Introduction
The main methods of biliary drainage to treat distal malignant biliary obstruction
(DMBO) are endoscopic retrograde cholangiopancreatography (ERCP). A self-expandable
metallic stent (SEMS) is recommended for both preoperative and non-resection cases
[1]
[2]
[3]
[4]
[5]
[6] for DMBO, with the European Society of Gastrointestinal Endoscopy recommending the
use of 10-mm-diameter SEMSs for DMBO [1]. A SEMS has the advantage of a longer time to recurrent biliary obstruction (TRBO)
compared to a plastic stent (PS). However, the expansion force of SEMSs leads to stent-related
adverse events (AEs), such as pancreatitis and cholecystitis [2]
[4]
[6]
[7]
[8]
[9]. The prevalence of stent-related AEs with SEMSs has been reported to be 1.5 % to
8.8 % for pancreatitis and 1.5 % to 10.0 % for cholecystitis [10]
[11]
[12]
[13]. The major problem is that these stent-related AEs may delay or stop treatment of
the primary disease. In general, TRBO is thought to increase in proportion to the
diameter of the stent [14]
[15]. However, a larger inner stent diameter can cause overexpansion of the bile duct,
which may lead to an increase in stent-related AEs, such as cholecystitis and pancreatitis
[16]. In other words, there is a trade-off between TRBO and stent-related AEs, and the
optimal stent diameter for DMBO is still debated.
Several studies have reported on TRBO and stent-related AEs based on stent diameter.
The following outcomes have been reported for 10-mm-diameter SEMS: TRBO, 240 to 385
days [10]
[16]
[17], stent-related AEs, 7.2 % to 20.0 % [2]
[4]
[5]
[10]
[16]
[17]
[18]. The results for the 12-mm-diameter FCSEMS [14] and 14-mm-diameter uncovered SEMS [19] showed median TRBOs of 184 and 190 days with rates of stent-related AEs of 21.1 %
and 28.9 %, respectively. In previous reports, there was no difference in TRBO between
a larger-diameter stent and 10-mm-diameter FCSEMS, and stent-related AEs were more
common with larger diameters. However, a prospective study compared the outcomes of
8-mm- and 10-mm-diameter FCSEMS with the aim of reducing AEs [16]. The results showed no significant difference in median TRBO between the 8-mm and
10-mm groups (275 and 293 days, respectively; P = 0.97), and there was no significant difference in the incidences of pancreatitis
(4.1 and 10.0 %, respectively; P = 0.10) and cholecystitis (6.0 and 10.2 %, respectively; P = 0.28). In other words, the non-inferiority of the 8-mm-diameter FCSEMS compared
to the 10-mm-diameter FCSEMS in TRBO was demonstrated, and there was no significant
difference between the two groups in terms of incident cases.
In the present study, the usefulness of the 6-mm-diameter FCSEMS was compared retrospectively
with that of the 10-mm-diameter FCSEMS, the standard treatment. To the best of our
knowledge, there are no previous reports comparing the results of the 6-mm and 10-mm-diameter
FCSEMS for DMBO.
Patients and methods
Ethics statements
This study was conducted in accordance with the principles of the Declaration of Helsinki
and approved by the Institutional Review Board of the National Cancer Center Hospital,
Japan (2018–149).
Study design and patients
This study was a single-center, retrospective study. Cases of FCSEMS deployed in a
transpapillary fashion initially for DMBO at our hospital between October 2017 and
December 2021 were retrieved from the ERCP database. The main eligibility criteria
for this study were as follows: (1) DMBO; (2) initial FCSEMS deployment (cases where
an FCSEMS was deployed for initial drainage or after PS or endoscopic nasobiliary
drainage); and (3) FCSEMS placement across the papilla. The exclusion criteria were
as follows: (1) cases with an 8-mm-diameter SEMS; (2) cases with FCSEMS placement
above the papilla; and (3) cases with an additional PS within the FCSEMS.
