616.329-008.6-07-08
/PREGLEDNI RAD
Primary esophageal motility disorders (Concise
Review for Clinicians)
..............................
A. Simi}, Z. Ra‘natovi}, O. Skrobi}, P. Pe{ko,
Department for Esophagogastric Surgery, First Surgical
University Hospital, Institute for Digestive Diseases, Clinical
Center of Serbia
rezime
Primary esophageal motility disorders comprise
various abnormal manometric patterns which
usually present with dysphagia or chest pain. Some, such as achalasia, are diseases with a well defined pathology, characteristic manometric features, and good response to treatments directed towards the palliation of symptoms. Other disorders, such as diffuse esophageal spasm and nutcracker
esophagus, have no well defined pathology and could
represent a range of motility abnormalities associated
with subtle neuropathic changes, gastresophageal reflux and anxiety states. On the other hand, hypocontracting esophagus is generally caused by weak musculature commonly associated with gastresophageal reflux
disease. Although manometric patterns have been defined for these disorders, the relation with symptoms
is poorly defined and in some cases the response to medical or surgical therapy unpredictable. The aim of
this paper is to present a wide spectrum of the primary esophageal motility disorders, as well as to give a
concise review for the clinicians encountering these
specific diseases.
Key words: esophagus, motility, manometry.
When liquid is swallowed, a portion goes to the lung
and from there is filtered into the pericardial sac, where it
lubricates the feverish heart. The rest of the liquid is exhaled as vapour” – Hippocrates1.
O
ur views on esophageal function have changed somewhat since Hippocrates description of what occurs
when liquid is swallowed. Eating requires the propulsion of food from the mouth to the stomach and, as
Meltzer noted century ago, is dependent on the "orderly
progress of peristaltic movements in the esophagus"2.
Abnormalities of this "orderly progress" are termed
esophageal motility disorders and comprise any condition
whose symptoms, especially dysphagia and chest pain, are
suspected of being esophageal in origin.
These disorders are primarily diagnosed by esophageal
manometry studies, which assess lower esophageal
sphincter pressure and relaxation, the presence of peristalsis in the esophageal bo-dy, and the characteristics of contraction waves including amplitude, duration, repetitive
nature, and presence of ei-ther non-transmitted or partly
transmitted waves.
Although authorities have proposed a number of classification systems for the various abnormalities found by
manometry, none of them has been universally accepted.
Furthermore, there is much controversy over the clinical
importance of many of these abnormal patterns, particularly as to whether they represent real disorders or they are
merely unusual findings associated with a patient’s symptoms. Considering all this, esophageal motility disorders
can be generally classified as primary and secondary. The
latter are due to systemic diseases such as: diabetes, connective tissue disorders, dermatomyositis, scleroderma,
amyloidosis, alcoholism, Chagas disease and neoplasms
of various sorts (most commonly adenocarcinoma of the
cardia), when there is a presence of pseudoachalasia. Primary esophageal motility disorders (PEMD) are currently
best explained on the basis of either defective inhibitory
or defective excitatory innervation of the LES and the body of the esophagus. Based on such classification all
PEMD’s can be divided in five distinctive groups: achalasia, diffuse esophageal spasm, hypercontracting esophagus (i.e. hipertensive "nutcracker" esophagus and hypertensive lower esophageal sphincter), hypocontracting esophagus (i.e. ineffective esophageal motility and hypotensive lower esophageal sphincter) and nonspecific esophageal motility disorders (Table 1).
The aim of this paper is to present a wide spectrum of
the PEMD’s, as to refer to their patophysiology, diagnostics and treatment modalities, and give a concise, every
day, review for the clinicians dealing with these specific
conditions.
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A. Simic et al.
