1. ESOFAGO DI BARRETT TERAPIA MEDICA & ENDOSCOPICA Massimo Conio Sanremo Massimo Conio Sanremo

2. Barrett's Esophagus & HGD Strategies Passive:surveillance Active:endotherapy surgery chemoprevention Passive:surveillance Active:endotherapy surgery chemoprevention

3. Barrett's Esophagus & HGD 58 patientsfollow-up: 10 years  26%invasive cancer  27%“regression” 58 patientsfollow-up: 10 years  26%invasive cancer  27%“regression” Gastroenterology 1996

4. ChemopreventionChemoprevention COX-2 inhibition Prostaglandins enhance:  Proliferation  Angiogenesis  Invasiveness  Apoptosis inhibition COX-2 inhibition Prostaglandins enhance:  Proliferation  Angiogenesis  Invasiveness  Apoptosis inhibition

5. 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Years of follow-up Dysplasia rate % El-Serag et al., Am J Gastroenterol 2004 No PPI Therapy PPI Therapy

6. Esophagectomy (40% simultaneous foci of intramucosal cancer)  Morbidity48%  Mortality2-3% Barrett’s Esophagus with High-Grade Dysplasia

7. CP1109264-26 Barrett’s with High-Grade Dysplasia On Biopsy. No Visible Lesion.

8. SCJ Barrett's Esophagus;Histologic Maps of Surgical Resections Barrett's, no dysplasia Low-grade dysplasia High-grade dysplasia Adenocarcinoma CP1109264-27

9. Photodynamic therapy (PDT) sodium porfimer (Photofrin®) 5-aminolevulinic acid Thermal Laser (Nd:YAG, KTP) Argon Plasma Coagulator (APC) MPEC Mechanical Ultrasonic Microwave Cryotherapy Endoscopic Ablative Therapies For Barrett’s Esophagus With HGD

10. Esophagus: Japanese data About 1000 patients “En-bloc” (< 3 cm)CR 100% Piecemeal (  3 cm)CR 86% (N1: 23%) About 1000 patients “En-bloc” (< 3 cm)CR 100% Piecemeal (  3 cm)CR 86% (N1: 23%) 5-year survival97.9%(surgery: 98%)

11.  Visible nodular abnormalities  Comorbidities/Advanced age  Efficacy to be determined Endoscopic Mucosal Resection (EMR) Barrett’s Esophagus

13. When not to do EMR 20 Mhz probe EUS at 7.5 MHz

14. Superficial cancers

16. m sm pm1 pm2

20. Oblique aspiration mucosectomy device Attached to tip of conventional endoscope. Tanabe et al. Gastrointest Endosc, 2004

22. GROUP A GROUP B N. Sessions (mean)*1.3  0.62.8  2.0 Complete remission* 97%59% Complications1 spurting1 oozing *statistically significant EMR in Barrett’s esophagus with HGD Ell et al., Gastroenterology 2000

23. EMR in Barrett’s esophagus Change in the diagnosis: 44% 32% up-staging Change in the diagnosis: 44% 32% up-staging Nijhawan et al., Gastrointest Endosc 2000

24. May 2000 – December 2003:  39 pts (mean age 62.8±11.4 yrs)  Mucosal abnormalities: 36  EUS 20-MHz May 2000 – December 2003:  39 pts (mean age 62.8±11.4 yrs)  Mucosal abnormalities: 36  EUS 20-MHz EMR for High-Grade Dysplasia and Intramucosal Cancer Conio, Repici, Cestari, World J Gastroenterol 2005

25. Histology of lesions HistologyPre-EMRPost-EMR LGD-5 (12.8%) HGD35 (89.7%)27 (69.2%) IM. AC4 (10.3%)2 (5.1%) Invasive AC-5 (12.8%) Change of the original diagnosis 25.6%

26. EMR for HGD and/or Intramucosal Cancer AC sm 3 AC >> Surgery (no residual disease) 2 AC >> Follow-up (cancer free) Complications Bleeding4 patients (endoscopic treatment) Follow-up (median 20 months) 1 recurrence (HGD) >> EMR AC sm 3 AC >> Surgery (no residual disease) 2 AC >> Follow-up (cancer free) Complications Bleeding4 patients (endoscopic treatment) Follow-up (median 20 months) 1 recurrence (HGD) >> EMR

29. EMR and PDT in Barrett’s esophagus Downstaging: 8 (47%) Follow-up 13 months:CR 16 (94%) Complications:stricture 30% bleeding 6% Downstaging: 8 (47%) Follow-up 13 months:CR 16 (94%) Complications:stricture 30% bleeding 6% Buttar, Gastrointest Endosc 2001 17 patients (EMR  1 cm) (PDT 200J/cm 2 )

30. Circumferential EMR Multifocal HGD & IM cancer  5 “visible” and 7 “no visible” lesions  Circumferential BE: median length 5 cm  Complications: 4/31 EMR sessions (bleeding)  Follow-up: no recurrences (median 9 mo) Multifocal HGD & IM cancer  5 “visible” and 7 “no visible” lesions  Circumferential BE: median length 5 cm  Complications: 4/31 EMR sessions (bleeding)  Follow-up: no recurrences (median 9 mo) Seewald et al., Gastrointest Endosc 2003

31. Circumferential EMR in Barrett’s Esophagus  21 pts (19 T1N0; 2 T0N0)  EUS 20-MHz  Polypectomy snare & saline  Circumferential BE: median length 5 cm  Complications: 4/21 (bleeding)  Follow-up: 2/21 (mean 18 months)  21 pts (19 T1N0; 2 T0N0)  EUS 20-MHz  Polypectomy snare & saline  Circumferential BE: median length 5 cm  Complications: 4/21 (bleeding)  Follow-up: 2/21 (mean 18 months) Giovannini et al., Endoscopy 2004

35. 1 st endoscope: lifting 2 nd endoscope:cutting Kuwano et al., Ann Surg 2004 Double Endoscopic Intraluminal Operation (DEILO)

38. CP1109264-1 Adenocarcinoma of Cardia with Short Barrett’s

39. Summary  Surveillance finds dysplasia or early cancer  New endoscopic diagnostic method  EMR: long term results awaited  EMR for non-dysplastic Barrett’s  Surveillance finds dysplasia or early cancer  New endoscopic diagnostic method  EMR: long term results awaited  EMR for non-dysplastic Barrett’s