radiofrequency ablation for barrett’s esophagus with hgd gregory g. ginsberg, m.d. professor of...
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Radiofrequency Ablation Radiofrequency Ablation for Barrett’s Esophagus for Barrett’s Esophagus
with HGDwith HGD
Gregory G. Ginsberg, M.D.
Professor of Medicine
University of Pennsylvania School of Medicine
Abramson Cancer Center
Gastroenterology Division
Executive Director of Endoscopic Services
University of Pennsylvania Health Systems
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Learning Objectives:Learning Objectives:
What is Radiofrequency Ablation? What are the indications for use of
RFA in Barrett’s? What are the clinical results? What are the risks and potential
limitations?
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What is Radiofrequency Ablation?What is Radiofrequency Ablation?
Implies destruction and, ultimately, removal of tissue
Mechanism: thermal energy to promote coagulative necrosis
Endpoint is irreversible cell injury and death
Seminal observation: BE, when ablated in an anacidic milieu, regenerates squamous epithelium
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RF Electrode TechnologyRF Electrode Technology
MagnifiedElectrode
• High power
• Rapid delivery (very short “on” time)
• Energy density control
• Tight electrode spacing
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Human Esophagus
Muscularis mucosa (Ablation Target Depth)
Submucosa with esophageal glands
Muscularis propria
Ablation Target
GG
Controlling ablation
depth avoids stricture
EMR Depth
Surgical Depth
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Radiofrequency Balloon-Based Radiofrequency Balloon-Based Ablation Therapy (BARRx)Ablation Therapy (BARRx)
Uniform circumferential ablation 3 cm in length Individualized with sizing balloon Precise energy delivery in < 1 sec
HALO 360 °
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HALO 360 RFAHALO 360 RFA
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HALOHALO9090 Device Device
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HALO 90 RFAHALO 90 RFA
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How does RFA compare with other How does RFA compare with other therapies for BE with HGD/ImCa ? therapies for BE with HGD/ImCa ?
Ablation Thermal (MPEC, LASER, APBC) Chryotherapy Cytotoxic (PDT)
Resection Endoscopic Mucosal Resection (EMR)
Provides histologic specimen for inspection
Reliable, reproducible, broad field, real time, endoscopically directed, immediately observed results, efficiently (time & cost)
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Acid Reflux
Barrett’s
LGD
HGD
EMC
Invasive Carcinoma
Intervention
Intervention
Why Do We Care About BE?Why Do We Care About BE?
AdenoCA Esophagus & EG-J is increasing
Most, if not all, associated with Barrett’s
30 to 125-fold increase cancer risk 1% - 5% life-time (0.5% per yr)
cancer risk
Pera et al. Gastro 1993;104:510, Corley et al. Gastro 2002;122:633.
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What is the Fate of BE Dysplasia?What is the Fate of BE Dysplasia?
Inter-observer variability (85% agree HGD) 13-43% HGD on Bx have CA at
esophagectomy 16-60% HGD on Bx develop CA in 5-7 yr However: ~ 50% remain stable
~ 25% regress to LGD Multi-focal >> Uni-focal HGD (56% vs 14%) LGD: 62-65% regress; 12-25% persist;
10-28% progress
Goal of surveillance is detection of dysplasia
Spechler. NEJM 2002;346:836; Omsby, et al. Gut 2002;51:671Schnell, et al. Gastro 2001;120:1607; AJG 2000;95:3383; 2001;96:1355; Gastro 2001;120:1630
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Selective Clinical Trial and Selective Clinical Trial and Observational HighlightsObservational Highlights
AIM Clinical Trial (n=102) Dosimetry & effectiveness trial, IM 2-6 cm, 1 year f/u Sharma VK, et al Gastrointest Endosc 2007;65:185-202. Short-term safety and efficacy for non-dysplastic BE
US HGD Registry HALO 360/90 for HGD indication Ganz R, et al. Gastrointest Endosc 2008; in press. 142 pt, median f/u 1 yr, 92 pt > 1 BX f/u:
CR-HGD 90.2% CR-D 80.4% CR-IM 54.3%
Combined modality therapy with ER ER followed by RFA in 6 pts. Gondrie JJ, et al. Endoscopy 2008; in press
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AIM Dysplasia Trial: DDW 2008AIM Dysplasia Trial: DDW 2008
U.S. multi-center, randomized, single-blind, sham-controlled trial 2:1 RFA vs sham length stratified (1-4 cm vs 4-8 cm) four maximum RFA sessions identical biopsy protocols, equal
sampling 12 mo cross-over to treatment for all 127 patients
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Interim Analysis Interim Analysis 12 month CR-D (HGD Cohort)12 month CR-D (HGD Cohort)
RFA Sham
ITT 67%* 0%
PP 83%** 0%
*p<0.05, **p<0.001
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Interim Analysis Interim Analysis 12 month CR-D (LGD Cohort)12 month CR-D (LGD Cohort)
RFA Sham
ITT 96%** 33%
PP 100%** 36%
*p<0.05, **p<0.001
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Interim Analysis Interim Analysis 12 month CR-IM (all)12 month CR-IM (all)
RFA Sham
ITT 74%** 0%
PP 83%** 0%
*p<0.05, **p<0.001
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Impact on Cancer Progression?Impact on Cancer Progression?
Treatment Group (n=1) Any dysplasia grade to AdenoCa (n=0, 0.0%) LGD to HGD: (n=1, 1.2%)
Sham Group (n=7) HGD to AdenoCa : (n=4, 19.0%)
All 4 removed from trial for treatment Patient #1 had EMR+HALO, now CR-IM at 12 months Patient #2-3: esophagectomy based on pathology
findings Patient #4: pending EMR staging
LGD to HGD: (n=3, 13.6%) remain in trial, will cross-over to treatment
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How about “Buried Barrett’s”?How about “Buried Barrett’s”?
Subsquamous IM: Baseline incidence of SSIM (25%)
21% of patients in HGD cohort 30% of LGD cohort
12 month incidence of SSIM 42% of patients in sham group 2% of patients in RFA group
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Adverse Events?Adverse Events?
Chest pain & odynophagia (manageable) Transient dysphagia Strictures (uncommon ~3%)
Circumferential ablation Excess dosing Adjunctive to ELR Respond to dilation
Bleeding (rare, coagulopathy) Perforation (rare, technique dependent)
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RFA for BE ConclusionsRFA for BE Conclusions
Appears to be safe and well tolerated Data from non-dysplastic cohorts resolved
dosimetry and durability issues Data from dysplastic cohorts demonstrate
differences in histological outcomes as well as cancer progression outcomes
Acceptable post ablation pain Few strictures “Buried Barrett’s” is uncommon Nuances to optimize therapy still emerging Needs validation & longer follow in BE with HGD Application in nondysplastic BE remains
unsupported