Intra-biliary cleansing during secondary duodenoscopic removal of duodenal bend biliary stents: A retrospective cohort study

Abstract

BACKGROUND

Biliary stent placement and removal are common medical procedures, but they carry risks of chyme regurgitation and residual common bile duct stones (CBDS), highlighting the necessity of intra-biliary cleansing during secondary endoscopic stent removal.

AIM

To compare the incidence of chyme reflux into the common bile duct and residual or recurrent CBDS, and the safety of intra-biliary cleansing during secondary duodenoscopic removal of duodenal bend vs single pigtail biliary stents.

METHODS

We included 554 patients undergoing secondary duodenoscopy for biliary stent removal and intra-biliary cleansing from March 2019 to September 2024. Patients were divided into a single pigtail biliary stent group and a duodenal bend biliary stent group (DBBSG). Chyme reflux and CBDS occurrences were compared using the Cox proportional hazards model.

RESULTS

The median age of the patients included was 62 years (interquartile range: 51-70), with 53.11% being female. During stent removal, DBBSG showed higher rates of chyme reflux (23.27% vs 9.65%, P < 0.001) and CBDS (42.77% vs 21.05%, P < 0.001) compared to the single pigtail biliary stent group. No significant differences were found in the incidence of adverse reactions between the two groups (P > 0.05), and no serious events or deaths occurred. DBBSG patients had increased risks of chyme reflux (hazard ratio = 2.793; 95% confidence interval: 1.695-4.603; P < 0.001) and CBDS (hazard ratio: 2.475; 95% confidence interval: 1.732-3.536; P < 0.001).

CONCLUSION

Duodenal bend biliary stents increase the risk of chyme reflux into the common bile duct and CBDS. The safety of intra-biliary cleaning during stent removal has been validated, and as a result, it is recommended that endoscopists perform intra-biliary cleaning during duodenoscopic removal of duodenal bend biliary stents.

Key Words: Biliary stent; Intra-biliary cleansing; Enterobiliary reflux; Common bile duct stones; Endoscopic retrograde cholangiopancreatography; Adverse reactions after endoscopic retrograde cholangiopancreatography

Core Tip: In clinical practice, compared to single-pigtail biliary stents, patients with duodenal bend biliary stent have a significantly increased risk of chyme reflux into the bile duct and common bile duct stones (residual or recurrent). Performing intra-biliary cleansing after stent removal can improve patient prognosis. The finding of this study will increase endoscopists’ awareness of the importance of intra-biliary cleansing during biliary stent placement and replacement, thereby optimising clinical practice and improving patient prognosis.

INTRODUCTION

Endoscopic biliary stenting is the primary minimally invasive treatment for failed choledochal stone retrieval[1-3], benign biliary strictures[1,4,5], palliative drainage of malignant biliary obstruction[1,6,7], and bile leakage[1,8,9]. In clinical practice, bile duct stenting is commonly used to manage duodenal papillary thermal injury caused by endoscopic sphincterotomy (EST) and mechanical injury to the duodenal papilla caused by stone retrieval baskets or balloons[10]. To prevent temporary bile duct drainage obstruction due to duodenal papillary oedema after endoscopic retrograde cholangiopancreatography (ERCP), bile duct stents are usually placed after achieving treatment goals [such as complete removal of common bile duct stones (CBDS)] to maintain bile duct patency[11], until the stent either dislodges naturally or is removed through reoperation in a short period. However, the type of biliary stent and the timing of its replacement not only affect biliary patency but may also contribute to the formation of medically induced choledochal stones[2,10,11].

Recent studies recommend that biliary stents should be replaced at regular intervals, with the usual recommended interval being every three months[2]. However, studies have found that some patients have their stents replaced when they become symptomatic; by this time, the stent is usually obstructed, which can lead to serious biliary infections such as acute cholangitis, with a high mortality rate, particularly in older adults[12]. When replacing a stent during an ERCP operation, it is common to find intestinal chyme reflux in the bile duct or stones forming between the end of the stent and the biliary wall[13]. Some of these were residual stones that were incompletely removed during the last extraction; however, the possibility of new stones cannot be ruled out. Therefore, endoscopists should perform intra-biliary cleansing during regular biliary stent replacement.

