Introduction
Cholecystectomy is one of the most commonly performed surgeries. Cholecystectomy is
typically approached in a minimally invasive laparoscopic fashion. The incidence of
bile leak following laparoscopic cholecystectomy is estimated to be approximately
1 % [1]. While a significant percentage of bile leaks resolve spontaneously and without
clinical sequelae in the early post-perative period, persistent bile leaks typically
require therapeutic intervention with endoscopic retrograde cholangiopancreatography
(ERCP). Among patients with post-cholecystectomy bile leak who undergo ERCP, the cystic
duct stump is the most frequently identified site of leak [1]
[2].
The goal of endoscopic management in patients requiring ERCP for post-cholecystectomy
bile leak without bile duct injury is to decrease the pressure gradient at the level
of the papilla, thereby creating a high flow pathway to siphon bile flow into the
duodenum and away from the site of leak to permit spontaneous leak healing and closure.
This can be achieved by placement of a biliary endoprosthesis, with or without biliary
sphincterotomy, or conceivably in some instances by biliary sphincterotomy alone [2]
[3]. Plastic biliary stents are first-line therapy for this indication given their efficacy,
ease of placement and subsequent removal, and low cost. Typical practice at our institution
is to place the shortest plastic stent available in order to minimize resistance to
transpapillary flow, as based on principles of fluid dynamics resistance to laminar
flow increases with increasing stent length.
In some patients undergoing cholecystectomy factors such as severe gallbladder inflammation
or limited anatomic exposure may prevent safe completion of a standard laparoscopic
cholecystectomy. In such cases, surgical options include conversion to an open surgical
approach and/or conversion to a subtotal cholecystectomy. Options for subtotal cholecystectomy
include a fenestrated technique in which the neck of residual gallbladder is left
open without attempt at ligation or closure, or a reconstituted technique in which
closure of the remaining gallbladder is attempted resulting in an intact gallbladder
lumen [4]. The prevalence of bile leaks following subtotal cholecystectomy may be as high
as 18 % [5], and patients who have undergone subtotal cholecystectomy are more likely to require
post-operative ERCP compared with patients who have undergone standard/total cholecystectomy
[6].
In our clinical experience, and although stent selection is ultimately at the discretion
of the endoscopist, a consultative request to perform ERCP for treatment of bile leak
following subtotal cholecystectomy is often accompanied by a request from the surgical
team to place a fully covered self expanding metal stent (FCSEMS) rather than a plastic
stent as therapeutic management. Given the perceived high-grade nature of the leak,
the premise is that a FCSEMS is necessary to “seal off” the cystic duct and prevent
leakage from the residual gallbladder. While FCSEMS have expanded indications for
treatment of benign biliary disease including benign bile duct strictures [7], and while use of FCSEMS has been reported for successful management of refractory
bile duct leaks [8]
[9], to our knowledge controlled or comparative data have not been reported to either
question the utility of plastic stents or support the use of FCSEMS as first-line
management for bile duct leaks following subtotal cholecystectomy.
The aim of this study was to compare outcomes of endoscopic plastic stent therapy
for post-cholecystectomy bile leak in patients undergoing standard (total) vs subtotal
cholecystectomy. The a priori hypothesis was that there would be no difference in
leak resolution rates following plastic stent placement in patients undergoing standard
vs subtotal cholecystectomy.
Patients and methods
This was a single-center retrospective study, with approval for study conduct granted
by the Vanderbilt University Medical Center Institutional Review Board.
Patients who had undergone ERCP for treatment of post-cholecystectomy bile leak between
2009 and 2020 were identified from an endoscopy database consisting of the cases of
two interventional endoscopists (PY and AG). Study inclusion criteria were strictly
restricted to patients with surgically unaltered foregut anatomy who had undergone
both cholecystectomy and ERCP at our institution. Patients who had undergone cholecystectomy
at an outside institution and who were then transferred to our institution for management
of bile leak, for whom full operative details of cholecystectomy were not available
for review, were excluded. Patients identified at ERCP to have leaks originating from
the gallbladder fossa/duct of Luschka were excluded, as were patients found at ERCP
to have common bile duct or right posterior sectoral duct injury. Patients who underwent
ERCP for bile leak following blunt or penetrating abdominal trauma, bile leak following
partial hepatectomy, or anastomotic bile leak following orthotopic liver transplantation
were also excluded. Patients lost to follow-up or otherwise without follow-up ERCP
at our institution to confirm leak resolution were excluded.