Procedure
We pre-evaluated bile duct confluence morphology using computed tomography (CT) and
magnetic resonance cholangiopancreatography. The length of bile duct stenosis was
measured using the catheter or guidewire to determine the length of the FCSEMS. Regarding
the choice of stent diameter, a 10-mm-diameter stent was mainly used until August
2019, and a 6-mm-diameter stent ([Fig. 1]) was primarily used after September 2019. Both the 6-mm and the 10-mm-diameter stents
used were braided-type FCSEMSs. The same diameter of SEMS was selected for each period
strategically, and not at random. In this study, all cases underwent transpapillary
stenting by the side-view endoscope; hence, no cases of metallic stenting for Billroth
II or Roux-en-Y reconstruction were included.
Fig. 1 The 6-mm-diameter, fully-covered, self-expandable metallic stent (HANAROSTENT; Boston
Scientific, Tokyo, Japan) placement for distal biliary obstruction under endoscopic
retrograde cholangiopancreatography; a fluoroscopic X-ray imaging; and b endoscopic imaging.
Definitions
The endpoints were the clinical success rate, procedure time, percentage of AEs, cumulative
incidence of recurrent biliary obstruction (RBO), factors involved in stent-related
AEs (pancreatitis and cholecystitis), and factors involved in RBO. These endpoints
are defined as follows in accordance with the Tokyo criteria 2014 [20]. The clinical success rate was defined as the percentage of patients with total
bilirubin normalization or reduction by ≥ 50.0 % within 2 weeks of stent placement.
RBO was defined as stent occlusion and migration (only if bile duct obstruction symptoms
were present). TRBO was defined as the period between stent placement and RBO (death
was censored). Pancreatitis was defined as cases with (1) new or worsened abdominal
pain; (2) new or prolonged hospitalization for at least 2 days; and (3) serum amylase ≥ 3-fold
the upper limit of normal, measured > 24 hours after procedure. Cholecystitis was
defined as fever > 38 °C or right upper abdominal pain occurring with supportive imaging
study findings. The procedure time was defined as the time from the frontal view of
the papilla to stent deployment. The bile duct stenosis length, pancreatic duct dilation,
and parenchyma length were measured using CT.
Statistical analysis
Continuous variables, such as age and procedure time, are presented as medians and
interquartile ranges (IQR), and the Mann-Whitney U test was used to analyze these
data. Categorical variables are presented as ratios and were analyzed using the Fischer
exact test. Logistic regression analysis was used to analyze factors involved in pancreatitis
and cholecystitis. Cumulative incidence of RBO was calculated, treating death or surgery
as a competing risk, and compared by the Gray’s test. Fine-Gray Sub-distribution hazard
regression analysis was used to analyze factors involved in RBO. In Fine-Gray sub-distribution
hazard regression (SHR) and logistic regression analyzes, the medians of all continuous
variables were changed to binary variables as the reference value in the analysis.
In logistic regression analyzes for AEs, factors with P < 0.20 were included in multivariate analysis. P < 0.05 was considered statistically significant. Statistical analysis was performed
using R software, version 4.2.1 (R Core Development Team: http://www.r-project.org)
and SPSS Statistics (version 23; IBM Corp, Armonk, New York, United States).
Results
Patient baseline characteristics
Of 324 cases of initial FCSEMS placement for DMBO, 243 cases were eligible ([Fig. 2]). Among the 243 eligible cases, there were 76 and 167 cases in the 10-mm and 6-mm
groups, respectively. There were more resectable/borderline resectable pancreatic
cancers (P < 0.01) and higher total bilirubin values (P < 0.01) in the 6-mm group than in the 10-mm group. There were no significant differences
in cases of biliary drainage before SEMS placement (P = 0.68) or cases of orifice of the cystic duct invasion (P = 0.38) between the groups ([Table 1]).
Fig. 2 Flowchart of patients in the current study showing results of inclusion and details
of the 10-mm and 6-mm groups.
