Keywords
Pancreatobiliary (ERCP/PTCD) - Endoscopic ultrasonography - Intervention EUS
Introduction
Biloma, which is an encapsulated collection of bile juice within the abdominal cavity,
can occur after hepatobiliary surgery such as partial liver resection, pancreatoduodenostomy,
or laparoscopic cholecystectomy [1]
[2]. Although most bilomas resolve with conservative treatment, abdominal pain, fullness,
fever, jaundice, or peritonitis may be observed in symptomatic patients [3]. Therefore, drainage should be considered in such cases, selected from among percutaneous,
endoscopic, or surgical drainage techniques. Compared with the percutaneous and surgical
approaches, endoscopic drainage under endoscopic retrograde cholangiopancreatography
(ERCP) has the advantages of being less invasive for the patient and enabling evaluation
of the point of bile leakage. Conventional endoscopic treatments for biloma include
biliary stenting, endoscopic sphincterotomy, and nasal biliary drainage [4]. According to a previous study, success rates for the endoscopic approach range
from 90% to 97% [5]; however, this technique is much more challenging in the case of complex biloma,
such as the presence of a long bile defect, hilar or intrahepatic leaks, or surgically
altered anatomy, for which the mortality rate is reportedly up to 18% [6]. Endoscopic ultrasound (EUS)-guided drainage techniques for biliary obstruction,
pancreatic fluid collection, and cholecystitis have recently emerged [7]
[8]
[9]. EUS-guided transluminal biloma drainage (EUS-TBD) has also been reported [10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]. However, almost all previous studies regarding the endoscopic approach have used
both internal and external drainage. In addition, a plastic stent is used in EUS-TBD,
which is less effective than a self-expandable metal stent (SEMS) in terms of drainage
effect. External drainage has the disadvantages of poor cosmetic appearance and self-tube
removal. To overcome these issues, we perform endoscopic management using internal
drainage alone, and deploy fully covered SEMS (FCSEMS), especially for EUS-TBD. The
aim of the present study was to evaluate the feasibility and safety of internal endoscopic
drainage for complex biloma after hepatobiliary surgery, by the ERCP- or EUS-guided
approach, without external drainage.
Patients and methods
This retrospective study included consecutive patients who had complicated biloma
between January 2014 and October 2022. The inclusion criteria were an initial attempt
by internal drainage alone and the presence of biloma due to surgery. Patients who
underwent external drainage for biloma by any other technique, such as percutaneous
drainage, were excluded. The study protocol conformed to the ethical guidelines of
the 1975 Declaration of Helsinki as reflected in the a priori approval given by the
Human Research Committee at Osaka Medical College (IRB No. 2022–210).
Endoscopic procedures and internal drainage devices
As per our drainage strategy, biloma was evaluated by EUS prior to drainage. If the
biloma could be clearly identified on EUS and a safe puncture route could be obtained
in patients with surgically altered anatomy, EUS-TBD was the first choice of procedure.
If no biloma could be identified, drainage under ERCP guidance was the first choice.
For drainage under ERCP guidance, a duodenoscope (JF260V, Olympus Optical, Tokyo,
Japan) was inserted into the duodenum. Biliary cannulation using a standard ERCP catheter
(MTW Endoskopie, Düsseldorf, Germany) was then attempted. After successful biliary
cannulation and deployment of a 0.025-inch guidewire (VisiGlide, Olympus) ([Fig. 1]
a), contrast medium was injected to evaluate the site of bile leakage ([Fig. 1]
b). Insertion of the guidewire into the biloma was then attempted ([Fig. 1]
c). Finally, a 7F double plastic stent was deployed from the biloma to the duodenum
([Fig. 1]
d).
Fig. 1
a Successful biliary cannulation and deployment of a 0.025-inch guidewire. b The contrast medium is injected to evaluate the site of bile leakage. c Insertion of the guidewire into the biloma is attempted. d Finally, a 7F plastic stent is deployed from the biloma to the duodenum.
[Fig. 2] shows a computed tomography (CT) image of biloma that occurred after partial hepatectomy.
For drainage under EUS guidance, an echoendoscope (UCT 260, Olympus) was inserted
into the stomach. The biloma was punctured using a 19G needle (Sono Tip Pro Control
19G; Medi-Globe GmbH, Rosenheim, Germany, or EZ Shot 3 Plus; Olympus) with color Doppler
guidance to avoid puncturing any intervening vessels, and contrast medium was injected
([Fig. 3]
a). After the 0.025-inch guidewire was deployed within the biloma ([Fig. 3]
b), the stomach and biloma wall were dilated using a 4-mm balloon catheter (REN biliary
balloon catheter; Kaneka, Osaka, Japan) ([Fig. 3]
c). Finally, a fully-covered self-expandable metal stent (FCSEMS) (10 mm×8 cm, Bonastent;
Standard Sci Tech, Seoul, South Korea) was deployed ([Fig. 3]
d). In all patients who underwent EUS-TBD or drainage under ERCP guidance, biloma size
was evaluated by CT on the day after the procedure ([Fig. 3]
e). For both procedures, in the case of persistent symptoms with inadequate decrease
in the size of the biloma or inadequate resolution of inflammation, additional stenting
with a pigtail plastic stent or necrosectomy was considered. Stent removal was considered
if clinical success was obtained.
