1. Endoluminal Treatment of Barrett’s and Early Cancer Brant K. Oelschlager, MD University of Washington

2. CENTER FOR VIDEOENDOSCOPIC SURGERY Paradigm Shifts in GI Diseases

3. CENTER FOR VIDEOENDOSCOPIC SURGERY Dilemma’s Associated with HGD/IM Cancer  Diagnostic  Confidence in the diagnosis has an impact on treatment  Malignant risk of the lesion  Is everyone’s risk the same?  Completeness of Resection/Ablation  How confident can we be?  Morbidity and Mortality of Treatment  Moving target and is provider specific  Eradication of Disease  Cancer, Dysplasia, Barrett’s, GERD

4. CENTER FOR VIDEOENDOSCOPIC SURGERY What we learned from surveillance?  With more accurate diagnosis  Better imaging  Better biopsies  Better pathologic recognition  The incidence of progression to cancer goes down  Fewer cancers go undetected

5. CENTER FOR VIDEOENDOSCOPIC SURGERY Prerequisites for Endoscopic Therapy  No Under-staging  Low failure rate  Accurate assessment of failures  Low complication rate  Excellent functional result  A method for dealing with the underlying disease  ? Consistency among practitioners

6. CENTER FOR VIDEOENDOSCOPIC SURGERY Prerequisites for Surgical Therapy  Low complication rate  Reasonable functional result  ? Consistency among practitioners

7. CENTER FOR VIDEOENDOSCOPIC SURGERY Risk Benefit Choice RISK BENEFIT Surgery 2010 Endo Tx circa 2000 Surgery circa 2000 Endo Tx 2010 FAVORABLE UNFAVORABLE

8. CENTER FOR VIDEOENDOSCOPIC SURGERY Problems with the Literature  Surgical Literature  All patients or those with unfavorable characteristics  Light on Quality of Life  Lack of consistent approach  Endoscopic Literature  Moving target  Lesions with favorable features  Short follow-up  All from the experts and innovators, none from the “community standard”

9. CENTER FOR VIDEOENDOSCOPIC SURGERY Post-Therapy Management  Post-Endoscopic Therapy  Monetary and emotional costs of surveillance  QOL of ongoing GERD  Anti-reflux Surgery  Post-Surgical Therapy  Few effective interventions for gastric emptying and dumping  Do they need surveillance as well  Can’t go back

10. CENTER FOR VIDEOENDOSCOPIC SURGERY Does One Shoe Fit All?  Young vs. Old  Long vs. Short Segment Barrett’s  Unifocal vs. Multifocal Disease  Well differentiated vs. Poorly differentiated  Nodular vs. Flat lesions  Symptomatic vs. Asymptomatic GERD

11. CENTER FOR VIDEOENDOSCOPIC SURGERY Initial Management of HGD/Early CA  Surveillance, Mapping biopsies  Diagnose Cancer  Length of Barrett’s  “Mapping” - Multi-focal disease  EUS  Depth of invasion – Submucosal involvement  Nodal Disease – Contraindication for Endoscopic Therapy  EMR  Diagnostic  Diagnosis of Cancer  Depth of Invasion  Therapeutic

12. CENTER FOR VIDEOENDOSCOPIC SURGERY Assuring the Stage – EUS/EMR KEY!

13. CENTER FOR VIDEOENDOSCOPIC SURGERY Risk of Lymph Node Metastases  15-25% for submucosal involvement  < 3% for intramucosal carcinoma  < 2cm in diameter, w/o ulcer/nodule <1%  Lower risk of metastases than mortality from surgery (0.36% vs. 0.5%)

14. CENTER FOR VIDEOENDOSCOPIC SURGERY Band-Ligation EMR

15. CENTER FOR VIDEOENDOSCOPIC SURGERY EMR: Band Ligation-Snare Technique

16. CENTER FOR VIDEOENDOSCOPIC SURGERY EMR in Early Esophageal Cancer

17. CENTER FOR VIDEOENDOSCOPIC SURGERY Endoscopic Mucosal Resection (EMR)

18. CENTER FOR VIDEOENDOSCOPIC SURGERY Outcome of EMR for HGD/Early Cancer EMR Therapy alone – UC experience 49 Complete EMR eradication 33 HGD 16 IMC 22 patients (45%) – Stage changed 18 (37%) developed stenosis Chennat J. Am J Gastro 2009

