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New advances in GERD investigation
- 1. What is new in GERD investigation? Samir Haffar M.D. Assistant Professor of Gastroenterology
- 2. What is new in GERD investigation? Bravo capsule Combined MII-pH High resolution manometry Imaging techniques in Barrett’s esophagus MII: Multiple Intraluminal Impedance
- 4. Normal 24 hours esophageal pH monitoring Composite DeMeester score: 8.4 DeMeester normal < 14.72 (95th percentile) Bremner CG et al. Esophageal disease & testing. Taylor & Francis Group, 2005.
- 5. Composite scoring systems Johnson & DeMeester is the most commonly used Percentage of total time pH < 4 Percentage of upright time pH < 4 Percentage of supine time pH < 4 Number of reflux episodes Number of reflux episodes >5 min Longest reflux episode DeMeester score Normal < 14,72
- 6. Normal values of DeMeester’s score 50 healthy volunteers DeMeester TR et al. Ann Surg 1976 ; 184 :459 – 470.
- 7. Symptom association • Symptom index: positive if ≥ 50% • Symptom sensitivity index: positive if 10 % • Symptom association probability calculation: 95% • Integrated acidity Simply giving impression of potential association
- 8. Limitations of esophageal pH monitoring Is it the gold standard? • Normal 24 hr pH in 25% of patients with erosive esophagitis • Some patients with very convincing histories but negative endoscopy & normal pH test • Differences in acid exposure documented between 2 pH probes attached to each other & used simultaneously • Day-to-day variability may be seen with normal pH study in one day & abnormal in another day
- 9. Bravo system (Medtronics) Esophageal Probe 25 x 6 x 5.5 mm Battery pH electrode Suction chamber Radio transmitter Delivery system Receiver 100 x 70 x 30 mm - 165 g
- 10. Advantages of Bravo capsule • Better tolerance by patients • Fixed position of the capsule (6 cm above SCJ*) • Prolonged monitoring under more physiologic conditions (48 hours) * SCJ: squamocolumnar junction
- 11. Bravo normal values 50 asymptomatic volunteers 1st 24 h 2nd 24 h Mean (+ SD) 95th percentile Mean (+ SD) 95th percentile % total time at pH < 4 1.79 (2.16 5.89 1.78 (1.78) 5.64 % upright time at pH < 4 2.45 (3.14) 7.81 2.54 (2.57) 7.46 % supine time at pH < 4 0.37 (1.18) 1.58 0.34 (1.28) 1.29 Number of reflux episodes 21.2 (18.5) 55.30 22.3 (19.8) 56.15 No of reflux episodes >5 min 0.62 (1.21) 3.55 0.75 (1.15) 3.00 Longest reflux episode 3.79 (4.31) 11.23 5.95 (4.52) 17.03 DeMeester score 6.02 (4.82) 15.93 5.95 (4.52) 15.48
- 12. Conventional pH vs Bravo capsule Head to head comparison – 40 patients Bruley des Varannes S. Gut 2005 ; 54 ; 1682 – 1686.
- 13. Bravo capsule Causes of under-recording • Data drop-up • Short reflux event not recorded • Reflux events appear shorter
- 14. Bravo capsule Data drop-out Malfunctions in the electronics or the receiver Interpreted as artifact & not represented in final pH report Improved by 7 cm antenna & use of fiberglass Gastrointest Endoscopy Clin N Am 2005 ; 15 : 307 – 318.
- 15. Bravo capsule Short reflux events not recorded Bruley des Varannes S. Gut 2005 ; 54 ; 1682 – 1686.
- 16. Bravo capsule Reflux events appear shorter Bruley des Varannes S. Gut 2005 ; 54 ; 1682 – 1686.
- 17. Trouble shooting in Bravo capsule • Severe odynophagia & chest pain (5%) Chest radiography to exclude perforation Viscous lidocaine Endoscopic removal if symptoms continue • Capsule detachment • Failure to disloge Endoscopic removal similar to polypectomy
- 18. Bravo capsule Classic early detachment (10% of patients) Easily recognized during inspection of pH tracing Gastrointest Endoscopy Clin N Am 2005 ; 15 : 307 – 318. Sudden prolonged drop in pH represents capsule in stomach Sharp rise as capsule enters small intestine through pylorus
- 19. Endoscopic removal of Bravo capsule Gastrointest Endoscopy Clin N Am 2005 ; 15 : 307 – 318.
