CLINICAL AND ENDOSCOPIC DIAGNOSTIC ASSESSMENT OF GERD AND COMPLICATIONS

1. İÜ.Cerrahpaşa Tıp Fakültesi Gastroenteroloji Bilim Dalı CLINICAL AND ENDOSCOPIC DIAGNOSTIC ASSESSMENT OF GERD AND COMPLICATIONS Prof.Dr.Ahmet Dobrucalı

2. NO2 HCL Pepcin NO Bile salts Pancreatic enzymes

3. 20% 9-17% 2-5% 2-5% -2% ? 12-15% Heartburn prevalence in the World Dent J. Gut 1999

4. Frequency of heartburn in the United States heartburn population P&G MRD#US972782, data in Sponsor’s file. http://www.fda.gov/ohrms/dockets/ac/02/briefing/3861b1_01_ProctorGamble-Zeneca.htm

5. Persistent symptoms and complications (<10%) Frequently symptomatic Seen by M.D. Occasionally symptomatic Not seen by M.D. GERD Iceberg Asymptomatic Barretts Kennedy T.Aliment Pharmacol Ther 2000

6. GERD and QOL Phychological well-being score (NL=104) Dimenas T.Scan J Gastroenterıl 1993

7. Typical Heartburn Regurgitation Atypical Chest pain Dysphagia Cough Asthma Laryngitis The clinical spectrum of GERD Physiological reflux Complicated esophagitis Esophagitis Symptomatic GERD • Complications • Ulceration • Hemorrhage • Stricture • Barrett • Adeno ca. With erosive esophagitis Without esophagitis (Requires abnormal pH-metry)

8. Heartburn Heartburn can be defined by the presence of substernal discomfort or pain, usually burning in quality, that starts at the epigastrium and radiates towards the mouth • - Heartburn generally is worse following meals and with reclining or lying down • - It is relieved by antacids or other therapies that inhibit gastric acid secretion

9. Severe Moderate Mild Severity of heartburn in patients with and without esophagitis Smout L. Aliment Pharmacol Therap 1997

10. Incidence of regurgitation and heartburn are unrelated to grade of esophagitis Carisson E,Gastroenterol 1996

11. GERD (NERD) Non-erosive reflux disease is characterised by the presence of GERD symptoms but without endoscopically visible breaks (60-70%)or Symptomatic reflux disease (S-GERD) (M-GERD) (Metaplasic reflux disease) Barrett (E-GERD) Erosive reflux disease Negative pH monitoring or (MII+pH) No symptom index Positive pH monitoring or (MII+pH) Presence of high symptom index Functional heartburn? Non acid related stimuli? Minor acid reflux? (pH>4) GERD Hypersensitive esophagus? Microscopic erosive reflux disease Fass R,Ofman JJ. Am J Gastroenterol 2002.

12. Chracteristic response of the esophagus in patients with GERD Fox M, BMJ 2006

13. GERD (NERD) Non-erosive reflux disease is characterised by the presence of GERD symptoms but without endoscopically visible breaks (50-65%)or Symptomatic reflux disease (S-GERD) (M-GERD) (Metaplasic reflux disease) Barrett (E-GERD) Erosive reflux disease Negative pH monitoring or (MII+pH) No symptom index Positive pH monitoring or (MII+pH) Presence of high symtom index Functional heartburn? Non acid related stimuli? Minor acid reflux? (pH>4) GERD Hypersensitive esophagus? Microscopic erosive reflux disease Fass R,Ofman JJ. Am J Gastroenterol 2002.

14. Erosive GERD Symptomatic GERD Barrett Is GERD a single spectrum disease? 3% is symptom free After 10 years 33 patients with NERD confirmed by positive pH monitoring Symptoms are moderate or severe in 67% 17 patients underwent repeat endoscopy 94% (16) have erosive esophagitis After 5 years Pace F. Dig Liver Dis 2004

15. Chest pain Epigastric pain Nausea Oral Dental eresions Atypical and extraesophageal manifestations of GERD Atypical Extraesophageal • Pulmonary • Chronic cough • Asthma • Aspiration • Pulmonary fibrosis • Recurrent pneumonia • Pharyngolaryngeal • Hoarseness • Globus sensation • Sore throat • Vocal cord irritation • Vocal cord granulomas/polyps • Posterior laryngitis • Other • Sleep abnormalities • Asthma • Sleep apnea ?

