Trastornos motores del esofago

1. Motor dysfunction is responsible for symptomatic illnesses
both in the proximal skeletal muscle region and in the distal
smooth muscle esophagus. Practical methods for diagnosing
and treating oropharyngeal dysphagia continue to reach
consensus. Achalasia, the most significant of the distal motor
disorders, is of investigative interest because of the expanded
armamentarium of treatment options. Minimally invasive surgi-
cal methods have taken an important foothold as a primary
treatment of this disorder. Appreciation is growing for sensory
dysfunction that accompanies distal motor disorders. Such
dysfunction may help explain the observed discrepancies
between symptoms and measurable motility abnormality. Curr
Opin Gastroenterol 2000, 16:360–368 © 2000 Lippincott Williams & Wilkins,
Inc.
Division of Gastroenterology, Washington University School of Medicine, St.
Louis, Missouri, United States
Correspondence to Ray E. Clouse, MD, Professor of Medicine and Psychiatry,
Division of Gastroenterology, Campus Box 8124, 660 S. Euclid Avenue, St.
Louis, MO 63110, USA; e-mail: rclouse@im.wustl.edu
Current Opinion in Gastroenterology 2000, 16:360–368
Abbreviations
UES upper esophageal sphincter
LES lower esophageal sphincter
ISSN 0267–1379 © 2000 Lippincott Williams & Wilkins, Inc.
Motor disorders can involve the skeletal muscles of the
pharyngoesophageal region or the smooth muscles of
the remaining esophageal body and lower esophageal
sphincter (LES). The former cause oropharyngeal
dysphagia, tracheobronchial aspiration, and other symp-
toms of abnormal bolus transit from the oral cavity into
the esophagus. The symptoms are perceived accurately
by the patient, and localization of symptoms is not diffi-
cult. In contrast, motor disorders involving the distal
esophagus produce less reliable syndromes—the symp-
toms being vague, variable, and typically nonprogres-
sive. Distal motor abnormalities can be separated into
hypomotility or hypermotility disorders reflecting inade-
quacy of the esophageal contractile apparatus or
inhibitory neural network, respectively [1•].
Hypomotility disorders expectedly predispose to
gastroesophageal reflux disease and produce symptoms
almost exclusively through this mechanism. In contrast,
hypermotility results in nonpropulsive, obstructive
motor patterns in addition to poor esophageal clearance.
Inhibitory nerve errors in the esophageal body cause
contractions of simultaneous onset at different
esophageal levels, exaggerated contractile response, and
incomplete LES relaxation [1•]. The hallmark hyper-
motility disorder achalasia, which is caused by inhibitory
nerve death, differs from the spastic disorders in which a
presumed dysfunctional imbalance between inhibitory
and excitatory influences intermittently produces the
characteristic motor abnormalities. A new theme is
surfacing that links the degree of esophageal sensitivity
to intraluminal stimuli with the motor pattern: hyposen-
sitivity accompanying hypomotility and hypersensitivity
accompanying hypermotility may be important factors in
influencing the clinical presentation of distal motor
disorders.
Diagnostic techniques
Proximal symptoms and disorders are primarily investi-
gated using radiological and endoscopic techniques.
Although the latter have been used typically to detect
structural lesions responsible for the symptoms, a
growing body of literature supports the use of videoen-
doscopic methods for evaluating the functional swallow.
Transnasal or transoral videoendoscopic techniques are
effective methods of detecting tracheobronchial aspira-
tion in neurogenic dysphagia and have the added
benefit of demonstrating aspiration of saliva, a clinically
relevant event [2]. Direct observation can also detect
backflow of recently swallowed cream into the
360
Esophageal motor disorders
Chandra Prakash, MD, MRCP, and Ray E. Clouse, MD

2. hypopharynx as a sign of Zenker diverticulum (“sign of
the rising tide”), a finding that seems specific for this
disorder [3•]. Videofluoroscopy, however, remains a
mainstay as an evaluation tool and accurately detects
structural and functional abnormalities responsible for
proximal symptoms [2]. Recent work suggests that radi-
ological assessment of oropharyngeal swallowing mecha-
nisms may be hampered by the presence of either fine-
or large-bore nasogastric tubes, and their removal is
recommended before evaluation is initiated [4].
Evaluation of distal esophageal symptoms typically
begins with endoscopy because of its diagnostic and
therapeutic potential and greater likelihood of common
structural lesions over motor disorders. The investiga-
tive sequence should be altered if achalasia is suspected
from the clinical presentation; a barium swallow and/or
manometric evaluation can streamline further testing
and therapy [5••]. Although insensitive to less signifi-
cant motor disorders, the barium swallow with videoflu-
oroscopy accurately detects achalasia (94%) and severe
hypomotility (100%) in the research setting [6•]. The
accurate differentiation of severe motor disorders can
also be accomplished at endoscopy when the operators
are focused on this purpose [7•]. Such accuracy has not
held up in the clinical arena, and manometry remains
the gold standard for identifying and classifying motor
dysfunction of the distal esophagus. Current reports
remind us that sedatives can influence LES pressure
and that manometric studies can be performed in all age
groups, if indicated [8,9]. Once structural lesions are
excluded, the precise utility of aggressive investigation
of esophageal function in symptomatic patients (includ-
ing ambulatory manometry and pH testing) remains
debatable. Data continue to suggest that clinical
management is influenced in a reasonable subset of
patients [10].
Proximal symptoms and disorders
Through their effects on coordination and contractile
strength of muscles involved in the swallowing process,
a variety of neurological and skeletal muscle diseases
predispose patients to tracheobronchial aspiration, an
outcome that can occur early in their courses [11,12].
Consensus guidelines for the evaluation and manage-
ment of oropharyngeal dysphagia in symptomatic
patients and in those with diseases that predispose to
this condition have been published recently (Table 1)
[13••,14••]. Modification of diet, swallowing posture,
and swallowing technique may improve oral nutrition
and reduce aspiration risk, even when definitive therapy
is unavailable [14••]. In fact, these techniques, when
correctly applied, allowed reversion to oral feeding and
removal of gastrostomy feeding tubes in more than 60%
of one group of subjects with neurogenic dysphagia
while simultaneously providing a cost-effective
improvement in quality of life [15•]. For some patients,
simple bougienage of the upper esophageal sphincter
also appears to improve symptoms [16].
