Introduction
Peroral endoscopic myotomy (POEM) is a recently developed treatment strategy for patients
with achalasia [1]
[2]
[3]. To date, a number of studies have demonstrated that POEM can achieve an 82 % – 100 %
success rate for palliation of dysphagia [4]. However, relatively few medical centers provide this procedure because of the technical
expertise required, and because laparoscopic Heller myotomy and pneumatic dilation
remain effective, time-honored therapeutic options.
On the other hand, endoscopic submucosal dissection (ESD) has been widely accepted
as a standard treatment for early gastrointestinal neoplasia, when the risk of lymph
node metastasis is very low [5]
[6]
[7], especially in Asia. This procedure is now being performed around the world, and
a variety of electrosurgical knives have been developed to improve the efficiency
and safety of ESD [8]
[9]
[10]
[11]
[12]. POEM requires techniques such as mucosal incision, submucosal tunneling, hemostasis,
and myotomy, which are derived from the basic methods used in performing ESD [3].
Not surprisingly, several electrosurgical knives that were initially developed for
ESD have since been applied to POEM. Although the use of several kinds of electrosurgical
knives in POEM has been reported [3]
[13]
[14], the best device has yet to be determined, with the choice of knife often depending
on the endoscopist’s experience, expertise, and preference. According to previous
reports, the triangle tip knife (KD-640L; Olympus Medical Systems, Japan) is most
commonly used for POEM, and the HybridKnife (Erbe Elektromedizin GmbH, Tübingen, Germany),
which has waterjet function, is also widely used [3]
[12]. In general, needle-type electrosurgical knives are preferred in esophageal ESD,
given the thin wall of the esophagus and the narrow working space. The FlushKnife
BT (DK2618JB; Fujifilm, Tokyo, Japan) is a waterjet-emitting, short needle-knife that
is equipped with a spherical tip 0.9 mm in diameter, for use not only in esophageal
ESD but also gastric or colorectal ESD. Because of the small, short ball tip of the
FlushKnife BT and its built in waterjet function [15]
[16]
[17], this device offers the potential to perform POEM more efficiently and safely than
other ESD knives; however, there have been no reports regarding the use of FlushKnife
BT to perform POEM. The aim of this study was to evaluate the feasibility and efficiency
of the FlushKnife BT for POEM.
Patients and methods
Study design
The study was performed at Kobe University Hospital, a tertiary referral center in
Japan. The data for POEM procedures were collected prospectively. Enrollment began
in January 2016, and consecutive patients with achalasia and other spastic esophageal
motility disorders such as jackhammer esophagus or distal esophageal spasm who were
candidates for POEM were recruited for this retrospective study. The current study
was approved by the Institutional Review Board. Written informed consent was obtained
from all participants, and the study was conducted according to the Declaration of
Helsinki.
FlushKnife BT
The FlushKnife BT is equipped with a spherical tip 0.9 mm in diameter and comes in
four lengths: 1.5, 2, 2.5, and 3 mm ([Fig. 1]). A waterjet emitted from the tip of the sheath enables lavage of the operating
field, as well as submucosal fluid injection without device exchange [16]. Generally, the 2.5 mm and 2 mm long types are used for the stomach, and the 1.5 mm
type is used for ESD in the esophagus and colorectum [16]
[18]
[19]. The 3 mm long type was selected for POEM in order to achieve more effective myotomy
using the longer arm of the knife ([Fig. 1]). The bulbous spherical tip is used to hook onto circular muscle fibers and to provide
gentle traction, prior to coagulation and cutting. The settings for FlushKnife BT
using the Erbe Vio 300 generator were as follows: spray coagulation mode, effect 1,
100 W was used for creating a submucosal tunnel; endo-cut I mode, effect 4, duration
3, interval 3, was used for mucosal incision and myotomy.
Fig. 1 The FlushKnife BT (Fujifilm, Tokyo, Japan). The 3 mm long type was selected for peroral
endoscopic myotomy.
POEM technique
A forward-viewing endoscope with a 3.2 mm instrumentation channel (GIF-H260J; Olympus
Medical Systems) and a short ST hood (DH-28GR; Fujifilm) were used. POEM was performed
under general anesthesia with endotracheal intubation and carbon dioxide insufflation.
