Gastroesophageal Reflux Disease

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Gastroesophageal Reflux Disease

• Rajeev Jain, MD
• November 27, 2006

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Outline

• Definition
• Epidemiology
• Pathophysiology
• Diagnosis
• Treatment
• Management

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Definition

• No gold standard
• Montreal Definition
• a condition which develops when the reflux of
  stomach contents causes troublesome symptoms
  and/or complications

Vakil N, et al. Am J Gastroenterol
101(8)1900-20.2006.
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Classification

• Endoscopy
• Erosive esophagitis
• Los Angeles classification
• Non-erosive reflux disease (NERD) or endoscopy
  negative reflux disease (ENRD)
• Symptoms
• Esophageal
• Extra-esophageal

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LA Classification
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Epidemiology

• Prevalence
• Symptoms in western populations
• 25 monthly
• 12 weekly
• 5 daily
• Incidence
• 1.5 3 develop weekly GERD per yr

Moayyedi P, Axon ATR. Aliment Pharmacol Ther
22(S1)11-9.2005.
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Risk Factors

• Demographic
• Age gender not a major difference
• Lifestyle Environmental
• Obesity, EtOH, tobacco have weak associations
  (OR 1.5 2.5) 1
• H. pylori has no impact 2
• Genetic
• Higher concordance in mono- than dizygotic twins 1

1. Moayyedi P Talley NJ. Lancet
3672086-100.2006. 2. Raghunath AS, et al.
Aliment Pharmacol Ther 20733-44.2004.
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Pathophysiology

• Primary mechanism impaired function of the
  lower esophageal sphincter (LES)
• In most patients with GERD, exposure of the
  esophagus to refluxate is greater than normal
• In a minority of patients, exposure is within
  normal limits in these patients, GERD may be due
  to decreased mucosal resistance to refluxate

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Mechanisms of Acid Reflux
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Defective Esophageal Clearance

• Ineffective peristalsis
• Reduced salivary secretion
• Reduced secretion from esophageal submucosal
  glands

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LES dysfunction

• Inappropriate and prolonged transient relaxations
• Reduction in basal LES pressure/tone

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Substances that Decrease LES Pressure

• Hormones
• Secretin
• Cholecystokinin
• Glucagon
• Somatostatin
• Progesterone

• Foods
• Fat
• Chocolate
• Ethanol
• Peppermint
• Medications

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Medications that Decrease LES Pressure

• ?-adrenergic agonists
• Theophylline
• Anticholinergics
• Tricyclic antidepressants

• ?-adrenergic antagonists
• Diazepam
• Calcium channel blockers

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Hiatal Hernia

• May trap a reservoir of gastric contents above
  the diaphragm, increasing reflux
• May compromise LES function

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Increased Intra-abdominal Pressure

• Pregnancy
• Obesity
• Bending
• Straining
• Coughing
• Tight clothes

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Delayed Gastric Emptying

• May result in an increase in the volume of
  gastric contents available for reflux into the
  esophagus
• Exact role in GERD remains to be clarified

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Diagnostic Methods

• History
• Endoscopy
• Empiric therapy
• pH monitoring
• Radiology

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History

• History taking is the primary diagnostic tool
  for GERD
• Heartburn sensation of discomfort or burning
  behind the sternum rising up to the neck
• Regurgitation effortless return of gastric
  contents into the pharynx
• Accuracy of symptoms when compared to endoscopy
  as gold standard
• Sensitivity 30-76
• Specificity 45-68

Moayyedi P, et al. JAMA 2951566-76.2006.
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Endoscopy

• Allows direct visualization of the esophageal
  mucosa and biopsy if necessary
• Presence and severity of erosive esophagitis
• Detection of complications such as stricture or
  Barretts esophagus

DeVault et al. Am J Gastroenterol 1999
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Advances in Endoscopy

• Ultra-thin endoscopes
• Transnasal or oral
• No sedation
• Magnification endoscopy
• Capsule endoscopy

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Referral for Endoscopy

• Chronic symptoms requiring continuous
  acid-suppression therapy
• Persistent suspected GERD symptoms that fail to
  respond to acid suppression
• Any new GERD patient over the age of 40
• Warning signs
• Weight loss
• Anemia or Bleeding
• Dysphagia

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Empiric TherapyPPI Test

• Logical as GERD is an acid-related disorder
• Normal or high-dose PPI for 1-4 wks in the
  diagnosis of GERD (gold standard was 24 hr
  ambulatory pH study)
• Sensitivity 78 (95 CI 66-86)
• Specificity 54 (95 CI 44-65)

Numans ME, et al. Ann Intern Med 140518-27.2006.
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pH Monitoring