Cricopharyngeal myotomy remains an essential element
of therapy for Zenker diverticula, because incomplete
relaxation of the UES produces high pharyngeal pres-
sures that appear responsible for diverticulum formation
[17••]. Myotomy significantly reduces the UES basal
pressure but may not pose the dangerous risk of
esophagopharyngeal reflux once presumed [18].
Diverticula more than 5 cm in length are resected at the
time of myotomy, whereas diverticulopexy suffices for
smaller pouches [17••]. Enthusiasm continues to mount
for minimally invasive endoscopic approaches to manag-
ing Zenker diverticula. One method divides the wall
separating the cervical esophagus from the diverticulum
with an endoscopically guided device [17••,19].
Endoscopic stapling diverticulostomy in which an
endostapler is used has been reported recently by two
groups of investigators [20,21•]. Operative time was as
short as 5 to 10 minutes in some instances and averaged
20 to 22 minutes. Oral intake was resumed on the first or
second postoperative day, and the patients were
discharged after an average hospital stay of less than 5
days. Complications were uncommon over extended
follow-up. A repeated endoscopic procedure, when
needed for persistence of the diverticular pouch, was
also successful [21•]. The short procedure times and low
morbidity make endoscopic therapy for Zenker divertic-
ulum very appealing, especially in elderly patients with
concomitant medical problems that preclude more inva-
sive approaches.
Achalasia
Pathogenesis
Additional information supports an immunogenetic
basis for achalasia. A T-cell lymphocytic infiltrate has
been demonstrated recently surrounding degenerating
nerve fibers in the myenteric plexus of biopsy speci-
mens and esophagectomy specimens from patients with
the disease [22•]. Resultant loss of nitrinergic inhibitory
Esophageal motor disorders Prakash and Clouse 361
Published with permission [13].
Perform careful history and physical examination to determine
whether oropharyngeal dysphagia is likely and to identify the
potential causes.
Identify structural origins of oropharyngeal dysfunction (eg,
osteophytes, cricopharyngeal bars, Zenker diverticulum) and
explore potential surgical or endoscopic therapies.
Determine the functional integrity of the swallow mechanism,
using tests such as videofluoroscopy, nasoendoscopy of the
oropharynx, and esophageal manometry.
Evaluate the risk of aspiration pneumonitis, typically by using
videofluoroscopy.
Determine whether the pattern of dysphagia is amenable to therapy.
Table 1. Guidelines for the evaluation and management of
oropharyngeal dysphagia

3. esophageal neurons extends throughout the distal
esophagus and into the proximal stomach (Fig. 1) [23•].
The stimulus for this inflammatory reaction remains
incompletely understood but may be driven by autoim-
mune factors. Presumably participating in the process,
autoantibodies against M2 muscarinic acetylcholine
receptors have been found in patients with either acha-
lasia from Chaga disease or idiopathic achalasia [24•].
These antibodies increase the contractile activity of the
LES through specific activation of the receptors [24•].
HLA typing confirms a genetic contribution to the
pathogenetic process that may vary with studied popula-
tions. An association between idiopathic achalasia and
the DQB1*0602 allele was found by Verne et al. [25•] in
a group of white subjects, whereas the DRB1*12 allele
was linked to this disease in African Americans.
Achalasia is also known to occur in association with
other genetically defined disorders, such as Down
syndrome [26] and familial glucorticoid deficiency with
alacrima [27].
Diagnosis
Conventional tests used to diagnose achalasia, includ-
ing manometry, cannot accurately separate idiopathic
achalasia from secondary causes of this disease. The
most common secondary cause is a malignant tumor of
the gastric cardia, although reports of an achalasia-like
picture after fundoplication are increasingly appearing
[28,29••]. Malignant “pseudoachalasia” resembles
idiopathic achalasia symptomatically but tends to
occur in older patients who have shorter symptom
histories and greater weight loss [30•]. As many as
18% of patients with cancer of the gastric cardia have
some manometric features of achalasia, although a
classic clinical presentation is seen in a much smaller
proportion [31]. Once more than 50% of the circumfer-
ence of the esophagogastric junction is involved, LES
relaxation may become impaired and secondarily
induce aperistalsis [31]. The poor accuracy of clinical
and manometric findings in segregating idiopathic
from secondary achalasia is an important consideration
with the increasing popularity of minimally invasive
surgery for initial treatment of the idiopathic disorder.
Serial endoscopies with biopsy of the esophagogastric
junction may be the most sensitive diagnostic method
in suspected cases, but transabdominal ultrasonogra-
phy has been reported recently to have some role in
this regard [32•]. Intrasphincteric injection of botu-
linum toxin may also provide useful information in
ambiguous cases of achalasia [33•]. Botulinum toxin
injection appears to produce symptomatic benefit
through several mechanisms, however, and interpreta-
tion of the symptomatic outcome from therapeutic
trials is difficult.
Esophageal cancer can develop late in the course of
achalasia. Early diagnosis is difficult, because lesions
remain asymptomatic until advanced. Predisposing
factors in addition to the long history of disease include
an enlarged, tortuous esophagus and marked retention
[34]. Although routine screening presently is not recom-
mended, samples of macroscopic changes visualized
during incidental endoscopies should be obtained in
biopsy to exclude neoplastic transformation. Yamamuro
et al. [35] reported improved endoscopic detection of
esophageal mucosal irregularities after staining with
Lugol iodine, a method that helps direct biopsy to
suspected sites.
