Introduction
Peroral Endoscopic Myotomy (POEM) was introduced in 2010 as an alternative endoscopic
treatment for achalasia [1]. The technique is suggested to combine the benefits of the current standard treatment
options for achalasia, the minimally invasive approach of endoscopic pneumodilation
with the efficacy of laparoscopic Heller myotomy. The POEM procedure is performed
entirely endoscopically and starts with a longitudinal incision of the mucosa allowing
entry to the submucosa. The endoscope is then advanced into the submucosa to create
a submucosal tunnel. After a myotomy of the circular muscle fibers within the submucosal
tunnel, the entry site of the submucosal tunnel is closed with endoscopic clips approximating
the mucosa again.
At expert centers worldwide, more than 4000 achalasia patients underwent a POEM procedure
for achalasia over the last 5 years. Initial outcomes for POEM concerning safety and
efficacy are encouraging. Short-term clinical success ranges from 82 % to 100 % [2]
[3].
Safety and clinical success of POEM are based on a careful execution of the subsequent
steps of which the procedure consists. Performing POEM is time consuming. Mean procedure
time of available studies approximates 120 minutes [2]. A recent publication showed a learning curve reducing procedure times to a median
of 97 [65 – 140] minutes after 93 patients [4]. As more experience is gained with performing POEM, modifying the procedure could
further improve the outcomes of efficacy and safety. Moreover, the procedure could
be shortened by optimizing the different phases of the procedure. For closure of the
mucosal entrance, endoscopic metal clips are often the method of choice because endoscopists
are experienced in using these clips. After placement of each clip, a clipping device
then has to be introduced through the working channel of the endoscope. Recently,
a new endoscopic clip system has been introduced, the Clipmaster3. The Clipmaster3
is based on the standard endoscopic clip but is able to place up to three consecutive
clips without having to reload clips after positioning. Using this clip system, closure
time of the mucosal entry site could potentially be reduced and this may help to shorten
the total POEM procedure time. Moreover, we hypothesize that Clipmaster3 is as safe
and effective as standard clip closure for POEM. In this study, we prospectively evaluated
closure time of the Clipmaster3, its safety, and ease of use. Moreover, closure using
Clipmaster3 was compared to closure with standard endoscopic clips.
Methods
Patients diagnosed with achalasia based on high resolution manometry and timed barium
esophagram who underwent a POEM between 2011 and 2014 were prospectively entered in
a database at the Academic Medical Center, Amsterdam, The Netherlands. From April
2013 until March 2014, in consecutive achalasia patients who underwent POEM, the Clipmaster3
was used for closure of the mucosal incision after the myotomy was completed. Selection
of patients was based on logistics, the same team of endoscopy nurse and endoscopist
performing all of the studied POEM procedures, as well as the availability of the
Clipmaster3 system. As a result, for 12 consecutive procedures, Clipmaster3 was planned
to be used for the mucosal closure during POEM. The Clipmaster3 is a clip applicator
in which three clips are preloaded. Patients undergoing closure with the Clipmaster3
were compared to a cohort of achalasia patients who underwent POEM in which standard
endoscopic clips were used for closure. Before the first procedure, both endoscopist
and endoscopy nurse were trained on an ex-vivo model to use Clipmaster3 by placing
30 clips. Data for the selected patients were collected by the same person for all
procedures in a prospective manner or during the procedure. Closure time was also
checked after the procedure for each patient with the video taken during the procedure.
POEM procedure
The POEM procedure was executed by an experienced gastroenterologist and performed
according to the previously described procedure [5]. In short, the following steps can be distinguished: (1) incision of the mucosa
to create an entrance for the submucosal tunnel; (2) creation of a submucosal tunnel
10 – 14 cm proximally to the lower esophageal sphincter to a maximum of 3 cm into
the cardia of the stomach; (3) myotomy of the circular muscle fibers starting 2 cm
distally from the lower end of the incision and into the stomach; (4) closure of the
mucosal entry site of the submucosal tunnel using the Clipmaster3 system or standard
endoscopic clips.
