Introduction
Endoscopic ultrasonography-guided gallbladder drainage (EUS-GBD) is recommended over
standard percutaneous or transpapillary approaches in fragile patients with acute
cholecystitis [1]
[2]. In this clinical scenario, EUS-GBD using an electrocautery-enhanced lumen-apposing
metallic stent (EC-LAMS) is preferred over plastic stents (PS) because of its simpler
procedural steps and fewer adverse events (AEs) [1]
[2].
We hypothesized that a single-step PS delivery system for EUS-GBD would reduce incidence
of AEs, particularly bile leakage [3]
[4]
[5]. To test this hypothesis, we conducted a preliminary experimental study simulating
EUS-GBD using a gallbladder model and a remnant porcine gallbladder obtained from
meat processing and compared its performance with that of a commercially available
PS.
Methods
Aim and study design
This preliminary experimental study simulated EUS-GBD to compare a single-step PS
delivery system with the current PS system using a gallbladder model and a porcine
gallbladder.
Prepared gallbladder and experimental system
The experimental setup is shown in ([Fig. 1], [Video 1]). First, a spheroidal gallbladder model was constructed from 3 mm-thick polyvinyl
alcohol artificial membrane with a major radius of 55 mm and a minor radius of 40
mm. The model was immersed in a 0.18 wt% saline solution maintained at 36.5°C using
an incubator. Subsequently, the gallbladder was connected to a manometer to establish
zero-calibration of intra-gallbladder pressure. Then, 50 mL of brown-colored 2.0 wt%,
13–18 mPa∙s methylcellulose solution was injected into the gallbladder. Intra-gallbladder
pressure was continuously monitored from the point of puncture until stent deployment.
The incubator, attached to a neutral pad, was connected to an electrosurgical generator
(VIO300D, ERBE, Tübingen, Germany) set to the monopolar mode with Endo Cut 1 and Effect
2.
Fig. 1 Experimental system. At the center, a gallbladder model is immersed in a 0.18 wt%
saline solution maintained at 36.5°C by the incubator. The gallbladder model is sealed
with a clip at the yellow line and connected to a manometer and an injection syringe
(yellow arrow). On the left, the zero-calibrated gallbladder is connected to a manometer
and a syringe filled with a brown-colored 2.0 wt%, 13–18 mPa∙ methylcellulose solution.
On the right side, the incubator was connected to a neutral pad and interfaced with
an electrosurgical generator.
EUS-GBD experiment using the current PS and a newly developed single-step PS system
for artificial and porcine gallbladders.Video 1
In addition, a residual porcine gallbladder obtained from meat processing was used
to examine bile leakage following drainage using a single-step PS delivery system.
Gallbladder drainage
Simulating EUS-GBD with the current PS system (Advanix J; Boston Scientific, Marlborough,
Massachusetts, United States) required multiple steps: puncture using a 19G lancet
needle, coiling with a 0.025-inch hydrophilic guidewire, removal of the needle, electrocautery
dilation (6F Cysto-Gastro-Sets; Endoflex GmbH, Voerde, Germany), delivery of a 7F/4-cm
double-pigtailed PS, and removal of the inner sheath [4]
[5]. The newly developed PS system (Japan Lifeline, Tokyo, Japan) was composed of a
tapered inner sheath with a 3F metal tip, which was equipped with electrocautery dilation.
The guidewire was passed through the inner sheath. A double-pigtail PS (7F/4 cm) connected
by a thread to the pusher sheath was mounted on the inner sheath. Withdrawal of the
inner sheath released the PS by detaching the thread from it. This system enabled
a single-step PS delivery without device exchange over the guidewire, and drainage
was performed in the following sequence: electrocautery puncture, guidewire advancement,
and PS deployment ([Fig. 2], [Video 1]). In both experiments, manual puncture-to-stent deployment was performed with as
vertical an orientation as possible against the walls.
Fig. 2 Newly developed PS system. The newly developed PS system includes a tapered inner
sheath with a 3F metal tip for electrocautery dilatation. The guidewire was passed
through the inner sheath. A double-pigtail PS (7F/4 cm) connected by a thread to the
pusher sheath was mounted on the inner sheath. The inner sheath disconnects the PS
from the pusher sheath. PS, plastic stent.
