Management of Barrett s: From Imaging to Resection

Transcription

1 Management of Barrett s: From Imaging to Resection Michael Wallace, MD, MPH, FACG Professor of Medicine Mayo Clinic Florida Goals of Endoscopic Evaluation in Barrett s Detect Barrett s and dysplasia Reduce/eliminate random biopsy Guide therapy in real time Apply effective therapy to reduce cancer risk 1

2 Barrett s, GERD, and Adenocarcinoma Normal Esophagus Chronic mucosal injury Replacement with Intestinal epithelium Progression to dysplasia Progression to cancer Current Guidelines for BE ACG: Wang and Sampliner Am J Gastro 2008;103:788 AGA: Spechler et al Gastro 2011;140:1084 ASGE: Evans et al GIE 2012;76:1087 2

3 Most Recent Recommendation: ASGE Screening in select pts with multiple risk factors. If first screening negative, no further NDBE Surveillance Q 3-5 years Biopsy Q 2cm x 4 quadrant LGD Expert path confirmation yearly surveillance or selected ablation Most Recent Recommendation: ASGE HGD Resection of nodules (EMR) EUS optional Complete eradication of BE with EMR or RFA ASGE: Evans et al. GIE 2012;76:1087 AGA: Spechler et al. Gastro 2011; 2011;140:1084 3

4 Clinical Factors For Progression of BE to Cancer Caucasian Young Age Male Long Segment Smoker Large Hiatal Hernia Obese Family History of BE & EAC ASGE: Evans et al. GIE 2012;76:1087 AGA: Spechler et al. Gastro 2011; 2011;140:1084 Imaging Technologies to Improve Detection of Dysplasia 4

5 Broad Field Techniques (screening) Narrow Band Imaging OCT/OFDI Chromoendoscopy Small Field Techniques (confirmation) NBI +/- zoom Confocal OCT/OFDI The Mosiaic of Barrett s Dysplasia Metaplasia Low-grade dysplasia High-grade dysplasia Adenocarcinoma 5

6 Prospective, controlled tandem endoscopy study of NBI for dysplasia detection EGD (Standard Resolution) Same day procedures back to back EGD (High resolution + NBI) Wolfsen H et al., Gastroenterology, 2008;135:24-31 NBI vs Standard EGD in Barrett s NBI Detects More Patients with Dysplasia NBI 57% Standard 43% p < NBI Detects Higher Grade of Dysplasia NBI 12/65 Standard 0/65 p< Fewer Biopsies Required with NBI NBI 4.7 bx/pt Standard 8.4 bx/pt p <

7 Meta Analysis of NBI for HGD Per patient Sensitivity: 95% Specificity: 97% Estimated NPV: 99.9%* (assumes prevalence 2%) PIVI Thresholds Per-patient sensitivity 90% for HGD Negative predictive value 98% for HGD Specificity 80% Mannath J, et al. Endoscopy 2010;42:351 Meta-Analysis for Advanced Imaging to Guide Bx in BE 34% increased yield for dysplasia with AI-guided bx Qumseya CGH 2013;11:

8 Goals of Endoscopic Therapy Precise imaging to localize neoplasia Complete removal of tumor for staging Endoscopic Resection with Path Staging Assessment of risk for distant (nodal) mets T1m vs deeper, differentiation, lymphovasc inv Eradication of underlying Barrett s RFA, Cryo, resection Minimize morbidity/mortality 2010 MFMER slide-15 Multimodal Therapy 1000 Re esection (m mm) 0 RFA EMR ESD Surgery 0 1mm 1cm Mediastinum Depth to Therapy (microns) 8

9 Tumor Invasion and Lymph nodes Metastasis <1% 25% m1 m2 m3 sm1 sm2 sm3 Epithelial Layer Lamina Propria Muscularis Mucosa Submucosa Technique for Endoscopic Resection Cap-suction methods Cap+snare ( Inoue ) Cap+band ligation ( Duette ) Endoscopic Submucosal Dissection (ESD) 2011 MFMER slide-18 9

10 2011 MFMER slide MFMER slide-20 10

11 Multiband Barrett s Mucosectomy 2010 MFMER slide-21 Endoscopic Treatment vs. Surgery 1618 pts HGD or T1aN0: U.S. Population (SEER-database) Stage, treatment, outcome identified from CMS-linked SEER database 306 (19%) Endoscopic RX 1312 (81%) Surgical Rx Ngamruengphong, Wolfsen, Wallace CGH 2013;11:

12 Survival Trends in Endoscopic vs Surgical Therapy 2010 MFMER slide-24 12

13 Adjuvant Endoscopic Therapies Goal Ablate remaining Barrett s Reduce risk of recurrence Options Radiofrequency ablation Cryotherapy Photodynamic therapy 2010 MFMER slide-25 Circumferential Ablation Focal Ablation US USA, September

14 Complete Response Dysplasia (CR-D) HGD Cohort (n=43) 100% 91% * 80% 80% * RFA Sham 60% * p< % 20% 11% 12% 0% Intention to Treat Per Protocol Shaheen, Sharma, Overholt, Wolfsen et al. NEJM 2009;22:2277 RFA for Dysplasia Is Durable Out to 3 Years AIM Dysplasia Trial Extension Ongoing assessment of 106 treatment arm & crossover pts 91 to 98% dysplasia & IM eradication rate at 2 & 3 yrs Shaheen, Gastroenterology,

15 RFA Reduces Progression in Confirmed Low-Grade Dysplasia Summary of SURF RCT Interim Results - Presented at DDW 2013 (Phoa, Gastroenterology, 2013) European multicenter RCT of 136 confirmed LGD pts Randomized 1:1 to RFA vs. surveillance Per-protocol analysis at 12 mo f/u RFA Control p value CE-D 98% 37% <0.01 CE-IM 98% 0% <0.01 Primary Outcome (Median 21 months follow-up) Progression to HGD/EAC RFA Control p value 1.5% 20.6% <0.01 Caveat: all confirmed LGD. 85% of LGD was not confirmed at expert path review Recommendations BE Surveillance per guidelines Screen high risk patients, Use HD-AI scope Surveillance Q 3-5 years, Use HD-AI scope Low Grade Dysplasia Confirm by expert path Treat if confirmed (RFA) High Grade Dysplasia/T1 cancer Consider referral to expert center HD exam + Adv Imaging (+/- EUS) EMR any focal abnormality Consider ESD if suspected T1 cancer RFA flat BE until fully ablated Surveillance Q 3mn x 1 year, Q 1yr x 5 15

16 Summary Advanced Endoscopic Imaging Increases yield for dysplasia Necessary for targeted therapy Focal (confocal) and widefield (NBI) Endoscopic Therapy Preferred method of HGIN/T1a Outcomes equivalent to surgery Focal (EMR/ESD) and widefield (RFA) Thank you 16

17 Future Directions: BE Imaging Whole esophagus endomicroscopy Direct image guided ablation Non-endoscopic screening/surveillance Confocal Endomicroscopy Pentax/Optiscan Mauna Kea, CellVizio 17

18 Optical Frequency-Domain Imaging Variant of Optical Coherence Tomography Much faster frame rate (100x) than OCT 7 micron resolution 3D imaging to 3.5mm (muscularis propria) Vakoc, GIE, 2007;6:90 Guided Biopsy Paradigm Histopathology Mark Suspect Areas Biopsy at Marks 18

19 Tethered Capsule Endomicroscopy: Gora MJ Nature Med 19:238,