Original article
Long-term outcomes of covered self-expandable metal stents for treating benign biliary strictures
Authors
Jin-Seok Park1, Sang Soo Lee2, Tae Jun Song2, Do Hyun Park2, Dong-Wan Seo2, Sung Koo Lee2, Sangbong Han3, Myung-Hwan Kim2
Institutions
1
Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea 3 Department of Applied Statistics, Gachon University, Incheon, Republic of Korea
submitted 3. June 2015 accepted after revision 1. December 2015
Bibliography DOI http://dx.doi.org/ 10.1055/s-0042-101406 Published online: 2016 Endoscopy © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X Corresponding author Sang Soo Lee, MD, PhD Department of Gastroenterology University of Ulsan College of Medicine Asan Medical Center Seoul 138-736 Republic of Korea Fax: +82-2-30103190 [email protected]
Background and study aim: Fully covered, self-expandable metal stents (FCSEMSs) are acceptable tools for treating benign biliary stricture (BBS). However, little is known about the long-term outcomes of this technique. The aim of the present study was to evaluate the procedural and longterm outcomes of FCSEMSs for treating BBSs. Patients and methods: A total of 134 consecutive patients (median age 56 years; range 21 – 83) with BBS were retrospectively reviewed. The main outcomes were technical and clinical success, stricture resolution, recurrence, and adverse events. Outcomes were analyzed by reviewing patient medical records. Results: The success rates of FCSEMS placement and removal were 99.3 % and 98.2 %, respectively. Stricture resolution occurred in 103/132 (78.0 %) of the patients (median stent duration, 93 days;
range 1 – 489). The associated factors for stricture resolution were longer stent indwelling period (≥ 120 days) and absence of stent migration. Stricture recurrence was seen in 26/103 patients (25.2 %; 95 % confidence interval [CI] 0.17 – 0.34) within a median of 390 days (range 4 – 903 days). Chronic pancreatitis was associated with stricture recurrence (hazard ratio [HR] 2.59, 95 % CI 1.20 – 5.61; P = 0.02). Stent migration occurred in 41/132 patients (31.1 %; 95 %CI 0.23 – 0.39). The FCSEMS with anchoring flaps appeared to protect against stent migration (HR 0.22, 95 %CI 0.08 – 0.63; P < 0.01). Conclusion: FCSEMSs had a high success rate for BBS resolution. Longer indwelling periods and the absence of stent migration might be important factors for stricture resolution.
Introduction
FCSEMSs in ameliorating BBS, and included relatively short follow-up periods. Only limited data are available for the long-term efficacy and safety of FCSEMSs as a treatment for BBSs [11]. Therefore, the aim of the current study was to analyze the procedural and long-term outcomes of FCSEMSs for the treatment of patients with BBSs. Factors associated with stricture resolution and stricture recurrence were also evaluated.
!
Benign biliary strictures (BBSs) are managed endoscopically by the placement of multiple plastic stents that provide the highest long-term biliary patency rate [1 – 3]. However, plastic stenting strategies usually require multiple endoscopic sessions over a 1-year period, which increases costs and may decrease patient compliance [4]. To overcome these disadvantages, fully covered, self-expandable, metal stents (FCSEMSs) have been explored as a treatment option for BBS. Because FCSEMSs have a larger lumen size compared with plastic stents, they can provide longer patency and eliminate the need for multiple, sequential stent exchanges [5]. In addition, FCSEMSs can prevent tissue ingrowth, thereby facilitating removal of the stent if required [6]. Overall, studies examining FCSEMSs as a treatment for BBS have produced positive results in terms of stricture resolution [7 – 10]. However, almost all previous investigations used a small sample size to determine the safety and feasibility of
Materials and methods !
Study design and study population Patients were retrospectively selected from established prospective registries based on the following inclusion criteria: (1) patients aged over 18 years, (2) patients with biliary obstruction diagnosed according to clinical symptoms of obstructive jaundice with confirmation of bile duct stricture by cholangiogram, and (3) patients who had undergone primary FCSEMS placement to treat BBS or (4) those who had undergone sec-
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2
Original article
134 BBSs Perforation: 1 133 FCSEMS placed Lost to follow-up: 1 132 FCSEMS removal indicated
Proximal migration: 21
Surgical removal for proximal migration: 2
Complete distal migration: 20
Removal difficulty: 5
Stricture resolution: 13
Failed stricture resolution: 7
110 Removal success Failed stricture resolution: 20
Stricture recurrence: 26 77 Stricture resolution
Fig. 1 Flow diagram of the study design, showing the number of patients at each step. BBS, benign biliary stricture; FCSEMS, fully covered, self-expandable, metal stent.
ondary FCSEMS placement following recurrence of strictures after plastic stent treatment. Patients were excluded if they had (1) a stricture located within 2 cm of the hilum, (2) concurrent intrahepatic and common bile duct (CBD) strictures, or (3) a history of FCSEMS treatment. All FCSEMSs were endoscopically placed to treat benign CBD strictures. A total of 134 consecutive patients with BBSs who underwent FCSEMS placement between September 2007 and October 2013 " Fig. 1). This original cohort of 134 were enrolled in the study (● patients contained FCSEMS-treated patients (n = 41) who had been included in a previously published dataset [12]. Strictures were divided into those caused by chronic pancreatitis and intrinsic factors including gallstone-related diseases, post-surgical complications, and other inflammatory diseases. Patient medical records were analyzed, and data on clinical characteristics, stent information, stenting-related complications, and clinical outcomes were collected. The length of the stricture was measured using an electronic ruler on the cholangiogram in the picture archiving and communications system. The stricture duration prior to FCSEMS placement was measured in patients with a history of plastic stent treatment in cases of secondary FCSEMS placement. The duration was defined from the date of starting plastic stent treatment to FCSEMS insertion. The study was approved by the institutional review board of Asan Medical Center (no. S2014-1675-0001).
Stent placement procedures All stents were inserted into the CBD across the stricture by one of six experienced pancreaticobiliary endoscopists. Each endoscopist performed more than 600 – 1200 ERCP procedures each year. All endoscopists had extensive (6 – 25 years) experience in ERCP. Endoscopic sphincterotomy was performed in all patients with a native anatomy before stent insertion.
The flexible and commercially available nitinol FCSEMSs were used (WallFlex– Boston Scientific Co., Natick, Massachusetts, USA; Bonastent– Standard Sci Tech, Seoul, Republic of Korea; Niti-S ComVI biliary stent– Taewoong Medical, Gimpo, Republic of Korea; and Anchoring-flap Hanaro stent– M. I Tech, Seoul, Republic of Korea). After stent placement, the patients’ symptoms and blood tests were assessed at every visit in the outpatient clinic, based on the endoscopists’ recommendation every month or at admission. When hepatic-biliary enzyme levels were elevated or patients developed additional symptoms, computed tomography (CT) was performed to estimate stent patency. The need for a repeat intervention during the study was determined by the recurrence of biliary obstructive symptoms and according to the decision of the investigator. The stent indwelling period was determined according to the discretion of the endoscopists and was measured from the date of stent insertion to the date of removal. In cases of complete distal stent migration, the period was defined from the date of stent insertion to the date of diagnosis of stent migration. Stent removal was usually performed 3 – 6 months after stent placement. Stent removal was typically accomplished by grasping the distal part of the stent with a rat-tooth forceps or snaring the distal end of the FCSEMS. The stent was then retracted gently with the endoscope or withdrawn through the working channel. For challenging stent removal cases, wire-guided balloon dilation within the stent was performed to help dissolve the impaction and to move the stent distally. The stents were subsequently removed using the snare or rat-tooth forceps. Prophylactic rectal indomethacin and pancreatic duct stenting were not applied regularly to prevent pancreatitis. The patients were followed up with a laboratory test 1 month after the removal of the FCSEMS. Laboratory tests and the assessment of stricture-related symptoms were performed every 3 months for the first year and every 6 months for the second and third years, in
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103 Stricture resolution
Original article
Table 1 Baseline characteristics of patients and fully covered self-expandable metal stents.
Characteristic
Value
Outcome assessment
Patients, n
134
The rates of technical success, stricture resolution, and stricture recurrence were evaluated. In addition, adverse events that were associated with stenting were assessed, including procedure-related pain, bleeding, pancreatitis, cholestasis, cholangitis, cholecystitis, stent migration, and removal difficulty. Technical success was defined as successful stent placement across the stricture. Stricture resolution was defined as ≥ 75 % improvement in stricture diameter as determined by comparing the cholangiograms obtained before stent insertion and after stent removal, drainage of contrast medium injected proximal to the stricture, and the ability to pass a retrieval balloon through the stricture. When malfunction of the stent was suspected and indicated by symptoms such as cholangitis, deterioration of liver function, or biliary pain, CT and endoscopic retrograde cholangiopancreatography (ERCP) were performed to determine the presence of stent dysfunction. Adverse events were classified as those occurring during stent insertion, the indwelling period, or with stent removal. Stricture recurrence was defined by abnormal liver function test results and the need for re-stenting based on the cholangiogram results. After stent removal, patients with stricture resolution were followed up every 3 – 6 months to monitor for stricture recurrence. The stent migration time was defined from the date of stent insertion to the date of diagnosis of stent migration. The stricture recurrence time was defined as the time from the date of stent removal to the date of diagnosis of stricture recurrence.