Mucosal closure using standard endoscopic clips
Endoscopic metal clips (HX-610 – 135 L Single Use Clips, Olympus) were used with a
rotatable Clip Reusable Rotatable Clip Fixing Device (HX-110UR EZ, Olympus). The width
of the open clip is 9 mm, the length of each arm of the clip is 5 mm, and the clip
is rotatable over 360 degrees. After placement of each clip, the device was removed
from the endoscope, reloaded with a new clip, and reintroduced through the working
channel of the endoscope.
Mucosal closure using Clipmaster3 system
The Clipmaster3 (SPE1-X3 – 26 – 220 – 502063, Medwork, GmbH, Aisch, Germany) is a
clip system with three clips preloaded. As a result, up to three clips can be placed
without reloading. The clip applicator has a diameter of 2.6 mm, the width of the
open clip is 12 mm, and the clip is rotatable over 360 degrees. The clips have small
hooks attached to its jaws for mucosal approximation. After usage of the three clips,
the device was removed after which a new device was introduced containing again three
clips ( [Fig.1]).
Fig. 1 Clipmaster3 clip versus standard endoscopic clip. a Clipmaster3 clip. b Clipmaster3 device. c Closed mucosal incision with Clipmaster3. d Olympus clip. e Rotatable Clip Delivery device. f Closed mucosal incision with Olympus clips (© 2016 olympus europa SE & Co. UG).
Outcome parameters
The following variables were collected for both groups: sex, age, achalasia subtype
based on high-resolution manometry, preoperative esophageal diameter based on soluble-contrast
X-swallow, disease duration, previous achalasia treatment, medication use, length
of the mucosal incision, procedure time, endoscopically successful closure, leakage
on X-swallow 1 day post-procedure, closure time, number of clips used for successful
closure, total number of clips, unsuccessfully placed clips, adverse events, postoperative
stay, readmission within 30 days, and mortality. The definition of successful endoscopic
closure was stated as the absence of submucosal leakage of water-soluble contrast
visible during the X-swallow 1 day post-procedure. Closure time was defined as the
time interval between the first appearance of a clip in the esophageal lumen until
placement of the last clip. Adverse events were defined as any deviation from the
normal postoperative course within 30 days after POEM. Moreover, handling of the Clipmaster3
was evaluated by means of a questionnaire where ease of use was scored on a VAS (visual
analogue scale, 0 = impossible, 10 = very easy) by both endoscopist as well as the
endoscopy nurse assisting with the closure procedure. Possible underlying causes related
to a difficult closure of the submucosal entrance by the Clipmaster3 were also noted
on the questionnaire.
Data analysis
In total, 12 consecutive POEM closures with Clipmaster3 were compared to 24 consecutive
standard procedures. The same physician and endoscopy nurse performed all procedures.
This hampered a case-match analysis and data were compared in a 1:2 manner.
Results
Between 2013 and 2014, 12 patients underwent a POEM procedure in which the mucosal
entry site was closed with Clipmaster3. From August 2011 to 2014, a total of 71 patients
underwent standard POEM. Of all patients who underwent standard POEM, 24 patients
underwent a POEM procedure by the same team of endoscopist and endoscopy nurse.
The Clipmaster3 and the standard group did not differ in sex distribution, age at
surgery (42 years [29 – 49] vs 41 years [34 – 54] P = 0.379), diagnosed type of achalasia (P = 0.181), preoperative esophageal diameter based on soluble-contrast X-swallow (27 mm
[23 – 37] vs 27 mm [22 – 35], P = 0.724), disease duration (57.0 months [39.3 – 121.3] vs 38.0 months [18.0 – 97.8],
P = 0.137), length of the mucosal incision (25.0 mm [20 – 30] vs 20.0 mm [20 – 30],
P = 1.0), or medication use ([Table 1]). More patients underwent previous therapy before POEM in the Clipmaster3 group
(11 out of 12 (91.7 %) vs 19 out of 24 (79.2 %), P = 0.020).