Table 1
Patient baseline characteristics.
|
|
FCSEMS
|
|
|
Patient characteristics
|
Total
n = 243
|
10-mm
n = 76
|
6-mm
n = 167
|
P value
|
|
Age, years
|
68 (57–75)
|
68 (57–72)
|
68 (58–75)
|
0.41
|
|
Female sex, n (%)
|
104 (42.8)
|
34 (44.7)
|
70 (41.9)
|
0.78
|
|
Causes of distal biliary obstruction, n (%)
|
|
Pancreatic cancer
|
186 (76.5)
|
58 (76.3)
|
128 (76.6)
|
0.87
|
|
R/BR
|
60 (24.7)
|
8 (10.5)
|
52 (31.1)
|
< 0.01
|
|
UR
|
126 (51.9)
|
50 (65.8)
|
76 (45.5)
|
< 0.01
|
|
Other cancers
|
57 (23.5)
|
18 (23.7)
|
39 (23.4)
|
0.87
|
|
Previous biliary drainage, n (%)
|
106 (43.6)
|
35 (46.1)
|
71 (42.5)
|
0.68
|
|
Previous cholecystectomy, n (%)
|
17 (7.0)
|
5 (6.6)
|
12 (7.2)
|
1.00
|
|
Laboratory data before ERCP
|
|
Total bilirubin, mg/dL
|
2.3 (1.2–6.0)
|
1.7 (1.0–3.9)
|
2.8 (1.3–6.8)
|
< 0.01
|
|
Amylase, U/L
|
68.0 (44.5–111.0)
|
112.0 (58.0–308.0)
|
96.0 (54.0–196.8)
|
0.18
|
|
Main pancreatic duct opacification, n (%)
|
111 (45.7)
|
25 (32.9)
|
86 (51.5)
|
< 0.01
|
|
Diameter of each duct, mm
|
|
Common bile duct
|
12.0 (9.0–14.9)
|
11.8 (8.8–13.5)
|
12.5 (9.3–15.7)
|
0.29
|
|
Main pancreatic duct
|
4.7 (2.8–6.6)
|
4.9 (3.2–7.0)
|
4.4 (2.6–6.2)
|
0.25
|
|
Diameter of the pancreatic body, mm
|
16.5 (13.0–20.5)
|
17.2 (13.0–20.8)
|
16.0 (13.1–20.1)
|
0.52
|
|
Length of the biliary stricture, mm
|
27.0 (23.7–31.0)
|
27.0 (20.0–33.0)
|
26.5 (24.0–34.3)
|
0.77
|
|
Duodenal stent[1], n (%)
|
6 (2.5)
|
2 (2.6)
|
4 (2.4)
|
1.00
|
|
Site of tumor invasion, n (%)
|
|
OCD
|
27 (11.1)
|
6 (7.9)
|
21 (12.6)
|
0.38
|
|
Duodenal papilla
|
16 (6.6)
|
5 (6.6)
|
11 (6.6)
|
1.00
|
|
Duodenum[2]
|
10 (4.1)
|
6 (7.9)
|
4 (2.4)
|
0.08
|
|
Therapy for malignancy, n (%)
|
|
Chemotherapy[3]
|
189 (77.8)
|
64 (84.2)
|
125 (71.0)
|
0.13
|
|
Best supportive care
|
17 (7.0)
|
6 (7.9)
|
11 (6.6)
|
0.79
|
|
Observation period, day
|
79 (35–166)
|
118 (39–219)
|
70 (34–132)
|
0.03
|
Continuous variables are expressed as median (interquartile range).
R, resectable; BR, borderline resectable; UR, unresectable; ERCP, endoscopic retrograde
cholangiopancreatography; OCD, orifice of the cystic duct; FCSEMS, fully covered self-expandable
metallic stent.
1 Duodenal stent cases were limited to those with stent placement within the TRBO (median)
period calculated for all cases.
2 Excluding cases of duodenal papillary infiltration.
3 Excluding preoperative chemotherapy cases that underwent surgery.
Procedure details
Cases of nonsteroidal anti-inflammatory drugs before ERCP and stent length as long
as 8 cm were significantly more common in the 6-mm group than in the 10-mm group. There
were no significant differences in the method of bile duct canulation, cases of pancreatic
duct stenting, and procedure time between the groups ([Table 2]).