Age, median (range), years
56 (21 – 83)
Sex, n (%) Male
89 (66.4)
Female
45 (33.6)
BBS etiology, n (%) Gallstone related
51 (38.1)
Chronic pancreatitis
47 (35.1)
Post surgical 1
24 (17.9)
Others
12 (9.0)
Previous treatment, n (%) First-line treatment
55 (41.0)
Previous plastic stenting
79 (59.0)
Stricture duration prior to stenting, median (range), days 2
268 (10 – 2548)
Stricture location, n (%) Papilla
20 (14.9)
Distal CBD
82 (61.2)
Middle CBD
12 (9.0)
Proximal CBD
20 (14.9)
Stricture length, median (range), mm
17 (5 – 44)
Stent diameter, n (%) 8 mm
18 (13.4)
10 mm
116 (86.6)
Stent length, n (%) 40 mm
37 (27.6)
50 mm
49 (36.6)
60 mm
24 (17.9)
70/80/90 mm
11/6/7 (8.2/4.5/5.2)
Anchoring flaps, n (%)
Statistical analysis
With flaps
Data analyses were performed using the R software (version 2.10.1; R Foundation for Statistical Computing, Vienna, Austria) [13] and IBM SPSS Statistics for Windows (version 20.0; IBM Corp., Armonk, New York, USA). Baseline patient characteristics and basic outcomes variables regarding FCSEMS were summarized with a median and range for continuous variables, or a frequency and a percentage for categorical variables. The student t test, chi-squared test, or Fisher’s exact test, was used for between group comparisons of continuous or categorical variables, when appropriate. For analysis of stricture resolution, both univariate and multivariate logistic regressions were fitted to determine any associations with patient characteristics and the FCSEMS placement. Variables with a P value of < 0.2 in the univariate analysis were included as potential candidate variables for the multivariate model. The final model was determined using the backward variable selection approach where the least significant variable was removed one by one. As stricture recurrence and stent migration are time-dependent outcome variables, a Cox proportional hazards model was employed to determine any associations with the patient characteristics and the FCSEMS placement. The proportional hazards assumption was examined using the Schoenfeld residual test, and P values of < 0.05 were considered to be statistically significant.
Without flaps
28 (20.9) 106 (79.1)
BBS, benign biliary stricture; CBD, common bile duct. 1 Post-surgical cases included individuals with strictures caused by cholecystectomy, liver transplantation, and ampullectomy. Other patients included ones with primary sclerosing cholangitis, ischemic changes, and BBS of unknown origin. 2 Measured in 79 patients with previous plastic stenting.
Results !
Patient demographics Baseline characteristics of the patients and the indications for " Table 1. Gallstone-relatFCSEMS placement are summarized in ● ed strictures were the most common cause of BBSs. The most common location for a BBS was the distal CBD. A total of 55 patients received FCSEMS as first-line therapy, and 79 patients with BBSs had been treated previously with plastic stents, which failed to achieve stricture resolution. The median stricture duration was 268 days (range 10 – 2548 days) prior to stenting in patients who received FCSEMS as second-line therapy.
Technical success FCSEMSs were successfully placed in 99.3 % of the patients (133/ 134; 95 %CI 0.98 – 1.0). In one case of chronic pancreatitis, stent placement failed because of duodenal perforation, which occurred during duodenoscope insertion. The median indwelling period was 93 days (range 1 – 489). A total of 106 patients received a standard FCSEMS and 28 received the FCSEMS with anchoring " Table1). flaps (FCSEMS-AF) (●
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order to check for strictures. Subsequently, patients were reminded to visit the outpatient clinic if they experienced any stricture-associated symptom.
Original article
Valuable
Value
Technical success, n (%)
133 (99.3)
Overall stricture resolution, n (%)
103 (77.4)
Period of indwelling stent, median (range), days
93 (1 – 489)
Adverse events, n (%) Stent insertion related
25 (18.8)
Pain
13
Post-ERCP pancreatitis
11
Duodenal perforation During stent indwell period
1 18 (13.5)
Cholangitis
8
Pancreatitis
4
Stent obstruction
5
Cholecystitis Stent removal related
1 10 (7.5)
Pancreatitis
2
Bleeding
1
Inability to remove
2
Difficult to remove Stent migration
5 41 (30.8)
Proximal migration
21
Distal migration
20
Follow-up period after stent removal, median (range), days Stricture recurrence, n (%) Period of stricture recurrence, median (range), days
960 (365 – 3162) 26 (25.2) 390 (4 – 903)
ERCP, endoscopic retrograde cholangiopancreatography.
Adverse events " TaAdverse events related to stent insertion are summarized in● ble 2. One patient was lost during the follow-up period after stent " Taplacement. Adverse events during the indwelling period (● ble 2) included cholangitis (n = 8), pancreatitis (n = 4), stent obstruction (n = 5), and cholecystitis (n = 1). For the underlying etiologies in patients with cholangitis, there were 3, 3, and 2 patients with gallstone-related diseases, chronic pancreatitis, and post-surgical diseases, respectively. All of the patients’ stents were removed earlier than the arranged date for stent removal. The median indwelling duration was 77 days (range 25 – 96 days) for these patients. Cholecystitis occurred in one patient, and the extremely low-lying cystic duct take off was recognized as a risk factor.
Clinical outcomes Stricture resolution In 78.0 % of all patients (103/132; 95 %CI 0.71 – 0.85), the stric" Table 2). A tures resolved without the need for re-stenting (● stent indwelling period of at least 120 days was positively associated with stricture resolution (OR 3.22, 95 %CI 1.21 – 8.56; P = " Table 3). Stent migration was associated with a low rate 0.02; ● " Taof stricture resolution (OR 1.48, 95 %CI 1.13 – 1.94; P < 0.01; ● ble 3). Based on the univariate analysis, chronic pancreatitis was significantly related to the failure of stricture resolution (OR 0.42, " Table3). However, in multivariate a95 %CI 0.18 – 0.97; P = 0.04; ● nalysis, chronic pancreatitis was not associated with stricture resolution. The length of the stricture was not significantly related " Tato stricture resolution (OR 0.96, 95 %CI 0.91 – 1.01; P = 0.12; ● ble 3). The median stricture length of patients with stricture resolution was 16 mm (range 5 – 44 mm), which was not different
Table 3 Univariate and multivariate analysis of factors associated with stricture resolution.
Variable
Stricture resolution P value
OR
95 %CI
Female
1
(reference)
Male
0.91
0.38 – 2.22
Intrinsic causes
1
(reference)
Chronic pancreatitis
0.42
0.18 – 0.97
Papilla
1
(reference)
Distal CBD
1.05
0.34 – 3.28
0.94
Middle CBD
4.23
0.43 – 41.88
0.22
Proximal CBD
7.31
0.76 – 70.02
0.09
No
1
(reference)
Yes
0.6
0.25 – 1.45
No
1
(reference)
Yes
2.78
0.78 – 9.96
≥ 55
1
(reference)
< 55
0.98
0.38 – 2.22
Univariate analysis Sex 0.84
BBS etiology 0.04
The location of stricture
Previous plastic stenting 0.26
Anchoring flap 0.12
Age 0.84
Migration Yes
1
(reference)
No
1.48
1.13 – 1.94
< 0.01
Duration of stent indwelling duration < 120 days
1
(reference)
≥ 120 days
3.22
1.21 – 8.56
0.02
Stricture length
0.96
0.91 – 1.01
0.12
Intrinsic causes
1
(reference)
Chronic pancreatitis
0.46
0.2 – 1.09
Multivariate analysis BBS etiology 0.08
Migration Yes
1
(reference)
No
4.24
1.75 – 10.29
< 120 days
1
(reference)
≥ 120 days
2.97
1.11 – 8.03
< 0.01
Duration of stent indwelling 0.03
OR, odds ratio; CI, confidence interval; BBS, benign biliary stricture; CBD, common bile duct.
from those in patients without stricture resolution (18.5 mm, range 8 – 44 mm; P = 0.42). Stricture resolution was achieved in 83.0 % (44/53) and 74.7 % (59/79, 95 %CI 0.65 – 0.84) of patients who received stents as first- and second-line therapies, respectively; this difference was not significant (P = 0.26). The stricture duration prior to FCSEMS insertion was not significantly associated with stricture resolution in the second-line treatment group. The median stricture duration prior to stenting in patients with stricture resolution was 248 days (range 10 – 2548 days), which was not significantly different from cases without stricture resolution (282 days, range 50 – 1359; P = 0.51).
Stent removal Of the 132 patients with strictures, 112 underwent stent removal and 20 experienced distal stent migration. Endoscopic removal was successfully completed in 98.2 % of the patients (110/112; 95 %CI 0.96 – 1.0). The remaining two patients required surgical removal because of stent adhesion to the surrounding tissue in
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Table 2 Outcomes and adverse events related to fully covered, self-expandable, metal stent placement for benign biliary stricture.
