Transcript No Slide Title

DISEASES OF THE
ESOPHAGUS
Prof. Ferenc Szalay MD, PhD
1st Department of Medicine of Semmelweis University
Budapest, Hungary
Budapest, 03.02.2003 lecture for students
Diseases of the esophagus
GERD
Motility disorders
Esophagitis (infection, chemicals, pills)
Neurological disorders
Skeletal muscle disorders
Varices
Mallory-Weiss sy.
Barrett’s
Tumors
Common complains
Wide range of symptoms
Swallowing
Many muscle
5 nerves : V, VII, IX, X, XII
Stages
oral
- voluntary
pharyngeal
- involuntary
esophageal
- LES relaxed
1 second 5 steps
5 steps within 1 second
1. Soft palate is elevated + retracted
to prevent nasopharingeal reflux
2. Vocal cords are closed
Epiglottis swings backward  closure the larynx
3. UES relaxes
4. Larynx is pulled upward
streching, opening E and UES
5. Contractions of pharyngeal muscle
Anatomy
Anatomy
Motility disorders of oropharynx
• Dysfunction of the UES
Zenker’s diverticulum, Cricopharingeal bar
• Neurologic disorders (stroke)
Cerebrovascular diseases, Poliomyelitis
Amyotrophic lateral sclerosis, Multiple sclerosis, Brain stem tumor
• Skeletal musclular disorders
Myastenia gravis, Metabolic myopathy (T4 toxicosis, myxedema, steroid)
Muscular dystrophies
• Local structural lesions
Neoplasms, extinsic compression (Thyroid, cervical spur), Surgery
Common problem in the elderly patients and frequently associated
with poor prognosis owing to a high incidence of aspiration
Zenker’s diverticulum
Motility disorders of the esophagus
 Smooth muscle diseases (scleroderma)
 Intrinsic nervous system
Achalasia, Chagas disease
 loss of ganglion cells in Auerbach plexus
 LES 
 no peristalsis
Diffuse esophagus spasm and its variants
Esophagus motility disorder: scleroderma
Achalasia: Chagas’ disease
Cause:
Tripanosoma Cruzi inf.
Diffuse esophageal spasms
Rings and Webs
Schatzki’s ring
- proximal or distal
- congenital or secondary to GERD
Plummer Vinson syndrome
- upper E web
- dysphagia
- irondeficiency anemia
Symptoms if diameter < 13 mm
- intermittent dysphagia for solid food
- sudden: “steak house syndrome”
Treatment
- mechanical dilators
Schatzki’s ring
Endoscopic image of the narrow
area in mid-esophagus
Post-mortem specimen from a similar case of esophageal
narrowing in a young boxer.
Map of lymph nodes near the
oesophagus
Radiographic evaluation
in suspected esophageal
cancer
Gastroesophageal junction
type II tumors
Esophageal cancer
AJCC Staging of Esophagus: TNM
Staging
Regional lymph nodes (N)
Nx
Regional lymph nodes cannot be assassed
N0
No regional lymph node metastasis
N1
Regional lymph node metastasis
Distant metastasis (M)
Mx
Distant metastasis cannot be assassed
M0
No distant metastasis
M1
Distant metastasis
Tumors of lower or upper esophagus
M1a
