Treatment Options for Barrett`s Esophagus and Other Complications

Treatment Options for
Barrett's Esophagus and
Other Complications of
Acid Reflux Disease
Andrew T. Pellecchia, MD
Crystal Run Healthcare and
Orange Regional Medical Center
1
Barrett’s Prevalence Estimates

1.6% of general adult population (3.3 M)


3.9 - 6.2% of general adult population (7.812.4 M)



Tristan J, et al. The Prevalence of BE in the US (model)...DDW 2009.
Hayeck TJ, et al. The Prevalence of BE in the US (model)…Dis Esophagus 2010; Mar 26.
6.8% of persons over age 40 (8.7 M)


Ronkainen J, et al. Prevalence of BE… Gastroenterology 2005;129:1825-31.
Rex DK, et al. Screening for Barrett’s... Gastroenterology 2003; 125:1670-77.
25% of persons without GERD > age 50 (20
M)

Gerson LB, et al. Prevalence of Barrett’s…Gastroenterology 2002;123:461-7.
2
Endoscopic Surveillance

Sampling error

Cost-ineffective
• Inter Observer Variability
• Inability to detect step-wise progression
2011 AGA Guidelines: “Endoscopic surveillance has become the standard of practice
based on the unproven assumption that the practice will reduce deaths from esophageal
adenocarcinoma…”
Endoscopic Mucosal Resection
HALOFLEX Energy Generator
5
HALO RFA Catheters
HAL0 360 / Circumferential Radio Frequency Ablation
HAL0 90 / Focal Radio Frequency Ablation
6
Baseline, Barrett’s esophagus
Courtesy of Charlie Lightdale, M.D., Columbia Presbyterian, New York
7
Courtesy of Charlie Lightdale, M.D., Columbia Presbyterian, New York
8
Focal RFA
Shaheen, et al. NEJM 2009.
9
Long-term Outcomes
Baseline
Post-RFA: 2 years
10
n
FU
CR‐IM
CR‐D
CR‐HGD
Buried Glands
Stricture Rate
61
30 mo
98.4%
‐‐
‐‐
None
0%
50
60 mo
92%
‐‐
‐‐
None
0%
AIM‐LGD
10
24 mo
90%
100%
‐‐
None
0%
HGD Registry
92
12 mo
54%
80%
90%
None
0.4%
AMC‐I
11
14 mo
100%
100%
‐‐
None
0%
AMC‐II
12
14 mo
100%
100%
‐‐
None
0%
Comm Registry
429
20 mo
77%
100%
‐‐
None
1.1%
EURO‐I
24
15 mo
96%
100%
‐‐
None
4.0%
EURO‐II
118
12+ mo
96%
100%
Emory
27
<12 mo
100%
100%
‐‐
None
0%
Dartmouth
25
20 mo
78%
‐‐
Henry Ford
66
varied
93%
‐‐
‐‐
None
6.0%
Mayo
63
24 mo
79%
89%
‐‐
None
0%
LGD
39
24 mo
87%
95%
‐‐
None
0%
HGD
24
23mo
67%
79%
‐‐
None
0%
127 (RFA 84)
12 mo
77% (83%)
86% (92%)
‐‐
5.1%
6.0%
88
24 mo
93%
95%
‐‐
‐‐
‐‐
47
24 mo
‐‐
‐‐
‐‐
RFA/ER
22
22 mo
96%
96%
‐‐
None
14.0%
SRER
25
25 mo
92%
100%
‐‐
8.0%
88.0%
Clinical Data Summary
AIM‐II Trial
AIM RCT (primary)
Long‐term FU
RFA/ER vs. SRER RT
11
60+ Peer-Reviewed Publications
Disease Eradication
RFA
Sham
CR-D (HGD)* 81.0% 19.0%
CR-D (LGD)* 90.5% 22.7%
CR-IM
77.4% 2.3%
(HGD/LGD)*
*P < 0.001
Disease Progression
RFA
3.6%
All
Progression*
*
Cancer
1.2%
Progression*
**P < 0.05
*
Sham
16.3%
9.3%
Note: These results are
drawn from an intention
to treat analysis.
EMR/RFA v Esophagectomy
Review
(DeMeester, J Thorac CV Surg, 2010)
• Retrospective review of HGD &
early cancer pts undergoing
EMR/RFA (n=40) & esophagectomy
(n=61)
• Median follow up
• 34 mos for esophagectomy
• 17 mos for EMR/RFA
• Similar survival of 94% at 3 yrs
• Morbidity
• 39% for esophagectomy
• 0% for EMR/RFA
• Metachronous lesions
AIM Trial: 5-Year Durability
(Fleischer, Endoscopy, 2010)
• Extension of AIM II Trial to 5 years
(n=50)
• Biopsy surveillance