Original article
Variable
Stricture recurrence P value
with stricture recurrence was chronic pancreatitis-related biliary " Table 4). Among stricture (HR 2.59, 95 %CI 1.20 – 5.61; P = 0.02; ● the 32 patients with chronic pancreatitis-related biliary strictures who achieved stricture resolution, 13 patients (40.6 %; 95 % CI 0.24 – 0.58) experienced stricture recurrence. Conversely, 13 (18.3 %; 95 %CI 0.09 – 0.27) of the 71 patients with other BBS etiol" Fig. 2). ogies (intrinsic causes) had stricture recurrences (●
HR
95 %CI
Female
1
(reference)
Male
2.13
0.8 – 5.64
Intrinsic causes
1
(reference)
Chronic pancreatitis
2.59
1.20 – 5.61
Papilla
1
(reference)
Distal CBD
0.96
0.32 – 2.85
0.94
Middle CBD
0.7
0.13 – 3.81
0.68
Proximal CBD
0.56
0.12 – 2.48
0.44
No
1
(reference)
Yes
0.99
0.45 – 2.15
No
1
(reference)
Yes
0.5
0.15 – 1.67
≥ 55
1
(reference)
< 55
1
0.97 – 1.03
0.81
1
0.99 – 1.05
0.92
< 120 days
1
(reference)
≥ 120 days
0.91
0.41 – 2.03
0.82
!
Stricture length
0.80
0.58 – 1.10
0.17
Intrinsic causes
1
(reference)
Chronic pancreatitis
2.59
1.20 – 5.61
The results of this study suggest that FCSEMS placement may be a reasonable treatment strategy for patients with BBS. Good clinical outcomes can be expected with longer stent indwelling periods (≥ 120 days), intrinsic causes of BBS, and the absence of migration during follow-up. The FCSEMS indwelling period has typically ranged from 3 to 6 months in previous published studies[7, 14, 17]. Even though a BBS can resolve with a relatively brief FCSEMS indwelling period owing to the benign characteristics of this condition, there is a lack of research on the appropriate indwelling periods required to achieve successful stricture resolution. In the current study, stricture resolution was significantly related to longer stent indwelling periods, especially those of at least 120 days (OR 2.97, 95 %CI 1.11 – 8.03; P = 0.03). The resolution rates for patients who had an indwelling period < 120 days and ≥ 120 days were 70.9 % (95 %CI 0.61 – 0.81) and 88.7 % (95 %CI 0.80 – 0.97), respectively (P = 0.02). Therefore, we recommend that the stent should be placed for at least 4 months for stricture resolution. The results concur with data from another prospective study in which patients who had indwelling stents for > 90 days were 4.3 times more likely to have stricture resolution than individuals with stents for ≤ 90 days (95 %CI 1.24 – 15.09) [18]. Migration of FCSEMSs has been reported to occur in 4 % – 38 % of BBS cases, which is higher than that in malignant stricture cases [19, 20]. Migration is considered to be a risk factor for failure of stricture resolution because it may lead to inadequate stricture dilation [18, 21, 22]. Stent migration also affected stricture resolution in the current study (P < 0.01). To date, various attempts have been made to prevent migration. One technique involves the use of a newly designed FCSEMS, known as the “bumpy stent,” which has anti-migration properties. However, in a recently published study, despite the proposed anti-migration feature of this FCSEMS, the stent migration rate was still significant [23]. Conversely, in the current study, the migration rate was sig-
Univariate analysis Sex 0.13
BBS etiology 0.02
Location of stricture
Previous plastic stenting 0.97
Anchoring flap 0.26
Age
Duration of stent indwelling
Stent migration Stent migration was observed in 41 (31.1 %; 95 %CI 0.23 – 0.39) out of the 132 patients (20 with complete distal migration and 21 with proximal migration), and the underlying etiologies included gallstone-related diseases (18), chronic pancreatitis (16), post-surgical diseases (5), and other inflammatory diseases (2). The median indwelling period was 70 days (range 25 – 169 days), which was shorter than the indwelling period in cases without stent migration. The FCSEMS-AF appeared to protect against stent migration (HR 0.26, 95 %CI 0.09 – 0.74; P = 0.01; ●" Fig. 3). However, other clinical outcomes including technical success, stricture resolution, other adverse events except migration, and removal difficulty, did not differ significantly between conventional FCSEMS and FCSEMS-AF. The cause of BBS (P = 0.51), stricture length (P = 0.17), or location of the stricture were " Table 5). not associated with stent migration (●
Discussion
Multivariate analysis BBS etiology 0.02
HR, hazards ratio; CI, confidence interval; BBS, benign biliary stricture; CBD, common bile duct.
one patient, and, in the other patient, because of migration of the proximal stent into the hepatic hilum where it could not be grasped by forceps. For patients in whom endoscopic stent removal was achieved, the procedure was completed without difficulty in almost all cases (105/110). However, difficulties with stent removal were encountered in five patients for the same reasons as in the surgical removal cases. Consequently, 2 – 4 sessions were required for stent removal. In four of these five patients, proximal stent migration occurred. Based on the univariate analysis, proximal migration was statistically significantly associated with difficulties in stent removal (OR 46.29, 95 %CI 5.19 – 413.15; P < 0.01). Other adverse events related to stent removal were post-ERCP pancreatitis (n = 2) and minor bleeding (n = 1). These events did not require specific treatment and subsided with conservative care.
Stricture recurrence Stricture recurrence was observed in 26 (25.2 %; 95 %CI 0.17 – 0.34) of 103 patients who achieved stricture resolution during the follow-up period (median 960 days; range 365 – 3162 days). All 103 patients remained alive during the follow-up period. The median period from stent removal to stricture recurrence was 390 days (range 4 – 903 days). The 1- and 2-year recurrence-free rates after stent removal were 87.5 % (95 %CI 0.82 – 0.94) and 73.3 % (95 %CI 0.65 – 0.83), respectively. The only factor associated
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Table 4 Univariate and multivariate analysis of factors associated with stricture recurrence.
Original article
Fig. 2 Comparison of stricture recurrence rates between chronic pancreatitis and other etiologies of benign biliary stricture using the Kaplan-Meier method. The red line indicates chronic pancreatitis and the black line corresponds to other etiologies.
100
Recurrence-free probability (%)
75
50
0 0
Other etiologies
20
40
60
80
71
66
50
29
22
15
11
8
4
3
1
Chronic pancreatitis 34
29
16
9
9
5
4
2
0
0
0
Fig. 3 A fully covered, self-expandable, metal stent with anchoring flaps at the proximal end of the stent.
nificantly lower for individuals who received the FCSEMS-AF compared with those who received the conventional FCSEMS (14.3 % vs. 36.9 %; P = 0.04). FCSEMS-AF has four anti-migration anchoring flaps at the proximal end and a flared portion at the distal end, which prevent distal and proximal migration, respectively. According to one multicenter prospective study, 22 patients with a BBS who received the FCSEMS-AF for stricture resolution did not experience migration during an indwelling period of up to 6 months [22]. In addition, Mangiavillano et al. reported only one incident of stent migration among 32 patients who underwent metal stenting with FCSEM-AF [24] Therefore, we believe that FCSEMS-AF designs may be very promising for the prevention of FCSEMS migration. Further study should confirm this hypothesis. Although a longer indwelling period was found to promote stricture resolution, there is concern that this could lead to difficulty in removing the stent. Furthermore, the optimal duration of stenting for safe removal has not been clearly identified. In the current investigation, however, removal difficulty did not vary according to indwelling period (3.8 % and 6.6 % in patients with ≥ 120 and < 120 days of indwelling duration, respectively; P = 0.699). These results are supported by findings from a previous
animal model study by Lee at al. [6], who studied 12 canines in order to identify histopathological changes in the bile duct in response to long-term FCSEMS placement. Results of this investigation demonstrated that FCSEMSs could be removed from the bile duct for up to 9 months after insertion without severe histopathological changes. The resolution rates in the patients with chronic pancreatitis were significantly lower than those with other type of BBSs (68.1 % vs. 83.5 %, P = 0.04). However, chronic pancreatitis was not found to be a factor associated with stricture resolution on multivariate analysis. The lack of statistical significance of chronic pancreatitis in stricture resolution may be due to the inadequate sample size (n = 29) of patients who failed to achieve stricture resolution. Therefore, further large-scale studies are needed to determine this association. In the current study, proximal stent migration was statistically significantly related to stent removal difficulties (OR 46.29, 95 % CI 5.19 – 413.15; P < 0.01). Proximal stent migration of FCSEMSs might result in permanent damage or obstruction of the biliary tree if the stent cannot be retrieved [25]. In our experience, grasping the stent with forceps or a snare was challenging when the distal end of the stent had migrated completely into the bile
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25
Original article
Table 5 Univariate and multivariate analysis of factors associated with stent migration.
Stent migration HR
95 %CI
Female
1
(reference)
Male
2.31
1.02 – 5.22
Intrinsic causes
1
(reference)
Chronic pancreatitis
1.24
0.65 – 2.36
1
(reference)
P value
Univariate analysis Sex 0.04
BBS etiology 0.51
Location of stricture Papilla Distal CBD
1.5
0.57 – 3.96
0.41
Middle CBD
0.37
0.04 – 3.22
0.37
Proximal CBD duct
0.78
0.24 – 2.55
0.68
Recurrence-free probability (%)
Variable
100
75
50
25
0
Previous plastic stenting No
1
(reference)
Yes
0.98
0.53 – 1.81
No
1
(reference)
Yes
0.26
0.09 – 0.74
≥ 55
1
(reference)
< 55
1.53
0.8 – 2.91
0.2
1.02
0.97 – 1.07
0.48
Female
1
(reference)
Male
2.56
1.12 – 5.89
No
1
(reference)
Yes
0.22
0.08 – 0.63
0 0.94
20
40 Time in months
60
80
Fig. 4
Stricture recurrence after stricture resolution.