• Allows investigation of
• the amount and timing of reflux
• the correlation between reflux and symptoms
• the effect of therapy on reflux
• In general, most useful in
• endoscopy-negative patients
• patients with chest pain or pulmonary/upper
  respiratory symptoms
• patients with refractory symptoms

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pH Monitoring

• 24 hr pH monitoring
• single best test
• 50-60 will have abnormalities
• new device
• BRAVO probe
• 48 hr monitoring

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pH Monitoring
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Barium Esophagram

• Now considered to be of very limited practical
  value in the diagnosis of GERD1
• May be helpful in the detection of subtle
  strictures and hiatal hernias in patients with
  dysphagia
• May be helpful in identifying pathologies
  unrelated to GERD

1Dent et al. Gut 1999
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The Pyramid of Diseases Associated with GERD
Yes
0
Misc
Asthma
ENT
Need to investigate role of acid
Prevalence of GERD
Chest pain
Non-erosive reflux disease
Erosive esophagitis
100
No
Richter. Am J Gastroenterol 2000
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Complications of GERD

• Esophageal
• Barretts esophagus
• adenocarcinoma
• stricture
• ulceration
• bleeding

• Extra-esophageal
• asthma
• reflux laryngitis
• vocal cord ulcers
• subglottic stenosis
• tracheal stenosis

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Esophageal stricture
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Barretts Esophagus
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Barretts Esophagus Clinical Significance

• Premalignant lesion for esophageal adenocarcinoma
• Patients with Barretts esophagus may be 3060
  times more likely to develop this cancer than the
  general population1
• The reported incidence of Barretts esophagus is
  rising

1Lagergren et al. New Engl J Med 1999
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The Risk of Esophageal Adenocarcinoma Increases
with

• Frequency of reflux symptoms
• OR 16.7 with gt 3/wk
• Duration of reflux symptoms
• OR 16.4 with greater than 20 yrs
• Severity of reflux symptoms
• OR 20 with most severe score

Lagergren et al. N Engl J Med 1999
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Treatment
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Treatment Options

• Lifestyle measures
• Pharmacological therapy
• Initial therapy
• Maintenance therapy
• Antireflux surgery
• Endoscopic techniques

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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

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Aggravating Dietary Factors

• Caffeinated products
• Peppermint
• Fatty foods
• Chocolate

• Spicy foods
• Citrus fruits and juices
• Tomato-based products
• Alcohol

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Pharmacological Therapy

• Antacids
• Prokinetics
• Acid suppression
• Histamine 2-receptor antagonists (H2RAs)
• Proton pump inhibitors (PPIs)

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Acid SuppressionErosive Esophagitis Initial
Therapy

• H2RA v placebo (4-8 wks of therapy)
• 18 trials, 2134 patients
• NNT 5 (95 CI, 3-22)
• PPI v placebo
• 5 trials, 635 patients
• NNT 2 (95 CI, 1.4-2.5)
• PPI v H2RA
• 26 trials, 4064 patients
• NNT 3 (95 CI, 2.8-3.6)

Khan M, et al. Cochrane Database Syst Rev.2006.
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Acid SuppressionErosive Esophagitis
Maintenance Therapy

• 80 relapse after 6-12 months off therapy
• PPI v H2RA
• 10 trials, 1583 patients, 24-52 wks of therapy
• Relapse rate
• 22 in PPI group
• 58 in H2RA group
• NNT 2.5 (95 CI, 2.0-3.4)

Donnellan C, et al. Cochrane Database Syst
Rev.42004.
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Antireflux Surgery Procedures
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Antireflux Surgery use and efficacy

• Antireflux surgery is an option as maintenance
  therapy for patients with well documented GERD1
• The efficacy of antireflux surgery is similar to
  that of chronic PPI therapy2
• The outcome of surgery is highly dependent on the
  skill and experience of the surgeon2

1DeVault et al. Am J Gastroenterol 1999 2Dent et
al. Gut 1999
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Endoscopic Therapy

• Three FDA approved techniques
• Stretta radiofrequency therapy to LES
• EndoCinch endoscopic gastroplication
• Enteryx 8 ethylene vinyl alcohol copolymer

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Endoscopic Gastroplication
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ManagementGoals

• Provide complete relief from heartburn and other
  symptoms
• Heal underlying erosive esophagitis
• Treat or prevent complications
• Prevent recurrence

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Management

• Clinical diagnosis
• Endoscopy in pts with alarm symptoms
• PPI once daily taken 30 min before breakfast for
  4-8 weeks
• If symptoms resolve, consider on-demand therapy
  or step down
• Relapse is common

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Management

• If symptoms persist despite daily PPI
• Nonadherence
• Inadequate dosing or timing
• Nocturnal acid breakthrough
• Rare
• Zollinger-Ellison syndrome
• Drug resistance
• Surgery right patient and right surgeon

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