prof.dr.ahmet dobrucalı clinical and endoscopic diagnostic assessment of gerd and complications...
TRANSCRIPT
Prof.Dr.Ahmet Dobrucalı
CLINICAL AND ENDOSCOPIC DIAGNOSTIC ASSESSMENT OF GERD AND COMPLICATIONS
İÜ.Cerrahpaşa Tıp FakültesiGastroenteroloji Bilim Dalı
NO2
NO
HCL
Pep
cin
Bile salts Pancreatic enzymes
20% 9-17% 2-5%
2-5%
12-15%
?
-2%
Heartburn prevalence in the World
Dent J. Gut 1999
62%12%
12%
6% 8% <1 per week
1 per week
2-3 per week
4-6 per week
daily
Frequency of heartburn in the United States heartburn population
P&G MRD#US972782, data in Sponsor’s file.
http://www.fda.gov/ohrms/dockets/ac/02/briefing/3861b1_01_ProctorGamble-Zeneca.htm
Asymptomatic Barretts
Occasionally symptomatic Not seen by M.D.
Frequently symptomatic Seen by M.D.
Persistent symptoms and complications (<10%)
Kennedy T.Aliment Pharmacol Ther 2000
GERD Iceberg
60 70 80 90 100 110
Untreated HTN
Normal Men
Normal women
CHF (mild)
Angina pectoris
Untreated DU
Untreated GER
Psychiatric diseases
GERD and QOL
Dimenas T.Scan J Gastroenterıl 1993
Phychological well-being score (NL=104)
The clinical spectrum of GERD
Typical
• Heartburn• Regurgitation
Atypical
• Chest pain• Dysphagia• Cough• Asthma• Laryngitis
Physiological reflux
Symptomatic GERD
Complicated esophagitisEsophagitis
Complications
• Ulceration• Hemorrhage• Stricture• Barrett• Adeno ca.
With erosive esophagitis
Without esophagitis (Requires abnormal pH-metry)
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
Heartburn
Patients with esophagitis
21%
48%
31%
Patients without esophagitis
12%
55%
33%
Severity of heartburn in patients with and without esophagitis
Smout L. Aliment Pharmacol Therap 1997
Severe Moderate Mild
72
40
76
45
74
47
64
48
0
10
20
30
40
50
60
70
80
Heartburn Regurgitation
Pat
ien
ts (
%) Grade 1
Grade 2
Grade 3
Grade 4
Incidence of regurgitation and heartburn are unrelated to grade of esophagitis
Carisson E,Gastroenterol 1996
(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)
Negative pH monitoring or
(MII+pH)
Microscopic erosive reflux disease
Presence of high
symptom index
No symptom index
GERD Hypersensitive
esophagus?
Functional heartburn?
Non acid related stimuli?
Minor acid reflux?
(pH>4)
(E-GERD)
Erosive reflux disease
(M-GERD) (Metaplasic
reflux disease)Barrett
GERD
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
PresentationHigh burden of typical and
atypical symptomsTypical 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
ComplicationsAssociated 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
Fox M, BMJ 2006
(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)
Negative pH monitoring or
(MII+pH)
Microscopic erosive reflux disease
Presence of high symtom
index
No symptom index
GERD Hypersensitive
esophagus?
Functional heartburn?
Non acid related stimuli?
Minor acid reflux?
(pH>4)
(E-GERD)
Erosive reflux disease
(M-GERD) (Metaplasic
reflux disease)Barrett
GERD
Fass R,Ofman JJ. Am J Gastroenterol 2002.
Symptomatic GERD
Erosive GERD
Barrett
Is GERD a single spectrum disease?
33 patients with NERD
confirmed by positive pH monitoring
3% is symptom free
Symptoms are moderate or severe in
67%
17 patients underwent
repeat endoscopy
94% (16) have erosive esophagitis
After 10 years
After 5 years
Pace F. Dig Liver Dis 2004
Atypical and extraesophageal manifestations of GERD
• Chest pain• Epigastric
pain• Nausea
Oral
• Dental eresions
Atypical Extraesophageal
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 ?
CHEST CHEST
PAIN PAIN
IN GERDIN GERD
CHEST CHEST
PAIN PAIN
IN GERDIN GERDMOTILITY DISORDERS
?
REFLUXVISCERAL
HYPERSENSITIVITY?
PHYSICOLOGICAL FACTORS
?