Most endoscopists clean bile ducts when replacing biliary stents in patients who require long-term stent placement and periodic replacement. However, in patients who have completed ERCP therapy and are scheduled for short-term stent removal, many endoscopists only remove the stent through duodenoscopy and observe the duodenal papilla for active bleeding, often ignoring the possible presence of chyme reflux and residual or new bile duct stones in the biliary tract. This increases the risk of distant, medically induced CBDS[2,10,11]. In the European Society of Gastrointestinal Endoscopy guidelines, the registration of biliary stents and timely recall of patients for their removal or replacement are emphasized; however, the importance of intra-biliary cleansing after short-term removal or replacement of the stent is not explicitly stated, and the risk of disruption of biliary airtightness and enterobiliary reflux (the retrograde movement of duodenal contents into the biliary tree) that may be associated with different types of biliary stents is ignored.

The types of biliary stents mainly include plastic stents and metal stents. According to different stent designs and clinical conditions, they also include duodenal bend, centre bend, straight, pigtail, winged stents, and so on. The metal stent is a type of mesh stent with self-expanding characteristics and large-diameter openings at both ends, which is mainly used for long-term drainage of malignant biliary obstruction. It is inherently prone to intestinal biliary reflux and CBDS and is therefore insufficient to serve the main population of this study. The single pigtail biliary stent is an improved type of stent that is now widely used in clinical practice. In addition to this, another widely used biliary stent in clinical practice is the duodenal bend biliary stent. However, the acute angulation inherent to duodenal bend biliary stent can disrupt the natural axis of bile flow, including regions of recirculation and vortex formation at the bend site. These flow disruptions create zones of stagnant bile flow and localized negative pressure, which can facilitate retrograde movement of duodenal contents into the bile duct. This effect is amplified when the stent tip is close to or within the duodenal lumen, as fluctuations in intraduodenal pressure during peristalsis further promote enterobiliary reflux. The mechanical pressure exerted by the stent’s bend on the sphincter of Oddi may further diminish its competence. The irregular inner surface and localized stagnation zones at the stent bend favor the deposition of bile sludge, bacterial colonization, and subsequent biofilm development[14-16], setting the stage for stone nucleation and growth.

Therefore, this study was based on a single pigtail biliary stent as a standard, and the main objective was to compare the incidence of chyme reflux into the bile duct and residual or recurrent CBDS and the safety of intra-biliary cleansing during secondary duodenoscopic removal of the duodenal bend biliary stent. We hope that this study will increase endoscopists’ awareness of the importance of intra-biliary cleansing during biliary stent removal and replacement, thereby optimizing clinical practice and improving patient prognosis.

MATERIALS AND METHODS

Study design and participants

This was a retrospective cohort study including 554 patients who underwent secondary duodenoscopy for biliary stent removal with intra-biliary cleansing between March 2019 and September 2024 at our institution. The inclusion criteria for selecting participants were: (1) Age ≥ 14 years old, regardless of sex; (2) Patients with a biliary stent placed during ERCP treatment in our hospital and had no stent dislodge as confirmed by abdominal computerized tomography review; (3) Detailed surgical records or ERCP imaging data retained; (4) Admitted to the hospital for duodenoscopic removal of biliary stent and had signed the informed consent form; and (5) Stenting of bile ducts or (and) pancreatic ducts met the indications for stenting. The exclusion criteria were: (1) Duodenoscopic removal of biliary stent without intra-biliary cleansing; (2) Due to previous choledocho-jejunal anastomosis, food easily flowed into the common bile duct; (3) Patient could not tolerate the surgery when removing the biliary stent and intra-biliary cleansing for various reasons, resulting in failure to assess the bile duct situation in detail; (4) For various reasons, it was impossible to determine the time of the last placement of the biliary stent; (5) Biliary stent type was unknown; (6) Repeated replacement of biliary stents (≥ 3 times); and (7) The presence of both duodenal bend biliary stent and single pigtail biliary stent in the body. A flowchart of the study is shown in Figure 1.

Figure 1 Flow diagram of patient selection. IBS: Integrated bile duct stent; SPBS: Single pigtail biliary stent; SPBSG: Single pigtail biliary stent group; DBBSG: Duodenal bend biliary stent group.

Ethical approval

The study was approved by the local Institutional Review Board, approval No.[2022] Research Review (107). Each patient provided written informed consent before the endoscopic interventions. All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Criteria for stent type selection

Stent type was chosen at the discretion of the attending endoscopist, based on anatomical considerations, anticipated risk of migration, and operator experience. While single pigtail biliary stents are the standard of care at our institution, duodenal bend stents are preferentially used in cases with a challenging anatomy or risk of migration.

