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Di fronte alla displasia intestinale Colon e Retto

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 intestinale Colon e Retto

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  1. Di fronte alla displasia intestinaleColon e Retto G C Sturniolo Università degli Studi di Padova Dipartimento di Scienze Chirurgiche e Gastroenterologiche

  2. Macroscopic heterogeneity DIAGNOSIS OF DYSPLASIA Elevated (polyp-like, DALM, ALM) Flat Itzkowitz et al., 2004 Gastroenterologia Padova, 2005

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Low Grade Tubuloglandular Adenocarcinoma (LGTGA): from LGD to Cancer Harpaz , Am J Surg Pathol, 2006

  10. 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

  11. 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

  12. Autofluorescence improves neoplasia detection NBI has a moderate accuracy for prediction of histology

  13. 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

  14. Probability of finding CRC at colectomy for LGD/HDG

  15. COLONOSCOPIC MARKERS FOR DYSPLASIA & CRC IN UC Multivariate analysis of Case Control Studies *Indicative of severe inflammation Rutter Gut 2004

  16. For any unit increase in inflammation score a 3-fold increase of advanced neoplasia Gupta, Gatroenterology 2007

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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)

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