Treatment
Pharmacologic treatment and botulinum toxin injection
produce short-term benefits that may be helpful in the
management of achalasia in some patients. Nifedipine
and short-acting nitrates are the most studied pharmaco-
logic agents. Nifedipine has a better side effect profile,
whereas nitrates may be more effective. In one study,
70% of patients with achalasia and minimal esophageal
dilatation (<5 cm) treated with sublingual nifedipine
before meals demonstrated a good to excellent initial
clinical response without severe side effects [36•]. It is
not easily shown that the symptomatic benefits of these
agents are uniformly related to improved esophageal
emptying, and, consequently, eventual complications of
achalasia may not be avoided. Pharmacological agents are
best used in those with early disease not accompanied by
esophageal dilatation and when there are contraindica-
tions to pneumatic dilation or surgery [37••].
Intrasphincteric botulinum toxin injection is popular
with patients who have achalasia and is efficacious in
the majority for short-term symptom management
362 Esophagus
Figure 1. Mean number of nitrinergic myenteric ganglion cells
Ganglioncells,mean#
0
10
5
15
20
Achalasia
Controls
Gastric
fundus
Gastric
component
LES
Esophageal
component
*
*
*
Number of cells in the esophageal and gastric components of the lower
esophageal sphincter (LES), as well as in the gastric fundus of achalasia patients
(light bars) and control participants (dark bars). P < 0.05 compared with control
participants. Published with permission [23•].

4. [38•,39•]. However, similar to pharmacologic treat-
ment, botulinum toxin has a greater effect on symp-
toms than on LES pressure and esophageal emptying
[39•,40••,41]. Consequently, it is not considered a
suitable alternative to pneumatic dilation or myotomy
in the average patient with this disease. Duration of
treatment response typically is brief. In separate
studies, investigators from three institutions reported a
60% to 75% initial benefit of botulinum toxin therapy,
but symptoms recurred in 50% to 100% during a 1- to
2.5-year follow-up [38•,40••,42•]. The duration of
symptom relief appears to lengthen with subsequent
injections, and treating patients on an as-needed basis
may be the most acceptable management plan for
patients who cannot tolerate pneumatic dilation or
surgery [38•,43]. The approach is not cost-effective
compared with pneumatic dilation and may actually
interfere with the success of subsequent myotomy, if
needed [44••].
Pneumatic dilation remains an important management
option for achalasia. The trend is to begin with smaller
balloons and shorter inflation times; the response can be
as good as with more aggressive approaches, and compli-
cation rates are reduced. This was highlighted by a
recent study comparing symptomatic outcomes in rela-
tion to dilation technique (Table 2) [45••]. A reduction
in LES resting pressure by more than 40% typically
identifies the symptomatic responder to pneumatic dila-
tion [46]. Likewise, and in contrast to observations with
pharmacologic therapy or botulinum toxin injection,
reduction in symptoms after treatment typically is asso-
ciated with improvement in esophageal emptying
[47••]. In clinical practice, emptying can be assessed in
a standardized way by measuring the height of the
barium column 1 and 5 minutes after the patient ingests
the barium in the upright position [47••]. Despite the
better association between objective emptying and
symptoms, a subset of older patients with good sympto-
matic response had less than 50% improvement in
barium height in one report (Fig. 2). These findings
reaffirm the peculiar association of achalasia symptoms
with transit impairment and may help explain differ-
ences across studies when various outcome measures are
used.
Primary surgery for achalasia has clearly shifted toward
minimally invasive approaches. Laparoscopic
esophageal procedures are as effective as their open
counterparts, yet they have the advantages of shorter
hospital stays, less time absent from work, less blood
loss during surgery, less parenteral narcotic use, and less
incisional morbidity [48•,49]. Video-assisted thoraco-
scopic surgery also has been used in the management of
achalasia [50]. Modest follow-up (mean 28 months) of
168 patients who underwent laparoscopic or thoraco-
scopic myotomy demonstrated lasting relief of dyspha-
gia [51•]. Although both approaches are associated with
good results in more than 85% of patients, the thoraco-
scopic approach may be associated with longer hospital
stay and higher incidences of postoperative dysphagia
and reflux [51•,52•]. Laparoscopic myotomy is rapidly
becoming an important alternative to pneumatic dilation
as initial therapy for achalasia. Its durable treatment
effect in a large majority of patients is the primary
attractive feature.
A fundoplication is typically performed in conjunction
with laparoscopic myotomy, because the degree of
mobilization at the esophagogastric junction increases
the likelihood of pathological reflux. This may not be
uniformly required; Richards et al. [53•] report that
reflux is uncommon in short-term follow-up, even when
a wrap is not performed. In their study of 16 patients
who underwent laparoscopic Heller myotomy without
concomitant fundoplication, pathologic reflux devel-
oped in only one patient during a mean follow-up of 8.3
months. This period of observation may have been too
short to draw meaningful conclusions, however, because
serious reflux-related complications often occur late
after surgical management. Partial fundoplication in
association with laparoscopic Heller myotomy is well
tolerated, and some evidence is already available to
support its routine use [54]. Additionally, available data
from traditional open thoracic or abdominal myotomy
indicate that the best postoperative symptomatic results
Esophageal motor disorders Prakash and Clouse 363
*P < 0.05. Published with permission [45••].
Balloon diameter
30 mm
35 mm
Inflation duration
15 sec
60 sec
Patients, n
12
12
12
12
Before dilation
10.7
9.7
8.4
10.0
1 month after dilation
2.5*
2.5*
2.5*
2.8*
6 months after dilation
2.7*
2.3*
2.3*
2.6*
Table 2. Effect of pneumatic dilation on dysphagia score in achalasia
Mean dysphagia score

5. are obtained when the myotomy is combined with an
antireflux procedure [55].
Prior botulinum toxin injections can interfere with
subsequent myotomy, resulting in difficulties with
dissection at the submucosal plane and occasional
mucosal perforation [56••]. This apparently is caused
by an inflammatory reaction incited by the injected
protein. Patti et al. [57•] found that fibrotic changes in
the region of the LES and mucosal perforation at the
time of myotomy were more likely if botulinum toxin
therapy was initially successful, compared with failed
botulinum toxin therapy, making the local response
potentially valuable for symptomatic improvement.