ACI Vol. LIII
TABLE 1
CLASSIFICATION OF PRIMARY ESOPHAGEAL MOTILITY DISORDERS3
Primary esophageal motility disorders
Manometric tracings
Achalasia
Absent esophageal peristalsis
Abnormal LES relaxation
Can have raised LES pressure (>45mmHg)
Diffuse esophageal spasm
Simultaneous contraction >20% of wet swallows
Intermittent peristalsis
Can have repetitive or multipeak contractions (>two peakas)
Can have contraction hot associated with swallows
Contraction amplitude >30 mmHg but usually not high
Hypercontracting esophagus
Hypertensive esophagus - "nutracker"
Incresed mean distal amplitude (>180mmHg)
Normal peristalsis
Can be of increased distal duration (>6s)
Hypertensive LES
Resting LES pressure >45mmHg
May be incomplete LES relaxation
Hypocontracting esophagus
Ineffectiuve esophageal motility
>30% low distal amplitude (<30 mmHg) or failed nontransmitted
contractions
Hypotensive lower esophageal sphincter
Resting LES pressure <10mmHg
Nonspecific esophageal motility disorders
Incomplete LES relaxation
Nontransmited contractions >20%
Retrograde contractions
Low amplitude contractions <35 mmHg
THE ESOPHAGEAL MANOMETRIC PROCEDURE
The "golden" tool procedure for all PEMDs is stationary
esophageal manometry. There is no clear consensus on
the ideal technique for performing esophageal manometry. To use the general classification system for esophageal motility abnormalities proposed above, the manometry
must at least provide an assessment of the completeness
of LES relaxation and an evaluation of peristaltic function
of the esophageal body. This can be accomplished as follows4: the motility catheter is passed through the nose until the pressure sensors are positioned in the stomach, and
gastric baseline pressure is recorded. While the patient
breathes quietly, a slow, 1 cm pull through is performed
for evaluation of LES pressure. LES pressure is measured
as the mid respiratory level in the area of maximal pressure (compared with gastric baseline pressure). Although it
is conventional to refer to this measured value as "LES
pressure", the value reflects pressure generated by the crural diaphragm as well as the LES muscle5. With the
pressu-re sensor positioned in the LES, the patient is
asked to perform at least five separate wet swallows (5 ml
of wa-ter) to assess the completeness of swallow induced
LES relaxation. Completeness of relaxation is determined
by measuring the residual LES pressure, that is, the difference between the pressure recorded at the nadir of LES relaxation and gastric baseline pressure. Peristalsis is evaluated by positioning four pressure sensors separated by intervals of 5 cm in the body of the esophagus, with the distal sensor positioned 5 cm proximal to the upper LES border, after which a series of 10 wet swallows is performed.
The swallows are separated by an interval of at least 20
seconds, and pressure wave amplitude, duration, and velocity are measured. In patients with a dilated and tortuous
esophagus, the LES may be difficult to intubate, requiring
fluoroscopic or endocopic guidance for manometry catheter placement. Normal values for esophageal manometry
were derived from a study that used the manometry protocol described above in 95 healthy adult volunteers6.
ACHALASIA
The first description of achalasia is attributed to Thomas
Willis, an English physician who in 1674 described a man
who vomited "whatsoever he had eaten"7. The name achalasia (gr. failure to relax) did not come into use until the
XX century when published as "achalasia of the cardia"
by Hurst8. Achalasia is defined as a primary esophageal
motor disorder characterized by manometric findings of
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incomplete lower esophageal sphincter (LES) relaxation
and esopahgeal aperistalsis. Achalasia is of unknown etiology and the most common of all esophageal motility disorders. It is an uncommon ailment with a reported incidence of 1 per 100,000 in the Western world. Achalasia affects both sexes equally, typically presenting between the
ages of 20 and 50, although it can occur in all ages. It is
characterized by ineffective relaxation of the LES combined with loss of esophageal peristalsis leading to impaired
emptying and gradual esophageal dilatation. The anatomical defect appears to be a decrease or loss of inhibitory
nonadrenergic, noncholinergic ganglion cells in the esophageal myenteric plexus. Histological analysis of esophagi resected from patients with end-stage achalasia demonstrates myenteric inflammation and progressive depletion of ganglion cells and subsequent neural fibrosis9. There
is also a significant reduction in the synthesis of nitric oxide and VIP, the most important mediators of relaxation in
the LES. Macroscopically there may often be thickening
of the circular layer of the distal esophagus. A long standing achalasia also carries a increased risk of squamous
cell carcinoma10.