First, approximately 5 mL of saline mixed with 0.3 % indigo carmine was injected into
the submucosa ([Fig. 2a]), and a longitudinal mucosal incision was made in the mucosal surface to gain access
to the submucosal space. This same saline mixture was used for subsequent injections
via the FlushKnife BT. Second, a submucosal tunnel was created and extended past the
esophagogastric junction (EGJ) for 2 – 3 cm into the gastric cardia ([Fig. 2b,c]). The submucosal tunnel was usually created in the 5 o’clock position, or the 7
o’clock position for patients with a history of prior Heller myotomy in order to avoid
fibrosis from the previous surgery. Complete gastric myotomy was confirmed by using
a second, small-caliber endoscope [20]. Third, a proximal-to-distal circular myotomy was performed, with care, to preserve
the longitudinal muscle layers of the esophagus and stomach ([Fig. 2 d,e]). The myotomy was extended 2 – 3 cm into the gastric cardia beyond the EGJ in patients
with achalasia and in those with other spastic esophageal motility disorders. Finally,
the mucosal entry was closed using endoscopic clips ([Fig. 2f]).
Fig. 2 Peroral endoscopic myotomy using the FlushKnife BT (Fujifilm, Tokyo, Japan). a A needle-knife was used for mucosal injection. b The FlushKnife BT was used to create a submucosal tunnel. c After creation of the submucosal tunnel. d The FlushKnife BT was used to cut the circular muscle. e The longitudinal muscle remained intact after myotomy. f The mucosal entry was closed using endoscopic clips.
Precoagulation
When small-to-medium-sized (less than 2 mm) blood vessels were encountered during
POEM, in endoscopic vessel sealing technique was performed, as described previously
[21]. The procedure is performed as follows. First, submucosal layer tissue surrounding
a blood vessel was dissected and the blood vessel was isolated ([Fig. 3a]). Second, both sides of the isolated blood vessel were compressed with the tip of
the FlushKnife BT and precoagulated in low power, forced coagulation mode (Effect
1, 10 W) until the blood vessel turned white ([Fig. 3b,c]). Finally, the blood vessel was dissected using the spray coagulation mode (effect
1, 100 W) ([Fig. 3d,e]).
Fig. 3 Endoscopic vessel sealing technique using the FlushKnife BT (Fujifilm, Tokyo, Japan).
a The blood vessel in the submucosal layer was isolated. b, c Both sides of the isolated blood vessel were clamped using the tip of the FlushKnife
BT, and then precoagulated in forced coagulation mode (effect 1, 10 W) until the vessel
turned white. d The blood vessel was dissected in the spray coagulation mode (effect 1, 100 W). e After dissection of the blood vessel.
Statistical analysis
Medians (interquartile range [IQR]) and percentages for categorical variables were
used to describe patient baseline characteristics and procedure-related parameters.
Eckardt scores and integrated relaxation pressures (IRP) before and after POEM were
compared, and changes in Eckardt score and IRP at 3 months after the POEM procedure
were assessed using Wilcoxon’s signed rank sum test.
Results
Clinical features of patients
POEM was carried out in 54 patients between January 2016 and August 2016. [Table 1] lists the patient demographic and perioperative characteristics. Of the 54 patients,
including 24 men and 30 women, the median age was 52.5 years (range 16 – 84 years).
Median body mass index was 20.6 kg/m2 (range 14.1 – 31.6 kg/m2). Median duration of symptoms was 4 years (range 0.5 – 60 years). Esophageal manometry
findings were classified according to the Chicago classification system, as type I
(22 patients, 40.7 %), type II (21 patients, 38.9 %), type III (3 patients, 5.6 %),
jackhammer esophagus (3 patients, 5.6 %), distal esophageal spasm (1 patient, 1.9 %).
In four patients, manometry was not completed because of difficulty in inserting the
catheter through the lower esophageal sphincter. Among the 50 achalasia patients,
39 (78.0 %) were classified as straight type and 11 (22.0 %) as sigmoid type. Prior
to POEM, pneumatic balloon dilation had been performed in 11 patients (20.4 %) and
2 patients (3.7 %) had undergone Heller myotomy.
