1. Barrett’s Esophagus: Does that Z-line look irregular to you?
Andrew Flynn, MD, PhD, FRCPC
Sept 22, 2017

2. Disclosures
None relevant.

3. Acknowledgments
Dr. Cheryl Wright, PATH

4. Table of Contents Epidemiology Screening/diagnosis
Surveillance/management
Quiz!

5. But first... the case 50 y.o. man referred for Barrett‘s screening.
8 year history of heartburn, well controlled with daily pantoprazole.
No dysphagia or other alarm symptoms.
Otherwise healthy. Smokes occasional cigar. Social EtOH.
Father and paternal aunt with esophageal adenocarcinoma.

6. Endoscopy

7. Barrett’s History Norman Barrett, 1950
“...in cases of congenital short oesophagus...the bare area is larger than usual.”
Barrett initially thought the phenomenon was due to congenitally short esophagus.

8. Definition
Metaplasia from normal stratified squamous epithelium to columnar epithelium with goblet cells (“intestinal metaplasia”).
May or may not be associated with dysplasia.
Replacement of one differentiated cell type with another. Goblet cells not found in stomach. Dysplasia = less differentiated.

9. Columnar epithelium more resistant to reflux-related damage.

10. Pathogenesis?
vs migration of stem cells from gastric cardia or circulation.
Souza et al., 2008

11. Epidemiology
Prevalence = 1.5% in general population, 15% in those with GERD
RFs = older age, male, smoking, obesity, white ethnicity, FHx
FHx Barrett’s or EAC.

12. So whats the problem 0.25% ~0.55% 4-8% Approximate annual risk.
Conteduca et al., 2012

13. Could be worse! 10 year risk of EAC 17.5% 2.5%
Earlier small studies severely over-estimated risk.
Wani et al., 2011

14. Adeno vs squamous “Lower third” Barrett’s, GERD, smoking, obesity
Incidence rising
“Upper two thirds”
Smoking, EtOH, dietary factors, caustic ingestion
Incidence falling
Not included: small cell carcinomas, sarcomas

15. Screening Points to keep in mind:
> 90% of patients with EAC have never been diagnosed with BE
40% of patients with BE do not have a clinical history of GERD
The majority of patients with BE will not die of EAC
Meta-analysis of ~4200 patients. Most common cause of death in BE patients = CAD.
Sikkema et al., 2010

16. Screening guidelines
Consider screening patients with > 5 yrs heartburn or acid regurgitation, and 2 of:
Age > 50 yrs
Caucasian race
Central obesity
Smoking history
History BE/EAC in first degree relative
ACG Guideline 2015
Strong recommendation, moderate (male) or low (female) level of evidence.
Male >> female. (Risk in female w/ GERD = risk in male w/o GERD.)

17. Diagnosis
Columnar epithelium ≥ 1 cm above GEJ + biopsy demonstrating intestinal metaplasia.
4 quadrant biopsies every 2 cm
> 3 cm = long segment
Columnar epithelium = pink, velvety; squamous epithelium = pale, shiny.
Longer mucosal inspection time & sufficient biopsies are predictors of increased dysplasia detection.
Harrison et al., 2007

19. Prague Classification
C1M4
Schoofs et al., 2017

20. 8 weeks PPI bid
Pointless to biopsy esophagitis. Patient had BE w/o dysplasia.

21. Imaging modalities Current recommendation: Goal:
High-definition white light endoscopy
Goal:
Imaging modality to improve targeted biopsies
VLE
HD-WLE
NBI
Chromo
CLE
WLE, NBI, chromo, confocal laser endomicroscopy, volumetric laser endomicroscopy.
Eluri and Shaheen, 2017
Leggett et al., 2016

22. Adherence to screening
Analysis of 2245 surveillance cases in the community setting. #1 = adherence to screening based on BE length. #2 = detection of dysplasia depending on BE length.
Abrams et al., 2009

23. Alternative screening options

24. Transnasal endoscopy
Unsedated TNE using disposable Endosheath. Well tolerated (>95%) and cost effective. Not for surveillance (biopsy forceps too small to reliably detect dysplasia).

25. Cytosponge
IHC done for Trefoil Factor-3. More sensitive/specific for long segment Barrett’s.

26. Surveillance/Management

27. Confirmed by 2nd (expert) pathologist
No BE = no surveillance. Significant proportion (~75%) of LGD will be downgraded by expert pathologist. Remainder have high risk of progression. Could consider surveillance if elderly. vs
Eluri and Shaheen, 2017

28. Radiofrequency ablation
Thermal injury. Recommended post-EMR to reduce risk of subsequent dysplasia.
Eluri and Shaheen, 2017

29. RFA results
N = 127 patients. Risk of stricture = ~6%. Eradication in controls likely = sampling error.
Shaheen et al., 2009

30. Recurrence post RFA
Recurrence of intestinal metaplasia in patients who have undergone complete eradication of intestinal metaplasia (CEIM). Comparable whether EMR done or not. ~25% recurrence at 2-3 years (vast majority as NDBE), necessitating endoscopic follow-up.
Pasricha et al., 2014

31. Death post RFA
EAC
Only 3% of ~5000 patients died. Most common cause of death = cardiac. EAC was 5th most common cause.
Wolf et al., 2015

32. RFA for LGD? RCT of 136 patients. Study ended prematurely.
Phoa et al., 2014

33. Map first, then biopsy abnormalities (nodularity, erosion, plaque, stricture), then 4 quadrant. Abnormalities are associated with higher rates of malignancy (risk = ~30% in patients with HGD on Bx).

34. Surveillance/Management
(submucosal invasion)
Esophagectomy ?
Unfavorable histology = poor differentiation or lymphovascular invasion. Risk of nodal metastases in T1b is up to 22% (depends on sm1/2/3). ? = if sm1 (upper third of submucosa) + small + poor surgical candidate.
Shaheen et al., 2015

35. EMR
Band-ligation technique- one option. Benefit = staging + removal of dysplasia. Usually not recommended for complete resection due to high stricture rate.
Sakai and Maluf-Filho, 2015

36. “Chemoprevention”? No PPI PPI
Cohort study: 40 of 540 patients (7%) developed HGD or EAC. (Conflicting data.) No reduction in Barrett’s length with PPI. No role for bid PPI unless severe esophagitis. No role for anti-reflux surgery. No role for ASA or NSAIDs.
PPI
Kastelein et al., 2013

37. Summary
Barrett’s esophagus (intestinal metaplasia) is common in older males with GERD
Screening involves EGD with 4 quadrant biopsies every 2 cm
Dysplasia is a significant risk factor for EAC
RFA +/- EMR is effective at eradicating Barrett’s with/without dysplasia
PPI therapy is recommended for Barrett’s

38. Back to the case
Referred for EMR/RFA, but repeat biopsies showed at least T1b disease. CT/PET showed no metastases. Due for esophagectomy.

39. Quiz time!

40. Yes!

41. No! (EoE)

42. No!

43. No!

44. Yes!

45. No! (sloughing)

46. No!

47. Yes!

48. Yes/No (EAC)

49. What we’re trying to avoid
41 y.o. with 4 weeks progressive dysphagia, chronic heartburn.