Dysphagia is the cardinal feature of achalasia, accompanied by varying degrees of aspiration, weight loss, and pain. Most patients with achalasia present with progressive
dysphagia to solids and liquids, although symptoms may
be subtle and nonspecific early in its course. The mean
duration of symptoms prior to presentation is 2 years, and
the diagnosis often takes much longer as the symptoms
are often attributed to GERD or other disorders. Initially
the patient may complain of the sensation of a retrosternal
"sticking" of foodstuffs. Stress or cold liquids may exacerbate dysphagia. Patients may regurgitate undigested
food, especially after meals or when lying supine. If unable to force food into the stomach by the ingestion of liquids or other means, spontaneous or forced regurgitation
are often used to evacuate the esophagus. As a result of
regurgitation, aspiration of esophageal contents may lead
to pulmonary disease. In fact, up to 10% of patients with
achalasia experience significant bronchopulmonary complications11. Many patients express a sensation of heartburn, explaining why many patients are initially diagnosed with GERD. Although patients with achalasia may
experience gastresophageal reflux12, more often heartburn
is secondary to fermentation of retained undigested food
in the esophagus. Chest pain, clearly distinguishable from
heartburn, occurs in 30 % of patients. The etiology of this
pain is unclear and is unpredictably relieved by esophageal myoto-my. Weight loss is variable and tends to be insidious. The magnitude of weight loss tends to correlate
with the severity of the underlying disease. Rapid onset of
symptoms (>6 months), advanced age (>50 years), or significant weight loss (>10 kg) should raise suspicion for
pseudoachalasia, usually secondary to malignancy or extraluminal obstruction. In these cases a thorough work-up
with a CT scan and/or endoscopic ultrasound must be performed before further therapy is considered.
11
A barium esophagram is typically the first imaging study used in the evaluation of dysphagia and it may demonstrate an air fluid level in the esophagus with a paucity of
gastric air. The classical appearance of achalasia on a barium study is the "bird’s beak" tapering of the distal esophagus with a column of contrast in the esophageal lumen. Variable esophageal dilation is seen, ranging from
mild in the early stages to the massive sigmoid-shaped
esophagus of end-stage achalasia. Fluoroscopic evaluation
may also reveal nonpropulsive, tertiary contractions of the
esophageal body with failure to clear the barium bolus
from the esophagus. The sensitiveness of barium meal for
achalasia, although higher than for endoscopy, is only
60%13. Endoscopic evaluation is used to rule out other
processes that may mimic achalasia. The characteristic
appearance is an atonic, dilated esophagus with a tightly
closed LES that does not open with insufflation. With
gentle pressure the scope is admitted through the LES
with a "pop", in contrast with a peptic stricture or a malignancy, which does not yield. The gastresophageal junction, including a retroflexed view of the gastric cardia,
should be carefully inspected. Biopsies of any mucosal
abnormality should be obtained. Manometry is the "gold
standard" for confirming the diagnosis of achalasia. The
manometric features proposed for a diagnosis of classic
achalasia are: 1) incomplete relaxation of the LES (defined as a mean swallow induced fall in resting LES pressure to a nadir value >8 mm above gastric pressure) and
2) aperistalsis in the body of the esophagus characterised
either by simultaneous and nonpropulsive esophageal
contractions with amplitudes <37 mm Hg or by no apparent esophageal contractions. Complete absence of peristalsis is the sine qua non of achalasia. Manometric features that are characteristic of classic achalasia but not required for the diagnosis include: 1) elevated resting LES
pressure (> 45 mmHg) and 2) resting pressure in the
esophageal body that exceeds resting pressure in the
stomach. A subgroup of patients with otherwise typical
features of classic achalasia have simultaneous contractions of their esopahgeal body which can be of high amplitude (>37mmHg). This manometric pattern has been
termed "vigorous achalasia", and a chest pain episodes
are a common finding in these patients. Differentiation of
vigorous achalasia from diffuse esopahegal spasm can be
done only manometrically. In both diseases video-graphic
exam can show a corkscrew deformity of the esophagus
and diverticulum formation14.
