Diagnostic and Therapeutic Approaches to Dysplasia in Inflammatory Bowel Diseases Parakkal Deepak, M.B.B.S., M.S. Assistant Professor of Medicine Division of Gastroenterology John T. Milliken Department of Medicine Washington University School of Medicine March 3, 2018 Colorectal Cancer Conference, Mercy Cancer Center, Des Moines, IA
Financial Disclosures American College of Gastroenterology Junior Faculty Development Award. Research grant: Takeda Pharmaceuticals USA Inc. Advisory board: Pfizer Inc., Janssen Inc. Speaker s bureau: Abbvie.
Case 43 Male AA with pancolonic UC with primary sclerosing cholangitis with bloody diarrhea and iron deficiency anemia Ascending colon Transverse colon Rectum with mass
Outline Inflammatory Bowel Diseases (IBD) 101 Risk of dysplasia in IBD Assessment of dysplasia Management of dysplasia Special considerations for chemotherapy and radiation in IBD
IBD 101
What are Inflammatory Bowel Diseases? Group of chronic diseases that causes inflammation in the large intestines (colon) and/or small intestines (small bowel) Dysregulated immune response to antigenic stimulation from intestinal microbiota on a background of genetic susceptibility Periods of relapse and remission Symptoms vary widely based on disease location and severity of inflammation
IBD 101: TWO MAIN TYPES Ulcerative Colitis (UC) Contiguous & circumferential inflammation from rectum Mucosa and submucosa Colon involvement Erythema, Edema, Loss of vascular pattern, Friability, Granularity Crohn s Disease (CD) Discontinuous, patchy, transmural inflammation Mouth-to-anus involvement Strictures Fistulas and abscesses
Risk of dysplasia in IBD
Risk of Colorectal Cancer in IBD Cumulative incidence of CRC 0.1% 1st decade 2.9% 2nd decade 6.7% 3rd decade 10.0% 4th decade
Risk of ANY Dysplasia in IBD Cumulative incidence of dysplasia 4.1% 10 yrs 14.1% 20 yrs 28% 30 yrs 38.9% 40 yrs
Risk Factors for Dysplasia in IBD Immutable Male sex Longer duration of disease Greater extent of colonic involvement Family history of CRC Younger age of diagnosis PSC Modifiable (potentially) Increased inflammatory activity Backwash ileitis Pseudopolyps Prior dysplasia Mass/stricture Krugliak Rubin. R.D. Cohen (ed.), Inflammatory Bowel Disease, Clinical Gastroenterology, DOI 10.1007/978-3-319-53763-4_7
Colitis-associated Colon Cancer: Genetics and Morphology Sporatic adenoma WLE Adenoma in Colitis WLE Adenoma in Colitis Chomoendoscopy Beaugerie. 2015. NEJM
Why Dysplasia Surveillance is Important?
Assessment of dysplasia in IBD
Guidelines for dysplasia surveillance Initial screening colonoscopy in all UC pts. at 8 10 years after onset of symptoms Crohn s disease pts. with at least one-third of their colon involved need surveillance Initial negative screening requires periodic surveillance every 1 2 years Active colitis and PSC pts. annual colonoscopies
Assessment of dysplasia: SCENIC consensus High definition is recommended rather than standard definition Chromoendoscopy is recommended rather than standard white-light colonoscopy
How to report likely dysplasia in IBD SCENIC, 2015 GIE. ASGE/AGA Dysplasia in IBD Consensus Statement
Chromoendoscopy: Technique Application of dye that is superficially absorbed by intestinal epithelial cells for contrast enhancement and visualization Methylene blue (0.2%,) or indigo carmine (0.4%) spay colon segmentally and visualize on withdrawal Important to have quiescent disease and excellent bowel preparation Chromoendoscopy increases the duration of colonoscopy by 11 min Two 10ml Methylene blue ampule into 500ml of water
WLE vs. CE: Flat lesion with dysplasia Deepak et al. Gastrointest Endosc. 2016 May;83(5):1005-12. Case Presentation: Intriguing enteritis Division of Gastroenterology
Chromoendoscopy: Evidence Chomoendoscopy increases detection of dysplasia per person by 2-3 fold compared to white light endoscopy. ASGE/AGA Dysplasia in IBD Consensus Statement. 2015. GIE; Kiesslich. 2007, Gastro; Wang. 2013, AJG; Marion. 2016 CGH
HD-WLE vs. CE Key limitation: Cross-over design and endoscopist experience Superiority of CE over HD-WLE is not settled Har-Noy et al. Dig Dis Sci. 2017 Nov;62(11):2982-2990.
