Transcript Madanik - GERD - UNC School of Medicine

Gastroesophageal Reflux
Disease and Barrett’s 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
GERD is a common and significant
problem: US study
Prevalence
(%)
80
males
females
60
Any episode
of GERD symptoms
40
At least weekly
episodes of GERD
symptoms
20
0
25–34
35–44
45–54
55–64
Age (years)
Locke GR et al. Gastroenterology 1997;112:1448.
65–74
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
60
70
80
90
PGWB Index score
Dimenas E. Scand J Gastroenterol 1993;28 Suppl 199:18.
100
110
Clinical Presentation of GERD
Typical/
Esophageal
Atypical/
Supraesophageal
• Heartburn
• Acid regurgitation
• Chest pain
• Laryngitis
• Asthma
• Sinusitis
• Chronic cough
• Aspiration pneumonia
• Tooth decay
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.
42%
n=196
Carlsson R et al. Scand J Gastroenterol 1998;33:1023
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
Pathophysiology of GERD
Impaired acid neutralization by
saliva and HCO3
Impaired esophageal
motility
LES (inappropriate
relaxation)
Hiatal hernia
Delayed gastric emptying/
gastroparesis
LES=lower esophageal sphincter
There is only weak evidence that lifestyle factors
aggravate GERD symptoms
• Obesity:
–
–
severity of esophagitis correlates with weight only when BMI
>30 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 2000;95:2692.
Medications may aggravate
GERD symptoms
Impairment of LES function:
Damage to the esophageal
• beta-adrenergic agonists
mucosa:
• theophylline
• acetylsalicylic acid and other
• anticholinergics
NSAIDs
• tricyclic antidepressants
• tetracycline
• progesterone
• quinidine
• alpha-adrenergic antagonists • bisphosphates.
• diazepam
• calcium channel blockers.
Cough and GERD: 2 Possible
Mechanisms
Aspiration to lower
respiratory tree
Esophageal–bronchial
transmission via
cough center
Stimulation of
vagus nerve
Cough
response
Gastric refluxate
Gastric refluxate
Phenotypic Classification of GERD
GERD
NERD*
60-70%
Erosive
Esophagitis
20-30%
*NERD: Non-Erosive
Reflux Disease
Fass et al. Alim Pharm Ther 2005
Barrett’s
Esophagus
6-10%
ARE YOU A
NERD?
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 Barrett’s esophagus
• The severity of these symptoms CANNOT PREDICT the subtype
of GERD into which a patient falls prior to endoscopic
examination
Taken from Medscape.com
Endoscopic Images
Normal Squamocolumnar junction
LA Grade A
Esophagitis
LA Grade D
Esophagitis
Esophageal stricture – endoscopic
appearance
Metaplasia of the esophagus: Barrett’s
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
Barrett’s esophagus is associated with
prolonged acid reflux
Number of
episodes
20
Time
(minutes)
3
15
Barrett’s esophagus
n=51
severe esophagitis
n=30
moderate esophagitis
n=45
controls
n=24
2
10
1
5
0
0
Reflux episodes >5 minutes
Coenraad M et al. Am J Gastroenterol 1998;93:1068.
Mean duration of reflux episode
The prevalence of Barrett’s esophagus increases with
the duration of reflux symptoms
Prevalence of endoscopic Barrett's esophagus
(%)
25
20
15
10
5
0
<1
1–5
5–10
>10
Duration of symptoms (years)
Lieberman DA et al. Am J Gastroenterol 1997;92:1293.
Does Barrett’s 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 >40 years
with no prior endoscopy
– LSBE is very uncommon
in patients who have no
history of heartburn
Rex D et al. Gastro 2003
HB (-)
Overall
(n=556)
(n=961)
Barrett’s
5.6%
6.8%
LSBE
0.36%
1.2%
Reported adenocarcinoma risk in Barrett’s
esophagus is dependent on the study size
Size of study
(patient-years)
1500
True risk is estimated as
0.5% per patient-year
1000
500
0
0
10
20
Cancer risk per 1000 patient-years
30
Shaheen & Ransohoff 2002
Dysplasia in Barrett’s
• Prevalence: LGD: 7.3%; HGD: 3%1
• 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
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?
Initial Management of Heartburn
A. Antacids and lifestyle changes
B. H2-receptor antagonists
C. Standard Proton pump inhibitor therapy
D. High-dose Proton pump inhibitor therapy
• Continuous?
• On-Demand?
E. Endoscopy and/or pH testing followed by
therapy based on results
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 2003;98: S15-23
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
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?
A. Increase proton pump inhibitor to twice a day
B. Refer for endoscopic treatment (Stretta)
C. Refer for surgical treatment
D. Perform pH study
E. Something else (like what?)
Why Do PPI’s Fail to Control
Symptoms?
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!!)
Wireless pH monitoring (Bravo®)
Placement of Bravo® capsule
What Is Impedance (Z) ?
Opposition to Current Flow
 Measurement of resistance in an
alternating current.
 Inversely related to the electrical
conductivity of an organ’s wall &
contents
The Impedance Circuit
A Voltage Is Applied Across Ring Set
AC
Generator
Why Does Impedance Change?
No bolus = few ions = high impedance
Bolus present = many ions = low impedance
Impedance Range
Low Conductivity = High Impedance
Air
Esophageal Lining
Saliva
Food
Refluxate
High Conductivity = Low Impedance
I
m
p
e
d
a
n
c
e
Z-1
Bolus Present
Bolus entry
Bolus exit
Time
Z-2
MII-pH detected reflux
Acid reflux
Non-acid reflux
17 cm
15 cm
9 cm
7 cm
5 cm
3 cm
4
esophageal
gastric
4
GERD DIAGNOSTIC
ALGORITHM
Possible GERD symptoms
Trial of PPI Rx
Success
(Confirm Dx)
Persistent symptoms
Ambulatory monitoring on Rx
(esophageal and gastric)
(Combined MII/pH preferred)
Acid GER with symptoms
No GER
Non-acid GER with symptoms
Treatment Goals for GERD
•
•
•
•
Eliminate symptoms
Heal esophagitis
Manage or prevent complications
Maintain remission
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 are
not met when diet and lifestyle changes
are recommended.
Dent 1992; Meining & Classen 2000
Mechanisms of Action
of GERD Pharmacotherapy
HCI
H+ K+
H2RAs block the
histamine receptor,
interfering with one
of
the stimulation
pathways
Gastrin
ACh
ACh=acetylcholine
Antacids
neutralize
secreted HCl
PPIs block acid at
its source in the
proton pump
Histamine
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
Nissen fundoplication and the
Toupet procedure
Nissen fundoplication
Toupet procedure
Predictors of success of surgery
Medication use in follow-up of patients
from VA cooperative GERD study
Spechler et al, JAMA 2001; 285: 2331
No evidence that antireflux surgery
protects against cancer development
Ye et al, Gastroenterology 2001; 121: 1286