This response, however, would best be avoided if
surgery were in the ultimate management plan. In spite
of operative difficulties, the laparoscopic myotomy is
still effective for symptom relief and should not be
discouraged in those with previous botulinum toxin
injections [56••,39•]. Similarly, laparoscopic myotomy
is safe and effective after previous pneumatic dilation,
with complication and success rates not dissimilar from
those in patients with patients who have not undergone
prior treatment [57•,58•,59].
Recent reports confirm the efficacy of pneumatic dila-
tion and minimally invasive myotomy in a variety of
special situations. Hamza et al. [60•] described good-to-
excellent symptomatic benefit from pneumatic dilation
in 91% of 11 children (1.5 to 14 years of age). All patients
needed at least two procedures, but during 2 to 7 years’
follow-up only one patient in their series needed surgery.
Although pneumatic dilation was once considered rela-
tively contraindicated in patients with widely ectatic
esophagi, Khan et al. [61•] demonstrated the safety, effi-
cacy, and response durability of pneumatic dilation, even
when the esophageal diameter exceeded 7 cm. The pres-
ence of a dilated esophagus also has little impact on the
outcome from laparoscopic myotomy [62•]. The achala-
sia pattern found in as many as 81% of patients with
severe postoperative dysphagia after a tight fundoplica-
tion for gastroesophageal reflux disease is also responsive
to pneumatic dilation. The procedure was safe in all and
effective in 9 of 16 patients in one series, with the
remainder requiring surgical revision [29••].
Long-term response data suggest a higher rate of unsat-
isfactory treatment than previously thought with either
pneumatic dilation or myotomy. In a telephone survey,
74% of patients who underwent pneumatic dilation and
67% of those who underwent myotomy reported symp-
toms, needed retreatment, or had procedure-related
complications during extended follow-up of more than 6
years. More than one third in each group did not pursue
medical intervention [63••]. Some of the dissatisfaction
may relate to the recent observation that chest pain from
achalasia is unlikely to respond to successful treatment
for dysphagia and may persist for years before gradually
abating spontaneously [64]. Additionally, the presence
of objectively defined pathologic reflux is poorly corre-
lated with symptoms in patients with achalasia [52•].
Confirmation of pathologic reflux using 24-hour pH
monitoring may be required to prevent late reflux
complications in those patients with asymptomatic
disease. Esophagectomy with gastric reconstruction
remains a reasonable final option for end-stage achalasia.
Banbury et al. [65•] reviewed the outcome of 32 patients
in a 10-year period who had undergone esophagectomy
for achalasia and found excellent dietary function and
weight maintenance with minimal postoperative symp-
toms in the majority.
Spastic disorders
The pathophysiology of spastic disorders remains poorly
understood. Rate et al. [66•] attempted to further char-
acterize the neuromuscular defects in diffuse esophageal
spasm and nonspecific spastic disorders using a combi-
nation of neurophysiological techniques: cortical-evoked
potentials in response to esophageal electrical stimula-
tion, esophageal motor-evoked potentials in response to
transcranial magnetic stimulation, and symptomatic
response to esophageal balloon distension. These disor-
ders were represented by variable abnormalities in
receptor sensitivity, central processing, and sensory
neuropathy, and there was no correlation between the
manometric diagnosis and abnormal neurophysiology.
364 Esophagus
Figure 2. Association between degree of symptom and barium
height improvements
Bariumdrainageimprovement
< 50%
< 50%
50–90%
91–100%
50–90%
Symptom improvement
91–100%
Degree of symptom and barium height improvements after 53 pneumatic dila-
tions in 37 patients with achalasia. Overall, in 38 of 53 dilations (72%), there
was similar improvement in both parameters. Minimal objective improvement in
the esophageal barium height occurred in eight of 26 dilations (31%) with nearly
complete symptom improvement. Published with permission [47••].

6. Esophageal motor disorders Prakash and Clouse 365
The vague neurophysiological basis underlies a very
indirect relationship of the spastic disorders with symp-
toms. Recent studies emphasize the high prevalence of
spastic disorders in some asymptomatic or mildly symp-
tomatic groups. Jaffin et al. [67] made these diagnoses in
more than a third of asymptomatic morbidly obese
subjects, and Annese et al. [68•] again demonstrated the
high rate of spastic abnormalities in diabetic patients.
Manometric findings were poorly predicted by symp-
toms or by autonomic neuropathy in the latter group,
supporting prior observations. Despite the poor associa-
tion with symptoms, these disorders probably represent
markers for other pathophysiological mechanisms that
are more directly linked to symptom production. This
may explain the poor outcome and persistence of chest
pain after surgical myotomy for spastic disorders [69].
Hypersensitivity to visceral stimuli appears to be an
important participant in symptom production from these
disorders, an abnormality not resolved by surgical
management.
Antidepressants have demonstrated utility in patients
with unexplained esophageal symptoms and nonspe-
cific spastic abnormalities (eg, nutcracker esophagus).
Recently, Handa et al. [70•] used antidepressants in
eight patients with diffuse esophageal spasm to see
whether the drugs were also effective for symptom
management in this spastic disorder. Previous therapy
with calcium channel blockers and nitrates had failed
in each patient. Symptoms rapidly abated in all eight
patients with low-dose trazodone or clomipramine, a
response that extended to at least 6 months in each
instance. Prakash and Clouse [71••] also demonstrated
the sustained effects of low-dose tricyclic antidepres-
sant regimens in open-label treatment of patients with
functional chest pain, a diagnosis commonly accompa-
nied by spastic disorders. Prolonged symptom remis-
sions (>6 months) were achieved in three fourths of the
81% who initially responded to antidepressant treat-
ment, and healthcare resource use for chest pain was
markedly reduced during treatment. How these
medications reduce symptoms and, more specifically,
whether they attenuate visceral hypersensitivity
remains unknown, but a recent meta-analysis convinc-
ingly demonstrates the benefits of antidepressants in a
large number of medical symptoms and syndromes that
have no defined pathological basis [72••].
