Transcript Discovery and Evaluation of Elemental Mercury

Chest pain of unknown
origin (CPUO): role of the
esophagus
Richard I. Rothstein, MD
Chief, Section of Gastroenterology and Hepatology
Dartmouth Hitchcock Medical Center
Professor of Medicine
Dartmouth Medical School
Chest Pain of Unknown Origin
Prognosis for angina-like pain
with normal coronary anatomy
Chambers, Prog Cardiovasc Dis 1990
Kemp, Am J Med 1973
Functional Status – normal
coronary anatomy
Ockene N Engl J Med 1980
Reflux common in pts with
coronary disease
n = 30, 164 chest pain episodes
Singh, Ann Intern Med,1992; 117:824-30
Abnormal esophageal motility
(n = 910)
(n = 255)
Katz, Ann Intern Med, 1987; 106:593-7
Edrophonium Testing
80 mcg/Kg IV
Diagnostic Yield of Esophageal
Testing
Katz, Ann Intern Med, 1987; 106:593-7
Intraesophageal Balloon Inflation:
Esophageal Hypersensitivity
n = 30 NCCP, 30 controls
Richter, Gastroenterol, 1986; 91:845-52
Provocative Testing
Barrish, Dig Dis Sci, 1986; 31:1292-8
Subgroups of Patients With Chest
Pain
With
Esophageal
Symptoms
Isolated
Chest
Pain
Anxiety/Somatization
Neurosis
Subgroups of Patients With Chest
Pain
Isolated
Chest
Pain
• Rare for esophageal pathology
• Question the “non-cardiac”
• Reassurance, tincture of time
Subgroups of Patients With Chest
Pain
With
Esophageal
Symptoms
• Heartburn
• Regurgitation
• Dysphagia
• Water brash
• Nausea
• Vomiting
Evaluate or treat for recognized esophageal disorders
Detection of Esophageal Disorders
Potentially Responsible for
Symptoms
Endoscopy
Barium swallow ±
manometry
pH
•
•
•
•
•
•
•
•
Reflux esophagitis
Infectious esophagitis
Pill esophagitis
Esophageal cancer
Esophageal stricture/web
Achalasia
Esophageal spasm
EGD-negative GERD
pH testing - Conventional
Catheter Based:

Patient Intolerance




Uncomfortable
Pharyngeal and
Throat Discomfort
Runny Nose
Artifact Prone

Alters Regular Diet
and Activity
Bravo pH System™
Catheter-Free pH
Monitoring System
 pH Capsule attached
to the esophageal wall
transmits data to
pager-sized Receiver
 Eliminates
uncomfortable 24-hr
trans-nasal catheter
 Allows normal
activities, showering
and does not interfere
with sleeping
Bravo pH Capsule with
Delivery System
Handle
Catheter
pH Capsule
Capsule Attachment
Step 1
Step 2
Step 3
Step 4
Step 5
Position Bravo
Capsule
Apply
Suction
Advance Pin
Release
Capsule
Begin pH
Recording
Bravo pH Receiver

Receiver
pH Capsule
pH Capsule transmits
data to pager-sized
Receiver
Digital Radio-Telemetry

Use Digital RadioTelemetry

Capsule measures pH
every 6 sec and
transmits data to
receiver every 12 sec

Keep the receiver
within 1m to prevent
data loss (range up to
3m)
Esophageal Testing in 123 Patients with Chest Pain
and Normal Coronary Arteriograms
Test% Abnormal
Ambulatory pH monitoring
Esophageal motility
Bernstein Test
Edrophonium
Endoscopy
Balloon distention
Treadmill with pH monitor
82
29
10
6
5
4
4
Chenan P, et al Dis Esophagus 1995; 8:129
Atypical presentations of
GERD
Pulmonary
ENT
Asthma
Hoarseness
Bronchitis
Cough
Aspiration
pneumonia
Globus
Apnea
Halitosis
Atelectasis
Vocal
Pulmonary
Chest Pain
fibrosis
cord granuloma
Laryngeal stenosis
Laryngeal cancer
Loss of dental enamel
Sinusitis, otitis
Esophageal Chest Pain Work-Up

Traditionally





Endoscopy
pH probe
Manometry
Provocative testing
Emerging role for up-front
empiricism
PPI Trial in GERD Patients With
Non-Cardiac Chest Pain