Table 1
Patient demographics.
|
Clipmaster3
(n = 12)
|
Standard
(n = 24)
|
P value
|
|
Female gender, n (%)
|
7 (58.3)
|
12 (50)
|
0.64
|
|
Age at surgery, median [range], years
|
42 [29 – 49]
|
41 [34 – 54]
|
0.38
|
|
Achalasia type, n (%)
|
|
|
0.18
|
|
Type I
|
5 (41.7)
|
7 (2.9)
|
|
|
Type II
|
6 (50)
|
12 (50)
|
|
|
Type III
|
0 (0)
|
5 (2.0)
|
|
|
Unknown
|
1 (0.8)
|
0 (0)
|
|
|
Disease duration, median [interquartile range], months
|
57.0 [39.3 – 121.3]
|
38 [18.0 – 97.8]
|
0.14
|
|
Previous therapy, n (%)
|
11 (91.7)
|
19 (79.2)
|
0.02
|
|
Botox
|
1 (9.0)
|
1 (5.3)
|
|
|
Pneumodilation
|
9 (81.8)
|
6 (31.6)
|
|
|
Heller myotomy
|
1 (9.0)
|
12 (63.2)
|
|
|
Medication at time of surgery, n (%)
|
0
|
4 (16.7)
|
0.59
|
|
NSAIDs
|
0
|
1
|
|
|
Anti-platelets
|
0
|
2
|
|
|
Corticosteroids
|
0
|
1
|
|
|
Esophageal diameter based on soluble-contrast X-swallow, median [interquartile range],
mm
|
27 [23 – 37]
|
27 [22 – 35]
|
0.72
|
|
Length of incision, median [interquartile range], mm
|
25.0 [20 – 30]
|
20.0 [20 – 30]
|
1.00
|
Esophageal diameter was measured during soluble-contrast X-swallow before POEM.
Endoscopically successful closure without mucosal gaps could be performed in both
groups in all patients. In none of the patients was leakage seen during water soluble-contrast
X-swallow on the morning after the procedure. Duration of closure time of the mucosal
incision did not differ between the groups (622 seconds [438 – 909] vs 599 seconds
[488 – 664], P = 0.72) ([Table 2]). Total procedure time did not differ between the groups (95 min [81 – 112] vs 98 min
[84.3 – 120] P = 0.909).
Table 2
Procedure and post-procedure outcomes.
|
Clipmaster3
(n = 12)
|
Standard
(n = 24)
|
P value
|
|
Procedure time, median [interquartile range], minutes
|
95 [81 – 112][*]
|
98 [84.3 – 120]
|
0.90
|
|
Successful macroscopic closure, n (%)
|
12 (100)
|
24 (100)
|
|
|
Closure time, median [interquartile range], seconds
|
622 [438 – 909]
|
599 [488 – 664]
|
0.72
|
|
Number of clips for successful closure, median [interquartile range], n
|
8 [7 – 9]
|
8 [7 – 9]
|
0.90
|
|
Total number of clips used, n
|
102
|
191
|
|
|
Number of unsuccessful clips, n (% of all clips)
|
9 (8.8)
|
4 (2.0)
|
0.00
|
|
Displaced clips
|
6
|
3
|
|
|
Discarded clips
|
3
|
1
|
|
|
Adverse events, n (%)
|
3 (25)
|
6 (25)
|
1.00
|
|
Nausea
|
1
|
1
|
|
|
Fever
|
1
|
1
|
|
|
Reflux
|
1
|
1
|
|
|
Bleeding
|
0
|
1
|
|
|
Allergic reaction
|
0
|
1
|
|
|
Hypotension
|
0
|
1
|
|
|
Postoperative hospital stay, n [range]
|
1 [1 – 1]
|
1 [1 – 2]
|
|
|
Readmission within 30 days, n
|
0
|
0
|
|
|
Mortality, n
|
0
|
0
|
|
* One missing value.
