Pyloric Endoscopic Myotomy as treatment for patients with symptom of gastric outlet obstruction after oesophagectomy with gastric conduit.

Oesophagectomy with gastric tube reconstruction is the cornerstone of the
treatment of patients diagnosed with a malignant esophageal tumor. In this
procedure, the vagal nerves are inevitably damaged. This has several potential
consequences. Since the vagal nerve has important regulatory effects on
gastroenteral motility, disturbances in this respect are commonly encountered.
As far as gastropyloric motility is concerned, truncal vagotomy can lead to
antral hypo- or dysmotility (also described as gastroparesis) and pylorospasm
(inability of the pylorus to relax when appropriate). This combination can
cause a significantly delayed empyting of the gastric tube, mainly for solids.
This subsequently may lead to an array of symptoms such as: postprandial
fullness, early satiety, heartburn, and regurgitation and aspiration (resulting
in recurrent pneumonias). On the other hand, however, vagotomy can result in
accelerated gastric emptying for liquids which can cause a syndrome often
referred to as dumping syndrome. In the one patient, dumping syndrome is more
prominent, whereas in the other gastroparesis (severely delayed gastric
emptying for solids) is predominant. There are no predictive factors for which
patient will develop what syndrome (if any). It is however a serious problem,
seen as 4-50% of patients suffer from symptoms of delayed gastric empyting (2).
Delayed gastric empyting caused by hypo- or dysmotility of the stomach,
otherwise described as gastroparesis, is also encountered in other situations
than post-oesophagectomy: gastroparesis is a well-known complication of
diabetes, but can occur in a variety of other diseases, and can be idiopathic.
The primary therapeutic approach is to prescribe dietary advises and/or
prokinetic drugs. These measures are usually not very effective. As an
alternative, more invasive treatments can be undertaken directed to the
pylorus, using either pneumatic dilatation, intrapyloric injection with
botulinum toxin (Botox), or surgical drainage (pyloroplasty of pyloromyotomy).
However, there is little data on the efficacy of these treatments, especially
in patients that underwent oesophagectomy; most studies are conducted in
patients suffering from gastroparesis of other causes.
Recently, a minimally invasive, endoscopic means to perform a myotomy has been
developed: in 2010, Inoue and colleagues described what they named a Per-Oral
Endoscopic Myotomy (POEM) of the lower esophageal sphincter in patients with
achalasia In this technique, endoscopic submucosal tunneling was utilized to
safely perform a full myotomy of the sphincter (3). POEM is nowadays considered
a safe and valid treatment option for achalasia. More recently, however, the
same principle has been directed to the pyloric sphincter, currently referred
to as G-POEM (Gastric Per-Oral Endoscopic myotomy) or PEM (Pyloric Endoscopic
Myotomy). This technique has been studied in small case series in patients with
various causes of gastroparesis, mainly in diabetes induced gastroparesis.
One single center study conducted by Gonzalez et al., evaluated the efficacy of
G-POEM in patients suffering from refractory gastroparesis. They reported a
clinical success rate of 85% and a 71 % success rate, without any adverse
events (4). Later , the same research group published a multicenter case series
of patients who underwent G-POEM for refractory gastroparesis. This study also
showed a clinical success rate of 85% (4).
As mentioned above, 4-50% patients who undergo oesophagectomy with gastric tube
reconstruction suffer from symptoms of delayed gastric empyting, without a
proper form of treatment up until now. However, the studies conducted in
patients with severe diabetes induced gastroparesis/delayed gastric empyting
are promising.
Therefore, this study aims to evaluate the feasibility, efficacy, safety and
durability of the G-POEM in patients suffering from delayed gastric empyting
after oesophagectomy with gastric tube reconstruction.
In addition, we wish to find objective markers for prediction of response to
G-POEM in this patient category; one of these being an EndoFlip measurement.
Measuring resting pressure and distensiblity of the pylorus has up until now
not been possible. Recently, there have been studies looking at the usefulness
of the EndoFlip device. Gourcerol et al. used the Endoflip device to assess
functional characteristics of the pylorus in patients with gastroparesis and
healthy volunteers. They concluded that in patients with gastroparesis the
pyloric compliance is decreased. Another study conducted by Malik et al. showed
similar results but also evaluated the distensibility of the pylorus at various
balloon volumes. The latter showed that symptoms of delayed gastric empyting
were increased when distensibility of the pylorus was less than 10mm2/mmHg.
Based on the above mentioned studies, this study also aims to identify if
pyloric resting pressures and distensibility correlate with patients suffering
from delayed gastric empyting and if this can be used as a predictive marker
for treatment success.

(See protocol for references).

Primary objectives
1. To evaluate the efficacy, feasibility and safety of G-POEM in patients with
symptoms delayed gastric emptying after oesophagectomy with gastric tube
reconstruction, based subsequently on the clinical success rate at 3 months,
technical success rate and the occurrence of severe adverse events.

Secondary objectives
1. To evaluate the durability of G-POEM in patients with symptoms of delayed
gastric emptying after oesophagectomy with gastric tube reconstruction, based
on clinical success rate at 12 months.
2. To evaluate the efficacy and durability of G-POEM based on:
- Objective parameters: gastric emptying time on nuclear scintigraphy, gastric
emptying time on barium swallow, gastroscopy, EndoFlip measurement.
- Subjective parameters: symptom scores for gastric emptying, dumping, and
nocturnal regurgitation.
3. To identify possible predictive factors for the success or failure of G-POEM
in this patient category, based on:
- Objective parameters: pre-G-POEM gastric emptying time on nuclear
scintigraphy, pre-G-POEM gastric emptying time on barium swallow, pre-G-POEM
gastroscopy, pre-G-POEM EndoFlip measurement, previous success on BOTOX
injection.
- Subjective parameters: symptom scores for gastric emptying, dumping, and
nocturnal regurgitation.
4. To evaluate the effect on Quality of Life.

Prospective uncontrolled multi center intervention study. Patients will be
recruited from the RAKU (University Medical Center Utrecht and St. Antonius
Hospital) and Amsterdam University Medical Centers. Study procedures can be
performed in all these three hospitals.

G-POEM, gastric per-oral endoscopic myotomy of pylorus. A minimally invasive
endoscopic pyloromyotomy.

With regards to the G-POEM patients will not be subjected to extra risks. If
patients don't enroll in the study they will be offered the same treatment
possibility. However, patients enrolling in this study will be asked to fill in
several questionnaires at 3 different timepoints. Firstly, at baseline,
followed by 3 months and 1 year after treatment. This will require circa 1.5-2
hours (for all questionnaires).
Furthermore, patients will undergo an EndoFlip measurement, as mentioned
earlier in this form, this measurement will not be subject to extra risks.