37 patients with daily chest pain and negative cardiologic
evaluation
 Categorized as GERD+ or GERD- by EGD and pH study
 Randomized to omeprazole (40 mg q AM and 20 mg q PM for 7
days) or placebo then crossed over after washout
 50% reduction in symptoms constituted positive response
GERD-Positive
• n=23
• 78% response
Fass et al. Gastroenterology. 1998;115:42-49.
GERD-Negative
• n=14
• 14% response
Characteristics of the Patients
Patients with NCCP
GERD-positive
GERD-negative
Subjects
23
Age (yr)
58.2± 2.3
Range (yr)
35-76
Sex (M / F)
22 / 1
Upper endoscopy results
Normal (grade 0-1)
7
Erosive esophagitis (grade 2-5)
16
Ambulatory 24-h esophageal pH
monitoring (%)*
Mean
9.6± 1.8
Range
0.5-29.1
*% total time pH<4
14
61.6± 2.8
47-83
14 / 0
14
1.2± 0.3
0.0-2.9
Fass R, et al Gastroenterol 1998; 115:42-9
Enrollment
Upper endoscopy &
Ambulatory 24-hour esophageal pH
monitoring
GERD +
GERD -
Week 1 Baseline symptom assessment
Randomization
Week 2
Week 3
Placebo
Omeprazole
(40 mg AM + 20 mg PM)
Washout period
Week 4 Baseline symptom assessment
Week 5
Omeprazole
Placebo
(40 mg AM + 20 mg PM)
Fass R, et al
Gastroenterol 1998;
115:42-9
Omeprazole Test in NCCP





18/23 GERD-positive (78%)
2/14 GERD-negative (14%)
Positive
OT
Sensitivity 78.3%
Sensitivity 85.7%
59% reduction in number of diagnostic
procedures
($573 savings per patient evaluation)
Fass R, et al Gastroenterol 1998; 115:42-9
Results of Economic Analysis
Conventional
work-up
OT
Difference
% Change
Cost ($)
2025
1452
573
28 Reduction
No. of endoscopies/
1000 patients
1000
190
810
81 Reduction
No. of ambulatory
24-hr pH tests/
1000 patients
650
140
510
79 Reduction
No. of esophageal
motility tests /
1000 patients
310
470
-160
52 Increase
Total no. of diagnostic
procedures /
1000 patients
1960
800
1160
59 Reduction
Fass R, et al Gastroenterol 1998; 115:42-9
Omeprazole Test in NCCP
Issues

Generalizability?




Male, veteran population
High % esophagitis, GERD symptoms
Pain pattern of frequent chest pain (≥ 3x/wk)
Small numbers, short course treatment

Medication dosing, strength

Role of endoscopy


Reassurance factor
Once-in-a-lifetime Barrett’s check
Los Angeles (LA) Grade
Classification of Erosive Esophagitis
LA Grade A
One or more
mucosal breaks
no longer than
5mm, not
bridging the tops
of mucosal folds
LA Grade C
One or more
mucosal breaks
bridging the tops of
mucosal folds
involving <75% of
the circumference
Lundell et al. Gut. 1999;45:172-180.
LA Grade B
One or more
mucosal breaks
longer than 5mm,
not bridging the
tops of mucosal
folds
LA Grade D
One or more
mucosal breaks
bridging the tops
of mucosal folds
involving >75% of
the circumference
The spectrum of heartburn frequency
and severity is similar in GERD patients
with and without esophagitis
Patients with esophagitis
Patients without esophagitis
Severity of
heartburn
Severe
Moderate
Mild
Smout 1997
GERD Therapeutic Options
Prokinetics
“First - aid” :
Life-style
modifications
and antacids
OTC or
prescription
H2RAs
Treatments
OTC or prescription
PPIs
Surgery
(Lap Nissen fundoplication)
Endoscopic techniques
(plication, RF, implant)
Life-style Modifications
Reduce weight
Stop smoking
Elevate head
of bed
Modifications
Avoid reflux-promoting
agents e.g, alcohol,
coffee; some foods

