February 20 2014 Fellow David Tang MD Faculty Marcelo Vela MD Case Presentation 36 year old White man Heartburn x 10 years Intermittent dysphagia and chest pressure x 2 years EGD in 2011 ID: 786661
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Slide1
Gastroenterology Grand Rounds
February 20, 2014Fellow: David Tang, M.D.Faculty: Marcelo Vela, M.D.
Slide2Case Presentation
36 year old White manHeartburn x 10 yearsIntermittent dysphagia and chest pressure x 2 yearsEGD in 2011
Long segment Barrett’s Esophagus, Prague C10M10, without dysplasia
Eosinophilic
esophagitisSymptoms resolved with twice daily Nexium
Slide3EGD
2013
Slide4EGD
2013
Slide5Case Presentation
HistologyEsophagus at 34 cm to 28 cm
Intestinal metaplasia with
low grade dysplasia
at multiple levelsEsophagus at 25 cm Squamous mucosa with > 40 intraepithelial
eosinophils
per high power field
Slide6Diagnosis
Eosinophilic EsophagitisAnd
Barrett’s Esophagus with Low Grade Dysplasia
Slide7Clinical Questions
What is the difference in recommendations for RFA in patients with LGD vs HGD?What is the efficacy and durability of RFA for Barrett’s Esophagus with LGD?Should RFA be performed for Barrett’s Esophagus with LGD?
What is the relationship between Barrett’s Esophagus and
Eosinophilic
Esophagitis?How safe is RFA of dysplastic Barrett’s in Eosinophilic Esophagitis?
Slide8Carcinogenesis in BE
Slide9Incidence of EAC in BE
Non dysplastic BE EAC 0.12% - 0.50% per year
LGD
EAC
1.7% per year
HGD
EAC
6.6% per year
Sikkema
Am J
Gastroenterol
2011
Hvid-jensen
NEJM 2011
Wani
Am J
Gastroenterol
2009
Slide10Inter-observer Variability in LGD
147 patients with a community diagnosis of LGD during BE surveillance15% with LGD confirmation by two other expert pathologists85 % down-staged to non dysplastic BEIncidence rate of progression to HGD/EAC
13.4% in patients with confirmed LGD
0.49% in patients down-staged to NDBE
Curvers
Am J
Gastroenterol
2010
Slide112011 AGA Guidelines
“We recommend endoscopic eradication therapy with radiofrequency ablation (RFA) … rather than surveillance for treatment
of
patients with confirmed
high-grade dysplasia”
Slide122011 AGA Guidelines
“Endoscopic eradication therapy with RFA should also be a therapeutic option for treatment of patients with confirmed low-grade dysplasia
in Barrett’s
esophagus.”
“In the absence of long-term studies showing efficacy, it is not clear that the potential benefit of ablation
in reducing cancer risk for patients who have
Barrett’s
esophagus with low-grade dysplasia warrants the risks and substantial expense of the ablative procedures
.”
Slide13AIM Dysplasia Trial
Multicenter RCT of RFA vs Sham procedure in dysplastic Barrett’s EsophagusN = 127 randomized in 2:1 ratioPrimary outcomes
Complete eradication of LGD @ 12
mos
Complete eradication of HGD @ 12 mosComplete eradication of IM @ 12 mos
Shaheen
NEJM 2009
Slide14AIM Dysplasia Trial
Eradication of HGD (N=43) @ 12
mos
Shaheen
NEJM 2009
Slide15AIM Dysplasia Trial
Eradication of LGD (N=58) @ 12
mos
Shaheen
NEJM 2009
Slide16AIM Dysplasia Trial
Progression of Dysplasia
Shaheen
NEJM 2009
Slide17AIM Dysplasia Extension
Shaheen
Gastro 2011
Eradication @ 24
mos
Allowed for 1 session of “touch up” RFA @ 15
mos
Slide18AIM Dysplasia Extension
Shaheen
Gastro 2011
Durability of CE-D
Slide19AIM Dysplasia Extension
Shaheen
Gastro 2011
Wani
Am J Gastroenterol
2009
Incidence of Progression to EAC [per year]
Slide20RFA Meta-analysis
Shaheen
Gastroenterology 2011
Shaheen
Gastrointest
Endosc
2012
Orman
Clin
Gastroenterol
Hepatol
2013
Eradication of Dysplasia
Slide21RFA Meta-analysis
Adverse Events
Shaheen
Gastroenterology 2011
Orman
Clin
Gastroenterol
Hepatol
2013
Slide22AIM Dysplasia Extension
Shaheen
Gastro 2011
Orman
Clin
Gastroenterol
Hepatol
2013
Wani
Am J
Gastroenterol
2009
Incidence of Progression to EAC
Slide23SURF Trial
Phoa
Gastroenterology 2013
European multicenter RCT of RFA vs Surveillance in LGD
N = 136 randomized in 1:1
Primary outcome
Neoplastic progression (HGD or EAC) at 3 years after randomization
Interim results at median 21
mos
follow up presented at DDW 2013
Slide24SURF Trial
Phoa
Gastroenterology 2013
Efficacy of RFA @ 12
mos
Slide25SURF Trial
Phoa
Gastroenterology 2013
Incidence Rate of Progression to ECA
Slide26Cost Effectiveness of RFA
Hur
Gastroenterology 2012
Computer model RFA and surveillance strategies of 50 year old “patients” followed until age 80 or death.
