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DISEASES%20OF%20THE%20ESOPHAGUS

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Title: DISEASES%20OF%20THE%20ESOPHAGUS


1
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
2
Diseases of the esophagus
GERDMotility disordersEsophagitis (infection,
chemicals, pills)Neurological disordersSkeletal
muscle disordersVarices Mallory-Weiss
sy.BarrettsTumors
Common complainsWide range of symptoms
3
Swallowing
Many muscle5 nerves V, VII, IX, X,
XIIStages oral - voluntary pharyngeal
- involuntary esophageal - LES relaxed1
second 5 steps
4
5 steps within 1 second
1. Soft palate is elevated retracted to
prevent nasopharingeal reflux2. Vocal cords are
closed Epiglottis swings backward ? closure
the larynx3. UES relaxes4. Larynx is pulled
upward streching, opening E and UES5.
Contractions of pharyngeal muscle
5
Anatomy
6
Anatomy
7
(No Transcript)
8
Motility disorders of oropharynx
  • Dysfunction of the UES
  • Zenkers 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
9
Zenkers diverticulum
10
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
11
Esophagus motility disorder scleroderma
12
Achalasia Chagas disease
Cause Tripanosoma Cruzi inf.
13
Diffuse esophageal spasms
14
Rings and Webs
Schatzkis ring - proximal or distal -
congenital or secondary to GERDPlummer Vinson
syndrome - upper E web - dysphagia -
irondeficiency anemiaSymptoms if diameter lt 13
mm - intermittent dysphagia for solid food -
sudden steak house syndromeTreatment -
mechanical dilators
15
Schatzkis ring
16
Endoscopic image of the narrow area in
mid-esophagus
17
Post-mortem specimen from a similar case of
esophageal narrowing in a young boxer.
18
Map of lymph nodes near the oesophagus
19
Radiographic evaluation in suspected esophageal
cancer
20
Gastroesophageal junction type II tumors
21
Esophageal cancer
22
(No Transcript)
23
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)

24



AJCC Staging of Esophagus TNM Staging Stage
Tumor Node Metastasis Stage 0
Tis N0 M0 Stage I T1 N0 M0
T2 N0 M0 Stage IIA T3 N0 M0
T1 N1 M0 Stage IIB T2 N1 M0
T3 N1 M0 Stage III T4 Any N M0 Stage IV
Any T Any N M1 Stage IV A Any T Any
N M1a Stage IV B Any T Any N M1b

25
Resected esophageal specimen
26
Other esophageal disorders
27
Coin in upper oesophagus
28
INFECTIONS OF THE OESOPHAGUS
Viral herpes, CMV Fungal Candida
Most common in immuncompromized
patients AIDS Immunosuppressive
treatment Immune defects Antibiotic os steroid
treatment
29
Candida oesophagitis
30
Acid-related diseases of the oesophagus GERD /
GORD
31
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 Barretts
  • Non-erosive reflux disease (NERD)
  • Reflux disease in which erosion does not occur


Talley et al., BMJ 2001 323 12947. de
Caestecker, BMJ 2001 323 7369. Nathoo, Int J
Clin Pract 2001 55 4659. Quigley, Eur J
Gastroenterol Hepatol 2001 13(Suppl 1) S1318.
32
Pathophysiology of GORD
salivary HCO3
Impaired mucosal defence
oesophageal clearance of acid (lying
flat, alcohol, coffee)
Impaired LOS (smoking, fat, alcohol)
transient LOS relaxations basal
tone
Hiatus hernia
acid output (smoking, coffee)
H Pepsin
Bile and pancreatic enzymes
intragastric pressure (obesity,
lying flat)
gastric emptying (fat)
de Caestecker, BMJ 2001 3237369. Johanson, Am
J Med 2000 108(Suppl 4A) S99103.
33
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

34
Bernstein test
Retrosternal pain for 0.1 N HCl
35
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 D
Grade C
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 ofthe oesophageal circumference
Lundell et al., Gut 1999 45 17280.
36
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 III
  • Erosions surrounding the oesophageal
    circumference
  • Grade IV
  • Ulcer(s), strictures, shortening of the
    oesophagus
  • Grade V
  • Barretts epithelium