4Q/1cm; central path lab
• If BE recurrence:

focal RFA; biopsy 2 months later
• Results:
92% (n=46) CR-IM at 5 yrs


8% (n=4) with NDBE
(no
neoplastic progression)
All re-established CR-IM after 1
focal RFA
No strictures or perforations

No buried glands in 1,473 bxs
• Conclusion:

CR-IM after RFA is durable

15
Community Practice Review
(Lyday, Endoscopy, 2010)
• 429 pts with IM (76%) & dysplastic
Barrett’s (24%) underwent RFA at
four community hospitals
• 20 months median follow up
• 100% dysplasia eradication rate
• 77% IM eradication rate
• Adverse events: 1.1% stricture rate
(9/788 cases)
• “The observed safety and efficacy
outcomes associated with RFA for
Barrett’s are comparable to those
previously reported in multicenter
trials from predominantly tertiary
academic centers”
Barrett’s Ablation Group:
Evidenced-Based Review of
Ablation for IM & LGD
(Fleischer, Dig Dis Sci, 2010)
•Written by 16 Barrett’s experts
•“ND or LGD BE commonly harbors
numerous genetic alterations”
•“Cancers develop from NDBE
without signs of progression”
•“Morphologic evaluation is fraught
with error”
•“Surveillance for ND & LGD BE is
cost-ineffective”
•“We recommend using RFA for ND &
LGD BE”
Ablation Effect on Natural History
NDBE
LGD
HGD
Polyp
Natural History
(53 studies)
0.6%
1.7%
6.6%
0.58%
After Ablation
(65 studies)
0.16%
0.16%
1.7%
0.06%
NNT=45
NNT=13
NNT= 4
NNT= 38
Progression risk expressed as “Per-patient-per-year” (%) risk of developing EAC
NNT calculated on 5-year basis (number needed to treat to avoid one cancer over 5 years)
Esophageal adenocarcinoma in BE: a meta-analysis. Wani S, et al. Am J Gastro 2009
Prevention of colorectal cancer by colonoscopic polypectomy. Winawer SJ, et al. NEJM 1993
18
Post-RFA Neosquamous
Epithelium Study
(Bergman, Am J Gastro, 2009)
• Evaluation of Barrett’s mucosa
prior to RFA & neo-squamous
epithelium after RFA in 22 pts with
LGD (n=3) & HGD (n=19)
• 100% dysplasia & IM eradication
rate
• No buried glands in NSE using
standard & keyhole bx & EMR
• Genetic abnormalities were
present in all pts at baseline, but
absent in post-RFA NSE
Colon Polypectomy & Barrett’s
Ablation: Intellectually the
Same
(El-Serag & Graham, Gastro, 2011)
• A review of the evolution of
Barrett’s management showing
how it has paralleled the colon
polyp paradigm shift of ~25 years
ago
• “Patients and providers are
unlikely to accept the possibility
of having a ‘precancerous’ lesion
watched in the presence of a
safe alternative.”
IM Progression to HGD &
Cancer
(Falk, Sampliner, Sharma et al, CGH, 2011)
• Multicenter outcomes
project
• 1204 pts were followed
for a mean of 5.5 yrs
• 2.9% of IM pts developed
cancer in 10 yrs
• 7.3% of IM pts developed
HGD or cancer in 10 yrs
• IM pts with a BE segment
> 6cm had a 7x increase
in cancer risk
SAGES GERD Guidelines
(SAGES Guidelines Committee, 2010)
•“Anti-reflux surgery may be
performed before, during or after
ablative therapy”
•“RFA has been shown to achieve
high rates of complete histological
eradication of IM, IND, and LGIN with
an acceptable adverse event profile”
•“Cost-utility studies show that
ablative therapy is the preferred
strategy over surveillance alone (all
grades)”