Possible causes of death
Age related all cause mortality
RFA complications
Surgical
esophagectomy
mortality
Esophageal
adenocarcinoma
Slide27Cost Effectiveness of RFA
Hur
Gastroenterology 2012
LGD cohort
Confirmed
a
ssume no initial diagnostic error
Stable
LGD found on more than one EGD at least 6 months apart
Management
Endoscopic surveillance q 6 months x 1 year, then yearly
RFA at 0, 2, 4, 9
mos
, then “touch up” RFA as needed
Slide28Cost Effectiveness of RFA
Hur
Gastroenterology 2012
RFA Outcomes
Residual dysplasia
CE-D
CE-IM
Recurrence of IM
Sub squamous intestinal metaplasia
Incremental cost effective ratio (ICER)
Willingness to pay (WTP) set at $100,000/QALY
Slide29Cost Effectiveness of RFA
Hur
Gastroenterology 2012
Surgery
RFA
RFA
Slide30Cost Effectiveness of RFA
Hur
Gastroenterology 2012
Willingness to Pay < $ 100,000 per QALY
Slide31Barrett’s Esophagus and EoE
Ravi Am J
Gastroenterol
2011
Cross sectional study of 200 patients with BE
14 of 200 patients with BE (
7
%) found to have > 15
eosinophils
/
hpf
on squamous biopsy
Slide32Post RFA Esophageal Eosinophilia
Villa Dis Esophagus 2013
Retrospective review of 148 patients with pre and post RFA esophageal biopsies
4 of 148 patients (2.7%) developed esophageal eosinophilia
at 12
months
All four had LGD
None had clinical or endoscopic findings suggestive of
EoE
No pre RFA biopsies of squamous epithelium
Adverse events not reported
Slide33Safety of Esophageal Dilation in EoE
Jung GIE 2011
Cohen
Clin
Gastroenterol
Hepatol
2007
Retrospective single center study
N = 293 dilations in 161 patients
9.2% mucosal tear
0.3% major bleeding
1% immediate perforation
All treated without surgery
Prior study of 36 patients with complication rate of 31% and perforation rate of 8%
Slide34Thank you
Dr. Marcelo Vela
Dr. Nicolas Villa
Slide35Prasad G, Talley N, Romero Y, et al. Prevalence and predictive factors of
eosinophilic esophagitis in patients presenting with dysphagia: a prospective study. The American journal of gastroenterology 2007;102:2627-2632.
Wolfsen
H, Hemminger L, Achem S. Eosinophilic esophagitis and Barrett's esophagus with dysplasia. Clinical gastroenterology and
hepatology
: the official clinical practice journal of the American Gastroenterological Association 2007;5.
Rodrigo S,
Abboud
G, Oh D, et al. High intraepithelial eosinophil counts in esophageal squamous epithelium are not specific for
eosinophilic
esophagitis in adults. The American journal of gastroenterology 2008;103:435-442.
Shaheen
N, Sharma P,
Overholt
B, et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. The New England journal of medicine 2009;360:2277-2288.
Wani
S,
Puli
S,
Shaheen
N, et al. Esophageal adenocarcinoma in Barrett's esophagus after endoscopic ablative therapy: a meta-analysis and systematic review. The American journal of gastroenterology 2009;104:502-513.
