1. Esophageal motility disorders & Achalasia
Division of Gastroenterology
Department of Internal Medicine
R4 Woo Yong Sik/Prof. Jang Jae young

2. Normal physiology of esophagus

3. Normal eosphageal manometer and fluroscopy of barium swallow

4. Examples of esophageal peristalsis and LES relaxation during three swallows each of 5 mL of water.

5. Classification of esophageal motility abnormalities
Inadequate LES relaxation
Classic achalasia
Atypical disorders of LES relaxation
Uncoordinated contraction
Diffuse esophageal spasm
Hypercontraction
Nutcracker esophagus
Isolated hypertensive LES
Hypocontraction
Ineffective esophageal motility
Gut 2001;49:145–151

6. Motility patterns in esophageal smooth muscle disorders
Motility patterns in esophageal smooth muscle disorders Harrison's Principles of Internal Medicine. 16th ed 1739–1745.

7. Esophageal manometric findings
in classic achalasia and vigorous achalasia

8. Esophageal manometric findings in diffuse esophageal spasm.

9. Esophageal manometric findings in Nutcracker esophagus

10. Esophageal manometric findings in systemic sclerosis.

11. Achalasia

12. Introduction Sir Thomas Willis, first described in 1674
who described a man in good health who vomited ‘whatever eaten’
treated with whale bone rod with small piece of sponge on its end inserted into esophagus to relieve obstruction
‘achalasia of the cardia’ by Hurst in 20th century
term achalasia comes from Greek for failure to relax

13. normal condition : excitatory, Ach motor neurons
inhibitory, NO motor neurons
Achalasia : resulting from loss of inhibitory neurons
results in elevation in basal LESP and absence of relaxation of LES
Achalasia with complete loss of myenteric neurons.
basal LESP is below normal owing to absent excitatory neurons,

14. Pathophysiology neurodegenerative insult secondary achalasia
inflammatory origin with possibly (slow) viral involvement.
genetic, autoimmune or infectious origin of the neural damage,
secondary achalasia
associated with Chagas disease caused by trypanozoma cruzi endemic to Southern America

15. Important causes of achalasia

16. Clinical feature Achalasia is a rare disease
affecting both genders
annual incidence between 0.5~1/ per yr
incidence peaks in the 3rd and 7th life decade
chest pain is reported by 1/3~1/2 of pt with achalsia
wt. loss is common, confused with eating disorder
combination of dysphagia for both “solid and liquids”
suggesting achalasia over mechanical obstruction
“symptoms rather than physical finding are hallmark”

17. Diagnosis typically delayed 2-3 yrs from onset of symptoms
suspected from carefully obtained history
duration correlation with esophageal diameter

18. Endoscopy Retention of undigested food in esophagus
regarded as a more specific parameter in diagnosing achalasia
only in pt with advanced disease and severe transit impairment
Candida esophagitis in immune competent pt

19. Radiographic studies Typical radiographic findings
smooth tapering in the distal esophagus with “bird´s beak” or “champagne glass” appearance
lack of primary peristalsis noticed during fluoroscopy
formation of a contrast column above LES
none be present in early phase of disease
normal barium esophagogram not rule out achalasia

20. Conventional barium esophagogram in achalasia
Bird’s beak
Conventional barium esophagogram in achalasia

21. “Timed barium” swallow in achalasia.
Images were 1, 3 and 5 min after ingestion of ml barium.
monitor patients after therapy in order to detect recurring disease before becoming clinically overt. Before (A), after (B) treatment.