Esophageal hypomotility
Gradual decay in contraction strength in the
esophageal body occurs with aging. Grande et al. [73•]
found an inverse correlation of age with peristaltic
wave amplitude and velocity, as well as length and
pressure of the sphincters in healthy volunteers. Some
illnesses, such as systemic sclerosis, are also associated
with esophageal hypomotility [74•]. Clinical features
of esophageal hypomotility are typically overshadowed
by other system manifestations in patients with
connective tissue diseases [75]. The accumulation of
buffering substances in the distal esophagus from
prolonged esophageal clearance time may contribute
to the favorable outcome, but some degree of
esophageal hyposensitivity may also be operational in
attenuating symptoms [76•]. Scintigraphic assessment
of esophageal transit has demonstrated that primary
Raynaud disease is less likely to influence motility
and emptying times than systemic sclerosis [77].
Varying degrees of hypomotility are common in
patients with gastroesophageal reflux disease. Low
amplitude (<30 mm Hg) or nontransmitted contractions
after at least 30% of wet swallows are the most common
esophageal motor abnormalities and have been labeled
ineffective esophageal peristalsis by some investigators.
These hypomotility features occur significantly more
often in patients with atypical reflux manifestations (eg,
cough, asthma) than in patients with heartburn [78••],
further suggesting an association of this motor pattern
with esophageal hyposensitivity. As would be expected,
esophageal acid exposure times are significantly longer
in patients with respiratory symptoms than in patients
with heartburn [78••].
References and recommended reading
Papers of particular interest, published within the annual period of review,
have been highlighted as:
• Of special interest
•• Of outstanding interest
•
1 Sifrim D: Role of deglutitive inhibition in the pathophysiology of esophageal
primary motor disorders [in Spanish]. Rev Esp Enferm Dig 1999,
91:711–715.
A review exploring the pathophysiology of esophageal motility disorders with
emphasis on deglutitive inhibition.
2 Schroter-Morasch H, Bartolome G, Troppmann N, Ziegler W: Values and
limitations of pharyngolaryngoscopy (transnasal, transoral) in patients with
dysphagia. Folia Phoniatr Logop 1999, 51:172–182.
•
3 Perie S, Dernis HP, Monceaux G, et al.: The “sign of the rising tide” during
swallowing fiberscopy: a specific manifestation of Zenker’s diverticulum.
Ann Otol Rhinol Laryngol 1999, 108:296–299.
A specific endoscopic sign of Zenker diverticulum is described.
4 Huggins PS, Tuomi SK, Young C: Effects of nasogastric tubes on the
young, normal swallowing mechanism. Dysphagia 1999, 14:157–161.
••
5 Spechler SJ: AGA medical position statement on treatment of patients with
dysphagia caused by benign disorders of the distal esophagus.
Gastroenterology 1999, 117:229–233.
Current guidelines on the management of benign but symptomatic disorders of
the distal esophagus, including motor disorders.
•
6 Fuller L, Huprich JE, Theisen J, et al.: Abnormal esophageal body function:
radiographic manometric correlation. Am Surg 1999, 65:911–914.
When manometry is used as the gold standard, barium studies have a sensitivity
of only 55% in detecting esophageal motility disorders.
•
7 Cameron AJ, Malcolm A, Prather CM, Phillips SF: Videoendoscopic diag-
nosis of esophageal motility disorders. Gastrointest Endosc 1999,
49:62–69.
Experienced endoscopists can accurately distinguish achalasia and scleroderma
esophagus from healthy subjects during endoscopy in the research setting.
8 Croffie JM, Ellett ML, Lou Q, Fitzgerald JF: A comparison of the effect of
three sedatives on esophageal sphincters in cats. Dig Dis 1999,
17:113–120.

7. 366 Esophagus
9 Omari T, Snel A, Barnett C, et al.: Measurement of upper esophageal
sphincter tone and relaxation during swallowing in premature infants. Am J
Physiol 1999, 277:G862–G866.
10 Netzer P, Gut A, Heer R, et al.: Five-year audit of ambulatory 24-hour
esophageal pH-manometry in clinical practice. Scand J Gastroenterol
1999, 34:676–682.
11 Ertekin C, Aydogdu I, Yuceyar N, et al.: Pathophysiological mechanisms of
oropharyngeal dysphagia in amyotrophic lateral sclerosis. Brain 2000,
123:125–140.
12 Modolell I, Mearin F, Baudet JS, et al.: Pharyngo-esophageal motility distur-
bances in patients with myotonic dystrophy. Scand J Gastroenterol 1999,
34:878–882.
••
13 American Gastroenterological Association. AGA medical position state-
ment on management of oropharyngeal dysphagia. Gastroenterology 1999,
116:452–454.
Current guidelines for the investigation and management of oropharyngeal
dysphagia.
••
14 Cook IJ, Kahrilas PJ: AGA technical review on management of oropharyn-
geal dysphagia. Gastroenterology 1999, 116:455–478.
In-depth literature review pertaining to management of oropharyngeal dysphagia.
•
15 Klor BM, Mikianti FJ: Rehabilitation of neurogenic dysphagia with percuta-
neous endoscopic gastrostomy. Dysphagia 1999, 14:162–164.
Dietary intervention and direct-swallow retraining can improve nutrition and avoid
the need for gastrostomy tubes in neurogenic dysphagia.
16 Hatlebakk JG, Castell JA, Spiegel J, et al.: Dilatation therapy for dysphagia
in patients with upper esophageal sphincter dysfunction: manometric and
symptomatic response. Dis Esophagus 1998, 11:254–259.
••
17 Sideris L, Chen LQ, Ferraro P, Duranceau AC: The treatment of Zenker’s
diverticula: a review. Semin Thorac Cardiovasc Surg 1999, 11:337–351.
A comprehensive review of treatment options in Zenker diverticulum.
18 Williams RB, Ali GN, Hunt DR, et al.: Cricopharyngeal myotomy does not
increase the risk of esophagopharyngeal acid regurgitation. Am J
Gastroenterol 1999, 94:3448–3454.
19 Prakash C, Clouse RE: Esophageal motor disorders. Current Opin
Gastroenterol 1999, 15:339–346.
