Psedo Aka
Psedo Aka
Psedo Aka
P. J. KAHRILAS, M.D.* Malignancies involving the gastric cardia or distal esophagus can result
S. M. KISHK, M.D. in a clinical syndrome termed pseudoachalasia that mimics idiopathic
J. F. HELM, M.D. achalasia. If not promptly recognized, pseudoachalasia can result in
W. J. DODDS, M.D. inappropriate pneumatic dilatation of the lower esophageal sphincter
J. M. HARIG, M.D. segment and delay appropriate treatment of the underlying malignan-
W. J. HOGAN, M.D. cy. During the past 14 years, six patients with pseudoachalasia and
Milwaukee, Wisconsin 161 patients with primary idiopathic achalasia were encountered.
Pseudoachalasia occurred mainly in the elderly and represented about
9 percent of these patients over 60 years of age with suspected
achalasia. Five of the six pseudoachalasia cases were secondary to
adenocarcinoma that originated in the gastric fundus, and one was
caused by a squamous cell carcinoma of the distal esophagus. Con-
ventional esophageal manometry did not discriminate achalasia from
pseudoachalasia. On the other hand, esophagogastroscopy with biop-
sy resulted in a diagnosis of pseudoachalasia in five of these cases and
in 24 of 32 cases reported previously. Ominous endoscopic findings
are mucosal ulceration or nodularity, reduced compliance of the eso-
phagogastric junction, or an inability to pass the endoscope into the
stomach. Radiographic evaluation, particularly in conjunction with
amyl nitrite inhalation, was also useful in discriminating pseudoachala-
sia from primary achalasia. It is concluded that pseudoachalasia gen-
erally mimics idiopathic achalasia imperfectly and can usually be
diagnosed prior to surgery by fastidious endoscopic and radiographic
examination.
TABLE I Clinical Features of Six Patients wlth ter swallows. Provocative tests with methacholine chloride
Pseudoachalasia (Mecholyl) and cholecystokinin octapeptide were generally
performed in patients with suspected achalasia. The meth-
Duration of acholine test was carried out by administering 5 mg of
Symptoms Weight Loss
methacholine chloride (Sigma Chemical Company, St. Lou-
Patient Age/Sex Clinical Symptoms (months) (pounds)
is, Missouri) subcutaneously while recording the intralu-
1 53/M Dysphagia, vomiting, 3 50 minal pressure of the esophageal body. A positive test
chest pain, regurgi- result is defined as one in which the pressure in the esopha-
tation geal body increases by at least 25 mm Hg for 30 seconds
2 67/F Dysphagia, regurgita- 9 a within eight minutes after methacholine administration
tion, chest pain [ 13,141. If the test result was negative with the 5 mg dose
3 41/M Dysphagia 5 25
of methacholine, the test was repeated with a 10 mg dose.
4 71/M Dysphagia, regurgita- 3 25
tion Prior to 1976, we often performed the methacholine test in
5 72/F Dysphagia, chest 6 21 conjunction with barium esophagraphy as well as during
pain, regurgitation manometry. In this case, the criterion for a positive test
6 70/M Dysphagia 2 25 result was the development of nonperistaltic, lumen-oblit-
erating contractions in the distal half of the esophagus that
lasted for more than 30 seconds. Pilot testing in 20 patients
indicated a 95 percent correlation between the manometric
and lung as well as lymphoma have all been reported to and fluoroscopic findings for a positive test result [ 151. The
cause what has been variably termed secondary achala- cholecystokinin provocative test was performed by giving
sia or pseudoachalasia [4-lo]. cholecystokinin octapeptide (E.R. Squlbb and Sons Inc.,
During the past 14 years at the Medical College of Princeton, New Jersey) 40 rig/kg intravenously while re-
Wisconsin, we have had a substantial referral of patients cording lower esophageal sphincter pressure activity with a
with suspected achalasia. In the same period, we have Dent-sleeve device. Any increases in this sphincter pres-
encountered six patients with pseudoachalasia, five of sure were assessed by comparing the highest end-expirato-
whom were referred with the initial diagnosis of idiopathic ry lower esophageal sphincter pressure for the two-minute
achalasia. This report compares our experience with interval before cholecystokinin octapeptide administration
these two entities in terms of their clinical presentation against the highest value occurring one to three minutes
after administration of the agents. All lower esophageal
and diagnostic findings. Combining our own data with that
sphincter pressures were referenced to end-expiratory gas-
obtained from the medical literature, we assess the age tric pressure as zero. Sphincter pressure increases of 5
distribution and other comparative features of these two mm Hg or more constituted a positive test result [lS]. In
diseases. addition to the methacholine and cholecystokinin octapep-
tide provocative tests, a small number of patients with
PATIENTS AND METHODS achalasia were challenged with four sniffs of amyl nitrite
From 197 1 to 1985, we performed esophageal manometric (Eli Lilly and Company, Indianapolis, Indiana) while the low-
studies in over 2,406 patients. The records of these proce- er esophageal sphincter pressure was monitored. The nor-
dures were reviewed and all patients were identified whose mal response to amyl nitrite (negative test result) was a
manometric findings suggested achalasia. Patients were substantial decrease in sphincter pressure [ 171.