The number of clips that were placed to achieve successful closure did not differ
between groups (8 [7 – 9] vs 8 [7 – 9], P = 0.902) ([Table 2]). For Clipmaster3 compared to standard closure, a larger proportion of all clips
used were either misplaced or discarded (8.8 % vs 2.0 %, P = 0.00782). The number of adverse events and postoperative stay did not differ between
groups. There was no mortality and there were no readmissions within 30 days in either
group. VAS score for the ease of use for handling of the Clipmaster3 for closure did
not differ between the endoscopist and endoscopy nurse and were both 7 ([6]
[7]
[8]
[9], [6]
[7]
[8]) out of 10 ([Table 3]). Reasons for difficult closure for the endoscopist were type of incision and the
anatomy of the esophagus, and for the endoscopy nurse, reasons for difficult placement
were unpredictable opening and handling of the clip ([Table 3]).
Table 3
Ease of use of Clipmaster3 based on VAS scale.
|
Clipmaster3
(n = 12)
|
|
Nurse
|
Endoscopist
|
|
Ease of use (0 – 10), median [interquartile range]
|
7.0 [6 – 9]
|
7.0 [6 – 8]
|
|
Reasons for difficult closure, n (%)
|
6 (50)
|
4 (33.3)
|
|
Anatomy of incision
|
0
|
1
|
|
Difficult positioning
|
0
|
1
|
|
Wide esophagus
|
0
|
1
|
|
Unreliable
|
1
|
1
|
|
Difficult detachment of clip
|
1
|
0
|
|
Difficult handling
|
2
|
0
|
|
Clip does not open enough
|
1
|
0
|
|
Difficult removal of clips
|
1
|
0
|
Ease of use is scored via a VAS (visual analogue scale) defined as 0 = impossible,
10 = very easy.
Discussion
In this study, we prospectively evaluated safety and efficacy, closure time, as well
as ease of use of the new Clipmaster3 system for endoscopic closure of the mucosal
incision after POEM. Clipmaster3 proved to be feasible and safe for mucosal closure
after POEM in the 12 patients studied. In contrast to our hypothesis, no reduction
in closure time was observed for Clipmaster3 compared to standard clip closure. More
clips from Clipmaster3 were misplaced during closure compared to the standard clips.
Handling the Clipmaster3 system was independently evaluated as moderately easy by
both endoscopist and endoscopy nurse and was scored as 7 out of 10 on a VAS. The patients
studied were compared based on the same trained endoscopy nurse attending all procedures
as well as the same physician performing all POEM procedures.
In the majority of publications on POEM, endoclips are used for closure of the mucosal
incision. An alternative closure modality has been described in only one small study.
Meireles et al. used surgical tissue glue to complete closure in addition to standard
clips in five patients [6]. However, their study showed that closure with endoclips alone was already sufficient
for effective mucosal closure. Several cases of rescue closure attempts for complicated
POEM procedures with modalities other than standard clips have been described. Endoscopic
suturing (Overstitch Endoscopic Suturing System; Apollo Endosurgery, Austin, TX, United
States) could be used successfully for closure of the mucosal entry site during a
procedure that was complicated by a full thickness muscular rupture [7]. In two other studies, the Over-the-Scope clip was used for closure of a difficult,
time consuming case after an initial attempt at closure with numerous endoclips, and
this resulted in successful closure [8]. For a perforation during a POEM procedure, fibrin sealant was used which was sprayed
into the distal end of the submucosal tunnel and a gastric mucosal penetration was
sealed successfully [9]. Moreover, after a failed attempt at closure with metallic clips due to swollen
mucosa, tightening of an Endoloop that was snared around the previously placed distal
clips resulted in closure of the mucosal incision (the so-called tulip bundle technique)
[10].
