Chen DX, Fang KX, Chen SX, Hou SL, Wen GH, Yang HK, Shi DP, Lu QX, Zhai YQ, Li MY. Optimal timing of endoscopic biliary drainage for bile duct leaks: A multicenter, retrospective, clinical study. World J Gastrointest Surg 2025; 17(3): 99425 [DOI: 10.4240/wjgs.v17.i3.99425]
Corresponding Author of This Article
Ming-Yang Li, MD, PhD, Chief Physician, Department of Gastroenterology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. mingyangli_pla@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
De-Xin Chen, Kai-Xuan Fang, Sheng-Xin Chen, Ya-Qi Zhai, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
De-Xin Chen, Kai-Xuan Fang, Graduate School, Chinese PLA General Hospital, Beijing 100853, China
Kai-Xuan Fang, Department of Gastroenterology and Hepatology, The 960th Hospital of PLA, Jinan 050035, Shandong Province, China
Sen-Lin Hou, Department of Gastroenterology and Hepatology, The Second Hospital of Hebei Medical University, Hebei 050035, China
Gui-Hai Wen, Department of Gastroenterology and Hepatology, Handan Central Hospital, Hebei 056001, China
Hai-Kun Yang, Department of Gastroenterology and Hepatology, Shanxi Provincial People’s Hospital, Shanxi 030012, China
Da-Peng Shi, Department of Gastroenterology and Hepatology, First Affiliated Hospital of Army Medical University of PLA, Chongqing 400042, China
Qing-Xin Lu, Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Army Medical University of PLA, Chongqing 400042, China
Ming-Yang Li, Department of Gastroenterology, Chinese PLA General Hospital, Beijing 100853, China
Co-corresponding authors: Ya-Qi Zhai and Ming-Yang Li.
Author contributions: Chen DX and Fang KX contributed to analysis, interpretation of data, drafting the article, they contributed equally to this article, they are the co-first authors of this manuscript; Chen SX, Hou SL, Wen GH, Yang HK, Shi DP, and Lu QX contributed to acquisition of data; Li MY is designated as the primary contact for all correspondence with the journal; Zhai YQ and Li MY contributed to revising, editing and drafting article, they contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors have read and approved the final manuscript.
Supported by the National Key Research and Development Program, China, No. 2022YFC2503603.
Institutional review board statement: This study was approved by the Medical Ethics Committee of the General Hospital of the People’s Liberation Army, approval No. S2023-067-01.
Informed consent statement: The informed consent was waived by the Institutional Review Board.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data sets used and analyzed during the current study are available from the corresponding author at mingyangli_pla@163.com.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming-Yang Li, MD, PhD, Chief Physician, Department of Gastroenterology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. mingyangli_pla@163.com
Received: July 22, 2024 Revised: January 14, 2025 Accepted: February 5, 2025 Published online: March 27, 2025 Processing time: 216 Days and 16.9 Hours
Abstract
BACKGROUND
Bile duct leaks (BDLs) are serious postsurgical adverse events. Typically, conservative management with abdominal drainage is the initial treatment option. However, prolonged abdominal drainage without improvement can lead to biliary stricture and delay the optimal timing of endoscopic retrograde cholangiopancreatography (ERCP).
AIM
To identify the optimal timing for ERCP and the period during which clinical observation with conservative management is acceptable, balancing ERCP success and the risk of biliary strictures.
METHODS
We conducted a multicenter retrospective study involving 448 patients with BDLs between November 2002 and November 2022. The patients were divided into four groups based on the timing of ERCP: 3 days, 7 days, 14 days, and 21 days. The primary outcome was clinical success, defined as the resolution of BDL and related symptoms within 6 months without additional percutaneous drainage, surgery, or death. The secondary outcome was incidence of biliary strictures. Univariate and multivariate logistic regression analyses were performed to identify factors associated with ERCP success and biliary stricture occurrence.
RESULTS
In a cohort of 448 consecutive patients diagnosed with BDLs, 354 were excluded, leaving 94 patients who underwent ERCP. Clinical success was achieved in 84% of cases (79/94), with a median ERCP timing of 20 days (9.5-35.3 days). Biliary strictures were identified in 29 (30.9%) patients. Performing ERCP within 3 weeks, compared to after 3 weeks, was associated with higher success rates [92.0% (46/50) vs 75.0% (33/44), P = 0.032] and a lower incidence of biliary stricture incidence [18.0% (9/50) vs 45.5% (20/44), P = 0.005]. Subsequent multivariate analysis confirmed the association with higher success rates (odds ratio = 4.168, P = 0.045) and lower biliary stricture rates (odds ratio = 0.256, P = 0.007).
CONCLUSION
Performing ERCP for BDLs within 3 weeks may be associated with a higher success rate and a lower biliary stricture rate. If patients with BDLs do not respond to conservative treatment, ERCP is suggested to be performed within 3 weeks.