0.01
Age
Stricture length Multivariate analysis Sex
0.03
Anchoring flap < 0.01
HR, hazards ratio; CI, confidence interval; BBS, benign biliary stricture; CBD, common bile duct.
duct. Multiple sessions of ERCP were necessary to address this situation. Although most proximal migrated FCSEMSs were successfully retrieved after 2 – 4 sessions of ERCP, two patients had to undergo surgical bile duct resection for stent removal. Thus, FCSEMS with lasso may be needed to prevent removal difficulty if the FCSEMS migrates proximally into the biliary tree [18]. However, we believe that the current study lacks sufficient evidence to show the clear correlation between proximal stent migration and stent removal difficulties because the differences were not statistically significant for the given sample size. The median follow-up period for the study cohort was 960 days (range 365 – 3162 days). We believe that this was sufficient to determine the long-term endurance of stricture resolution. Stricture recurrence developed in 26 patients, and the median period of stricture recurrence was 390 days (range 4 – 903 days). Almost all of the 26 patients in the study who developed a stricture recurrence experienced the condition within 2 years, and only " Fig. 4). A retrotwo cases occurred 2 years after stent removal (● spective study of FCSEMSs reported a stricture recurrence rate of 8.3 % (10/120, 95 %CI 0.03 – 0.13) for patients who experienced stricture resolution [10]. Among these individuals, only one had a stricture recurrence 2 years after stent removal. These results were similar to the current findings. Therefore, we suggest that clinicians should monitor for stricture recurrence in patients who achieve stricture resolution within 2 years after stent re-
moval. In addition, it is advisable for patients to undergo regular follow-up after stent removal for a minimum of 2 years. The stricture recurrence rate was significantly higher for individuals with chronic pancreatitis than cases with other BBS etiologies (40.6 % vs. 18.3 %; OR 2.59, 95 %CI 1.2 – 5.61; P = 0.02). We suspect that this higher recurrence rate was due to the fibrotic encasing process (extrinsic cause of BBS) that is more frequently seen in cases of chronic pancreatitis compared with other BBS etiologies. In contrast, fibrosis is often focal and confined to the duct wall in cases of other BBS etiologies [10, 26]. In addition, the higher stricture recurrence rate associated with chronic pancreatitis could be affected by the inaccurate estimation of stricture resolution. In the current and previous studies [10, 26], stricture resolution was measured during the same ERCP session after stent removal. Although strictures associated with chronic pancreatitis appeared to improve during stent removal on cholangiogram, this may be a transient occurrence. We suspect that there would be a risk of inadequate dilation of the strictures. This is because early stricture recurrence (< 90 days) was more frequently observed in patients with chronic pancreatitis (3 out of 13 patients with stricture recurrence) compared with those with other types of BBS (none of 13), when the time between stricture resolution and stricture recurrence was analyzed (data not shown). Based on these results, we recommend that assessment of stricture resolution should be performed a few days after stent removal. There were some limitations of this study. First, the study was a retrospective investigation. The enrolled patients were treated using FCSEMS from various companies and the analysis of each stent was impossible owing to the small numbers with each stent. The choice of FCSEMS was at the discretion of the six different pancreaticobiliary endoscopists, and together with the wide variety of stents used might also be a weakness of the study. However, we assume that the results could be informative to clinicians as data were based on the actual clinical utilization of various commercially available stents. Second, the absence of a control group is a major limitation of the study. In conclusion, FCSEMSs had a high success rate for stricture resolution. However, stricture recurrence appeared frequently in pa-
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Anchoring flap
tients with chronic pancreatitis. A longer indwelling period and the absence of stent migration might be important factors for stricture resolution. Competing interests: None
References 1 Dumonceau JM, Tringali A, Blero D et al. Biliary stenting: indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy 2012; 44: 277 – 298 2 Draganov P, Hoffman B, Marsh W et al. Long-term outcome in patients with benign biliary strictures treated endoscopically with multiple stents. Gastrointest Endosc 2002; 55: 680 – 686 3 Catalano MF, Linder JD, George S et al. Treatment of symptomatic distal common bile duct stenosis secondary to chronic pancreatitis: comparison of single vs. multiple simultaneous stents. Gastrointest Endosc 2004; 60: 945 – 952 4 Costamagna G, Tringali A, Mutignani M et al. Endotherapy of postoperative biliary strictures with multiple stents: results after more than 10 years of follow-up. Gastrointest Endosc 2010; 72: 551 – 557 5 Kaassis M, Boyer J, Dumas R et al. Plastic or metal stents for malignant stricture of the common bile duct? Results of a randomized prospective study Gastrointest Endosc 2003; 57: 178 – 182 6 Lee SS, Song TJ, Joo M et al. Histological changes in the bile duct after long-term placement of a fully covered self-expandable metal stent within a common bile duct: a canine study. Clin Endosc 2014; 47: 84 – 93 7 Mahajan A, Ho H, Sauer B et al. Temporary placement of fully covered self-expandable metal stents in benign biliary strictures: midterm evaluation (with video). Gastrointest Endosc 2009; 70: 303 – 309 8 Sauer B, Talreja J, Ellen K et al. Temporary placement of a fully covered self-expandable metal stent in the pancreatic duct for management of symptomatic refractory chronic pancreatitis: preliminary data (with videos). Gastrointest Endosc 2008; 68: 1173 – 1178 9 Tarantino I, Barresi L, Curcio G et al. Definitive outcomes of self-expandable metal stents in patients with refractory post-transplant biliary anastomotic stenosis. Dig Liver Dis 2015; 47: 562 – 565 10 Irani S, Baron TH, Akbar A et al. Endoscopic treatment of benign biliary strictures using covered self-expandable metal stents (CSEMS). Dig Dis Sci 2014; 59: 152 – 160 11 Baron TH. Covered self-expandable metal stents for benign biliary tract diseases. Curr Opin Gastroenterol 2011; 27: 262 – 267 12 Ryu CH, Kim MH, Lee SS et al. Temporary placement of fully covered self-expandable metal stents in benign biliary strictures. Korean J Gastroenterol 2013; 62: 49 – 54 13 Venables W, Smith D. The R Development Core Team (2008). An Introduction to R. Network Theory Limited. Bristol: 2010: https://www.rproject.org/
14 Moon JH, Choi HJ, Koo HC et al. Feasibility of placing a modified fully covered self-expandable metal stent above the papilla to minimize stent-induced bile duct injury in patients with refractory benign biliary strictures (with videos). Gastrointest Endosc 2012; 75: 1080 – 1085 15 Poley JW, Cahen DL, Metselaar HJ et al. A prospective group sequential study evaluating a new type of fully covered self-expandable metal stent for the treatment of benign biliary strictures (with video). Gastrointest Endosc 2012; 75: 783 – 789 16 Wagh MS, Chavalitdhamrong D, Moezardalan K et al. Effectiveness and safety of endoscopic treatment of benign biliary strictures using a new fully covered self expandable metal stent. Diagn Ther Endosc 2013; 2013: 183513 17 Sauer P, Chahoud F, Gotthardt D et al. Temporary placement of fully covered self-expandable metal stents in biliary complications after liver transplantation. Endoscopy 2012; 44: 536 – 538 18 Kahaleh M, Brijbassie A, Sethi A et al. Multicenter trial evaluating the use of covered self-expanding metal stents in benign biliary strictures: time to revisit our therapeutic options? J Clin Gastroenterol 2013; 47: 695 – 699 19 Isayama H, Mukai T, Itoi T et al. Comparison of partially covered nitinol stents with partially covered stainless stents as a historical control in a multicenter study of distal malignant biliary obstruction: the WATCH study. Gastrointest Endosc 2012; 76: 84 – 92 20 Tarantino I, Mangiavillano B, Di Mitri R et al. Fully covered self-expandable metallic stents in benign biliary strictures: a multicenter study on efficacy and safety. Endoscopy 2012; 44: 923 – 927 21 Costamagna G. Covered self-expanding metal stents in benign biliary strictures: not yet a “new paradigm” but a promising alternative. Gastrointest Endosc 2008; 67: 455 – 457 22 Park do H, Lee SS, Lee TH et al. Anchoring flap versus flared end, fully covered self-expandable metal stents to prevent migration in patients with benign biliary strictures: a multicenter, prospective, comparative pilot study (with videos). Gastrointest Endosc 2011; 73: 64 – 70 23 Walter D, Laleman W, Jansen JM et al. A fully covered self-expandable metal stent with antimigration features for benign biliary strictures: a prospective, multicenter cohort study. Gastrointest Endosc 2015; 81: 1197 – 1203 24 Mangiavillano B, Manes G, Baron TH et al. The use of double lasso, fully covered self-expandable metal stents with new “anchoring flap” system in the treatment of benign biliary diseases. Dig Dis Sci 2014; 59: 2308 – 2313 25 Cahen DL, Rauws EA, Gouma DJ et al. Removable fully covered self-expandable metal stents in the treatment of common bile duct strictures due to chronic pancreatitis: a case series. Endoscopy 2008; 40: 697 – 700 26 Katanuma A, Maguchi H, Takahashi K et al. Endoscopic management of benign biliary stricture: should we treat more aggressively? Dig Endosc 2014; 26: 536 – 537
Park Jin-Seok et al. Long-term outcomes of covered SEMS in benign biliary strictures … Endoscopy
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Original article
Long-term outcomes of covered self-expandable metal stents for treating benign biliary strictures
Authors
Jin-Seok Park1, Sang Soo Lee2, Tae Jun Song2, Do Hyun Park2, Dong-Wan Seo2, Sung Koo Lee2, Sangbong Han3, Myung-Hwan Kim2
Institutions
1
Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea 3 Department of Applied Statistics, Gachon University, Incheon, Republic of Korea
submitted 3. June 2015 accepted after revision 1. December 2015
Bibliography DOI http://dx.doi.org/ 10.1055/s-0042-101406 Published online: 2016 Endoscopy © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X Corresponding author Sang Soo Lee, MD, PhD Department of Gastroenterology University of Ulsan College of Medicine Asan Medical Center Seoul 138-736 Republic of Korea Fax: +82-2-30103190 [email protected]
Background and study aim: Fully covered, self-expandable metal stents (FCSEMSs) are acceptable tools for treating benign biliary stricture (BBS). However, little is known about the long-term outcomes of this technique. The aim of the present study was to evaluate the procedural and longterm outcomes of FCSEMSs for treating BBSs. Patients and methods: A total of 134 consecutive patients (median age 56 years; range 21 – 83) with BBS were retrospectively reviewed. The main outcomes were technical and clinical success, stricture resolution, recurrence, and adverse events. Outcomes were analyzed by reviewing patient medical records. Results: The success rates of FCSEMS placement and removal were 99.3 % and 98.2 %, respectively. Stricture resolution occurred in 103/132 (78.0 %) of the patients (median stent duration, 93 days;
range 1 – 489). The associated factors for stricture resolution were longer stent indwelling period (≥ 120 days) and absence of stent migration. Stricture recurrence was seen in 26/103 patients (25.2 %; 95 % confidence interval [CI] 0.17 – 0.34) within a median of 390 days (range 4 – 903 days). Chronic pancreatitis was associated with stricture recurrence (hazard ratio [HR] 2.59, 95 % CI 1.20 – 5.61; P = 0.02). Stent migration occurred in 41/132 patients (31.1 %; 95 %CI 0.23 – 0.39). The FCSEMS with anchoring flaps appeared to protect against stent migration (HR 0.22, 95 %CI 0.08 – 0.63; P < 0.01). Conclusion: FCSEMSs had a high success rate for BBS resolution. Longer indwelling periods and the absence of stent migration might be important factors for stricture resolution.