Not evidence-based
Eat small meals,
no late meals,
reduce fat
Consider alternatives to
reflux-promoting drugs
e.g., theophilline,
anticholinergics
POSITION AND REFLUX
8
pH
4
0
8
pH
4
0
(Katz,LC. Et al, J Clin Gastro 1994;18(4):280-3
GERD HEALING AND ACID CONTROL
Patients Healed (%)
100
80
60
40
20
0
2
4
6
8
10
12 14
16 18 20
22
Duration Intragastric pH >4.0 (Hours)
(Bell et al. Digestion. 1992;51(suppl 1):59-67.)
Medical Rx Outcomes
(with H2RAs)
 Relief
of symptoms
 Healing esophagitis
 Prevent complications
 Remission
50%
<50%
--25%
Medical Rx Outcomes (PPIs)
 Relief
of symptoms
 Healing esophagitis
 Prevent complications
 Remission
85-95%
85-95%
80%
90%
GERD: Endoscopic Therapies





Endoscopic suturing – i.e., Endocinch
(this leads to partial thickness plication)
Full thickness plication – i.e., NDO
Radiofrequency ablation – i.e., Stretta
Injection therapy with augmentation of
LES – i.e., Enteryx
Bulking procedures with augmentation of
LES – i.e., Gatekeeper
BARD EndoCinch
Suction of tissue
just beneath z-line
Needle with
pre-loaded
suture advanced
Cinching/cutting
catheter
advanced to
tissue
Final appearance
of plication in
cardia
NDO Plicator™
and gastroscope
Arms opened, tissue
1 Plicator
2 retractor advanced
retroflexed
pre-tied implant
4 Single,
deployed.
3
Gastric wall retracted,
arms closed.
plication
5 Full-thickness
completed
Antegrade technique
Balloon inflation
Needle deployment
1 cm above z-line
Injection at the Z-Line
Gatekeeper™ System
Stabilize site
Create pocket
Deliver prosthesis
Access pocket
Expansion
MAINTENANCE THERAPY OF GERD
% in remission
Omeprazole vs surgery
100
90
80
70
60
50
40
30
20
10
0
Surgery (N=122)
Omeprazole (N=133)
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
Years
(Lundel et al: J Am Col Surg, 192:172, 2001)
Outcomes of Atypical GERD
Symptoms Treated by LNF
Preoperative
Postoperative
Symptom Score
10
• Overall 58% of patients
8
– Pulmonary 48%
6
– Atypical chest pain
58%
4
– Pharyngo/
laryngeal 76%
2
0
Atypical Sx
Improvement
Typical Symptoms Atypical Symptoms
(n=115)
(n=35)
Improvement
Improvement
6.2 points
4.4 points
So et al. Surgery. 1998;124:28-32.
Esophageal Chest Pain

GERD related

Motility related

Esophageal hyperalgesia
Esophageal Hyperalgesia

“Irritable esophagus”

Abnormal nociception

Lower threshold for pain
Esophageal Hyperalgesia

Noxious stimulus in esophagus

Decrease in nociceptor threshold

Disorder of CNS nociceptive
pathway
Chest Pain - Imipramine



50 mg nightly for 3 wks
52% reduction in chest pain episodes
Suggested visceral analgesic effect
Cannon R, et al. N Engl J Med 1994; 330:1411-7


15 healthy male volunteers
Balloon inflation volume at pain threshold
higher on imipramine
Peghini PL, et al. Gut 1998; 42:807-13
NCCP Non-GERD
Esophageal Therapies








Calcium channel blockers
Anticholinergics
Nitrates
Botox
Antidepressants (Imipramine, Trazodone)
Octreotide
Bougienage
5 HT3 antagonists
Initial Perception Threshold (S1) Before and 40
Minutes after Octreotide Injection
>30
p < 0.02
CC
30
20
10
0
Base
40 min
Johnson BT, et al Am J Gastroenterol 1999; 94:65-70
Maximally Tolerated Pain Threshold (S2) Before and 40
Minutes after Octreotide Injection
>30
CC
30
20
10
0
Base
40 min
Johnson BT, et al Am J Gastroenterol 1999; 94:65-70
Overlap Syndrome of Altered Pain
Sensitivity
Approach to the NCCP Patient







Take a history
Exclude coronary / cardiac disease
Check for musculoskeletal disease
Look for GERD
Check for dysmotility
Consider esophageal hyperalgesia
Collaborative management