1. New Endoscopic Imaging Techniques Ross M Bremner MD, PhD Director, Norton Thoracic Institute St Joseph’s Hospital and Medical Center William Pilcher Chair Thoracic Surgery and Transplantation Professor Surgery, Creighton Medical School Phoenix AATS 2015

2. Disclosures None relevant to this talk

3. Problem of Barrett’s 1.Barrett’s greatest risk factor for Cancer 2.Most will not develop cancer 3.No way to stratify risk at present with exception of degrees of dysplasia 4.Biopsies VERY unreliable Histology difficult Biopsies random! 5.Expense of surveillance very, very high

4. Biopsies are UNRELIABLE While 84% of GI’s will endoscope every 2 years, only 42% do adequate biopsies** –(4 quadrant every 2 cm) Barrett’s segment is heterogeneous Sampling error can lead to major error “1% of 1%” **Abrams, J: Ther Adv Gastroenterol 2009(2)73

5. How to improve biopsy “yield” Focussed biopsies Chromoendoscopy Non-dye chromoendoscopy OCT/VLE - (Optical Coherence Tomography, Volume Laser Endoscopy) Confocal Endomicroscopy The Future Future – cell surface markers (Glycans/Lectin) Periostin – Ab-dye congugate Peptides with flourescent labelling

6. Dye-less chromoendoscopy NBI High resolution white light Little mucosal or vascular detail Narro Band Imaging – Blue light Superficial layer and vascularity Dectect dysplasia

7. Chromoendoscopy Acetic Acid 20 cc 1.5% Acetic acid (Balsamic 3% also been used) Disulfide bonds of glycoproteins Denatures intracellular proteins Pit Patterns Pattern I-II: round pits/circular pattern predicting gastric epithelium; Pattern III-IV: ridged/villous pattern predicting Barrett's epithelium SCE Enhances borders.

8. Chromoendoscopy Lugol’s Iodine 10 cc 1.2% Lugol’s Iodine Stains Glycogen of healthy Squamous cells Can detect Dysplasia in SCC Unstained streaks may be useful in NERD Normal Sq regrowth after ablation Watch for iodine allergy! Gastrointest Endosc 2005;62:698-703 Endoscopy 2001 Jan; 33(1):75-9

9. Optical Coherence Tomography (Volume laser endomicroscopy) Backscattering of light to get cross-sectional images of tissue Similar to Ultrasound but used light (near infra-red) Limited to 1-3 mm SCE – multilayer, homogenous Barrett’s, glands and crypts, mucin

10. Optical Coherence Tomography (Volume laser endomicroscopy) 25x higher resolution than EUS No dye’s or injectables Excellent software for later analysis

11. Optical Coherence Tomography (Volume laser endomicroscopy)

12. Confocal Laser Endomicroscopy Illumination of tissue with low power laser and detecting fluorescent light reflected from tissue Intravenous flourescein (vasculature, LP and intracellular spaces)

13. Confocal endomicroscopy Fundic glands, red cells “Optical Biopsies” Real-time cytologic images Clean mucous with Mucolytic Relies on flourescence –Flourescein

14. Confocal endomicroscopy Barrett’s – No Dysplasia Goblet cells No nuclear atypia No stratification Surface maturation Concensus Panel - Human Pathology: 2001; 32: 368

15. Indefinite for Dysplasia Human Pathology: 2001; 32: 368 Goblet cells Prominent hyperchromasia Glandular crowding Increased mitotic activity Mild cytologic atypia Surface maturation

16. Low Grade Dysplasia Human Pathology: 2001; 32: 368 Maintenance of nuclear polarity No architectural complexity No Surface maturation

17. Confocal endomicroscopy Barrett’s – HGD Dysplasia Nuclear atypia Loss Nuclear polarity Architectural complexity Basement membrane in tact No Surface maturation Concensus Panel - Human Pathology: 2001; 32: 368

18. Confocal endomicroscopy Intramucosal Carcinoma Complex glandular budding Desmoplasia Barrett’s cells below Basement membrane Concensus Panel - Human Pathology: 2001; 32: 368

19. Summary NBI – Enables better imaging of surface detail and vascular patterns Acetic Acid, and Lugols add value OCT/VLE – early days, resolution is impressive Confocal (CLE)– really helps focus biopsies

20. Summary Focussed biopsies and new imaging technologies will help our diagnostic yield Help to stratify those patients with early cancer and those at risk for developing cancer.