Core Tip: In this multicenter study, 94 patients with bile duct leaks who underwent endoscopic retrograde cholangiopancreatography (ERCP) were retrospectively analyzed. We found that performing ERCP within 3 weeks was associated with higher success rates and a lower incidence of biliary stricture than later interventions. Multivariate analysis confirmed that early ERCP was a key factor for improved outcomes. If patients with bile duct leaks do not respond to conservative treatment, ERCP is suggested to be performed within 3 weeks.
Citation: Chen DX, Fang KX, Chen SX, Hou SL, Wen GH, Yang HK, Shi DP, Lu QX, Zhai YQ, Li MY. Optimal timing of endoscopic biliary drainage for bile duct leaks: A multicenter, retrospective, clinical study. World J Gastrointest Surg 2025; 17(3): 99425
Bile duct leaks (BDLs) are common adverse events (AEs) associated with hepatobiliary surgery, including cholecystectomy, partial hepatectomy, and liver transplantation[1,2]. BDLs can result in potentially life-threatening conditions, including electrolyte imbalance, peritonitis, abdominal abscesses, or sepsis[3]. In clinical practice, a drainage tube is usually retained after hepatobiliary surgery or percutaneous drainage is performed if no drain is placed during surgery. Most BDLs can be conservatively managed with abdominal drainage. Therefore, observation and conservative treatment with abdominal drains are advisable[4]. During the observation period, improvements in symptoms, such as relief of abdominal pain, reduction in abdominal drainage fluid, and normalization of laboratory values, should be closely monitored. If no symptom improvement occurs during the clinical observation period, endoscopic retrograde cholangiopancreatography (ERCP) is recommended. ERCP is an effective treatment for BDLs, with endoscopic biliary stent drainage and nasobiliary drainage as the primary techniques[5-7]. The rationale is to reduce the pressure gradient, promote preferential bile flow from the bile duct to the duodenum, and facilitate healing of BDLs[8].
Several studies have investigated the timing of ERCP on the outcome of BDLs and concluded that ERCP can be performed electively rather than urgently, with conservative management and observation recommended[9-11]. However, these studies did not specify an observation period, which could delay treatment and burden the patients. Prolonged BDLs may lead to infections and complications, making ERCP alone insufficient and requiring additional procedures. In addition, prolonged inflammation at the BDL site results in fibrosis and adhesive strictures[12]. Therefore, determining the optimal timing for ERCP is crucial to ensure successful outcomes without increasing the risk of biliary strictures. We conducted a multicenter retrospective study to examine the effect of ERCP timing on the success rate and occurrence of bile duct strictures in patients with BDLs. This study aimed to identify the optimal observation period for conservative management to ensure a high success rate with minimal risk of biliary stricture.
MATERIALS AND METHODS
Patients and data collection
We established a comprehensive database of six centers. All participating centers received training on the study objectives, case report form completion, and standardized data collection procedures. Medical data including basic demographic characteristics, laboratory test results, etiology of BDLs, characteristics of different methods, and procedural characteristics were collected and reviewed retrospectively.
The inclusion criteria were as follows: (1) Adults (> 18 years old); and (2) Either increasing or persistent bilious output from abdominal drainage, new fluid collection consistent with biloma on imaging studies, or extravasation of contrast outside the biliary tree on radiography. The exclusion criteria were as follows: (1) Inability to tolerate ERCP due to poor general condition; (2) Successful treatment with abdominal drainage and surgery; (3) Diagnostic ERCP; (4) Combined with advanced pancreatobiliary tumors; (5) Inability to reach the duodenal papilla via duodenoscope; and (6) Pregnancy. A total of 448 patients with BDLs who were treated between November 2002 and November 2022 were included. All patients provided informed consent before undergoing ERCP, and the study protocol was approved by the Ethics Committee of the Chinese PLA General Hospital, approval No. S2023-067-01. This study was conducted in accordance with the tenets of the Declaration of Helsinki.
Procedures
The procedures were performed by experts with > 10 years of experience in ERCP. Patients were placed in the prone position and received sedation or general intravenous anesthesia with close monitoring of their vital signs during the procedure. A duodenoscope (TJF-240/260; Olympus, Tokyo, Japan) was inserted into the descending part of the duodenum and carefully positioned at the papilla. Selective cannulation of the bile duct was performed using a papillotome or catheter directed toward the 11-12 o’clock position. After successful cannulation, cholangiography was performed to confirm the characteristics of the BDL and identify any associated stones or strictures. Under guidewire guidance, a biliary stent or nasobiliary drain was placed, with the aim of crossing over the leak site. Specific details of the procedure, including the need for endoscopic sphincterotomy and choice of biliary stent or nasobiliary drain in terms of length and diameter, were at the discretion of the endoscopist. If associated stones were present, stone retrieval was performed using a retrieval basket or balloon prior to drainage.
