Introduction
Endoscopic biliary stenting is considered the standard treatment for distal malignant
biliary obstruction (dMBO) [1 ]. Because sufficient and prolonged biliary drainage is essential to continue effective
palliative chemotherapy, self-expandable metal stents (SEMSs) are recommended because
of their durability and reduced needs for reintervention [2 ]
[3 ]. Fully covered SEMSs (FCSEMSs) have advantages over uncovered SEMSs (USEMSs) in
terms of the problem of in-stent restenosis due to tumor ingrowth or epithelial hyperplasia
[4 ]
[5 ]. FCSEMSs can also be easily removed and replaced after stent clogging during chemotherapy
[6 ]. However, the recent drastic improvement in the efficacy of chemotherapy warrants
further caution with regard to stent migration, which occurs more frequently with
FCSEMSs than with USEMSs.
Recently, we demonstrated the antimigratory efficacy of an internally anchored double-pigtail
plastic stent (DPPS) for dMBO in a randomized comparative study [7 ]. However, we noted some cases where the DPPS was removed along with the migrated
FSEMS, thereby requiring immediate reintervention, which may have occurred because
of the shared axis of the two stents in the stricture. To solve the problem caused
by the DPPS being coaxial to the FCSEMS, we have devised an alternative antimigration
technique. It was assumed that the placement of a 7-Fr DPPS side-by-side with the
FCSEMS would not only reduce the stent migration rate but also prolong stent patency
with an increased chance of the DPPS remaining in the original position, even after
migration of the FCSEMS. In this study, we aimed to evaluate the effect on increasing
stent patency of a novel technique of externally anchoring a DPPS to an FCSEMS in
dMBOs.
Methods
Subjects and study design
We conducted a multicenter retrospective study to evaluate the efficacy and safety
of an externally anchored plastic stent (EPS) with an FCSEMS. Patients who underwent
endoscopic retrograde biliary drainage (ERBD) for dMBO at two tertiary care institutions
between March 2017 and December 2020 were included. Those patients with previous bile
duct surgery, or a stricture of the hilar or intrahepatic ducts were excluded. The
cutoff date for data analysis was 15 November 2021. The final data included 185 dMBO
patients, with 65 having an FCSEMS alone and 120 having an FCSEMS with an EPS.
This study was approved by the Institutional Review Boards (H-1911–088–1079, Seoul
National University Hospital [SNUH]; NCC 2020–0118, National Cancer Center [NCC],
South Korea).
Procedure
All endoscopies were carried out by qualified endoscopists who had performed more
than 1000 endoscopic retrograde cholangiopancreatography (ERCP) procedures. After
the site of the suspicious malignant biliary stricture had been visualized on a cholangiogram,
an FCSEMS was deployed across the stricture. Two types of FCSEMS design were used,
with either a nitinol hook and cross wire structure with a polygonal mesh surface
(Bonastent; Standard Sci Tech, Seoul, Korea) or a nitinol wire with a silicone-covered
membrane (Aristent; Daewoong, Seoul, Korea).
For the subjects in the EPS group, two guidewires were placed after selective biliary
cannulation. A 7-Fr DPPS (Zimmon Biliary Stent; Cook Medical, Bloomington, Indiana,
USA) was placed first, then an FCSEMS was deployed side-by-side ([Fig. 1 ]). The proximal tip of the DPPS was placed over the FCSEMS, and intrahepatic anchoring
of a DPPS longer than 10 cm was preferred, if possible, to ensure that the proximal
end was sufficiently anchored in the intrahepatic bile duct to reduce dislodgement
of the DPPS from the stricture site [7 ].
Fig. 1 Fluoroscopic (upper row) and endoscopic images (lower row) during the placement of
a fully covered self-expandable metal stent (FCSEMS) with external plastic stent anchoring
showing: a–d two guidewires placed in the bile ducts; e, f a double-pigtail plastic stent placed first in the bile duct; g, h an FCSEMS deployed side by side.