The treatment of achalasia is directed at the palliation of
symptoms, unable to correct the underlying neuromuscular pathology. The goal of all therapeutic options is to relieve the functional obstruction of the distal esophagus,
thus improving esophageal emptying. Drugs that relax
smooth muscle and decrease LES pressure such as nitrates
and calcium-channel blockers have been used to treat achalasia. Unpredictable and incomplete absorption of oral
formulations secondary to poor esophageal emptying is
one limitation, thus, sublingual administration is the most
efficacious route. Relief from these agents is inconsistent
and generally short-lived, with most patients showing
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A. Simic et al.
continued progression of their disease15. Their usefulness
is limited to temporizing symptoms until more effective
the-rapy can be implemented, or in those patients deemed
too frail to undergo a more invasive treatment16. Botox
(Botu-linum toxin type A) is a neurotoxin delivered from
Clostridum botulinum, and is capable of biding holinergic
ner-ves and therefore irreversibly inhibits acetylcholine
secretion. Botox is injected into the LES through the
working port of a flexible endoscope, with minimal incidence of immediate complications. Early enthusiasm has
waned as results have not proven to be durable. Botox injection is initially effective in 70% of patients but 50% develop recurrent symptoms within 6 months17. Repeat administration is possible, but efficacy is diminished with
subsequent injections. Another problem with this therapy
is that Botox injection can cause an intense inflammatory
reaction of the GE junction with subsequent fibrosis. This
may impact future surgical therapy, as most patients have
continued or progressive symptoms. While not well understood, Botox appears to be more effective in older patients and in those with vigorous achalasia. Botox should
be reserved for patients unwilling or deemed unfit to undergo an invasive procedure18.
The oldest treatment of achalasia is forceful dilation of
the LES, originally accomplished by Willis more than 300
years ago, by the passage of a piece of whalebone with a
sponge affixed to the end7. This is essentially tearing of
the esophageal muscle, resulting in an imprecise, uncontrolled myotomy. This therapy has become more effective
by the development of graded pneumatic polyethylene
balloons. Under fluoroscopic or endoscopic guidance, balloons (at least 30 mm in diameter) are passed through the
LES and inflated, disrupting the fibers of the LES. The
balloon is kept inflated from 1 to 3 minutes and then deflated. The "graded" approach refers to the use of serially
larger balloons (up to 40 mm) with subsequent dilations
for initial nonresponders and only a single dilation is performed per session19. Response rates of 60–80% can be
achieved, with approximately 70% of patients obtaining
substantial relief of dysphagia after one year20. Repeat dilation is often used, but its efficacy is diminished after
two sessions. Patients with a poor result after initial dilation or early return of their symptoms are predictably less
likely to respond with subsequent dilations. Interestingly,
younger patients do not respond as well as older patients21. This is thought to be due to their tissues being more
compliant and simply stretching during dilation rather that
tearing. The presence of a hiatal hernia, significantly dilated esophagus (>7 cm), or an epiphrenic diverticulum
increases the risk of perforation and the presence of these
factors is a relative contraindication22. While the likelihood of improving dysphagia increases with increasing
balloon diameter, so does the likelihood of perforation.
Overall, the incidence of perforation is about 2 – 4 % per
dilation attempt10,22.
Surgical therapy was originally described in 1914 by Ernest Heller, who performed the first cardiomyotomy for
achalasia23. His original description called for the performance of two myotomies along the gastresophageal
ACI Vol. LIII
junction, one anterior and one posterior. This has subsequently been modified by Zaaijer24, and since then only
an anterior myotomy is performed. Excellent results with
cardiomyotomy can be achieved in 90–100 % of patients.
Extramucosal cardiomyotomy provides more reliable relief of dysphagia than pneumatic dilation as it allows accurate division of LES muscle fibers rather than blind disruption25. Traditionally, this was accomplished by either a
transabdominal or a transthoracic approach. Each approach is associated with an obvious incision and postoperative stays of 7 to 10 days. For this reason, despite superior long-term results from surgical myotomy, most patients were treated by less invasive therapies such as
pneumatic dilation. Recent developments in minimally invasive techniques now allow performance of cardiomyotomy by either a laparoscopic or a thoracoscopic approach26. The first laparoscopic Heller procedure was performed by Shimi and Cushieri in 199127, while the first
thoracoscopic myotomy for achalasia was done by Pellergrini in 199228. The first successful laparoscopic operation
for achalasia in our country, Serbia, in the form of Heller’s myotomy and Dor’s anterior partial fundoplication
was performed by the authors of this review, at the First
Surgical University Hospital in Belgrade, in April 2006.