After the procedure, patients fasted and received symptomatic supportive treatment, including acid suppression, infection prevention, and fluid replacement. Vital signs and abdominal symptoms were closely monitored to observe for any postoperative complications. Follow-up examinations were scheduled 1 months, 3 months, and 6 months after the procedure. The nasobiliary drain was removed after cholangiography, indicating complete healing of the BDL. For patients with a biliary stent, stent exchange was performed every 3 months after the procedure until cholangiography confirmed leak closure.
Definitions and outcomes
The primary outcome was clinical success, whereas the secondary outcome was the incidence of biliary strictures. This study aimed to determine the optimal timing of ERCP for BDLs, and the period during which clinical observation with conservative management is acceptable, balancing ERCP success and the risk of biliary strictures. The optimal timing of ERCP was defined as the time point with a relatively high success rate and a low occurrence rate of biliary strictures. Clinical success was defined as the resolution of BDL and related clinical symptoms within 6 months without additional percutaneous drainage, surgery, or death[9,13]. The timing of ERCP was defined as the number of days from the hepatobiliary surgery or trauma to the initial ERCP. AEs were defined in accordance with the guidelines of the American Society of Gastrointestinal Endoscopy[14] and included pancreatitis, cholangitis, bleeding, perforation, and cardiopulmonary complications. The Charlson comorbidity index (CCI) was used to quantitatively analyze patient comorbidities[15]. Biliary stricture was defined according to the American College of Gastroenterology Clinical Guideline[16]. The location of the BDL was classified as the cystic duct, common bile duct, hilar bile duct, or intrahepatic bile duct.
Statistical analysis
Continuous data were reported as mean ± SD or median with interquartile range, as appropriate. Categorical data were presented as frequencies and proportions. The association between potential risk factors and ERCP success was evaluated using univariate analysis, namely Student’s t-test and Wilcoxon rank-sum test for continuous data, and the χ2 test and Fisher’s exact test for categorical data. Potential factors with a P value lower than 0.1 in the univariate analysis and baseline variables considered clinically relevant were included in the multivariate logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated, and a two-sided P-value lower than 0.05 was considered statistically significant. Statistical analyses were conducted using IBM SPSS Statistics (version 26.0; IBM Corp., Armonk, NY, United States).
RESULTS
Patients and therapeutic procedures
Total of 448 consecutive patients with clinically confirmed BDLs, 354 were excluded (Figure 1A). The final cohort of 94 patients (66 men, 28 women) had a mean age of 52.5 ± 12.9 years, a mean body mass index of 23.1 ± 3.4, and a median CCI score of 3 (interquartile range: 1-4). The etiologies of BDLs included cholecystectomy (69.1%), liver transplantation (13.8%), hepatectomy (8.5%), trauma (4.3%), and other causes (pancreatectomy and choledocholithotomy) (4.3%). The median timing of ERCP was 20 days (interquartile range: 9.5-35.3). The BDLs were located in the cystic duct (56.4%), common bile duct (21.3%), hilar bile duct (12.8%), and intrahepatic bile duct (9.6%). Seventy-six patients (80.9%) underwent abdominal drainage prior to ERCP. Plastic stents were used in most patients (55.3%), 10Fr plastic stents were used most frequently (35/53, 66.0%). Nasobiliary drainage tubes were used in 31 patients (33.0%), and metal stents were used in three patients (3.0%). The baseline characteristics, laboratory test results, and Strasberg classification of the 94 patients with BDLs are shown in Table 1.
Figure 1 Flowchart of patients included in the study and flowchart of endoscopic retrograde cholangiopancreatography timing.
A: Flowchart of patients included in the study; B: Flowchart on the timing of endoscopic retrograde cholangiopancreatography. BDLs: Bile duct leaks; ERCP: Endoscopic retrograde cholangiopancreatography.
Table 1 Baseline characteristics of 94 patients with bile duct leaks, n (%).