Table 1
Patient demographics and perioperative characteristics.
|
|
n = 54
|
|
Age, median (IQR), [range], years
|
52.5 (43 – 66), [16 – 84]
|
|
Sex
|
|
|
24
|
|
|
30
|
|
BMI, median (IQR), [range], kg/m2
|
20.6 (19.0 – 22.2), [14.1 – 31.6]
|
|
Duration of symptoms, median (IQR), [range], years
|
4 (1.5 – 15), [0.5 – 60]
|
|
Type of achalasia, n
|
|
|
39
|
|
|
11
|
|
Chicago classification, n
|
|
|
22
|
|
|
21
|
|
|
3
|
|
|
3
|
|
|
1
|
|
|
4
|
|
Primary procedure, n
|
|
|
11
|
|
|
2
|
|
Myotomy length, median (IQR), [range], cm
|
13 (10.3 – 16), [4 – 23]
|
|
Submucosal fibrosis, n
|
6
|
IQR, interquartile range; BMI, body mass index.
The median total length of the endoscopic myotomy was 13.0 cm (range 4 – 23 cm). Submucosal
fibrosis was confirmed in six patients (11.1 %).
Procedure-related outcomes
[Table 2] shows the procedure-related outcomes. The median operating time was 73.0 minutes
(range 39 – 184 minutes). All procedures were completed using only the FlushKnife
BT without exchange to another electrosurgical device. The median number of additional
submucosal injections requiring an injection needle was 0 (range 0 – 1). The median
number of bleeding episodes requiring treatment with hemostatic forceps was 0 (range
0 – 5). Endoscopic vessel sealing was performed a median of 3 times per POEM procedure
(range 0 – 7).
Table 2
Procedure-related outcomes.
|
Operation time, median (IQR), [range], minutes
|
73 (55.3 – 91), [39 – 184]
|
|
Endoknife changes, median (IQR), [range], n
|
0 (0), [0]
|
|
Additional submucosal injection with injection needle, median (IQR), [range], n
|
0 (0), [0 – 1]
|
|
Bleeding requiring hemostatic forceps, median (IQR), [range], n
|
0 (0 – 1.8), [0 – 5]
|
|
Number of times vessel sealing required during procedure, median (IQR), [range], n
|
3 (1 – 4), [0 – 7]
|
|
Complications, n (%)
|
|
|
5 (9.3)
|
|
|
3 (5.6)
|
IQR, interquartile range.
Treatment outcomes
Esophageal manometry, upper endoscopy, and interview (Eckardt score, symptoms of gastroesophageal
reflux disease [GERD]) were performed in all patients, 3 months following POEM. Two
patients did not receive follow-up examinations for personal reason. [Table 3] shows the treatment outcomes. A significant reduction in symptoms was achieved (median
[range], preoperative Eckardt score 6 [2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11] vs. postoperative 0 [0 – 4]; P < 0.001), with a significant reduction in IRP (median [range], preoperative 26.0 mmHg
[2.3 – 75] vs. postoperative 9 mmHg [0.1 – 23.8]; P < 0.001). Thirty-six of 52 patients (69.2 %) had endoscopic findings of reflux esophagitis.
Seven of 52 patients (13.5 %) complained of GERD symptoms such as heartburn or acid
reflux.
Table 3
Treatment outcomes.
|
Before POEM
|
3 months after POEM
|
P value
|
|
Eckardt score, median (IQR), [range]
|
6 (4 – 7), [2 – 11]
|
0 (0 – 1), [0 – 4]
|
< 0.001
|
|
IRP, median (IQR), [range], mmHg
|
26 (18.9 – 33.5), [2.3 – 75]
|
9 (5.9 – 11.9), [0.1 – 23.8]
|
< 0.001
|
|
Endoscopic reflex esophagitis findings, n (%)
|
|
Grade N: 16 (30.8)
Grade A: 17 (32.7)
Grade B: 15 (28.8)
Grade C: 3 (5.8)
Grade D: 1 (1.9)
|
|
|
GERD symptoms, n (%)
|
|
7 (13.5)
|
|
POEM, peroral endoscopic myotomy; IQR, interquartile range; IRP, integrated relaxation
pressure; GERD, gastroesophageal reflux disease.
Discussion
Our results of POEM with the FlushKnife were similar to those in other published series.