16. Non-cardiac chest pain REFLUX VISCERAL HYPERSENSITIVITY ? CHEST PAIN IN GERD MOTILITY DISORDERS ? PHYSICOLOGICAL FACTORS ?

17. Esophageal chest pain usually; Produces pressure like squeezing or burning Can radiate to neck,jaw,back or arms May be sharp and severe Resolves or abates often spontaneously when treated with antacids or nitrates Features in the history that help to distinguish esophageal pain from cardiac pain; Aytipical response to exercise Pain that continued as a background ache Retrosternal pain without lateral radiation Pain that disturbed sleep Presence of certain esophageal symptoms (eg. heartburn, regurgitation, dysphagia) Classical symptoms of angina pectoris versus those arising from esophageal causes

18. Chest pain Epigastric pain Nausea Oral Dental eresions Atypical and extraesophageal manifestations of GERD Atypical Extraesophageal • Pulmonary • Chronic cough • Asthma • Aspiration • Pulmonary fibrosis • Recurrent pneumonia • Pharyngolaryngeal • Hoarseness • Globus sensation • Sore throat • Vocal cord irritation • Vocal cord granulomas/polyps • Posterior laryngitis • Other • Sleep abnormalities • Asthma • Sleep apnea ?

19. Reflux related pulmonary disease • Reflux penetrates UES, and eventually the pulmonary system, leading to asthma symptoms. • It might be a vasovagal reflex, where acidification of the distal esophagus is sufficient to trigger bronchospasm without having acid penetrating the UES. Dumot et al. Contemporary Internal Medicine 1997

20. Prevalence of abnormal acid exposure in adult asthmatics Sontag, Gastroesophageal Reflux Disease and Airway Disease,New York 1999

21. Clues to GERD related asthma • Adult onset • Nonallergic • Poorly responsive to medical therapy • Nocturnal cough • Increase in symptoms after meals, in the supine position. Simpson et al.et al.Arch Int Med 1995

22. Asthma symptom score in responders to PPI therapy Harding SM. Am J Med 1996.

23. Hoarsenes (55-80%) Globus and thoroat clearing (40-58%) Persistent cough (20-52%) Chronic laryngitis (40-60%) Laryngeal carcinoma (25-50%) Laryngeal stenosis (40-75%) Relationship between GERD symptoms and laryngeal lesions *Gaynor L.. Am J Gastroenterol 1991 **Koufman M.Laryngoscope 1991

24. Patients with a clinical profile highly suggestive of silent GERD as a cause of their cough are characterized by the following findings; • Normal or nearly normal chest X-ray • No smoking or exposure to environmental irritants, • No use of ACE inhibitors • Failure of cough to treatment of asthma • Failure of cough to improve with treatment of postnasal drip syndrome

25. Reflux laryngitis Bilateral erythema of medial arythenoid walls Red streaks on the vocal cords

26. Effect of omeprazole on oropharyngeal symptoms *p<0.005, **p<0.05 compared to baseline Wo JM. Am J Gastroenterol 1997

27. Possible GERD symptoms Trial of PPI Rx Persistent symptoms Success Ambulatory MII-pH monitoring on Rx Acid GER with symptoms (20%) No GER (40%) Non-acid GER symptoms (40%) Shay S. Gastroenterology 2003

28. Invasive tests, when? Barium esophagogram -Dysphagia 24 h. esophageal pH monitoring -PPI failure (on medication) -Pre-antireflux surgery Endoscopy - Alarm symptoms Dysphagia,weight loss odynophagia,anorexiableeding - Exclude Barrett’s esophagus Dysphagia - Patients requiring chronic therapy 24 h. Impedance-pH monitoring Acid perfusion test (Bernstein)

29. Hiatal hernia • 96% of patients with long-segment (>3cm) Barrett’s esophagus • 72% of patients with short-segment (<3cm) Barrett’s esophagus • 71% of patients with erosive esophagitis • 30% of patients with NERD Hiatal hernia

30. Classification systems for esophagitis • Los Angeles (LA) • New Savary-Miller • Hetzel • MUSE (Metaplasia,Ulcer, Stricture,Erosions)

31. Grade 5 Grade 3 Grade 2 Grade 1 Grade 4 Stomach Stomach Stomach Stomach Stomach New Savary-Miller endoscopic grading system • Grade 1: Single erosion or exudate; taking only 1 longidutinal fold • Grade 2: Noncircular multiple erosions or exudative lesions taking more than 1 longidutinal fold, with or without confluence • Grade 3: Circular erosive or exudative lesion • Grade 4: Chronic lesions; Ulcers, strictures or short esophagus, isolated or associated with grades 1-3 • Grade 5: Barrett’s esophagus alone or associated with lesions grade 1-3