Demographic and clinical data were extracted from the electronic medical record. Operative
notes from cholecystectomy and ERCP were manually reviewed to identify relevant technical
and procedural details. A high-grade bile leak was defined as cholangiographic evidence
of bile leak without requirement for balloon occlusion cholangiography; conversely,
a low-grade bile leak was defined as cholangiographic evidence of bile leak elicited
only by balloon occlusion cholangiogram.
The primary outcome of interest was resolution of bile leak on repeat interval ERCP.
Standard protocol at our institution is to schedule repeat elective ERCP at 6 to 8
weeks following placement of a stent for a bile leak, unless warranted sooner for
reintervention if there is clinical suspicion for refractory leak. Additional outcomes
of interest included need for additional endoscopic, radiologic, or surgical intervention
for refractory bile leak. In cases requiring additional endoscopic intervention, procedural
details were noted. Adverse events (AEs) associated with ERCP were recorded including
pancreatitis, hemorrhage, or perforation, with pancreatitis severity graded according
to standard criteria proposed by Cotton et al [10].
Extracted data were stored in de-identified fashion in REDCap (Research Electronic
Data Capture) housed at Vanderbilt University. REDCap is a secure, web-based application
that provides an intuitive user interface that streamlines project development and
improves data entry through real-time validation rules (with automated data type and
range checks). REDCap also provides easy data manipulation (with audit trails for
reporting, monitoring and querying patient records) and an automated export mechanism
to common statistical packages [11].
Statistical analysis was performed using IBM SPSS Statistics 26 (Armonk, New York,
United States). Univariate testing of significance for categorical values was performed
using Chi square or Fisher’s exact testing. Univariate testing of significance for
continuous variables was performed using one-way analysis of variance (ANOVA). A two-sided
P < 0.05 was accepted as the threshold for statistical significance.
Results
Demographics
A total of 61 subjects fulfilled study inclusion criteria. Of subjects, 53 % (32/61)
were male and mean age was 53.1 years. The most common indication for cholecystectomy
was acute cholecystitis (72 %) and the operative approach was laparoscopic in the
majority of cases (74 %). Of the patients, 44 % (27/61) had undergone total/standard
cholecystectomy while 56 % (34/61) had undergone subtotal cholecystectomy. Patients
who underwent subtotal cholecystectomy were more likely to be male (65 % vs 37 %,
P = 0.03) and more likely to be older (58.6 years vs 46.2 years, P < 0.01) than patients who underwent total cholecystectomy. Full demographic details
and details of cholecystectomy are listed in [Table 1].
Table 1
Cohort demographic and cholecystectomy details.
|
N = 61 total
|
|
Age
|
53.1 years
|
|
Male sex
|
32 (53 %)
|
|
Current smoker
|
7 (12 %)
|
|
Preoperative ERCP performed
|
9 (15 %)
|
|
Indication for cholecystectomy
|
|
|
44 (72 %)
|
|
|
8 (13 %)
|
|
|
7 (12 %)
|
|
|
2 (3 %)
|
|
Surgical approach
|
|
|
44 74 %)
|
|
|
14 (23 %)
|
|
|
2 (3 %)
|
ERCP, endoscopic retrograde cholangiopancreatography.
Technical aspects of ERCP
Mean time to ERCP following cholecystectomy was 5.2 days. High-grade bile leak was
evident in 51 % of cases (31/61). Biliary sphincterotomy was performed in 67 % of
cases (41/61). A single plastic stent was placed as the index endoprosthesis in 87 %
of cases (53/61), while FCSEMS was placed in 13 % of cases (8/61). Full details of
index endoscopic intervention are listed in [Table 2].