Introduction
FCSEMSs in ameliorating BBS, and included relatively short follow-up periods. Only limited data are available for the long-term efficacy and safety of FCSEMSs as a treatment for BBSs [11]. Therefore, the aim of the current study was to analyze the procedural and long-term outcomes of FCSEMSs for the treatment of patients with BBSs. Factors associated with stricture resolution and stricture recurrence were also evaluated.
!
Benign biliary strictures (BBSs) are managed endoscopically by the placement of multiple plastic stents that provide the highest long-term biliary patency rate [1 – 3]. However, plastic stenting strategies usually require multiple endoscopic sessions over a 1-year period, which increases costs and may decrease patient compliance [4]. To overcome these disadvantages, fully covered, self-expandable, metal stents (FCSEMSs) have been explored as a treatment option for BBS. Because FCSEMSs have a larger lumen size compared with plastic stents, they can provide longer patency and eliminate the need for multiple, sequential stent exchanges [5]. In addition, FCSEMSs can prevent tissue ingrowth, thereby facilitating removal of the stent if required [6]. Overall, studies examining FCSEMSs as a treatment for BBS have produced positive results in terms of stricture resolution [7 – 10]. However, almost all previous investigations used a small sample size to determine the safety and feasibility of
Materials and methods !
Study design and study population Patients were retrospectively selected from established prospective registries based on the following inclusion criteria: (1) patients aged over 18 years, (2) patients with biliary obstruction diagnosed according to clinical symptoms of obstructive jaundice with confirmation of bile duct stricture by cholangiogram, and (3) patients who had undergone primary FCSEMS placement to treat BBS or (4) those who had undergone sec-
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2
Original article
134 BBSs Perforation: 1 133 FCSEMS placed Lost to follow-up: 1 132 FCSEMS removal indicated
Proximal migration: 21
Surgical removal for proximal migration: 2
Complete distal migration: 20
Removal difficulty: 5
Stricture resolution: 13
Failed stricture resolution: 7
110 Removal success Failed stricture resolution: 20
Stricture recurrence: 26 77 Stricture resolution
Fig. 1 Flow diagram of the study design, showing the number of patients at each step. BBS, benign biliary stricture; FCSEMS, fully covered, self-expandable, metal stent.
ondary FCSEMS placement following recurrence of strictures after plastic stent treatment. Patients were excluded if they had (1) a stricture located within 2 cm of the hilum, (2) concurrent intrahepatic and common bile duct (CBD) strictures, or (3) a history of FCSEMS treatment. All FCSEMSs were endoscopically placed to treat benign CBD strictures. A total of 134 consecutive patients with BBSs who underwent FCSEMS placement between September 2007 and October 2013 " Fig. 1). This original cohort of 134 were enrolled in the study (● patients contained FCSEMS-treated patients (n = 41) who had been included in a previously published dataset [12]. Strictures were divided into those caused by chronic pancreatitis and intrinsic factors including gallstone-related diseases, post-surgical complications, and other inflammatory diseases. Patient medical records were analyzed, and data on clinical characteristics, stent information, stenting-related complications, and clinical outcomes were collected. The length of the stricture was measured using an electronic ruler on the cholangiogram in the picture archiving and communications system. The stricture duration prior to FCSEMS placement was measured in patients with a history of plastic stent treatment in cases of secondary FCSEMS placement. The duration was defined from the date of starting plastic stent treatment to FCSEMS insertion. The study was approved by the institutional review board of Asan Medical Center (no. S2014-1675-0001).
Stent placement procedures All stents were inserted into the CBD across the stricture by one of six experienced pancreaticobiliary endoscopists. Each endoscopist performed more than 600 – 1200 ERCP procedures each year. All endoscopists had extensive (6 – 25 years) experience in ERCP. Endoscopic sphincterotomy was performed in all patients with a native anatomy before stent insertion.
The flexible and commercially available nitinol FCSEMSs were used (WallFlex– Boston Scientific Co., Natick, Massachusetts, USA; Bonastent– Standard Sci Tech, Seoul, Republic of Korea; Niti-S ComVI biliary stent– Taewoong Medical, Gimpo, Republic of Korea; and Anchoring-flap Hanaro stent– M. I Tech, Seoul, Republic of Korea). After stent placement, the patients’ symptoms and blood tests were assessed at every visit in the outpatient clinic, based on the endoscopists’ recommendation every month or at admission. When hepatic-biliary enzyme levels were elevated or patients developed additional symptoms, computed tomography (CT) was performed to estimate stent patency. The need for a repeat intervention during the study was determined by the recurrence of biliary obstructive symptoms and according to the decision of the investigator. The stent indwelling period was determined according to the discretion of the endoscopists and was measured from the date of stent insertion to the date of removal. In cases of complete distal stent migration, the period was defined from the date of stent insertion to the date of diagnosis of stent migration. Stent removal was usually performed 3 – 6 months after stent placement. Stent removal was typically accomplished by grasping the distal part of the stent with a rat-tooth forceps or snaring the distal end of the FCSEMS. The stent was then retracted gently with the endoscope or withdrawn through the working channel. For challenging stent removal cases, wire-guided balloon dilation within the stent was performed to help dissolve the impaction and to move the stent distally. The stents were subsequently removed using the snare or rat-tooth forceps. Prophylactic rectal indomethacin and pancreatic duct stenting were not applied regularly to prevent pancreatitis. The patients were followed up with a laboratory test 1 month after the removal of the FCSEMS. Laboratory tests and the assessment of stricture-related symptoms were performed every 3 months for the first year and every 6 months for the second and third years, in
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103 Stricture resolution
Original article
Table 1 Baseline characteristics of patients and fully covered self-expandable metal stents.
Characteristic
Value
Outcome assessment
Patients, n
134
The rates of technical success, stricture resolution, and stricture recurrence were evaluated. In addition, adverse events that were associated with stenting were assessed, including procedure-related pain, bleeding, pancreatitis, cholestasis, cholangitis, cholecystitis, stent migration, and removal difficulty. Technical success was defined as successful stent placement across the stricture. Stricture resolution was defined as ≥ 75 % improvement in stricture diameter as determined by comparing the cholangiograms obtained before stent insertion and after stent removal, drainage of contrast medium injected proximal to the stricture, and the ability to pass a retrieval balloon through the stricture. When malfunction of the stent was suspected and indicated by symptoms such as cholangitis, deterioration of liver function, or biliary pain, CT and endoscopic retrograde cholangiopancreatography (ERCP) were performed to determine the presence of stent dysfunction. Adverse events were classified as those occurring during stent insertion, the indwelling period, or with stent removal. Stricture recurrence was defined by abnormal liver function test results and the need for re-stenting based on the cholangiogram results. After stent removal, patients with stricture resolution were followed up every 3 – 6 months to monitor for stricture recurrence. The stent migration time was defined from the date of stent insertion to the date of diagnosis of stent migration. The stricture recurrence time was defined as the time from the date of stent removal to the date of diagnosis of stricture recurrence.
