Gastroesophageal Reflux Disease and Barrett

1
Gastroesophageal Reflux Disease and Barretts
Esophagus

• Ryan D. Madanick, MD
• Assistant Professor of Medicine
• Director, UNC GI/Hepatology Fellowship Program
• Center for Esophageal Diseases and Swallowing
• UNC School of Medicine

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GERD is a common and significant problem US study
Prevalence ()
80
males
females
60
Any episodeof GERD symptoms
40
At least weeklyepisodes of GERDsymptoms
20
0
2534
3544
4554
5564
6574
Age (years)
Locke GR et al. Gastroenterology 19971121448.
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GERD has a greater impact on quality of life
than other common diseases
Psychiatric patients
Esophagitis, untreated
Duodenal ulcer, untreated
Angina pectoris
Heart failure (mild)
Normal female
Normal male
Hypertension, untreated
110
60
70
80
90
100
PGWB Index score
Dimenas E. Scand J Gastroenterol 199328 Suppl
19918.
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Clinical Presentation of GERD

• Typical/
• Esophageal
• Heartburn
• Acid regurgitation

• Atypical/
• Supraesophageal
• Chest pain
• Laryngitis
• Asthma
• Sinusitis
• Chronic cough
• Aspiration pneumonia
• Tooth decay

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Patients do not always correctly identify the
symptom of heartburn
Describing heartburn as a burning feeling rising
from the stomach or lower chest up towards the
neck can help patients recognise this symptom.

• Clinician interview/endoscopy
• Functional dyspepsia diagnosed
• Predominant heartburn excluded
• Reflux questionnaire
• Identified a burning feeling rising from the
  stomach or lower chest up towards the neck as
  their main symptom

42
n196
Carlsson R et al. Scand J Gastroenterol
1998331023
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Pathophysiology of GERD
Impaired acid neutralization by saliva and HCO3
Impaired esophageal motility
LES (inappropriate relaxation)
Hiatal hernia
Delayed gastric emptying/ gastroparesis
LESlower esophageal sphincter
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There is only weak evidence that lifestyle
factors aggravate GERD symptoms

• Obesity
• severity of esophagitis correlates with weight
  only when BMI gt30 kg/m2
• contradictory studies into weight loss indicate
  no effect/improvement in GERD.
• Smoking
• lowers LES pressure and the acid-neutralising
  effect of saliva.
• Physical activity
• running might provoke GERD by increasing TLESRs.

Meining A et al. Am J Gastroentero 2000952692.
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Medications may aggravate GERD symptoms

• Impairment of LES function
• beta-adrenergic agonists
• theophylline
• anticholinergics
• tricyclic antidepressants
• progesterone
• alpha-adrenergic antagonists
• diazepam
• calcium channel blockers.

• Damage to the esophageal mucosa
• acetylsalicylic acid and other NSAIDs
• tetracycline
• quinidine
• bisphosphates.

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Cough and GERD 2 Possible Mechanisms
Aspiration to lowerrespiratory tree
Esophagealbronchial transmission via cough
center
Stimulation of vagus nerve
Cough response
Gastric refluxate
Gastric refluxate
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Phenotypic Classification of GERD
NERD Non-Erosive Reflux Disease
Fass et al. Alim Pharm Ther 2005
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• ARE YOU A NERD?

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What are the Symptoms of Symptomatic GERD?

• Heartburn
• Regurgitation
• Chest pain
• Impaired QOL
• Others (burning mouth/tongue)
• Atypical (supraesophageal) symptoms

• These are the same symptoms as patients with
  erosive esophagitis and Barretts esophagus
• The severity of these symptoms CANNOT PREDICT the
  subtype of GERD into which a patient falls prior
  to endoscopic examination

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Taken from Medscape.com
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Endoscopic Images
Normal Squamo-columnar junction
LA Grade A Esophagitis
LA Grade D Esophagitis
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Esophageal stricture endoscopic appearance
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Metaplasia of the esophagus Barretts esophagus
Definition a change in the esophageal
epithelium of any length that can be recognised
at endoscopy and is confirmed to have intestinal
metaplasia by biopsy of the tubular esophagus and
excludes intestinal metaplasia of the cardia.
Squamous epithelium
Columnar epithelium
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Barretts esophagus is associated with prolonged
acid reflux
Barretts esophagus n51
Number of episodes
Time(minutes)
severe esophagitis n30
20
3
moderate esophagitisn45
controlsn24
15
2
10
1
5
0
0
Reflux episodes gt5 minutes
Mean duration of reflux episode
Coenraad M et al. Am J Gastroenterol 1998931068.
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The prevalence of Barretts esophagus increases
with the duration of reflux symptoms
Prevalence of endoscopic Barrett's esophagus ()
25
20
15
10
5
0
lt1
15
510
gt10
Duration of symptoms (years)
Lieberman DA et al. Am J Gastroenterol
1997921293.
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Does Barretts Esophagus Occur in the Absence of
Heartburn?