Table 2
ERCP details.
|
N = 61 total
|
|
High-grade bile leak identified
|
31 (51 %)
|
|
Choledocholithiasis identified at ERCP
|
10 (16 %)
|
|
Biliary sphincterotomy performed
|
41 (67 %)
|
|
Plastic biliary stent placed
|
53 (87 %)
|
|
FCSEMS placed
|
8 (13 %)
|
|
Plastic biliary stent diameter:
|
|
|
49 92 %)
|
|
|
4 (8 %)
|
|
Plastic biliary stent length:
|
|
|
34 64 %)
|
|
|
8 (15 %)
|
|
|
6 (11 %)
|
|
|
4 (8 %)
|
|
|
1 (2 %)
|
|
FCSEMS diameter:
|
|
|
4 (50 %)
|
|
|
4 (50 %)
|
|
FCSEMS length:
|
|
|
1 (13 %)
|
|
|
5 (63 %)
|
|
|
2 (25 %)
|
ERCP, endoscopy retrograde cholangiopancreatography; FCSEMS, fully covered self-expanding
metal stent
Adverse events of ERCP
Identified AEs associated with ERCP were limited to two cases of pancreatitis, one
of which was mild and one of which was moderate in severity. There were no instances
of sphincterotomy-induced hemorrhage requiring either immediate or delayed endoscopic
intervention, and no instances of duodenal or retroperitoneal perforation.
Clinical outcomes of ERCP and stent therapy
There was no difference in the proportion of patients receiving plastic stents vs
FCSEMS, and no difference in the proportion of patients receiving biliary sphincterotomy
when comparing the total and subtotal cholecystectomy groups. Difference in mean time
to ERCP following total cholecystectomy (6.6 days) vs subtotal cholecystectomy (4.1
days) did not meet the threshold for statistical significance (P = 0.10). Comparison of demographic and treatment details in the total vs subtotal
cholecystectomy groups is depicted in [Table 3].
Table 3
Demographic and ERCP comparison of total vs subtotal cholecystectomy groups.
|
Total
|
Subtotal
|
P value
|
|
N = 27
|
N = 34
|
|
|
Age
|
46.2 years
|
58.6 years
|
< 0.01
|
|
Male
|
10 (37 %)
|
22 (65 %)
|
0.03
|
|
High-grade bile leak identified
|
11 (41 %)
|
20 (59 %)
|
0.16
|
|
Choledocholithiasis identified at ERCP
|
5 (19 %)
|
5 (15 %)
|
0.74
|
|
Biliary sphincterotomy performed
|
19 (70 %)
|
22 (65 %)
|
0.64
|
|
Plastic biliary stent placed
|
24 (89 %)
|
29 (85 %)
|
1.0
|
|
FCSEMS placed
|
3 (11 %)
|
5 (15 %)
|
|
|
Time from cholecystectomy to ERCP
|
6.6 days
|
4.1 days
|
0.10
|
ERCP, endoscopic retrograde cholangiopancreatography; FCSEMS: fully covered self-expanding
metal stent
Overall leak resolution rate following index ERCP with stent placement was 96 % (26/27)
following total cholecystectomy and 91 % (31/34) following subtotal cholecystectomy
(P = 0.25). Mean time to repeat ERCP for stent removal was 53.2 days following total
cholecystectomy and 54.9 days following subtotal cholecystectomy. Excluding patients
treated with FCSEMS, 96 % of patients (23/24) treated with plastic stents following
total cholecystectomy achieved complete leak resolution without requirement for reintervention
compared to 90 % of subjects (26/29) treated with plastic stents following subtotal
cholecystectomy (P = 0.62).
Of the four patients with evidence of persistent leak on follow-up ERCP, all had been
treated with plastic stents at the index ERCP (one following total cholecystectomy,
three following subtotal cholecystectomy). At repeat ERCP documenting persistent leak,
all were treated with extended duration stent therapy (mean 134 days, range 53 – 309).
One patient also required interventional radiology intervention, consisting of percutaneous
drainage of a biloma, for refractory bile leak following index ERCP with stent placement.
