Download GERD

Gastroesophageal
Reflux Disease
Rajeev Jain, MD
November 27, 2006
GERD
Outline
Definition
Epidemiology
Pathophysiology
Diagnosis
Treatment
Management
GERD
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.
GERD
Classification
 Endoscopy
– Erosive esophagitis
 Los Angeles classification
– Non-erosive reflux disease (NERD) or endoscopy
negative reflux disease (ENRD)
 Symptoms
– Esophageal
– Extra-esophageal
LA Grade A
LA Grade B
LA Grade C
LA Grade D
GERD
LA Classification
GERD
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.
GERD
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 367:2086-100.2006.
2. Raghunath AS, et al. Aliment Pharmacol Ther 20:733-44.2004.
GERD
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
GERD
Mechanisms of Acid Reflux
Defective Esophageal
Clearance
Ineffective peristalsis
Reduced salivary
secretion
Reduced secretion
from esophageal
submucosal glands
GERD
GERD
LES ‘dysfunction’
Inappropriate
and prolonged
transient
relaxations
Reduction in
basal LES
pressure/tone
GERD
Substances that Decrease
LES Pressure
Hormones
–
–
–
–
–
Secretin
Cholecystokinin
Glucagon
Somatostatin
Progesterone
Foods
–
–
–
–
Fat
Chocolate
Ethanol
Peppermint
Medications
GERD
Medications that Decrease
LES Pressure
-adrenergic
agonists
Theophylline
Anticholinergics
Tricyclic
antidepressants
-adrenergic
antagonists
Diazepam
Calcium channel
blockers
GERD
Hiatal Hernia
May trap a
reservoir of gastric
contents above the
diaphragm,
increasing reflux
May compromise
LES function
GERD
Increased Intra-abdominal
Pressure
Pregnancy
Obesity
Bending
Straining
Coughing
Tight clothes
GERD
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
GERD
Diagnostic Methods
History
Endoscopy
Empiric therapy
pH monitoring
Radiology
GERD
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 295:1566-76.2006.
GERD
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
Barrett’s esophagus
DeVault et al. Am J Gastroenterol 1999
GERD
Advances in Endoscopy
Ultra-thin endoscopes
– Transnasal or oral
– No sedation
Magnification endoscopy
Capsule endoscopy
GERD
Referral for Endoscopy
 Chronic symptoms requiring continuous acidsuppression 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
GERD
Empiric Therapy
PPI 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 140:518-27.2006.
GERD
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
GERD
pH Monitoring
24 hr pH
monitoring
– single best test
– 50-60% will have
abnormalities
– new device:
BRAVO probe
48 hr monitoring
GERD
pH Monitoring
GERD
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
GERD
The Pyramid of Diseases
Associated with GERD
0%
Yes
Misc
Asthma
ENT
Prevalence
of GERD
Need to
investigate
role of acid
Chest pain
Non-erosive reflux disease
Erosive esophagitis
100%
No
Richter. Am J Gastroenterol 2000
GERD
Complications of GERD
Esophageal
–Barrett’s
esophagus
–adenocarcinoma
–stricture
–ulceration
–bleeding
Extraesophageal
–asthma
–reflux laryngitis
–vocal cord ulcers
–subglottic
stenosis
–tracheal stenosis
GERD
Esophageal stricture
Barrett’s Esophagus
GERD
Barrett’s Esophagus
Clinical Significance
GERD
Premalignant lesion for esophageal
adenocarcinoma
Patients with Barrett’s esophagus may
be 30–60 times more likely to develop
this cancer than the general
population1
The reported incidence of Barrett’s
esophagus is rising
1Lagergren
et al. New Engl J Med 1999
GERD
The Risk of Esophageal
Adenocarcinoma Increases with:
 Frequency of reflux
symptoms
– OR 16.7 with > 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
Treatment
GERD
Treatment Options
Lifestyle measures
Pharmacological therapy
–Initial therapy
–Maintenance therapy
Antireflux surgery
Endoscopic techniques
GERD
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
GERD
Aggravating Dietary Factors
Caffeinated
products
Peppermint
Fatty foods
Chocolate
Spicy foods
Citrus fruits and
juices
Tomato-based
products
Alcohol
GERD
Pharmacological Therapy
Antacids
Prokinetics
Acid suppression
–Histamine 2-receptor antagonists (H2RAs)
–Proton pump inhibitors (PPIs)
GERD
Acid Suppression
Erosive 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.
GERD
Acid Suppression
Erosive 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.4:2004.
Antireflux Surgery –
Procedures
GERD
Antireflux Surgery –
use and efficacy
GERD
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
GERD
Endoscopic Therapy
Three FDA approved techniques
–Stretta: radiofrequency therapy to LES
–EndoCinch: endoscopic gastroplication
–Enteryx: 8% ethylene vinyl alcohol
copolymer
GERD
Endoscopic Gastroplication
GERD
Management
Goals
Provide complete relief from heartburn
and other symptoms
Heal underlying erosive esophagitis
Treat or prevent complications
Prevent recurrence
GERD
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 ondemand therapy or step down
Relapse is common
GERD
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