• EGD done on 961 pts scheduled for colonoscopy
  556 never had heartburn
• Conclusions
• BE is relatively common in persons age gt40 years
  with no prior endoscopy
• LSBE is very uncommon in patients who have no
  history of heartburn

HB (-) (n556) Overall (n961)
Barretts 5.6 6.8
LSBE 0.36 1.2
Rex D et al. Gastro 2003
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Reported adenocarcinoma risk in Barretts
esophagus is dependent on the study size
Size of study(patient-years)
1500
True risk is estimated as0.5 per patient-year
1000
500
0
0
10
30
20
Cancer risk per 1000 patient-years
Shaheen Ransohoff 2002
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Dysplasia in Barretts

• Prevalence LGD 7.3 HGD 31
• Dysplasia MUST be confirmed
• HGD must aggressively look for prevalent cancers
• Screening and surveillance intervals?
• Management options for HGD
• Esophagectomy
• Ablation
• Endoscopic mucosal resection

1Sharma et al. Clin Gastro Hep 2006
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• A 35-year old woman presents to her primary care
  physician because of six months of heartburn.
  Her medical history is only notable for chronic
  migraines. She has no dysphagia, odynophagia, or
  weight loss. She experiences symptoms several
  times a week, usually during stressful days at
  her job as a high school teacher.
• What should be done at this point?

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Initial Management of Heartburn

• Antacids and lifestyle changes
• H2-receptor antagonists
• Standard Proton pump inhibitor therapy
• High-dose Proton pump inhibitor therapy
• Continuous?
• On-Demand?
• Endoscopy and/or pH testing followed by therapy
  based on results

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Proton Pump Inhibitor Test

• Empiric therapy with PPI for heartburn
• Functions as both diagnostic test and therapeutic
  trial
• Sensitivity 68-80 as defined by abnormal pH test
  or endoscopy
• May be falsely positive (does not actually make a
  true diagnosis or GERD)

Kahrilas PJ. Am J Gastro 200398 S15-23
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Indications for additional investigations

• Atypical history.
• Symptoms are frequent and long-standing or do not
  respond to therapy.
• Alarm symptoms are present
• severe dysphagia
• weight loss
• bleeding
• hematemesis
• mass in the upper abdomen
• anemia

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• The PCP places her on H2-receptor antagonists
  and recommends lifestyle changes and intermittent
  antacids. She returns a month later with no
  change in her symptoms. She is placed on once
  daily PPI therapy and referred for an upper
  endoscopy 2 weeks later, which is normal. She is
  still symptomatic.

What should be done now?
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1. Increase proton pump inhibitor to twice a day
2. Refer for endoscopic treatment (Stretta)
3. Refer for surgical treatment
4. Perform pH study
5. Something else (like what?)

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Why Do PPIs Fail to Control Symptoms?
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Reasons for PPI Failure

• Patient non-compliance
• Persistent esophageal acid exposure
• Hypersecretory state
• Large hiatal hernia
• Nocturnal acid breakthrough
• Acid-sensitive esophagus
• Non-acid reflux
• Wrong diagnosis
• Functional heartburn (NOT GERD!!)

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Wireless pH monitoring (Bravo)
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Placement of Bravo capsule
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What Is Impedance (Z) ?

• Opposition to Current Flow

• Measurement of resistance in an alternating
  current.
• Inversely related to the electrical conductivity
  of an organs wall contents

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The Impedance Circuit
A Voltage Is Applied Across Ring Set
AC Generator
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Why Does Impedance Change?

• No bolus few ions high impedance

Bolus present many ions low impedance
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Impedance Range
Low Conductivity High Impedance
Air
Esophageal Lining
Saliva
Food
Refluxate
High Conductivity Low Impedance
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Impedance
Bolus Present
Bolus entry
Bolus exit
Time
Z-1
Z-2
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MII-pH detected reflux
Acid reflux
Non-acid reflux
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GERD DIAGNOSTIC ALGORITHM
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Treatment Goals for GERD

• Eliminate symptoms
• Heal esophagitis
• Manage or prevent complications
• Maintain remission

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Changes to diet and lifestyle can impair quality
of life without improving GERD symptoms

• Changes to diet and lifestyle are difficult for
  some patients and can significantly impair
  patient quality of life.
• Studies into the negative effects of diet and
  lifestyle on GERD are few in number and the
  findings are statistically weak.
• The criteria for evidence-based medicine arenot
  met when diet and lifestyle changes are
  recommended.

Dent 1992 Meining Classen 2000
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Mechanisms of Actionof GERD Pharmacotherapy
Antacids neutralize secreted HCl
HCI

• PPIs block acid at its source in the proton pump

H
K
H2RAs block the histamine receptor, interfering
with one of the stimulation pathways
Gastrin
ACh
Histamine
AChacetylcholine
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Antireflux surgery an alternative to
pharmacological therapy

• The efficacy of antireflux surgery in controlling
  GERD is similar to that of chronic PPI therapy.
• The outcome of antireflux surgery is highly
  dependent on the skill and experience of the
  surgeon.
• Surgery does not always end the need for
  antisecretory therapy to control the symptoms of
  GERD.

Lundell et al 2001 Spechler et al 2001
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Nissen fundoplication and the Toupet procedure
Nissen fundoplication
Toupet procedure
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Predictors of success of surgery
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Medication use in follow-up of patientsfrom VA
cooperative GERD study
Spechler et al, JAMA 2001 285 2331
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No evidence that antireflux surgery protects
against cancer development
Ye et al, Gastroenterology 2001 121 1286