Updates Surg

DOI 10.1007/s13304-013-0224-1

REVIEW ARTICLE

The management of esophageal achalasia: from diagnosis

to surgical treatment
Adrian Dobrowolsky • P. Marco Fisichella

Received: 8 February 2013 / Accepted: 21 June 2013

Ó Springer-Verlag Italia 2013

Abstract The goal of this review is to illustrate our Pathophysiology

approach to patients with achalasia in terms of preoperative
evaluation and surgical technique. Indications, patient Research is ongoing to determine the specific neurohor-
selection and management are herein discussed. Specifi- monal dysfunction implicated in the disease. Despite the
cally, we illustrate the pathogenetic theories and diagnostic smooth muscled nature of the lower esophageal sphincter
algorithm with current up-to-date techniques to diagnose (LES), it receives both cholinergic and noncholinergic
achalasia and its manometric variants. Finally, we focus on signals. Acetylcholine, usually reserved as the primary
the therapeutic approaches available today: medical and neurotransmitter in skeletal muscle, has been shown to play
surgical. A special emphasis is given on the surgical treat- a role in peristaltic function of the LES [3]. Many studies
ment of achalasia and we provide the reader with a detailed also suggest that an absence of nitric oxide (NO), whose
description of our pre and postoperative management. role it is to aide in relaxation of the LES, plays an
important role [4–6]. In fact, reduction of NO synthase
Keywords Achalasia
Pneumatic dilatation
Heller activity in the esophageal myenteric plexus has appeared in
myotomy
Esophageal function testing
Laparoscopic repair those with sporadic achalasia and Allgrove syndrome
(mentioned later) [4, 7, 8]. In addition, vasoactive intestinal
peptide has been implicated in the relaxation of the LES
History and esophageal peristalsis [9, 10]. While still other hor-
mones and neurotransmitters have been shown to play a
Achalasia was first described more than 300 years ago by role, other factors such as infectious, autoimmune, and
Sir Thomas Willis who characterized the disorder as car- genetic factors have also been extensively studied.
diospasm, an obstruction of the esophagus at the cardia. Studies have tried to demonstrate an association
His treatment for the disorder was to pass a piece of carved between viral infections and achalasia, but the data have
whalebone with a sponge at its end through the esophagus not been conclusive [11]. Widely accepted is that Chagas
[1]. In 1924, Dr. Hurst disputed the notion that achalasia disease, caused by Trypanosoma cruzi, may lead to acha-
was due to cardiospasm. Instead, he postulated that the lasia with resultant megaesophagus [12].
disorder was a result of absence of normal relaxation of the The attribution of autoimmune factors to the pathogen-
cardia as evidenced by his inability to find a hypertrophied esis of achalasia, while early in its discovery, shows much
sphincter upon operation, thus leading to the term achalasia promise. Goldblum et al. [13] note in their study of 42
by Sir Cooper Perry [2]. histopathologic esophageal specimens, that myenteric
inflammation by lymphocytes is apparent with the loss of
ganglion cells, and fibrosis in severe cases. Based on
A. Dobrowolsky
P. M. Fisichella (&) immunohistochemical staining, it has been found that T
Swallowing Center, Department of Surgery, Loyola University
lymphocytes are the predominant cells responsible for
Chicago, Health Sciences Campus, 2160 South First
Avenue-Room 3226, Maywood, IL 60153, USA myenteric nerve degeneration [14]. In as high as 64 % of
e-mail: [email protected] subjects, anti-myenteric autoantibodies were detected and