- 21. Principle of “MII” • 2 steel rings separated by isolator • Alternating-current generator to apply electrical PD • Circuit closed through electrical charges (ions) contained in structures surrounding the catheter Gastrointest Endoscopy Clin N Am 2005 ; 15 : 257 – 264.
- 22. Impedance scale Refluxate: High conductivity & low impedance Air: Low conductivity & high impedance Bremner CG et al. Esophageal disease & testing. Taylor & Francis Group, New York, 1st edition, 2005.
- 23. Advantages of MII • Content of refluxate Liquid – Gas – Mixed • Direction of bolus Anterograde – retrograde • Height of refluxate • pH characteristics Acid (combined MII-pH) Weekly acid Weekly alkaline Acid re-reflux
- 24. Liquid bolus Gastrointest Endoscopy Clin N Am 2005 ; 15 : 257 – 264. 1) Initial drop Liquid enters impedance-measuring segment 2) Rise Bolus cleared from this segment 3) Overshoot Decreased luminal cross-section during contraction 4) Return to baseline
- 25. Air bolus (Belch, Air swallow) 1) Rapid rise Presence of air bolus inside esophagus 2) Rapid decrease Air bolus clears from this segment Gastrointest Endoscopy Clin N Am 2005 ; 15 : 257 - 264.
- 26. Mixed air – liquid Bolus 1) Rapid Rise Air in front of the bolus 2) Rapid drop Liquid component of mixed bolus 3) Rise Liquid being cleared from this segment 4) Return to baseline Gastrointest Endoscopy Clin N Am 2005 ; 15 : 257 – 264.
- 27. Antegrade bolus movement (MII) Observed during swallowing Progression of impedance from proximal to distal Gastrointest Endoscopy Clin N Am 2005 ; 15 : 257 – 264.
- 28. Retrograde bolus movement (MII) Observed in reflux Progression of impedance from distal to proximal Gastrointest Endoscopy Clin N Am 2005 ; 15 : 257 – 264.
- 29. Combined MII • MII used clinically only in combination – With esophageal manometry (MII-EM) – With pH (MII-pH) • MII not considered as replacement for manometry & pH techniques but as complementary procedure that expands diagnostic potential of esophageal function testing & reflux monitoring
- 30. Combined MII-pH probe • Impedance orifices 3, 5, 7, 9, 15, & 17 cm from the tip • pH orifice 5 cm from the tip • MII-pH probe = pH probe Do not change patient comfort Bremner CG et al. Esophageal disease & testing. Taylor & Francis Group, NY, 1st edition, 2005.
- 31. “Sleuth” monitor – Sandhill “Sleuth” monitor attached to the catheter & worn around a belt during the recording period
- 32. GERD classification by combined MII-pH Acid reflux Reflux with drop of pH from above 4.0 to below 4.0 Superimposed acid reflux (Acid re-reflux) Acid reflux occurs while pH < 4.0 Weakly acidic reflux Reflux results in esophageal pH between 4.0 & 7.0 Weakly alkaline reflux Reflux with nadir esophageal pH does not drop < 7.0 Sifrim D et al. Gut 2004 ; 53 ; 1024 – 1031.
- 33. Acid reflux (MII-pH) Gastrointest Endoscopy Clin N Am 2005 ; 15 : 361 – 371.
- 34. GERD classification by combined MII-pH Acid reflux Reflux with drop of pH from above 4.0 to below 4.0 Superimposed acid reflux (Acid re-reflux) Acid reflux occurs while pH < 4.0 Weakly acidic reflux Reflux results in esophageal pH between 4.0 & 7.0 Weakly alkaline reflux Reflux with nadir esophageal pH does not drop < 7.0 Sifrim D et al. Gut 2004 ; 53 ; 1024 – 1031.
- 35. Superimposed acid reflux (MII-pH) Gastrointest Endoscopy Clin N Am 2005 ; 15 : 361 – 371.
