Barrett’s Esophagus Endoscopic Diagnosis

1. Barrett’s EsophagusEndoscopic Diagnosis Alessandro Repici Dept of Gastroenterology Molinette Hospital, Torino

2. Historical notes “peptic ulcer of the esophagus” with a close resemblance of the mucous membrane to that found in the stomach 1906, Tileston “The lower esophagus lined by columnar epithelium” (erroneously considered as congenital) 1957, Barrett “Columnar-lined oesophagus: an acquired lesion with malignant predisposition” 1975, Naef

3. Barrett’s Esophagus: diagnostic issues Which length? Which metaplasia?

4. 1998 A.C.G.: …”a change in the esophageal epithelium of any length that can be recognized at endoscopy and is confirmed to have intestinal metaplasia by biopsy” Presence of Goblet Cells becomes a “must”

5. Histomorphological changes in Barrett‘s esophagus A: Damage to the superficial compartments through acid or bile B: Damage to the cellular layers and activation of toti- potential cells

6. Histomorphological changes in Barrett‘s esophagus Development of areas with mucin secreting cells with resistance against acid and bile Jankowski, AJP 1999

7. Macroscopic classification > 3 cm, Barrett < 3 cm, Short Barrett Super Short Barrett AJG 2000

8. Easy to identify Long-segment Barrett

9. Correct definition of OGJ allows detection of short segments of Barrett’s esophagus SCJ=„squamocolumnar junction“ OGJ=„oesophagogastric junction“

10. BE: Progression BE (no dysplasia) Low-grade dysplasia High-grade dysplasia Esophageal adenocarcinoma

11. Biomarkers in BE • Multiple genetic lesions occur during the neoplastic progression of BE • Biomarkers may be used for risk assessment of patients as well as intermediate endpoints in trials • 17p (p53) LOH and p16 abnormalities seem to predict progression to cancer in BE patients • No realiable markers of Cancer progression are currently available Reid BJ, DDW 2001 Wong DJ, DDW 2001

12. Endoscopic diagnosis • Surveillance • Detection of dysplasia • Staging of the disease

13. Endoscopic Surveillance of Barrett’s Esophagus • Optimal endoscopic technique • Biopsies of all mucosal abnormalities (ulcer, nodule, plaque) • Four quadrant (jumbo) biopsies at 1 – 2 cm intervals • Recommended surveillance intervals • No dysplasia 3 yrs after 2 EGD • LGD 6m for 1 yr, then 1yr • HGD Confirm and resect vs. 3 m

14. LIMITATIONS OF SURVEILLANCE STRATEGY • Cancer/Dysplasia -- multifocal and patchy • “Seattle Protocol” – cumbersome and tedious • Compliance is poor • Unsuspected Cancer -- up to 53% of HGD • Surveillance Intervals - poorly defined biology • Dilemma with HGD – variable interpretation • surveillance vs. surgery? • Costly with unproven benefit

15. NEEDED TECHNIQUE • Highly sensitive to dysplasia – must detect changes at a nuclear level • High resolution but also able to scan wide area in real-time • Specific – not affected by esophageal inflammation • High interobserver agreement • Localize dysplastic area for biopsy • Cost not prohibitive

16. Alternative Methods for Surveillance • Blind balloon cytology – sensitivity limited • High Magnification Endoscopy • Confocal Microscopy • Chromoendoscopy (methylene blue) • Endoscopic Ultrasound (EUS) • Laser Induced Fluorescence • Optical Coherence Tomography • Light Scattering Spectroscopy • Raman Spectroscopy

17. BE SURVEILLANCE --BLIND CYTOLOGY • Advantages • Sample larger area • Quick and Inexpensive • Disadvantages • Limited sensitivity (< 25% for LGD) • Future Hope • Molecular probes • Immunostains • FISH

18. HIGH MAG – DETECTING BE • Contrast Agents • Acetic acid • Indigo carmine • Methylene blue • Distinct morphology for IM • High Sensitivity (> 95%) for IM • Still inaccurate for LGD/HGD

19. HIGH MAG – DETECTING DYSPLASIA • Sharma et al. – 80 patients • Distinct morphology - Ridged/villous/ Circular/ Irregular&Distorted • All 6 HGD were irregular and distorted • Limitations -Cannot distinguish LGD; Difficult for surveillance of large area; Results very preliminary

20. High Grade Dysplasia Intestinal Metaplasia

21. METHYLENE BLUE CHROMOENDOSCOPY • Rationale • MB absorption by absorptive columnar cells (small bowel and colon) • MB not absorbed by dysplastic cells

22. Methylene blue selectively stains SCE in Barrett’s esophagus Focal Diffuse

23. Summary of Studies

24. LIMITATIONS OF MB DIRECTED SURVEILLANCE • Stains inflammation • Staining paradox • No time saving • Messy • Operator dependent; not sensitive enough

25. EUS For Surveillance • Theory of Ultrasound Imaging • Sound reflects at tissue interface • Higher frequency equals higher resolution but lower penetration • Useable frequencies do not provide cellular resolution

26. When not to do EMR 20 Mhz probe EUS at 7.5 MHz

27. LIMITATIONS OF EUS • CANNOT DETECT DYSPLASIA • May or may not identify cancer reliably in HGD • Accuracy for identifying malignant nodal spread is limited.

28. LASER INDUCED FLUORESCENCE (LIF) • Theory • Dysplastic tissue is biochemically different and thus fluoresces differently from normal; • Dysplastic tissue may also absorb fluorophores differentially • Autofluorescence alone not accurate enough • Local or systemic ALA (Messman et al.) absorbed by dysplastic cells

29. DIFFICULTIES WITH L.I.F. • Inflammation may cause false positives • Dysplasia -- sensitivity < 80%, specificity < 70% • Cost of fluorophore • Cost of LIF scopes • More research; better fluorophores needed

30. OPTICAL COHERENCE TOMOGRAPHY • Theory – Coherent back scattered light provides imaging resolution at microscopic level.

31. Figure 3A

32. Figure 3B

33. Figure 4A

34. DIFFICULTIES WITH OCT • Limited sensitivity • Surveillance of large areas • Further studies of dysplastic tissue required