Age, median (range), years
56 (21 – 83)
Sex, n (%) Male
89 (66.4)
Female
45 (33.6)
BBS etiology, n (%) Gallstone related
51 (38.1)
Chronic pancreatitis
47 (35.1)
Post surgical 1
24 (17.9)
Others
12 (9.0)
Previous treatment, n (%) First-line treatment
55 (41.0)
Previous plastic stenting
79 (59.0)
Stricture duration prior to stenting, median (range), days 2
268 (10 – 2548)
Stricture location, n (%) Papilla
20 (14.9)
Distal CBD
82 (61.2)
Middle CBD
12 (9.0)
Proximal CBD
20 (14.9)
Stricture length, median (range), mm
17 (5 – 44)
Stent diameter, n (%) 8 mm
18 (13.4)
10 mm
116 (86.6)
Stent length, n (%) 40 mm
37 (27.6)
50 mm
49 (36.6)
60 mm
24 (17.9)
70/80/90 mm
11/6/7 (8.2/4.5/5.2)
Anchoring flaps, n (%)
Statistical analysis
With flaps
Data analyses were performed using the R software (version 2.10.1; R Foundation for Statistical Computing, Vienna, Austria) [13] and IBM SPSS Statistics for Windows (version 20.0; IBM Corp., Armonk, New York, USA). Baseline patient characteristics and basic outcomes variables regarding FCSEMS were summarized with a median and range for continuous variables, or a frequency and a percentage for categorical variables. The student t test, chi-squared test, or Fisher’s exact test, was used for between group comparisons of continuous or categorical variables, when appropriate. For analysis of stricture resolution, both univariate and multivariate logistic regressions were fitted to determine any associations with patient characteristics and the FCSEMS placement. Variables with a P value of < 0.2 in the univariate analysis were included as potential candidate variables for the multivariate model. The final model was determined using the backward variable selection approach where the least significant variable was removed one by one. As stricture recurrence and stent migration are time-dependent outcome variables, a Cox proportional hazards model was employed to determine any associations with the patient characteristics and the FCSEMS placement. The proportional hazards assumption was examined using the Schoenfeld residual test, and P values of < 0.05 were considered to be statistically significant.
Without flaps
28 (20.9) 106 (79.1)
BBS, benign biliary stricture; CBD, common bile duct. 1 Post-surgical cases included individuals with strictures caused by cholecystectomy, liver transplantation, and ampullectomy. Other patients included ones with primary sclerosing cholangitis, ischemic changes, and BBS of unknown origin. 2 Measured in 79 patients with previous plastic stenting.
Results !
Patient demographics Baseline characteristics of the patients and the indications for " Table 1. Gallstone-relatFCSEMS placement are summarized in ● ed strictures were the most common cause of BBSs. The most common location for a BBS was the distal CBD. A total of 55 patients received FCSEMS as first-line therapy, and 79 patients with BBSs had been treated previously with plastic stents, which failed to achieve stricture resolution. The median stricture duration was 268 days (range 10 – 2548 days) prior to stenting in patients who received FCSEMS as second-line therapy.
Technical success FCSEMSs were successfully placed in 99.3 % of the patients (133/ 134; 95 %CI 0.98 – 1.0). In one case of chronic pancreatitis, stent placement failed because of duodenal perforation, which occurred during duodenoscope insertion. The median indwelling period was 93 days (range 1 – 489). A total of 106 patients received a standard FCSEMS and 28 received the FCSEMS with anchoring " Table1). flaps (FCSEMS-AF) (●
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order to check for strictures. Subsequently, patients were reminded to visit the outpatient clinic if they experienced any stricture-associated symptom.
Original article
Valuable
Value
Technical success, n (%)
133 (99.3)
Overall stricture resolution, n (%)
103 (77.4)
Period of indwelling stent, median (range), days
93 (1 – 489)
Adverse events, n (%) Stent insertion related
25 (18.8)
Pain
13
Post-ERCP pancreatitis
11
Duodenal perforation During stent indwell period
1 18 (13.5)
Cholangitis
8
Pancreatitis
4
Stent obstruction
5
Cholecystitis Stent removal related
1 10 (7.5)
Pancreatitis
2
Bleeding
1
Inability to remove
2
Difficult to remove Stent migration
5 41 (30.8)
Proximal migration
21
Distal migration
20
Follow-up period after stent removal, median (range), days Stricture recurrence, n (%) Period of stricture recurrence, median (range), days
960 (365 – 3162) 26 (25.2) 390 (4 – 903)
ERCP, endoscopic retrograde cholangiopancreatography.
Adverse events " TaAdverse events related to stent insertion are summarized in● ble 2. One patient was lost during the follow-up period after stent " Taplacement. Adverse events during the indwelling period (● ble 2) included cholangitis (n = 8), pancreatitis (n = 4), stent obstruction (n = 5), and cholecystitis (n = 1). For the underlying etiologies in patients with cholangitis, there were 3, 3, and 2 patients with gallstone-related diseases, chronic pancreatitis, and post-surgical diseases, respectively. All of the patients’ stents were removed earlier than the arranged date for stent removal. The median indwelling duration was 77 days (range 25 – 96 days) for these patients. Cholecystitis occurred in one patient, and the extremely low-lying cystic duct take off was recognized as a risk factor.
Clinical outcomes Stricture resolution In 78.0 % of all patients (103/132; 95 %CI 0.71 – 0.85), the stric" Table 2). A tures resolved without the need for re-stenting (● stent indwelling period of at least 120 days was positively associated with stricture resolution (OR 3.22, 95 %CI 1.21 – 8.56; P = " Table 3). Stent migration was associated with a low rate 0.02; ● " Taof stricture resolution (OR 1.48, 95 %CI 1.13 – 1.94; P < 0.01; ● ble 3). Based on the univariate analysis, chronic pancreatitis was significantly related to the failure of stricture resolution (OR 0.42, " Table3). However, in multivariate a95 %CI 0.18 – 0.97; P = 0.04; ● nalysis, chronic pancreatitis was not associated with stricture resolution. The length of the stricture was not significantly related " Tato stricture resolution (OR 0.96, 95 %CI 0.91 – 1.01; P = 0.12; ● ble 3). The median stricture length of patients with stricture resolution was 16 mm (range 5 – 44 mm), which was not different
Table 3 Univariate and multivariate analysis of factors associated with stricture resolution.
Variable
Stricture resolution P value
OR
95 %CI
Female
1
(reference)
Male
0.91
0.38 – 2.22
Intrinsic causes
1
(reference)
Chronic pancreatitis
0.42
0.18 – 0.97
Papilla
1
(reference)
Distal CBD
1.05
0.34 – 3.28
0.94
Middle CBD
4.23
0.43 – 41.88
0.22
Proximal CBD
7.31
0.76 – 70.02
0.09
No
1
(reference)
Yes
0.6
0.25 – 1.45
No
1
(reference)
Yes
2.78
0.78 – 9.96
≥ 55
1
(reference)
< 55
0.98
0.38 – 2.22
Univariate analysis Sex 0.84
BBS etiology 0.04
The location of stricture
Previous plastic stenting 0.26
Anchoring flap 0.12
Age 0.84
Migration Yes
1
(reference)
No
1.48
1.13 – 1.94
< 0.01
Duration of stent indwelling duration < 120 days
1
(reference)
≥ 120 days
3.22
1.21 – 8.56
0.02
Stricture length
0.96
0.91 – 1.01
0.12
Intrinsic causes
1
(reference)
Chronic pancreatitis
0.46
0.2 – 1.09
Multivariate analysis BBS etiology 0.08
Migration Yes
1
(reference)
No
4.24
1.75 – 10.29
< 120 days
1
(reference)
≥ 120 days
2.97
1.11 – 8.03
< 0.01
Duration of stent indwelling 0.03
OR, odds ratio; CI, confidence interval; BBS, benign biliary stricture; CBD, common bile duct.
from those in patients without stricture resolution (18.5 mm, range 8 – 44 mm; P = 0.42). Stricture resolution was achieved in 83.0 % (44/53) and 74.7 % (59/79, 95 %CI 0.65 – 0.84) of patients who received stents as first- and second-line therapies, respectively; this difference was not significant (P = 0.26). The stricture duration prior to FCSEMS insertion was not significantly associated with stricture resolution in the second-line treatment group. The median stricture duration prior to stenting in patients with stricture resolution was 248 days (range 10 – 2548 days), which was not significantly different from cases without stricture resolution (282 days, range 50 – 1359; P = 0.51).
Stent removal Of the 132 patients with strictures, 112 underwent stent removal and 20 experienced distal stent migration. Endoscopic removal was successfully completed in 98.2 % of the patients (110/112; 95 %CI 0.96 – 1.0). The remaining two patients required surgical removal because of stent adhesion to the surrounding tissue in
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Table 2 Outcomes and adverse events related to fully covered, self-expandable, metal stent placement for benign biliary stricture.
