1 IBDandNeoplasticProgression:AContemporaryApproachtoDiagnosisandManagement Maui,HI2018 Robert D. Odze, MD, FRCPC Chief, Division of GI Pathology Professor of Pathology Brigham and Women’s Hospital Harvard Medical School Boston, MA Lecture Outline 1. Malignancy risk 2. Surveillance 3. Pathology of dysplasia 4. Natural history and management 5. Summary 3 Comprehensive meta-analysis of the risk of colorectal cancer in ulcerative colitis and Crohn’s disease • 48 studies included in the meta- analysis • Included both population based and referral centers • Included 131,743 persons-years of follow up • Overall cumulative risk at 10, 20 and 20 + years is 1%, 3% and 7% • Rate higher in referral centers and those with extensive disease Lutgens MW, et al. DDW 2008: #194 10 20 >20 Years from diagnosis Cumulative probability (%) Overall Population based Referral center Cumulative risk in IBD patients
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IBD and Neoplastic Progression: A Contemporary Approach to Diagnosis and Management
Maui, HI 2018
Robert D. Odze, MD, FRCPCChief, Division of GI Pathology
Professor of PathologyBrigham and Women’s Hospital
Harvard Medical SchoolBoston, MA
Lecture Outline
1. Malignancy risk
2. Surveillance
3. Pathology of dysplasia
4. Natural history and management
5. Summary
3
Comprehensive meta-analysis of the risk of colorectal cancer in ulcerative colitis and Crohn’s disease
• 48 studies included in the meta-analysis
• Included both population based and referral centers
• Included 131,743 persons-years of follow up
• Overall cumulative risk at 10, 20 and 20 + years is 1%, 3% and 7%
• Rate higher in referral centers and those with extensive disease
Lutgens MW, et al. DDW 2008: #194
10 20 >20
Years from diagnosis
Cum
ulat
ive
prob
abil
ity
(%)
Overall Population based
Referral center
Cumulative risk in IBD patients
2
Factors That Increase Risk of CRC in IBD
• Duration of colitis
• Anatomic extent of disease– No increase in proctitis patients, SIR 2.8 (CI 1.6-4.4) in left sided UC and 14.8
(11.4-18.9) in pancolitis
• Primary sclerosing cholangitis
• Family history of colorectal cancer– Two fold increase
• Age of IBD onset (possibly)
• Severity of endoscopic and histologic inflammationFarraye FA, Odze R, Eaden J, Itzkowitz S. Diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010; 138:746-774.
Extent of Colitis and Cancer Risk(Ekbom et al NEJM 1990)
Extent R.R.
Proctitis 1.7
Left sided 2.8Pancolitis 14.8
Severity of Inflammation is a Risk Factor for Colorectal Neoplasia in Ulcerative Colitis
Variable Cases (neoplasia)* Controls
N=68 N=136 P
Colonoscopy inflammation score
2.22 (0.78) 1.89 (0.52) 0.001
Histology inflammation score
2.38 (0.56) 2.05 (0.41) <0.001
Rutter et al, Gastroenterology 2004;126:451-9Neoplasia = Dysplasia or cancerInflammation grade 0 = normal, 1 = chronic inflammation
2 = mild (cryptitis) 3 = mod (few crypt abscesses)4 = severe (numerous crypt abscesses)
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Inflammation is an Independent Risk Factor for Colonic Neoplasia in Patients with UC: A Case-Control Study
Effect of Surveillance on Mortality from Colorectal Cancer in UC
Author Locale and study dates
Cancers within surveillance
5-yearsurvival
Cancers outside of surveillance
5 yearsurvival
P value
Guiardeillo28 Johns Hopkins, 1956-1991
18* 88% 22 15% <0.001
Choi27 Lahey Clinic, 1974-1991
19 77% 22 36% 0.026
Connell29 St. Mark’s,1947-1992
16 87% 114 55% 0.024
*Includes cancers detected at surveillance colonoscopy or prophylactic colectomy
Chromoendoscopy Examples
(A) The native colonic mucosa shows areas of focal erythema
(B) After CE, a flat lesion is seen that correlates with HGD on histology
Kiesslich R, et al. Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Gastro 2003;124:880-8.
Controlled Studies on the Use of Chromoendoscopy in Patients with Ulcerative Colitis
Study Number of patients
DyeMB=methylene blueIC=Indigocarmine
Number of lesions Difference (x-fold)
Kiesslich et al. (2003) 165 MB 42 (32 vs 10) 3.07
Hurlstone et al. (2004) 324 IC and magnification 93 (69 vs 24) 3.81
Rutter et al. (2004) 100 IC 7 (7 vs 0) 4.50
Kiesslich et al. (2007) 153 MB and Confocal Endomicroscopy
23 (19 vs 4) 4.75
Marion et al. (2008) 102 MB 20 (17 vs 9) 5.66
Kiesslich R, et al. Endoscopic Surveillance in UC: Smart biopsies do it better. Gastro 2007;133:742-5. Kiesslich R, et al. Is chromoendoscopy the new standard for cancer surveillance in patients with ulcerative colitis? Nat Clin Pract Gastroenterol Hepatol. 2009 Mar;6(3):134-5.
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The Future of Endoscopic Imaging in Patients with IBD
Kiesslich R, et al. Endoscopic Surveillance in UC: Smart biopsies do it better. Gastro 2007;133:742-5.
What role do the newer imaging techniques play in identifying and managing dysplasia?
• The sensitivity of chromoendoscopy for detecting dysplasia is higher than white light endoscopy in the hands of endoscopists who have expertise with this technique.
• The natural history of chromoendoscopically detected dysplasia is unknown.
• Additional studies are needed to evaluate the efficiency of other imaging methods, such as narrow band imaging and confocal endomicroscopy, in detecting dysplasia.
Farraye FA, Odze R, Eaden J, Itzkowitz S. Diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology 2010; 138:746-774.
Cairns SR, Scholefield JH, Steele RJ, et al. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut. 2010;59(5):666-89.
1. Negative for neoplasia/dysplasia Negative for dysplasia2. Indefinite for neoplasia/dysplasia Indefinite for dysplasia3. Non-invasive low-grade neoplasia Low-grade dysplasia