20 Omote K, Feussner H, Stein HJ, et al.: Endoscopic stapling diverticu-
lostomy for Zenker’s diverticulum. Surg Endosc 1999, 13:535–538.
•
21 Narne S, Cutrone C, Bonavina L, et al.: Endoscopic diverticulotomy for the
treatment of Zenker’s diverticulum: results in 102 patients with staple-
assisted endoscopy. Ann Otol Rhinol Laryngol 1999, 108:810–815.
Another study demonstrating the safety, efficacy, and advantages of endoscopic
diverticulotomy for Zenker diverticulum, with use of a stapling device.
•
22 Raymond L, Lach B, Shamji FM: Inflammatory aetiology of primary
oesophageal achalasia: an immunohistochemical and ultrastructural study
of Auerbach’s plexus. Histopathology 1999, 35:445–453.
Evidence for inflammation as a cause of esophageal neuronal degeneration in
achalasia.
•
23 De Giorgio R, Di Simone MP, Stanghellini V, et al.: Esophageal and gastric
nitric oxide synthesizing innervation in primary achalasia. Am J
Gastroenterol 1999, 94:2357–2362.
Loss of inhibitory neurons in achalasia is not restricted to the esophagus but
may extend into the proximal stomach.
•
24 Goin JC, Sterin-Borda L, Bilder CR, et al.: Functional implications of circu-
lating muscarinic cholinergic receptor autoantibodies in chagasic patients
with achalasia. Gastroenterology 1999, 117:798–805.
Although found significantly more often in achalasia from Chaga disease, anti-
bodies against M2 muscarinic acetylcholine receptors have also been demon-
strated in idiopathic achalasia.
•
25 Verne GN, Hahn AB, Pineau BC, et al.: Association of HLA-DR and -DQ
alleles with idiopathic achalasia. Gastroenterology 1999, 117:26–31.
Demonstration of race-specific associations of idiopathic achalasia with HLA
alleles.
•
26 Zarate N, Mearin F, Gil-Vernet JM, et al.: Achalasia and Down’s syndrome:
coincidental association or something else? Am J Gastroenterol 1999,
94:1647–1677.
A series of five cases of achalasia associated with Down syndrome.
•
27 Verma S, Brown S, Dakkak M, Bennett JR: Association of adult achalasia
and alacrima. Dig Dis Sci 1999, 44:876–878.
A case-report describing the association of achalasia with alacrima.
28 Floch NR, Hinder RA, Klingler PJ, et al.: Is laparoscopic reoperation for
failed antireflux surgery feasible? Arch Surg 1999, 134:733–737.
••
29 Gaudric M, Sabate JM, Artru P, et al.: Results of pneumatic dilatation in
patients with dysphagia after antireflux surgery. Br J Surg 1999,
86:1088–1091.
Pneumatic dilation is feasible and safe for postoperative dysphagia after antire-
flux surgery. It was successful in relieving symptoms in more than 50% of the
patients in this retrospective report.
•
30 Moonka R, Patti MG, Feo CV, et al.: Clinical presentation and evaluation of
malignant pseudoachalasia. J Gastrointest Surg 1999, 3:456–461.
Pseudoachalasia caused by occult malignancy tends to occur in persons at a
more advanced age with shorter duration of symptoms and greater weight loss
than in idiopathic achalasia. Careful investigation may be necessary to differenti-
ate one from the other.
31 Song CW, Chun HJ, Kim CD, et al.: Association of pseudoachalasia with
advancing cancer of the gastric cardia. Gastrointest Endosc 1999,
50:486–491.
•
32 Tanomkiat W, Chongchitnan P: Transabdominal sonography of gastroe-
sophageal junctions. J Clin Ultrasound 1999, 27:505–512.
Transabdominal sonography may distinguish infiltrative cancer that is causing
pseudoachalasia from idiopathic achalasia when circumferential narrowing of the
gastroesophageal junction is encountered.
•
33 Katzka DA, Castell DO: Use of botulinum toxin as a diagnostic/therapeutic
trial to help clarify an indication for definitive therapy in patients with achala-
sia. Am J Gastroenterol 1999, 94:637–642.
Response to botulinum toxin injection used as a therapeutic trial may help direct
more definitive therapy in atypical clinical presentations of achalasia.
34 Loviscek LF, Cenoz MC, Badaloni AE, Agarinakazato O: Early cancer in
achalasia. Dis Esophagus 1998, 11:239–247.
35 Yamamuro EM, Cecconello I, Iriya K, et al.: Lugol dye endoscopy for analy-
sis of esophageal mucosa in achalasia. Hepatogastroenterology 1999,
46:1687–1691.
•
36 Bortolotti M: Medical therapy of achalasia: a benefit reserved for few.
Digestion 1999, 60:11–16.
Nifedipine administered 30 to 45 minutes before each meal can provide sympto-
matic benefit in up to 70% of patients with achalasia with minimal esophageal
dilatation (<5 cm).
••
37 Bassotti G, Annese V: Review article: pharmacological options in achala-
sia. Aliment Pharmacol Ther 1999, 13:1391–1396.
An excellent review regarding the role of pharmacologic therapy in the manage-
ment of achalasia.
•
38 Prakash C, Freedland KE, Chan MF, Clouse RE: Botulinum toxin injections
for achalasia symptoms can approximate the short term efficacy of a single
pneumatic dilation: a survival analysis approach. Am J Gastroenterol 1999,
94:328–333.
Botulinum toxin injections used on an as-needed basis can provide a short-term
alternative to more definitive therapy. Second injections may provide longer-
lasting benefit than the first injection.
•
39 Andrews SE, Anvari M, Dobranowski J: Laparoscopic Heller’s myotomy or
botulinum toxin injection for management of esophageal achalasia. Patient
choice and treatment outcomes. Surg Endosc 1999, 13:742–746.
Although botulinum toxin injection is popular with patients, this therapy is less
optimal than laparoscopic myotomy in improving esophageal clearance.