Characteristics
Overall (n = 94)
< 3 weeks (n = 50)
> 3 weeks (n = 44)
P value
Basic demographics
Sex
-
-
-
0.392
Female
28 (29.8)
13 (26)
15 (34.1)
-
Male
66 (70.2)
37 (74)
29 (65.9)
-
Age, years, mean ± SD
52.5 ± 12.9
54.1 ± 13.3
50.6 ± 12.4
0.192
BMI, mean ± SD
23.1 ± 3.4
23.1 ± 3.2
23.1 ± 3.7
0.830
CCI, (Q1, Q3)
3 (1, 4)
2 (1, 4)
3 (1, 5)
0.163
Laboratory test within 3 days before ERCP
WBC, × 109/L (Q1, Q3)
8.2 (6.3, 16.9)
8.5 (7.2, 11.6)
8.1(6.0, 12.8)
0.909
ALT, U/L (Q1, Q3)
36.4 (25.9, 80.6)
32.3 (25.9, 57.3)
38 (24.7, 98.0)
0.480
Tbil, μmol/L (Q1, Q3)
20.2 (12.3, 38.8)
20.5 (13.5, 60.0)
18.5 (11.7, 36.5)
0.191
Albumin, g/L, mean ± SD
35.2 ± 5.9
35.4 ± 6.8
35.0 ± 4.8
0.728
Creatinine, μmol/L (Q1, Q3)
58.4 (48.9, 71.7)
57.2 (46.6, 71.1)
59.2 (46.4, 71.2)
0.796
Etiology of BDLs
-
-
-
0.307
Cholecystectomy
65 (69.1)
39 (78.0)
26 (59.1)
-
Liver transplantation
13 (13.8)
6 (12.0)
7 (15.9)
-
Partial hepatectomy
8 (8.5)
3 (6.0)
5 (11.4)
-
Trauma
4 (4.3)
1 (2.0)
3 (6.8)
-
Others
4 (4.3)
1 (2.0)
3 (6.8)
-
Treatment methods
-
-
-
0.149
Plastic stent
52 (55.3)
28 (56)
32 (64)
-
5 Fr
2 (2.1)
0 (0)
2 (4.5)
-
7 Fr
3 (3.2)
3 (6.0)
0 (0)
-
8.5 Fr
12 (12.8)
5 (10.0)
7 (15.9)
-
10 Fr
35 (37.2)
20 (40.0)
23 (52.3)
-
Metal stent (10 mm)
3 (3.2)
2 (4.0)
1 (2.3)
-
Nasobiliary drainage tube
31 (33.0)
20 (40.0)
11 (25.0)
-
Procedure characteristics
Location of BDLs
-
-
-
0.488
Cystic duct
53 (56.4)
29 (58.0)
24 (54.5)
-
Common bile duct
20 (21.3)
10 (20.0)
10 (22.7)
-
Hilar bile duct
12 (12.8)
8 (16.0)
4 (9.1)
-
Intrahepatic bile duct
9 (9.6)
3 (6.0)
6 (13.6)
-
Abdominal drainage
76 (80.9)
42 (84.0)
34 (77.3)
0.410
Strasberg classification
-
-
-
0.259
A
38 (40.4)
24 (48.0)
14 (31.8)
-
C
11 (11.7)
5 (10.0)
6 (13.6)
-
D
32 (34.0)
13 (26.0)
19 (43.2)
-
E1
5 (5.3)
4 (8.0)
1 (2.3)
-
E2
8 (8.5)
4 (8.0)
4 (9.1)
-
Patient outcomes
Clinical success was achieved in 79 patients (84.0%), and the median duration from the primary ERCP to resolution was 89 days (interquartile range: 60-99 days). Among the 15 patients who did not achieve clinical success with ERCP, 14 required additional unplanned procedures, including surgery and percutaneous drainage, while one patient died of septic shock caused by BDLs. Biliary strictures were found in 29 patients (30.9%), and all strictures were located at the site of the leak. Twelve patients (12.8%) experienced AEs, including ten cases of pancreatitis, two cases of bleeding, and one case of cholangitis. All complications were classified as mild and successfully managed with medical treatment. The average number of ERCP procedures per patient was 1.3 ± 0.7 and most of the patients (84.8%, 67/79) needed only one ERCP to solve the BDLs. The median follow-up time was 29.6 months (interquartile range: 8.1-145.0 months), and none of the patients had recurrent BDLs during the follow-up.
Timing of ERCP and effect on success and biliary stricture
The median time from the initial injury to the initial ERCP was 20 days (interquartile range: 9.5-35.3). Considering previous studies, median timing, and clinical experience, we divided the patients into the following four groups according to the timing of ERCP: 3 days, 7 days, 14 days, and 21 days. After converting the timing of ERCP into a binary variable based on these time points, we summarized the success rate, biliary stricture rate, OR, and P-value at each time point (Table 2). Performing ERCP within 21 days resulted in higher success rates (OR = 3.833, 95%CI: 1.122-13.097, P = 0.032) and lower rates of biliary strictures (OR = 0.263, 95%CI: 0.103-0.670, P = 0.005). There were no statistically significant differences in basic demographics, laboratory test results, etiology of BDLs, treatment methods, or procedural characteristics between patients who underwent ERCP within 21 days and those who underwent ERCP after 21 days (Table 1).
Table 2 Success rate and biliary stricture associated with the timing of endoscopic retrograde cholangiopancreatography.