Over the time transthoracic or thoracoscopic approach
proved to be insufficient due to limited gastric myotomy
and therefore higher incidence of postoperative dysphagia. For these reasons, today we as well as most esophageal surgeons perform a modified Heller’s, or should we
say Zaaijers myotomy, via laparotomic or laparoscopic
approach29. The advantages include excellent visualization
of the distal esophagus and the stomach, so that an extended gastric myotomy and an antireflux procedure may be
easily performed. There are two main controversies surrounding Heller’s myotomy30. One is the extent of the esophageal myotomy; the other is whether an antireflux procedure should be performed, and if so which one. While
there is agreement that the proximal extent of the myotomy should reach up to 6 cm above the gastresophageal junction, the distal extent of the myotomy is controversial.
There is no length of esophageal myotomy that maximally
relieves dysphagia and minimizes the occurrence of reflux. A more traditional approach (a 1.5- to 2-cm gastric
myotomy) was compared with an extended gastric myotomy (at least 3 cm). It has been found that the longer myotomy resulted in less dysphagia and fewer interventions
for recurrent dysphagia31. Since advocating an extended
gastric myotomy, it is felt that an antireflux procedure is
prudent in most cases. Some consider the goal in performing a myotomy is to adequately relieve dysphagia without
unnecessarily disrupting the antireflux barrier especially
the hiatal attachments32. Those who advocate not performing an antireflux procedure cite good clinical results and
low incidence of heartburn33. On the other hand, most surgeons find that performing an antireflux procedure in conjunction with laparoscopic myotomy does not add significant time or morbidity to the operation and is not associated with increased postoperative dysphagia34. Certainly, a
partial fundoplication (Dor or Toupet) is the best option.
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A total fundoplication (e.g., Nissen fundoplication) can
also be applied but if inefficiently performed it can cause
a functional obstruction for a nonpropulsive esophagus,
resulting in a high incidence of dysphagia. An anterior
(Dor) fundoplication requires less posterior dissection,
thus is easier and theoretically preserves more of the natural antireflux barrier35. Also, since the wrap is brought anterior to the myotomy, it potentially covers any undetected mucosal injuries. A posterior (Toupet) fundoplication is the preferred partial fundoplication when indicated
for GERD. Since it holds the edges of the myotomy open,
a Toupet may provide a better protection against recurrent
dysphagia. However, its superiority in preventing reflux
after myotomy has not been demonstrated. While each of
these antireflux techniques has its own theoretical benefits
and champions, there is still no strong evidence supporting one over the other36,37. In conclusion, at the begining
of the XXI century, all the questions considering operative tretament of achalasia remain still open.
2. DIFFUSE ESOPHAGEAL SPASM
Diffuse esophageal spasm (DES) was originally described by Osgood in 188938. Diffuse esophageal spasm is
PEMD of unknown aetiology which appears to be due to
a disturbance of the normal pharmacological timing of
propulsive contractions occurring in the esopahgeal body
after swallowing. It is found in 3–5% of patients evaluated for esophageal motility disorders and is manometrically distinguished by relatively normal motility punctuated
by simultaneous contractions39. DES is defined by the
presence of simultaneous contractions in greater than 20%
of wet swallow trials during manometry testing. Manometry may also demonstrate long-duration contractions,
high-amplitude waves, spontaneous contractions not associated with swallows, and elevated lower esophageal
sphincter (LES) pressures. The etiology of DES is unknown. Patients are hypersensitive to provocative agents
such a cholinergic agonists and pentagastrin. Recent evidence suggests that there may be a defect in neural inhibition that is normally mediated by nitric oxide (NO) within
the esophageal body40.
Diffuse esophageal spasm is characterized clinically by
intermittent chest pain and dysphagia. Chest pain can vary
from mild to crushing, extend to the back and jaw, and
last from seconds to minutes. The pain with DES does not
always occur with swallowing. Dysphagia in patients with
DES can be due to solids or liquids and often occurs more
commonly with ingestion of either very cold or very hot
foods. The symptoms of DES can range from mild to severe but are classically intermittent, may or may not occur
with eating, and are typically not progressive. This lack of
symptomatic and manometric progression separates DES
from other esophageal causes of chest pain and angina,
such as achalasia and esophageal cancer41. The classic
finding of DES, most commonly seen during a barium
swallow study, is the "corkscrew" or "rosary-bead" appearance of the esophageal body during a simultaneous
contraction. Primary (normal) peristalsis is often seen in
the upper thi-rd of the esophagus, and so-called tertiary
13
(abnormal) activity is seen in the region of the spasm.