This is the first study to analyze closure time and investigate improvements in this
part of the procedure. Procedure time is mentioned in the majority of the studies,
however, closure time is usually not described separately. Procedure time is predominantly
determined by creation of the submucosal tunnel which is a time consuming phase of
the POEM procedure. However, we are not aware of significant alternative techniques
for submucosal tunneling that have been reported in the literature. Moreover, this
is the first study that evaluates an alternative closure modality as the initial closure
technique and compares it to the established technique.
It was hypothesized that, without subsequent loading of each new clip and without
each introduction into the esophagus, closure time could be diminished. However, duration
of closure did not differ between standard endoclip closure and closure with the Clipmaster3. It
is possible that closure time is not only affected by the subsequent loading and introduction
needed before placement of each new clip, but other factors might play a role as well.
One explanation could be that the time that was saved by not exchanging devices was
invested in clip placement with the slightly more bulky multi-firing device. In the
Clipmaster3 group, more clips were misplaced which could have determined closure time
more than the time needed to reload each endoclip. Moreover, both endoscopist and
endoscopy nurse had less experience with using Clipmaster3 compared to endoclip despite
the fact that they had been trained specifically with this device. The above mentioned
reasons could have resulted in more clips that failed during placement and resulted
in Clipmaster3 being more time consuming. In general for POEM, we learned that the
key factor for successful closure seems mainly determined by whether the first and
second clips are adequately placed. Placement of the first clip just distally to the
incision allows the wound edges to align parallel and angle up into the lumen of the
esophagus making subsequent clipping easier. Less experience with the Clipmaster3
could have meant less adequate placement of the first clip and therefore result in
more clips being either displaced or discarded. Furthermore, as we gained experience
in performing POEM, we observed that the esophageal diameter seemed to influence the
level of difficulty of closure as well. We observed that a larger diameter due to
long-standing achalasia causes stretching of the mucosa with a wider deviation of
the wound edges as a result. Easy and fast approximation of tissue and thus closure
could therefore be hampered. However, as measured during X-swallow, the groups did
not differ in esophageal diameter before the procedure. Therefore, in this study,
this parameter would not have determined closure.
Ease of use of Clipmaster3 was scored as 7 out of 10 for both endoscopist as well
as endoscopy nurse, compatible with, on average, moderately easy closure. However,
reasons for difficult placement differed between the endoscopist and nurse. For the
endoscopy nurse, reasons for difficult placement were unpredictable opening and handling
of the clip. For the endoscopist, the type of incision and the anatomy of the esophagus
determined difficult closure with Clipmaster3.
Limitations of this study include the small number of patients studied. Moreover,
the study was not designed as a randomized controlled trial.
In the authors’ opinion, an ideal closure modality for closing the mucosal entry site
after POEM should have the ability to rotate easily inside the esophageal space and
have a confined opening width to ensure complete grasping of mucosal edges and quick
closure. Moreover, the closure modality also determines total costs and therefore
should be low cost. In total, standard (Olympus) clips and the fixing device cost
around 800 euro per procedure (clipping device 700 euro + 10 euro per clip). For Clipmaster3,
this sum approximates 450 euro per procedure. The delivery device can however be sterilized
and used in multiple patients.
This study demonstrates that Clipmaster3 for closure of the mucosal entrance during
POEM is as safe and effective for endoscopic closure of a mucosal incision after POEM
as standard clips. However, compared to standard metal clips, Clipmaster3 was not
associated with reduced closure time as was hypothesized. Possible reasons for failure
of our hypothesis could be associated with the Clipmaster3 being a more voluminous
clip system compared to standard clips. Moreover, closure with Clipmaster3 resulted
in more dislocated clips and the endoscopy team had less experience with using Clipmaster3
compared to the standard clips.