Clinical data

Basic information of all patients at the time of initial ERCP biliary stent placement was collected from the electronic medical record system, including sex, age, body mass index, hypertension, hyperlipidaemia, diabetes mellitus, coronary heart disease, and biliary system diseases (fatty liver, gallstones, congenital choledochal cysts, and extrahepatic bile duct stenosis). Additionally, history of pancreatitis and biliary surgeries (ERCP, cholecystectomy, and common bile duct exploration) and hospitalization duration (for the second ERCP procedure to remove the biliary stent, with durations categorized as ≤ 1 day, 2 days, 3 days, and ≥ 4 days) were collected.

Tests included lipid markers (serum total cholesterol and triglyceride levels at the time of initial ERCP choledochal stent placement) and liver function (within 24 hours of the second duodenoscopy to remove the biliary stent and perform intra-biliary cleansing).

ERCP surgical records included classifications of duodenal papillopathy (DP)[17], the presence of periampullary diverticula and their relative position to the papilla, sphincter of Oddi dysfunction (SOD)[18], pancreaticobiliary maljunction (PBM)[17,19], length of EST incision (mm), final dilated diameter achieved during endoscopic papillary balloon dilation (mm), pancreatic duct stent (PDS), and types of biliary stents (single pigtail biliary stents, duodenal bend biliary stents, and metal-covered stents).

Definitions

DP can be categorised into different types based on its relative position to the diverticulum[17]: (1) Papilla adjacent to the duodenal diverticulum. The root of the papillae was within 3 cm of the diverticulum; and (2) Papilla within the duodenal diverticulum. The root of the papillae was located inside the diverticulum, including the lateral wall and base of the diverticulum.

Intra-biliary cleansing: Following intubation of the descending part of the duodenum with the duodenoscope, the duodenal papilla was identified. The existing biliary stent was then captured and removed using a snare. A sphincterotomy was performed, and a guidewire was advanced into the bile duct. Cholangiography was conducted to observe the morphology of the bile ducts and the possible presence of lesions. Subsequently, the bile ducts were cleared using a stone extraction basket and balloon catheter, followed by repeated irrigation. The procedure was concluded after confirming the absence of contrast extravasation on final cholangiography. Prior to the procedure, all patients and their families were thoroughly informed of the purpose and potential adverse effects of the operation. The biliary cleansing intervention was only performed after obtaining written informed consent.

Grouping and definition of biliary stent indwelling time

The patients were divided into either a control group or a study group according to the type of biliary stent selected during the initial ERCP procedure. The control group consisted of patients who received a single pigtail biliary stent during initial ERCP, which represents the routine standard of care. This group was also designated as the single pigtail biliary stent group (SPBSG). The study group, also designated as the duodenal bend biliary stent group (DBBSG), consisted of patients who underwent single pigtail biliary stent placement during the initial ERCP procedure. Biliary stent indwelling time was defined as the time from the date of successful placement of the biliary stent during the initial ERCP procedure to the date of removal of the biliary stent and intra-biliary cleansing during the second ERCP procedure. This time (in weeks) was used as the follow-up period in this study. Indwelling duration was analyzed as a time-dependent variable using Cox proportional risk models.

Outcomes

The primary endpoints were the occurrence of chyme reflux into the bile duct (defined as the presence of visible, macroscopic food particles or turbid, non-biliary fluid aspirated from the bile duct at the time of ERCP) and CBDS (the presence of stones in the common bile duct during the second ERCP for stent removal and intra-biliary cleansing, regardless of whether they were residual or recurrent stones, source surgical records, or ERCP images retained). The above results were assessed by both the endoscopist and the assistant. For reliability, a blinded second reviewer independently evaluated procedural images and endoscopy videos for all cases with suspected reflux.

The secondary endpoints included the occurrence of acute cholangitis (symptoms that met the diagnostic criteria for acute cholangitis during the second ERCP for stent removal) and stent displacement rates[20].