- 36. GERD classification by combined MII-pH Acid reflux Reflux with drop of pH from above 4.0 to below 4.0 Superimposed acid reflux (Acid re-reflux) Acid reflux occurs while pH < 4.0 Weakly acidic reflux Reflux results in esophageal pH between 4.0 & 7.0 Weakly alkaline reflux Reflux with nadir esophageal pH does not drop < 7.0 Sifrim D et al. Gut 2004 ; 53 ; 1024 – 1031.
- 37. Weakly acidic reflux (MII-pH) Gastrointest Endoscopy Clin N Am 2005 ; 15 : 361 – 371.
- 38. GERD classification by combined MII-pH Acid reflux Reflux with drop of pH from above 4.0 to below 4.0 Superimposed acid reflux (Acid re-reflux) Acid reflux occurs while pH < 4.0 Weakly acidic reflux Reflux results in esophageal pH between 4.0 & 7.0 Weakly alkaline reflux Reflux with nadir esophageal pH does not drop < 7.0 Sifrim D et al. Gut 2004 ; 53 ; 1024 – 1031.
- 39. Weakly alkaline reflux (MII-pH) Gastrointest Endoscopy Clin N Am 2005 ; 15 : 361 – 371.
- 40. Recommendations for MII-pH monitoring • Endoscopy-negative patients with heartburn or regurgitation despite PPI & performed on PPI therapy • Utility of impedance in refractory reflux patients with chest pain or extraesophageal symptoms unproven • Current interpretation relies on SI, SSI or SAP • Therapeutic implications of abnormal test unproven ACG Practice Guidelines: Esophageal reflux testing. Am J Gastroenterol 2007 ; 102 : 668 – 685.
- 41. High Resolution Manometry (HRM)
- 42. High-resolution manometry catheter 4.2 mm in diameter 36 solid-state pressure sensors 12 loci in each sensor (arrow) Spaced at 1-cm intervals Recording segment of 35 cm Conklin J, Pimentel M, Soffer E. Color atlas of high resolution manometry. Springer Science & Business Media, NY, USA, 2009.
- 43. Normal High Resolution Manometry Spatiotemporal plot Time on the x-axis Pressure on the y-axis Pressure represented by color Cooler color = lower pressure Warmer color = higher pressure UES pressure esophagus (*) LES pressure stomach (**) Conklin J, Pimentel M, Soffer E. Color atlas of high resolution manometry. Springer Science & Business Media, NY, USA, 2009.
- 44. Hiatus hernia in HRM 2 zones of high pressure in GEJ One at 41 cm: LES (arrow) One at 49 cm: Diaphragm (*) Conklin J, Pimentel M, Soffer E. Color atlas of high resolution manometry. Springer Science & Business Media, NY, USA, 2009.
- 45. pH catheter positioning High Resolution Manometry Conventional manometry Difficult pH catheter positioning in conventional manometry Up to 4 cm too distal compared to positioning based on HRM Fox M R et al. Gut 2008 ; 57 ; 405 – 423.
- 46. Comparison of different manometric methods Conventional pull- through manometry Conventional Sleeve manometry HRM Cost Inexpensive Inexpensive Expensive Fox M R et al. Gut 2008 ; 57 ; 405 – 423. Execution Relatively elaborate Time consuming Relatively elaborate Time consuming Relatively simple Fast Interpretation Requires experience Requires experience Relatively easy LES function & relaxation Limited Yes Yes UES function & relaxation No Limited Yes
- 47. Imaging techniques in Barrett’s esophagus
- 48. Barrett’s esophagus Light white endoscopy Contrast between squamous & columnar epithelium is characteristic of Barrett‟s esophagus
- 49. NBI Endoscopy in short segment BE Image obtained by NBI endoscope Hamamoto Y. J Gastroenterol 2004 ; 39 : 14 – 20. Image obtained by conventional endoscope
- 50. Various imaging techniques in BE • Light endoscopy Magnification endoscopy (ME) Chromoendoscopy (dyes) High-resolution endoscopy (HRE) • Optical endoscopy Narrow band imaging (NBI) Autofluorescence imaging (AFI) Optical coherence tomography • Endomicroscopy Endocytoscopy Confocal microscopy • Optical spectroscopy Fluorescence spectroscopy Raman spectroscopy Elastic scattering spectroscopy • Biomarker-based imaging Sharma P et al. Gastrointest Endosc 2006 ; 64 : 188 – 92.