22. Esophageal manometry “gold standard” in diagnosing calssic achalasia
three characteristic manometric features
elevated resting LES pr (above 45 mmHg)
incomplete LES relaxation after swallow
aperistalsis in smooth muscle portion of esophageal body
Vigorous achalasia
simultaneous esophageal contractions amplitudes >60 mmHg
prognostic & therapeutic value of this separation controversial

23. Esophageal manometric findings
in classic achalasia and vigorous achalasia

24. Treatment of achalasia
goal in management of achalasia
early diagnosis and treatment before reaching this end-stage phase when esophagectomy becomes inevitable
restoring neurons of myenteric plexi
Not available
currently aim at facilitating bolus transit across LES
Phamacologic treatment
Botulinum toxin injections
Pneumatic balloon dilatation
Surgical lower esophageal myotomy

25. Oral pharmacologic treatment
smooth muscle relaxants
CCB, nitrates and phosophodiestarase inhibitors
aimed at reducing LES pr.
clinically available pharmacologic therapies
limited value in treatment of achalasia.
Indication
pts not willing or unable to undergo any other procedure
pts waiting for more definitive therapy
supportive treatment for refractory chest pain in achalasia.

26. Botulinum toxin injections
Pasricha et al reported on use of botulinum toxin A (Botox) injections in LES to treat achalasia NEJM 1995;332:
original protocol, 80~100IU of BoTox are injected in 4 quadrants just above Z-line, an area LES
Initial beneficial effect occurs in 60~75%
duration of BoTox treatment varies according to various studies , generally on average 6-12 mo.

27. Mechanism of Action of Botulinum Toxin
A, Release of acetylcholine at the neuromuscular junction is mediated by the assembly of a synaptic fusion complex
that allows the membrane of the synaptic vesicle containing acetylcholine to fuse with the neuronal cell membrane.
The synaptic fusion complex is a set of SNARE proteins, which include synaptobrevin, SNAP-25, and syntaxin.
After membrane fusion, acetylcholine is released into the synaptic cleft and then bound by receptors on the
muscle cell.
B, Botulinum toxin binds to the neuronal cell membrane at the nerve terminus and enters the neuron by endocytosis.
The light chain of botulinum toxin cleaves specific sites on the SNARE proteins, preventing complete assembly
of the synaptic fusion complex and thereby blocking acetylcholine release. Botulinum toxins types B, D, F, and
G cleave synaptobrevin; types A, C, and E cleave SNAP-25; and type C cleaves syntaxin. Without acetylcholine
release, the muscle is unable to contract.
SNARE indicates soluble NSF-attachment protein receptor; NSF, N-ethylmaleimide-sensitive fusion protein; and
SNAP-25, synaptosomal-associated protein of 25 kd.
JAMA 2001;285;1059~1070

28. Dilatation
oldest treatment modality and first described > 300 yrs ago with a tool of time – whale fishbone
Pneumatic dilators are conventionally used
no clear consensus on technical details of balloon dilatation
trend to begin with smaller diameter (3cm in adult)
dilator increase diameter in graded fashion subsequently
Good response was reported 60~95%
Symptomatic outcome depends on reduction LES pr. and emptying unlike phamacologic treatment and BoTox

29. Efficacy reduced by half for subsequent dilatation
poor initial result or rapid recurrence lesser response
Morbidity in 3% of patients, Mortality rarely reported
most related to esophageal perforation,
Perforation more likely in severe malnurished pt.
Disadvantages - lesser short- and long-term efficacy
in comparison with myotomy, particlularly in young patients

30. Esophagomyotomy Goal of surgical theraphy
to reduce LES resting pr without completely compromising reflux
Ernst Heller first described in 1914
two-cardiomyotomy technique
(one ant. and one post.) along GEJ
Modification of this procedure
(Heller myotomy and Toupet posterior fundoplication)

31. Esophagomyotomy Good results from open myotomy occur in 80~90%
reduces LED pr. more than pneumatic dilatation accounting for greater efficacy
Minimally invasive approaches to myotomy
as effective as open counterpart
surgical procedure of choice as limited long-term data

32. Comparison of Primary Treatments for Idiopathic Achalasia

33. Complication related to retention and stasis in esophagus
esophagitis, up to 30% nocturnal coughing
Prevelence of carcinoma is higher in achalasia
rate of ranging from 2~7% in larger case series
50 times in general population
Squamous hyperplasia, apperance of p53 mutation in response to chronic stasis