Our median operation time was 73.0 minutes (range 39 – 184 minutes) whereas previous
studies reported a range of 22.9 – 148 minutes [22]
[23]
[24]
[25]. We observed a significant reduction in symptoms: (median [range], preoperative
Eckardt score 6 [2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11] vs. postoperative 0 [0 – 4]; P < 0.001), with a significant reduction in IRP (median [range], preoperative 26.0 mmHg
[2.3 – 75] vs. postoperative 9 mmHg [0.1 – 23.8]). Seven of 52 patients (13.5 %) complained
of GERD symptoms such as heartburn or acid reflux, which is also comparable to that
reported in published literature [22]
[23]
[24]
[25]. No patient experienced a serious adverse event.
We consider the primary benefit of the FlushKnife BT to be the need for fewer device
exchanges during the procedure, which we attribute both to its waterjet function and
to its good hemostatic capability [16]. In our study, the number of knife exchanges, additional submucosal injections with
an injection needle, and episodes of bleeding requiring hemostatic forceps were very
few. This enabled endoscopists to perform their procedure continuously, without interruption.
Waterjet function effectively provided submucosal injection without requiring re-introduction
of an injection needle. Even the initial submucosal injection can occasionally be
performed by the FlushKnife itself, instead of an injection needle. In this study,
submucosal injection using an injection needle was performed only once in one patient.
Waterjet irrigation via the FlushKnife is especially useful when passing through a
tight EGJ in a patient with achalasia during submucosal tunnel creation. Repeated
submucosal injection is often required to maintain enough space to allow safe passage
through to the gastric side ([Fig. 4]). However, the risk of mediastinitis due to the leakage of liquid into the mediastinum
is a concern. To reduce the risk of mediastinitis, it is better to use the waterjet
function as little as possible during myotomy.
Fig. 4 Submucosal injection using the FlushKnife BT (Fujifilm, Tokyo, Japan). a The submucosal space is very tight at the esophagogastric junction. b Submucosal injection using the FlushKnife BT. c Enough space was thus created to allow safe passage through to the gastric side.
Intraoperative bleeding is a serious problem that can complicate POEM. Prevention
of bleeding is important not only for the hemodynamic stability of the patient, but
also to maintain a clear operative field. If bleeding develops within the submucosal
tunnel, the submucosal layer is easily obscured by blood and/or excessive charring,
and the rate of mucosal perforation or further bleeding may consequently be increased.
To prevent bleeding, it is important to identify and isolate blood vessels and precoagulate
them before transection [26]. Theoretically, the current density in the FlushKnife BT is decreased at its spherical
tip. This provides better hemostatic capability, allowing for small vessels to be
precoagulated and cut by the knife itself [16]. Furthermore, the endoscopic vessel sealing technique using FlushKnife BT was easy
and effective for coagulation of small-to-medium-sized vessels without the need for
hemostatic forceps [21]. This technique was frequently employed during POEM, and contributed to a reduction
of bleeding episodes that required hemostatic forceps, as well as maintaining a clear
operative field.
Another technical challenge encountered during POEM is the management of fibrotic
areas [27]. In this study, six patients had submucosal fibrosis. Even in these patients, however,
POEM could be completed with the FlushKnife BT alone, without changing to another
electrosurgical device. Previous literature indicates that the FlushKnife BT is effective
for overcoming submucosal fibrosis in ESD [17]
[28]. To dissect a severely fibrotic area, it is important to proceed by 1 – 2 mm increments,
and to start in an area that is least fibrotic. This approach enables clear exposure
of new fibrotic areas, little by little, and helps to identify an appropriate line
of dissection through a severely fibrotic area. If dissection using spray coagulation
mode is difficult, the change to swift coagulation mode or cut mode will enable sharp
cutting.
Although the FlushKnife BT has several advantages as indicated above, there is also
a disadvantage. The tip of the FlushKnife BT is small, which enables very precise
manipulation; however, compared with the triangle tip knife, it is less efficient
at creating the submucosal tunnel, and this stage can become time-consuming in patients
requiring a long myotomy.
In conclusion, the FlushKnife BT enabled effective POEM with very few device changes,
and with minimal need for additional submucosal injections or use of the hemostatic
forceps. The ability of the FlushKnife BT to efficiently perform nearly all aspects
of the POEM procedure makes it particularly well suited to this procedure. To determine
the relative safety, efficacy, and potential cost savings associated with the use
of FlushKnife BT for POEM, compared with other available electrosurgical knives, a
multicenter, randomized controlled study should be considered.