Grade I - V
Savary Miller. The Esophagus. In Handbook
Atlas of Endoscopy. Solothurn, Switzerland
Verlag Gassman AG, 1978 119205.
37
Grade I oesophagitis
Savary-Miller classificationOne or several
erosions in one mucosal fold
Quigley, Eur J Gastroenterol Hepatol 2001
13(Suppl 1) S1318. Nathoo, Int J Clin Pract
2001 55 4659. www.gastrolab.net
38
Grade II oesophagitis
Savary-Miller classification Several erosions
in several mucosal folds, the erosions can merge
www.gastrolab.net
39
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/inde
xe.htm
40
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/inde
xe.htm
41
Grade IV oesophagitis
Savary-Miller classification Stricture
Nadel, UCHC
42
Grade V oesophagitis
Savary-Miller classification Moderate Barretts
oesophagus
Freytag et al., Atlas of gastrointestinal
endoscopy. www.home.t-online.de/home/afreytag/inde
xe.htm
43
Grade V oesophagitis
Savary-Miller classification Moderate Barretts
oesophagus
Chromoendoscopic picture
Freytag et al., Atlas of gastrointestinal
endoscopy. www.home.t-online.de/home/afreytag/inde
xe.htm
44
Barretts dysplasia
Columnar cells instead of squamous cells
45
Grade V oesophagitis
Savary-Miller classification Severe Barretts
oesophagus
Freytag et al., Atlas of gastrointestinal
endoscopy. www.home.t-online.de/home/afreytag/inde
xe.htm
46
Adenocarcinoma of the oesophagus
Nadel/Saint Francis Hospital. In
Gastrointestinal Pathology. Fenoglio-Preiser, New
York Raven Press, 1989 96100.
47
Range of presentations of GORD
Typical symptoms (Heartburn/regurgitation)
Atypical symptoms
Complications
With oesophagitis
Chest pain(visceral hyperalgesia)
Oesophageal erosions and/or ulcers
Without oesophagitis
Stricture
Hoarseness (reflux laryngitis)
Barretts oesophagus
Asthma, chronic cough, wheezing
Oesophageal adenocarcinoma
Dental erosions
Nathoo, Int J Clin Pract 2001 55 4659.
48
Prevalence of heartburn or acid regurgitation

Women at least weekly episodes Men at least
weekly episodes
40
Prevalence ()
0
2534 3544 4554 5564 6574 Age (years)
Locke et al., Gastroenterology 1997 112 144856.
49
GORD can be a trigger for asthma
100
77
80
72
65
60
Asthma patients experiencing GORD symptoms ()
40
20
0
Perrin-Fayolle et al. (n150)
OConnell et al. (n189)
Field et al. (n109)
Harding Sontag, Am J Gastroenterol 2000
95(Suppl) S2332.
50
Correlation of respiratory and oesophageal
symptoms with oesophageal acid events
Asthmatic patients with GORD (n118)
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 6549.
51
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
  • Evidence of airway inflammation
  • Substance P and tachykinin release
  • Increase
  • minute ventilation
  • respiratory rate

Harding Sontag, Am J Gastroenterol 2000
95(Suppl) S2332.
52
Chronic cough and GORD
? Receptors ? Cough centre VN Vagus
nerve N Cortical input
Irwin Madison, Am J Med 2000 108(Suppl 4A)
S12630.
53
Effect of PPI on pulmonary and GI symptoms in
asthma patients
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
14
Pulmonary symptoms score Gastric symptom score
12
10
Symptom score
8
6
4
2
0
Weeks
Placebo
PPI
Kiljander et al., Chest 1999 16 125764.
54
Consequences of severe and prolonged GORD
Savary-Miller Grade IV and above
  • Oesophageal stricture
  • Barretts OE
  • OE Adenocarcinoma
  • Anemia
  • Oesophageal stricture
  • Barretts oesophagus
  • Oesophageal adenocarcinoma
  • Anaemia

Nathoo, Int J Clin Pract 2001 55 4659.
55
Differential diagnosis of oesophageal stricture
  • Oesophageal cancer
  • Oesophageal spasm
  • GORD
  • Globus hystericus
  • Epiglottitis
  • Ingestion of caustic substances
  • Pharyngitis
  • Peritonsillar abscess
  • Foreign body
  • Oesophageal candidiasis

56
Prevalence and risks of Barretts oesophagus in
Europe/USA
  • Barretts found at endoscopy 0.521
  • Barretts found while investigating GORD
    10152,3
  • Barretts is common in white males4
  • Prevalence of adult heartburn 20403
  • Barretts increases the risk of oesophageal
    cancer 50100-fold4

