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Di fronte alla displasia intestinale Colon e Retto. G C Sturniolo Università degli Studi di Padova Dipartimento di Scienze Chirurgiche e Gastroenterologiche. Macroscopic heterogeneity. DIAGNOSIS OF DYSPLASIA. Elevated (polyp-like, DALM, ALM). Flat. Itzkowitz et al., 2004.
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Di fronte alla displasia intestinaleColon e Retto G C Sturniolo Università degli Studi di Padova Dipartimento di Scienze Chirurgiche e Gastroenterologiche
Macroscopic heterogeneity DIAGNOSIS OF DYSPLASIA Elevated (polyp-like, DALM, ALM) Flat Itzkowitz et al., 2004 Gastroenterologia Padova, 2005
8-10 years for Crohn’s disease colitis and extensive ulcerative colitis 15-20 years left sided ulcerative colitis Two-four random biopsies every 10 cm, additional samples of suspicious areas no<33biopsies (British and American guidelines recommendations 2003) SURVEILLANCE IN IBD Case-control studies Colonoscopic surveillance is able to reduce CRC-related mortality Vleggaar,AP&T,2007
40 pancolitis 30 Proctitis or ileal CD 20 10 0 0 20 30 40 50 Age at diagnosis RISK OF CRC IN UC & CD Cumulative Incidence for CRC Based on Extent of Disease and Age at Diagnosis Cumulative CRC (%) Oldenburg, UEGW, 2008
NOT ALL PATIENTS WITH IBD HAVE THE SAME CRC RISK! Factors that increase CRC risk Factors that decrease CRC risk Rubin, World J Gastroenterol,2008
EARLY COLORECTAL CANCER IN IBD 6.7% simoultaneously IBD/CRC 22% early CRC *patient with left-sided colitis who developed CRC before 15 or 20 years Lutgens, Gut 2008
DIAGNOSIS OF DYSPLASIA Microscopic classification Interobserver agreement for LGD 0.06 – 0.39 between each pair of the 5 gastrointestinal pathologists Indefinite for Dysplasia Low Grade Dysplasia High Grade Dysplasia Itzkowitz et al., 2004; Lim et al 2003
Low Grade Tubuloglandular Adenocarcinoma (LGTGA): from LGTGA to Cancer • LGTGA not a rare entity (11%) • Relatively young patients (mean age 41.5 years) with extensive and long-standing colitis • 23% small size (max 2.2 cm) and flat, escape detection during initial gross examination Harpaz , Am J Surg Pathol, 2006
Low Grade Tubuloglandular Adenocarcinoma (LGTGA): from LGD to Cancer Harpaz , Am J Surg Pathol, 2006
PROSPECTIVE TRIAL CHROMOENDOSCOPY vs RANDOM BIOPSIES 79 UC 23 CD colitis MEDIAN TIME Random/Non-dye targed: 22:11min Dye targed: 15:12 min p=0.001 p=0.057 n° of patients Random Non-dye targed Dye targed POST COLECTOMY FINDINGS Marion, Am J Gastroenterol, 2008
Mild chronic inflammation LGD HGD NBI for the study of DYSPLASIA in UC: a pilot study Honeycomb like Incidence if dysplasia NBI + Tortuos pattern * + + Tortuos pattern + p=0.003, * p=0.038,not confirmed with multiple testing Matsumoto, Gastrointest Endosc, 2007
Autofluorescence improves neoplasia detection NBI has a moderate accuracy for prediction of histology
Chromoscopy-guided endomicroscopy increases the diagnostic yield of intra-epithelial neoplasia in UC Gastroenterologia Padova, 2008 More detection of neoplasia 4.75-fold with 50% fewer biopsies Kiesslich, Gastroenterology, 2007
COLONOSCOPIC MARKERS FOR DYSPLASIA & CRC IN UC Multivariate analysis of Case Control Studies *Indicative of severe inflammation Rutter Gut 2004
For any unit increase in inflammation score a 3-fold increase of advanced neoplasia Gupta, Gatroenterology 2007
Anti TNF-α administration reduces number and tumor size BLOCKING TNF-α IN MICE REDUCES CRC CARCINOGENESIS TNF-alfa increases with time after AOM and DSS treatment proportionately to tumor formation m-RNA level Popivanova, J Clin Invest, 2008
SECONDARY CANCER PREVENTION in LGD: COLECTOMY? • 20% of concurrent CRC • No clinical feature discriminates progressors to no progressors • Progression to CRC even with surveillance • Once detected 9 X risk of CRC and 12 x risk of any advanced lesion (HGD, DALM, CRC) during surveillance • NNC(olonoscope) 6 for advanced histology and NNC 8 for CRC once LGD detected PALAZZO DELLA RAGIONE, PADOVA • Incontinence • Adhesions • Pouchitis • Fertility
Understanding the definition, pathogenesis and biological significance of dysplasia is crucial to the proper management of CRC Chronic inflammation, the persistent state of tissue repair and cell renewal play a key role in colorectal carcinogenesis associated with IBD Colonoscopy plus biopsies is the main method for CRC prevention Dysplasia, CRC and IBD
Chromoendoscopy and targeted biopsies have a greater yield for detection of dysplasia LGD is clinically important endpoint in the surveillance Endoscopic resectability determine the management of polypoid dysplasia in IBD Dysplasia, CRC and IBD
lymphnode +ve if LGD polpys: • Colacchio 4% • Cranley 0% • Geraghty 0% • Kyzer 0% • Dell’Abate 0% • lymphnode +ve if HGD polpys: • Cranley 18% • Geraghty 11.1% • Kyzer 5.6% • Dell’Abate 14.3% Prognostically significant histologic features • distance between the invasive tumor and the cauterized biopsy margin • tumor differentiation • status of lymphatic or vascular invasion (present or absent)