Tertiary activity can occasionally be seen in normal subjects. Episodes of pain do not always correlate with spastic esophageal contractions, and patients can feel intense
pain even when swallows appear radiographically normal.
Upper endoscopy is typically unremarkable. The esophagus is usually normal in appearance in patients with DES
but a thorough search for signs of GERD (esophagitis, ulcerations, stricture, etc) should be performed at the time
of upper endoscopy. The classic abnormality seen during
esophageal manometry in patients with DES is a pattern
of abnormal simultaneous contractions of the esophageal
body. These must be present in greater than 20% of wet
swallows during formal testing to make a confident diagnosis. Minor manometric diagnostic criteria for DES include frequent, repetitive esophageal contractions (>3
peaks) of a high amplitude (>180 mm Hg) that are prolonged (>6 seconds). The LES can occasionally have high
baseline pressure in DES but is usually normal, as is the
upper esophageal sphincter42. A subgroup of DES is a segmental distal esophageal spasm that is defined by manometric presentation of simultaneous contractions but
only in the distal two channels. The importance of such
manometric finding is the length of the myotomy that is
required for the treatment of these pateints.
Treatment should be aimed at symptomatic relief once
cardiac disease has been definitively excluded through
formal testing. Medical therapy is first in line and effective to some extent in up to 70% of patients43. Patients
should be reassured that they have no underlying cardiac
disease or malignancy to reduce their anxiety, to reduce
their utilization of health care, and to produce some improvement in chest pain44. Various pharmacological
agents (nitroglycerin, isosorbide-dinitrate, and calcium
channel blockers) acting on smooth muscle are used, with
none demonstrating superior efficacy45. As previously
mentio-ned, a psychological component may be an important contributor in patients with "esophageal angina". Several psychoactive agents (benzodiazepines, tricyclics, and
trazodone) demonstrate some efficacy, possibly to a
greater extent than smooth muscle agents46. Endoscopic
application of botulinum toxin A (Botox) for DES has not
been studied adequately to make definite conclusions
about its efficacy. However, with DES where there is diffuse abnormality, the question arises as to where in the
esophagus to focus the therapy. Esophageal pneumatic dilation has shown promising results in patients with DES
in retrospective, uncontrolled studies and thus can be considered; however, the decision of where to dilate the balloon in the esophagus is difficult. Duration of symptomatic improvement is highly variable.
The traditional surgical approach to spastic disorders of
the esophagus has been esophageal myotomy. Myotomy
performed either via thoracotomy or thoracoscopically is
primarily reserved for patients with DES in whom medical therapy has failed. Several important points should be
remembered when surgical myotomy is being considered
in patients with DES. First, myotomy will decrease only
the intensity of esophageal contractions, not the frequen-
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A. Simic et al.
cy; thus, symptoms may still occur after surgery. Second,
myotomy can lead to a hypocontractile esophagus, which
can result in dysphagia (a symptom the operation is meant
to improve). Third, the chest pain that occurs with DES
responds better to myotomy than does the dysphagia associated with these illnesses. To date, only small studies of
myotomy for spastic disorders of the esophagus have been
reported47,48, and none of the studies were controlled trials.
Given these limitations, the data on surgical myotomy
suggest a trend toward symptomatic relief in the subgroup
of patients with severe, refractory symptoms. Patients,
whose main problem is dysphagia and whose esophagus
empties poorly, will benefit from transthoracic longitudinal myotomy. The extent of myotomy is determined from
the preoperative manometry, and in avarage it extends
from the aortic arch toward the sling fibers of the LES at
the esopahgogastric junction. As a matter of necessity,
when there is a presence of LES high basal pressure, the
myotomy is extended distally across the LES to reduce
outflow resistance. Consequently, some form of antireflux
protection is needed to avoid gastroesopahegal reflux,
Dor’s procedure being the most frequently used. Most authors prefer a partial fundoplication so as not to add resisatnce that will interfere further with the ability of the myotomized esopahgus to empty. The recent advent of minimally invasive approaches has dramatically decreased the
morbidity of esophageal myotomy, perhaps allowing an
expansion of its indications to these entities.
