Chromoendoscopy and Endomicroscopy for detecting colonic dysplasia Ralf Kiesslich I. Medical Department Johannes Gutenberg University Mainz, Germany Cumulative cancer risk in ulcerative colitis 0.5-1.0% /year after 10 years of disease duration Eaden et al., Gut 2001 1
The incidence of colitis associated cancer is declining! Cumulative cancer risk Study Year Country 10 years 20 years 30 years Eaden 01 2001 Meta-Analyse 1.6% 8.3% 18.4% Winther 04 2004 Denmark 0.4% 1.1% 2.1% Rutter 06 2006 UK 0% 2.5% 7.6% Lakatos 06 2006 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
Three Essential Diagnostic Steps Confirmation Characterization Recognition Recognition 3
Chromoendoscopy Kiesslich et al., Gastroenterology 2003 Magnification & Chromoendoscopy Kiesslich et al., Gastroenterology 2003 4
Circumscribed lesion Pit Pattern Classification Non-Neoplastic Neoplastic (targeted Bx) Kudo et al. Gastrointest Endosc 1996 5
Proofed value of Chromoendoscopy White light imaging versus Pan-Chromoendoscopy in UC Total number of patients = 1544! Neurath, Kiesslich Nat Clin Pract Gastroenterol Hepatol. 2009 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] www.ecco-ibd.deu 6
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 2008 7
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 2008 8
High Definition Endoscopy 9
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. 50 7-7 96% 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
Characterization Digital Chromoendoscopy Filter Techniques: NBI Olympus FICE Fujinon I-Scan Pentax 11
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 2004 12
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 2009 13
I-Scan Endoflag Intelligent Filter System Adaptive differentiation between noise and signal 14
Value of Endoflag in screening colonoscopy Prospective randomized controlled trial Colonoscopy Without With Endoflag Patients 70 50 Patients with at least one adenoma or cancer 15 P=0.044 22 No. of adenomas 17 (17 LGIN) P=0.004 32 (26 LGIN, 4 HGIN, 2 Ca) Kiesslich et al., DDW 2010, submitted 15
Confirmation Endomicroscopy It s not about predicting histology It is about seeing histology 16
Endomicroscopy Field of view: 500x500µm Range: 0-250µm Lateral resolution: <1µm 17
12/17/2009 Fluorescein aided Endomicroscopy Normal Low-grade IN High-grade IN Cancer Fluorescein aided Endomicroscopy Normal colonic crypt architecture 18
12/17/2009 Fluorescein aided Endomicroscopy Low-grade IN Fluorescein aided Endomicroscopy High-grade IN 19
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 2007 20
Confocal Classification Normal Hyperplasia Neoplasia Endomicroscopy of colonic lesions Histology Confocal diagnosis Sites Normal Hyperplasia Inflammation IN Cancer Normal tissue 256 255 1 0 0 0 Regeneration 95 5 78 11 1 0 Neoplasia 39 0 1 1 34 3 Prediction of Neoplasia Sensitivity: 97,4%; Specificity: 99,4%; Accuracy: 99,2% Kiesslich et al., Gastroenterology 2004 21
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 2009 22
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 2007 23
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 2004 24
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 2006 25
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 2009 26
In vivo analysis of EGFR resected human specimens Goetz et al. Gastroenterology 2010, in press Molecular Imaging Anti-VEGF IHC 27
Conclusions: Advanced imaging in IBD Standard Resolution (WLE) Chromoendoscopy Magnification High Definition Endoscopy Virtual Chromoendoscopy Endomicroscopy Molecular Imaging Thank you 28
The future of endoscopic imaging -Videos- Ralf Kiesslich I. Medical Department Johannes Gutenberg University Mainz, Germany Endomicroscopy 29
High Definition, I-Scan, Chromoendoscopy, Endomicroscopy 30
Endoflag new filter system 31
Endomicroscopy In vivo identification of gaps and mucosal bacteria 32
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