Gastroesophageal Reflux Disease and Barrett’s Esophagus

1. Gastroesophageal Reflux Disease and Barrett’s Esophagus Ryan D. Madanick, MD Assistant Professor of Medicine Director, UNC GI/Hepatology Fellowship Program Center for Esophageal Diseases and Swallowing UNC School of Medicine

2. GERD is a common and significant problem: US study Prevalence (%) 80 males females 60 Any episodeof GERD symptoms 40 At least weeklyepisodes of GERDsymptoms 20 0 25–34 35–44 45–54 55–64 65–74 Age (years) Locke GR et al. Gastroenterology 1997;112:1448.

3. GERD has a greater impact on quality of life than other common diseases Psychiatric patients Esophagitis,untreated Duodenal ulcer, untreated Angina pectoris Heart failure (mild) Normal female Normal male Hypertension, untreated 60 70 80 90 100 110 PGWB Index score Dimenas E. Scand J Gastroenterol 1993;28 Suppl 199:18.

4. Clinical Presentation of GERD Typical/ Esophageal • Heartburn • Acid regurgitation • Atypical/ • Supraesophageal • Chest pain • Laryngitis • Asthma • Sinusitis • Chronic cough • Aspiration pneumonia • Tooth decay

5. Patients do not always correctly identify the symptom of heartburn Describing heartburn as “a burning feeling rising from the stomach or lower chest up towards the neck” can help patients recognise this symptom. Clinician interview/endoscopy • Functional dyspepsia diagnosed • Predominant heartburn excluded Reflux questionnaire • Identifieda burning feeling rising from the stomach or lower chest up towards the neck as their main symptom 42% n=196 Carlsson R et al. Scand J Gastroenterol 1998;33:1023

6. Pathophysiology of GERD Impaired acid neutralization by saliva and HCO3 Impaired esophageal motility LES (inappropriate relaxation) Hiatal hernia Delayed gastric emptying/ gastroparesis LES=lower esophageal sphincter

7. There is only weak evidence that lifestyle factors aggravate GERD symptoms • Obesity: • severity of esophagitis correlates with weight only when BMI >30 kg/m2 • contradictory studies into weight loss indicate no effect/improvement in GERD. • Smoking: • lowers LES pressure and the acid-neutralising effect of saliva. • Physical activity: • running might provoke GERD by increasing TLESRs. Meining A et al. Am J Gastroentero 2000;95:2692.

8. Medications may aggravate GERD symptoms Impairment of LESfunction: • beta-adrenergic agonists • theophylline • anticholinergics • tricyclic antidepressants • progesterone • alpha-adrenergicantagonists • diazepam • calcium channel blockers. Damage to the esophageal mucosa: • acetylsalicylic acid and other NSAIDs • tetracycline • quinidine • bisphosphates.

9. Cough and GERD: 2 Possible Mechanisms Aspiration to lowerrespiratory tree Esophageal–bronchial transmission via cough center Stimulation of vagus nerve Cough response Gastric refluxate Gastric refluxate

10. GERD NERD* 60-70% Erosive Esophagitis 20-30% Barrett’s Esophagus 6-10% Phenotypic Classification of GERD *NERD: Non-Erosive Reflux Disease Fass et al. Alim Pharm Ther 2005

11. ARE YOU A NERD?

12. What are the Symptoms of Symptomatic GERD? • Heartburn • Regurgitation • Chest pain • Impaired QOL • Others (burning mouth/tongue) • Atypical (“supraesophageal”) symptoms • These are the same symptoms as patients with erosive esophagitis and Barrett’s esophagus • The severity of these symptoms CANNOT PREDICT the subtype of GERD into which a patient falls prior to endoscopic examination

14. Taken from Medscape.com

15. Endoscopic Images Normal Squamo-columnar junction LA Grade A Esophagitis LA Grade D Esophagitis

17. Esophageal stricture – endoscopic appearance

18. Metaplasia of the esophagus: Barrett’s esophagus Definition: a change in the esophageal epithelium of any length that can be recognised at endoscopy and is confirmed to have intestinal metaplasia by biopsy of the tubular esophagus and excludes intestinal metaplasia of the cardia. Squamous epithelium Columnar epithelium

19. Barrett’s esophagus is associated with prolonged acid reflux Barrett’s esophagus n=51 Number of episodes Time(minutes) severe esophagitis n=30 20 3 moderate esophagitisn=45 controlsn=24 15 2 10 1 5 0 0 Reflux episodes >5 minutes Mean duration of reflux episode Coenraad M et al. Am J Gastroenterol 1998;93:1068.

20. The prevalence of Barrett’s esophagus increases with the duration of reflux symptoms Prevalence of endoscopic Barrett's esophagus (%) 25 20 15 10 5 0 <1 1–5 5–10 >10 Duration of symptoms (years) Lieberman DA et al. Am J Gastroenterol 1997;92:1293.