- 51. Which imaging modalities should be used? • In practice, it is routine to use “screening‟‟ test followed by test with ‘‘higher specificity‟‟ to confirm diagnosis • In future, use an approach based on „„coverage‟‟ by: Screening: HRE, NBI & AFI High specificity: endocytoscopy & confocal endoscopy Sharma P et al. Gastrointest Endosc 2006 ; 64 : 188 – 92.
- 52. Magnification Endoscopy with NBI • Classifications: Mucosal pattern Capillary pattern • Different classification in different studies One simple accepted classification desirable • Lack of large randomized studies • Assess of intra- & interobserver reproducibility Messmann H et al. Gastrointest Endosc 2007 ; 65 : 47 – 49.
- 53. Magnifying endoscopy with NBI in Barrett’s Mucosal pattern 1: Round or oval Goda K et al. Gastrointest Endosc 2007 ; 65 : 36 – 46.
- 54. Goda K et al. Gastrointest Endosc 2007 ; 65 : 36 – 46. Magnifying endoscopy with NBI in Barrett’s Mucosal pattern 2: Long straight
- 55. Goda K et al. Gastrointest Endosc 2007 ; 65 : 36 – 46. Magnifying endoscopy with NBI in Barrett’s Mucosal pattern 3: Villous
- 56. Goda K et al. Gastrointest Endosc 2007 ; 65 : 36 – 46. Magnifying endoscopy with NBI in Barrett’s Mucosal pattern 4: Cerebriform
- 57. Goda K et al. Gastrointest Endosc 2007 ; 65 : 36 – 46. Magnifying endoscopy with NBI in Barrett’s Mucosal pattern 5: Irregular
- 58. Magnifying endoscopy with NBI in Barrett’s Vascular pattern I: Honeycomb-like Goda K et al. Gastrointest Endosc 2007 ; 65 : 36 – 46.
- 59. Magnifying endoscopy with NBI in Barrett’s Vascular pattern II: Vinelike Goda K et al. Gastrointest Endosc 2007 ; 65 : 36 – 46.
- 60. Magnifying endoscopy with NBI in Barrett’s Vascular pattern III: Coiled or curly haired Goda K et al. Gastrointest Endosc 2007 ; 65 : 36 – 46.
- 61. Magnifying endoscopy with NBI in Barrett’s Vascular pattern IV: DNA-spiral like Goda K et al. Gastrointest Endosc 2007 ; 65 : 36 – 46.
- 62. Magnifying endoscopy with NBI in Barrett’s Vascular pattern V: Irregular Goda K et al. Gastrointest Endosc 2007 ; 65 : 36 – 46.
- 63. Combination of mucosal & vascular pattern 58 patients • Barrett’s epithelium Mucosal pattern 4 & capillary pattern IV Significantly raised possibility of SIM (OR: 4.78 & 51.6) • Carcinomas Mucosal pattern 5 & capillary pattern V Detect all carcinomas (100% sensitivity & specificity) SIM: Specialized Intestinal Metaplasia Goda K et al. Gastrointest Endosc 2007 ; 65 : 36 – 46.
- 64. Autofluorescence Imaging (AFI) Prototype endoscopy system • Two separate charge-coupled devices (CCD) One for white-light endoscopy (WLE) & one for AFI • AFI Nondysplastic BE appears green Potentially neoplastic areas appear blue/violet • In a pilot study, AFI detects more dysplastic & neoplastic changes than conventional endoscopy with biopsies Kara MA et al. Gastrointest Endosc 2005 ; 61 : 679 – 85.
- 65. Autofluorescence Imaging in BE Barrett‟s esophagus White-light endoscopy Blue/purple color: HGD/EC Biopsy of blue/purple area: EC Biopsy of green area: no dysplasia Autofluorescence Imaging Kara MA et al. Gastrointest Endosc 2005 ; 61 : 679 – 85.