classified as having primary idiopathic achalasia when they Manometric findings supportive of the diagnosis of acha-
exhibited endoscopic, radiographic, and manometric find- lasia are: (1) aperistalsis in the thoracic esophagus, (2)
ings consistent with this diagnosis, underwent successful failure of the lower esophageal sphincter to relax com-
treatment with either pneumatic dilatation or surgical myot- pletely with deglutition, (3) elevated lower esophageal
omy, and were followed for a minimum of one year. The sphincter pressure (normal less than 35 mm Hg in our
patients classified as having pseudoachalasia were either laboratory), and (4) positive results of methacholine or cho-
referred to our laboratory with a diagnosis of idiopathic lecystokinin octapeptide provocative tests. Items 1 and 2
achalasia or our initial diagnostic impression was achala- were considered major criteria whereas items 3 and 4 were
sia. These patients, however, were subsequently shown to considered minor criteria. The manometric findings were
have a malignancy accounting for their dysphagia. considered consistent with the diagnosis of achalasia if
The methodology employed in the manometric studies both major criteria were met. In some instances, lower
varied as improvements in instrumentation occurred. A esophageal sphincter relaxation could not be assessed, in
low-compliance pneumohydraulic pump [I I] has been which case the findings of aperistalsis and one minor crite-
used as part of our infusion manometry apparatus since rion were considered consistent with the diagnosis of acha-
1978. Since 1977, we have used a Dent-sleeve device to lasia.
assess lower esophageal sphincter relaxation [ 121. Prior to On radiologic examination, all patients with achalasia
these dates, studies were performed with syringe pump exhibited: (1) abnormal opening of the lower esophageal
infusion systems, and lower esophageal sphincter pressure sphincter segment, (2) absent peristalsis in the thoracic
was evaluated only by pull-through technique. In all in- esophagus, (3) moderate to severe esophageal dilation, and
stances, esophageal peristalsis was assessed by 5 ml wa- (4) a substantial delay in esophageal clearance. In some
1 Aperistalsis (distal three fourths), Aperistalsis, dilated Rigid endoscopy: Infiltrating adeno-
LESP 61 mm Hg, incomplete LES esophagus, tapered stricture carcinoma of fun-
relaxation, methacholine positive GE junction, ulcer at dus
GE junction
2 Aperistalsis, LESP 60 mm Hg, no LES Aperistalsis, narrowed Hardened, friable Adenocarcinoma of
relaxation, methacholine positive, GE junction, nodule distal esophagus; fundus with ex-
CCK negative at cardia, amyl polypoid lesion tensive spread
nitrite + on lesser curva-
ture; Bx: adeno-
carcinoma
3 Aperistalsis, LESP 48 mm Hg, no LES Aperistalsis (distal), di- Narrowing of stom- Adenocarcinoma of
relaxation, methacholine, CCK lated esophagus, ach below Z-line, fundus with ex-
negative, amyl nitrite positive mass lesion at GE polypoid lesion in tensive metasta-
junction stomach; Bx: sus- sis
picious
4 Aperistalsis, LESP 68 mm Hg, no LES Aperistalsis, dilated Stiff, narrowed GE Linitis plastica, peri-
relaxation, methacholine positive, esophagus, tapered junction; Bx: ade- toneal metastasis
CCK positive, amyl nitrite positive GE junction, small nocarcinoma
fundus
5 Aperistalsis (distal three fourths), Weak peristalsis, mild Stenosis below Z- Adenocarcinoma at
LESP 54 mm Hg, incomplete LES dilation, tertiary con- line, scope would GE junction
relaxation, methacholine negative, tractions, tapered GE not pass; Bx:
CCK positive junction, amyl negative
nitrite +
6 Aperistalsis, could not pass GE junc- Aperistalsis, dilated Slightly friable distal Squamous cell car-
tion esophagus, symmet- esophagus, endo- cinoma forming a
ric fixed GE junction scope would not ring around GE
pass; Bx: squa- junction
mous cell carci-
noma
Bx = biopsy; CCK = cholecystokinin; GE = gastroesophageal; LES = lower esophageal sphincter; LESP = lower esophageal sphincter
pressure.