Jacobs J,
Spechler
S. A systematic review of the risk of perforation during esophageal dilation for patients with
eosinophilic
esophagitis. Digestive diseases and sciences 2010;55:1512-1515.
American Gastroenterological A,
Spechler
S, Sharma P, et al. American Gastroenterological Association medical position statement on the management of Barrett's esophagus. Gastroenterology 2011;140:1084-1091.
Hvid
-Jensen F, Pedersen L,
Drewes
A, et al. Incidence of adenocarcinoma among patients with Barrett's esophagus. The New England journal of medicine 2011;365:1375-1383.
Ravi K,
Katzka
D,
Smyrk
T, et al. Prevalence of esophageal
eosinophils
in patients with Barrett's esophagus. The American journal of gastroenterology 2011;106:851-857.
References
Slide36Shaheen N, Overholt B, Sampliner R, et al. Durability of radiofrequency ablation in Barrett's esophagus with dysplasia. Gastroenterology 2011;141:460-468.
Spechler
S, Sharma P, Souza R, et al. American Gastroenterological Association technical review on the management of Barrett's esophagus. Gastroenterology 2011;140.
Hur
C, Choi S, Rubenstein J, et al. The cost effectiveness of radiofrequency ablation for Barrett's esophagus. Gastroenterology 2012;143:567-575
.
Dellon
E,
Gonsalves
N, Hirano I, et al. ACG clinical guideline: Evidenced based approach to the diagnosis and management of esophageal eosinophilia and
eosinophilic
esophagitis (
EoE
). The American journal of gastroenterology 2013;108:679
.
Orman
E, Li N,
Shaheen
N. Efficacy and durability of radiofrequency ablation for Barrett's Esophagus: systematic review and meta-analysis. Clinical gastroenterology and
hepatology
: the official clinical practice journal of the American Gastroenterological Association 2013;11:1245-1255
.
Villa N, El-
Serag
H,
Younes
M, et al. Esophageal eosinophilia after radiofrequency ablation for Barrett's esophagus. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus / I.S.D.E 2013;26:674-677
.
Falk G. Update on ablation for Barrett's esophagus. Current gastroenterology reports 2014;16:368.
Fitzgerald R, di Pietro M,
Ragunath
K, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's
oesophagus
. Gut 2014;63:7-42.
References
Slide37AIM Dysplasia Trial
Eradication of IM @ 12
mos
Shaheen
NEJM 2009
Slide38AIM Dysplasia Extension
Shaheen
Gastro 2011
2 year extension of AIM Dysplasia
Original control arm offered cross over to RFA
N = 119
106 patients completed 2
nd
year of follow up
100 eligible for extension through year 5
56 completed 3
rd
year of follow up at time of publication
Durability of eradication of both dysplasia and metaplasia assessed at 2
nd
and 3
rd
year
Slide39AIM Dysplasia Extension
Shaheen
Gastro 2011
Durability of CE-IM
Slide40AIM Dysplasia Extension
Shaheen
Gastro 2011
Progression of Dysplasia
5 of 119 (4.3%) with progression of any type
3 LGD
HGD
2 with eventual CE-IM
1 with EMR of focal HGD and withdrew from study
1 LGD to EAC
Initially randomized to Sham arm x 12
mos
RFA x 3 after crossing over
Eventual EMR of focal EAC
1 HGD to EAC
EMR of focal EAC
Eventual CE-IM at 3 years
Slide41RFA Meta-analysis
Efficacy of RFA3802 patients2135 patients in RFA registry from 148 community and academic practices
Durability of RFA
540 patients
Orman
Clin
Gastroenterol
Hepatol
2013
Slide42RFA Meta-analysis
Orman
Clin
Gastroenterol
Hepatol
2013
IM Recurrence
Slide43Cost Effectiveness of RFA
Hur
Gastroenterology 2012
Assumptions
NDBE
EAC 0.12%, 0.33%, 0.50%
LGD EAC 0.19%, 0.5%, 0.75%
Slide44Eosinophilic Esophagitis
Symptoms
Dysphagia, Food impaction
Reflux
DyspepsiaAssociated with
atopy
Requires > 15
eos
per HPF on biopsy
Slide45Overlap of EoE and GERD
Attwood Am J
Gastroenterol
1993
Slide46Overlap of EoE and GERD
Rodrigo Am J
Gastroenterol
2008
Slide47Diagnosis of EoE
Dellon
Am J
Gastroenterol
2013