Timing
Success (%)
OR
P value
Biliary stricture (%)
OR
P value
Yes
No
Yes
No
< 3, n = 6
5 (83.3)
1 (16.7)
0.946 (0.103-8.725)
0.961
2 (33.3)
4 (66.7)
0.130 (0.195-6.545)
0.892
> 3, n = 88
74 (84.1)
14 (15.9)
-
-
27 (30.7)
61 (69.3)
-
-
< 7, n = 18
16 (88.9)
2 (11.1)
1.651 (0.338-8.068)
0.536
3 (16.7)
15 (83.3)
0.385 (0.102-1.450)
0.158
> 7, n = 76
63 (82.9)
13 (17.1)
-
-
26 (34.2)
50 (65.8)
-
-
< 14, n = 32
28 (87.5)
4 (12.5)
1.510 (0.440-5.185)
0.513
4 (12.5)
28 (87.5)
0.211 (0.066-0.677)
0.009
> 14, n = 62
51 (82.3)
11 (17.7)
-
-
25 (40.3)
37 (59.7)
-
-
< 21, n = 50
46 (92.0)
4 (8.0)
3.833 (1.122-13.097)
0.032
9 (18.0)
41 (82.0)
0.263 (0.103-0.670)
0.005
> 21, n = 44
33 (75.0)
11 (25.0)
-
-
20 (45.5)
24 (54.5)
-
-
Fifteen variables were analyzed to determine their influence on ERCP success. Univariate analysis revealed that body mass index (P = 0.049), CCI (P = 0.031), cystic duct disease (P = 0.002), and ERCP within 3 weeks (P = 0.032) were associated with clinical outcomes of ERCP (P < 0.1). Multivariable analysis was subsequently performed, and the following variables remained associated with ERCP success: ERCP within 3 weeks (OR = 4.168; 95%CI: 1.031-16.841, P = 0.045) and cystic duct leak (OR = 12.219; 95%CI: 2.317-64.433, P = 0.003) (Table 3). Similarly, 13 variables were analyzed for their potential association with biliary strictures. Univariate analysis indicated that CCI (P = 0.021), liver transplantation (P = 0.053), and ERCP within 3 weeks (P = 0.005) were potentially associated with biliary strictures (P < 0.1). Multivariate analysis showed that ERCP performed within 3 weeks was significantly associated with biliary strictures (OR = 0.256; 95%CI: 0.096-0.683, P = 0.007) (Table 4).
Table 3 Univariable and multivariable analysis of factors associated with successful endoscopic retrograde cholangiopancreatography, n (%).
Variable
Univariable analysis
Multivariable analysis
Success (n = 79)
Failure (n = 15)
P value
OR
95%CI
P value
Basic demographics
Sex, female
24 (30.4)
4 (26.7)
0.773
-
-
-
Age, years, mean ± SD
52.8 ± 12.7
51.0 ± 14.6
0.638
-
-
-
BMI, mean ± SD
23.4 ± 3.4
21.5 ± 3.1
0.049
0.814
0.653-1.014
0.067
CCI, (Q1, Q3)
2.5 (1, 4)
3.0 (2, 7)
0.031
0.864
0.704-1.062
0.164
Laboratory test within 3 days before ERCP
WBC, × 109/L, mean ± SD
9.4 ± 4.3
10.4 ± 5.1
0.390
-
-
-
ALT, U/L (Q1, Q3)
36.1 (25.9, 81.2)
39.6 (22.8, 82.0)
0.812
-
-
-
Tbil, μmol/L (Q1, Q3)
19.3 (12.1, 39.4)
34.0 (12.6, 80.0)
0.715
-
-
-
Albumin, g/L, mean ± SD
35.3 ± 6.0
34.6 ± 5.6
0.659
-
-
-
Creatinine, μmol/L (Q1, Q3)
58.0 (47.0, 69.0)
59.3 (52.0, 99.0)
0.196
-
-
-
Etiology of BDLs
-
-
0.126
-
-
-
Cholecystectomy
58 (73.4)
7 (46.7)
-
-
-
-
Liver transplantation
9 (11.4)
4 (26.7)
-
-
-
-
Partial hepatectomy
7 (8.9)
1 (6.7)
-
-
-
-
Trauma
2 (2.5)
2 (13.3)
-
-
-
-
Others
3 (3.8)
1 (6.7)
-
-
-
-
Characteristics of different methods
--
-
0.326
-
-
-
Plastic stent
50 (63.3)
10 (66.7)
-
-
-
-
Metal stent (10 mm)
2 (2.5)
1 (6.7)
-
-
-
-
Nasobiliary drainage tube
27 (34.2)
4 (26.7)
-
-
-
-
Location of BDLs, cystic duct
51 (64.6)
2 (13.3)
0.002
12.219
2.317-64.433
0.003
Biliary stricture
23 (29.1)
6 (40.0)
0.403
-
-
-
Performing ERCP within 3 weeks
46 (58.2)
4 (26.7)
0.032
4.168
1.031-16.841
0.045
Abdominal drainage
64 (81.0)
12 (15.8)
0.938
-
-
-
Table 4 Univariable and multivariable analysis of variables associated with biliary stricture, n (%).