Flexible endoscopy with biopsy in five patients yielded dilation, absent peristalsis in the thoracic esophagus, and
findings that were either diagnostic of or strongly sugges- segmental narrowing of the distal esophagus. Overall, the
tive of malignancy. An ominous endoscopic clue, found in distal esophageal segment was smooth and tapered, but
two patients, was our inability to pass the endoscope into morphologic findings suggestive or diagnostic of neo-
the stomach. In the one patient in whom the diagnosis of plasm were present in four of six patients. One patient
pseudoachalasia was not made preoperatively, rigid en- (Patient 1) exhibited a small ulceration within the nar-
doscopy had failed to yield the correct diagnosis. In this rowed esophageal segment that was overlooked on the
patient, the correct diagnosis was subsequently made initial examination, but was clearly present on retrospec-
during laparotomy carried out with the intent of performing tive evaluation of the films (Figure 1, left). This index case
a Heller myotomy. of pseudoachalasia in our series was diagnosed at lapa-
In all six patients with pseudoachalasia, esophagraphy rotomy, carried out with the intention of performing a
including fluoroscopy and spot films showed esophageal Heller myotomy. In another patient (Patient 2). a small
tumor nodule was detected at the cardia (Figure 1, right).
TABLE Ill A third patient (Patient 3) exhibited a fundal mass adjacent
Tumors Causing Pseudoachalasla
to the cardia, and the fourth (Patient 4) had a shrunken
Number fundus due to neoplastic linitis plastica. In the remaining
Type of Neoplasm of Cases Reference two patients, the narrowing of the distal esophagus had a
Primary completely benign appearance indistinguishable from that
Adenocarcinoma of stomach 28 [3,4,19-30’1 of idiopathic achalasia. However, the result of an amyl
Squamous cell of esophagus 1 l
nitrite test performed in one of these patients (Patient 5)
Secondary was positive; namely, the caliber of the narrowed lumen
Adenocarcinoma of lung [71
Anaplastic neoplasm did not increase after amyl nitrite inhalation as is invariably
[aI
Bronchogenic squamous cell the case with achalasia [ 171: In the last patient (Patient 6),
Hepatoma [;iy the esophagraphic findings were normal, but a computed
Lymphoma tomographic examination demonstrated modest thicken-
Oat cell carcinoma of lung [?? ing of the distal esophageal wall suggestive of tumor. A
Pancreatic ductal carcinoma [41
Prostatic carcinoma computed tomographic examination performed in Patient
FJI
3 confirmed the presence of a fundal mass with involve-
* Five patients in the present study had adenocarcinoma of the
stomach and one patient had squamous cell carcinoma of the ment of the distal esophagus and regional lymph nodes.
esophagus. The pathologic findings from surgery, endoscopy, or
l Mean f SD.
+ Five of our cases and six culled from the medical literature.
TABLE V Weight Loss and Symptom Duration in more. These clinical features in a middle-age or elderly
Achalasia and Pseudoachalasia patient are suspicious for pseudoachalasia, but they are
not specific as shown by Sandler et al [21] and here
Weiaht Loss Symptom Duration
(pounds) . imonths) (Table V). Nevertheless, only 5 percent of our patients
Condition Number Median Range Median Range wit.bachalasia presented with symptoms for less than 12
Achalasia 161 5 O-50 24 l-600
months and weight loss in excess of 20 pounds.