21. Does Barrett’s Esophagus Occur in the Absence of Heartburn? • EGD done on 961 pts scheduled for colonoscopy; 556 never had heartburn • Conclusions: • BE is relatively common in persons age >40 years with no prior endoscopy • LSBE is very uncommon in patients who have no history of heartburn Rex D et al. Gastro 2003

22. Reported adenocarcinoma risk in Barrett’s esophagus is dependent on the study size Size of study(patient-years) 1500 True risk is estimated as0.5% per patient-year 1000 500 0 0 10 20 30 Cancer risk per 1000 patient-years Shaheen & Ransohoff 2002

23. Dysplasia in Barrett’s • Prevalence: LGD: 7.3%; HGD: 3%1 • Dysplasia MUST be confirmed • HGD: must aggressively look for prevalent cancers • Screening and surveillance intervals? • Management options for HGD: • Esophagectomy • Ablation • Endoscopic mucosal resection 1Sharma et al. Clin Gastro Hep 2006

24. A 35-year old woman presents to her primary care physician because of six months of heartburn. Her medical history is only notable for chronic migraines. She has no dysphagia, odynophagia, or weight loss. She experiences symptoms several times a week, usually during stressful days at her job as a high school teacher. • What should be done at this point?

25. Initial Management of Heartburn • Antacids and lifestyle changes • H2-receptor antagonists • Standard Proton pump inhibitor therapy • High-dose Proton pump inhibitor therapy • Continuous? • On-Demand? • Endoscopy and/or pH testing followed by therapy based on results

26. Proton Pump Inhibitor Test • Empiric therapy with PPI for heartburn • Functions as both diagnostic test and therapeutic trial • Sensitivity 68-80% as defined by abnormal pH test or endoscopy • May be falsely positive (does not actually make a true diagnosis or GERD) Kahrilas PJ. Am J Gastro 2003;98: S15-23

27. Indications for additional investigations • Atypical history. • Symptoms are frequent and long-standing or do not respond to therapy. • Alarm symptoms are present: • severe dysphagia • weight loss • bleeding • hematemesis • mass in the upper abdomen • anemia

28. The PCP places her on H2-receptor antagonists and recommends lifestyle changes and intermittent antacids. She returns a month later with no change in her symptoms. She is placed on once daily PPI therapy and referred for an upper endoscopy 2 weeks later, which is normal. She is still symptomatic. What should be done now?

29. Increase proton pump inhibitor to twice a day • Refer for endoscopic treatment (Stretta) • Refer for surgical treatment • Perform pH study • Something else (like what?)

30. Why Do PPI’s Fail to Control Symptoms?

31. Reasons for PPI “Failure” • Patient non-compliance • Persistent esophageal acid exposure • Hypersecretory state • Large hiatal hernia • Nocturnal acid breakthrough • Acid-sensitive esophagus • Non-acid reflux • Wrong diagnosis • Functional heartburn (NOT GERD!!)

33. Wireless pH monitoring (Bravo®)

34. Placement of Bravo® capsule

35. What Is Impedance (Z) ? Opposition to Current Flow • Measurement of resistance in an alternating current. • Inversely related to the electrical conductivity of an organ’s wall & contents

36. The Impedance Circuit A Voltage Is Applied Across Ring Set AC Generator

37. Why Does Impedance Change? No bolus = few ions = high impedance Bolus present = many ions = low impedance

38. Impedance Range Low Conductivity = High Impedance Air Esophageal Lining Saliva Food Refluxate High Conductivity = Low Impedance

39. Impedance Bolus Present Bolus entry Bolus exit Time Z-1 Z-2

40. 17 cm 15 cm 9 cm Impedance 7 cm 5 cm 3 cm esophageal 4 4 pH gastric MII-pH detected reflux Acid reflux Non-acid reflux

41. Possible GERD symptoms Trial of PPI Rx Success (Confirm Dx) Persistent symptoms Ambulatory monitoring on Rx (esophageal and gastric) (Combined MII/pH preferred) Acid GER with symptoms No GER Non-acid GER with symptoms GERD DIAGNOSTIC ALGORITHM

42. Treatment Goals for GERD • Eliminate symptoms • Heal esophagitis • Manage or prevent complications • Maintain remission

43. Changes to diet and lifestyle can impair quality of life without improving GERD symptoms • Changes to diet and lifestyle are difficult for some patients and can significantly impair patient quality of life. • Studies into the negative effects of diet and lifestyle on GERD are few in number and the findings are statistically weak. • The criteria for evidence-based medicine arenot met when diet and lifestyle changes are recommended. Dent 1992; Meining & Classen 2000

44. Mechanisms of Actionof GERD Pharmacotherapy Antacids neutralize secreted HCl HCI • PPIs block acid at its source in the proton pump H+ K+ H2RAs block the histamine receptor, interfering with one of the stimulation pathways Gastrin ACh Histamine ACh=acetylcholine

45. Antireflux surgery – an alternative to pharmacological therapy • The efficacy of antireflux surgery in controlling GERD is similar to that of chronic PPI therapy. • The outcome of antireflux surgery is highly dependent on the skill and experience of the surgeon. • Surgery does not always end the need for antisecretory therapy to control the symptoms of GERD. Lundell et al 2001; Spechler et al 2001

46. Nissen fundoplication and the Toupet procedure Nissen fundoplication Toupet procedure

47. Predictors of success of surgery

48. Medication use in follow-up of patientsfrom VA cooperative GERD study Spechler et al, JAMA 2001; 285: 2331

49. No evidence that antireflux surgery protects against cancer development Ye et al, Gastroenterology 2001; 121: 1286