Per-oral endoscopic submucosal myotomy (POEM) for treatment of achalasia: International multi-center trial

Achalasia is a rare neurodegenerative esophageal motility disorder, which is
characterized by incomplete lower esophageal sphincter (LES) relaxation,
increased LES tone, and aperistalsis of the esophagus. Clinical symptoms
include dysphagia, regurgitation, and chest pain. Available treatment
strategies are either endoscopic or surgical. Endoscopic therapies consist of
either balloon dilatation (EBD) or botulinum toxin injection. The surgical
treatment for achalasia is Heller Myotomy with or without fundoplication, which
can be performed either open or by laparoscopy. Surgical therapy has superior
long-term efficacy compared to EBD and EBTI, with sustained therapeutic effects
in approximately 90% of patients. The concept of Natural Orifice Transluminal
Endoscopic Surgery (NOTES) has inspired endoscopists to modify existing
surgical techniques towards purely endoscopic approaches. This has led to the
development of Endoluminal submucosal myotomy (POEM) for the treatment of
achalasia.

Primary Objective:
• To evaluate treatment success, defined as successful symptom relief based on
an Eckhard score <=3.

Secondary Objectives:
• Safety standards, defined as a rate of serious adverse events <2%. SAE are
defined as death, mediastinitis, peritonitis, any complication requiring
emergency/salvage surgery.
• Other adverse events
• Lower esophageal sphincter (LES) pressure (manometry) pre- and post POEM.
• Reflux scores before, and 3 and 6 months, and 1, 2, 3, and 5 years aft post
procedure.
• Functional changes pre- and post therapy of the gastro-esophageal junction as
measured by the functional endoscopic probe (Endoflip).

Prospective, single arm, European multi centre trial

POEM procedures will be conducted as described by Inoue et al. A
forward-viewing upper endoscope (GIF 180J) is used with a transparent distal
cap attachment. Carbon dioxide gas is necessary for insufflation during the
procedures. An ESD knife is used to access the submucosa, dissect the
submucosal tunnel and also to divide circular muscle bundles over a length of
approximately 10cm, extending a minimum of 2cm onto the cardia. A
electrogenerator is used with spray coagulation mode (effect 2, 50 watt). A
coagulating forceps is used for hemostasis as needed. Closure of the mucosal
entry site is performed using standard endoscopic clips. The procedure steps
are illustrated in Figure 1.

For this study patients will be treated with a new complete endoscopic
technique for the treatment of achalasia. Feasibility and long-term
effectiveness will be scored. Risks associated with the POEM procedure include
a bleeding during or after treatment and a perforation of the oesophagus or
stomach during the treatment procedure. These severe complications need to be
treated immediately; this may imply additional endoscopic or surgical
procedures with extension of admission time. To determine long term
effectiveness patients are followed for a period of five years and need to
undergo different esophageal examinations, additionally, they need to fill out
questionnaires regularly. The procedure does not require abdominal incisions.
Compared to surgical treatment of achalasia this can be a possible benefit as
abdominal incisions are associated with pain, infection and longer admission
time.