CLINICAL AND ENDOSCOPIC DIAGNOSTIC
ASSESSMENT OF GERD AND COMPLICATIONS
Prof.Dr.Ahmet Dobrucalı
İÜ.Cerrahpaşa Tıp Fakültesi
Gastroenteroloji Bilim Dalı
NO2
NO
Bile salts
Pancreatic
enzymes
Heartburn prevalence in the World
20%
9-17%
2-5%
2-5%
-2%
?
12-15%
Dent J. Gut 1999
Frequency of heartburn in the United States heartburn population
6%
8%
<1 per week
1 per week
12%
2-3 per week
4-6 per week
12%
62%
daily
P&G MRD#US972782, data in Sponsor’s file.
http://www.fda.gov/ohrms/dockets/ac/02/briefing/3861b1_01_ProctorGamble-Zeneca.htm
Persistent symptoms and
complications (<10%)
Frequently symptomatic
Seen by M.D.
Occasionally
symptomatic
Not seen by M.D.
GERD Iceberg
Asymptomatic
Barretts
Kennedy T.Aliment Pharmacol Ther 2000
GERD and QOL
Psychiatric diseases
Untreated GER
Untreated DU
Angina pectoris
CHF (mild)
Normal women
Normal Men
Untreated HTN
60
70
80
90
100
110
Phychological well-being score (NL=104)
Dimenas T.Scan J Gastroenterıl 1993
The clinical spectrum of GERD
Physiological
reflux
Symptomatic
GERD
Typical
• Heartburn
• Regurgitation
With erosive esophagitis
Without esophagitis
(Requires abnormal pH-metry)
Complicated
esophagitis
Esophagitis
Atypical
•
•
•
•
•
Chest pain
Dysphagia
Cough
Asthma
Laryngitis
Complications
•
•
•
•
•
Ulceration
Hemorrhage
Stricture
Barrett
Adeno ca.
Heartburn
Heartburn can be defined by the
presence of substernal discomfort or pain,
usually burning in quality, that starts at the
epigastrium and radiates towards the
mouth
- Heartburn generally is worse following
meals and with reclining or lying down
- It is relieved by antacids or other
therapies that inhibit gastric acid secretion
Severity of heartburn in patients with and without esophagitis
Patients without esophagitis
12%
Patients with esophagitis
33%
21%
31%
55%
48%
Severe
Moderate
Mild
Smout L. Aliment Pharmacol Therap 1997
Incidence of regurgitation and heartburn are unrelated to
grade of esophagitis
80
72
76
74
64
70
Patients (%)
60
50
40
45
47
40
48
Grade 1
Grade 2
Grade 3
30
Grade 4
20
10
0
Heartburn
Regurgitation
Carisson E,Gastroenterol 1996
GERD
(NERD)
Non-erosive reflux disease
is characterised by the
presence of GERD
symptoms but without
endoscopically visible
breaks (60-70%)
or
Symptomatic reflux disease
(S-GERD)
Positive pH
monitoring or
(MII+pH)
Microscopic erosive
reflux disease
(E-GERD)
Erosive reflux disease
Negative pH
monitoring or
(MII+pH)
Presence of
high symptom
index
GERD
Hypersensitive
esophagus?
(M-GERD)
(Metaplasic reflux
disease)
Barrett
No symptom
index
Functional
heartburn?
Non acid related
stimuli?
Minor acid reflux?
(pH>4)
Fass R,Ofman JJ. Am J Gastroenterol 2002.