The type and length of the FCSEMS was determined at the discretion of the endoscopist,
with consideration of the length of the biliary stricture. The stent deployment time
was measured as the time between the initial placement of the guidewire into the intrahepatic
bile duct and the deployment of the FCSEMS with/without an EPS.
Outcomes and definitions
The primary outcome was the comparative efficacy of an EPS-anchored FCSEMS to an FCSEMS
alone in terms of stent patency. Stent patency was defined as the time between stent
placement and stent revision for any stent dysfunction attributable to migration or
occlusion, or other causes requiring reintervention [2 ]
[7 ]. Stent migration and occlusion were investigated using laboratory findings, abdominal
radiographs, or computed tomography images during clinical follow-up.
Technical success was defined as the successful placement of an FCSEMS, with/without
an EPS, in the intended location without disturbing the passage of bile/contrast dye.
Clinical success was defined as a decrease in the total bilirubin level to less than
half of the pretreatment value within the first month after ERBD. Adverse events followed
the American Society for Gastrointestinal Endoscopy (ASGE) lexicon [8 ].
Statistical analysis
Continuous variables were presented as medians and ranges, and categorical variables
were expressed as percentages. To compare the two groups, the Mann–Whitney U test was used for continuous variables and the chi-squared test or Fisher’s exact
test was used for categorical variables. Proportions are presented with exact confidence
intervals owing to the uneven sample sizes of the two groups. The probability of stent
patency was estimated using the Kaplan–Meier method and compared with a log-rank test.
Patients who underwent surgery or died prior to the event were censored.
Univariable analysis was performed to identify the independent risk factors for stent
patency. Variables with P values < 0.2 were included in the follow-up multivariable Cox proportional hazard
regression model. A hazard ratio (HR) and 95 %CIs were calculated. P values < 0.05 were considered statistically significant.
Statistical analyses were conducted with SPSS version 25.0 (IBM SPSS Inc., Chicago,
Illinois, USA) and R version 4.2.1 (R foundation for Statistical Computing, Vienna,
Austria).
Results
Study population
The baseline characteristics of 185 subjects (SNUH 107, NCC 78; median age 66; 76
women) are summarized in [Table 1 ]. The majority of patients had pancreatic cancer, 98 had metastatic disease at the
time of the procedure. No significant difference was found between the two study groups,
except for cystic duct visualization on cholangiogram. The cystic duct was less frequently
visualized in the FCSEMS with an EPS group than in the FCSEMS alone group (P < 0.01).
Table 1
Baseline characteristics of the 185 patients with distal malignant biliary obstruction
who were treated with insertion of a fully covered self-expandable metal stent (FCSEMS)
with or without an externally anchored plastic stent (EPS).
Variable
FCSEMS + EPS (n = 120)
FCSEMS alone (n = 65)
P value
Patient-related factors
Age, median (range), years
66.0 (39–90)
66.0 (33–88)
0.46
Female, n (%)
51 (42.5)
25 (38.5)
0.71
Previous ERBD, n (%)
47 (39.2)
25 (38.5)
> 0.99
Previous PTBD, n (%)
9 (7.5)
5 (7.7)
> 0.99
Cholecystectomy state, n (%)
116 (96.7)
61 (93.8)
0.46
Total bilirubin, median (range), mg/dL
4.0 (0.2–32)
4.0 (0.3–26)
0.51
Cancer-related factors
Tumor size, median (range), mm
30.0 (10–67)
28.0 (2–90)
0.12
Cancer type, n (%)
87 (72.5)
52 (80.0)
0.31
16 (13.3)
4 (6.2)
17 (14.2)
9 (13.8)
Metastatic disease, n (%)
66 (55.0)
32 (49.2)
0.55
25 (20.8)
12 (18.5)
15 (12.5)
8 (12.3)
Anticancer treatment, n (%)
106 (88.3)
55 (84.6)
0.63
Subsequent surgery, n (%)
15 (12.5)
12 (18.5)
0.27
Procedure-related factors
Endoscopic sphincterotomy, n (%)
76 (63.3)
40 (61.5)
0.94
Cystic duct visible on cholangiogram, n (%)
54 (45.0)
45 (69.2)
< 0.01
ERBD, endoscopic retrograde biliary drainage; PTBD, percutaneous transhepatic biliary
drainage.
