MOTILITY DISORDERS OF
UPPER GI TRACT
ACHALASIA
GASTROPARESIS
Tiberiu Hershcovici, MD
Director, Gastrointestinal Motility Lab
Hadassah University Hospital
ACHALASIA
DEFINITION
CARDINAL SYMPTOM
• Dysphagia to solids and liquids
EPIDEMIOLOGY
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•
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Incidence : 1 in 100,000 individuals annually
Prevalence :10 in 100,000
There is no gender predominance.
The disease can occur at any age, although
diagnosis before the second decade is rare.
• The incidence increases with age, with the
highest incidence in the seventh decade and a
second smaller peak of incidence at 20–40 years
of age.
PATHOPHYSIOLOGY
• Normally, a food bolus introduced to the
esophagus is moved to the stomach via a
coordinated peristaltic wave and relaxation of the
lower esophageal sphincter (LES)
• The disruption of these functions results from
degeneration of ganglion cells in the myenteric
plexus of the esophageal body and the LES.
• The triggering event that leads to ganglion cell
degeneration is unclear.
PATHOPHYSIOLOGY
• The esophageal plexopathy results in loss of
nitric oxide (inhibitory neurotransmitter) in
the LES and esophageal body.
• This is associated with:
– disruption of normal peristalsis
– LES hypertonicity and incomplete relaxation of
tone with swallowing
SECONDARY ACHALASIA
• Amyloidosis infiltrating the esophagus and LES
• Extrinsic compression of the gastroesophageal
junction:
– tight fundoplication during antireflux surgery
– laparoscopic adjustable gastric banding (LABG)
• Infection by Trypanosoma cruzi (Chagas disease) :
– diffuse enteric myenteric destruction including small
bowel dilatation and megacolon
– heart disease
– neurologic disorders
SECONDARY ACHALASIA TO NEOPLASIA
(PSEUDOACHALASIA)
• Tumors that infiltrate the gastroesophageal
junction may cause extrinsic pressure or direct
tumor invasion of the myenteric plexus:
– adenocarcinoma of the gastroesophageal junction
or proximal stomach
– pancreatic, breast, lung, or hepatocellular cancers
• Paraneoplastic effect by secretion of an
antineuronal antibody: small cell lung cancer
CLINICAL PRESENTATION
• Esophageal dysphagia (in up to 90% of patients) often
for both solids and liquids
• Chest pain
• Heartburn and regurgitation
• Weight loss
CLINICAL PRESENTATION
• More subtle symptoms owing to accommodation: slow
eating, stereotactic movements with eating, and
avoidance of social functions that involve meals.
• The progression of symptoms in patients can be slow.
• Many patients experience symptoms for years before
coming to medical attention.
DIAGNOSIS
• Patients who have a history suggesting
achalasia commonly require at least 2, and
sometimes 3 modalities for diagnosis.
• Barium esophagogram
• Endoscopy
• Esophageal manometry
BARIUM ESOPHAGOGRAM
• Dilated esophagus
• Absence of peristalsis,
• Narrowing of the distal
esophagus in a typical
“bird’s beak” appearance
UPPER ENDOSCOPY
• Endoscopic evaluation of the esophagus and
stomach is recommended in every patient to
ensure that there is not a malignancy causing
the disease or esophageal squamous cell
carcinoma complicating achalasia.
• A dilated esophagus with a tight LES that
“pops” open with gentle pressure is often
observed, as well as retained food and saliva.
ESOPHAGEAL MANOMETRY
• The gold standard diagnostic modality for
achalasia.
• Manometrically, achalasia is defined by:
– absence of peristalsis in the esophageal body
– a poorly relaxing LES:
• residual pressure > 8 mm Hg (classic manometry)
• IRP > 15 mm Hg (high resolution manometry)
HIGH-RESOLUTION MANOMETRY
IRP=INTEGRATED RELAXATION PRESSURE
IRP<15 mmHg
TYPE I CLASSIC ACHALASIA
complete absence of peristaltic contractile activity
minimal pressurization
TYPE II ACHALASIA
absence of peristaltic contractile activity with
panesophageal pressurization to a level 30
mmHg
TYPE III ACHALASIA
evidence of spasm using conventional
criteria
ACHALASIA DIAGNOSTIC FLOWCHART
TREATMENT
• Therapy focuses on relaxation or mechanical
disruption of the LES.
• There is no treatment method that addresses
esophageal hypomotility.
• Endoscopic Treatments:
– Endoscopic botulinum toxin injection into the LES
– Pneumatic dilation of LES
• Surgery:
– Esophagomyotomy (Heller myotomy) to divide LES
from serosa to mucosa, thereby completely disrupting
the muscular layers
• Peroral endoscopic myotomy (POEM).
TREATMENT
• Pneumatic dilation and surgical myotomy effectively
disrupt the LES and these therapies are comparable and
much more effective than management with botulinum
toxin or smooth muscle relaxants.
• A recent randomized, multicenter, European trial
compared the 2 modalities by assessing the outcome of
200 patients randomized to myotomy with Dor
fundoplication or pneumatic dilation.
• The success rates for these approaches after 2 years were
both approximately 90% if one allowed a maximum of 3
dilations to be the equivalent of a single myotomy.
European Achalasia Trial
 Prospective protocol using large number of patients to
determine whether the pre-intervention subtype could
predict outcome.