Chracteristic response of the esophagus in patients with GERD
Chracteristics
NERD
ERD
MERD (Barrett)
Prevalence
50%
40%
10%
Extent of acid
exposure
Mild to moderate
Mild to severe
Moderate to severe
Response of
mucosa
Highly sensitive and reactive to
acid reflux (repeated
swallowing may protect
mucosa from severe disease)
Increasing severity or grade
of inflammation with
increasing exposure to acid
Increasing lenght of
metaplastic columnar lined
esophagus with increasing
exposure to acid
High burden of typical and
atypical symptoms
Typical symptoms of
reflux, heartburn prominent
Delayed presentation or
comparatively mild
symptoms due to relative
intensitivity to acid
Response to acid
suppression
Often incomplete (especially
of atypical symptoms)
Good symptomatic
response and healing of
mucosa
Prompt symptomatic
response but little or no
regression of columnar
lined esophagus
Complications
Associated with other
functional bowel disease;
impaired qualityof life
Risk of peptic stricture with
severe disease
Ulceration and stricture
with severe disease
Malignant potential
Low
Low
Relatively high
Presentation
Fox M, BMJ 2006
GERD
(NERD)
Non-erosive reflux disease
is characterised by the
presence of GERD
symptoms but without
endoscopically visible
breaks (50-65%)
or
Symptomatic reflux disease
(S-GERD)
Positive pH
monitoring or
(MII+pH)
Microscopic erosive
reflux disease
(E-GERD)
Erosive reflux disease
(M-GERD)
(Metaplasic reflux
disease)
Barrett
Negative pH
monitoring or
(MII+pH)
No symptom
index
Presence of
high symtom
index
Functional
heartburn?
GERD
Hypersensitive
esophagus?
Non acid related
stimuli?
Minor acid reflux?
(pH>4)
Fass R,Ofman JJ. Am J Gastroenterol 2002.
Is GERD a single spectrum disease?
Erosive
GERD
Symptomatic
GERD
33 patients
with NERD
confirmed by
positive pH
monitoring
After 10 years
After 5 years
17 patients
underwent
repeat
endoscopy
94% (16)
have erosive
esophagitis
Barrett
3% is
symptom free
Symptoms
are moderate
or severe in
67%
Pace F. Dig Liver Dis 2004
Atypical and extraesophageal manifestations of GERD
Atypical
• Chest pain
• Epigastric
pain
• Nausea
Extraesophageal
•
•
•
•
•
•
•
Oral
Dental eresions
Pharyngolaryngeal
Hoarseness
Globus sensation
Sore throat
Vocal cord irritation
Vocal cord
granulomas/polyps
Posterior laryngitis
•
•
•
•
•
•
•
•
Pulmonary
Chronic cough
Asthma
Aspiration
Pulmonary fibrosis
Recurrent
pneumonia
Other
Sleep
abnormalities
Asthma
Sleep apnea ?
Non-cardiac chest pain
VISCERAL
HYPERSENSITIVITY
?
MOTILITY
DISORDERS
?
REFLUX
CHEST
PAIN
IN GERD
PHYSICOLOGICAL
FACTORS
?
Classical symptoms of angina pectoris versus those arising
from esophageal causes
Esophageal chest pain usually;
• Produces pressure like
squeezing or burning
• Can radiate to neck,jaw,back
or arms
• May be sharp and severe
• Resolves or abates often
spontaneously when treated
with antacids or nitrates
Features in the history that help
to distinguish esophageal pain
from cardiac pain;
• Aytipical response to exercise
• Pain that continued as a
background ache
• Retrosternal pain without
lateral radiation
• Pain that disturbed sleep
• Presence of certain
esophageal symptoms (eg.
heartburn, regurgitation,
dysphagia)
Atypical and extraesophageal manifestations of GERD
Atypical
• Chest pain
• Epigastric
pain
• Nausea
Extraesophageal
•
•
•
•
•
•
•
Oral
Dental eresions
Pharyngolaryngeal
Hoarseness
Globus sensation
Sore throat
Vocal cord irritation
Vocal cord
granulomas/polyps
Posterior laryngitis
•
•
•
•
•
•
•
•
Pulmonary
Chronic cough
Asthma
Aspiration
Pulmonary fibrosis
Recurrent
pneumonia
Other
Sleep
abnormalities
Asthma
Sleep apnea ?
Reflux related pulmonary disease
• Reflux penetrates UES,
and eventually the
pulmonary system,
leading to asthma
symptoms.
• It might be a vasovagal
reflex, where acidification
of the distal esophagus is
sufficient to trigger
bronchospasm without
having acid penetrating
the UES.
Dumot et al. Contemporary Internal Medicine 1997
Percentage of patients
Prevalence of abnormal acid exposure in adult asthmatics
100
90
80
70
60
50
40
30
20
10
0
Asthma
recurrent
bronchitis
Asthma
Asthma
cough
Asthma
Asthma
cough
Asthma
Sontag, Gastroesophageal Reflux Disease and Airway Disease,New York 1999
Clues to GERD related asthma
•
•
•
•
•
Adult onset
Nonallergic
Poorly responsive to medical therapy
Nocturnal cough
Increase in symptoms after meals, in the supine
position.