••
40 Vaezi MF, Richter JE, Wilcox CM, et al.: Botulinum toxin versus pneumatic
dilatation in the treatment of achalasia: a randomized trial. Gut 1999,
44:231–239.
Botulinum toxin therapy results in symptomatic benefit without objective
evidence of improvement in LES pressure, esophageal diameter or esophageal
barium column height. The trial provides further evidence that durability of botu-
linum toxin therapy is inferior to that of pneumatic dilation.
41 Greaves RR, Mulcahy HE, Patchett SE, et al.: Early experience with intras-
phincteric botulinum toxin in the treatment of achalasia. Aliment Pharmacol
Ther 1999, 13:1221–1225.
•
42 Muehldorfer SM, Schneider TH, Hochberger J, et al.: Esophageal achala-
sia: intrasphincteric injection of botulinum toxin A versus balloon dilation.
Endoscopy 1999, 31:517–521.
A prospective study demonstrating brevity of effectiveness of botulinum toxin
therapy, with 100% recurrence of symptoms during a 2.5-year follow-up.
43 Wehrmann T, Kokabpick H, Jacobi V, et al.: Long-term results of endo-
scopic injection of botulinum toxin in elderly achalasic patients with tortu-
ous megaesophagus or epiphrenic diverticulum. Endoscopy 1999,
31:352–358.
••
44 Panaccione R, Gregor JC, Reynolds RP, Preiksaitis HG: Intrasphincteric
botulinum toxin versus pneumatic dilatation for achalasia: a cost minimiza-
tion analysis. Gastrointest Endosc 1999, 50:492–498.

8. Esophageal motor disorders Prakash and Clouse 367
In a head-to-head retrospective comparison of treatment costs, botulinum toxin
therapy was more costly than pneumatic dilation, mainly because of the added
expense of retreatment sessions.
••
45 Gideon RM, Castell DO, Yarze J: Prospective randomized comparison of
pneumatic dilatation technique in patients with idiopathic achalasia. Dig Dis
Sci 1999, 44:1853–1857.
Conservative pneumatic dilation techniques using smaller diameter balloons for
shorter inflation times can approximate benefit from more aggressive
approaches.
•
46 Alonso P, Gonzalez-Conde B, Macenlle R, et al.: Achalasia: the usefulness
of manometry for evaluation of treatment. Dig Dis Sci 1999, 44:536–541.
A decrease of LES pressure to 40% of pretreatment levels is associated with a
successful therapeutic outcome in achalasia.
••
47 Vaezi MF, Baker ME, Richter JE: Assessment of esophageal emptying post-
pneumatic dilation: use of the timed barium esophagram. Am J
Gastroenterol 1999, 94:1802–1807.
Post–pneumatic dilation esophageal emptying, measured according to barium
column height, 1 and 5 minutes after upright barium ingestion, identifies a
subset of patients who may benefit from a second dilation despite improvement
in symptoms.
•
48 Dempsey DT, Kalan MM, Gerson RS, et al.: Comparison of outcomes
following open and laparoscopic esophagomyotomy for achalasia. Surg
Endosc 1999, 13:747–750.
Laparoscopic myotomy results in excellent symptomatic outcome with good
patient satisfaction, shorter hospital stay, and less time absent from work than
with the open procedure.
49 Richardson WS, Bowen JC: Minimally invasive esophageal surgery. Surg
Clin North Am 1998, 78:795–803.
50 McFadden PM, Robbins RJ: Thoracoscopic surgery. Surg Clin North Am
1998, 78:763–772.
•
51 Patti MG, Pellegrini CA, Horgan S, et al.: Minimally invasive surgery for
achalasia: an 8-year experience with 168 patients. Ann Surg 1999,
230:587–593.
During a modest long-term follow-up, laparoscopic myotomy with a partial fundo-
plication resulted in lesser postoperative dysphagia and pathologic reflux when
compared with the thoracoscopic approach.
•
52 Champion JK, Delisle N, Hunt T: Comparison of thoracoscopic and laparo-
scopic esophagomyotomy with fundoplication for primary motility disorders.
Eur J Cardiothorac Surg 1999, 16(suppl 1):S34–S36.
This retrospective review also demonstrates the higher incidence of postopera-
tive dysphagia after thoracoscopic myotomy compared with the laparoscopic
abdominal approach in primary motility disorders of the esophagus.
•
53 Richards WO, Clements WH, Wang PC, et al.: Prevalence of gastroe-
sophageal reflux after laparoscopic Heller myotomy. Surg Endosc 1999,
13:1010–1014.
The incidence of reflux symptoms after myotomy without fundoplication was
14% on short-term follow-up in this retrospective study; however, there was
poor correlation of symptoms with pathologic reflux on 24-hour pH measure-
ment.
54 Swanstrom LL: Partial fundoplications for gastroesophageal reflux disease:
indications and current status. J Clin Gastroenterol 1999, 29:127–132.
55 Shiino Y, Filipi CJ, Awad ZT, et al.: Surgery for achalasia: 1998. J
Gastrointest Surg 1999, 3:447–455.
••
56 Horgan S, Hudda K, Eubanks T, et al.: Does botulinum toxin injection make
esophagomyotomy a more difficult operation? Surg Endosc 1999,
13:576–579.
Although prior botulinum toxin therapy makes subsequent myotomy more techni-
cally difficult, eventual clinical outcome after myotomy is no different from that in
patients who are not treated with this therapy.
•
57 Patti MG, Feo CV, Arcerito M, et al.: Effects of previous treatment on
results of laparoscopic Heller myotomy for achalasia. Dig Dis Sci 1999,
44:2270–2276.
Fibrotic changes at the LES after successful botulinum toxin therapy can
increase operative complications during subsequent myotomy for achalasia.
•
58 Ponce J, Juan M, Garrigues V, et al.: Efficacy and safety of cardiomyotomy
in patients with achalasia after failure of pneumatic dilatation. Dig Dis Sci
1999, 44:2277–2282.
This retrospective review confirms the safety and efficacy of conventional
myotomy after failed pneumatic dilation in achalasia.