Variable
Univariable analysis
Multivariable analysis
Biliary stricture (n = 29)
No biliary stricture (n = 65)
P value
OR
95%CI
P value
Basic demographics
Sex, female
12 (41.4)
16 (24.6)
0.104
-
-
-
Age, years, mean ± SD
54.14 ± 13.3
50.6 ± 12.39
0.585
-
-
-
BMI, mean ± SD
23.1 ± 3.2
23.1 ± 3.7
0.316
-
-
-
CCI, (Q1, Q3)
2 (1, 4)
3 (1, 5)
0.021
1.109
0.918-1.338
0.217
Laboratory test within 3 days before ERCP
WBC, × 109/L (Q1, Q3)
8.4 (3, 4)
10.0 (4, 8)
0.110
-
-
-
ALT, U/L (Q1, Q3)
32.3 (25.9, 57.3)
38 (24.7, 98.0)
0.245
-
-
-
Tbil, μmol/L (Q1, Q3)
20.5 (13.5, 60.0)
18.6 (11.7, 36.5)
0.327
-
-
-
Albumin, g/L, mean ± SD
35.4 ± 6.8
35.0 ± 4.8
0.341
-
-
-
Creatinine, μmol/L (Q1, Q3)
57.2 (50.4, 73.8)
59.2 (46.4, 71.2)
0.916
-
-
-
Etiology of BDLs, liver transplantation
7 (24.1)
6 (9.2)
0.053
2.657
0.562-12.551
0.284
Location of BDLs
-
-
0.438
-
-
-
Cystic duct
14 (48.3)
39 (60.0)
-
-
-
-
Common bile duct
9 (31.0)
11 (16.9)
-
-
-
-
Hilar bile duct
4 (13.8)
8 (12.3)
-
-
-
-
Intrahepatic bile duct
2 (6.9)
7 (10.8)
-
-
-
-
Performing ERCP within 3 weeks
9 (31.0)
41 (63.1)
0.005
0.256
0.096-0.683
0.007
DISCUSSION
BDLs are serious AEs that usually occur after hepatobiliary surgery and trauma, leading to peritonitis, sepsis, or in severe cases, death[13,17]. ERCP is an important treatment option for BDLs, with relatively high success rates in some cases. In this retrospective study, ERCP demonstrated a clinical success rate of 84.0% for BDLs, which is consistent with the success rates reported in previous studies (71%-94.4%)[7,9,10,18-23]. Performing ERCP within 3 weeks, compared with after 3 weeks, was associated with higher success rates and lower biliary stricture incidence. Several studies have investigated the effect of ERCP timing on the success rate of BDLs[9-11]. These studies categorized the timing of ERCP into < 1 day, 2-3 days, and > 3 days and found no statistically significant differences among the groups. These studies suggest that ERCP for BDLs can be performed electively rather than urgently. However, they did not specify an observation period, which may have burdened patients and delayed treatment.
Most cases of BDL can be treated with abdominal drainage tubes repaired during surgery, with a success rate ranging from 75% to 94%[24-29]. Viganò et al[25] reported a success rate of 76.5% in patients with BDLs within a median time of 15 days (range: 4-180 days). However, prolonged BDLs may result in intra-abdominal infections, sepsis, and other complications, making it difficult to manage BDLs with ERCP alone, requiring additional debridement or drainage procedures[4]. Persistent bile leakage may induce inflammation, leading to inflammatory strictures at the leak site[4,12]. In our study, 29 patients (30.9%) had no prior history of biliary stricture; however, biliary strictures at the site of the leak were discovered during ERCP, indicating that these biliary strictures are related to BDLs. In a retrospective study of 119 patients with bile duct injury and leakage, 21.8% had biliary strictures[30]. Lokesh et al[31]found that bile leaks lasting > 4 weeks increased the risk of biliary strictures, which is consistent with our study.
In contrast to previous studies, this study determined an acceptable observation period for conservative treatment, during which ERCP success rates remained high without increasing the risk of biliary strictures. The relationship between the timing of ERCP and success rate was not linear; thus, we categorized the timing of ERCP as a categorical variable. In our study, we attempted to identify a turning point and demonstrated that performing ERCP within this timeframe was more appropriate. The division at 3 days aligns with previous literature[9-11]. Viganò et al[25] found that the median time for the successful treatment of BDLs with an abdominal drainage tube was approximately 2 weeks, whereas drainage fluid exceeding 100 mL for more than 10 days (approximately 1 week) was associated with poor outcomes. Additionally, using a weekly division as a cutoff is more suitable for the observation period in clinical practice. Therefore, we chose weekly division as the cutoff point, categorizing the timing of ERCP into two binary variables.