Outcome measures
Outcome measures included procedure time from puncture to PS deployment during gallbladder
drainage in the artificial gallbladder model and the ratio of the intra-gallbladder
pressure drop. The ratio of intra-gallbladder pressure drop was calculated as (ΔP/
pre-puncture pressure) × 100. ΔP was defined as the difference between the intra-gallbladder
pressure at the time of puncture and the pressure at stent deployment. This procedure
was repeated three times for both current and single-step PS systems. All procedures
were recorded and analyzed using video footage. Bile leakage was observed at the puncture
site. In addition, a video of bile leakage from the porcine gallbladder following
gallbladder drainage using the single-step PS delivery system was recorded.
Statistical analysis
Procedure time and ratio of intra-gallbladder pressure drop were expressed as means
with standard deviations (SDs). Statistical analyses were performed using Student’s
t-test with the IBM statistical package for social sciences statistics 28 (IBM Japan,
Ltd., Tokyo, Japan), and statistical significance was set at P < 0.05. Finally, a post-hoc power analysis was performed using G*Power software (https://www.psychologie.hhu.de/arbeitsgruppen/allgemeine-psychologie-und-arbeitspsychologie/gpower). We entered each mean and SD to calculate the effect size (Cohen's d). After that,
the statistical power (1–β error) was calculated using an α error of 0.05, a sample
size of three, and the obtained effect size.
Results
Time from puncture to PS deployment during gallbladder drainage
[Table 1] summarizes procedure time from puncture to PS deployment during gallbladder drainage
using an artificial gallbladder model. Mean duration times for the three attempts
were 2 min 59 s and 27 s for the current PS system and the newly developed PS system
groups, respectively (P < 0.001). The newly developed PS system was significantly more time efficient ([Fig. 3], [Fig. 4]) with a statistical power of 1.0.
Fig. 3 Time from puncture to PS deployment during gallbladder drainage. The newly developed
PS system saved significantly more time (mean, 27 s; SD, 3 s) than the current PS
system (mean, 2 min, 59 s; SD, 14 s). PS, plastic stent; SD, standard deviation.
Fig. 4 Intra-gallbladder pressure during gallbladder drainage. The newly developed PS system
quickly completes the drainage process, causing a slight decrease in the intra-gallbladder
pressure. In contrast, the current PS system takes longer, resulting in a sharp decrease
in pressure. Notably, the pressure drop accelerated further after dilation (around
the midpoint of the orange lines).
Table 1 Time from gallbladder puncture to PS deployment during gallbladder drainage.
|
PS system
|
Attempt
|
Procedure time
|
Mean (SD)
|
P value
|
|
PS, plastic stent; SD, standard deviation.
|
|
Current
|
1
|
3 min 16 s
|
2 min 59 s (14 s)
|
< 0.001
|
|
2
|
2 min 55 s
|
|
|
|
3
|
2 min 47 s
|
|
|
|
Newly developed
|
1
|
31 s
|
27 s (3 s)
|
|
|
2
|
25 s
|
|
|
|
3
|
24 s
|
|
|
Intra-gallbladder pressures during gallbladder drainage
[Table 2] summarizes intra-gallbladder pressures, including pre-puncture, pre-stent deployment,
ΔP, and pressure drop ratio during gallbladder drainage for the artificial gallbladder
model across three attempts. Mean pressure drop ratios were 86.7% and 7.6% for the
current PS system and newly developed PS system groups, respectively (P < 0.001). The newly developed PS system was significantly effective in maintaining
intra-gallbladder pressure ([Fig. 4], [Fig. 5]) with a statistical power of 0.99.
Fig. 5 Intra-gallbladder pressure drop ratio during gallbladder drainage. The newly developed
PS system (mean, 7.6%; SD, 4.4%) demonstrated a significantly lower intra-gallbladder
pressure drop ratio than the current PS system (mean, 86.7%; SD, 13.6%).
