Capsule endoscopy for the foregut- a pill worth swallowing?

1. Capsule endoscopy for the foregut- a pill worth swallowing? Glenn Eisen, MD, MPH Professor of Medicine Director of Endoscopy Oregon Health & Science University Portland, Oregon

2. Relevant disclosures • Consultant- Given, Mirocam • Speaker-Given

3. Fantastic Voyage (1966)

4. Yes, the ultimate manifestation of this technology is inherently superior to what is currently being used: Example: capsule vs conventional endoscopy Ok, maybe ultimately but first it needs to be developed to a level where it provides: Performance Cost-effectiveness Improve patient related outcomes Acceptability Safety Is new technology destined to disrupt current methods? Two views:

5. Capsule Palooza • Pillcam SB • Endocapsule • Pillcam ESO • Pillcam Colon • SMART Pill Capsule on a string Tethered capsule Versions 2.0, 3.0 et al….

6. What they can do… • First line noninvasive imaging for OGIB • Integral piece of algorithm for small bowel assessment (with ct enterography, balloon enteroscopy) • Role in Crohn’s; ? Celiac diagnosis • Alternative to endoscopy for esophageal varices screening • Assess GI motility

7. What capsules might be able to do.. • Screen for Barrett’s esophagus • Screen for colorectal cancer • First line motility assessment tool • Take biopsies/ perform treatment • Deliver drug therapy

8. Capsule Endoscopy of the Small Bowel • The gold standard, non-invasive diagnostic tool for visualizing the entire small bowel • >1,000,000 ingestions to date • >800 peer-reviewed journal articles published • Produces 55,000+ images per study • 15 to 40 minutes reading time per study

9. Small Bowel Image Spectrum: PillCam Capsule Endoscopy Suspected Crohn’s Bleeding Tumors Celiac Disease

10. ASGE Technology Status Evaluation Report: Indications for Capsule Endoscopy PillCam SB Obscure GI bleeding including iron deficiency anemia (IDA) Suspected Crohn’s disease Suspected small intestinal tumors and surveillance in patients with polyposis syndromes Suspected or refractory malabsorptive syndromes (celiac disease) Gastrointestinal Endoscopy 2006;63(4):539-545.

11. Obscure Gastrointestinal Bleeding Size of the Problem 3-5% of all patients with gastrointestinal bleeding All GI bleeding accounts for >300,000 admissions to U.S. hospitals each year >150 per 100,000 population Approximately 15,000 - 25,000 patients each year have obscure bleeding

12. IY (fixed) IY (fixed) Study 95% CI 95% CI Selby 2001 0.38 [-0.04, 0.79] Demedts 2002 0.60 [0.25, 0.95] Ell 2002 0.38 [0.15, 0.60] Lewis 2002 0.25 [-0.05, 0.55] Lim 2002 0.25 [-0.05, 0.55] Yousfi 2002 0.30 [0.02, 0.58] Hartmann 2003 0.55 [0.34, 0.75] Mata 2003 0.48 [0.21, 0.74] Mylonaki 2003 0.36 [0.18, 0.54] Saurin 2003 0.31 [0.14, 0.48] Toth 2003 0.25 [0.01, 0.49] Van Gossum 2003 0.00 [-0.24, 0.24] Adler 2004 0.45 [0.17, 0.73] Saunders 2004 0.21 [-0.03, 0.44] Total (95% CI) 0.33 [0.27, 0.40] Total yield: 62% (CE), 29% (Push) Test for heterogeneity: P = 0.14, I² = 29.6% Test for overall effect: P < 0.00001 -1 -0.5 0 0.5 1 Yield higher in PE Yield higher in CE Total Yield CE versus PE (for OGIB) Triester, Leighton, Fleischer, et al. Mayo Scotsdale

13. OGIB and capsule • Indicated after negative EGD/colonoscopy • Data suggests 50% increased yield if done within 48-72 hrs of event • Superior to SBFT/PE • Trials ongoing vs. CT enterography • Should be used to direct balloon enteroscopy

14. Image Spectrum of Crohn’sConfirmed by histology

15. CE vs. Ileoscopy in detecting Crohn’s Triester et al Am J Gastroenterol 2006;101;954-964

16. CE vs. SB Radiography (in detecting Crohn’s) Triester et al Am J Gastroenterol 2006;101;954-964h

17. Comparing SB capsules • Single published study – GIE 2007 -patients ingested both capsules 40 minutes apart -75% agreement on significant findings; kappa 0.48 -readers preferred endocapsule images -highlights that CE misses lesions

18. Screening for esophageal varices

19. Pillcam ESO vs. EGD • 2 pilot trials Eisen et al Endoscopy 2006, Lapulus Endoscopy 2006- < 40 patients each- feasible, reasonable test characteristics • Issues- insufflation, esophageal transit, gastric evaluation • Recommended altering grading scale- medium/large varices same therapy recommendations

20. PillCam ESO for esophageal varicesMethods: PillCam ESO grading of varices C0 C1 C2

21. Pillcam ESO vs. EGD • Multi center intl trial- 288 patients DeFranchis et al Hepatology 2008 - Sens 85%, Spec 88%, PPV 92%, NPV 77% • Agreement in treatment decision 91% (kappa 0.77) • No need for endoscopic treatment- beta blockade • Able to discern med/large varices without insufflation • Esophageal transit not an issue

22. Capsule EndoscopySuspected Barrett’s Esophagus Eliakim R et al. A novel diagnostic tool for detecting oesophageal pathology:the PillCam™ oesophageal video capsule. Aliment Pharmacol Ther. 2004;20:1-7.