Evaluation of safety of the second ERCP for stent removal and intra-biliary cleansing was based on the following parameters: Changes in liver function, inflammatory markers, and ERCP-related adverse events within 24 hours postoperatively (ERCP-related adverse events[21] occurring during hospitalization after the second ERCP for stent removal and intra-biliary cleansing, based on electronic medical records and nursing records), primarily including post-ERCP acute cholangitis, post-ERCP pancreatitis, hyperamylasemia[22], postoperative nausea and vomiting, bleeding, and duodenal perforation during hospitalization.

Sample size

Based on preliminary data from our institution, the incidence of chyme reflux was estimated at 21% in the DBBSG and 8% in the SPBSG. To ensure adequate statistical power, we performed a sample size calculation using PASS software, specifying a two-sided alpha of 0.05 and 90% power (1-β = 0.9). PASS determined that a minimum of 142 subjects per group would be required to detect this difference. Our final sample comprised 318 DBBSG and 228 SPBSG patients.

Statistical analysis

Continuous data are summarized as the mean and standard deviation or median and interquartile range, and comparisons between groups were performed using independent samples t-tests or Mann-Whitney U tests. Count data are summarized as numbers and percentages, and comparisons between groups were performed using the χ² test or Fisher’s exact test. In this study, missing data were addressed using the “mice” package in R for multiple imputation, under the assumption of missing at random. Predictive mean matching was applied for continuous variables and logistic regression for categorical variables, generating five complete datasets. Results were combined using Rubin’s rules. Sensitivity analyses with complete-case data were performed to confirm the robustness of our findings.

The Kaplan-Meier method was used to estimate the cumulative risks, and the results were compared using the log-rank test. Cox proportional hazard regression models were used to determine the effect of covariates on outcomes and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Model 1 was an unadjusted Cox proportional hazards model. Model 2 was based on model 1 and additionally adjusted for age, sex, PBM, and extrahepatic bile duct strictures. Model 3 was based on model 2 and further adjusted for duodenal papilla length, EST incision length, DP, SOD, metal-covered biliary stents, and PDS. Restricted cubic splines were used to explore potential nonlinear relationships between the covariates of age, EST incision length, and CBDS.

To observe the effects of different biliary stents on primary outcomes in various subgroups, we set up six subgroups based on age (< 60 and ≥ 60), sex, hyperlipidaemia, extrahepatic biliary strictures, SOD, and PDS and assessed interactions in the Cox model. Regarding sensitivity analyses, we excluded two patient groups to avoid confounding the primary outcomes: (1) Patients with SOD, due to their potentially compromised biliary integrity; and (2) Those with metal-covered biliary stents, because the larger openings of these stents may facilitate reflux. Both the loss of normal regulation of the duodenal papilla due to SOD and the large-calibre opening of the metal stent itself, by design, predispose patients to enterobiliary reflux. We, therefore, excluded the above groups from the sensitivity analysis.

All statistical analyses were performed using R language (version 4.3.2) and SPSS software (version 27.0, IBM Corp, Armonk, NY, United States). Statistical significance was defined as P < 0.05.

RESULTS

Baseline patient demographics and disease characteristics

The median age of the overall population was 62 (interquartile range: 51-70) years, and 290 individuals (53.11%) were females (Table 1). Regarding the previous EST incision length and history of gallstones, the DBBSG was significantly longer than the SPBSG; however, the SPBSG had a higher proportion of patients with a history of cholecystectomy and pancreatic duct stenting (all P < 0.05). There were no significant differences in other demographic or disease characteristics between the two groups (all P > 0.05) (Table 1).

Table 1 Baseline patient demographics and disease characteristics, n (%).