Fig. 2 Computed tomography imaging of biloma. Huge bimola connected to surgical resection
site is observed (a, c sagittal; c, d coronal).
Fig. 3
a Doppler to avoid puncturing any intervening vessels, and contrast medium is injected.
b After the 0.025-inch guidewire is deployed within the biloma. c The stomach and biloma wall are dilated using a 4-mm balloon catheter. d Finally, a fully covered self-expandable metal stent is deployed.
Definitions, outcomes, and statistical analysis
The primary outcome of this study was the technical success rate for endoscopic stenting
during ERCP and EUS. Technical success was defined as successful stenting from the
biloma to the duodenum in ERCP, and to the stomach in EUS-TBD. Secondary outcomes
were the evaluated clinical success rate and the rate of adverse events (AEs) associated
with these procedures. The final clinical success rate was defined as a complete or
partial decrease in biloma size (>50% reduction in diameter and size < 3 cm in maximum
diameter of the biloma on cross-sectional CT) without adding external drainage and
disappearance of symptoms such as abdominal pain and fever, with resolution of inflammation
on blood examination during clinical follow-up [16]
[17]. AEs associated with the procedures were evaluated using the severity grading system
of the American Society for Gastrointestinal Endoscopy lexicon [18]. Biloma diameter was measured on CT at the maximum diameter. Procedure time was
measured from endoscope insertion to removal. Duration of hospital stay was measured
from the day of biloma drainage. The follow-up period was measured from the day of
biloma drainage to the last follow-up day. Descriptive statistics are presented as
the mean±standard deviation (SD) or as the median and range for continuous variables,
and as the frequency for categorical variables. In univariate analysis, the x
2 or Fisher’s exact test was used for categorical variables and the Mann–Whitney test
or Student’s t test was used for continuous variables. All data were statistically analyzed using
SPSS version 13.0 statistical software (SPSS, Chicago, Illinois, United States).
Results
Patients
A total of 54 patients were enrolled. All patients first underwent EUS. Among them,
bilomas could not be identified in 41 patients by EUS; therefore, they underwent ERCP.
In this group, bilomas also could not be detected by cholangiogram; therefore, they
underwent surgical treatment. In total, 34 patients underwent biloma drainage during
ERCP (median age, 73.5 years; 25 males, 9 females; ERCP group). EUS-TBD was successfully
performed in 13 patients (median age, 76 years; 8 males, 5 females; EUS-TBD group).
[Table 1] lists patient demographic and clinical characteristics. The primary diseases were
hepatocellular carcinoma (n=18), metastatic liver tumor (n=11), gallbladder stone
(n=5), and other (n=13). The main types of surgery prior to complicating biloma were
partial hepatectomy (n=26) and right or left hepatectomy (n=10). There was no significant
difference in disease type or surgery type between the two groups. There was no significant
difference in median biloma diameter between the ERCP group (90 mm) and the EUS-TBD
group (93 mm) (P=0.700). Biloma was observed at a median of 20.5 days after surgery in the ERCP group
and at 23 days in the EUS-TBD group (P=0.626). The mean values of inflammatory indices prior to biloma drainage were white
blood count, 7556.8±4706 and 10803.1±6128.9 /mm3 (P=0.212) and C-reactive protein, 7.78±6.83 and 11.6±8.89 mg/L (P=0.096) in the ERCP and EUS-TBD groups, respectively. There was no significant difference
between the groups in terms of hemoglobin, total bilirubin, aspartate aminotransferase,
or alanine aminotransferase.
Table 1 Patient characteristics.
