Barrett’s Ablation – Who to Rx & What Modality

1. Barrett’s Ablation – Who to Rx & What Modality Richard E. Sampliner, MD Southern Arizona VA Health Care System University of Arizona Health Sciences Center Tucson, Arizona

2. Microscopic Squamous Islands Without Surgery • Sampliner RE, Steinbronn K, Garewal HS, et al. Squamous mucosa overlying columnar epithelium in Barrett’s esophagus in the absence of antireflux surgery. Am J Gastroenterol1988;83:510-12 2

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4. Microscopic Squamous Over Columnar Epithelium • 7 of 45 Barrett’s patients • 6 treated with H2RA • Length 0.4 – 1.9mm • One had prior anti-reflux surgery Sampliner, Am J Gastroenterol 1988;83:510 4

5. Squamous Regrowth • Occurs over intestinal metaplasia • Occurs with medical therapy 5

6. Squamous Islands With Underlying Intestinal Metaplasia • Sharma P, Morales TG, Bhattacharyya A, Garewal HS, Sampliner RE. Squamous islands in Barrett’s esophagus: what lies underneath? Am J Gastroenterol1998;93:332-35 6

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8. Squamous Islands • 22 Barrett’s patients squamous islands biopsied • 18 on PPI, mean duration 2.3 years • 10 underlying intestinal metaplasia • Not necessarily regression Sharma, Am J Gastroenerol 1998;93:332 8

9. Partial Regression an Inadequate Endpoint • 58 year old white male with Barrett’s with HGD – • Open fundoplication 7 months later • 60mg lansoprazole daily 16 months later • Esophagectomy 2 years later after acute respiratory failure due to gastric herniation • Extensive squamous re-epithelialization with underlying intramucosal cancer in resection Sampliner, Am J Gastroenerol 1993;88:2092 9

10. Squamous Repopulation • Can be a cover-up • Goal: No intestinal metaplasia 10

11. Impact of Prolonged Proton Pump Inhibitor in Barrett’s Esophagus • Sampliner RE. Effect of up to three years of high dose lansoprazole on Barrett’s. Am J Gastroenterol1994;89:1844-48 • Sharma P, Sampliner RE, Camargo E. Normalization of esophageal pH with high dose proton pump inhibitor therapy does not result in regression of Barrett’s esophagus. Am J Gastroenterol 1997;92:582-85 11

12. High Dose PPI • 27 long segment Barrett’s • 60mg lansoprazole daily • Mean follow-up 2.9 years • Mean length 5.7+2.3 to 5.3+2.3cm • 6 squamous islands at baseline, 20 at final visit Sampliner, Am J Gastroenterol 1994;89:1844 12

13. Normalization of Esophageal pH With PPI • 8 of 13 patients on 60mg lansoprazole • Mean pH <4 0.8% • Mean length baseline 5.6cm, at 5.7 years 5.0cm • Even normal esophageal pH over an extended period does not eliminate Barrett’s Sharma, Am J Gastroenterol 1997;92:582 13

14. Incidence of Adenocarcinoma • Drewitz DJ, Sampliner RE, Garewal HS. The incidence of adenocarcinoma in Barrett’s esophagus – a prospective study of 170 patients followed 4.8 years. Am J Gastroenterol1997;92:212-15 14

15. Incidence of Adenocarcinoma – 170 Barrett’s Patients Followed 4.8 Years • Prevalence cancers 4% • Incidence – 0.5% per year, 1/208 patient years • Mean age 62, 98% male • Prior estimates up to 2% Drewitz, Am J Gastroenterol 1997;92:212 15

16. Definition of Barrett’s Esophagus • Sharma P, Morales TG, Bhattacharyya A, Garewal HS, Sampliner RE. Dysplasia in short segment Barrett’s esophagus – a prospective 3 year follow up. Am J Gastroenterol1997;92:2012-16 • Sharma P, Morales TG, Sampliner RE. Short segment Barrett’s esophagus: the need for standardization of the definition and of endoscopic criteria. Am J Gastroenterol1998;93:1033-36 • Sharma P, Weston AP, Morales T, Topalovski M, Mayo MS, Sampliner RE. Relative risk of dysplasia for patients with intestinal metaplasia in the distal oesophagus and the gastric cardis. Gut2000;46:9-13 16