Variable	Total (n = 546)	SPBSG (n = 228)	DBBSG (n = 318)	P value
Age, median (Q1, Q3)	62.00 (51.00, 70.00)	61.00 (51.00, 69.00)	62.00 (51.00, 71.00)	0.320
Sex				0.875
Female	290 (53.11)	122 (53.51)	168 (52.83)
Male	256 (46.89)	106 (46.49)	150 (47.17)
BMI (kg/m²), median (Q1, Q3)	21.56 (20.07, 23.23)	21.83 (20.07, 23.23)	21.30 (19.84, 23.23)	0.501
TC, median (Q1, Q3)	4.34 (3.65, 5.25)	4.27 (3.58, 5.14)	4.43 (3.71, 5.26)	0.116
TG, median (Q1, Q3)	1.19 (0.87, 1.72)	1.16 (0.86, 1.63)	1.20 (0.88, 1.87)	0.222
Duodenal papilla length (cm), median (Q1, Q3)	1.00 (0.78, 1.30)	1.02 (0.80, 1.39)	1.00 (0.76, 1.30)	0.111
Length of EST incision (mm), median (Q1, Q3)	3.00 (2.00, 3.58)	2.40 (1.00, 3.00)	3.00 (2.00, 4.00)	< 0.001
Diameter of EPBD (mm), median (Q1, Q3)	6.00 (6.00, 7.80)	6.00 (6.00, 7.12)	6.00 (6.00, 8.00)	0.888
Time (week), median (Q1, Q3)	11.00 (7.00, 14.00)	12.00 (7.25, 14.00)	11.00 (7.00, 14.00)	0.010
EST				< 0.001
No	139 (25.46)	78 (34.21)	61 (19.18)
Yes	407 (74.54)	150 (65.79)	257 (80.82)
EPBD				0.162
No	82 (15.02)	40 (17.54)	42 (13.21)
Yes	464 (84.98)	188 (82.46)	276 (86.79)
Diameter of the stents				< 0.001
5 Fr	35 (6.41)	35 (15.35)	0 (0)
7 Fr	193 (35.35)	172 (75.44)	21 (6.6)
8.5 Fr	105 (19.23)	19 (8.33)	86 (27.04)
10 Fr	213 (39.01)	2 (0.88)	211 (66.35)
Hyperlipidaemia				0.070
No	474 (86.81)	205 (89.91)	269 (84.59)
Yes	72 (13.19)	23 (10.09)	49 (15.41)
DM				0.100
No	481 (88.10)	207 (90.79)	274 (86.16)
Yes	65 (11.90)	21 (9.21)	44 (13.84)
CHD				0.408
No	504 (92.31)	213 (93.42)	291 (91.51)
Yes	42 (7.69)	15 (6.58)	27 (8.49)
Fatty liver				0.414
No	486 (89.01)	200 (87.72)	286 (89.94)
Yes	60 (10.99)	28 (12.28)	32 (10.06)
Gallstones				< 0.001
No	264 (48.35)	139 (60.96)	125 (39.31)
Yes	282 (51.65)	89 (39.04)	193 (60.69)
Congenital choledochal cysts				1.000
No	544 (99.63)	227 (99.56)	317 (99.69)
Yes	2 (0.37)	1 (0.44)	1 (0.31)
Extrahepatic bile duct stenosis				0.059
No	484 (88.64)	209 (91.67)	275 (86.48)
Yes	62 (11.36)	19 (8.33)	43 (13.52)
History of pancreatitis				0.327
No	503 (92.12)	207 (90.79)	296 (93.08)
Yes	43 (7.88)	21 (9.21)	22 (6.92)
History of ERCP				0.983
No	460 (84.25)	192 (84.21)	268 (84.28)
Yes	86 (15.75)	36 (15.79)	50 (15.72)
History of cholecystectomy				0.002
No	359 (65.75)	133 (58.33)	226 (71.07)
Yes	187 (34.25)	95 (41.67)	92 (28.93)
History of common bile duct exploration				0.165
No	527 (96.52)	223 (97.81)	304 (95.60)
Yes	19 (3.48)	5 (2.19)	14 (4.40)
DP				0.138
Simple or acute type	301 (55.13)	126 (55.26)	175 (55.03)
Hyperplastic or sclerotic type	118 (21.61)	58 (25.44)	60 (18.87)
Constrictive type	41 (7.51)	13 (5.70)	28 (8.81)
Atrophic type	86 (15.75)	31 (13.60)	55 (17.30)
PAD				0.377
No	384 (70.33)	165 (72.37)	219 (68.87)
Yes	162 (29.67)	63 (27.63)	99 (31.13)
Location of DP to PAD				0.406
Outside	392 (71.79)	168 (73.68)	224 (70.44)
Inside	154 (28.21)	60 (26.32)	94 (29.56)
SOD				0.209
No	477 (87.36)	204 (89.47)	273 (85.85)
Yes	69 (12.64)	24 (10.53)	45 (14.15)
PBM				0.152
No	506 (92.67)	207 (90.79)	299 (94.03)
Yes	40 (7.33)	21 (9.21)	19 (5.97)
PDS				< 0.001
No	256 (46.89)	74 (32.46)	182 (57.23)
Yes	290 (53.11)	154 (67.54)	136 (42.77)
Metal-covered stents				0.239
No	534 (97.80)	221 (96.93)	313 (98.43)
Yes	12 (2.20)	7 (3.07)	5 (1.57)

