CLINICAL AND ENDOSCOPIC DIAGNOSTIC ASSESSMENT OF GERD AND

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

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

Frequency of heartburn in the United States heartburn population P&G MRD#US 972782, data in Sponsor’s file. http: //www. fda. gov/ohrms/dockets/ac/02/briefing/3861 b 1_01_Proctor. Gamble-Zeneca. htm

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

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

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

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 otherapies that inhibit gastric acid secretion

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

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

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 (SGERD) Positive p. H monitoring or (MII+p. H) Microscopic erosive reflux disease (E-GERD) Erosive reflux disease Negative p. H monitoring or (MII+p. H) Presence of high symptom index GERD Hypersensitive esophagus? (M-GERD) (Metaplasic reflux disease) Barrett No symptom index Functional heartburn? Non acid related stimuli? Minor acid reflux? (p. H>4) Fass R, Ofman JJ. Am J Gastroenterol 2002.

Chracteristic response of the esophagus in patients with GERD Chracteristics NERD MERD (Barrett) Prevalence 50% 40% 10% Extent of acid exposure Mild to moderate Mild to severe Moderate to severe Response of mucosa Highly sensitive and reactive to acid reflux (repeated swallowing may protect mucosa from severe disease) Increasing severity or grade of inflammation with increasing exposure to acid Increasing lenght of metaplastic columnar lined esophagus with increasing exposure to acid High burden of typical and atypical symptoms Typical symptoms of reflux, heartburn prominent Delayed presentation or comparatively mild symptoms due to relative intensitivity to acid Response to acid suppression Often incomplete (especially of atypical symptoms) Good symptomatic response and healing of mucosa Prompt symptomatic response but little or no regression of columnar lined esophagus Complications Associated with other functional bowel disease; impaired qualityof life Risk of peptic stricture with severe disease Ulceration and stricture with severe disease Malignant potential Low Relatively high Presentation Fox M, BMJ 2006

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 (SGERD) Positive p. H monitoring or (MII+p. H) Microscopic erosive reflux disease (E-GERD) Erosive reflux disease Negative p. H monitoring or (MII+p. H) Presence of high symtom index GERD Hypersensitive esophagus? (M-GERD) (Metaplasic reflux disease) Barrett No symptom index Functional heartburn? Non acid related stimuli? Minor acid reflux? (p. H>4) Fass R, Ofman JJ. Am J Gastroenterol 2002.

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

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

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

Classical symptoms of angina pectoris versus those arising from esophageal causes 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)

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

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

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

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. Arch Int Med 1995

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

Relationship between GERD symptoms and laryngeal lesions • • • 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%) *Gaynor L. . Am J Gastroenterol 1991 **Koufman M. Laryngoscope 1991

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

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

Effect of omeprazole on oropharyngeal symptoms *p<0. 005, **p<0. 05 compared to baseline Wo JM. Am J Gastroenterol 1997

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

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

Hiatal hernia • • 96% of patients with longsegment (>3 cm) Barrett’s esophagus 72% of patients with shortsegment (<3 cm) Barrett’s esophagus 71% of patients with erosive esophagitis 30% of patients with NERD

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

New Savary-Miller endoscopic grading system Grade 1 Grade 2 Grade 3 Grade 4 Stomach Grade 5 Stomach • 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

Grade A Grade B LA classification of esophagitis • Grade A: >1 mucosal break <5 mm long confined to the mucosal folds • Grade B: >1 mucosal break >5 mmfor longthe confined to the Stomach The International Working Group Stomach the mucosal folds but not between the tops Classification of Oesophagitiscontinious (IWGCO) of 2 folds Grade D Grade C Stomach • 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 Lundell et al Gut 1999

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 5 mm 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

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

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

Tobey N. Gastroenterolgy 1996

MUSE classification of esophagitis

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

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

Barium radiography in peptic stricture • 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.

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)

Barrett’s esophagus • Displacing of squamocolumnar junction proximal to gastroesophageal junction • Intestinal metaplasia characterized by acid mucin containing goblet cells using combined H&E-alcian blue p. H 2. 5 stain is detected by performing a biopsy

Endoscopic recognition of Barrett’s esophagus requires; Squamocolumnar junction Gastroesophageal junction Dia phragmatic hiatus

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

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

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

Chromoendoscopy Lugol’s iodine Methylen blue

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

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

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

Irregular / distorted pattern of villus for the presence of high grade dyasplasia • Sensitivity 100% • Specificity 98. 7% • Positive predictive value 95% Abnormal vascularity for the presence of high grade dyasplasia • Sensitivity 93. 5% • Specificity 86. 7% • Positive predictive value 94. 7% Sharma P, Gastrointestinal Endoscopy, 2006

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