17. Barrett’s Esophagus - Diagnosis Barrett’s Esophagus - Diagnosis Columnar-appearing distal esophagus Intestinal metaplasia Sampliner RE, Am J Gastroenterol 2002; 97:1888 17

18. Proposed Classification of Intestinal Metaplasia TerminologyLength Adenocarcinoma Surveillance RiskRecommended LSBE >3cm Yes Yes SSBE <3cm Yes Yes Gastric cardia IM Unclear No Sharma, Am J Gastroenterol 1998;93:1033 18

19. Endoscopic Reversal of Barrett’s Esophagus • Sampliner RE, Hixson LJ, Fennerty MB, Garewal HS. Regression of Barrett’s esophagus by laser ablation in an anacid environment. Dig Dis Sci1993;38:365-68 • Sharma P, Jaffe PE, Bhattacharyya A, Sampliner RE. Durability of new squamous epithelium following endoscopic reversal of Barrett’s esophagus. Gastrointest Endosc1999;50:159-64 • Sampliner RE, Faigel D, Fennerty MB, et al. Effective and safe endoscopic reversal of nondysplastic Barrett’s esophagus with thermal electrocoagulation combined with high dose acid inhibition: a multicenter study. Gastrointest Endosc2001;53:554-58 19

20. Hypothesis for Reversal • Metaplasia result of squamous injury with replacement by abnormal differentiation of esophageal stem cell • Decrease acid and refluxate, reinjure Barrett’s epithelium new squamous repopulation Sampliner, Dig Dis Sci 1993;38:365 20

21. PPI + MPEC • 58 patients with 2-6cm Barrett’s • 40mg omeprazole bid • 6 month post treatment follow-up • 4-quadrant large capacity biopsy every 2cm • No endoscopic Barrett’s – 85% • No endoscopic or histologic – 78% Sampliner, Gastrointest Endosc 2001;53:554 21

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23. New Squamous DurabilityPost Reversal • 11 patients, Barrett’s 4.4cm, omeprazole 49mg/d • Mean 36 month F/U • 7 with interval intestinal metaplasia,½ of times sampled Sharma, Gastrointest Endosc 1999;50:159 23

24. Two Year Durability (IM) - ITT

25. Esophageal Adenocarcinoma & Other Malignancies Pohl, JNCI 2005;97:142 25

26. Esophageal Adenocarcinoma • Lethal • All patients 5 year survival 13% • Most present with advanced, non-curable disease Eloubeide, Am J Gastroenterol 2003;98:627 26

27. Long-Term Survival: Endoscopic & Surgical Therapy of HGD in Barrett’s EMR+PDT Esophagectomy n 129 70 *F/U (mo) 65 60 (p.008) Mortality 9% 8.5% *BE length 5 7 (.003) Cardiac disease 30 14 (.015) Comorbidity 2 0 (<.0001) Wang, Gastroenterology 2007;132:1226 27

28. Cancer Free Survival in the PDT and Surgical Groups Wang, Gastroenterology 2007;132:1226 28

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31. EMR • Excellent specimens • True T staging • Therapeutic role 31

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33. Results Baseline Demographics “Two Year Efficacy Group” 11 patients (22%) had focal RFA at 15 mo per protocol for uneven z-line (not histology-based). No further RFA was allowed unless prior visit histology demonstrated IM (n=3). 33

34. Two Year Durability (IM) - ITT

35. RFA Safety – n=119 • SAE: 4 (3.4%) • 1 bleed, 3 admitted for chest pain (24 hr) • Strictures: 9 (7.6% per patient, 1.9% per case) • 6 after circumferential RFA, 3 after focal RFA • 3/9 had stricture prior to RFA • All resolved with median of 1.5 dilations

36. Endoscopic Ablation – Decision Making Adapted from Wang KK, 2004 36

37. Planning Endoscopic Therapy for Barrett’s Esophagus 37

38. Ablation Techniques • Argon plasma coagulation • Cryotherapy • Endoscopic resection • Multipolar electrocoagulation • Photodynamic therapy • Radio-frequency ablation 38

39. Barrett’s Reversal • Goal: No endoscopic abnormal lining No intestinal metaplasia – sampling a problem • New squamous is durable • Can be done safely • Who should be reversed? 39

40. Target Lesions for Endoscopic Therapy • High-grade dysplasia • Intramucosal adenocarcinoma 40