- 66. Endocytoscopy Based on principle of contact light microscopy • 2 prototypes: probe-based & endoscope-based systems • Mucosa treated with mucolytic agent (N-acetylcysteine) • Staining with methylene blue or toluidine blue • Assessment of cytological & architectural features: Size & shape of nuclei – nucleus-to-cytoplasm ratio • Promising technique with potential clinical benefits but further studies are needed ASGE Technology Committee. Gastrointest Endosc 2009 ; 70 : 610 – 613.
- 67. Endocytoscopy images in esophagus (1400x) Small rounded regularly arranged nuclei of normal mucosa Densely packed darkly stained & enlarged nuclei of SCC ASGE Technology Committee. Gastrointest Endosc 2009 ; 70 : 610 – 613.
- 68. Use of HRE & NBI with careful examination of the BE segment for any lesions suspicious for neoplasia appears to be the best practice ‘Spend more time looking and less time biopsying’’ Sharma P et al. Gastrointest Endosc 2006 ; 64 : 188 – 92.
- 69. Thank You
Editor's Notes
- Intragastric pH Monitoring:The evidence supporting the clinical significance and applicability of gastric pH monitoring is insufficient to recommend its routine use inclinical practice.Proximal pH Recording:available evidence does not support the routine use of proximal pH monitoring in clinical practice.
- Therefore, pH recordings using the wireless pH system improve patients’ ability to perform their daily activities and thus provide a more accurate picture of their acid exposure profile as well as improve their compliance with the study.
- Using the wireless pH system, the 95th percentile for distal esophageal acid exposure for control subjects was 5.3%, a value higher than values reported in several although not all catheter-based system studies. The higher acid exposure threshold reported in healthy controls using the wireless pH system may be the consequence of less restriction in daily activities or the result of a thermal calibration error that existed in the pH catheter systems.The 48-h data could be interpreted using an average of the 2 days or only the 24-h period with the greatest acid exposure (worst day analysis). A significant increase in the sensitivity of pH testing and small decrease in specificity were evident when utilizingthe worst day data compared with either the initial 24-h or overall 48-h data in comparing controls with GERD patients.
- Strong correlation in esophageal acid exposure between 2 systemsCFS under recorded acid exposure
- Relatively new technique developed in early 1990s at Helmholtz Institute in Aachen (Germany)Silny* provided first description of this technique that assesses intraluminal bolus movement by measuring changes in conductivity of intraluminal content
- A recent, multicenter study examined the impedance characteristics of 60 healthy subjects during 24-h ambulatory monitoring. Based on impedance values 5 cm above the LES, the median number of total reflux episodes per 24 h was 30, the majority of which occurred in the upright position.Approximately two-thirds of the episodes were acid and another third weakly acidic reflux. Weakly alkaline reflux was distinctly uncommon in this healthy cohort. Similar frequencies were recently reported from a multicenter European study. References:Shay S, Tutuian R, Sifrim D, et al. Twenty-four hour ambulatory simultaneous impedance and pH monitoring: A multicenter report of normal values from 60 healthy volunteers. Am J Gastroenterol 2004;99:1037–43.Zerbib F, Bruley des Barannes S, Roman S, et al. 24 hour ambulatory esophageal multichannel intraluminal impedance-pH in healthy European subjects. Gastroenterology 2005;128:A396.
- In the esophagus, this enables simultaneous recording from all segments, including the sphincteric regions, pharynx, and stomach, without the need to reposition the catheter during the study, the so-called pull-through technique.
- 2 major potential indications for NBI and HRE:1- Detecting specialized intestinametaplasia (SIM) in the short form of the condition 2- More importantly, identifying areas of dysplasia/carcinoma in patients with BO under surveillance
- As neoplastic foci in the oesophagus may not be recognisable at endoscopy. The recommended surveillance protocol (the so-called Seattle protocol) consists of random four-quadrant biopsies at1–2 cm intervals cm in the absence of morphologically distinct lesions such as plaques, nodules, or ulcers.This protocol, however, is time consuming, costly, and insensitive due to the patchy nature of HGIN and early cancer in BE.Of note, the distribution of SIM in the columnar lined distal oesophagus has also been shown to be patchy, with a yield for standard biopsy of 80% for long-segment BO (> 3 cm) and 30% for short segment BO (< 3 cm).An ideal technique would be one that could detect the maximum number of cases of metaplasia and dysplasia with the minimum (or none) number of biopsy specimens.