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the alleles responsible for these changes have been reported with achalasia includes fermentation of retained food with
to reside on the MHC class II allele HLA-DQ [15–19]. subsequent nitrosamine production by bacterial over-
A genetic study of 1,012 first-degree relatives of 159 growth [33]. Therefore, a common implication of these
adult patients failed to identify any cases of familial findings is that duration of symptoms may be directly
inheritance of the disease [20]. However, 75 % of patients related to cancer risk induced by long standing chronic
with Allgrove (triple-A) syndrome, characterized by inflammation. A study from Meijssen et al. [34] has
achalasia, alacrima, and ACTH resistant adrenal insuffi- shown an interval of 17 years between the onset of dys-
ciency, have achalasia. In this disorder, mutations of the phagia and the diagnosis of squamous cell carcinoma in
AAAS gene result in dysfunction of the ALADIN protein patients followed longitudinally. In addition, adenocarci-
[21]. noma in Barrett’s metaplasia has been reported in patients
secondary to the development of gastroesophageal reflux
after treatment for achalasia. In fact, Csendes et al. [35]
Epidemiology have shown that the risk of Barrett’s esophagus after
Heller myotomy and Dor fundoplication for achalasia is
The yearly incidence of achalasia is reported as 0.3 to 1.6 13.4 %, which predisposes the patient to a small risk of
per 100,000 people [22–24]. The prevalence has been progression to adenocarcinoma.
shown to be increasing from 2.5/100,000 in 1996 to 10.82/ In summary, treatment for achalasia does not diminish
100,000 in 2007 [24]. the risk of developing squamous cell carcinoma and
increases the risk of adenocarcinoma in Barrett’s meta-
plasia. These findings should be discussed with the patient
Symptoms of achalasia once treatment is planned, as well as the need for periodical
endoscopic and histologic follow-up.
In a study conducted by one of the authors, dysphagia was
present in 94 %, regurgitation in 76 %, and chest pain in
41 % of patients. In 43 %, the LES was hypertensive, in Diagnosis
25 % it was hypotensive, and incomplete or absent LES
relaxation was noted in 87 % with all patients experiencing Endoscopy is likely the first test to be performed in patients
aperistalsis of the esophageal body [25]. In addition, with any esophageal disorder to rule out mechanical
patients with achalasia may present with symptoms of obstructions, peptic ulcer strictures, esophagitis, or even
heartburn and are prescribed acid-reducing medications. cancer. Although, others would turn to barium swallow first
However, the underlying mechanism for their heartburn is in the evaluation of dysphagia [36, 37]. However,
different. The symptoms of heartburn are thought to be due manometry is the most sensitive diagnostic tool and is
to stasis and fermentation of food in the esophagus after considered the gold standard for the diagnosis of achalasia
impaired emptying causing irritation rather than by reflux [38, 39]. Fluoroscopic barium swallow provides additional
of acidic gastric contents [26–28]. Long-term effects of information; a bird’s beak appearance of the esophagus,
food retention include progressive esophageal dilation, esophageal dilation, delayed esophageal emptying, and
nocturnal regurgitation, aspiration in 12 %, and weight loss tertiary contractions are all characteristics of achalasia [29,
in 35 % [25, 29]. 40]. Important criteria for diagnosis of achalasia are lack of
peristalsis, absent or incomplete relaxation of the LES in
response to swallowing on manometry, and diagnostic
Cancer risk findings on barium swallow [25, 39]. A variant of achalasia
has also been described. Vigorous achalasia, while typical
Recent large population studies suggest an overall of younger patients, is thought to be an earlier stage of the
2.2–3.4 % total risk of developing esophageal carcinoma disease and it is characterized by high amplitude, simul-
with the majority (1.3–2.7 % of cases) as squamous cell taneous nonperistaltic contractions [37 mmHg, and a high
carcinoma; a 16–28 fold increased risk over the general incidence of chest pain [41, 42].
population [30, 31]. The analysis of esophageal resection
specimens in patients with end-stage achalasia has shown
that diffuse squamous hyperplasia associated with papil- High resolution manometry (HRM) and the Chicago
lomatosis and basal cell hyperplasia, and lymphocytic classification
esophagitis were present and may be related to the
increased risk of squamous cell carcinoma [32]. In fact, a In 2008, the Chicago Classification was developed and
proposed etiology of squamous cell carcinoma in patients researchers using HRM subdivided achalasia into three