Table 2
Procedure details.
|
|
FCSEMS
|
|
|
Procedure details
|
Total
n = 243
|
10-mm
n = 76
|
6-mm
n = 167
|
P value
|
|
NSAIDs used before ERCP, n (%)
|
203 (83.5)
|
51 (67.1)
|
152 (91.0)
|
< 0.01
|
|
Canulation method, n (%)
|
|
|
193 (79.4)
|
60 (78.9)
|
133 (79.6)
|
0.98
|
|
|
39 (16.0)
|
13 (17.1)
|
26 (15.6)
|
|
|
|
8 (3.3)
|
2 (2.6)
|
6 (3.6)
|
|
|
|
3 (1.2)
|
1 (1.3)
|
2 (1.2)
|
|
|
|
238 (97.9)
|
75 (98.7)
|
163 (97.6)
|
1.00
|
|
|
72 (29.6)
|
20 (26.3)
|
52 (31.1)
|
0.55
|
|
|
16 (6.6)
|
3 (3.9)
|
13 (7.8)
|
0.40
|
|
|
27 (17–36)
|
23.5 (17–34)
|
27 (20–38)
|
0.11
|
|
FCSEMs length, n (%)
|
|
|
59 (24.3)
|
52 (68.4)
|
7 (4.2)
|
< 0.01
|
|
|
167 (68.7)
|
24 (31.6)
|
143 (85.6)
|
< 0.01
|
|
|
16 (6.6)
|
0 (0.0)
|
16 (9.6)
|
< 0.01
|
|
|
1 (0.4)
|
0 (0.0)
|
1 (0.6)
|
1.00
|
Continuous variables are expressed as median (interquartile range).
NSAIDs, nonsteroidal anti-inflammatory drugs; ERCP, endoscopic retrograde cholangiopancreatography;
EST, endoscopic sphincterotomies; FCSEMS, fully-covered self-expandable metallic stent.
Clinical outcomes
Clinical success rates were 94.7 % and 92.8 % (P = 0.78) in the 10-mm and 6-mm groups, respectively, with no significant difference.
The median observation period (IQR) was 233 days (91–438 days), and RBO occurred in
74 patients (30.4 %) during the observation period (38.2 % and 26.9 % in the 10-mm
and 6-mm groups, respectively; P = 0.10). Regarding details of RBO, rates of migration and obstruction cases were
7.9 % and 14.4 % (P = 0.10) and 30.3 % and 12.6 % (P < 0.01) in the 10-mm and 6-mm groups, respectively ([Table 3]). Cumulative incidence of RBO in all cases was 14.5 % versus 17.0 %, 26.3 % versus
26.5 %, and 49.6 % versus 38.0 % at 3, 6, and 12 months (P = 0.46 by Gray’s test) in the 10-mm versus 6-mm groups, respectively ([Fig. 3]). Adverse events occurred in 43 cases (17.7 %) overall, and the incidence of AEs
was significantly less in the 6-mm group than in the 10-mm group (11.4 % versus 31.6 %;
P < 0.01). Pancreatitis occurred in 10.5 % and 3.6 % of patients and cholecystitis
occurred in 11.8 % and 3.0 % of patients in the 10-mm and 6-mm groups, respectively;
both AEs occurred significantly less in the 6-mm group than in the 10-mm group (P = 0.04 and P = 0.03, respectively). Other AEs were not significantly different between the groups
([Table 3]). In summary, the 6-mm group showed no significant difference in the cumulative
incidence of RBO of all cases and significantly fewer stent-related AEs compared to
the 10-mm group.
Table 3
Clinical outcomes in all patients.
