Endoscopic versus Laparoscopic Myotomy for Treatment of Idiopathic Achalasia: A Randomized Controlled Trial

Idiopathic achalasia is a rare motility disorder of the oesophagus that is
characterised by aperistalsis of the oesophageal body and dysrelaxation of the
lower oesophageal sphincter caused by progressive destruction and degeneration
of the neurons in the myenteric plexus. This leads to subsequent retention of
food and saliva in the oesophagus, resulting in the typical symptoms of
achalasia such as dysphagia, chest pain, regurgitation of undigested food and
weight loss. The cause of the neuronal degeneration found in achalasia is
unknown.

Treatment of achalasia is focused on symptom relief, which is obtained by
destroying the occluding function of the spastic lower oesophageal sphincter.
Endoscopic therapies consist of either balloon dilatation or botulinum toxin
injection. Endoscopic botulinum toxin injections can induce an effective
reduction of the pressure in the lower oesophageal sphincter and thereby
reduced symptoms. However the treatment is reversible and as a consequence has
a high reccurence rate. Usually, endoscopic balloon dilatation is the first
step in the treatment of achalasia. The success rate varies widely between
60-85% and symptom reccurence continues to occur with time which requires
subsequent treatment sessions. Also, approximately 3% of the endoscopic balloon
dilatation is complicated by a perforation, which is potentially a
life-threatening situation. The surgical treatment for achalasia is Heller
Myotomy, nowadays almost exclusively performed laparoscopically. During a
surgical myotomy the circular muscle fibers of the lower oesophageal sphincter
and the distal oesophagus are cut. A recent meta-analysis of 105 studies
reporting on 7855 patients demonstrated that laparoscopic Heller myotomy is the
most effective therapy for achalasia, especially on the long-term. However,
this technique can also be associated with severe complications, is more
invasive than endoscopic treatment and is more expensive as it involves
laparoscopic instrumentarium and an operation theatre.

Recently, per-oral endoscopic myotomy (POEM) has been introduced as an
alternative to surgical myotomy. The POEM technique is entirely endoscopic.
Using an endoscopic knife, an entry to the submucosal space is made in the
oesophagus and after creating a submucosal tunnel towards the lower oesophageal
sphincter the circular muscle layers are cut. At the end of the procedure the
mucosal opening is closed with clips. Single center studies demonstrate
promising short-term results of POEM for the treatment of achalasia. At
present, POEM has the potential to be the first scarless flexible endosurgical
intervention to become an established clinical treatment. For this to happen,
however, comparative data with established treatments such as surgical myotomy
regarding safety and efficacy are necessary.

We hypothesize that the long-term efficacy of POEM is comparable to the
efficacy of laparoscopic Heller myotomy in treatment of patients with
symptomatic idiopathic achalasia. The assumption is thus that POEM is
non-inferior to laparoscopic Heller myotomy with respect to efficacy and
safety. Therefore the objective of the study is to compare safety and long-term
efficacy of POEM to laparoscopic Heller myotomy, the current gold-standard.

International multicentre randomised clinical trial.

Study subjects undergo a Laparoscopic Heller Myotomy or a POEM.

Laparoscopic Heller Myotomy (LHM): The LHM is a laparoscopic procedure
performed by a surgeon. A five trocar technique is used, a midline or left
paramedian trocar is used for the camera: two lateral trocars for elevating the
liver and retraction of the stomach and two trocars for dissection and
suturing. The myotomy is performed by dividing both muscle layers, extending
upwards into the thoracic cavity at least 4 cm above the gastro-oesophageal
junction and at least 3 cm inferiorly over the stomach. An anterior
fundoplication according to Dor is routinely performed. The fundus is sutured
to the right lateral edge of the myotomy.

Per-oral Endoscopic Myotomy (POEM): The POEM technique is entirely endoscopic.
Using an endoscopic knife, an netry to the submucosal space is made in the
oesophagus and after creating a submucosal tunnel towards the lower oesophageal
sphincter the circular muscle layers are cut. At the end of the procedure the
mucosal opening is closed with clips.

Study subjects with symptomatic idiopathic achalasia will undergo a POEM or
LHM. LHM is a safe and regularly performed procedure for patients with
achalasia and will be performed by an experienced surgeon (* 30 laparoscopic
gastro-esophageal junction operations of which 5 myotomies). POEM is a relative
new procedure in the treatment of achalasia and will be performed by
experienced endoscopists that have performed over 10 POEM procedures. For both
treatments complications such as a perforation and bleeding can occur. In most
cases these complications can be treated directly during the procedure but in
some cases it is possible that an additional endoscopic or surgical procedure
is needed with extension of admission time.

To determine long term effectiveness patients are followed for a period of five
years and need to undergo different oesophageal examinations like a
gastroscopy, a timed barium oesophagography, high resolution manometry and a 24
hour pH-impedance monitoring. These measurements are routinely performed in all
treated achalasia patients to monitor reccurence of symptoms. All the
additional measurements are safe procedures with minimal complications and
routinely performed in the clinical setting. Furthermore the study subjects
need to fill out questionnaires. After the initial procedure study subjects
need to visit the outpatient clinic five times for follow-up.

The first results of the POEM are very promosing and suggest that this
treatment is comparable to LHM or even better. The risk of both procedures are
the same. Patients that are not participating in this trail will in any case
undergo a treatment because of persisting symptoms. The study will give
insight in the optimal treatment for symptomatic idiopathic achalasia which
will have consequences for the choice of the treatment for this disease.