Update in Endoscopic Therapy for Upper GI Malignancies

1. Update in Endoscopic Therapy for Upper GI Malignancies Jon P Walker, MD MS The Ohio State University Medical Center October 8th, 2010

2. Disclosure • No financial disclosures to report • Will discuss off-label usage of a product.

3. Overview • Endoscopic management of high grade dysplasia • Endoscopic management of superficial malignancies • Maintenance of Luminal Patency

4. Management of High Grade Dysplasia and Superficial Malignancy • Surgical management (resection) • First consideration • Surgical candidate? • Radiofrequency ablation • BARRX • Photodynamic therapy • Endoscopic mucosal resection • Nodule • Clearing of focal area of dysplasia

5. Management of High Grade Dysplasia and Superficial Malignancy • Endoscopic therapy for superficial malignancy only! • No seriously…really superficial malignancy. • T1sm vs T1m very important • Mucosal involvement 5-8% LN involvement • Submucosal involvement 25-40% LN involvement

6. Endoscopic Mucosal Resection • Procedure • Submucosal injection of saline/epinephrine/dye • Banding of the lesion; snare resection of the lesion • Benefit: Both staging & resection • Planning of next step in treatment • Inaccuracy of EUS staging • EUS 29% accurate for T1 tumors & 45% accurate for T2 tumors. (Zuccaroet al Am J Gastroenterol2005) • Recent studies showing accuracy 70-80% • Risks • Bleeding, perforation, chest pain, stricture • Follow up ablative therapy

7. Endoscopic Mucosal Resection

8. Endoscopic Mucosal Resection Courtesy Todd Baron MD; Dave Project.org

9. Endoscopic Mucosal Resection • 68y/o WM with recent EGD for epigastric pain. • EGD: Approx 1cm sessile lesion in setting of short segment Barretts esophagus • Biopsy: high grade dysplasia with at least intramucosal adenocarcinoma • Multiple medical problems. Considered poor candidate for elective esophagectomy • EUS: T1m lesion; No lymphadenopathy

10. Endoscopic Mucosal Resection

11. Endoscopic Mucosal Resection

12. Endoscopic Mucosal Recection • Follow up pathology: HGD w/ intramucosal carcinoma. • No evidence of lymphovascular invasion • No evidence of submucosal invasion • Scheduled for subsequent Barrett’s ablation

13. Endoscopic Mucosal Resection • 75y/o WM with recent EGD for anemia • Demonstrated 1.5cm distal esophageal lesion • Biopsy revealed high grade dysplasia w/ at least intramucosal carcinoma • Poor surgical candidate for elective esophagectomy • EUS: T1m lesion. No lymphadenopathy • EMR performed

14. Endoscopic Mucosal Resection

15. Endoscopic Mucosal Resection

16. Endoscopic Mucosal Resection • Pathology: Well-differentiated adenocarcinoma with foci of submucosal invasion. • Surgical options offered.

17. Endoscopic Mucosal Resection 64 patients w/ HGD (n=3) or T1 EC (n=61) treated with EMR Low Risk Group High Risk Group N=29 Some invasion of submucosa Greater than 2cm lesion Poorly differentiated 59% achieved CR @12mos • N=35 • Limited to mucosa • Less than 2cm lesion • 97% achieved CR @12mos vs Ell et al Gastroenterology 2000

18. Endoscopic Mucosal Resection 64 patients w/ HGD (n=3) or T1 EC (n=61) treated with EMR Low Risk Group High Risk Group N=29 Some invasion of submucosa Greater than 2cm lesion Poorly differentiated 59% achieved CR @12mos • N=35 • Limited to mucosa • Less than 2cm lesion • 97% achieved CR @12mos vs Ell et al Gastroenterology 2000

19. Endoscopic Mucosal Resection • Follow up to prior study • 100 patients • Low risk • 37 months follow up • 99% local remission at 12 months • 11% metachronous lesion • Approx 50% ablative therapy of non-dysplastic Barretts Ell et al GastrointestEndoscop 2007

20. Ablative Therapies • Laser • Argon Plasma Coagulation • Bipolar Electric Coagulation • Cryotherapy • Photodynamic Therapy • Radiofrequency Ablation

21. Ablative Therapies • Laser • Argon Plasma Coagulation • Bipolar Electric Coagulation • Cryotherapy • Photodynamic Therapy • Radiofrequency Ablation

22. Photodynamic Therapy • Nonthermal ablative therapy • Administration of photosensitizing agent followed by focal exposure of lesion to specific wavelength of light • Overholt et al Gastrointest Endoscopy 2003 • 105pts w/ HGD or Superficial Cancer • 78% eradication w/ HGD; 44% w/ cancer • Overholt et al Gastrointest Endoscopy 2005 • Similar findings w/ HGD • Recurrence rate of up to 20%

