Keywords
benign biliary stricture - biliary stent - biodegradable - percutaneous transhepatic
cholangiopathy
Benign biliary strictures are usually iatrogenic.[1]
[2] These strictures can be difficult to treat and cause significant morbidity and health
care cost due to the need for repeated interventions.
The use of biodegradable biliary stents (BBS) is a relatively new treatment option
for these strictures. It is thought to have comparable patency to endoscopic treatment
and plastic stent insertion, with less need for reintervention and recurrent admissions.[2]
[3]
[4]
This study is a continuation of a previous article published in 2019,[5] with a larger number of patients and longer follow-up duration.
Materials and Methods
This is a single-center retrospective observational study conducted in a tertiary
hospital. Institutional review board approval was obtained. The study included all
adult patients who had benign biliary strictures treated using BBS between July 2016
and August 2019. This study is a continuation of the article by Arabi et al,[5] with a larger number of patients, longer follow-up duration, and additional cause
of benign stricture (inadvertently clipped left duct during cholecystectomy). The
current study includes 19 patients, of which 12 were included in the previous cohort.
Patients with malignant stricture were excluded.
The related laboratory information, demographic data, and imaging data were reviewed.
Baseline bilirubin (total and direct), aspartate aminotransferase, alanine aminotransferase,
and alkaline phosphatase were obtained for all patients and then used for a follow-up
in conjunction with imaging.
A total of 20 patients who underwent BBS insertion were identified; one patient died
after 2 months due to progressive hepatic failure and was excluded. Nineteen patients
were included in the study (15 males, 79%) with a mean age of 55 years (range: 23–72
years).
Seventeen patients had liver transplant (15 choledochocholedochal anastomosis and
2 hepaticojejunal anastomosis; [Table 1], [Fig. 1]). One patient had hepaticojejunostomy due to primary sclerosing cholangitis and
one patient had iatrogenic left main bile duct occlusion, which was inadvertently
closed by surgical clips during cholecystectomy ([Fig. 2]).
Table 1
Stricture features
|
Total
|
Reintervention
|
|
Level of stricture
|
N
|
Percent
|
No (n = 12)
|
Yes (n = 7)
|
|
Hepaticojejunal
|
4
|
21.05
|
2
16.67
|
2
28.57
|
|
Choledochocholedocal
|
14
|
73.68
|
9
75.00
|
5
71.43
|
|
Left main bile duct
|
1
|
5.26
|
1
8.33
|
0
0.00
|
|
Etiology of stricture
|
|
Anastomotic stricture post–liver transplant
|
16
|
84.21
|
10
83.33
|
6
85.71
|
|
primary sclerosing cholangitis (PSC)
|
2
|
10.53
|
1
8.33
|
1
14.29
|
|
Iatrogenic bile duct occlusion during cholecystectomy
|
1
|
5.26
|
1
8.33
|
0
0.00
|
Fig. 1 Intraprocedure images from a patient who presented with jaundice and abnormal liver
function test 10 months after liver transplant. She underwent four sessions of cholangioplasty
with recurrent anastomotic stricture. (a) Initial cholangiogram shows high-grade anastomotic stricture. (b) Cholangiogram after deployment of BBS shows patent stent with contrast flow to the
duodenum. On follow-up for the next 3 years, the patient remained tube-free with normalized
liver functions.
Fig. 2 A 72-year-old female with history of cholecystectomy complicated by iatrogenic left
bile duct occlusion. (a, b) Cholangiograms showing abrupt cutoff of the left main bile duct. Three surgical
clips are noted at the site of occlusion. Initial trial to cross the occlusion was
not successful; so, an 8-Fr external biliary drain was inserted. (c) The patient was brought later for recanalization. The right-side bile ducts were
accessed and a balloon was inserted and then targeted by a needle from the left side.
(d) The area of stricture was predilated and then 8 mm × 4 cm BBS was placed. Cholangiogram
shows patent stent with contrast flow to the duodenum.
The mean time since surgery was 40.8 months (range: 1.8–199 months). All patients
had previous sessions of percutaneous transhepatic balloon cholangioplasty with an
average of three sessions (range: 1–6). Patients received preprocedural antibiotics
with 1 g cefazolin IV as per protocol. The BBS used was (ELLA-CS, s.r.o., Hradec Kralove,
Czech Republic) a self-expandable bare stent made of biodegradable material (polydioxanone).
The placement was done according to the instruction for use from the manufacturer
(the technique was described in the previous article).[5]
Clinical success was evaluated using laboratories, imaging, and being tube-free post
BBS placement. Technical success was defined as correct deployment of the stent and
documenting its patency immediately postdeployment. Endpoints were either last follow-up
(at least 6 months) or reintervention (endoscopic, percutaneous, or surgical). Time
to reintervention was defined as the time interval between initial stent placement
and any subsequent intervention (endoscopic or percutaneous) done due to stricture
recurrence (diagnosed by laboratory and/or imaging evidence).