Metastasis in nonregional lymph node
M1b
Distant metastasis (eg: liver, bone, brain)
Tumors of middle esophagus
M1a
Not applicable
M1b
Metastasis in nonregional lymph node or distant metastasis (eg: liver,
bone, brain)
AJCC Staging of Esophagus: TNM
Staging
Stage
Tumor
Node
Metastasis
Stage 0
Stage I
Tis
T1
T2
T3
T1
T2
T3
T4
Any T
Any T
Any T
N0
N0
N0
N0
N1
N1
N1
Any N
Any N
Any N
Any N
M0
M0
M0
M0
M0
M0
M0
M0
M1
M1a
M1b
Stage IIA
Stage IIB
Stage III
Stage IV
Stage IV A
Stage IV B
Resected esophageal
specimen
Other esophageal disorders
Coin in upper oesophagus
INFECTIONS OF THE OESOPHAGUS
Viral
Fungal
herpes, CMV
Candida
Most common in immuncompromized patients:
AIDS
Immunosuppressive treatment
Immune defects
Antibiotic os steroid treatment
Candida oesophagitis
Acid-related
diseases of the
oesophagus
GERD / GORD
Definitions
Heartburn:
• Burning retrosternal pain radiating upward due to
exposure of the oesophagus to acid
Oesophagitis:
• Endoscopically demonstrated damage to the
oesophageal mucosa
Gastro-oesophageal reflux disease (GORD):
• Pathological reflux ranges from simple to erosive to
Barrett’s
Non-erosive reflux disease (NERD):
• Reflux disease in which erosion does not occur
Talley et al., BMJ 2001; 323: 1294–7.
de Caestecker, BMJ 2001; 323: 736–9.
Nathoo, Int J Clin Pract 2001; 55: 465–9.
Quigley, Eur J Gastroenterol Hepatol 2001; 13(Suppl 1): S13–18.
Pathophysiology of GORD
salivary HCO3
Impaired
mucosal
defence
oesophageal clearance
of acid
(lying flat, alcohol, coffee)
Impaired LOS
Hiatus hernia
(smoking, fat, alcohol)
–
–
transient LOS
relaxations
basal tone
Bile and
pancreatic
enzymes
H+
Pepsin
acid output
(smoking, coffee)
intragastric pressure
(obesity, lying flat)
bile reflux
gastric emptying (fat)
de Caestecker, BMJ 2001; 323:736–9.
Johanson, Am J Med 2000; 108(Suppl 4A): S99–103.
Diagnosis of GORD
• History
1. Does reflux exist?
2. Is acid R responsible for symptoms?
3. Has R led to esophagus damage?
•
•
•
•
•
•
Barium swallow
Radionuclide scintigraphy (99mTc sulfur colloid)
E. manometry
Bernstein test
pH monitoring
Endoscopy
Bernstein test
Retrosternal pain for
0.1 N HCl
Los Angeles classification
system for oesophagitis
Grade A
Grade B
One or more mucosal
breaks, no longer than
5 mm, that do not extend
between the tops of two
mucosal folds
One or more mucosal
breaks, more than 5 mm
long, that do not extend
between the tops of two
mucosal folds
Grade C
Grade D
One or more mucosal breaks,
that are continuous between
the tops of two or more
mucosal folds, but which
involve less than 75% of the
circumference
One or more mucosal
breaks, that involve at
least 75% of
the oesophageal
circumference
Lundell et al., Gut 1999; 45: 172–80.
Savary-Miller classification
of oesophagitis
Grade I