|
|
FCSEMS
|
|
|
Clinical outcomes
|
Total
n = 243
|
10-mm
n = 76
|
6-mm
n = 167
|
P value
|
|
Clinical success, n (%)
|
227 (93.4)
|
72 (94.7)
|
155 (92.8)
|
0.78
|
|
RBO, n (%)
|
74 (30.4)
|
29 (38.2)
|
45 (26.9)
|
0.10
|
|
Migration
|
30 (12.3)
|
6 (7.9)
|
24 (14.4)
|
0.10
|
|
Obstruction
|
44 (18.1)
|
23 (30.3)
|
21 (12.6)
|
< 0.01
|
|
Debris
|
28 (11.5)
|
14 (18.4)
|
14 (8.4)
|
0.03
|
|
Food impaction
|
7 (2.9)
|
2 (2.6)
|
5 (3.0)
|
1.00
|
|
Kinking
|
1 (0.4)
|
0 (0.0)
|
1 (0.6)
|
1.00
|
|
Overgrowth
|
7 (2.9)
|
6 (7.9)
|
1 (0.6)
|
< 0.01
|
|
Hyperplasia
|
1 (0.4)
|
1 (1.3)
|
0 (0.0)
|
1.00
|
|
Total adverse events, n (%)
|
43 (17.7)
|
24 (31.6)
|
19 (11.4)
|
< 0.01
|
|
Pancreatitis
|
14 (5.8)
|
8 (10.5)
|
6 (3.6)
|
0.04
|
|
Cholecystitis
|
14 (5.8)
|
9 (11.8)
|
5 (3.0)
|
0.03
|
|
Non-occlusion cholangitis
|
10 (4.1)
|
4 (5.3)
|
6 (3.6)
|
1.00
|
|
Liver abscess
|
5 (2.1)
|
3 (3.9)
|
2 (1.2)
|
1.00
|
RBO, recurrent biliary obstruction; FCSEMS, fully covered self-expandable metallic
stent.
Fig. 3 Cumulative incidence of recurrent biliary obstruction in all cases in the 10-and
6-mm groups was analyzed, treating surgery and death as a competing risk, and compared
with the Gray’s test. There was no significant difference in the cumulative incidence
of RBO between either group (P = 0.46). CI, confidence interval.
In patients with preoperative pancreatic cancer (resectable/borderline resectable
cases), the incidence of total AEs was 37.5 % and 7.7 % in the 10-mm and 6-mm groups,
respectively, and the incidence was significantly lower in the 6-mm group than in
the 10-mm group (P = 0.04). Pancreatitis occurred in 25.0 % and 3.8 % of patients (P = 0.08) and cholecystitis occurred in 12.5 % and 0.0 % of patients (P = 0.13) in the 10-mm and 6-mm groups, respectively. The median time to surgery was
83 days (IQR 42–142 days), with no significant difference between the groups. The
non-RBO rates within this period were 75.0 % and 80.8 % (P = 0.66) in the 10-mm and 6-mm groups, respectively, with no significant difference
between the groups ([Table 4]). Furthermore, in unresectable cases (68 and 115 in the 10-mm versus 6-mm groups,
respectively), the cumulative incidence of RBO was 14.5 % versus 19.2 %, 26.3 % versus
31.7 %, and 52.4 % versus 43.5 % at 3, 6, and 12 months (P = 0.96 by Gray’s test) ([Fig. 4]).
Table 4
Clinical outcomes in patients with preoperative pancreatic cancer (resectable and
borderline-resectable cases).
|
|
FCSEMS
|
|
|
Clinical outcomes
|
Total
n = 60
|
10-mm
n = 8
|
6-mm
n = 52
|
P value
|
|
Surgeries performed, n (%)
|
37 (61.7)
|
6 (75.0)
|
31 (59.6)
|
0.70
|
|
Time to surgery, day
|
83 (42–142)
|
83 (41–152)
|
83 (50–134)
|
0.94
|
|
Non-RBO rate, n (%)
|
48 (80.0)
|
6 (75.0)
|
42 (80.8)
|
0.70
|
|
Total adverse events, n (%)
|
7 (11.7)
|
3 (37.5)
|
4 (7.7)
|
0.04
|
|
Pancreatitis
|
4 (6.7)
|
2 (25.0)
|
2 (3.8)
|
0.08
|
|
Cholecystitis
|
1 (1.7)
|
1 (12.5)
|
0 (0.0)
|
0.13
|
|
Non-occlusion cholangitis
|
2 (3.3)
|
0 (0.0)
|
2 (3.8)
|
1.00
|
Continuous variables are expressed as median (interquartile range).
RBO, recurrent biliary obstruction; FCSEMS, fully covered self-expandable metallic
stent.
Fig. 4 Cumulative incidence of recurrent biliary obstruction of unresectable cases in 10-and
6-mm groups was analyzed, treating surgery and death as a competing risk and compared
with the Gray’s test. There was no significant difference in the cumulative incidence
of RBO between either group (P = 0.96). CI, confidence interval.