- Magnifying electronic endoscope used was a GIF-Q240ZAuthors used for the first time the combination of a mucosal surface and capillary pattern. Maximum magnification ratio, X 80; Olympus Medical Systems Co, Tokyo, Japan
- Magnifying electronic endoscope used was a GIF-Q240ZMaximum magnification ratio, X 80; Olympus Medical Systems Co, Tokyo, JapanAuthors used for the first time the combination of a mucosal surface and capillary pattern.
- Magnifying electronic endoscope used was a GIF-Q240ZMaximum magnification ratio, X 80; Olympus Medical Systems Co, Tokyo, JapanAuthors used for the first time the combination of a mucosal surface and capillary pattern.
- Magnifying electronic endoscope used was a GIF-Q240ZMaximum magnification ratio, X 80; Olympus Medical Systems Co, Tokyo, JapanAuthors used for the first time the combination of a mucosal surface and capillary pattern.
- Magnifying electronic endoscope used was a GIF-Q240ZMaximum magnification ratio, X 80; Olympus Medical Systems Co, Tokyo, JapanAuthors used for the first time the combination of a mucosal surface and capillary pattern.
- Magnifying electronic endoscope used was a GIF-Q240ZMaximum magnification ratio, X 80; Olympus Medical Systems Co, Tokyo, Japan.Authors used for the first time the combination of a mucosal surface and capillary pattern. Combining the narrow band imaging system and a magnifying endoscope allows simple and clear visualization of micropatterns of the superficial mucosal layer, its fine mucosal pattern and its capillary pattern, simply by switching the lighting system, without the need for dye or acetic acid.
- Vinelike: تشبة الكرمةMagnifying electronic endoscope used was a GIF-Q240ZMaximum magnification ratio, X 80; Olympus Medical Systems Co, Tokyo, JapanAuthors used for the first time the combination of a mucosal surface and capillary pattern. Combining the narrow band imaging system and a magnifying endoscope allows simple and clear visualization of micropatterns of the superficial mucosal layer, its fine mucosal pattern and its capillary pattern, simply by switching the lighting system, without the need for dye or acetic acid.
- Coiled: سلسلة أنابيبMagnifying electronic endoscope used was a GIF-Q240ZMaximum magnification ratio, X 80; Olympus Medical Systems Co, Tokyo, JapanAuthors used for the first time the combination of a mucosal surface and capillary pattern. Combining the narrow band imaging system and a magnifying endoscope allows simple and clear visualization of micropatterns of the superficial mucosal layer, its fine mucosal pattern and its capillary pattern, simply by switching the lighting system, without the need for dye or acetic acid.
- Magnifying electronic endoscope used was a GIF-Q240ZMaximum magnification ratio, X 80; Olympus Medical Systems Co, Tokyo, JapanAuthors used for the first time the combination of a mucosal surface and capillary pattern. Combining the narrow band imaging system and a magnifying endoscope allows simple and clear visualization of micropatterns of the superficial mucosal layer, its fine mucosal pattern and its capillary pattern, simply by switching the lighting system, without the need for dye or acetic acid.
- Magnifying electronic endoscope used was a GIF-Q240ZMaximum magnification ratio, X 80; Olympus Medical Systems Co, Tokyo, JapanAuthors used for the first time the combination of a mucosal surface and capillary pattern. Combining the narrow band imaging system and a magnifying endoscope allows simple and clear visualization of micropatterns of the superficial mucosal layer, its fine mucosal pattern and its capillary pattern, simply by switching the lighting system, without the need for dye or acetic acid.
- Prototype AF endoscopy system used in this study includes a high resolution videoendoscope and an AF imaging (AFI) modality.The high-resolution videoendoscope in this system has two separate monochromatic charge-coupled devices (CCD); one for white-light endoscopy (WLE), and one for AFI. The AF image, therefore, has 3 spectral components: (1) total AF in response to blue light excitation, (2) green reflectance light, and (3) red reflectance light. WLE and AFI can be alternated by means of a switch located conveniently on the endoscope.