This document discusses the management of Barrett's esophagus, which is the development of intestinal metaplasia in the esophagus. It presents the stages of progression from non-dysplastic Barrett's to low-grade dysplasia to high-grade dysplasia and eventually cancer. It reviews the risks of progression and recommends surveillance strategies. It also discusses endoscopic treatment options like endoscopic mucosal resection and radiofrequency ablation to remove dysplastic tissue, with the goal of complete eradication of Barrett's. Acid suppression with proton pump inhibitors is an essential part of co-therapy.

1. Management of Barrett’s
Esophagus

2. 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”

3. BE: Significance
§
Risk of esophageal adenocarcinoma
(EAC)
§
EAC associated with:
–
BE
–
White males
–
Chronic GERD
–
Obesity
–
Family history of EAC

7. PROGRESSION OF BARRETT’S
TO ADENOCARCINOMA
§
simple Barrett’s (no dysplasia)
§
Barrett’s with low grade dysplasia
§
Barrett’s with high grade dysplasia
§
adenocarcinoma

11. Is it Really Dysplastic?
Home Institution Diagnosis

12. 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?

13. 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

14. Surveillance vs Intervention

15. 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

16. 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

17. 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.

18. 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

19. What is the Risk of Death with
Esophagectomy?
Birkmeyer et al, N Engl J Med 2002;346:1128-37

20. High frequency probe
(20MHz) EUS in HGD and IMC
– 9 patients
§
Correct – 45%
§
Understaged – 33%
§
Overstaged – 22%
–
Waxman et al AJG 2006;101:1773

21. Clinical response to EMR
staging
EMR stage Risk of lymph node met
§
T1a (mucosa only) 0-7%
§
T1b (submucosa) ~ 15-20%

22. Devices for EMR

23. Pre-EMR

24. Post-EMR

29. EMR of IM cancer

30. EMR of esophageal cancer

31. 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

33. Stricture after EMR

34. Stricture after EMR

35. 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

36. General Rule:
§
If ablation is undertaken should go for full
eradication
§
Basic strategy
–
Nodular disease by EMR
–
Flat disease by RFA

37. 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

38. HALO360 Ablation Catheter

39. HALO90 Focal Ablation
Device

45. Baseline
Insertion
of
Electrode
Result of
followed
1 second
by Inflation
ablation

46. Endoscopic Appearance
Baseline, 4 cm IM Clean base after
immediate slough (10
J/cm2 twice)

47. Randomized, Sham-Controlled Trial of Radio-
frequency Ablation of Dysplasia in Barrett’s
% with No Dysplasia at
12 months (ITT)
10
8
6
4
2
0
High-Grade Low-Grade
Dysplasia Dysplasia
Shaheen. N Engl J Med 2009;360:2277-88

48. Randomized, Sham-Controlled Trial of Radio-
frequency Ablation of Dysplasia in Barrett’s
at 12 Months (ITT)
10
% with No IM
8
6
4
2
0
Halo 360 Sham
Ablation Ablation
Shaheen. N Engl J Med 2009;360:2277-88

49. Randomized, Sham-Controlled Trial of Radio-
frequency Ablation of Dysplasia in Barrett’s
% with Progression
10
8
6
4
2
0
Progression of Progression
Neoplasia to Cancer
Shaheen. N Engl J Med 2009;360:2277-88

50. If RFA can’t be applied or is
unsuccessful?
§
Cryotherapy
§
APC
§
MPC

51. 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

52. 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

53. 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

54. Other considerations:
(tailored therapy)
§
Age
§
Comorbidities
§
Patient preferences

55. Ablation is 2 part therapy
§
Acid suppression – §
Destruction of the
patient must be on Barrett’s mucosa
double dose PPIs
and take them
properly and
consistently

56. 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

57. 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