Risk factors for total adverse events, pancreatitis, cholecystitis, and RBO
Results of univariate and multivariate analyses of risk factors involved in total
AEs, pancreatitis, and cholecystitis are shown in [Table 5]. For total AEs, 6-mm FCSEMS (odds ratio [OR], 0.18; 95 % confidence interval [CI],
0.07–0.46; P < 0.01) was extracted as an independent risk-reducing factor. For pancreatitis, 6-mm
FCSEMS (OR, 0.30; 95 % CI, 0.10–0.96; P = 0.04) was similarly extracted as an independent risk-reducing factor. However,
the use of nonsteroidal anti-inflammatory drugs was not extracted as a risk-reducing
factor. For cholecystitis, 6-mm FCSEMS (OR, 0.13; 95 % CI, 0.03–0.61; P = 0.01) was an independent risk-reducing factor, and tumor invasion to the orifice
of the cystic duct (OR, 9.90; 95 % CI, 2.62–37.3; P < 0.01) was extracted as an independent risk factor. Thus, 6-mm FCSEMS was extracted
as an independent risk-reducing factor for total AEs, pancreatitis, and cholecystitis.
The results of univariate and multivariate analyses of factors involved in RBO are
shown in [Table 6]. Resectable/borderline resectable cases were extracted as an independent risk-reducing
factor for RBO (SHR, 2.59; 95 % CI, 1.26–5.32; P < 0.01). However, 6-mm FCSEMS was not extracted as a risk factor for RBO (SHR, 1.30;
95 % CI, 0.48-3.50; P = 0.61).
Table 5
Univariate and multivariate analyses for risk factors for adverse events.
|
|
|
|
Univariate
|
Multivariate
|
|
Risk factors
|
|
n
|
Event
|
OR
|
95 % CI
|
P value
|
OR
|
95 % CI
|
P value
|
|
Total adverse events
|
|
Pancreatic cancer
|
Yes
|
186
|
34
|
1.23
|
0.55–2.73
|
0.62
|
|
|
|
|
Previous biliary drainage
|
Yes
|
106
|
20
|
1.15
|
0.60–2.23
|
0.67
|
|
|
|
|
NSAIDs use before ERCP
|
Yes
|
203
|
34
|
0.69
|
0.30–1.60
|
0.39
|
|
|
|
|
Stent length
|
≥ 8 cm
|
184
|
28
|
0.53
|
0.26–1.07
|
0.08
|
1.69
|
0.65–4.43
|
0.28
|
|
Stent diameter
|
6 mm
|
167
|
19
|
0.28
|
0.14–0.55
|
< 0.01
|
0.18
|
0.07–0.46
|
< 0.01
|
|
Pancreatitis
|
|
Female sex
|
Yes
|
104
|
5
|
0.73
|
0.24–2.24
|
0.58
|
|
|
|
|
Pancreatic cancer
|
Yes
|
186
|
10
|
0.77
|
0.23–2.56
|
0.67
|
|
|
|
|
Previous biliary drainage
|
Yes
|
106
|
4
|
0.50
|
0.15–1.63
|
0.25
|
|
|
|
|
Diameter of the pancreatic body
|
≥ 16.5 mm
|
93
|
6
|
1.19
|
0.35–4.03
|
0.78
|
|
|
|
|
Main pancreatic duct opacification
|
Yes
|
111
|
9
|
2.24
|
0.73–6.90
|
0.16
|
2.96
|
0.92–9.50
|
0.07
|
|
NSAIDs use before ERCP
|
Yes
|
203
|
11
|
0.71
|
0.19–2.66
|
0.61
|
|
|
|
|
PGW
|
Yes
|
39
|
4
|
2.22
|
0.66–7.47
|
0.20
|
|
|
|
|
Stent diameter
|
6 mm
|
167
|
6
|
0.32
|
0.10–0.95
|
0.04
|
0.25
|
0.07–0.82
|
0.02
|
|
Cholecystitis
|
|
Previous biliary drainage
|
Yes
|
106
|
6
|
0.97
|
0.33–2.88
|
0.95
|
|
|
|
|
Tumor invasion to the OCD
|
Yes
|
27
|
6
|
7.43
|
2.35–23.5
|
< 0.01
|
11.30
|
3.10–41.2
|
< 0.01
|
|
OCD occluded by the stent
|
Yes
|
162
|
10
|
1.27
|
0.39–4.20
|
0.69
|
|
|
|
|
Stent length
|
≥ 8 cm
|
184
|
8
|
0.40
|
1.21–1.32
|
0.11
|
1.22
|
0.28–5.39
|
0.80
|
|
Stent diameter
|
6-mm
|
167
|
5
|
0.23
|
0.07–0.71
|
0.01
|
0.13
|
0.03–0.65
|
0.01
|
ERCP, endoscopic retrograde cholangiopancreatography; PGW, pancreatic duct guidewire
technique; OCD, orifice of the cystic duct; NSAIDs, non-steroidal anti-inflammatory
drugs; OR, odds ratio; CI, confidence interval.