DBBSG: Duodenal bend biliary stent group; SPBSG: Single pigtail biliary stent group; BMI: Body mass index; TC: Total cholesterol; TG: Total triglycerides; EST: Endoscopic sphincterotomy; EPBD: Endoscopic papillary balloon dilation; ERCP: Endoscopic retrograde cholangiopancreatography; DP: Duodenal papillopathy; DM: Diabetes mellitus; CHD: Coronary heart disease; PAD: Periampullary diverticula; SOD: Sphincter of Oddi dysfunction; PBM: Pancreaticobiliary maljunction; PDS: Pancreatic duct stent.

Primary and secondary outcomes

In secondary duodenoscopy to remove the biliary stent and for intra-biliary cleansing, the incidences of chyme reflux into the bile duct [74/318 (23.27%) vs 22/228 (9.65%), P < 0.001] and CBDS [136/318 (42.77%) vs 48/228 (21.05%), P < 0.001] were significantly higher in the DBBSG than in the SPBSG. There were no significant differences in the incidence of acute cholangitis or stent displacement rates between the two groups (all P > 0.05) (Table 2).

Table 2 Primary and secondary outcomes, n (%).

Variable	Total (n = 546)	SPBSG (n = 228)	DBBSG (n = 318)	P value
Chyme				< 0.001
No	450 (82.42)	206 (90.35)	244 (76.73)
Yes	96 (17.58)	22 (9.65)	74 (23.27)
CBDS				< 0.001
No	362 (66.30)	180 (78.95)	182 (57.23)
Yes	184 (33.70)	48 (21.05)	136 (42.77)
Acute cholangitis				0.816
No	521 (95.42)	217 (95.18)	304 (95.60)
Yes	25 (4.58)	11 (4.82)	14 (4.40)
Stent displacement				0.335
No	524 (95.97)	221 (96.93)	303 (95.28)
Yes	22 (4.03)	7 (3.07)	15 (4.72)

DBBSG: Duodenal bend biliary stent group; SPBSG: Single pigtail biliary stent group; Chyme: Chyme reflux into the bile duct; CBDS: Common bile duct stones.

Evaluation of postoperative safety following intra-biliary cleansing

In secondary duodenoscopy to remove the biliary stent and for intra-biliary cleansing, the DBBSG had a longer hospital stay than the SPBSG (P = 0.039); however, overall, most patients (369 individuals, 67.58%) had a hospital stay of no more than 2 days (Supplementary Table 1). The postoperative 24-hour gamma-glutamyl transpeptidase levels were higher in the DBBSG than in the SPBSG (P = 0.009), but the median levels remained within the normal range (Supplementary Table 1). There were no significant differences between the two groups in postoperative adverse reactions (Table 3), liver function at 24 hours postoperatively, inflammatory markers, or amylase levels (all P > 0.05) (Supplementary Table 1).

Table 3 Incidence of postoperative adverse events in both groups, n (%).

Variable	Total (n = 546)	SPBSG (n = 228)	DBBSG (n = 318)	P value
Post-ERCP acute cholangitis				0.311
No	532 (97.44)	224 (98.25)	308 (96.86)
Yes	14 (2.56)	4 (1.75)	10 (3.14)
PEP				0.418
No	545 (99.82)	227 (99.56)	318 (100.00)
Yes	1 (0.18)	1 (0.44)	0 (0.00)
Bleeding				1.000
No	544 (99.63)	227 (99.56)	317 (99.69)
Yes	2 (0.37)	1 (0.44)	1 (0.31)
Duodenal perforation
No	546 (100)	228 (100)	318 (100)	NA
Yes	0 (0)	0 (0)	0 (0)

DBBSG: Duodenal bend biliary stent group; SPBSG: Single pigtail biliary stent group; ERCP: Endoscopic retrograde cholangiopancreatography; PEP: Post-endoscopic retrograde cholangiopancreatography pancreatitis; NA: Not available.

