Anterior Orientation vs Posterior Orientation in Per Oral Endoscopic Myotomy POEM for the Treatment of Achalasia

Achalasia is one of the most studied esophageal motility disorders. The etiology of Achalasia
is autoimmune, neurodegenerative, or viral immune. Achalasia is a consequence of the
degeneration of ganglion cells in the myenteric plexus of the esophageal body and the lower
esophageal sphincter (LES). The end result of the inflammatory process is the loss of
inhibitory neurotransmitters nitrous oxide and vasoactive intestinal peptide causing the
imbalance between excitatory and inhibitory neurons. This results in failure of the lower
esophageal sphincter (LES) to relax and is associated with aperistalsis of the esophageal
body, leading to difficulty swallowing, food and fluid stasis; regurgitation of undigested
food, fluid and saliva; and weight loss. Achalasia is an incurable disease and treatments are
only focused on the relaxation of the lower esophageal sphincter in order to allow for
passage of food fluid and saliva into the stomach. It has an estimated prevalence of 10 cases
per 100,000 populations and an incidence of 1-3 cases per 100,000 populations per year in the
Western world.

The armamentarium of Achalasia treatment includes pharmacologic management with the use of
calcium channel blockers, nitrites, phosphodiesterase inhibitor (sildenafil),
anticholinergics, and beta-adrenergic agonists; endoscopy using botulinum toxin injections
just above the squamocolumnar junction or pneumatic balloon dilation of the lower esophageal
sphincter; open Heller Myotomy, laparoscopic Heller Myotomy, and Per Oral Endoscopic myotomy
(POEM). Per oral endoscopic myotomy (POEM) is the most recent innovative treatment in the
armamentarium of Achalasia treatment. Per oral endoscopic myotomy (POEM) is a natural orifice
transluminal endoscopic surgery (NOTES) approach to a Heller myotomy for the treatment of
Achalasia. In 2008, POEM was first performed successfully in a human subject by Haruhiro
Inoue in Japan. The POEM was performed on a 36 year old patient without any documented
post-operative complications. In 2009, Stavros Stavropoulos at Winthrop University Hospital
(WUH) performed the first per oral endoscopic myotomy (POEM) procedure outside of Japan. The
POEM was performed on a 42 year old male without documented post-operative complications. The
subject had a marked improvement in objective manometric and barium esophagram findings; and
improvement in subjective dysphagia score. Consequently there has been a rapidly increasing
volume of POEM procedures performed in Japan, China, and throughout the United States.
Stavropoulos at Winthrop University Hospital has the highest single-operator volume in the
United States. The performance of POEM is still in evolution with various centers around the
world performing variations on technique.

The International Per Oral Endoscopic Myotomy Survey (IPOEMS) was conducted by Stavropoulos
and Savides during the July 2012 annual meeting of Natural Orifice Surgery Consortium for
Assessment and Research (NOSCAR). This survey was conducted to address the scarceness of POEM
literature at the time. IPOEM provided a "snapshot" of the status of POEM worldwide. The
survey included 5 Asian, 7 North American, and 4 European expert centers with a combined
total of 841 POEM procedures performed by July 2012. At the time most centers (14) performed
right anterior myotomy (2 o'clock orientation) with only a few of centers performing
posterolateral myotomy (5 o'clock orientation) determined using the usual endoscopic
convention of 12 o'clock representing the most anterior aspect of the esophagus on
endoluminal view.

The esophagus in humans is a complex structure with multiple muscles, nerves, vascular, and
lymphatic components. Branches of the vagus nerve and visceral branches of the sympathetic
trunk provide nerve fibers to the esophageal plexus. The vagus nerve delivers two fiber types
to the esophageal plexus: preganglionic parasympathetic fibers and afferent fibers. These
vagal fibers in the esophageal plexus reform to make the anterior vagal trunk (left vagus)
and the posterior vagal trunk (right vagus). The anterior and posterior terms for the vagal
trunks are used in relation to the esophagus. The visceral branches of the sympathetic trunk
delivers two fiber types to the esophageal plexus: sympathetic postganglionic fibers and the
afferent fibers. The afferent fibers originating from the sympathetic trunk are primarily
involved with pain. The critical anatomical component of the esophagus in the treatment of
Achalasia is the lower esophageal sphincter. Per common convention, the most anterior point
of the LES point is assigned as the 12 o'clock position. The strong oblique sling fiber
component is centered at 7o'clock on the posterolateral wall and wraps over the anterior and
posterior walls at 11 o'clock and 5 o'clock, respectively. The weaker circular clasp fiber
component location is centered at 2 o'clock to 3 o'clock. The question of investigating the
optimal orientation to perform the myotomy is unique to POEM. Open Heller myotomy and
laparoscopic Heller myotomy are limited to the anterior aspect of the esophagus. Myotomy
orientation is constrained by the anatomical locations of the left bronchus, left atrium and
spine. Anterior orientation is forced between the 1 o'clock - 2 o'clock position secondary to
the locations of the left bronchus and left atrium between 10 o'clock -11 o'clock and 12
o'clock - 1 o'clock, respectively. Posterior orientation is forced between the 4 o'clock - 5
o'clock positions secondary to the location of the spine located between 8 o'clock-9 o'clock
positions .The sling fibers maintain the angle of His and are a significant antireflux
barrier. Stavropoulos et al, reported on a single operator series of 284 POEM subjects at
Digestive Disease Week in May 2016. A statistical difference was found in the number of
subjects requiring narcotics post POEM procedure Subjects who had an anterior myotomy were
less likely to require narcotics post POEM procedure than those subjects who had a posterior
myotomy, 35% versus 53% respectively (p=0.007).

To date, there have been no prospective randomized controlled studies conducted comparing
anterior versus posterior myotomy technique in POEM analyzing perioperative pain, procedure
duration, incidence of mucosotomy, capnoperitoneum, and the postoperative sequelae of
gastrointestinal reflux disease (GERD).

Inclusion Criteria:

1. Subjects who have been diagnosed with Achalasia Type I, II, or III by positive
manometric findings and supporting findings by timed barium esophagram and endoscopy.

2. Subjects who are willing and competent to sign Informed Consent and to comply with
study related visits and procedures.

Exclusion Criteria:

1. Subjects who are under 18 years of age

2. Subjects with Achalasia Type I, II, or III who have had a prior failed open or
laparoscopic Heller myotomy; or have an esophageal diverticula, or anatomical variant
dictating the approach of the myotomy

3. Subjects diagnosed with other motility disorders such as distal esophageal spasm
(DES), hypertensive peristalsis (Nutcracker), or hypercontractile esophagus
(Jackhammer)

4. Subjects with coagulopathy

5. Pregnant females

6. Subjects who in the investigators' opinion, are medically unstable , are unable to
give informed consent, or whose risks outweigh the benefits of participating in the
study

7. Subjects with decisional incapacity who are unable to comply with study related visits
and procedures