Table 6
Univariate and multivariate analyses for factors involved in time to recurrent biliary
obstruction.
|
|
|
|
Univariate
|
Multivariate
|
|
Factors
|
|
n
|
Event
|
SHR
|
95 % CI
|
P value
|
SHR
|
95 % CI
|
P value
|
|
Pancreatic cancer
|
Yes
|
186
|
58
|
1.29
|
0.74–2.22
|
0.37
|
1.45
|
0.79–2.66
|
0.24
|
|
Resectable/borderline resectable status
|
Yes
|
60
|
12
|
0.48
|
0.25–0.92
|
0.03
|
0.38
|
0.19–0.78
|
< 0.01
|
|
Chemotherapy
|
Yes
|
189
|
69
|
4.9
|
0.65–37.5
|
0.12
|
4.65
|
0.62–36.4
|
0.13
|
|
Duodenal stent[1]
|
Yes
|
6
|
2
|
0.92
|
0.21–4.03
|
0.91
|
1.20
|
0.25–5.85
|
0.82
|
|
Diameter of the common bile duct
|
≥ 12 mm
|
157
|
44
|
1.05
|
0.66–1.65
|
0.85
|
1.16
|
0.72–1.86
|
0.55
|
|
Length of the biliary stricture
|
≥ 27 mm
|
154
|
41
|
0.83
|
0.53–1.30
|
0.40
|
0.80
|
0.50–1.28
|
0.35
|
|
Tumor invasion to the duodenal papilla
|
Yes
|
16
|
6
|
1.31
|
0.59–2.88
|
0.51
|
1.05
|
0.45–2.42
|
0.92
|
|
Tumor invasion to the duodenum[2]
|
Yes
|
10
|
3
|
0.76
|
0.25–2.28
|
0.62
|
0.57
|
0.19–1.72
|
0.32
|
|
Stent length
|
≥ 8 cm
|
184
|
46
|
0.63
|
0.40–0.99
|
0.05
|
0.66
|
0.24–1.77
|
0.41
|
|
Stent diameter
|
6-mm
|
167
|
44
|
0.79
|
0.50–1.29
|
0.29
|
1.30
|
0.48–3.48
|
0.61
|
ERCP, endoscopic retrograde cholangiopancreatography; SHR, sub-distribution hazard
ratio; CI, confidence interval.
1 Duodenal stent cases were limited to those with stent placement within the TRBO (median)
period calculated for all cases.
2 Excluding cases of duodenal papillary infiltration.
Discussion
This study compared outcomes of using 10-mm and 6-mm FCSEMS for DMBO. Stent-related
AEs were significantly less frequent in the 6-mm group than in the 10-mm group, and
cumulative incidence of RBO was not significantly different between the groups. In
addition, 6-mm FCSEMS was identified as an independent factor associated with a reduced
risk of total AEs, pancreatitis, and cholecystitis. Hence, the 6-mm FCSEMS may be
a safe, well-balanced, and useful stent that can ensure longer TRBO.