19. CENTER FOR VIDEOENDOSCOPIC SURGERY EMR +/- Ablation for Early Cancer  178 patients with T1a AdenoCA  132 Endoscopically Tx  Older  More Comorbidities  46 Esophagectomy  Longer Segment BE  Mean f/u 64 mo  12% recurrence rate in ENDO group  All successfully retreated Prasad GA. Gastroenterology 2009;137:815

20. CENTER FOR VIDEOENDOSCOPIC SURGERY EMR +/- Ablation for Early Cancer = Prasad GA. Gastroenterology 2009;137:815

21. CENTER FOR VIDEOENDOSCOPIC SURGERY Magnified electrode Controlled ablation depth by: Bipolar balloon based electrodeBipolar balloon based electrode Fixed energy densityFixed energy density Fixed powerFixed power Automated RF deliveryAutomated RF delivery Radiofrequency Energy Ablation

22. CENTER FOR VIDEOENDOSCOPIC SURGERY Radiofrequency Energy Ablation

23. CENTER FOR VIDEOENDOSCOPIC SURGERY

24. RFA Ablation for HGD  Multi-centered RCT  Treatment/Sham - 2/1  LGD/HGD  Complications:  Hemorrhage - 1 Patient  Stricture – 5 Patients (6%) Shaheen N. N Eng J Med. 2009;360:2277 n=43/84 n=22/42 n=21/42 77%91%81%

25. CENTER FOR VIDEOENDOSCOPIC SURGERY Multi-Modality Therapy for Early Barrett’s Neoplasia: Endoscopic Resection Followed by Radiofrequency Energy Ablation

26. CENTER FOR VIDEOENDOSCOPIC SURGERY Ablation of Non-Dysplastic Barrett’s  8 Centers – 70 Patients w/ IM (2-6cm)  f/u 1, 3, 6, 12, 30 mo  At 12 months  CR in 48/65 (69% ITT)  -Additional focal ablation-  At 30 months  CR in 60/61 (97% ITT)  No Strictures or buried glandular mucosa  No Serious Adverse Events Fleischer DE. Gastrointest Endosc 2008;68:867.

27. CENTER FOR VIDEOENDOSCOPIC SURGERY Spray Cryotherapy for Dysplastic Barrett’s Esophagus 10 Sites - Retrospective case series for BE with HGD N = 98 patients 29.4% had prior EMR Mean length of BE of cohort was 5.4 cm Mean age was 64.1 years Mean procedure time was 31.4 minutes 10.5 month mean follow up 1 progression to cancer NO SAE’s, Stricture rate 3% patients and 1% of treatments 96.7% with no, mild or moderate pain Median of 4 tx sessions, Treatment complete for 61 patients Efficacy results: 97% complete eradication of HGD 86% complete eradication of dysplasia Segment of BE Before (top) and During Spray Cryotherapy

28. Spray Cryotherapy for Esophageal Cancer 10 Sites - Retrospective case series for Esophageal Cancer N = 79 patients - All patients refused, failed, or were ineligible for conventional therapies! Previous tx: EMR-27, PDT-11, XRT-7, Chemo/XRT-9, Chemo/XRT/Surgery-2, Concurrent XRT-12, Chemo-1, Stent-1, RFA-1, Concurrent EMR-9 Mean age of 76 years 3.7 cm mean tumor length (T1= 60, T2 =16, T3 = 2, T4 =1) 10.8 month average follow up Median of 3 tx sessions Treatment complete for 44 patients CR- CA = 70.5%; CR-HGD = 68.2%, CR-D = 69.1% BD Greenwald et al.: DDW 2009 (10 Centers) Adenocarcinoma 82 year-old T1sm Before After BeforeDuring1 Year After Squamous Carcinoma

29. CENTER FOR VIDEOENDOSCOPIC SURGERY Submucosal Dissection  Major advantage: complete specimen for histopathologic analysis  Uses a electrocautery knife to acquire a single en bloc specimen (higher success rate vs EMR)  Technically difficult, prolonged procedure times  Scarred lesions more difficult  Higher complication rate vs EMR: bleeding, perforation  Limited data: only retrospective with majority performed in Japan studying gastric cancer, no comparative data

30. CENTER FOR VIDEOENDOSCOPIC SURGERY Treatment Algorithm Staging Endoscopy & EUS EMR Frequent Surveillance Esophagectomy Endoscopic Ablation Uni-focal HGD/IM CA Negative Deep/Peripheral Margins Positive Peripheral Margins Positive Deep margins or Lympho-vascular Invasion Multi-focal HGD/IM CA Good Risk Multi-focal HGD/IM CA Poor Risk