|
|
ERCP
|
EUS
|
P value
|
|
ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound;
WBC, white blood cell; SD, standard deviation; CRP, C-reactive protein; Hb, hemoglobin;
T-Bil, total bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
|
|
Total patients (n)
|
34
|
13
|
–
|
|
Median age (y, range)
|
73.5 (47–83)
|
76 (66–90)
|
0.105
|
|
Sex (male:female)
|
25/9
|
8/5
|
0.421
|
|
Disease, n
|
0.234
|
|
|
10
|
1
|
|
|
13
|
5
|
|
|
4
|
1
|
|
|
7
|
6
|
|
Kinds of surgery
|
0.217
|
|
|
16
|
10
|
|
|
5
|
2
|
|
|
2
|
1
|
|
|
4
|
0
|
|
|
7
|
0
|
|
Median diameter of biloma (mm, range)
|
90 (31–145.7)
|
93 (31–153)
|
0.700
|
|
Median days between surgery and drainage (range)
|
20.5 (7–73)
|
23 (7–58)
|
0.626
|
|
WBC (/μL, mean±SD)
|
7756.8±4706.7
|
10803.1±6128.9
|
0.212
|
|
CRP (mg/dL, mean±SD)
|
7.78±6.83
|
11.6±8.89
|
0.096
|
|
Hb (mg/dL, mean±SD)
|
10.5±1.85
|
10.7±1.58
|
0.625
|
|
T-Bil (mg/dL, mean±SD)
|
2.41±3.46
|
1.62±1.37
|
0.757
|
|
AST (U/L, mean±SD)
|
65.4±118.0
|
45.0±25.6
|
0.830
|
|
ALT (U/L, mean±SD)
|
75.1±158.8
|
46.2±28.7
|
0.295
|
Procedure outcomes
[Table 2] shows the results of biloma drainage. In the ERCP group, stent deployment was successful
in 34 of 36 patients and failed in two patients due to inability to identify the site
of bile leakage on cholangiography despite successful biliary cannulation. These two
patients underwent percutaneous biloma drainage. Stent deployment was successful in
all 13 patients in the EUS-TBD group. Therefore, the technical success rate was similar
between the groups (P=0.371); however, median procedure time was significantly shorter in the EUS-TBD group
(16 minutes) than in the ERCP group (26 minutes) (P=0.009). There was no significant difference in procedure-associated AEs between the
groups and all AEs resolved with conservative treatment.
Table 2 Procedure results.
|
|
ERCP
|
EUS
|
P value
|
|
ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound.
|
|
Technical success rate, % (n)
|
94 (32/34)
|
100 (13/13)
|
0.371
|
|
Median size of biloma after initial drainage (mm, range)
|
61.6 (23.7–113.6)
|
45.5 (20–55.5)
|
0.022
|
|
Median procedure time (min, range)
|
26 (11–50)
|
16 (8–21)
|
0.009
|
|
Number of sessions (mean±SD)
|
2.14±1.44
|
1.62±0.91
|
0.170
|
|
Clinical success rate, % (n)
|
87 (25/32)
|
84 (11/13)
|
0.482
|
|
Median period of stent deployment (day, range)
|
50 (8–260)
|
32.5 (12–108)
|
0.601
|
|
Adverse event
|
0.787
|
|
|
4
|
2
|
|
|
1
|
0
|
|
Median hospital stay (days, range)
|
46 (8–102)
|
22 (14–63)
|
0.038
|
|
Median follow-up period (days, range)
|
188 (21–2028)
|
182 (21–2000)
|
0.168
|
After initial biloma drainage, median biloma diameter was significantly smaller in
the EUS-TBD group (45.5 mm) than in the ERCP group (61.6 mm) (P=0.022). The mean number of endoscopic sessions required was higher in the ERCP group
(2.14 times) than in the EUS-TBD group (1.62 times), although the difference was not
significant (P=0.170). The median duration of stent deployment was shorter in the EUS-TBD group
(32.5 days) than the ERCP group (50 days), which was also not significant (P=0.601). The clinical success rate was 87% (25 of 32 patients) in the ERCP group and
84% (11 of 13 patients) in the EUS-TBD group. Of the patients in the ERCP group for
whom clinical success was not achieved, six underwent additional percutaneous biloma
drainage and one died due to sepsis. Among the corresponding patients in the EUS-TBD
group, one underwent additional percutaneous biloma drainage and one died due to sepsis.
The duration of median hospital stay was significantly shorter in the EUS-TBD group
(22 days) than the ERCP group (46 days) (P=0.038). No stent migration or dislocation
was observed in any patient in either group prior to stent removal. No recurrence
of biloma was observed in either group during clinical follow-up.
Discussion
Small and asymptomatic bilomas generally resolve with conservative treatment. However,
in the case of large size and in when patients have symptoms, intervention is required.
Recent developments in endoscopic procedures and the high morbidity rates [19] associated with surgical drainage have led to a decrease in surgical treatment.
With endoscopic and percutaneous approaches, external and/or internal drainage tube
deployment may be the first consideration [20]
[21]
[22]
[23]. Deployment of a drainage tube decreases the internal pressure of the biliary tract,
after which the biloma may resolve. However, external drainage requires a percutaneous
drainage tube, which has several disadvantages, including self-removal of the tube.
More recently, various interventions have emerged that are performed under EUS guidance.