23. Published StudiesGERD Screening-BE results Last 3 studies based on histology as gold standard

24. Screening for Barrett’s with CE:meta analysis • 9 studies, 618 pts • Pooled sensitivity/specificity • With EGD as gold standard : sens 77%,spec 86% • With histology : sens 78%, spec 73% • Heterogeneity issues of pooling • Nevertheless-not yet recommended AJG 2009

25. Issues in using ECE for screening for Barrett’s • Visualization !!!!! • Bubbles/saliva/debris- positional? Simethicone? • Incomplete assessment of Z line • ECE transit • Conundrum of short segment BE • Inter/intra observer variability of CE readers/endoscopists • Positive cases need histologic confirmation • EGD as gold standard?

26. Original Simplified Patient ingests lying on right side 00 2 min 300 2 min 600 1 min Capsule propelled by water (15cc every 30 sec) Simplified Ingestion Procedure

27. Image Comparison A Simplified Ingestion Procedure for Esophageal Capsule Endoscopy: Initial Evaluation in Healthy Subjects. Gralnek et al. Endoscopy 2006; 38(9):913-918.

28. Tethered capsule (high tech) Early in vitro/in vivo feasibility data Seibel EJ et al 2008 IEEE Trans Biomed Eng

29. Capsule on a string (low tech) 4 human trials vs. EGD for screening BE/varices Ramirez FC et al GIE 2008

30. Using magnetic forces to control the movement and location of the capsule within the GI tract Procedure time15-20Min Real time image viewing Back and forth navigation Active Capsule – Maneuvering Capabilities

31. ESO EGD Capsule Hand Held maneuvering • Developing simple maneuvering devices for possible application in an EGD capsule • concept: • Substitute for traditional EGD with modality that does not require sedation • Evaluation of the Esophagus for esophageal disorders

32. Flexible Intelligent Color Enhancement • FICE™ is a spectral image processing technology that uses high resolution color discrimination technology • FICE uses software image processing and allows for selectable wavelength combinations that are chosen after the images are collected and reviewed prior to a final report

33. Flexible Intelligent Color Enhancement CE Software • What are the potential benefits? • Enhanced detection of pathological images • Tissue characterization may be easier to see • Can we differentiate between neoplastic lesions and non-neoplastic tissue? • Can this software enhancement be useful with Capsule Endoscopy images? Real-time switch between an ordinary image and an image with Intelligent Color Enhancement

34. Ulceration Normal gastric Ulcer CH1 CH2 CH3

35. Submucosal Tumor with Blood Normal CH1 CH2 CH3

36. Increasing the screening pool • Intent of non invasive diagnostic tests is to increase compliance • Tradeoff of acceptance for ? decreased sensitivity/ diagnosis only • Shifts in screened pool-what if no additional screening, just movement to tests other endoscopy

37. pH SENSOR TRANSMITTER BATTERIES PRESSURE SENSOR MICROPROCESSOR SmartPill Capsule • Ingestible Capsule (5+ days battery life) • Senses and records pH, pressure and temperature data from within the entire GI tract • Wirelessly transmits data to the SmartPill Data Receiver

38. Indications for Use The SmartPill GI Monitoring System measures pressure, pH and temperature throughout the GI tract for use in evaluating patients with suspected delayed gastric emptying (gastroparesis). • These measurements are used to: • Determine gastric emptying time • Determine combined small/large bowel transit time • Determine whole gut transit time • Characterize pressure patterns and provide motility indices for the antrum and duodenum

39. SmartPill – Whole Gut Transit & Motility Gastric Transit Combined Small/Large Bowel Transit

40. Smart Pill Capsule • R=.82 with scintigraphy • May be able to assess colonic/SB transit times distinctly • May help ascertain normal/disease state pH profiles in the gut • Can bring motility assessment to GI docs • retention

41. A Schematic Representation of the Brain-Gut Axis Underlying IBS Central Nervous System Role of capsule Efferent Afferent Enteric Nervous System Intestinal Motility Visceral Hypersensitivity Endoluminal Image Analysis Causes of IBS Hypothesis on Irritable Bowel Syndrom pathophysiology: • Undiagnosed organic disease • Abnormal motility • Intestinal flora disturbances (bacterial overgrowth) • Psychological influences that could cause hypersensitivity • Above conditions could be caused by genetics or environment

42. Endoluminal Image Analysis • Endoluminal imaging provides continuous visualization of intestinal walls, lumen, and content • Permits detection of contractile events, noncontractile patterns, types of contents • Detection and movement of parietal and endoluminal structures • Small bowel motor function can be quantitatively evaluated • Computer algorithms provide the analysis of various endoluminal features Gastroenterology 2008;135:1155-1162

43. Discrimination between patients and healthy subjects Machine learning technique Learning program finds combinations of parameters that best identifies both groups and defines a separating plane Separating IBS patient populations Gastroenterology 2008;135:1155-1162

44. CE of the foregut can… • Provide non invasive assessment of SB ( even beyond foregut..) • Be an alternative to EGD for esophageal varices screening • Be an alternative for gastric emptying assessment

45. CE of the foregut cannot… • Be considered an alternative for Barrett’s screening • Evaluate the stomach completely • Be controlled, perform biopsies or therapy YET

46. The future…. • “I never think about the future it comes soon enough” –A Einstein • Therapeutic CE- magnetic steered CE with nitinol clip released to clip iatrogenic bleeding site- Endoscopy Dec 2008 • Versions 2.0, 3.0 et al- higher frame rates, improved optics, NBI, increased field of view, longer battery lives- all happening now • Integration of physiologic measurements • Therapeutic CE- brushing, cytology, aspiration, drug delivery, external control

47. Thank you

48. Questions????