Original article
Variable
Stricture recurrence P value
with stricture recurrence was chronic pancreatitis-related biliary " Table 4). Among stricture (HR 2.59, 95 %CI 1.20 – 5.61; P = 0.02; ● the 32 patients with chronic pancreatitis-related biliary strictures who achieved stricture resolution, 13 patients (40.6 %; 95 % CI 0.24 – 0.58) experienced stricture recurrence. Conversely, 13 (18.3 %; 95 %CI 0.09 – 0.27) of the 71 patients with other BBS etiol" Fig. 2). ogies (intrinsic causes) had stricture recurrences (●
HR
95 %CI
Female
1
(reference)
Male
2.13
0.8 – 5.64
Intrinsic causes
1
(reference)
Chronic pancreatitis
2.59
1.20 – 5.61
Papilla
1
(reference)
Distal CBD
0.96
0.32 – 2.85
0.94
Middle CBD
0.7
0.13 – 3.81
0.68
Proximal CBD
0.56
0.12 – 2.48
0.44
No
1
(reference)
Yes
0.99
0.45 – 2.15
No
1
(reference)
Yes
0.5
0.15 – 1.67
≥ 55
1
(reference)
< 55
1
0.97 – 1.03
0.81
1
0.99 – 1.05
0.92
< 120 days
1
(reference)
≥ 120 days
0.91
0.41 – 2.03
0.82
!
Stricture length
0.80
0.58 – 1.10
0.17
Intrinsic causes
1
(reference)
Chronic pancreatitis
2.59
1.20 – 5.61
The results of this study suggest that FCSEMS placement may be a reasonable treatment strategy for patients with BBS. Good clinical outcomes can be expected with longer stent indwelling periods (≥ 120 days), intrinsic causes of BBS, and the absence of migration during follow-up. The FCSEMS indwelling period has typically ranged from 3 to 6 months in previous published studies[7, 14, 17]. Even though a BBS can resolve with a relatively brief FCSEMS indwelling period owing to the benign characteristics of this condition, there is a lack of research on the appropriate indwelling periods required to achieve successful stricture resolution. In the current study, stricture resolution was significantly related to longer stent indwelling periods, especially those of at least 120 days (OR 2.97, 95 %CI 1.11 – 8.03; P = 0.03). The resolution rates for patients who had an indwelling period < 120 days and ≥ 120 days were 70.9 % (95 %CI 0.61 – 0.81) and 88.7 % (95 %CI 0.80 – 0.97), respectively (P = 0.02). Therefore, we recommend that the stent should be placed for at least 4 months for stricture resolution. The results concur with data from another prospective study in which patients who had indwelling stents for > 90 days were 4.3 times more likely to have stricture resolution than individuals with stents for ≤ 90 days (95 %CI 1.24 – 15.09) [18]. Migration of FCSEMSs has been reported to occur in 4 % – 38 % of BBS cases, which is higher than that in malignant stricture cases [19, 20]. Migration is considered to be a risk factor for failure of stricture resolution because it may lead to inadequate stricture dilation [18, 21, 22]. Stent migration also affected stricture resolution in the current study (P < 0.01). To date, various attempts have been made to prevent migration. One technique involves the use of a newly designed FCSEMS, known as the “bumpy stent,” which has anti-migration properties. However, in a recently published study, despite the proposed anti-migration feature of this FCSEMS, the stent migration rate was still significant [23]. Conversely, in the current study, the migration rate was sig-
Univariate analysis Sex 0.13
BBS etiology 0.02
Location of stricture
Previous plastic stenting 0.97
Anchoring flap 0.26
Age
Duration of stent indwelling
Stent migration Stent migration was observed in 41 (31.1 %; 95 %CI 0.23 – 0.39) out of the 132 patients (20 with complete distal migration and 21 with proximal migration), and the underlying etiologies included gallstone-related diseases (18), chronic pancreatitis (16), post-surgical diseases (5), and other inflammatory diseases (2). The median indwelling period was 70 days (range 25 – 169 days), which was shorter than the indwelling period in cases without stent migration. The FCSEMS-AF appeared to protect against stent migration (HR 0.26, 95 %CI 0.09 – 0.74; P = 0.01; ●" Fig. 3). However, other clinical outcomes including technical success, stricture resolution, other adverse events except migration, and removal difficulty, did not differ significantly between conventional FCSEMS and FCSEMS-AF. The cause of BBS (P = 0.51), stricture length (P = 0.17), or location of the stricture were " Table 5). not associated with stent migration (●
Discussion
Multivariate analysis BBS etiology 0.02
HR, hazards ratio; CI, confidence interval; BBS, benign biliary stricture; CBD, common bile duct.
one patient, and, in the other patient, because of migration of the proximal stent into the hepatic hilum where it could not be grasped by forceps. For patients in whom endoscopic stent removal was achieved, the procedure was completed without difficulty in almost all cases (105/110). However, difficulties with stent removal were encountered in five patients for the same reasons as in the surgical removal cases. Consequently, 2 – 4 sessions were required for stent removal. In four of these five patients, proximal stent migration occurred. Based on the univariate analysis, proximal migration was statistically significantly associated with difficulties in stent removal (OR 46.29, 95 %CI 5.19 – 413.15; P < 0.01). Other adverse events related to stent removal were post-ERCP pancreatitis (n = 2) and minor bleeding (n = 1). These events did not require specific treatment and subsided with conservative care.
Stricture recurrence Stricture recurrence was observed in 26 (25.2 %; 95 %CI 0.17 – 0.34) of 103 patients who achieved stricture resolution during the follow-up period (median 960 days; range 365 – 3162 days). All 103 patients remained alive during the follow-up period. The median period from stent removal to stricture recurrence was 390 days (range 4 – 903 days). The 1- and 2-year recurrence-free rates after stent removal were 87.5 % (95 %CI 0.82 – 0.94) and 73.3 % (95 %CI 0.65 – 0.83), respectively. The only factor associated
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Table 4 Univariate and multivariate analysis of factors associated with stricture recurrence.
Original article
Fig. 2 Comparison of stricture recurrence rates between chronic pancreatitis and other etiologies of benign biliary stricture using the Kaplan-Meier method. The red line indicates chronic pancreatitis and the black line corresponds to other etiologies.
100
Recurrence-free probability (%)
75
50
0 0
Other etiologies
20
40
60
80
71
66
50
29
22
15
11
8
4
3
1
Chronic pancreatitis 34
29
16
9
9
5
4
2
0
0
0
Fig. 3 A fully covered, self-expandable, metal stent with anchoring flaps at the proximal end of the stent.
nificantly lower for individuals who received the FCSEMS-AF compared with those who received the conventional FCSEMS (14.3 % vs. 36.9 %; P = 0.04). FCSEMS-AF has four anti-migration anchoring flaps at the proximal end and a flared portion at the distal end, which prevent distal and proximal migration, respectively. According to one multicenter prospective study, 22 patients with a BBS who received the FCSEMS-AF for stricture resolution did not experience migration during an indwelling period of up to 6 months [22]. In addition, Mangiavillano et al. reported only one incident of stent migration among 32 patients who underwent metal stenting with FCSEM-AF [24] Therefore, we believe that FCSEMS-AF designs may be very promising for the prevention of FCSEMS migration. Further study should confirm this hypothesis. Although a longer indwelling period was found to promote stricture resolution, there is concern that this could lead to difficulty in removing the stent. Furthermore, the optimal duration of stenting for safe removal has not been clearly identified. In the current investigation, however, removal difficulty did not vary according to indwelling period (3.8 % and 6.6 % in patients with ≥ 120 and < 120 days of indwelling duration, respectively; P = 0.699). These results are supported by findings from a previous
animal model study by Lee at al. [6], who studied 12 canines in order to identify histopathological changes in the bile duct in response to long-term FCSEMS placement. Results of this investigation demonstrated that FCSEMSs could be removed from the bile duct for up to 9 months after insertion without severe histopathological changes. The resolution rates in the patients with chronic pancreatitis were significantly lower than those with other type of BBSs (68.1 % vs. 83.5 %, P = 0.04). However, chronic pancreatitis was not found to be a factor associated with stricture resolution on multivariate analysis. The lack of statistical significance of chronic pancreatitis in stricture resolution may be due to the inadequate sample size (n = 29) of patients who failed to achieve stricture resolution. Therefore, further large-scale studies are needed to determine this association. In the current study, proximal stent migration was statistically significantly related to stent removal difficulties (OR 46.29, 95 % CI 5.19 – 413.15; P < 0.01). Proximal stent migration of FCSEMSs might result in permanent damage or obstruction of the biliary tree if the stent cannot be retrieved [25]. In our experience, grasping the stent with forceps or a snare was challenging when the distal end of the stent had migrated completely into the bile
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25
Original article
Table 5 Univariate and multivariate analysis of factors associated with stent migration.
Stent migration HR
95 %CI
Female
1
(reference)
Male
2.31
1.02 – 5.22
Intrinsic causes
1
(reference)
Chronic pancreatitis
1.24
0.65 – 2.36
1
(reference)
P value
Univariate analysis Sex 0.04
BBS etiology 0.51
Location of stricture Papilla Distal CBD
1.5
0.57 – 3.96
0.41
Middle CBD
0.37
0.04 – 3.22
0.37
Proximal CBD duct
0.78
0.24 – 2.55
0.68
Recurrence-free probability (%)
Variable
100
75
50
25
0
Previous plastic stenting No
1
(reference)
Yes
0.98
0.53 – 1.81
No
1
(reference)
Yes
0.26
0.09 – 0.74
≥ 55
1
(reference)
< 55
1.53
0.8 – 2.91
0.2
1.02
0.97 – 1.07
0.48
Female
1
(reference)
Male
2.56
1.12 – 5.89
No
1
(reference)
Yes
0.22
0.08 – 0.63
0 0.94
20
40 Time in months
60
80
Fig. 4
Stricture recurrence after stricture resolution.