Several reports regarding EUS-TBD have been published to date [10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]. In the first published case series, Shami et al described EUS-guided drainage in
five patients who had complicated symptomatic biloma [12]. In these patients, the biloma was punctured using a 19G needle under EUS guidance
and a 0.035-inch guidewire was then deployed. Tract dilation was performed using a
6- or 8-mm balloon and one or two double-pigtail plastic stents were deployed. After
performing these steps successfully, biloma resolution was obtained in all patients
without any AEs. Recently, Lorenzo et al conducted a retrospective comparison study
between ERCP and EUS-TBD for complex biloma [17]. They enrolled 30 patients with biloma secondary to refractory biliary leak who
were treated by ERCP (n=16) or EUS-TBD (n=14). The technical success rate was 88%
(14 of 16) for ERCP and 100% (16 of 16) for EUS-TBD. During clinical follow-up (median,
33.2 months), clinical success was obtained in 75% of patients who underwent EUS-TBD
and in 67% of patients who underwent ERCP. Regarding biloma size, partial biloma regression
(>50%, and size <3 cm) and complete biloma resolution was obtained in 85% and 59%
of patients, respectively, with no significant difference between EUS-TBD and ERCP.
Surgical treatment was required in one patient. Serious AEs associated with the procedures
occurred in one patient who underwent EUS-TBD and three who underwent ERCP. Based
on these favorable clinical results, they concluded that ERCP and EUS-TBD are technically
feasible with high clinical success and may avoid the need for additional surgery.
According to these previous reports, EUS-TBD appears to be a safe and effective treatment
for biloma. However, most of these reports evaluated EUS-TBD combined with external
drainage. Of these, the study with the largest number of patients [17] included deployment of one or two double pigtail plastic stents combined with an
endoscopic nasal cyst drainage tube if needed. In addition, previous percutaneous
drainage had been performed in 87% (26 of 30), and the drain was placed during initial
surgery (n=6), by interventional radiology (n=15), or during redo surgery (n=5). To
avoid the influence of external drainage in evaluating the true safety and effectiveness
of EUS-TBD, it is necessary to perform a clinical study of EUS-TBD without external
drainage. In contrast, Tonozuka et al evaluated the technical feasibility and safety
of EUS-guided drainage for infected biloma [16]. Although only six patients were included in their study, the technical success
rate was 100% and the clinical success rate at the first session was 83.3% with no
procedure-related AEs. Interestingly, they evaluated EUS-TBD performed using either
a metal or plastic stent but not in combination with external drainage. However, the
study had several limitations, including lack of a historical control group and variation
in length of the metal stents.
The major findings of the present study were that EUS-TBD was superior to ERCP in
several respects, including short procedure time, biloma size after drainage, and
short hospital stay. Although previous reports have mainly used plastic stents, metal
stents might be suitable for EUS-TBD, for two reasons. First, drainage might be more
effective with the 10-mm diameter metal stent in EUS-TBD than with a plastic stent
in ERCP. Second, if no adhesion is created between the biloma and the stomach wall,
the complication of leak from biloma into the abdominal cavity may occur due to the
gap between the plastic stent and the fistula. In contrast, if FCSEMS is used during
EUS-BD, leakage from a biloma into the abdominal cavity may be prevented. Recently,
a lumen-apposing metal stent (LAMS) has been developed. Compared with tubular SEMS,
a LAMS has a large diameter and strong anchoring force. Therefore, LAMS might be preferable
compared with tubular SEMS, although Cassis et al reported successful treatment of
biloma with EUS-guided drainage using LAMS [14]. While this treatment might be promising, there are no clinical trials of EUS-guided
drainage using LAMS for biloma. Therefore, clinical trials are needed of EUS-guided
drainage using LAMS and also assessing different kinds of stents, such as LAMS, tubular
SEMS, and plastic stents.
To the best of our knowledge, the present study is the first to report evaluation
of endoscopic internal drainage for biloma without additional external drainage and
to compare the use of ERCP and EUS-TBD. However, our study also has several critical
limitations such as the retrospective nature and small sample size. Because the diameter
of SEMS is large compared with plastic stents, a comparison between two groups might
not be fair because the difference might influence the drainage effect. Also, because
our study period was relatively long, operator technique may have differed during
study period. Moreover, our study has selection bias. In our study, EUS-TBD was first
considered. If a biloma could not be detected, ERCP was attempted as the next drainage
technique. Therefore, more challenging cases might have been included in the ERCP
group. This fact influences clinical results for both procedures, and therefore, our
result may not be generalizable. Finally, a cost-effectiveness analysis could not
be performed. The approximate cost per patient in the ERCP group was $4392 and in
the EUS-TBD group was $4821, but because our study period was very long and costs
were not definitively documented in our hospital, it was not possible to do an accurate
cost analysis.
Conclusions
In conclusion, ERCP and EUS-TBD are complementary techniques, each with its own merits
in specific clinical scenarios. If both techniques are feasible for a patient, EUS-TBD
should be considered in view of the shorter times for the procedure, hospital stay,
and biloma resolution associated with it.