Narrow Band Imaging (NBI) Conventional Filters decrease the red light, allowing only narrow band of blue light and green light to illuminate the mucosal surface NBI uses blue narrow band light (390-445 nm) and green narrow band light (530-550 nm) Blue light has short wavelength that penetrates most superficially NBI improves the image of mucosal surface patterns and highlights vasculature 400 450 500 550 NBI Slide courtesy David H. Bruining, MD
NBI vs. HD-WLE HD-WLE vs NBI (3 studies): Per-patient analysis OR 0.97 (95% CI 0.59-1.59) Per-lesion analysis OR 1.03 (95% CI 0.66-1.60) NBI similar to HD-WLE with shorter withdrawal times Har-Noy et al. Dig Dis Sci. 2017 Nov;62(11):2982-2990.
NBI vs. CE Two studies included 104 patients/32 lesions in the CE and 104 patients/27 lesions in the NBI group NBI performed as well as CE Per-patient analysis: OR 1.0 (95% CI 0.51-1.95) Per lesion analysis: OR 1.29 (95% CI 0.69-2.41) All used HD scopes NBI performed similar to CE Har-Noy et al. Dig Dis Sci. 2017 Nov;62(11):2982-2990.
CE vs. NBI Per-patient: OR 1.02 (95% CI 0.44-2.35) Per lesion: OR 1.09 (95% CI 0.59-1.99) Total procedural time~7 min shorter with NBI NBI compared to CE: Similar lesion detection Shorter withdrawal times Bisschops R, et al. Gut 2017;0:1 8.
Where to do CE History of dysplasia Up to 57% will have lesion on 1st CE, a new finding in > 50% Considerations for CE in IBD: Primary sclerosing cholangitis (PSC) Multiple pseudopolyps Family history of colon cancer Potentially in pancolitis Deepak et al. Gastrointest Endosc. 2016 May;83(5):1005-12.
Kudo Pit Patterns I IIIs II IV IIIL V
Management of dysplasia in IBD
Shergill et al. Role of endoscopy in IBD. GIE. May 2015Volume 81, Issue 5, Pages 1101 1121.
Shergill et al. Role of endoscopy in IBD. GIE. May 2015Volume 81, Issue 5, Pages 1101 1121.
Surgery for dysplasia Cumulative incidence of colon surgery for dysplasia 1.9% 10 yrs 10.8% 20 yrs 17.4% 30 yrs 24.3% 40 yrs
Special considerations for chemotherapy and radiation in IBD
Effect of cancer treatment on IBD N = 84 IBD patients MGH study: 66.7% with active IBD experienced remission 17.4% of patients in remission experienced a flare Risk of flare greatest among patients who received Adjuvant hormone therapy HR = 12.25 (1.51-99.06) Hormone monotherapy HR = 11.56 (1.39-96.43) Axelrad JE, et al. Clin Gastroenterol Hepatol. 2012;10:1021 1027.
Effect of IBD on cancer treatment 3 studies: N = 47, 66, 28, effect of preop RT in IBD patients Overall, treatment results comparable to those reported for non-ibd-related rectal cancer No excessive rates of toxicity or post-operative complications Low risk of IBD flare Green S, et al. Int J Radiat Oncol Biol Phys. 1999;44:835 840. Bosch, et al. Radiotherapy and Oncology, 2017;123:147 153. Pierre Annede, et al. J Gastrointest Oncol. 2017 Feb; 8(1): 173 179.
Conclusions IBD patients are at increased risk of dysplasia and require surveillance colonoscopy Till better data, chromoendoscopy definitely in: Prior history of dysplasia PSC Family history of colon cancer Multiple pseudopolyps Active pancolitis Dysplasia managed by endoscopic and surgical approaches Optimal chemotherapy and RT is possible in IBD patients
Thank you deepak.parakkal@wustl.edu