Simpson et al.et al.Arch Int Med 1995
Asthma symptom score in responders to PPI therapy
asthma symptom score
40
35
30
25
20
15
10
5
0
Baseline
Tx1
Tx2
Tx3
Time (Months)
Harding SM. Am J Med 1996.
Relationship between GERD symptoms and laryngeal lesions
•
•
•
•
•
•
Hoarsenes (55-80%)
Globus and thoroat clearing (40-58%)
Persistent cough (20-52%)
Chronic laryngitis (40-60%)
Laryngeal carcinoma (25-50%)
Laryngeal stenosis (40-75%)
*Gaynor L.. Am J Gastroenterol 1991
**Koufman M.Laryngoscope 1991
Patients with a clinical profile highly suggestive of silent
GERD as a cause of their cough are characterized by the
following findings;
•
•
•
•
•
Normal or nearly normal chest X-ray
No smoking or exposure to environmental irritants,
No use of ACE inhibitors
Failure of cough to treatment of asthma
Failure of cough to improve with treatment of postnasal
drip syndrome
Reflux laryngitis
Bilateral erythema of medial arythenoid walls
Red streaks on the vocal cords
Symptom score (0-3)
Effect of omeprazole on oropharyngeal symptoms
2
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
1.8
1.7
1.3
1.4
1.3
1.2
1
0.9
1
1
0.7
Before
4 wk
Hoarseness
Throat burning/Pain
0.8
8 wk
Throat clearing
Cough
*p<0.005, **p<0.05 compared to baseline
Wo JM. Am J Gastroenterol 1997
Possible GERD symptoms
Trial of PPI Rx
Persistent symptoms
Success
Ambulatory MII-pH monitoring
on Rx
Acid GER with symptoms
(20%)
No GER (40%)
Non-acid GER symptoms (40%)
Shay S. Gastroenterology 2003
Invasive tests, when?
Barium
esophagogram
24 h. esophageal pH
monitoring
-Dysphagia
-PPI failure (on medication)
-Pre-antireflux surgery
Endoscopy
- Alarm symptoms
Dysphagia,weight loss odynophagia,anorexia
bleeding
- Exclude Barrett’s esophagus
Dysphagia
- Patients requiring chronic therapy
24 h. Impedance-pH
monitoring
Acid perfusion test
(Bernstein)
Hiatal hernia
•
•
•
Hiatal hernia
•
96% of patients with longsegment (>3cm) Barrett’s
esophagus
72% of patients with shortsegment (<3cm) Barrett’s
esophagus
71% of patients with
erosive esophagitis
30% of patients with
NERD
Classification systems for esophagitis
•
•
•
•
Los Angeles (LA)
New Savary-Miller
Hetzel
MUSE (Metaplasia,Ulcer, Stricture,Erosions)
New Savary-Miller endoscopic grading system
Grade 1
Grade 2
Grade 3
Grade 4
Stomach
Stomach
Stomach
Stomach
Grade 5
Stomach
•
Grade 1: Single erosion or exudate; taking only 1 longidutinal fold
•
Grade 2: Noncircular multiple erosions or exudative lesions taking more than 1
longidutinal fold, with or without confluence
•
Grade 3: Circular erosive or exudative lesion
•
Grade 4: Chronic lesions; Ulcers, strictures or short esophagus, isolated or
associated with grades 1-3
•
Grade 5: Barrett’s esophagus alone or associated with lesions grade 1-3
Grade A
Grade B
LA classification of
esophagitis
•
Grade A: >1 mucosal break
<5mm long confined to the
mucosal folds
•
Grade B: >1 mucosal break
>5mmfor
longthe
confined to the
Stomach
The International
Working Group
Stomach
the mucosal folds but not
between the tops
Classification of Oesophagitiscontinious
(IWGCO)
of 2 folds
Grade D
Grade C
Stomach
•
Grade C: Mucosal breaks
continious between the tops
of 2 or more folds involving
<75% of the esophageal
circumference
•
Grade D: Mucosal breaks
involving >75% of the
esophageal circumference
Stomach
Lundell et al Gut 1999
Hetzel classification of esophagitis
Grade 0: Normal
Grade 1: Edema, hyperemia and/ or friability of the
mucosa
Grade 2: Superficial erosions involving <10% of the
mucosal surface of last 5mm of the esophageal
squamous mucosa