Clinically problematic stent-related AEs include pancreatitis and cholecystitis. In
previous reports, the risk factors for pancreatitis were pancreatography [21], volume preservation of the pancreatic parenchyma [22]
[23], and high axial force SEMS [24], whereas the risk factors for cholecystitis were tumor invasion into the orifice
of the cystic duct [25] and FCSEMS placement [26]. In terms of the inner diameter of SEMSs, 8-mm [16]
[22], 10-mm [2]
[4]
[5]
[10]
[16]
[18], and 12-mm [14]
[27] diameters are reported; however, none of these reports examined factors related
to the stent diameter. Nevertheless, reducing the stent diameter to 8 mm [16] does not reduce the risk of stent-related complications. In the present study, 6-mm
FCSEMS was extracted as the first risk-reducing factor for pancreatitis and cholecystitis.
A 6-mm FCSEMS is a slim stent that approximates the physiologic diameter of the common
bile duct, which minimizes bile duct overexpansion and reduces pressure to the duodenal
papilla and the orifice of the cystic duct, and these factors may have resulted in
fewer AEs.
TRBO has been reported to be 240 to 385 days [10]
[16]
[17] for 10-mm FCSEMSs in previous randomized controlled trials. Although TRBO for 6-mm
FCSEMSs has been reported in patients with preoperative pancreatic cancer, there is
no previous report showing long-term results. In this study, considering the competing
risks, cumulative incidence was calculated using the Gray’s test. The present study
evaluated cumulative incidence of RBO in all cases and in unresectable cases, and
no significant difference was found between the 10-mm and 6-mm groups in either type
of case. Migration was a cause of RBO, which is a risk associated with FCSEMS use,
but there was no significant difference between the groups (P = 0.10). In terms of the causes of RBO, the 6-mm stent caused less debris and overgrowth
than the 10-mm stent. We consider that the narrower 6-mm stent may have reduced the
reflux of the duodenal fluid and thus prevented the formation of debris. In addition,
the 6-mm FCSEMS allows for a longer stent with a lower shortening rate, which provides
adequate tumor coverage and prevents overgrowth.
In this study of preoperative pancreatic cancer cases, the non-RBO rates in the time
to surgery were 75.0 % and 80.8 % (P = 0.66) in the 10-mm and 6-mm groups, respectively. Furthermore, the 6-mm group had
significantly fewer total AEs than the 10-mm group. Thus, the 6-mm FCSEMS may be useful
in preoperative biliary drainage. Kataoka et al [28] compared the outcomes of a 6-mm FCSEMS and 7F to 8.5F PS retrospectively in patients
with preoperative pancreatic cancer; they found that TRBO was longer in the 6-mm FCSEMS
group (P = 0.02) than in the 7F to 8.5F PS group, and stent-related complications were not
significantly different between the groups (P = 0.47). In summary, a 6-mm FCSEMS could be a well-balanced stent that reduces the
risk of stent-related AEs as much as a PS, while ensuring TRBO comparable to the standard
10-mm FCSEMS. Regarding the possibility of shortening TRBO, which is a concern with
thin stents, this study examined palliative drainage of unresectable cases and found
no significant difference in the cumulative incidence of RBO with the 10-mm and 6-mm
FCSEMS. In addition, the 6-mm group had more resectable/borderline resectable cases,
which were considered as a competing risk for RBO and were analyzed using Fine-Gray
sub-distribution hazard regression compared to the 10-mm group. Resectable/borderline
resectable cases were extracted as a risk-reducing factor for RBO due to the limited
observation period, in the cases of 6-mm FCSEMS, but not as a risk factor for RBO
(SHR,1.30; 95 % CI, 0.48–3.48; P = 0.61). In other words, a 6-mm FCSEMS may be the first choice for a large number
of patients, including preoperative and unresectable cases.
This study has several limitations. This study was a single-center, retrospective
study and had small sample size. It is possible that the 6-mm group had more cases
of preoperative pancreatic cancer due to selection bias, which may have affected the
outcome of the study. A randomized controlled trial is needed to confirm this study’s
results.
Conclusions
In conclusion, this is the first report to compare the outcomes of the thinner-diameter
6-mm FCSEMS with those of the standard 10-mm FCSEMS. In the 6-mm FCSEMS, a cumulative
incidence of RBO was comparable to that of the 10-mm FCSEMS, and furthermore, the
risk of pancreatitis and cholecystitis was reduced. A prospective study is planned
to evaluate these findings.