Pseudoachalasia 38 22 o-52 3 l-48 In our experience, conventional esophageal manome-
try is of negligible value in discriminating pseudoachalasia
from achalasia. This is true regardless of the sophistica-
tion of the manometric instrumentation, such as a low-
our six patients and 32 established cases culled from the compliance infusion system or a Dent-sleeve device for
medical literature [3-10,19-301. Similar comparisons recording lower esophageal sphincter relaxation. Addi-
were made between the weight loss and the duration of tionally, pharmacologic challenge with methacholine or
symptoms at the time of presentation of the patients with cholecystokinin octapeptide had no discriminatory value
achalasia and the patients with pseudoachalasia (Table (Table IV). On the other hand, pharmacologic provocation
V). Twenty-five percent of patients with achalasia had with amyl nitrite is potentially useful in making this dis-
symptoms for less than one year and 23 percent had lost crimination. Amyl nitrite, which decreases the lower
in excess of 20 pounds at the time of presentation. esophageal sphincter pressure substantially in idiopathic
However, only 5 percent of the patients with achalasia achalasia [ 171, would be expected to have no effect on a
had both lost more than 20 pounds and had symptoms for malignant stenosis. In both cases of pseudoachalasia so
less than one year. Inspection of Table I reveals that 83 tested, there was no significant decrease in the lower
percent of patients with pseudoachalasia had both lost esophageal sphincter pressure following inhalation of
more than 20 pounds and had symptoms for less than one amyl nitrite.
year. Thus, although there is overlap in the categories The radiographic examination was of considerable val-
examined, elderly patients with symptoms for a short ue in discerning pseudoachalasia from achalasia. A thor-
interval and substantial weight loss were likely to have ough radiographic examination showed morphologic ab-
pseudoachalasia. normalities suggestive or diagnostic of malignancy in four
of the six patients with pseudoachalasia. Amyl nitrite
COMMENTS inhalation was a useful adjunct to the radiographic exami-
Esophageal pseudoachalasia is a rare entity. Only 38 nation in that it discriminated the cardiospasm of achala-
well-documented cases are reported in the medical litera- sia, which was relaxed by amyl nitrite, from fixed malig-
ture, including the six cases described herein. Although nant strictures, which were unaffected. When performing
the true incidence of pseudoachalasia is not established, this test, however, the examiner must verify, by detecting
we approximated its prevalence in our own referral prac- an increase in pulse rate, that the patient has received an
tice by reviewing all cases of achalasia seen at our adequate dose of amyl nitrite. Results of the radiologic
institution during the past 14 years. Overall, pseudoacha- amyl nitrite test were positive in an additional two patients.
lasia accounted for six of 167, or 4 percent, of patients In some instances, computed tomographic scanning of
with esophageal manometric findings suggestive of idio- the lower thorax and upper abdomen may verify the
pathic achalasia. However, the age distributions of pa- diagnosis of suspected pseudoachalasia by demonstrat-
tients with achalasia and pseudoachalasia are different. ing thickening or tumor nodular@ of the distal esophageal
Whereas patients with achalasia have a nearly uniform wall and adjacent stomach or metastasis to regional
age distribution between 10 and 70 years when initially lymph nodes.
seen, the youngest reported case of pseudoachalasia Flexible endoscopy with biopsy was diagnostic in all
occurred in a 32-year-old and the frequency of occur- five patients in whom it was performed. A similar impres-
rence increased with increasing age (Figure 2). Thus, the sion is obtained from a review of the medical literature; in
possibility of pseudoachalasia is remote in persons less 32 patients with pseudoachalasia who underwent endos-
than 32 years old, and the peak incidence occurs in the copy with biopsy [3- IO,1 g-301, the procedure was diag-
seventh and eighth decades of life. From our experience, nostic of malignancy in 66 percent [4,9,19,21-
pseudoachalasia accounted for about 6 percent of per- 23,25-28]. Additionally, there were two cases in which
sons over 40 years of age, and 9 percent of persons over the endoscopic result was interpreted as being negative
60 years of age who presented with manometric findings despite the the fact that the endoscopist was unable to
of achalasia. Clinical features suggestive of pseudoacha- pass the endoscope into the stomach [3,29]. This finding
lasia are a duration of symptoms of less than one year and should strongly suggest the diagnosis of pseudoachalasia.