23. Photodynamic TherapyLimitations • Chest pain • Odynophagia • Cutaneous Photosensitivity • Stricture • 27-40% stricture formation reported • Risk factors for stricture • Prior EMR • Prior stricture • Number of applications • Usually treatable with dilations

24. Radiofrequency Ablation • Topical focal application of radiofrequency ablation. • Superficial uniform thermal therapy over wide-field • Application by 360 or 90 degree delivery system • Most frequent complication:chest pain • Stricture rate: 0-8%

25. Radiofrequency Ablation Shaheen et al NEJM 2009 Ganz et al Gastointest Endosc 2006 22 patients w/ RFA for HGD 73% complete eradication No stricture or serious adverse effects • Evaluation of BARRX therapy for eradication of Barretts dysplasia • 127 patients randomized to RFA vs sham • 81% vs 19% total eradication of HGD • 1.2% vs 9.3% development of cancer • 6% stricture

26. Factors to Consider When Offering Endoscopic Therapy • HGD only • Early Cancer within the mucosa only • Visible lesion less than 20mm • Well-differentiated to moderate • No lymph node involvement • No mets on CT • Patient desire to avoid surgery and compliance with endoscopic follow-up Sarah Rodriguez Esophageal Cancer 2009

27. Luminal Access • Stent placement • Polyflex stent placement • Metal stents • Uncovered stent placement • Partially covered stent placement • Fully covered stents • Photodynamic therapy • Laser therapy – Argon Beam Coagulation • Brachytherapy

28. Stent Placement

29. Stent Placement

30. Stent Placement • Issues to keep in mind • Chest pain • Migration • Palliation • Will stent really improve current diet • Tolerance for endoscopy • Reflux

31. Plastic Stent Placement • Polyflex stent - silicone • Removability • Temporary • Easy placement • Bridge to surgery • Difficult to assemble • Bulky (poorly tolerated) • Migration

32. Polyflex Stent Placement Adler et al Gastrointestinal Endoscopy 2009 Bowers et al Annals of Surgical Oncology 2009 58 patients received stent, feeding tube or nothing Statistically better outcome in the stent group Rate of interruption of chemo Albumin level Weight loss Migration rate: 24% • 13 patient w/ Polyflex stent for neoadjuvant therapy • No bleeding/perforation • Chest pain 12/13 patients • Dysphagia score from 3 to 1.1, 0.8,0.9,1.0 on weeks 1,2,3,4, respectively. • Migration 6/13 patients at some point

33. Esophageal StentPolyflex

34. Metal Stent Placement – Partially Covered • Primarily esophageal • Permanent placement • Epithelialization • Complication:better get them out early • Primarily palliation • Luminal access • Fistula • Decreased tumor ingrowth • Overgrowth or Undergrowth • Re-stent if needed

35. Metal Stent – Fully Covered • New product • Minimal migration • Minimal epithelialization • Permanent • ?Removable • Easy to place • Bridging therapy • Radiaton is the issue • Removability is the issue

36. Stent Placement

37. Esophageal Stent Full-covered

38. Esophageal StentsOther roles in esophageal malignancy • Sticture patency maintenance • Post-radiation • Post-ablative therapy of high grade dysplasia • Post-operative anastomotic stricture • Post-operative anastomotic leaks • Requires removable/temporary stent • Fistulas • Tracheoesophageal fistula • Secondary to tumor or radiation therapy • Determination of stent type • Condition duration • Patient prognosis • Luminal diameter • Location of defect

39. Metal Stent - Uncovered • Primarily palliation • Distal stomach and small bowel • Must consider biliary access prior to placement • Tumor ingrowth factor

40. Duodenal Stent

41. Distal Gastric/Proximal Duodenal Tumors • Gastric outlet obstruction • Options • Surgical Gastrojejunostomy (GJJ) • Endoscopic intraluminal stent placement • Dutch SUSTENT Study Group • Long term multicenter trial comparing palliative measures for GOO secondary to malignant obstruction • Stent placement for palliation better than GJJ in patients with life expectancy less than 2 months • GJJ better if longer survival anticipated • Jeurnink Gastrointestinal Endoscopy, 2010 • JeurninkJournal of Gastroenterology, 2010

42. Metal Wall Stent – UncoveredDistal Small Bowel

43. Distal Small Bowel Obstruction

44. Time is shortening. But every day that I challenge this cancer and survive is a victory for me.Ingrid Bergman