3. HYPERCONTRACTING ESOPHAGUS
A. NUTCRACKER ESOPHAGUS
Nutcracker esophagus (NE) was first described by Pope
and his associates in 197849. The term was coined by Benjamin and Castell50 in which patients with non-cardiac
chest pain and/or dysphagia exhibit peristaltic waves in
the distal esophagus with mean amplitudes exceeding normal values by more than 2 standard deviations (SD). The
manometric feature proposed for a diagnosis of nutcracker
esophagus is a mean distal esophageal peristaltic wave
amplitude larger than 180 mmHg (measured as the average amplitude of 10 swallows at two recording sites positioned 5 and 10 cm above the LES) that may be prolonged
in nature (>6 seconds). These two manometric findings
often coexist, suggesting that they might represent a syndrome of a hypercontractile oesophagus. Apart from these
contractions of increased pressure, all other contractions
are peristaltic. Resting pressure in the LES is usually normal but may be elevated, in which case patients are categorised as having nutcracker esophagus with a hypertensive LES. Since no pathological equivalent has been
found, the cause of hypercontracting esophagus is uncertain; however, some high-pressure contractions could be
secondary to exogenous factors such as gastresophageal
reflux or stress51.
The main complaint in patients with a hypercontracting
esophagus is chest pain; dysphagia is relatively uncommon. In fact, NE is the most common motility disorder reported in patients with chest pain who undergo mano-
ACI Vol. LIII
metry, being seen in 27–48%. Nevertheless, the precise
relation between chest pain and hypercontracting esophagus is still uncertain. Patients are usually symptom-free
when the diagnosis is established by esophageal manometry. Additionally, relief from chest pain does not predictably correlate with amplitude reduction by either pharmacotherapy or surgical myotomy52.
By definition, all patients with hypercontracting esophagus have normal peristalsis, so barium radiographs are
usually normal. As with DES, patients with NE may have
a hypersensitive esophagus. Intraesophageal balloon distention reproduces the chest pain experienced by these patients53. LES pressures may be normal but are often elevated, with relaxation being normal. As the pattern of peristalsis is not altered, barium esophagram is usually unremarkable. Upper endoscopy is normal but endoscopic ultrasonography may demonstrate thickening of the muscularis propria54. Interestingly, psychiatric disorders such as
anxiety, depression, and somatoform disorders appear to
be found in higher than predicted frequencies in this population, as first described by Clouse55. The association
with high stress and irritants to the esophagus (eg, acid reflux) suggests that these hypercontracting motility abnormalities might represent an epiphenomenon rather than a
primary motility disorder. Treatment of these syndromes
is similar to treatment of diffuse esophageal spasm, and
results are just as unpredictable56.
B. HYPERTENSIVE LOWER ESOPHAGEAL SPHINCTER
Hypertensive lower esophageal sphincter (HLES) is an
abnormality diagnosed when there is an elevated LES pressure (>45 mmHg) with normal relaxation in the absence
of a concomitant disorder of esophageal body peristalsis57.
Although the hypertensive LES was described more than
40 years ago by Code et al. in patients with chest pain and
dysphagian58, it remains unclear whether this condition
per se has any clinical or physiological consequences. A
hypertensive LES can be defined as one with a resting
pressure value more than 2 SD above the normal mean
value with an exaggerated contraction of the LES after relaxation. Even by this definition however the lower limit
will vary depending on the technique used to measure
resting LES pressure (rapid pull through versus station
pull through; end expiratory, mid respiratory, end inspiratory). If mid respiratory LES pressure is measured using
the stati-on pull through technique, a hypertensive LES
can be defined as one with a resting pressure of >45
mmHg. The manometric feature proposed for a diagnosis
of isolated hypertensive LES is a mean resting LES pressure of >45 mmHg measured in mid respiration using the
station pull through technique. Patients who also have a
mean distal esophageal peristaltic wave amplitude >180
mmHg are categorized as nutcracker esophagus with a hypertensive LES59. Patients with incomplete LES relaxation
are categorized as having an atypical disorder of LES relaxation, not as having an isolated hypertensive LES. The
optimum way of treatment are pneumatic dilatation and
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Primary esophageal motility disoreders
esophagocardiomiotomy with or without subsequent fundoplication regarding the hiatal dissection60 .