One or several erosions in one mucosal fold
Grade II

Several erosions in several mucosal folds,
the erosions can merge
Grade
Grade III

Grade IV

I-V
Erosions surrounding the oesophageal circumference
Ulcer(s), strictures, shortening of the oesophagus
Grade V

Barrett’s epithelium
Savary & Miller. The Esophagus. In: Handbook & Atlas of Endoscopy. Solothurn,
Switzerland: Verlag Gassman AG, 1978: 119–205.
Grade I oesophagitis
Savary-Miller classification
One or several erosions in
one mucosal fold
Quigley, Eur J Gastroenterol Hepatol 2001; 13(Suppl 1): S13–18.
Nathoo, Int J Clin Pract 2001; 55: 465–9.
www.gastrolab.net
Grade II oesophagitis
Savary-Miller classification
Several erosions in several
mucosal folds, the erosions
can merge
www.gastrolab.net
Grade III oesophagitis
Savary-Miller classification
Erosions surrounding the
oesophageal circumference
Freytag et al., Atlas of gastrointestinal endoscopy. www.home.t-online.de/home/afreytag/indexe.htm
Grade IV oesophagitis
Savary-Miller classification
Ulcer(s), shortening of the
oesophagus
Freytag et al., Atlas of gastrointestinal endoscopy. www.home.t-online.de/home/afreytag/indexe.htm
Grade IV oesophagitis
Savary-Miller classification
Stricture
Nadel, UCHC
Grade V oesophagitis
Savary-Miller classification
Moderate Barrett’s
oesophagus
Freytag et al., Atlas of gastrointestinal endoscopy. www.home.t-online.de/home/afreytag/indexe.htm
Grade V oesophagitis
Savary-Miller classification
Moderate Barrett’s
oesophagus
Chromoendoscopic picture
Freytag et al., Atlas of gastrointestinal endoscopy. www.home.t-online.de/home/afreytag/indexe.htm
Barrett’s dysplasia
Columnar cells instead of squamous cells
Grade V oesophagitis
Savary-Miller classification
Severe Barrett’s
oesophagus
Freytag et al., Atlas of gastrointestinal endoscopy. www.home.t-online.de/home/afreytag/indexe.htm
Adenocarcinoma of the
oesophagus
Nadel/Saint Francis Hospital. In: Gastrointestinal Pathology. Fenoglio-Preiser, New York: Raven Press, 1989: 96–100.
Range of presentations of GORD
Typical symptoms
(Heartburn/regurgitation)
With
oesophagitis
Chest pain
(visceral
hyperalgesia)
Without
oesophagitis
Complications
Atypical symptoms
Oesophageal
erosions
and/or ulcers
Stricture
Hoarseness
(‘reflux
laryngitis’)
Asthma,
chronic cough,
wheezing
Dental erosions
Barrett’s
oesophagus
Oesophageal
adenocarcinoma
Nathoo, Int J Clin Pract 2001; 55: 465–9.
Prevalence of heartburn
or acid regurgitation
%
Women: at least weekly episodes
40
Prevalence (%)
Men: at least weekly episodes
0
25–34
35–44
45–54
55–64
65–74
Age (years)
Locke et al., Gastroenterology 1997; 112: 1448–56.
Asthma patients experiencing GORD
symptoms (%)
GORD can be a trigger
for asthma
100
80
72
77
65
60
40
20
0
Perrin-Fayolle et al.
(n=150)
O’Connell et al.
(n=189)
Field et al.
(n=109)
Harding & Sontag, Am J Gastroenterol 2000; 95(Suppl): S23–32.
Correlation of respiratory and oesophageal
symptoms with oesophageal acid events
Asthmatic patients with GORD (n=118)
Wheezing or
shortness of breath
65
Cough
98
Chest pain
60
Heartburn
83
Regurgitation
87
Nausea
91
0
20
40
60
80
100
Respiratory and oesophageal symptoms associated with
oesophageal acid events (%)
Harding et al., Chest 1999; 115: 654–9.
Mechanism of asthma symptoms on exposure to
oesophageal acid
Asthma symptoms plus
oesophageal acid
Oesophageal acid-induced
bronchoconstriction:
 vagally mediated oesophageal
bronchial reflex
 heightened bronchial reactivity
 microaspiration
Increase:
 minute ventilation
 respiratory rate
Evidence of airway inflammation:
 Substance P and tachykinin release
Harding & Sontag, Am J Gastroenterol 2000; 95(Suppl): S23–32.
Chronic cough
and GORD