0.01
Age
Stricture length Multivariate analysis Sex
0.03
Anchoring flap < 0.01
HR, hazards ratio; CI, confidence interval; BBS, benign biliary stricture; CBD, common bile duct.
duct. Multiple sessions of ERCP were necessary to address this situation. Although most proximal migrated FCSEMSs were successfully retrieved after 2 – 4 sessions of ERCP, two patients had to undergo surgical bile duct resection for stent removal. Thus, FCSEMS with lasso may be needed to prevent removal difficulty if the FCSEMS migrates proximally into the biliary tree [18]. However, we believe that the current study lacks sufficient evidence to show the clear correlation between proximal stent migration and stent removal difficulties because the differences were not statistically significant for the given sample size. The median follow-up period for the study cohort was 960 days (range 365 – 3162 days). We believe that this was sufficient to determine the long-term endurance of stricture resolution. Stricture recurrence developed in 26 patients, and the median period of stricture recurrence was 390 days (range 4 – 903 days). Almost all of the 26 patients in the study who developed a stricture recurrence experienced the condition within 2 years, and only " Fig. 4). A retrotwo cases occurred 2 years after stent removal (● spective study of FCSEMSs reported a stricture recurrence rate of 8.3 % (10/120, 95 %CI 0.03 – 0.13) for patients who experienced stricture resolution [10]. Among these individuals, only one had a stricture recurrence 2 years after stent removal. These results were similar to the current findings. Therefore, we suggest that clinicians should monitor for stricture recurrence in patients who achieve stricture resolution within 2 years after stent re-
moval. In addition, it is advisable for patients to undergo regular follow-up after stent removal for a minimum of 2 years. The stricture recurrence rate was significantly higher for individuals with chronic pancreatitis than cases with other BBS etiologies (40.6 % vs. 18.3 %; OR 2.59, 95 %CI 1.2 – 5.61; P = 0.02). We suspect that this higher recurrence rate was due to the fibrotic encasing process (extrinsic cause of BBS) that is more frequently seen in cases of chronic pancreatitis compared with other BBS etiologies. In contrast, fibrosis is often focal and confined to the duct wall in cases of other BBS etiologies [10, 26]. In addition, the higher stricture recurrence rate associated with chronic pancreatitis could be affected by the inaccurate estimation of stricture resolution. In the current and previous studies [10, 26], stricture resolution was measured during the same ERCP session after stent removal. Although strictures associated with chronic pancreatitis appeared to improve during stent removal on cholangiogram, this may be a transient occurrence. We suspect that there would be a risk of inadequate dilation of the strictures. This is because early stricture recurrence (< 90 days) was more frequently observed in patients with chronic pancreatitis (3 out of 13 patients with stricture recurrence) compared with those with other types of BBS (none of 13), when the time between stricture resolution and stricture recurrence was analyzed (data not shown). Based on these results, we recommend that assessment of stricture resolution should be performed a few days after stent removal. There were some limitations of this study. First, the study was a retrospective investigation. The enrolled patients were treated using FCSEMS from various companies and the analysis of each stent was impossible owing to the small numbers with each stent. The choice of FCSEMS was at the discretion of the six different pancreaticobiliary endoscopists, and together with the wide variety of stents used might also be a weakness of the study. However, we assume that the results could be informative to clinicians as data were based on the actual clinical utilization of various commercially available stents. Second, the absence of a control group is a major limitation of the study. In conclusion, FCSEMSs had a high success rate for stricture resolution. However, stricture recurrence appeared frequently in pa-
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Anchoring flap
tients with chronic pancreatitis. A longer indwelling period and the absence of stent migration might be important factors for stricture resolution. Competing interests: None
References 1 Dumonceau JM, Tringali A, Blero D et al. Biliary stenting: indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy 2012; 44: 277 – 298 2 Draganov P, Hoffman B, Marsh W et al. Long-term outcome in patients with benign biliary strictures treated endoscopically with multiple stents. Gastrointest Endosc 2002; 55: 680 – 686 3 Catalano MF, Linder JD, George S et al. Treatment of symptomatic distal common bile duct stenosis secondary to chronic pancreatitis: comparison of single vs. multiple simultaneous stents. Gastrointest Endosc 2004; 60: 945 – 952 4 Costamagna G, Tringali A, Mutignani M et al. Endotherapy of postoperative biliary strictures with multiple stents: results after more than 10 years of follow-up. Gastrointest Endosc 2010; 72: 551 – 557 5 Kaassis M, Boyer J, Dumas R et al. Plastic or metal stents for malignant stricture of the common bile duct? Results of a randomized prospective study Gastrointest Endosc 2003; 57: 178 – 182 6 Lee SS, Song TJ, Joo M et al. Histological changes in the bile duct after long-term placement of a fully covered self-expandable metal stent within a common bile duct: a canine study. Clin Endosc 2014; 47: 84 – 93 7 Mahajan A, Ho H, Sauer B et al. Temporary placement of fully covered self-expandable metal stents in benign biliary strictures: midterm evaluation (with video). Gastrointest Endosc 2009; 70: 303 – 309 8 Sauer B, Talreja J, Ellen K et al. Temporary placement of a fully covered self-expandable metal stent in the pancreatic duct for management of symptomatic refractory chronic pancreatitis: preliminary data (with videos). Gastrointest Endosc 2008; 68: 1173 – 1178 9 Tarantino I, Barresi L, Curcio G et al. Definitive outcomes of self-expandable metal stents in patients with refractory post-transplant biliary anastomotic stenosis. Dig Liver Dis 2015; 47: 562 – 565 10 Irani S, Baron TH, Akbar A et al. Endoscopic treatment of benign biliary strictures using covered self-expandable metal stents (CSEMS). Dig Dis Sci 2014; 59: 152 – 160 11 Baron TH. Covered self-expandable metal stents for benign biliary tract diseases. Curr Opin Gastroenterol 2011; 27: 262 – 267 12 Ryu CH, Kim MH, Lee SS et al. Temporary placement of fully covered self-expandable metal stents in benign biliary strictures. Korean J Gastroenterol 2013; 62: 49 – 54 13 Venables W, Smith D. The R Development Core Team (2008). An Introduction to R. Network Theory Limited. Bristol: 2010: https://www.rproject.org/
14 Moon JH, Choi HJ, Koo HC et al. Feasibility of placing a modified fully covered self-expandable metal stent above the papilla to minimize stent-induced bile duct injury in patients with refractory benign biliary strictures (with videos). Gastrointest Endosc 2012; 75: 1080 – 1085 15 Poley JW, Cahen DL, Metselaar HJ et al. A prospective group sequential study evaluating a new type of fully covered self-expandable metal stent for the treatment of benign biliary strictures (with video). Gastrointest Endosc 2012; 75: 783 – 789 16 Wagh MS, Chavalitdhamrong D, Moezardalan K et al. Effectiveness and safety of endoscopic treatment of benign biliary strictures using a new fully covered self expandable metal stent. Diagn Ther Endosc 2013; 2013: 183513 17 Sauer P, Chahoud F, Gotthardt D et al. Temporary placement of fully covered self-expandable metal stents in biliary complications after liver transplantation. Endoscopy 2012; 44: 536 – 538 18 Kahaleh M, Brijbassie A, Sethi A et al. Multicenter trial evaluating the use of covered self-expanding metal stents in benign biliary strictures: time to revisit our therapeutic options? J Clin Gastroenterol 2013; 47: 695 – 699 19 Isayama H, Mukai T, Itoi T et al. Comparison of partially covered nitinol stents with partially covered stainless stents as a historical control in a multicenter study of distal malignant biliary obstruction: the WATCH study. Gastrointest Endosc 2012; 76: 84 – 92 20 Tarantino I, Mangiavillano B, Di Mitri R et al. Fully covered self-expandable metallic stents in benign biliary strictures: a multicenter study on efficacy and safety. Endoscopy 2012; 44: 923 – 927 21 Costamagna G. Covered self-expanding metal stents in benign biliary strictures: not yet a “new paradigm” but a promising alternative. Gastrointest Endosc 2008; 67: 455 – 457 22 Park do H, Lee SS, Lee TH et al. Anchoring flap versus flared end, fully covered self-expandable metal stents to prevent migration in patients with benign biliary strictures: a multicenter, prospective, comparative pilot study (with videos). Gastrointest Endosc 2011; 73: 64 – 70 23 Walter D, Laleman W, Jansen JM et al. A fully covered self-expandable metal stent with antimigration features for benign biliary strictures: a prospective, multicenter cohort study. Gastrointest Endosc 2015; 81: 1197 – 1203 24 Mangiavillano B, Manes G, Baron TH et al. The use of double lasso, fully covered self-expandable metal stents with new “anchoring flap” system in the treatment of benign biliary diseases. Dig Dis Sci 2014; 59: 2308 – 2313 25 Cahen DL, Rauws EA, Gouma DJ et al. Removable fully covered self-expandable metal stents in the treatment of common bile duct strictures due to chronic pancreatitis: a case series. Endoscopy 2008; 40: 697 – 700 26 Katanuma A, Maguchi H, Takahashi K et al. Endoscopic management of benign biliary stricture: should we treat more aggressively? Dig Endosc 2014; 26: 536 – 537
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