Gastroesophageal Reflux Disease (GERD) and Barrett s Esophagus (BE)

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Gastroesophageal Reflux Disease

(GERD) and Barrett’s Esophagus (BE)

Hashem El-Serag, M.D., M.P.H.

Dan L. Duncan Professor of Medicine Chief, Gastroenterology and Hepatology

Baylor College of Medicine Houston, Texas


Prevalence of GERD

Population-based studies of at least 1-2 episodes per week


Erosive esophagitis (10-30%) Esophageal stricture with chronic erosive esophagitis (1-2%)

Barrett’s esophagus (1-12%) Esophageal adenocarcinoma with Barrett’s esophagus (0.5%


Barrett’s is the Precursor of


Non-Dysplastic BE Low-Grade Dysplasia

High-Grade Dysplasia Adenocarcinoma


Risk factors for Barrett’s


Definite factor associated with increased risk Possible factors associated with increased risk Chronic GERD symptoms Older age Male sex

White race / Caucasian ethnicity

Tobacco smoking

Family history of


GERD Symptoms

Erosive Esophagitis




Variations along the Spectrum of


Men Western countries Whites Women Eastern countries Non- Whites



Nucleus tractus solitarius Dorsal vagal nucleus

Nucleus ambiguus

Respiratory center Phrenic nucleus

Vagus nerve Phrenic nerve

Transient LES relaxation (TLESR)


Distension of proximal stomach


Pathophysiology of GERD increased pressure gradient TLOSRs weak LOS impaired peristalsis

excessive acid secretion

oesophageal hypersensitivity

acid pocket

hiatus hernia

delayed gastric emptying


Large Amount of Visceral Abdominal Fat

Increases Risk of Erosive Esophagitis and

Barrett’s Esophagus

El-Serag HB et al. Gut 2013

173 BE cases, 343 colonoscopy controls and 172 endoscopy controls

BE esp ≥3 cm twice as likely to be in the highest tertile of VAT to SAT ratio


Does it Make “epidemiological”


• Both obesity and GERD are

increasing in parallel

• Abdominal obesity more


– Men more than women – Caucasians more than


Helicobacter pylori (Hp) and the Risk of

Esophageal Disease

• GERD symptoms:

– no consistent association with Hp or Hp treatment

• Esophageal erosions

– Weak inverse association with Hp

• BE and esophageal adenocarcinoma

– Consistent inverse association

– 25-50% lower likelihood of Hp in the presence of



• The Trends

– GERD is a global problem that has high prevalence, and an increasing incidence

– GERD is a risk factor for Barrett’s esophagus and esophageal adenocarcinoma

– Remarkable variations related region, gender and race • Stories behind the Trends

– Increasing obesity

– Increasing chronic GERD – Declining H. pylori


Lifestyle Changes

• Weight loss

• Elevation of head end of bed

• Small frequent meals • Avoid eating before


Over the Counter Meds

• Antacid

• Histamine receptor antagonists


Updated from: Kahrilas PJ, JAMA 1996;276:983 0 10 20 30 40 50 60 70 80 90 100 0 10 20 30 40 50 60 70 80 90 100 Therapeutic gain (% greater than placebo) Placebo Response (%) Disease severity Mild Severe Antacid qid Nizatidine 150mg bid Cimetidine 400mg bid Cimetidine 300mg qid Nizatidine 300mg bid Nizatidine 300mg bid Famotidine 20mg bid Ranitidine 150mg qid Ranitidine 150mg bid Omeprazole 20-40mg qd Lansoprazole 30mg qd Rabeprazole 20mg qd Pantoprazole 40mg qd


PPI efficacy for potential manifestations of GERD

Estimates based on available RCT data

Modified from Kahrilas PJ, et al. Gut 2012;61:1501

0% 25% 50% 75% 100% Esophagitis healing Mild Severe Heartburn relief Esophagitis NERD Regurgitation relief Chest pain (50% relief)

GERD (+pH) GERD (-pH)

Hoarseness (improved)

GERD (-)

Placebo Therapeutic gain

Chronic cough (improved)

GERD (+pH) GERD (-pH)


Which PPI should

you use?






PPIs may decrease the risk of

esophageal cancer in patients with BE

• PPI use was associated with  70% reduction in risk of EAC and/or BE-HGD in patients with BE

Singh S et al. Gut 2013

Prolonged PPIs use may have side effects

• Iron malabsorption

• Bone density loss (and fractures) • Low magnesium

• Low B12

• Increased C difficile


SCJ 6 cm Capsule LES 5 cm Catheter Esophageal pH monitoring


08 10 12 14 16 18 20 22 24 02 04 06 08

symptom episodes • Temporal association between symptom episodes and reflux events

• Esophageal acid exposure

% of time with pH < 4


pH monitoring

Symptomatic GERD

No GERD, functional

GERD, but symptoms not caused by acid reflux

Symptomatic GERD

Esophageal pH monitoring identifies 4 groups

excessive acid exposure

negative symptom association excessive acid exposure

positive symptom assocation

physiological acid exposure negative symptom association physiological acid exposure

positive symptom association

Hypersensitive esophagus

These patients will not respond to any form of antireflux therapy


pH 7 4 1 60 seconds ‘Non-acid’ reflux reflux pH 5.4



Perception modulators tested in GERD:

• acupuncture

• citalopram


Viazis N et al. Am J Gastroenterol 2011; 1662-1167

Effect of citalopram on symptoms in patients with hypersensitive esophagus


Barrett’s Classification and Management

• Non-dysplastic IM

– Surveillance every 3 years

– Detect progression to dysplasia or cancer

• LGD (low-grade dysplasia)

– Surveillance every 6-12 months

– Detect progression to HGD or cancer

• HGD (high-grade dysplasia)

– Surveillance every 3 months

– EMR and ablation: options at select institutions – Esophagectomy


Management Summary

• Treatment

– Life style changes – Antacids

– Gaviscon

– Histamine receptor antagonists – Life style modifications

– Acid suppression (PPI)

• BE


– Ablation for BE with dysplasia

– Endoscopic resection for BE with dysplasia or early cancer