VN
N
Receptors
Cough centre
Vagus nerve
Cortical input
Irwin & Madison, Am J Med 2000; 108(Suppl 4A): S126–30.
Effect of PPI on pulmonary and GI symptoms in
asthma patients
14
Pulmonary symptoms
score
12
Symptom score
Gastric symptom score
10
8
6
4
2
0
0
1
2
3
4
5
Placebo
6
7
8
9
10 11 12 13 14 15 16 17 18
Weeks
PPI
Kiljander et al., Chest 1999; 16: 1257–64.
Consequences of severe and
prolonged GORD
Savary-Miller Grade IV and above
• Oesophageal stricture
Oesophageal stricture
Barrett’s oesophagus
• Barrett’s OE
Oesophageal adenocarcinoma
Anaemia
• OE Adenocarcinoma
• Anemia
Nathoo, Int J Clin Pract 2001; 55: 465–9.
Differential diagnosis of
oesophageal stricture
Oesophageal cancer
Oesophageal spasm
GORD
Globus hystericus
Epiglottitis
Ingestion of caustic substances
Pharyngitis
Peritonsillar abscess
Foreign body
Oesophageal candidiasis
Prevalence and risks of Barrett’s oesophagus in
Europe/USA
Barrett’s found at endoscopy: 0.5–2%1
Barrett’s found while investigating GORD: 10–15%2,3
Barrett’s is common in white males4
Prevalence of adult heartburn: 20–40%3
Barrett’s increases the risk of oesophageal cancer 50–100fold4
1. Jankowski et al., The Lancet 2000; 356: 2079–85.
2. Gore et al., Aliment Pharmacol Ther 1993; 7: 623–8.
3. Spechler. Digestion 1992; 51(Suppl 1): 24–9.
4. Peters et al., Gut 1999; 45: 489–94.
Mortality due to oesophageal adenocarcinoma in
England and Wales
4000
Mortality
3500
3000
2500
2000
1500
1000
500
0
79
84
89
94
97
Year
Office of National Statistics, 1999.
Heartburn as a risk factor for
oesophageal adenocarcinoma
Frequency and duration of symptoms
20
Frequency
16.7
16.4
Odds ratio
Chronicity
7.5
6.3
5.2
5.1
1
1
0
None
1
2–3
>3
Heartburn episodes/week
0
<12
12–20
>20
Duration of symptoms (years)
Lagergren et al., N Engl J Med 1999; 340: 825–31.
Management of upper GI symptoms
in primary care
Clinical history
Heartburn
(GORD)
Upper abdominal
pain/dyspepsia
Alarm
features
Manage with
antisecretory
agents
Age >45
Early
endoscopy
Appropriate
treatment
Test-and-treat
for H. pylori
Treat
empirically
Alarm features for GORD
Odynophagia
Dysphagia
Bleeding
Alarm
features
Vomiting
Weight loss
Nathoo, Int J Clin Pract 2001; 55: 465–9.
European practice guidelines:
GORD
Careful analysis of symptoms and history is key to diagnosis
Diagnosis based on symptoms can be aided by a trial of
treatment
Clear endoscopic abnormalities are found in <50% of patients
Treatment should start with a proton pump inhibitor (PPI)
Most patients will require long-term treatment; anti-reflux
surgery may be as effective as PPIs, but is less predictable
Summary of conclusions from a multidisciplinary workshop held in Genval, Belgium in 1999.
Dent et al., BMJ 2001; 322: 344–7.
When should endoscopy be considered
in patients with GORD?
Alarm symptoms (e.g. dysphagia, weight loss,
bleeding, abdominal mass)
Diagnostic problems (e.g. atypical symptoms)
Heartburn for 5 years or longer
Failure to respond to initial treatment
Pre-operative assessment
Dent et al., BMJ 2001; 322: 344–7.
Differential diagnosis of GORD
Hiatus hernia
Oesophageal stricture
Oesophageal cancer
Chest pain of cardiac origin
Functional dyspepsia
Nathoo, Int J Clin Pract 2001; 55: 465–9.
Treatment options in GORD
• Simple (lifestyle) measures
• Medical treatment
antacids
acid secretion suppressors PPI, H2RAs, H.p. erad.
prokinetics
• Surgery (laparascopic)
Lifestyle modifications
for the management of GORD
Reduce weight
Elevate head
of bed
Stop smoking
Modifications
Avoid reflux-promoting
agents (e.g. alcohol,
coffee, some foods)
(not evidence based)
Consider
alternatives to
reflux-promoting drugs
(e.g. theophylline,
anticholinergics)
Eat small meals,
no late meals, reduce
fat
Antacids
Antacids
Increase the pH of gastric refluxate

Reduce the erosive effect and hence reduce symptoms
Suitable for quick relief of mild symptoms
Most antacids are not suitable therapies for established
GORD or oesophagitis

Less effective than H2RAs or PPIs for treatment of GORD
Adverse effects include:




Accumulation in patients with renal impairment
Milk-alkali syndrome with high doses
Constipation
Sonnenberg A, Pharmacoeconomics 2000; 17: 391–401.
Diarrhoea
de Caestecker, BMJ 2001; 323: 736–9.
Hatlebakk & Berstad, Clin Pharmacokinet 1996; 31: 386–406.
Scott & Gelhot, Am Fam Physic 1999; 59: 1161–9.
H2-receptor antagonists (H2RAs)
H2-receptor antagonists (H2RAs)
Inhibit histamine stimulation of gastric parietal
cell, resulting in reduced gastric acid secretion
Slower onset but longer duration of action
than antacids
Cimetidine is associated with more drug
interactions than other H2RAs, such as ranitidine
H2RAs are generally not as effective as PPIs for
symptom relief or healing
de Caestecker, BMJ 2001; 323: 736–9.
Sonnenberg, Pharmacoeconomics 2000; 17: 391–401.
Available PPIs in Europe in 2002
Available PPIs in Europe in 2002
Omeprazole
Lansoprazole
Pantoprazole
Rabeprazole
Esomeprazole
But are they all the same?
Bioavailability (%)
PPI bioavailability after the first dose
90
80
70
60
50
40
30
20
10
0
80
77
64
52
40
Lansoprazole Pantoprazole Esomeprazole
Rabeprazole
Omeprazole
Tolman et al, J Clin Gastroenterol 1997; 24: 65–70.
Fitton & Wiseman, Drugs 1996; 51: 460–82.
Hassan-Alin et al, Gastroenterology 2000; 118: A16.
Swan et al., Aliment Pharmacol Ther 1999; 13(Suppl 3): 11–7.
Howden, Clin Pharmacokinet 1991; 20: 38–49.
Lansoprazole metabolism is
unaltered with repeated dosing
LAN
LAN
LANSOPRAZOLE
CYP3A4
CYP2C19
Lansoprazole
sulphone
Hydroxy
lansoprazole
Liver
enzymes
unaffected
LAN
Tolman et al., J Clin Gastroenterol 1997; 24: 65–70.
Welage & Berardi, J Am Pharm Assoc 2000; 40: 52–62.
Healing rates for various
PPIs in GORD
L = lansoprazole
P = pantoprazole
O = omeprazole
R = rabeprazole
30 = 30 mg/day, 20 = 20 mg/day, 40 = 40 mg/day
Petite et al. L30/O20
Castell et al. L30/O20
Mee et al. L30/O20
Mulder et al. L30/O40
Mossneret al. P40/O20
Corinaldesi et al. P40/O20
Hotz et al. P40/O20
Vicari et al. P40/O20
Thjodleifsson et al. R20/O20
Dekkers et al. R20/O20
0
20
40
60
80
100
Patients healed at 8 weeks (%)
Thomson, Curr Gastroenterol Rep 2000; 2: 482–93.
Nissen’s fundoplication for GORD
Clinical management of
Barrett’s oesophagus
Acid suppression therapy with PPIs1
Surveillance endoscopy with biopsies
Mucosal ablation (electrocautery, laser or
photodynamic therapy) combined with
high-dose acid suppression
Oesophageal resection
1. de Caestecker, BMJ 2001; 323: 736–9.
Conclusions
Reflux symptoms are frequent throughout life
Incidence of oesophageal adenocarcinoma
is rising:

Associated with increasing incidence of reflux
and decreasing incidence of H. pylori
Heartburn is a risk factor for oesophageal
adenocarcinoma:



Frequency
Duration
Severity
Hennessy, Postgrad Med J 1996; 72: 458–63.
Malfertheiner & Gerards, Baillière’s Clin Gastroenterol 2000; 14: 731–41.
Key points
Long-term GORD can result in serious
complications, which may prove fatal
Early treatment of GORD is associated with
excellent outcomes
Late treatment is associated with an increased
risk of complications and potentially poor
outcomes
Early intervention relieves symptoms and helps
prevent serious complications
Mallory-Weiss syndrome
Bleeding from rupture
of esophageal mucosa
Pill induced esophageal mucosal lesion
Portal hypertension – Esophageal varices
Esophageal varices