substantial weight loss. All of our patients had symptoms In our experience with patients with idiopathic achalasia, it
for less than 10 months and all but one lost 20 pounds or is only in the circumstance of a severe “sigmoid esopha-
gus” that we were unable to traverse the lower esophage- lesion was removed and the esophagus was allowed to
al sphincter with an endoscope, and in this instance, the regain normal tone, peristalsis returned in three of four
failure was a function of inadequate instrument length patients tested and results of repeated methacholine stim-
rather than encountering excessive resistance. Experi- ulation were negative in two of three patients tested. Thus,
ence with our index case of pseudoachalasia suggests the positive methacholine test finding resulted from
that a rigid endoscope may be passed across a neoplastic esophageal body decompensation rather than from de-
stenosis without recognizing rigidity of the lower esopha- nervation. The lower esophageal sphincter response to
geal sphincter segment. cholecystokinin octapeptide, however, is dependent on
The type of neoplasm causing pseudoachalasia varies, an alteration of the innervation of the lower esophageal
but the most common tumor is adenocarcinoma of the sphincter, and the incidence of false-positive results
gastric fundus, Fundal adenocarcinoma accounted for five might be expected to be less. This was the case in our
of our six cases and 23 of 32 cases reported from other experience: however, due to the small number of patients
institutions (Table IV). Thus, 28 of 38 cases were secon- studied with cholecystokinin octapeptide, no definitive
dary to fundal adenocarcinoma. Two patterns of tumor conclusion can be made.
involvement are evident.- The most prevalent type con- Because Heller myotomy is generally not the initial
sists of a malignant stricture involving the cardia, such that therapy for idiopathic achalasia, the clinician must dis-
the tumor forms a stenotic segment in the region of the criminate pseudoachalasia from achalasia prior to any
lower esophageal sphincter. Such a malignant stricture therapeutic intervention. Pneumatic dilatation of a malig-
acts as a physical barrier to the passage of food. The most nant stricture will be ineffective, potentially dangerous,
orad level of the stricture may be slightly above or below and delay appropriate therapy. From the observations
the proximal margin of the lower esophageal sphincter made in this study, we conclude that despite similarities in
segment. Pathologic examination reveals a circumferen- the patients’ histories and manometric findings, pseudoa-
tial or nearly circumferential tumor mass involving the chalasia usually mimics primary idiopathic achalasia im-
cardia. The second, less common, pattern occurs when perfectly. Endoscopic examination and biopsy with partic-
the tumor mimics achalasia by submucosal infiltration ular attention to muoosal irregularity, compliance of the
with impairment of postganglionic lower esophageal gastroesophageal junction, the gastric cardia, and the
sphincter innervation. This circumstance occurred in only gastric fundus are of cardinal importance and generally
one of our six cases and, as best can be determined, in 12 yield the correct diagnosis. Similarly, a carefully per-
of the 32 cases reported by others [4,7,9,10,22,26,30]. formed barium study with amyl nitrite inhalation is also
With either pattern of neoplastic involvement, there is useful in distinguishing pseudoachalasia from achalasia.
dilation of the esophageal body accompanied by loss of Finally, esophageal manometry with amyl nitrite inhalation
peristalsis in the thoracic esophagus. In some cases, may distinguish between these two entities, but convinc-
decompensation of the esophageal body and a positive ing supporting data for this possibility are not available
methacholine test finding seem to clearly result from the currently. In cases in which the clinical history and diag-
distal stricture and obstruction. Such appeared to be the nostic tests generate a high index of suspicion of pseu-
case in five of six patients in the literature [19,20,24, doachalasia, myotomy should be considered as initial
28,301 and in three of the five patients with pseudoacha- therapy rather than risking an ill-advised pneumatic dilata-
lasia we tested with methacholine. When the obstructing tion.
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