The 21-day mark appears to be the turning point. The results showed that the success rate of ERCP for BDLs performed within 3 weeks was significantly higher than that for ERCP performed after 3 weeks. In addition, there were significantly fewer cases of biliary strictures if ERCP was performed within 3 weeks than if ERCP was performed after 3 weeks. We considered several factors that could influence outcomes, including the etiology and location of the BDL, the presence of abdominal drainage, laboratory test results, basic demographic characteristics, and the CCI. Potential confounders, such as liver transplant history, bile duct location, and preoperative laboratory values, were considered in the analysis of biliary strictures. To account for these confounding factors, we conducted univariate and multivariate analyses of the results, revealing that performing ERCP within 3 weeks was an independent factor for the success of ERCP and the lower incidence of biliary strictures. This may be attributed to prolonged bile stimulation, leading to infection, inflammation, and stenosis around the leakage site, which hinders the healing process. Further studies are required to validate these findings. Furthermore, cystic duct leakage was identified as a protective factor associated with ERCP success, which is consistent with previous research[31].
In 2021, the World Society of Emergency Surgery published guidelines for the management of bile duct injury during cholecystectomy[4]. They recommended that, for minor bile duct injuries, if no improvement or worsening of symptoms occurs during the clinical observation period after percutaneous drain placement, ERCP becomes mandatory. In cases of major bile duct injury diagnosed between 72 hours and 3 weeks, ERCP should be considered. Additionally, the acute inflammatory period typically requires several weeks (2-3 weeks) to resolve, making surgical treatment unsuitable within 3 weeks. This further emphasizes that ERCP performed within 3 weeks is a reasonable clinical management strategy.
Therefore, based on the guidelines and results of this study, we recommend that for patients diagnosed with BDLs, if there is abdominal drainage, it is advisable to initially observe. If there is no improvement in symptoms or signs or a decrease in drainage volume, ERCP can be performed. If there is improvement, re-evaluation can be done after 1-2 weeks. If there is no improvement or worsening of symptoms within 3 weeks, endoscopic management should be considered mandatory. These recommendations are summarized in Figure 1B. Our study has several limitations. First, the retrospective nature of the study introduced a potential bias in patient selection and data collection. Second, treatment preferences may have varied across centers, with some preferring nasobiliary drainage tubes and others opting for stents. However, both options have comparable efficacy; therefore, center preference is unlikely to significantly affect the results[7]. Third, the study did not include patients who underwent endoscopic sphincterotomy alone, as endoscopists at some centers believed that its clinical efficacy was relatively low, leading to surgical referrals[32].
CONCLUSION
Performing ERCP within 3 weeks may be associated with a higher success rate and lower incidence of biliary strictures. This finding highlights the significance of timely intervention in improving patient outcomes. When abdominal drainage does not improve within 3 weeks, early transition to ERCP is recommended. This facilitates better communication and collaboration between surgeons and endoscopists, ultimately benefiting the patients.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade A, Grade C
Novelty: Grade A, Grade C
Creativity or Innovation: Grade A, Grade C
Scientific Significance: Grade A, Grade B
P-Reviewer: He XY; Moghadam ARE S-Editor: Bai Y L-Editor: A P-Editor: Xu ZH
Tsolakis AV, James PD, Kaplan GG, Myers RP, Hubbard J, Wilson T, Zimmer S, Mohamed R, Cole M, Bass S, Swain MG, Heitman SJ. Clinical prediction rule to determine the need for repeat ERCP after endoscopic treatment of postsurgical bile leaks.Gastrointest Endosc. 2017;85:1047-1056.e1.
[PubMed] [DOI][Cited in This Article: ][Cited by in RCA: 1][Reference Citation Analysis (0)]