•
59 Beckingham IJ, Callanan M, Louw JA, Bornman PC: Laparoscopic
cardiomyotomy for achalasia after failed balloon dilatation. Surg Endosc
1999, 13:493–496.
Laparoscopic myotomy is effective and safe after failed pneumatic dilation, but
the operation may be technically more difficult.
•
60 Hamza AF, Awad HA, Hussein O: Cardiac achalasia in children: dilatation
or surgery? Eur J Pediatr Surg 1999, 9:299–302.
Pneumatic dilation is feasible in children with achalasia, with a successful
outcome in 90% during a 2- to 7-year follow-up.
•
61 Khan AA, Shah SW, Alam A, et al.: Massively dilated esophagus in achala-
sia: response to pneumatic balloon dilation. Am J Gastroenterol 1999,
94:2363–2366.
Pneumatic dilation can be successful, even when the esophagus is massively
dilated.
•
62 Patti MG, Feo CV, Diener U, et al.: Laparoscopic Heller myotomy relieves
dysphagia in achalasia when the esophagus is dilated. Surg Endosc 1999,
13:843–847.
Laparoscopic myotomy with Dor fundoplication resulted in a good to excellent
outcome in more than 83% of patients with esophagi more than 6 cm in diame-
ter, no different from patients with esophagi of smaller diameter.
••
63 Torbey CF, Achkar E, Rice TW, et al.: Long-term outcome of achalasia
treatment: the need for closer follow-up. J Clin Gastroenterol 1999,
28:125–130.
Treatment failures during long-term follow-up of achalasia may be higher than
previously suspected.
64 Eckardt VF, Stauf B, Bernhard G: Chest pain in achalasia: patient charac-
teristics and clinical course. Gastroenterology 1999, 116:1300–1304.
•
65 Banbury MK, Rice TW, Goldblum JR, et al.: Esophagectomy with gastric
reconstruction for achalasia. J Thorac Cardiovasc Surg 1999,
117:1077–1084.
Esophagectomy remains an effective, definitive surgical option in achalasia.
•
66 Rate AJ, Hobson AR, Barlow J, Bancewicz J: Abnormal neurophysiology in
patients with oesophageal motility disorders. Br J Surg 1999,
86:1202–1206.
Excepting achalasia, esophageal motility disorders have no consistent neuro-
physiologic correlates on standardized testing using cortical-evoked potentials
and esophageal motor-evoked potentials.
•
67 Jaffin BW, Knoepflmacher P, Greenstein R: High prevalence of sympto-
matic esophageal motility disorders among morbidly obese patients. Obes
Surg 1999, 9:390–395.
Esophageal symptoms correlate poorly with manometric diagnoses of nonspe-
cific spastic disorders.
•
68 Annese V, Bassotti G, Caruso N, et al.: Gastrointestinal motor dysfunction,
symptoms and neuropathy in noninsulin-dependent (type 2) diabetes melli-
tus. J Clin Gastroenterol 1999, 29:171–177.
Although esophageal motility disorders were common in patients with type 2
diabetes, their incidence did not correlate with the presence of autonomic
neuropathy in this retrospective report.
69 Ellis FH Jr: Long esophagomyotomy for diffuse esophageal spasm and
related disorders: an historical overview. Dis Esophagus 1998,
11:210–214.
•
70 Handa M, Mine K, Yamamoto H, et al.: Antidepressant treatment of patients
with diffuse esophageal spasm: a psychosomatic approach. J Clin
Gastroenterol 1999, 28:228–232.
Low-dose tricyclic antidepressants are effective for symptomatic diffuse
esophageal spasm.
••
71 Prakash C, Clouse RE: Long-term outcome from tricyclic antidepressant
treatment of functional chest pain. Dig Dis Sci 1999, 44:2373–2379.
Three fourths of functional chest pain patients initially responding to low-dose
tricyclic antidepressants continued taking these agents continuously or for
symptom relapses for more than 2 years with symptomatic benefit in this retro-
spective report.
••
72 O’Malley PG, Jackson JL, Santoro J, et al.: Antidepressant therapy for unex-
plained symptoms and symptom syndromes. J Fam Pract 1999,
48:980–990.
Meta-analysis of randomized studies confirms clinical benefit of low-dose
tricyclic antidepressant therapy for various pain syndromes, including functional
gastrointestinal disorders.
••
73 Grande L, Lacima G, Ros E, et al.: Deterioration of esophageal motility with
age: a manometric study of 79 healthy subjects. Am J Gastroenterol 1999,
94:1795–1801.
There is a gradual decay in the strength of contraction of the esophageal body
with age.
•
74 Generini S, Fiori G, Pignone AM, et al.: Systemic sclerosis: a clinical
overview. Adv Exp Med Biol 1999, 455:73–83.
An extensive review of the pathogenesis and clinical spectrum of systemic scle-
rosis.

9. 368 Esophagus
75 Burdt MA, Hoffman RW, Deutscher SL, et al.: Long-term outcome in mixed
connective tissue disease: longitudinal clinical and serologic findings.
Arthritis Rheum 1999, 42:899–909.
•
76 Carola F, Bianchi PA, Basilisco G: Intraesophageal pH monitoring during
acid infusion in patients with systemic sclerosis. Dig Dis Sci 1999,
44:1716–1720.
Accumulation of buffering substances improves acid-buffering capacity in
patients with esophageal hypomotility and poor esophageal clearance due to
systemic sclerosis.
77 Bestetti A, Carola F, Conciato L, et al.: Esophageal scintigraphy with a
semisolid meal to evaluate esophageal dysmotility in systemic sclerosis and
Raynaud’s phenomenon. J Nucl Med 1999, 40:77–84.
••
78 Fouad YM, Katz PO, Katlebakk JG, Castell DO: Ineffective esophageal
motility: the most common motility abnormality in patients with GERD-asso-
ciated respiratory symptoms. Am J Gastroenterol 1999, 94:1464–1467.
Esophageal hypomotility is more common in patients with nonesophageal mani-
festations of GERD, which suggests that esophageal hyposensitivity may play a
role in these patients.