromoendoscopy is an alternative to random biopsies for appropriately trained endoscopists and is superior to random biopsies in the detection rate of neoplastic lesions [EL1b, RG B] 6

7 Autofluorescence Autofluorescence 50 patients with long standing UC: surveillance colonoscopy Each colonic segment was inspected twice: AFI WLE random order. Detected lesions: Crypt analysis with NBI Targeted Biopsies Additional random biopsies were taken. van den Broek et al. Gut

8 Autofluorescence van den Broek et al. Gut 2008 Autofuorescence - Results AFI first (n = 25) 10 neoplastic lesions were primarily detected No additional neoplasia in WLE WLE first (n = 25) 3 neoplastic lesions were detected 3 additional neoplasias with AFI No additional patients with neoplasia were detected by random biopsies. van den Broek et al. Gut

9 High Definition Endoscopy 9

10 High definition & Chromoendoscopy Patients with long lasting known CD (>8 years) in stable clinical remission and colonic involvement (without known IN) Age and disease (duration) matched with UC patients and controls (screening for colorectal cancer). Panchromoendoscopy with methylene blue targeted biopsies followed by random biopsies Hoffman et al. DDW 2010, submitted High Definition & Chromoendoscopy N=164; mean age: 44.3 years N No. of IN No. of IN in random Bx No. of circumscribed lesions Prediction of histology (accuracy) Pts. with CD 55 5* 0.0% 22 92% Pts. with UC 59 14* 0.4% 65 93% Control pts % Patients with Crohn s diseases showed a lower prevalence of intraepithelial neoplasia compared to a disease and age matched group of patients with ulcerative The prevalence of IN in patients with CD did not exceed in our study the neoplasia risk of patients undergoing screening colonoscopy. Hoffman et al. DDW 2010, submitted 10

11 Characterization Digital Chromoendoscopy Filter Techniques: NBI Olympus FICE Fujinon I-Scan Pentax 11

12 NBI, I-Scan, FICE Narrowing of light spectrum NBI Post Processing of emitted light I-Scan - FICE Effect: Vessel analyis Effects: Surface analysis Tissue analysis Vessel analyis Narrow Band Imaging Chromoendoscopy Machida et al., Endoscopy

13 NBI in Ulcerative Colitis 42 pts. cross over = No difference between white light endoscopy and NBI Dekker et al., Endoscopy 2007 NBI in Ulcerative Colitis NBI does not improve the detection rate of neoplasia in ulcerative colitis compared to high definition white light endoscopy 49 patients cross over trial NBI 6 patients with neoplasia WLE 11 patients with neoplasia Random biopsies: 0.2% with dysplastic tissue Van den Broek et al., DDW

14 I-Scan Endoflag Intelligent Filter System Adaptive differentiation between noise and signal 14

15 Value of Endoflag in screening colonoscopy Prospective randomized controlled trial Colonoscopy Without With Endoflag Patients Patients with at least one adenoma or cancer 15 P= No. of adenomas 17 (17 LGIN) P= (26 LGIN, 4 HGIN, 2 Ca) Kiesslich et al., DDW 2010, submitted 15

16 Confirmation Endomicroscopy It s not about predicting histology It is about seeing histology 16

17 Endomicroscopy Field of view: 500x500µm Range: 0-250µm Lateral resolution: <1µm 17

18 12/17/2009 Fluorescein aided Endomicroscopy Normal Low-grade IN High-grade IN Cancer Fluorescein aided Endomicroscopy Normal colonic crypt architecture 18

19 12/17/2009 Fluorescein aided Endomicroscopy Low-grade IN Fluorescein aided Endomicroscopy High-grade IN 19

20 Fluorescein aided Endomicroscopy Cancer Colon Cancer Fluorescein aided Endomicroscopy Tissue and vessel analysis of the whole mucosal layer (intravenous injection) Kiesslich et al., Nature Clinical Practice Oncology

21 Confocal Classification Normal Hyperplasia Neoplasia Endomicroscopy of colonic lesions Histology Confocal diagnosis Sites Normal Hyperplasia Inflammation IN Cancer Normal tissue Regeneration Neoplasia Prediction of Neoplasia Sensitivity: 97,4%; Specificity: 99,4%; Accuracy: 99,2% Kiesslich et al., Gastroenterology

22 Colon Cancer Acriflavine aided Endomicroscopy Tissue and nuclei analysis of the superficial mucosal layer (local application) Kiesslich et al., Nature Clinical Practice Oncology 2007 Endomicroscopy of colorectal lesions 116 colorectal polyps (68 adenomas, 6 invasive carcinomas, 30 hyperplastic and 12 inflammatory polyps) from 72 patients Endomicroscopic Adenoma Dysplasia Score (ADS) reliably discriminated high-grade dysplasia from low-grade dysplasia - accuracy, 96.7%. Interobserver agreement was high (kappa: pathologist, 0.92, endomicroscopist, 0.88). In vivo histology predicted ex vivo findings with sensitivity of 97.3%, specificity of 92.8% and accuracy of 95.7%. Sanduleanu et al., Clin Gastroenterol Hepatol

23 Endomicroscopy in Ulcerative Colitis Patients at risk Modern approach in ulcerative colitis Chromoendoscopy 4-fold increased diagnostic yield of intraepithelial neoplasias Endomicroscopy 10-times reduction of biopies per patient ~ 4 Bx/patient Kiesslich et al., Gastroenterology

24 Management of polypoid dysplasia ALM= polypoid within inflamed or uninflamed mucosa Goal - Endoscopic Therapy Preconditions: complete(!) resection Independent of stage (low grade or high grade IN) Absence of neoplastic changes in the surrounding mucosa No other or residual neoplasia in the colon Engelsgjerd et al., Gastroenterology 1999 Rubin et al., Gastroenterology 1999 Odze et al., Clin Gastro Hepatol

25 Early Cancer Low-Grade Tubulo-Glandular Adenocarcinoma (LGTGA) Develops directly from Low-grade IN Association with IBD 11% (!) of all IBD related neoplasias Prevalence similar in CD and UC Multifocal occurrence may be present Often unknown entity Levi and Harpaz, Am J Surg Pathol

26 Endomicroscopy Cell shedding and abnormal gaps can be seen Patients with IBD are showing more dysfunctional gaps Moussata et al. DDW 2008, DDW 2009 Endomicroscopy Intramucosal bacteria can be seen Luminal bacteria can induce shedding and micro erosions Moussata et al. DDW 2008, DDW

27 In vivo analysis of EGFR resected human specimens Goetz et al. Gastroenterology 2010, in press Molecular Imaging Anti-VEGF IHC 27

28 Conclusions: Advanced imaging in IBD Standard Resolution (WLE) Chromoendoscopy Magnification High Definition Endoscopy Virtual Chromoendoscopy Endomicroscopy Molecular Imaging Thank you 28

29 The future of endoscopic imaging -Videos- Ralf Kiesslich I. Medical Department Johannes Gutenberg University Mainz, Germany Endomicroscopy 29

30 High Definition, I-Scan, Chromoendoscopy, Endomicroscopy 30

31 Endoflag new filter system 31

32 Endomicroscopy In vivo identification of gaps and mucosal bacteria 32

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34 Thank you 34