4. HYPOCONTRACTING ESOPHAGUS
Most patients who are diagnosed as having non-specific
esophageal motility disorders have motility tracings characterised by either low-amplitude peristaltic or simultaneous contractions in the distal esophagus, or failed peristalsis in which the wave does not traverse the entire length
of the distal esophagus. These abnormalities have been renamed ineffective esophageal motility (IEM) and are defined by the manometric presence of non-transmitted contractions or distal esophageal amplitudes less than 30 mm
Hg seen in more than 30% of contractions in the distal
esophagus61. The impact of this disorder on esophageal
bolus transit, however, has not been critically assessed.
Most patients with ineffective esophageal motility have
gastroe-sophageal reflux disease often associated with
respiratory or ear, nose, and throat complaints62. A low
pressure in the LES commonly seen in patients with gastroesophageal reflux, suggesting that the hypocontractile
esophagus could be secondary to chronic acid damage to
the distal esophagus. The LES hypotension might not be
severe, however, and studies suggest that the abnormal
acid exposure in these patients correlates better with the
weak esophageal pump than with the resting LES pressure. For these reasons, LES hypotension is not required
as a diagnostic criterion for ineffective esophageal motility. Dysphagia is usually mild in patients with IEM and
heartburn and acid regurgitation are more common. Severe dysphagia sugge-sts the presence of an anatomical
problem such as esophagitis or a peptic stricture. Treatment is directed at controlling the acid reflux. Unfortunately, no drug can reliably increase peristaltic amplitude63.
5. NONSPECIFIC ESOPHAGEAL MOTILITY DISORDERS
The conditions discussed above are those that have been
recognized and named by investigators, and for which
there are published series. Many patients previously categorized as having nonspecific esophageal motility disorders (NSMD) would be included in the category of ineffective esophageal motility. The diagnosis of NSMD is
often used in the evaluation of a patient with dysphagia
and/or chest pain who has abnormal findings on esophageal motility tracing but does not fulfill the fixed criteria
for other discrete diagnoses. The only required finding for
NSMD is "peristaltic abnormalities of insufficient severity
to establish any (other) diagnosis, yet not felt to be normal". The list of associated findings for NSMD includes
contractions that are variously nontransmitted, retrograde,
repetitive, high amplitude, low amplitude, prolonged, or
spontaneous. Incomplete LES relaxation can also be seen
in patients with NSMD. These findings can be found in
any combination. Treatment of NSMD is nonstandardized
at present, and treatment decisions are often aimed at symptomatic relief and guided by the dominant pattern (spastic, hypocontractile, etc) seen during esophageal mano-
15
metry. Pending further advances in our understanding of
the pathophysiology of motility abnormalities, non-specific esophageal motility abnormalities should be reported
descriptively. On the other hand, as we have noticed in
our everyday clinical practice, many NSMD represent just
the beginning or an early stage of yet completely undifferentiated PEMD, so continuous regular manometric checkups are strongly advised .
SA@ETAK
Primarni poreme}aji motiliteta jendjaka predstavljaju
mnogobrojne patolo{ke manometrijske nalaze koji se
uglavnom manifestuju u vidu disfagije ili retrosternalnog
bola. Pojedina oboljenja, kao {to je ahalazija, predstavljaju stanja koja imaju dobro definisanu patologiju,
karakteristi~ne manometrijske nalaze kao i dobar odgovor
na le~enje u vidu palijacije samih simptoma. Druga oboljenja, kao {to su difuzni spazam jednjaka i jednjak u vidu
krckalice za orah, nemaju jasno definisanu patologiju i
mogu predstavljati spektar poreme}aja motliteta koji su
povezani sa subtilnim neuropatolo{kim promenama, gastroezofagealnim refluksom ili stresnim stanjima. Sa druge
strane, hipokontraktilni jednjak je uglavnom uzrokovan
postojanjem slabe muksulature naj~e{}e uzrokovane gastroezofagelanim refluksom. Iako su manometrijske vrednosti za sva ova stanja jasno definisane, povezanost sa
simptomima je nespecifi~na, dok je u pojedinim slu~ajevima odgovor bolesnika na medikamentoznu terapiju ili
hirur{ko le~enje nepredvidiv. Cilj ovog rada je da prika‘e
{iroki spektar primarnih poreme}aja motliteta jendjaka
kao i da ponudi sa‘et pregled za klini~are koji se susre}u
sa ovim specifi~nim oboljenjima.
Klju~ne re~i: jednjak, motlitet, manometrija
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