32. The International Working Group for the Classification of Oesophagitis (IWGCO) Grade A Grade B LA classification of esophagitis • Grade A: >1 mucosal break <5mm long confined to the mucosal folds • Grade B: >1 mucosal break >5mm long confined to the the mucosal folds but not continious between the tops of 2 folds • Grade C: Mucosal breaks continious between the tops of 2 or more folds involving <75% of the esophageal circumference • Grade D: Mucosal breaks involving >75% of the esophageal circumference Stomach Stomach Grade D Grade C Stomach Stomach Lundell et al Gut 1999

33. Hetzel classification of esophagitis Grade 0: Normal Grade 1: Edema, hyperemia and/ or friability of the mucosa Grade 2: Superficial erosions involving <10% of the mucosal surface of last 5mm of the esophageal squamous mucosa Grade 3: Superficial erosions / ulcerations involving 10% to 50% of the mucosal surface of the distal esophagus Grade 4: Deep peptic ulcerations anywhere in the esophagus or confluent erosion >50% of the distal esophagus

34. Squamous epithelium Muscularis mucosa Lamina propria Submucosa Circular muscle layer Longidutinal muscle layer Squamous epithelium Papillary extensions Basal layer

35. Normal GERD Squamous epithelium Papillary extentions Bazal cell hyperplasia and elongation of rete pegs Basal layer

36. Tobey N. Gastroenterolgy 1996

37. MUSE classification of esophagitis

38. Complications of GERD Erosive or ulcerative (2-7%) esophagitis Peptic stricture (1-23%) Barrett’s esophagus (10-15%) Bleeding (<2%) Anemia Esophageal cancer Dysphagia Chronic cough Asthma Sleep disturbances Hoarseness Larynx ca? Extraesophageal complications

39. Peptic stricture Uncomplicated reflux-related esophageal strictures are; - Typically located at the squamocolumnar mucosal junction and are less than 1cm in lenght. - A long history of heartburn with intermittent dysphagia over a period of months to years without weight loss

40. These patients are typically older and have long-standing GERD symptoms and severity of reflux symptoms decrease gradually with development of esophageal stricture Once a true stricture has been confirmed, the challenge is to determine the etiology as benign or malignant by endoscopy, biopsy and cytologic examination. Barium radiography in peptic stricture

41. Barrett’s esophagus • Development of reflux symptoms at an earlier age • Increased duration of reflux symptoms • Increased severity of nocturnal reflux sypmtoms • Increased complications of GERD (esophagitis, ulceration, stricture and bleeding)

42. Displacing of squamocolumnar junction proximal to gastroesophageal junction Intestinal metaplasia characterized by acid mucin containing goblet cells using combined H&E-alcian blue pH 2.5 stain is detected by performing a biopsy Barrett’s esophagus

43. Endoscopic recognition of Barrett’s esophagus requires; Squamocolumnar junction Gastroesophageal junction Diaphragmatic hiatus

44. Diaphragmatic hiatus Top of lineer gastric fold Mucosal folds best demonstrated by partial deflation of the esophagus

45. The longidutinal esophageal palisade vessels, present in the mucosal layer of the lower esophagus, disappear into the submucosal layer at the GEJ Palisade vessels

46. Long segment and short segment Barrett’s esophagus >3cm < 3cm Long segment BE Short segment BE

47. Lugol’s iodine Methylen blue Chromoendoscopy

48. Prague criteria C&M Maximal extent of columnar metaplasia 3cm 5cm Circumferential extent of columnar metaplasia 2cm Barrett Gastroesophageal junction (Tops of gastric mucosal folds) Prague C2 M5 IWGCO (Working Group for the Classification of Reflux Eesophagitis )

49. New endoscopic techniques in the disagnosis of intestinal metaplasia • Magnification endoscopy • Autofluorescence endoscopy • Narrow band imaging (NBI)

50. A C B Ridge / villous pattern Circular pattern Regular and orderly thin caliber vessels E D Irregular and distorded pattern (normal) Increased density of irregular,dilated and corkscrew type vessels (abnormal) Sharma P,Gastrointestinal Endoscopy, 2006