Stent placement
The results of stent placement are summarized in Table 1 s . Technical success was achieved in all subjects in both groups. The clinical success
rates were 95.8 % and 93.8 % in the FCSEMS with an EPS and FCSEMS only groups, respectively.
The nine patients who did not achieve clinical success showed clinical improvement
after stent revision (n = 7) or percutaneous biliary drainage (n = 2).
The stent deployment time was significantly longer in the FCSEMS with an EPS group
than in the FCSEMS only group. The types of FCSEMS used were marginally different
between the two groups, while they were markedly different between the institutions.
An FCSEMS of 5 or 6 cm in length was used most frequently for dMBO, In the FCSEMS
with an EPS group, 6-cm (28.3 %) or 12-cm DPPSs (26.7 %) were used most frequently.
Study outcomes
Treatment outcomes are presented in [Table 2 ]. The median stent patency was significantly longer in the FCSEMS with an EPS group
(342 days, 95 %CI 237–386 days) compared with the FCSEMS only group (240 days, 95 %CI
127–NA days; P = 0.04) during a median follow-up of 218 days and 243 days, respectively ([Fig. 2 ]).
Table 2
Overall outcomes of endoscopic biliary drainage with a fully covered self-expandable
metal stent (FCSEMS) with/without an externally anchored plastic stent (EPS).
Variable
FCSEMS + EPS (n = 120)
FCSEMS alone (n = 65)
P value
Stent patency, median (95 %CI), days
342 (237–386)
240 (127–NA)
0.04
Stent migration, n (%)
13 (10.8)
18 (27.7)
0.01
1 (0.8)
4 (6.2)
12 (10.0)
14 (21.5)
Stent occlusion, n (%)
32 (26.7)
14 (21.5)
0.55
15 (12.5)
10 (15.4)
17 (14.2)
7 (10.8)
Reason for reintervention, n (%)
43 (35.8)
27 (41.5)
0.55
10 (8.3)
11 (16.9)
31 (25.8)
12 (18.5)
2 (1.7)
4 (6.2)
Adverse event, n (%)
26 (21.7)
11 (16.9)
0.56
8 (6.7)
4 (6.2)
8 (6.7)
4 (6.2)
6 (5.0)
2 (3.1)
5 (4.2)
1 (1.5)
1 (0.8)
0 (0.0)
Fig. 2 Cumulative rates of stent patency for the fully covered self-expandable metal stent
(FCSEMS) with an externally anchored plastic stent (EPS) group and the FCSEMS alone
group.
As of the cutoff date, the stent migration rate was significantly lower for the patients
with an EPS (10.8 %, 95 %CI 5.9 %–17.8 %) than for those with an FCSEMS only (27.7 %,
95 %CI 17.3 %–40.2 %; P = 0.01). Among 13 patients in the FCSEMS with an EPS group whose stents migrated,
10 patients had the DPPS remaining in the original position. Stent occlusion occurred
in 26.7 % (95 %CI 19.0 %–35.5 %) in the FCSEMS with an EPS group and 21.5 % (95 %CI
12.3 %–33.5 %) in the FCSEMS only group, and the mechanism of occlusion did not differ
between the two groups. Stent revision due to migration was performed more frequently
in the FCSEMS alone group (17 %, 95 %CI 8.8 %–28.3 %) than in the FCSEMS with an EPS
group (8 %, 95 %CI 4.1 %–14.8 %), but this trend was not statistically significant
(P = 0.09). With regard to adverse events, there were no significant differences between
the two groups, and no procedure-related mortality occurred.