Cumulative risks of chyme reflux into the bile duct and CBDS

The Kaplan-Meier survival curves for chyme reflux into the bile duct and CBDS in the DBBSG and SPBSG groups are shown in Figure 2. The overall incidence of chyme reflux into the bile duct in the DBBSG was significantly higher than that in the SPBSG, with a HR of 2.643 (95%CI: 1.641-4.255; P < 0.001; Figure 2A). The overall incidence of CBDS in the DBBSG group was significantly higher than that in the SPBSG group, with a HR of 2.275 (95%CI: 1.632-3.172; P < 0.001; Figure 2B). There were no significant differences in the incidence of chyme reflux into the bile duct or CBDS between sexes (Figure 2C and D).

Figure 2 Kaplan-Meier curves for primary outcomes. A: Probability of chyme reflux by types of biliary stent; B: Probability of common bile duct stones by types of biliary stent; C: Probability of chyme reflux by sex; D: Probability of common bile duct stones by sex. HR: Hazard ratio; CI: Confidence interval; BS: Biliary stent; CBDS: Common bile duct stones; SPBS: Single pigtail biliary stent; DBBS: Duodenal bend biliary stent.

Types of biliary stents and chyme reflux into the bile duct and CBDS

Multivariate Cox proportional hazards regression models revealed that the type of biliary stent was associated with the risk of chyme reflux into the bile duct and CBDS (Tables 4 and 5, Figure 3). When adjusted for factors such as age, sex, PBM, extrahepatic bile duct stricture, duodenal papilla length, length of EST incision, DP, SOD, metal-covered biliary stents, and diameter of the stents and PDS, the DBBSG had a higher risk of developing chyme reflux into the bile duct (HR = 2.793; 95%CI: 1.695-4.603; P < 0.001) and CBDS (HR = 2.475; 95%CI: 1.732-3.536; P < 0.001) than the SPBSG (Tables 4 and 5, Figure 3). Model 3 revealed statistical differences in the continuous variables of age and EST incision length concerning CBDS (both P < 0.05). Further exploration of the nonlinear relationships through RCS revealed no significant nonlinear relationship between age, EST incision length, and CBDS (P-non-linear > 0.05; Supplementary Figure 1).

Figure 3 Hazard ratios and 95% confidence intervals of chyme reflux into the bile duct and common bile duct stones according to types of biliary stents. A: Hazard ratios and 95% confidence intervals of chyme reflux into the bile duct according to types of biliary stents; B: Hazard ratios and 95% confidence intervals of common bile duct stones according to types of biliary stents. HR: Hazard ratio; CI: Confidence interval; PBM: Pancreaticobiliary maljunction; EST: Endoscopic sphincterotomy; DP: Duodenal papillopathy; SOD: Sphincter of Oddi dysfunction; PDS: Pancreatic duct stent.

Table 4 Hazard ratios and 95% confidence interval of chyme reflux into the bile duct according to types of biliary stents.

Group	Model 1		Model 2		Model 3
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
0	1.00 (reference)	-	1.00 (reference)	-	1.00 (reference)	-
1	2.643 (1.641-4.255)	< 0.001	2.868 (1.774-4.637)	< 0.001	2.793 (1.695-4.603)	< 0.001

Model 1 was unadjusted; model 2 was based on model 1 and additionally adjusted for age, sex, pancreaticobiliary maljunction, and extrahepatic bile duct stricture; model 3 was based on model 2 and further adjusted for duodenal papilla length, length of endoscopic sphincterotomy incision, duodenal papillopathy, sphincter of Oddi dysfunction, metal-covered biliary stents, and diameter of the stents and pancreatic duct stent. HR: Hazard ratio; CI: Confidence interval.

Table 5 Hazard ratios and 95% confidence intervals of common bile duct stones according to types of biliary stents.

Group	Model 1		Model 2		Model 3
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
0	1.00 (reference)	-	1.00 (reference)	-	1.00 (reference)	-
1	2.275 (1.632-3.172)	< 0.001	2.319 (1.659-3.242)	< 0.001	2.475 (1.732-3.536)	< 0.001

Model 1 was unadjusted; model 2 was based on model 1 and additionally adjusted for age, sex, pancreaticobiliary maljunction, and extrahepatic bile duct stricture; model 3 was based on model 2 and further adjusted for duodenal papilla length, length of endoscopic sphincterotomy incision, duodenal papillopathy, sphincter of Oddi dysfunction, metal-covered biliary stents, and diameter of the stents and pancreatic duct stent. HR: Hazard ratio; CI: Confidence interval.