Table 2 Intra-gallbladder pressures during gallbladder drainage.
|
PS system
|
Attempt
|
Pre-puncture, kPa
|
Pre-deployment, kPa
|
ΔP, kPa
|
Pressure drop ratio, %
|
Mean, % (SD)
|
P value
|
|
PS, plastic stent; SD, standard deviation.
|
|
Current
|
1
|
1.97
|
0.56
|
1.41
|
71.6
|
86.7 (13.6)
|
< 0.001
|
|
2
|
1.76
|
0.04
|
1.72
|
97.7
|
|
|
|
3
|
0.88
|
0.08
|
0.80
|
90.9
|
|
|
|
Newly developed
|
1
|
1.58
|
1.38
|
0.20
|
12.7
|
7.6 (4.4)
|
|
|
2
|
0.87
|
0.83
|
0.04
|
4.6
|
|
|
|
3
|
0.89
|
0.84
|
0.05
|
5.6
|
|
|
Bile leakage from the puncture site on the gallbladder
During gallbladder drainage using the current PS system, the artificial gallbladder
shrinks due to continuous bile leakage from the puncture site because a multistep
procedure is required for stent deployment. As a result, the PS loses its drainage
effect ([Video 1]). In contrast, the artificial gallbladder retained its shape throughout gallbladder
drainage with the newly developed PS system, and bile was efficiently drained only
from the PS ([Video 1]). Similarly, during drainage of the porcine gallbladder using the newly developed
PS system, the gallbladder maintained its shape, and bile was gradually drained from
the PS ([Video 1]).
Discussion
In this study, we compared a single-step PS delivery system with the current PS system
in experimental EUS-GBD and observed the following outcomes. First, the single-step
PS delivery system significantly reduced procedure time, and second, it could potentially
minimize bile leakage during EUS-GBD. EUS-GBD with the current PS system requires
multiple steps after needle puncture for PS deployment, including needle exchange
with a dilator and exchange of the dilator with the PS. Therefore, as expected, the
single-step PS system saves time. As shown in Video 1, bile leakage occurred at the
gallbladder puncture site during device exchange when the current PS system was used
for drainage. In contrast, the single-step PS system prevented bile leakage from the
puncture site and maintained intra-gallbladder pressure until stent deployment. This
may prevent bile-induced peritonitis and ensure effective gallbladder drainage into
the alimentary tract through a stent after EUS-GBD. Recently, we demonstrated that
the inner sheath of a PS delivery system can aspirate and lavage infectious bile from
the gallbladder [6]. Therefore, this single-step PS system with gallbladder lavage may provide technical
and clinical success rates comparable to those of EUS-GBD with EC-LAMS for managing
patients with acute cholecystitis. However, risk of bile leakage remains despite the
potential of 7F PS to seal the puncture site following 3F electrocautery dilation.
The risk arises because excessive cauterization may enlarge the puncture site beyond
expectation. Therefore, electrocautery dilation should be completed as quickly as
possible to minimize risk of excessive electrocauterization. Optimal electrocautery
settings should be explored further in future animal studies.
Incidence of gallstone-induced acute cholecystitis is expected to increase with age
[7]. However, elderly patients with fragility are unsuitable candidates for surgery.
Thus, this single-step PS system may be suitable for long-term PS placement in the
elderly, because EC-LAMS may be costly and is associated with bleeding and buried
stent syndrome [8]. Furthermore, if a patient's performance status improves, elective laparoscopic
cholecystectomy may become feasible. Previous reports indicate that EUS-GBD with LAMS
does not prevent patients from eventually undergoing laparoscopic surgery [9]. However, pericholecystic adhesions and/or fistulas associated with LAMS have reportedly
hindered laparoscopic procedures and necessitated open surgery in some cases [10]. Consequently, feasibility of laparoscopic cholecystectomy following EUS-GBD with
LAMS remains under discussion. It is anticipated that affordable PSs may offer improved
biocompatibility compared with LAMS.
This experimental and preliminary study of a single-step PS system during simulation
of EUS-GBD used three artificial gallbladder models. Therefore, there is a need to
proceed to the next stage of experimental animal studies. The appropriate degree of
stent curling, adequate tip stiffness, and diameter of the electrocautery inner sheath,
sufficient pushability against the walls, and optimal settings of the electrosurgical
generator should be determined in the EUS-GBD animal model. Subsequently, Phase 1
clinical trials and additional studies should be conducted to obtain approval for
commercialization. In the future, we anticipate well-designed comparative studies
that will include EC-LAMS, current PS, and single-step PS systems.
Conclusions
The newly developed PS system saved significant time, maintained intra-gallbladder
pressure, and prevented bile leakage during the procedure when compared with the current
PS system.
Bibliographical Record
Tesshin Ban, Yoshimasa Kubota, Takashi Joh. Newly developed plastic stent delivery
system for endoscopic ultrasonography-guided gallbladder drainage: Experiments on
gallbladder models. Endosc Int Open 2025; 13: a27340383.
DOI: 10.1055/a-2734-0383