Complications were evaluated and classified according to the new adverse event classification
published by the Society of Interventional Radiology Standards of Practice Committee.[6]
Results
Stents were successfully deployed in all 19 patients (technical success: 100%). The
median follow-up time was 468 days (range: 8–1,211 days).
Twelve patients (63.2%) remained tube-free during the follow-up and had improved laboratory
results from baseline and did not need further intervention at median follow-up time
of 650 days (range: 168–1,333 days). Patency rate was 90% (17/19) at 6 months and
80% (12/15) at 12 months without the need for additional interventions.
Seven patients (36.8%) in the study had stricture recurrence and needed reintervention
with median time to reintervention of 418 days (range: 8–1,155 days; [Table 2]).
Table 2
Reintervention types
|
Type of reintervention
|
Frequency
|
|
Balloon cholangioplasty alone
|
1
|
|
Balloon cholangioplasty and internal–external biliary drain
|
2
|
|
Endoscopic retrograde cholangiopancreatography (ERCP) with insertion of plastic stent
|
2
|
|
External biliary drain
|
1
|
|
Internal–external biliary drain
|
1
|
The total procedure-related complication rate was 21% (4/19). Three patients had minor
complications (one to two spikes of fever with negative blood cultures; no further
intervention or prolonged management was needed). One patient had major complications
presented with fever and positive blood culture with Escherichia coli diagnosed with cholangitis and sepsis that required a treatment course with piperacillin/tazobactam
for 10 days. The same patient had stent migration to the duodenum noticed in follow-up
tube cholangiogram after 5 days of insertion but did not need further intervention.
No procedure-related pancreatitis or deaths occurred.
Patients who did not need reinterventions after BBS placement were noted to have higher
rate of prior sessions of intervention with balloon cholangioplasty prior to stenting
(median: 3, range: 1–6). While those who required reinterventions were noted to have
lower number of prior interventions (median: 2, range: 1–3).
Discussion
Biodegradable stents have been used to treat esophageal strictures with promising
results. It is also being studied for airways and intestinal and colonic strictures
caused by various benign and malignant causes.[7]
[8]
[9]
Biodegradable stents are a novel treatment option for benign biliary strictures that
obviate the need for stent removal. Studies have shown low migration rate, less need
for reintervention, and acceptable patency.[3]
[10]
In a retrospective multicenter study by Mauri et al, 107 patients with refractory
benign biliary strictures treated using BBS were reviewed. Technical success was 98%
without major complications. The study suggested that percutaneous placement of BBS
is a safe and feasible procedure for the management of refractory biliary stricture,
with estimated stricture recurrence rate of 7.2, 26.4, and 29.4% at 1, 2, and 3 years,
respectively. The estimated mean time to stricture recurrence was 38 months.[4]
Battiste et al reported the outcome of BBS stents use to treat refractory benign biliary
anastomotic strictures post–liver transplantation. Success rate of complete resolution
of anastomotic stricture was achieved in 72% of patients after a median follow-up
time of 27 months. Only one complication of hemobilia was observed.[10]
In a recent systematic review and meta-analysis reported by Almeida and Donato comparing
BBS versus multiple plastic stents (MPS), three studies regarding BBS and six regarding
MPS were included. The overall success rate was comparable (83% for BBS, 84% for MPS).
Reintervention was less with BBS. However, cholangitis and hemobilia postprocedure
were higher with BBS (cholangitis: 24.1% with BBS vs. 6.1% with MPS; hemobilia: 3%
with BBS vs. <1% with MPS).[2]
A larger prospective, multicenter, observational, nonrandomized study (the BiELLA
study) was conducted in 11 tertiary hospitals in Spain and included 150 patients to
study safety and efficacy of BBS in the treatment of benign biliary strictures. The
primary mean patency rates for stent were 86.7, 79.6, and 78.9% at 12, 36, and 60
months, respectively. Biliary restenosis and occlusion occurred in 40 patients (26.6%).[11]
In our study, results show that BBS stents are feasible and a relatively safe method
for the treatment of benign biliary strictures, with one reported major complication.
Success rate was slightly lower than in the previously mentioned studies, with 63%
resolution of strictures and improved biochemical markers with the patient being free
from tube dependency. A third of patients needed reintervention after mean follow-up
time of 13.9 months. These patients were found to have a smaller number of previous
interventions (median: 2, range: 1–3) prior to stent placement compared with the group
who did not require reintervention (median: 3, range: 2–6). This suggests that BSS
can be helpful in patients who require multiple cholangioplasty to reduce the need
for further interventions.
Limitations of the study include its small sample size that is related to the infrequent
procedure, the retrospective nature of the study, and lack of comparison group.
The use of biodegradable stents is a safe and effective treatment option for benign
biliary strictures and can help obviate the need for repeated interventions and long-term
tube-dependency. Additional studies with a larger sample size are suggested to confirm
these results and further assess the cost-effectiveness and impact on quality of life
compared with other methods of treatment.