The risk factors associated with stent dysfunction were examined using Cox regression
models (Table 2 s ). The cystic duct being visible on cholangiogram and the type of FCSEMS, which were
significantly different between the two groups, were not associated with stent patency.
Sex and placement of an EPS were significantly associated with stent patency in multivariable
analyses.
Discussion
The present study demonstrated that a novel technique of anchoring an EPS to a FCSEMS
can significantly prolong stent patency compared with the stand-alone placement of
an FCSEMS. Use of an EPS may be associated with a significantly reduced chance of
stent migration and decreased need for reintervention for stent migration.
Although a significantly prolonged patency of FCSEMSs was reported in a meta-analysis,
one major concern with FCSEMSs is their higher likelihood of stent migration than
USEMSs [9 ]. Several prior studies have shown the antimigratory properties of an anchoring flap,
partially covered design, or novel structure of the stent [10 ]
[11 ]
[12 ]; however, an increased chance of mucosal injury and potential bleeding during removal,
or the unique design itself may be important limitations to be considered. On the
other hand, the addition of an EPS to an FCSEMS appears to be a simple, safe, and
effective method to confer an antimigration effect.
Recently, we reported that anchoring a 7-Fr DPPS inside an FCSEMS prevented stent
migration and prolonged stent patency compared with an FCSEMS alone in a randomized
controlled study [7 ]. In the present study, a DPPS was externally anchored first, then an FCSEMS was
deployed side-by-side. The antimigration efficacy may not be different between the
two techniques, 14 % for internally anchoring DPPS and 7 % for an EPS [13 ]. One notable advantage of an EPS is the retention of biliary drainage by a DPPS
remaining in the original position even after migration of the FCSEMS. We observed
a trend of less reinterventions for stent migration in the FCSEMS with an EPS group
than in the FCSEMS only group. The increased time for the anchoring with an EPS may
be negligible when considering the total procedure time. Further studies are warranted
to directly compare the cost-effectiveness of the two methods.
The migration rate of FCSEMSs has been reported to be between 5 % to 37 % [2 ]. In this study, the migration rate was 27.7 % in the FCSEMS only group, which is
higher than in previous studies. The high radial force is thought to be an antimigration
property of FCSEMSs [6 ]
[14 ]. The radial force of the FCSEMSs used in the present study is lower than other commercially
available FCSEMSs, which may contribute to a higher migration rate [7 ]. Chemotherapy can also affect stent migration and patency through tumor shrinkage
in MBO [6 ]. Meanwhile, a Japanese multicenter study reported that chemotherapy increased recurrent
biliary obstruction caused by biliary sludge formation and cholangitis [15 ]. In our univariate analysis, the use of chemotherapy was not associated with stent
patency. The variety of cancer types and chemotherapy regimens included in the study
may have affected the effect of chemotherapy on stent patency. In our study, the placement
of an EPS, through its antimigration effect, was the only correctable factor in prolonged
stent patency.
Some limitations of our study arise from its retrospective design. The rate of technical
success might be overestimated owing to incomplete recording of the detail in the
procedure record. The fact that subjects were included at two different centers might
be a confounding factor. In real clinical practice, the instrument and techniques
used during the endoscopic procedure differed between the institutions. All endoscopists
involved in this study were experts in ERCP, with experience of more than 1000 procedures,
so technical variations between the institutions would be negligible. Although the
type of FCSEMS used at each institution was different in this study, it did not affect
the stent patency. Further studies to evaluate the efficacy of an EPS with various
types of FCSEMS are warranted for its generalizability in dMBO.
In conclusion, our findings suggest that the external anchoring of a DPPS to an FCSEMS
is a simple and effective method to prevent stent migration and prolong stent patency,
without increasing the chance of adverse events. We did not include patients who received
a USEMS in the present study, which warrants the results from our ongoing clinical
trial comparing the use of an FCSEMS with an EPS and a USEMS (NCT05220475).