Non-cardiac chest pain
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
• Chest pain• Epigastric
pain• Nausea
Oral
• Dental eresions
Atypical Extraesophageal
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
0
10
2030
40
50
60
7080
90
100
Asthmarecurrentbronchitis
Asthma Asthmacough
Asthma Asthmacough
Asthma
Per
cen
tag
e o
f p
atie
nts
Prevalence of abnormal acid exposure in adult asthmatics
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
0
5
10
15
20
25
30
35
40
Baseline Tx1 Tx2 Tx3
Time (Months)
asth
ma
sym
pto
m s
core
Asthma symptom score in responders to PPI therapy
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
• 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
Patients with a clinical profile highly suggestive of silent GERD as a cause of their cough are characterized by the
following findings;
Reflux laryngitis
Bilateral erythema of medial arythenoid walls
Red streaks on the vocal cords
Effect of omeprazole on oropharyngeal symptoms
1.8
1 1
1.3
0.9
0.7
1.7
1.4
1.21.3
10.8
00.2
0.40.6
0.81
1.2
1.41.6
1.82
Before 4 wk 8 wk
Sym
ptom
sco
re (
0-3)
Hoarseness Throat burning/Pain Throat clearing Cough
Wo JM. Am J Gastroenterol 1997
*p<0.005, **p<0.05 compared to baseline
Possible GERD symptoms
No GER (40%)
Non-acid GER symptoms (40%)
Acid GER with symptoms (20%)
Ambulatory MII-pH monitoring on Rx
Persistent symptomsSuccess
Trial of PPI Rx
Shay S. Gastroenterology 2003
Invasive tests, when?
Barium
esophagogram
-Dysphagia
24 h. esophageal pH
monitoring
-PPI failure (on medication)
-Pre-antireflux surgeryEndoscopy
- 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 • 96% of patients with long-
segment (>3cm) Barrett’s esophagus
• 72% of patients with short-segment (<3cm) Barrett’s esophagus
• 71% of patients with erosive esophagitis
• 30% of patients with NERD
Hiatal hernia
• Los Angeles (LA)• New Savary-Miller • Hetzel • MUSE (Metaplasia,Ulcer, Stricture,Erosions)
Classification systems for esophagitis
• 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
New Savary-Miller endoscopic grading system
Stomach StomachStomach Stomach Stomach
Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
Stomach
StomachStomach
Stomach
• Grade A: >1 mucosal break <5mm long confined to the mucosal folds
• Grade B: >1 mucosal break >5mm long confined to the the mucosal folds but not continious between the tops of 2 folds
• 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
Grade A Grade B
Grade C Grade D
LA classification of esophagitis
Lundell et al Gut 1999
The International Working Group for the Classification of Oesophagitis (IWGCO)
Hetzel classification of esophagitis
Grade 0: NormalGrade 1: Edema, hyperemia and/ or friability of the
mucosaGrade 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
Basal layer
Squamous epithelium
Papillary extensions
Squamous epithelium
Muscularis mucosa
Submucosa
Lamina propria
Circular muscle layer
Longidutinal muscle layer
Basal layer
Squamous epithelium
Papillary extentions
Bazal cell hyperplasia and
elongation of rete pegs
NormalGERD
Tobey N. Gastroenterolgy 1996
MUSE classification of esophagitis
Complications of GERD
Erosive or ulcerative (2-
7%) esophagitis
Peptic stricture (1-
23%)
Barrett’s esophagus
(10-15%)
Bleeding (<2%)
AnemiaDysphagia Esophageal cancer
Extraesophageal
complications
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.
• 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
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
Top of lineer gastric fold
Diaphragmatic hiatus
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>3cm
Long segment BE Short segment BE
Chromoendoscopy
Lugol’s iodine Methylen blue
Maximal extent
of columnar
metaplasia
Gastroesophageal
junction (Tops of
gastric mucosal folds)
Circumferential extent of
columnar metaplasia
Prague C2 M5
Prague
criteria
C&M5cm
2cm
3cm
IWGCO
(Working Group for the
Classification of Reflux Eesophagitis )
Barrett
New endoscopic techniques in the disagnosis of intestinal metaplasia
• Magnification endoscopy
• Autofluorescence endoscopy
• Narrow band imaging (NBI)
Ridge / villous pattern Circular pattern Regular and orderly thin caliber vessels
Irregular and distorded pattern (normal)
Increased density of irregular,dilated and
corkscrew type vessels (abnormal)Sharma P,Gastrointestinal Endoscopy, 2006
A C
D E
B
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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