An additional patient treated with FCSEMS at index ERCP following subtotal cholecystectomy
and who underwent stent removal with documentation of leak resolution at follow-up
ERCP, presented in delayed fashion with recurrent biloma and underwent repeat ERCP
with replacement of a plastic biliary stent as well as radiologic intervention with
percutaneous fibrin glue injection. No patients required surgical reintervention for
refractory bile leak. All achieved ultimate leak resolution.
Discussion
Subtotal cholecystectomy has emerged as a viable option for surgical management of
gallbladder disease in technically complex cases, with data suggesting that the practice
of subtotal cholecystectomy has increased considerably over the past decades. A study
from the National Inpatient Sample reported that the rate of laparoscopic subtotal
cholecystectomy increased from 0.12 % of all cholecystectomies in 2003 to 0.28 % in
2014, and the rate of open subtotal cholecystectomy increased from 0.10 % to 0.52 %
within the same timeframe. Factors associated with likelihood of subtotal cholecystectomy
in this study included male sex, Asian American ethnicity, surgery performed in a
teaching hospital, and surgery performed in a rural location [12]. ERCP with biliary stent placement is first-line therapy for treatment of bile leaks
following cholecystectomy. Endoscopic intervention offers high rates of durable leak
resolution in minimally invasive fashion and with low rates of morbidity. Yet scant
data are available reporting outcomes of endoscopic therapy for bile leaks specifically
following subtotal cholecystectomy, which was a focus of this study. Given the reported
high prevalence of bile leaks following subtotal cholecystectomy [5], continued increase in the practice of subtotal cholecystectomy would have major
implications on post-cholecystectomy ERCP volume and mandates a need for high-quality
data to guide optimal endoscopic management for this patient population.
This study reports high rates of leak resolution (91 %) with biliary stent placement
following subtotal cholecystectomy, including a 90 % resolution rate with a single
plastic stent as used in the majority of patients in this cohort. Although not evaluated
in this study, placement of multiple plastic biliary stents for treatment of high-grade
leaks [13] could also be an alternative to single plastic stents or FCSEMS.
This study has clear limitations. The size of the cohort was smaller than anticipated,
as due to the stringent inclusion and exclusion criteria the majority of patients
who underwent ERCP for treatment of bile leak during the study time period were excluded
from analysis. Due to the single-center, retrospective nature of the study as well
as the strict exclusion criteria, the modest size of the cohort may result in a type
II error, failing to detect a true difference in leak resolution rates following total
vs subtotal cholecystectomy. For instance, if the true refractory leak rate is 4 %
for plastic stent therapy following total cholecystectomy and 10 % following subtotal
cholecystectomy, a study would require 378 subjects in each group to detect this difference
with 90 % power at an alpha level of 0.05.
As an additional limitation, the size of the cohort precluded meaningful multiple
variable analysis to both control for potential confounders and identify factors associated
with refractory leak. A larger cohort would be necessary to identify independent associations
between refractory leak rates and specific technical aspects of cholecystectomy and/or
technical aspects of ERCP (plastic stent vs FCSEMS, performance of biliary sphicterotomy,
etc).
Furthermore, the objective criteria used to adjudicate outcomes and categorize data
do not eliminate the fact that there is some heterogeneity in endoscopic techniques
within the cohort. Performance of biliary sphincterotomy was not standardized, and
stent selection was at the discretion of the treating endoscopist. These endoscopic
variables likely reflect the contribution of subjective judgment of the endoscopist,
perhaps influenced by worry about the size, location, or characteristics of a given
leak and affecting treatment decisions at the time of the procedure, yet not granular
in the operative report at the time of data extraction. With respect to cholecystectomy
operative reports, variability in the detail of these notes limited consistent assessment
of whether subtotal cholecystectomy was of the fenestrated or reconstituted type [4], which could conceivably impact the nature of the post-operative leak and response
to endoscopic therapy.
Conclusions
In summary, in this retrospective study the majority of patients undergoing treatment
for bile leak following either total or subtotal cholecystectomy were treated with
a single plastic biliary stent. This study demonstrated no difference in the rate
of successful leak resolution with plastic biliary stent placement following total
vs subtotal cholecystectomy. These data support the use of plastic stents as first-line
therapy for bile leaks following either total or subtotal cholecystectomy.