 Their results confirmed that after a minimum follow-up
period of 2 years the overall outcomes of treatment (both
surgery and dilatation) were significantly better in type II
(96%) than type I (81%) and type III (66%) patients.
However, their data do not support an initial observation
that surgical myotomy is associated with better outcomes
in types I and III achalasia. This could be related to the fact
that the success rates of both techniques were very high.
Peroral endoscopic myotomy (POEM)
GASTROPARESIS
DEFINITION
• Gastroparesis is a syndrome characterized by
delayed gastric emptying in absence of
mechanical obstruction of stomach.
CARDINAL SYMPTOMS
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Postprandial fullness (early satiety)
Nausea
Vomiting
Bloating, particularly among women and
overweight patients, and is severe in many
individuals
• Abdominal pain-predominant in the idiopathic
type
ETIOLOGY
• Diabetes Mellitus -one third of cases
• Idiopathic causes - one third of cases
– post-viral gastroparesis
• Other causes:
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postsurgical : vagotomy or vagal injury
collagen vascular: scleroderma
neurological disorders: Guillain-Barre syndrome
medications: amylin analogs (e.g. pramlintide) or GLP-1
agonists (e.g. exenatide) that inhibit vagal function
PATHOPHYSIOLOGY
• Extrinsic autonomic neuropathy affecting the
vagus nerve:
– diabetes mellitus
– postsurgical vagal injury
• Intrinsic or enteric neuropathy: affecting
excitatory and inhibitory intrinsic nerves, with
loss of nNOS
• Pathology of the interstitial cells of Cajal (ICC)
• Myopathy: increased fibrosis of the muscle layer,
hypoplasia, or degeneration of smooth muscle
cells
DIAGNOSIS
• There is poor correlation between currently
available methods to assess global gastric
emptying and symptoms.
• However, documentation of delayed gastric
emptying to solids is required before a diagnosis
of gastroparesis can be made.
• Abnormal gastric emptying still remains the only
objective marker of an underlying defect in the
neuromuscular apparatus of the stomach.
GASTRIC EMPTYING TESTS
• Scintigraphy is the most common and widely available
modality. The standard technique involves:
– scintigraphic determination of emptying of a solid meal:
99mTc (technetium) sulfur colloid-labeled egg sandwich
– it is required that scintigraphic measurement continues to
4 h. Shorter tests are not reliable.
– Abnormal: gastric retention>10% at 4 h
• Breath tests using non-radioactive forms of carbon(13C)
incorporated in ingestible food. Advantages:
– Can be carried out in office settings
– Correlate well with scintigraphy
DIAGNOSIS
DIAGNOSIS
• Gastroduodenal manometry can differentiate
neuropathic from myopathic processes.
• Neuropathic gastroparesis :
– increased frequency of migrating motor complexes during fasting
– reduced frequency of distal antral contractions postprandially
(typically <1/ min during the first postprandial hour)
– poorly developed intestinal fed pattern
• Myopathic gastroparesis:
– normal patterns of motility
– low amplitude:
• postprandial distal antral pressure activity is <40 mmHg
• duodenojejunal pressure activity is <10 mmHg
TREATMENT
• Nutritional support
• Prokinetics to improve gastric emptying:
– metoclopramide
– domperidone
• Symptom control: for pain
• Tight glycemic control in diabetes
• Gastric electric stimulator in refractory cases
NUTRITIONAL SUPPORT
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Small frequent meals
Well chewed food
Avoid fiber
Diet low in fat
There are few data to show:
– how these nutritional interventions compare with
other treatment modalities for gastroparesis
– if they affect the natural history and outcome of
patients with diabetic gastroparesis.
PROKINETIC MEDICATION –
DOPAMINE ANTAGONISTS
• Metoclopramide (Pramin) and domperidone (Motilium)
are dopamine-2 receptor antagonists and equally
effective in reducing symptoms of nausea and vomiting.
• Metoclopramide is available in liquid and oral dissolving
tablets which may be tolerated better. It has also been
shown to be effective by the subcutaneous route, by
passing issues associated with delayed gastric emptying.
• A well recognised complication of metoclopramide is
tardive dyskinesia that can be irreversible.
• Domperidone does not cross the blood-brain barrier and
is associated with fewer central nervous system effects.
PROKINETIC MEDICATIONMOTILIN AGONISTS
• Erythromycin is a potent prokinetic agent which acts
by activating the motilin receptor, probably on the
cholinergic neurons.
• It is a useful agent for short-term treatment of patients
in the hospital.
• Its long-term benefit is limited due to development of
tachyphylaxis.
• Several other motilin agonists have been developed to
avoid tachyphylaxis. They are still in phase of clinical
trials.
GASTRIC ELECTRICAL STIMULATION
• Is being increasingly used for patients with diabetic
gastroparesis with refractory nausea and vomiting.
• Symptoms of nausea and vomiting improve with
implantation of the device, as do quality of life and
nutritional status.
• The mechanism of action of gastric electrical
stimulation is still not known.
• It should be considered only in refractory diabetic
gastroparesis after exhaustion of other therapeutic
options and only when the main symptoms are
nausea and vomiting and not pain.
PAIN MANAGEMENT
• Is often challenging in patients with
gastroparesis as there is a lack of clear
understanding of the physiological defect
causing pain in these patients.
• Tricyclic and tetracyclic antidepressants
• Gabapentin and pregabalin
• Opiates should be used very sparingly and
only in refractory cases
DIABET GASTROPARESIS PATHOPHYSIOLOGY