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types. Type I, classic, is defined as achalasia with minimal patients as they tend toward a better response and are
esophageal pressurization, type II is defined as achalasia higher operative risks [54].
with panesophageal pressurization, and type III is defined
as achalasia with spasm and premature contractions [43,
44]. Pandolfino et al. [44] showed that type II patients had Pneumatic dilation (PD)
the best response to intervention, up to 96 %, while type I
had up to a 56 % response and type III had a dismal 29 % The first documented attempt at alleviating symptoms of
response. Using the same classification system, Salvador achalasia included whalebone with a sponge affixed at its
et al. [45] find that failure rates were the following: type I end to dilate the esophagus [1]. Today, pneumatic esoph-
14.6 %, type II 4.7 %, type III 30.4 %. ageal dilation is performed under fluoroscopic or endo-
scopic guidance. The mechanism of action is to weaken the
LES by tearing its muscle fibers by generating radial force
Medical management of achalasia by rapid inflation of the balloon [55]. In an analysis of
current literature, Katzka and Castell found that most
Calcium channel blockers and nitrates are the two most practitioners utilized 30–40 mm balloons with variable
common medications used for treating achalasia. They inflation pressures and times. They noted a 2 % esophageal
work by relaxing smooth muscle and lower LES resting perforation rate with pneumatic dilation (PD) with the
pressure for a limited amount of time. Of the available majority undergoing medical management of the perfora-
calcium channel blockers, sublingual nifedipine is the usual tion, and only 1 % requiring surgical intervention. In
agent and its effect on the LES include a 28–48 % decrease addition, there was a 66 % response rate at 1 year and
in resting LES pressure with a 20–45 min lag to time of 25 % at 10 years, respectively. Using the newer Rigiflex
maximal effect and a greater than 60 min duration [46]. balloon, response rates are 88 and 29 % at 1 and 10 years,
Alternatively, sublingual isosorbide dinitrate decreases the respectively. With subsequent dilation sessions, however,
LES pressure by 64–66 % with approximately 15 min the perforation rate rises to 4 % [56]. In a meta-analysis
before maximal onset and lasts 60–90 min [47–49]. performed by Weber et al. [57] the 10-year remission for
Despite the efficacy of these pharmacologic agents, at least PD was 47.9 % while the perforation rate was 2.4 %. Tuset
in the short term, their side effects, such as headaches, et al. [58] note in their prospective study that clinically
hypotension, and pedal edema can be very limiting [46]. symptomatic reflux was seen in 10 % of patients after PD.
Even with the improvement in dysphagia, symptoms tend
to persist and authors suggest that medical therapy should
be reserved for those who are unable to undergo more Peroral esophageal myotomy (POEM)
definitive treatment [46, 50].
POEM has emerged recently as a new technique for the
treatment of achalasia. In 2010, Inoue et al. [59] developed
Botulinum toxin the technique in which a submucosal tunnel is created and a
longitudinal incision is made through the circular muscle
Botulinum toxin has been used to treat achalasia and acts fibers of the esophagus and onto the gastric cardia under
by inhibiting the calcium-dependent release of acetylcho- endoscopic guidance. The total length of the incision was a
line from nerve terminals. In a literature review performed mean of 8.1 cm, 6.1 cm in the distal esophagus and 2 cm in
by Bassotti and Annese, a single injection of botulinum the cardia. While long-term outcomes have yet to be
toxin has been shown to be effective in approximately studied, significantly lower LES pressures, rates of dys-
85 % of patients with achalasia but its effect diminishes phagia, and improved symptom scores have been reported
over time with 50 % at 6 months, and 30 % at 1 year [51]. by patients [59, 60]. However, in a prospective study per-
In a review by Vaezi and Richter [46], 26 % of patients formed by von Renteln et al. [60] 9 of 16 patients expe-
were resistant to botulinum toxin and showed no clinical rienced a full thickness dissection into the peritoneal cavity
response which was thought to be due to antibodies to the at the cardia, and 13 of 16 patients experienced full
protein. Its effects diminish over time by terminal and thickness dissection into the mediastinum, some requiring
nodal sprouting which lead to axons that form new syn- needle decompression, but without infectious sequelae or
apses [52]. In a study by Sweet et al., preoperative treat- spillage. In a study of 119 patients by Ren et al. [61] 25 %
ment with botulinum toxin was the only factor that was developed a pneumothorax, 49 % developed pleural effu-
associated with poor outcome after Heller myotomy [53]. sions, and 44 % experienced heartburn postoperatively.
Therefore, botulinum toxin is generally reserved for older Another concern is that POEM does not allow for

