A prospective randomized multi-center study comparing endoscopic pneumodilation and per oral endoscopic myotomy (POEM) as treatment of idiopathic achalasia

Achalasia is a rare esophageal motor disorder with an annual incidence of 1 per
100 000 persons, clinically characterized by dysphagia, chest pain and
regurgitation of undigested food. These symptoms result from esophageal
aperistalsis combined with a defective relaxation of the lower esophageal
sphincter (LES), leading to impaired propulsion of the bolus and stasis of food
in the esophagus. Abundant evidence illustrates that degeneration and
dysfunction of the intrinsic inhibitory innervation of the esophagus, with
absence of nitric oxide releasing neurons is the underlying abnormality. The
exact cause remains to be determined, although a genetic, auto-immune or an
infectious origin of the neural damage has been suggested1.
The treatment of achalasia consists of reduction of LES pressure either by
forceful endoscopic pneumatic dilatation (PD) or by surgical myotomy
(laparoscopic Heller myotomy or LHM)7. Forceful endoscopic dilation of the LES
can be accomplished with a balloon dilator designed to distend the LES to a
diameter of 30-40 mm aimed at reducing LES pressure by disrupting the
sphincteric muscle. The success rate of this technique varies widely between 60
and 85 %, strongly depending on the criteria used to define success and the
length of follow-up. The other most commonly used treatment is surgical
myotomy. With the introduction of the laparoscopic technique, the surgical
approach has gained a lot of interest, especially since the morbidity has
significantly improved and the results so far are excellent, ranging between
90-95 %. Until recently, it was unclear however which of these two treatments
was superior and should be considered as treatment of choice. In a multicenter
European randomized clinical trial, we therefore compared PD and LHM in a large
cohort (n=201). This study revealed that both treatments were equally effective
2.
In 2010, Inoue et al. introduced a new minimal invasive technique, i.e. per
oral endoscopic myotomy or POEM, as new treatment for achalasia6. In brief, a
long submucosal tunnel is created, followed by endoscopic myotomy of the
circular muscle bundles of the distal esophagus (8-10 cm) and cardia (2-3 cm).
The advantage of this technique is that the muscle bundles are electively
transsected and not stretched as with PD. On the other hand, in contrast to
LHM, there is no need for a laparoscopic procedure. The results reported so far
are excellent with relief of dysphagia in all patients (n=18) and relief of
chest pain in 83% after a mean follow-up of 11 months 8. One drawback may be
the absence of an anti-reflux procedure, leading to increased risk of
gastro-esophageal reflux.
To date, POEM is embraced with great enthusiasm, however, before accepting this
technique as new treatment of achalasia in clinical practice, it should be
compared with the current treatment modalities. In Germany, a randomized trial
will be preformed comparing POEM with LHM. In the present multicentre
randomized trial, POEM will be compared with PD.

This study is designed to evaluate which of the two treatment modalities
results in the highest success rate after 2 years. Thereafter, follow-up will
continue and a similar analysis will be performed 5 years after treatment (and
every 5 years thereafter) to determine the long-term outcome of both treatment
arms.
As described in more detail later, symptoms will be evaluated using the Eckardt
scoring system. Therapeutic success is defined as a reduction to an Eckardt
score of 3 or less. This implies that only patients with an Eckardt score > 3
will be included in order to be able to detect a relevant drop in symptom
score.
Two years after treatment, the number of patients with a successful symptom
control will be determined for both groups of treatment. If symptoms recur
within the first year of follow-up in patients randomized to pneumatic
dilation, retreatment with pneumatic dilation is allowed. If retreatment
however does not result in reduction of the symptom score below 4, the patient
will be considered as a failure. In case of a failure, patients will be offered
the choice to undergo an alternative treatment (surgery, botox), and will be
excluded from the study. Data collection will however be continued.
When patients successfully treated with pneumatic dilation develop recurrent
symptoms during follow-up, retreatment is allowed. Again, treatment is started
with a 35 mm balloon, and symptoms are evaluated 4 weeks later. In case the
Eckardt score is still above 3, redilation with a 40 mm balloon will be
performed. After this second series of pneumodilation, symptoms should be
controlled for at least 2 year before a third and last session is allowed. If
symptoms occur before this 2 year interval, the patient is considered as a
failure. In total, only three dilation sessions will be allowed. If symptoms
recur after the third
series of dilations, this patient is considered as a failure.
If symptoms recur after POEM, the patient is considered as a failure and other
treatment options are discussed with the patient.

This study is a prospective randomized multi-center study, executed in fourteen
different centers.
Treatment comparing endoscopic pneumodilation and POEM will be evaluate in the
highest success rate after 2 years. THereafter follow-up will continue and a
similair analysis will be performed 5 years after treatment an every 5 years
thereafter to determine the long-term outcome of both treatments arms.
Therapeutic success is defined as reduction to an Eckardt score of 3 or less.

POEM and PD

Side effects of Pneumodilatatie
Respiratory tract infections or pneumonia may be caused by the choke on food or
drink. Risk is small (1 in 1000) because patients must be sober during
treatment.
There may occur a crack in the esophagus or in the stomach during the inflation
of the balloon (at 1 to 3 at 100). This will be checked by a radiography. De
sphincter can be stretched (less than 10 in 100) so that the stomach can no
longer close good enough. Reflux, this can be treated with medication.
Side effects of POEM
Respiratory infection or pneumonia (1 in 1000)
(1-6 in 100) there may be a crack or leak in the lining of the esophagus. As
check there will be made on the day after surgery a radiography.
At (10 in 100), the probability exists that after the cutting of the sphincter
muscle can not close the stomach this good enough anymore. As a result, The
stomach contents from flowing back into the esophagus (reflux) This can be
treated with medication.
Small chance that the submucosal tunnel can not be created. The POEM procedure
can not be executed.