1. Jankowski et al., The Lancet 2000 356
207985. 2. Gore et al., Aliment Pharmacol Ther
1993 7 6238. 3. Spechler. Digestion 1992
51(Suppl 1) 249. 4. Peters et al., Gut 1999
45 48994.
57
Mortality due to oesophageal adenocarcinoma in
England and Wales
4000
3500
3000
2500
Mortality
2000
1500
1000
500
0
79
89
94
84
97
Year
Office of National Statistics, 1999.
58
Heartburn as a risk factor for oesophageal
adenocarcinoma
Frequency and duration of symptoms
20
Frequency Chronicity
16.7
16.4
Odds ratio
7.5
6.3
5.2
5.1
1
1
0
None 1 23 gt3 0 lt12 1220 gt20
Heartburn episodes/week Duration of symptoms
(years)
Lagergren et al., N Engl J Med 1999 340 82531.
59
Management of upper GI symptoms in primary care
Clinical history
Heartburn (GORD)
Upper abdominal pain/dyspepsia
Alarm features
Age gt45
Manage with antisecretory agents
Treat empirically
Early endoscopy
Test-and-treat for H. pylori
Appropriate treatment
60
Alarm features for GORD
Odynophagia
Dysphagia
Bleeding
Alarm features
Vomiting
Weight loss
Nathoo, Int J Clin Pract 2001 55 4659.
61
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 lt50
    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 3447.
62
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 3447.
63

Differential diagnosis of GORD
  • Hiatus hernia
  • Oesophageal stricture
  • Oesophageal cancer
  • Chest pain of cardiac origin
  • Functional dyspepsia

Nathoo, Int J Clin Pract 2001 55 4659.
64
Treatment options in GORD
  • Simple (lifestyle) measures
  • Medical treatment
  • antacids
  • acid secretion suppressors -
  • PPI, H2RAs, H.p. erad.
  • prokinetics
  • Surgery (laparascopic)

65
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
66
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
  • Diarrhoea

Sonnenberg A, Pharmacoeconomics 2000 17
391401. de Caestecker, BMJ 2001 323
7369. Hatlebakk Berstad, Clin Pharmacokinet
1996 31 386406. Scott Gelhot, Am Fam Physic
1999 59 11619.
67
Mosapride a novel prokinetic motility agent
  • 1st selective 5-HT4 agonist
  • Available in Japan since 1998
  • Enhances gastrointestinal motility and emptying
  • Improved effect on gastric emptying vs cisapride
  • Better tolerated than cisapride
  • No cardiotoxicity issues (unlike cisapride)

Mine et al., Pharmacol Exper Ther 1997 283
10008. Ruth et al., Aliment Pharmacol Ther 1998
12 3540.
68
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 7369. Sonnenberg,
Pharmacoeconomics 2000 17 391401.
69
Available PPIs in Europe in 2002
Available PPIs in Europe in 2002
  • Omeprazole
  • Lansoprazole
  • Pantoprazole
  • Rabeprazole
  • Esomeprazole
  • But are they all the same?

70
PPI bioavailability after the first dose
90 80 70 60 50 40 30 20 10 0
80
77
64
52
40
Bioavailability ()
Lansoprazole Pantoprazole Esomeprazole
Rabeprazole Omeprazole
Tolman et al, J Clin Gastroenterol 1997 24
6570. Fitton Wiseman, Drugs 1996 51
46082. Hassan-Alin et al, Gastroenterology 2000
118 A16. Swan et al., Aliment Pharmacol Ther
1999 13(Suppl 3) 117. Howden, Clin
Pharmacokinet 1991 20 3849.
71
LAN
Lansoprazole metabolism is unaltered with
repeated dosing
LAN
LANSOPRAZOLE
CYP3A4
CYP2C19
Liver enzymes unaffected
Lansoprazole sulphone
Hydroxy lansoprazole
  • LAN

Tolman et al., J Clin Gastroenterol 1997 24
6570. Welage Berardi, J Am Pharm Assoc 2000
40 5262.
72
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 48293.
73
Nissens fundoplication for GORD
74
Clinical management of Barretts 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 7369.
75
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
45863. Malfertheiner Gerards, Baillières Clin
Gastroenterol 2000 14 73141.
76
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

77
Mallory-Weiss syndrome
Bleeding from rupture of esophageal mucosa
78
Pill induced esophageal mucosal lesion
79
Portal hypertension Esophageal varices
80
Esophageal varices
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