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fundoplication. As a result, Swanson et al. [62] note a 44 % achieve superior outcomes. The LES is an anatomical
incidence of heartburn. complex formed by circular muscle fibers of the esophagus,
the U (or clasp) fibers, and the sling fibers of the lesser
curvature of the stomach [70]. Mattioli et al. [71] showed
Surgical treatment of achalasia that the myotomy should be extended far into the anterior
wall of the stomach near the lesser curvature, so to divide
Heller first proposed a surgical repair for achalasia in 1913 only the muscular clasps and not the gastric sling fibers,
by performing an anterior and a posterior myotomy which should remain as the last component of the sphinc-
through the chest [63]. In 1924, Ziegler showed that one teric function of the LES.
myotomy achieved equal results as two separate myoto- There remains debate whether Heller myotomy with
mies. The operation evolved as Cuschieri performed the fundoplication is superior to pneumatic dilation. In a study
first thoracoscopic myotomy in 1991 and showed that the published in the New England Journal of Medicine in 2011,
procedure was effective with an average hospital stay of it was discovered that 1 and 2-year treatment successes
three days [64]. In the 1990s, a laparoscopic approach were 90 and 86 % in the PD group versus 93 and 90 % in
became available. Patti et al., in reviewing both laparo- the LHM group, respectively. In addition, LES pressure
scopic and thoracoscopic approaches found that the lapa- was 10 mm Hg in the LHM group versus 12 mm Hg in PD
roscopic Heller myotomy (LHM) combined with a Dor group, and no difference was seen in patient quality of life
fundoplication, a 180° wrap with the proximal extension of [72]. However, Patti and Pellegrini question the experience
the myotomy 7 cm onto the esophagus and 1.5 cm onto the of the surgeons performing the procedures. They point out
stomach, achieved a good or excellent relief of dysphagia there was on average only one procedure performed at each
in 93 %. The average length of stay was 48 h, and reflux by institution per year, and inadequate extension of the
pH monitoring was 17 %. However, patients treated tho- myotomy onto the stomach [73]. While short-term out-
racoscopically had a 60 % prevalence of asymptomatic comes may be equal between medical and surgical groups,
reflux by pH monitoring [65]. Moreover, in a prospective long-term results show a clear advantage of LHM with Dor
randomized study, when an antireflux procedure was per- over PD. In devising a treatment plan for a patient, one
formed, only 9 % showed reflux by pH monitoring [66]. must weigh the risks/benefits of each therapy for the given
These findings explain why today a partial antireflux pro- patient (Table 1).
cedure is always performed in conjunction with a laparo-
scopic Heller myotomy [66–68]. Finally, the optimal
length of a myotomy is still debated. Undoubtedly, this Long-term surgical outcomes and end-stage achalasia
needs to be extended to some level onto the stomach.
Oelschlager et al. [69] have shown that when the myotomy Studies suggest that patients report good outcomes
was extended to 3 cm onto the stomach, patients experi- 1–3 years after esophagomyotomy, but long-term out-
enced less dysphagia than those in whom the myotomy was comes show a decline in results. Chen et al. note that at
only 1.5 cm long. A careful understanding on the anatomy 5 years 77 % of patients achieved relief of symptoms after
of the LES may explain why a longer myotomy can LHM and fundoplication [74]. At 10 years, surgical

Table 1 Medical versus surgical treatment of achalasia

LES pressure Duration 1 year 5 year 10 year Limitations
decrease (min) effectiveness effectiveness effectiveness

Nifedipine [45] 28–48 % 60 – – – Side effects

Isosorbide dinitrate 64–66 % 60–90 – – – Side effects
[46–48]
Botulinum toxin – – 30 % – – Nerve regeneration
[50]
PD [55, 56, 70] – – 66–90 % – 48 % 2.4 % risk of esophageal perforation. Up to
4 % with subsequent dilations
POEM [58–61] 57–62 % – – – – 25 % risk pneumothorax, 49 % pleural
effusion, 46–50 % reflux
LHM with Dor – – 93 % 77 % 69–80 % 4.8 % risk of esophageal perforation
[56, 70, 72, 73]
PD pneumatic dilation, POEM peroral esophageal myotomy, LHM laparoscopic Heller myotomy

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success is reported at 69–79.6 % (versus 47.9 % in the PD risk of carcinoma, Zaninotto et al. [33] recommend
group) [57, 73, 75, 76]. Other studies suggest similar screening with an upper endoscopy every 3–4 years.
decline in effectiveness over time, however, the technique
of 3 cm extension of the myotomy onto the cardia and Dor Conflict of interest The authors have no conflicts of interest.
fundoplication were not universally utilized [76–78].
Reasons for failure of surgical therapy have been studied
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