Grade 3: Superficial erosions / ulcerations involving 10%
to 50% of the mucosal surface of the distal esophagus
Grade 4: Deep peptic ulcerations anywhere in the
esophagus or confluent erosion >50% of the distal
esophagus
Squamous epithelium
Lamina propria
Muscularis mucosa
Submucosa
Circular muscle layer
Longidutinal muscle layer
Squamous epithelium
Papillary extensions
Basal layer
GERD
Normal
Squamous epithelium
Papillary extentions
Bazal cell hyperplasia
and
elongation of rete pegs
Basal layer
Tobey N. Gastroenterolgy 1996
MUSE classification of esophagitis
Complications of GERD
Erosive or
ulcerative (2-7%)
esophagitis
Bleeding (<2%)
Anemia
Peptic stricture
Barrett’s esophagus
(1-23%)
(10-15%)
Dysphagia
Extraesophageal
complications
Esophageal cancer
Chronic cough
Asthma
Sleep disturbances
Hoarseness
Larynx ca?
Peptic stricture
Uncomplicated reflux-related
esophageal strictures are;
- Typically located at the squamocolumnar
mucosal junction and are less than 1cm in
lenght.
- A long history of heartburn with intermittent
dysphagia over a period of months to
years without weight loss
Barium radiography in peptic stricture
•
These patients are typically
older and have long-standing
GERD symptoms and severity
of reflux symptoms decrease
gradually with development of
esophageal stricture
•
Once a true stricture has been
confirmed, the challenge is to
determine the etiology as
benign or malignant by
endoscopy, biopsy and
cytologic examination.
Barrett’s esophagus
• Development of reflux
symptoms at an earlier age
• Increased duration of reflux
symptoms
• Increased severity of
nocturnal reflux sypmtoms
• Increased complications of
GERD
(esophagitis, ulceration,
stricture and bleeding)
Barrett’s esophagus
• Displacing of squamocolumnar
junction proximal to
gastroesophageal junction
• Intestinal metaplasia
characterized by acid mucin
containing goblet cells using
combined H&E-alcian blue pH
2.5 stain is detected by
performing a biopsy
Endoscopic recognition of Barrett’s esophagus requires;
Squamocolumnar junction
Gastroesophageal junction
Diaphragmatic hiatus
Diaphragmatic
hiatus
Top of lineer
gastric fold
Mucosal folds best demonstrated by partial deflation of the esophagus
Palisade vessels
The longidutinal
esophageal palisade
vessels, present in the
mucosal layer of the
lower esophagus,
disappear into the
submucosal layer at the
GEJ
Long segment and short segment Barrett’s esophagus
>3cm
Long segment BE
< 3cm
Short segment BE
Chromoendoscopy
Lugol’s iodine
Methylen blue
Maximal extent
of columnar
metaplasia
3cm
5cm
Gastroesophageal
junction
Prague
criteria
C&M
Barrett
2cm
Circumferential
extent of columnar
metaplasia
(Tops of gastric
mucosal folds)
IWGCO
(Working Group for the
Classification of Reflux Eesophagitis )
Prague C2 M5
New endoscopic techniques in the disagnosis of
intestinal metaplasia
• Magnification endoscopy
• Autofluorescence endoscopy
• Narrow band imaging (NBI)
A
C
B
Ridge / villous pattern
D
Irregular and distorded
pattern (normal)
Circular pattern
Regular and orderly thin
caliber vessels
E
Increased density of irregular,dilated and
corkscrew type vessels (abnormal)
Sharma P,Gastrointestinal Endoscopy, 2006
Irregular / distorted pattern of
villus for the presence of high
grade dyasplasia
• Sensitivity 100%
• Specificity 98.7%
• Positive predictive
value 95%
Abnormal vascularity for the
presence of high grade
dyasplasia
• Sensitivity 93.5%
• Specificity 86.7%
• Positive predictive
value 94.7%
Sharma P,Gastrointestinal Endoscopy, 2006
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