de'Angelis N, Catena F, Memeo R, Coccolini F, Martínez-Pérez A, Romeo OM, De Simone B, Di Saverio S, Brustia R, Rhaiem R, Piardi T, Conticchio M, Marchegiani F, Beghdadi N, Abu-Zidan FM, Alikhanov R, Allard MA, Allievi N, Amaddeo G, Ansaloni L, Andersson R, Andolfi E, Azfar M, Bala M, Benkabbou A, Ben-Ishay O, Bianchi G, Biffl WL, Brunetti F, Carra MC, Casanova D, Celentano V, Ceresoli M, Chiara O, Cimbanassi S, Bini R, Coimbra R, Luigi de'Angelis G, Decembrino F, De Palma A, de Reuver PR, Domingo C, Cotsoglou C, Ferrero A, Fraga GP, Gaiani F, Gheza F, Gurrado A, Harrison E, Henriquez A, Hofmeyr S, Iadarola R, Kashuk JL, Kianmanesh R, Kirkpatrick AW, Kluger Y, Landi F, Langella S, Lapointe R, Le Roy B, Luciani A, Machado F, Maggi U, Maier RV, Mefire AC, Hiramatsu K, Ordoñez C, Patrizi F, Planells M, Peitzman AB, Pekolj J, Perdigao F, Pereira BM, Pessaux P, Pisano M, Puyana JC, Rizoli S, Portigliotti L, Romito R, Sakakushev B, Sanei B, Scatton O, Serradilla-Martin M, Schneck AS, Sissoko ML, Sobhani I, Ten Broek RP, Testini M, Valinas R, Veloudis G, Vitali GC, Weber D, Zorcolo L, Giuliante F, Gavriilidis P, Fuks D, Sommacale D. 2020 WSES guidelines for the detection and management of bile duct injury during cholecystectomy.World J Emerg Surg. 2021;16:30.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 16][Cited by in RCA: 84][Article Influence: 21.0][Reference Citation Analysis (0)]
Dumonceau JM, Tringali A, Papanikolaou IS, Blero D, Mangiavillano B, Schmidt A, Vanbiervliet G, Costamagna G, Devière J, García-Cano J, Gyökeres T, Hassan C, Prat F, Siersema PD, van Hooft JE. Endoscopic biliary stenting: indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline - Updated October 2017.Endoscopy. 2018;50:910-930.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 259][Cited by in RCA: 436][Article Influence: 62.3][Reference Citation Analysis (0)]
Raza A, Omer A, Iqbal S, Gudsoorkar V, Koduru P, Krishnan K. Efficacy of Nasobiliary Tubes and Biliary Stents in Management of Patients with Bile Leak after Liver Transplantation: A Systematic Review.Clin Endosc. 2019;52:159-167.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 6][Cited by in RCA: 7][Article Influence: 1.2][Reference Citation Analysis (0)]
Adler DG, Papachristou GI, Taylor LJ, McVay T, Birch M, Francis G, Zabolotsky A, Laique SN, Hayat U, Zhan T, Das R, Slivka A, Rabinovitz M, Munigala S, Siddiqui AA. Clinical outcomes in patients with bile leaks treated via ERCP with regard to the timing of ERCP: a large multicenter study.Gastrointest Endosc. 2017;85:766-772.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 26][Cited by in RCA: 29][Article Influence: 3.6][Reference Citation Analysis (0)]
Sendino O, Fernández-Simon A, Law R, Abu Dayyeh B, Leise M, Chavez-Rivera K, Cordova H, Colmenero J, Crespo G, Rodriguez de Miguel C, Fondevila C, Llach J, Navasa M, Baron T, Cárdenas A. Endoscopic management of bile leaks after liver transplantation: An analysis of two high-volume transplant centers.United European Gastroenterol J. 2018;6:89-96.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 11][Cited by in RCA: 15][Article Influence: 1.9][Reference Citation Analysis (0)]
ASGE Standards of Practice Committee; Chandrasekhara V, Khashab MA, Muthusamy VR, Acosta RD, Agrawal D, Bruining DH, Eloubeidi MA, Fanelli RD, Faulx AL, Gurudu SR, Kothari S, Lightdale JR, Qumseya BJ, Shaukat A, Wang A, Wani SB, Yang J, DeWitt JM. Adverse events associated with ERCP.Gastrointest Endosc. 2017;85:32-47.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 405][Cited by in RCA: 502][Article Influence: 62.8][Reference Citation Analysis (0)]
Rerknimitr R, Sherman S, Fogel EL, Kalayci C, Lumeng L, Chalasani N, Kwo P, Lehman GA. Biliary tract complications after orthotopic liver transplantation with choledochocholedochostomy anastomosis: endoscopic findings and results of therapy.Gastrointest Endosc. 2002;55:224-231.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 218][Cited by in RCA: 215][Article Influence: 9.3][Reference Citation Analysis (0)]
Yabe S, Kato H, Mizukawa S, Akimoto Y, Uchida D, Seki H, Tomoda T, Matsumoto K, Yamamoto N, Horiguchi S, Tsutsumi K, Okada H. Predictive factors for outcomes of patients undergoing endoscopic therapy for bile leak after hepatobiliary surgery.Dig Endosc. 2017;29:353-361.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 4][Cited by in RCA: 8][Article Influence: 1.0][Reference Citation Analysis (0)]
de Reuver PR, Rauws EA, Vermeulen M, Dijkgraaf MG, Gouma DJ, Bruno MJ. Endoscopic treatment of post-surgical bile duct injuries: long term outcome and predictors of success.Gut. 2007;56:1599-1605.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 47][Cited by in RCA: 39][Article Influence: 2.2][Reference Citation Analysis (0)]
Lokesh HM, Pottakkat B, Prakash A, Singh RK, Behari A, Kumar A, Kapoor VK, Saxena R. Risk factors for development of biliary stricture in patients presenting with bile leak after cholecystectomy.Gut Liver. 2013;7:352-356.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 9][Cited by in RCA: 10][Article Influence: 0.8][Reference Citation Analysis (0)]
Schaible A, Schemmer P, Hackert T, Rupp C, Schulze Schleithoff AE, Gotthardt DN, Büchler MW, Sauer P. Location of a biliary leak after liver resection determines success of endoscopic treatment.Surg Endosc. 2017;31:1814-1820.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 7][Cited by in RCA: 12][Article Influence: 1.3][Reference Citation Analysis (0)]
