Ablation for Barrett s Esophagus: Burn or Freeze

Transcription

1 Ablation for Barrett s Esophagus: Burn or Freeze John R. Saltzman MD Director of Endoscopy Brigham and Women s Hospital Professor of Medicine Harvard Medical School

2 Disclosures No relevant disclosures

3 Objectives To understand the indications for endoscopic ablative therapy in Barrett s esophagus Non-dysplastic Barrett s, LGD and HGD To know the efficacy of treatment with RFA for Barrett s esophagus To be familiar with the side effects of RFA To be aware of the role of cryotherapy for ablation of Barrett s esophagus To understand how to follow patients after endoscopic ablation therapy has been performed

4 Cases/Million Increasing incidence of esophageal adenocarcinoma Adenocarcinoma Squamous Cell Carcinoma Not otherwise specified Pohl H. J Natl Cancer Inst 2005;97:142-6

5 Pathogenesis of Barrett s esophagus Squamous esophagus Chronic inflammation Barrett's metaplasia Injury Acid & bile reflux nitrous oxide Genetics Gender, race,? other factors (cox-2) Low-grade dysplasia High-grade dysplasia Adenocarcinoma Accumulate Genetic Changes Reid BJ. Am J Gastroenterol 2000;95:

6 Barrett s progression to cancer Pathology Annual risk for progression to cancer Non-dysplastic BE % Low grade dysplasia 0.7% High grade dysplasia 7% Hvid-Jensen F. N Engl J Med 2011;365:

7 Low grade dysplasia

8 Is LGD really LGD? LGD in 147 subjects in a community practice in the Netherlands Path reviewed by 2 expert pathologists Disagreement resolved by consensus Results: 85% of cases of LGD down-graded In the 15% with LGD, incidence in followup of HGD or EAC was 13.4%/patient-year Curvers Wl. Am J Gastroenterol 2010;105:

9 Factors that increase risk for progression of LGD Extent of dysplasia (focal versus diffuse) Agreement between pathologists 0% versus 41% versus 80% Biomarkers p53 overexpression (40% versus 10%) Aneusomy, tetraploidy (29% versus 0%) Factors may be additive (p53 and agreement between pathologists) Srivastava A. Am J Gastroenterol 2007;102:483-93

10 High grade dysplasia

11 Treatment of HGD in Barrett s Endoscopic ablation Endoscopic mucosal resection (EMR) Endoscopic submucosal dissection (ESD) Surgical esophagectomy High morbidity and mortality

12 Rationale for endoscopic therapy of Barrett s HGD Risk for progression of the lesion is high Surgical therapy is highly morbid Patients want to be proactive and are prefer a less invasive endoscopic strategy Decreases risk of esophageal cancer

13 Ablative therapy for Barrett s esophagus Attempt to reverse Barrett s esophagus Mainly used to treat LGD and HGD Replace columnar epithelium with squamous epithelium Multiple endoscopic techniques have been tried

14 Ablation techniques Nd-yag laser Photodynamic therapy (PDT) Argon beam plasma coagulation (APC) Radiofrequency ablation (RFA) Cryotherapy

15 Ablation techniques Nd-yag laser Photodynamic therapy (PDT) Argon beam plasma coagulation (APC) Radiofrequency ablation (RFA) Cryotherapy

16 Candidates for endoscopic ablative therapy Patients with flat HGD Patients with nodular HGD (after EMR) Patients with intramucosal carcinoma (after EMR) Patients with LGD (after path confirmation of LGD) Non-dysplastic BE with high-risk factors?

17 Nodular disease must be removed before ablation Ell C. Gastrointest Endosc 2007:65:3-10

18 Depth of therapy Ablation Target Muscularis mucosa RF and cryotherapy depth of ablation Submucosa with esophageal glands G G EMR/PDT Depth Muscularis propria Surgical Depth

19 Ablation of HGD in Barrett s Radiofrequency (BARRX) Bipolar electrode array generates heat to burn < 600 micron depth

20 Radiofrequency ablation catheter 20

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26 Complete response to RFA Before After

27 Standard circumferential ablation regimen Ablation catheter placed over a wire followed by endoscope alongside Ablation catheter inflated to 3 PSI and energy delivered Entire length of BE treated Everything removed and endoscope reintroduced with cap to scrape of coagulum Everything reintroduced and a second round of treatment given to entire BE segment

28 Simplified circumferential ablation regimen Similar procedure as for standard treatment regimen except no cleaning/scraping phase Reduces procedure time by 25 minutes Seems to be equally safe and effective Should not use in patients with complex or tortuous BE (e.g. relative stenosis, narrowing at a resection site) as need to assess completeness of first ablation pass and treat any skipped/missed areas Van Vilsteren FG. Clin Gastroenterol Hepatol 2013;11:

29 Ablation devices

30 Focal ablation of Barrett s Attach flat electrode array to scope tip Use to ablate small areas of BE or to perform touch up after circumferential RFA More difficult to pass in about 10% cases A through the scope small probe is also available mainly for touch up or GE junction RFA

