Adam F.

Barrison, MD Department of Gastroenterology Summit Medical Group

Typical symptoms of GERD

Heartburn Regurgitation (an effortless return

of gastric contents into the esophagus and frequently into the mouth; often confused with vomiting)

Younes and Johnson. Gastroenterol Clin North Am 1999

Atypical symptoms of GERD

Dysphagia Throat clearing Globus Laryngospasm Dental erosion Chest pain Hoarseness Chronic cough Sore throat Wheezing

Mujica et al. Postgrad Med 1999 DeVault et al. Am J Gastroenterol 1999

1

Symptom patterns in GERD

Reflux-related symptoms occur predominantly after meals. Reflux-related symptoms are often triggered by unusually large meals bending, stooping, or lying down strenuous activities The frequency of reflux-related symptoms varies widely
Johnsson et al. Gullet 1992

The GERD iceberg

Persistent symptoms and complications
Titanic

Frequent symptoms (seen by MD) Occasional symptoms (not seen by MD)

Adapted from Castell Gastroesophageal Reflux Disease. Futura Publishing. 1985

Approximately half of all patients with reflux symptoms have erosive esophagitis
Patients presenting with reflux symptoms (n = 97)
Barretts esophagus Erosive esophagitis 46% 12%

42%

No erosive esophagitis

Winters et al. Gastroenterology 1987

Severity of heartburn symptoms does not predict the presence of erosive esophagitis
100 80

Patients (%)

60 40 20 0

Severe Heartburn Grade Moderate Mild

EE Positive

EE Negative

(n=316)

(n=677)

The presence of erosive esophagitis should be diagnostically confirmed. Venables et al. Scand J Gastroenterol 1997

Severity of GERD symptoms does not correlate with severity of disease

No heartburn Mild heartburn Severe heartburn

Patients with heartburn (%)

60 50 40 30 20 10 0 Grade A (n=1466)
N=4283

Moderate heartburn

Grade B (n=1634)

Grade C (n=869)

Grade D (n=314)

Levine et al. Am J Gastroenterol 1999

Frequency of heartburn does not correlate with the presence of erosive esophagitis

100 80 46 18 18 36 Endoscopy negative 24 Endoscopy positive 58 Heartburn frequency 7 days/wk 5 to 6 days/wk 2 to 4 days/wk

% patients

60 40 20 0

Smout. Aliment Pharmacol Ther 1997

Erosive Esophagitis

GERD is a chronic condition that is likely to relapse

100 No mucosal breaks LA grade A LA grade B LA grade C

% patients in symptomatic remission

80 60 40 20 0

Time after cessation of therapy (months)

Lundell et al. Gut 1999

GERD has a greater impact on quality of life than other common diseases
Normal Score

67 Psychiatric patients 84 GERD (untreated) 85 Duodenal ulcer (untreated) 87 Angina pectoris 94 Heart failure (mild) 101 Normal female 103 Normal male 105 Hypertension (untreated) Worse 60 70 80 90 100 110 Better

Population

Psychological General Well-being Index (PGWBI) score

Dimens. Scand J Gastroenterol 1993

Mechanisms that cause GERD

Theophylline Anticholinergics TCAs Progesterone Ca channel blockers Diazapam

Complications of GERD
Esophageal: - Barretts esophagus - Adenocarcinoma - Stricture - Ulceration - Bleeding Extra-esophageal: - Asthma - Chronic Cough - Reflux laryngitis - Dental enamel loss - Vocal cord injury - Subglottic stenosis

Endoscopy
Allows direct mucosal visualization and biopsy Gold standard for diagnosis of erosive esophagitis Only method for reliable detection of Barretts

DeVault et al. Am J Gastroenterol 1999

Esophageal stricture

Barretts esophagus

Barretts esophagus clinical significance

Premalignant lesion for esophageal adenocarcinoma Patients with Barretts esophagus may be 30 60 times more likely to develop this cancer than the general population The reported incidence of adenocarcinoma of the esophagus is rising
Lagergren et al. New Engl J Med 1999

The prevalence of Barretts esophagus increases with the duration of reflux symptoms

Prevalence of probable Barrett's esophagus (%)

25 21 20 15 11 10 5 0 <1 1 to 5 5 to 10 >10 Duration of symptoms (years)

Lieberman et al. Am J Gastroenterol 1997

17

Esophageal adenocarcinoma

The risk of esophageal adenocarcinoma increases with the frequency of reflux symptoms
18 16 14 12 10 8 6 4 2 0

Odds ratio for esophageal adenocarcinoma

16.7

5.1 1.0 None 1/week

6.3

23/week

>3/week

Frequency of symptoms
Lagergren et al. N Engl J Med 1999

The incidence of esophageal adenocarcinoma is rising

Connecticut Cancer Registry 1.2 National Cancer Institute Birmingham, England Canton Vaud, Switzerland *Greatest increase in white males

Cases/100,000/year

1.0 0.8 0.6 0.4 0.2 0 1940 1950 1960 1970 1980 1990

2000

Pera et al. Gastroenterology 1993

Management options in GERD

Lifestyle measures

Medications

Antireflux surgery

Newer endoscopic techniques

What is the role of lifestyle factors in GERD?

Lifestyle factors probably play a lesser role in the pathogenesis of GERD than originally thought
1 .

Dent et al. Gut 1998

Lifestyle measures
Raise the head of the bed, or lie on left side Decrease fat intake? Avoid certain foods Avoid lying down for 3 hours after eating Stop smoking Lose weight if appropriate

Dietary factors that may aggravate GERD symptoms

Caffeinated products (coffee, tea, chocolate) Peppermint Fatty foods?? Spicy and tomato-based foods Citrus foods and juices Alcohol

Evolution of pharmacological therapy

Antacids (Tums, Rolaids) Prokinetics (Reglan, Cisapride) H2-receptor antagonists (Pepcid, Zantac) Proton pump inhibitors (Prilosec, Prevacid)

Mechanisms of Action of GERD Medications

Prokinetics increase esophageal clearance and gastric emptying HCI Antacids neutralize secreted HCl PPIs block acid at its source in the proton pump H2RAs block the histamine receptor, interfering with one of the stimulation pathways

H+

K+

Gastrin ACh
ACh=acetylcholine

Histamine

Stretta Procedure
Approved by FDA in May, 2000 Heat is applied to the deep layer in the lower esophagus Success rate similar to fundoplication: Complete resolution in 70% at 1 year Partial resolution in 10 -15% at 1 year Complication rate considered low: Pain Perforation

Post-procedure appearance

Enteryx
Approved by FDA in April, 2003. Bio-compatible non-biodegradable liquid polymer implanted in the wall of lower esophagus Success rate similar to fundoplication: 74% off medications at 1 year Complication: Damage from injection outside of the esophagus Recalled in October, 2005