2 rex barretts esophagus
TRANSCRIPT
Management of Barrett’s Esophagus
BE: Definition§ Red (columnar) mucosa in the
esophagus; variable length– Described by the Prague classification
• C: length of the circumferential section• M: length of the any circumferential section plus
the length of any tongues§ Biopsies demonstrate goblet cells
– Goblet cells are not seen in the normal stomach but are seen in the intestine• Goblet cells define “intestinal metaplasia”
BE: Significance
§ Risk of esophageal adenocarcinoma (EAC)
§ EAC associated with:– BE– White males– Chronic GERD– Obesity– Family history of EAC
PROGRESSION OF BARRETT’S TO ADENOCARCINOMA
§ simple Barrett’s (no dysplasia)§ Barrett’s with low grade dysplasia § Barrett’s with high grade dysplasia§ adenocarcinoma
Is it Really Dysplastic?
Home Institution Diagnosis
Outline
§ What are the risks of progression of BE stages to cancer?
§ What are the management options for LGD, HGD and early stage cancer?
§ Can we define a management algorithm for endoscopic intervention in BE?
Surveillance strategies
Interval
Barrett’s no dysplasia in 1 year, then q 3y
LGD in 3 mo, then 1 year
HGD intervention best (q 3 mo X 4, then qy)Wang et al AJG 2008;103:788-97
Surveillance vs Intervention
Interventions in Barrett’s
§ Nodular disease – must be removed by EMR
– Provides effective therapy for nodules with HGD or IM CA
– Provides more accurate staging than EUS§ Flat disease
– Best treatment: RFA (BARRX)– Alternatives:
• Cryotherapy• Photodynamic therapy• Argon plasma coagulation or multipolar cautery
Risk of progression to EAC determines appropriateness of
intervention per year intervene ?
§ Barrett’s 0.1-0.2% controversial
§ LGD 1.7 -3.7% optional
§ HGD 5-8% yes
How Benign is Low-Grade Dysplasia?
§ 147 subjects with a diagnosis of LGD made in a community practice in the Netherlands
§ Path reviewed by 2 expert pathologists– Disagreements resolved by consensus
§ 85% of cases were down-graded§ In the 15% who were not, the incidence rate of
HGD or EAC was 13.4%/pt-yr (mean f/u: 51 months)
Curvers WL et al. Am J Gastroenterol 2010, pub pend.
Progression to Cancer in HGD
0% 20% 40% 60%
Reid et al Am J gastro 2000;95:1669-76 Schnell et al Gastro 2001;120:1607-19 Buttar et al Gastro 2001;120:1630-9
What is the Risk of Death with Esophagectomy?
Birkmeyer et al, N Engl J Med 2002;346:1128-37
High frequency probe (20MHz) EUS in HGD and IMC
– 9 patients§ Correct – 45%§ Understaged – 33%§ Overstaged – 22%
– Waxman et al AJG 2006;101:1773
Clinical response to EMR staging
EMR stage Risk of lymph node met
§ T1a (mucosa only) 0-7%
§ T1b (submucosa) ~ 15-20%
Devices for EMR
Pre-EMR
Post-EMR
EMR of IM cancer
EMR of esophageal cancer
Why not use EMR for entire long segments of Barrett’s?
§ Distortion of anatomy for subsequent RFA§ Stricture formation
– Limit the extent of resection§ Bleeding
– Clip placement§ Perforation
– Removable stent placement
Stricture after EMR
Stricture after EMR
Is EMR adequate therapy in Barrett’s?
§ Yes if it fully removes the Barrett’s§ No if there is residual Barrett’s – especially
after there resection of IM EAC– 11% rate of metachronous cancer if EMR
alone• Ell et al GIE;2007:65:3-10
– 12% rate of metachronous cancer if EMR alone• Prasad et al Gastroenterology 2009;137:815-23
General Rule:
§ If ablation is undertaken should go for full eradication
§ Basic strategy– Nodular disease by EMR– Flat disease by RFA
PDT for HGD
§ RCT of 208 patients § 2:1 PDT plus PPI vs PPI alone§ Reduced risk of cancer by 50% (did not
eliminate it – 15% vs 29%)§ HGD eliminated in 78% vs 39%
– Overholt GIE;2005;62:488-98
HALO360 Ablation Catheter
HALO90 Focal Ablation Device
Baseline
Insertion of
Electrode followed
by Inflation
Result of 1 second ablation
Endoscopic Appearance
Baseline, 4 cm IM Clean base after immediate slough (10
J/cm2 twice)
Randomized, Sham-Controlled Trial of Radio-frequency Ablation of Dysplasia in Barrett’s
0
2
4
6
8
10
% w
ith N
o D
yspl
asia
at
12 m
onth
s (IT
T)
High-Grade Dysplasia
Low-Grade Dysplasia
Shaheen. N Engl J Med 2009;360:2277-88
Randomized, Sham-Controlled Trial of Radio-frequency Ablation of Dysplasia in Barrett’s
0
2
4
6
8
10
% w
ith N
o IM
at 1
2 M
onth
s (IT
T)
Shaheen. N Engl J Med 2009;360:2277-88
Halo 360 Ablation
ShamAblation
Randomized, Sham-Controlled Trial of Radio-frequency Ablation of Dysplasia in Barrett’s
0
2
4
6
8
10
% w
ith P
rogr
essi
on
Shaheen. N Engl J Med 2009;360:2277-88
Progression of Neoplasia
Progression to Cancer
If RFA can’t be applied or is unsuccessful?
§ Cryotherapy§ APC§ MPC
Cryotherapy in HGD: An Initial Report
• 98 subjects w/ HGD§ treated at 10
institutions§ - 61 completed Rx, 27§ ongoing• 281 total procedures§ - 4.0/pt• No perfs, no buried § glands, no bleeds or § chest pain requiring § hospitalization• One progression to CA
Should non-dyplastic Barrett’s be ablated?
§ AIM Trial – rates of CR – IM– 2.5 y : 98% with sustained CR– 5 y: 92% with sustained CR
Should non-dysplastic Barrett’s be ablated? Cost
issues§ Das; Endoscopy 2009;41:750-8
– RFA > cost by more QALYs– $48,626/QALY
§ Inadomi; Gastroenterology 2010;136:2101-14
– RFA more CE if rate of CR-IM 40% and surveillance continued
– RFA more CE for LGD if CR-D achieved in 28% and CR-IM in 0% and surveillance continued
Other considerations: (tailored therapy)
§ Age§ Comorbidities§ Patient preferences
Ablation is 2 part therapy
§ Acid suppression – patient must be on double dose PPIs and take them properly and consistently
§ Destruction of the Barrett’s mucosa
Related issues - Chemoprevention
§ NSAIDs– OR for cancer - case control studies
0.57(0.47-0.71)– RCT of celecoxib: no benefit
§ PPIs– 2 retrospective cohort studies suggest
benefit
• Large scale trials with aspirin and PPIs are underway
Conclusions
§ EMR for nodular disease– Fulfills dual role of treatment and staging
§ RFA for flat disease§ PPI co-therapy essential§ Ablate all Barrett’s if possible§ Widely accepted to treat HGD and LGD§ Increasing acceptance of treating ND-BE§ Therapy also tailored to patient age, comorbidities and
preferences