31 Two focal RFA regimens Standard regimen: Double application of 15 J/cm 2 to all areas Use leading edge of electrode array to scrape off coagulum and spray rinse area Repeat a double application of RFA Treat entire Z line with RFA Simplified regimen: As above except 3 applications of therapy and no scraping Seems as effective but may have higher rates of stricture formation (may reduce to 12 J/cm 2 ) Kunzi HT. Endoscopy 2015;47:

32 Post treatment care Acid suppressive therapy key to reduce patient pain and to allow proper healing PPI (esomeprazole) 40 BID Ranitidine 300 QHS Sucralfate susp QID, all for 2 weeks Pain control prn Acetaminophen/codeine Antacid/lidocaine slurry Maintenance PPI after 2 weeks

33 Adverse events Esophageal strictures in 5% Often with prior EMR, especially if >50% circumference removed Narrow esophagus at baseline from GERD Can treat with dilations (1-3 sessions) Post procedure pain in 3% Bleeding in 1% Oman ES. Clin Gastroenterol Hepatol 2013;11:

34 Complete eradication of Barrett s P< % P<0.001 P< % 77.4% 22.7% 19.0% 2.3% Shaheen N. N Engl J Med 2009;360:

35 RFA of high-grade dysplasia Randomized, sham controlled trials have demonstrated excellent efficacy RFA of HGD: Resolution of Barrett s: 67-81% (>75%) Resolution of dysplasia: % (>85%) Molecular markers of Barrett s (Ki67, p53) are lost after RFA Most common complication is stricture formation (7.3%) Shaheen NJ. Gastroenterology 2011;141:460-8

36 RFA of low-grade dysplasia RCT of RFA for Barrett s LGD in 136 pts in 9 centers 26.5% progression rate in control group (HGD or IMC) RFA reduced risk of progression to 1.5% 19% RFA complication rate and stricture rate of 12% Phoa KN. JAMA 2014;311:

37 RFA vs. surveillance of LGD Retrospective multicenter study of RFA vs. surveillance for Barrett s LGD in 170 patients in 3 centers Annual progression rate to HGD or IMC in RFA vs. control group of 0.7 vs. 6.6% Small AJ. Gastroenterology 2015;149:

38 Non-dysplastic Barrett s Decision to whether to perform RFA in NDBE is controversial Risk of progression to cancer is small Many patients with BE are older When to consider ablation of NDBE Young patient (<50 years of age) Long segment of BE Family H/O esophageal cancer

39 Cryotherapy ablation Cold nitrogen gas applied by spray catheter to freeze tissue 87% eradication of dysplasia 5% complication rate Stricture and severe chest pain 3% buried glands Shaheen NJ. Gastrointest Endosc 2010;71:680-5

40 Cryotherapy technique Low pressure liquid nitrogen or CO 2 delivered into esophageal lumen NGT suction to eliminate expandable gas Direct visualization Physician controlled treatment area Broad, focal, deep, or superficial Short procedure times (mean 20 minutes)

41 Cryotherapy

42 Cryotherapy in HGD: retrospective study HGD in 98 subjects at 9 institutions 333 treatments (mean 3.4 per subject) 60 patients completed all cryo treatments Shaheen NJ. Gastrointest Endosc 2010;71:680-5

43 Cryotherapy in HGD: prospective study LGD or HGD (67%) in 96 subjects enrolled in a national cryotherapy registry 321 treatments (mean 3.3 per subject) 80 pts (83%) completed all cryo treatments Results: LGD 91% compete eradication of dysplasia HGD 81% compete eradication of dysplasia Complications of 1 stricture and 1 bleed Ghorbani S. Dis Esophagus 2016;29:241-7

44 Cryoablation balloon Delivers nitrous oxide (N 2 0) cryogen Contained within a balloon Self contained system Results: Preliminary thus far promising Canto MI. Gastrointest Endosc 2016;83(5S):AB159

45 What about buried glands?

46 Esophageal adenocarcinoma under squamous mucosa after ablation Shand A. Gut 2001; 48:580-1 Van Laethem JL. Gut 2000; 46:574-7

47 What do we know? Buried Barrett s seen in up to 28% of patients with Barrett s without treatment RFA ablates most buried glands (after treatment in about 1% of patients) False positive biopsies occur post RFA due to residual Barrett s and tissue artifacts Clinical relevance is still uncertain

48 Follow-up endoscopy Meticulous high quality endoscopic follow-up is a cornerstone of therapy Repeat exam in 12 weeks after ablation Repeat every 12 weeks until ablation is complete Thereafter different recommendations but for HGD I repeat Q 3months x 1 year, then Q 6 months x 1 year then yearly for first 5 years

49 Recurrence post ablation Pasricha S. Clin Gastro Hepatol 2014;12:

50 Barrett s ablation summary Nodular dysplasia should be removed 1 st by EMR Highly effective at eradicating non-dysplastic intestinal metaplasia Eradicates dysplasia (both LGD and HGD) Prevents progression of LGD to HGD Prevents progression of HGD to cancer Technique is easy to perform and quite safe Cryotherapy is an alternative to RFA