Subgroup and sensitivity analyses

In the main patient subgroups categorized by age (< 60 years and ≥ 60 years), sex, history of hyperlipidaemia, extrahepatic bile duct stricture, SOD, and PDS, there were no significant differences in the relationship between DBBSG and SPBSG with chyme reflux into the bile duct and CBDS (all P-interactions > 0.05, Supplementary Figures 2 and 3). In the sensitivity analysis, the relationship between duodenal bend biliary stent and chyme reflux into the bile duct was similar to that in the primary analysis. When the analysis was limited to patients without SOD, the connection between the two was slightly weakened (Supplementary Table 2). However, when the analysis was limited to patients without metal-covered bile duct stents, the connection between the two was slightly strengthened (Supplementary Table 3). The relationship between duodenal bend biliary stent and CBDS was similar to the results of the primary analysis. When the analysis was limited to patients without SOD or metal-covered bile duct stents, the connection between the two was slightly weakened (Supplementary Tables 4 and 5).

DISCUSSION

In the current management strategies for biliary stents, the type of stent and the timing of replacement are critical factors; however, there is a lack of clear guidelines regarding the performance of biliary cleaning after stent removal. This study, based on a retrospective cohort analysis of 556 patients, investigated the impact of different types of biliary stents and their dwelling time on the incidence of chyme reflux into the bile duct and CBDS (residual or recurrent) during secondary duodenoscopic stent retrieval and assessed the safety of intra-biliary cleansing. Our study results showed that compared to single pigtail biliary stents, patients with duodenal bend biliary stents had a significantly higher risk of chyme reflux into the bile duct (HR = 2.67; 95%CI: 1.59-4.50; P < 0.001) and CBDS (HR = 2.58; 95%CI: 1.78-3.75; P < 0.001). We performed adjusted Cox regression incorporating length of EST incision, stent diameter, and PDS as potential covariates that may affect the results. The relationship between stent type and primary outcomes was unchanged after adjustment, supporting the robustness of the findings. This result may be related to the design characteristics of the duodenal bend biliary stents, such as their larger diameter and relatively rigid structure, which may increase the pressure in the bile duct and impede the normal drainage of bile, in turn leading to the reflux of intestinal contents into the bile duct[23-25]. In addition, some patients are co-positioned with metal-coated stents because of the complexity of their condition, and the material properties of metal-coated stents may promote chronic inflammatory responses and fibrous tissue proliferation in the biliary lining, further exacerbating the risk of biliary obstruction and reflux[26,27]. This is supported by current literature, which states that differences in the biocompatibility and mechanical properties of different types of biliary stents can significantly affect clinical outcomes[28,29]. The surface properties of duodenal bend biliary stents may be more prone to induce biofilm formation, and the bacteria in these biofilms are able to attach to and colonise the bile ducts, increasing the risk of infection and stone formation[30,31]. These mechanisms explain why endoscopists should be more careful when selecting duodenal bend biliary stents in clinical practice[25], especially in high-risk patients, and should take appropriate precautions during placement and retrieval. The choice of the stent type should be assessed individually according to the patient’s anatomy and disease characteristics.

Studies have shown that in patients undergoing stent placement, the status of the stent should be regularly assessed and replaced in a timely manner[2,12]. The longer the stent was left in place, the higher the incidence of chyme reflux into the bile duct and stone formation. This finding is related to the chronic inflammatory and fibrotic processes in the biliary tract caused by prolonged stent retention, which may lead to cholestasis and bile duct stenosis[24,32]. This study further found that these risks were more prominent when duodenal bend biliary stents were used. It has been shown that regular stent replacement reduces the risk of bile duct infection and stone formation and improves the disease-free survival of patients[27,29]. In addition, the present study further supports the practice of intra-biliary cleansing during biliary stent removal. The study analyzed the safety of patients after secondary duodenoscopic removal of the biliary stent with intra-biliary cleansing and showed no significant difference between the two groups in terms of adverse effects, such as postoperative acute cholangitis and pancreatitis, indicating a similar short-term safety profile. Safety was high in the overall population, with no patients experiencing serious adverse events or deaths related to intra-biliary cleansing. Additionally, this study found that the incidence of acute cholangitis after bile duct stent placement was 4.58%, and the stent displacement rate was 4.03%, which is similar to previous studies[23-28]. Although postoperative gamma-glutamyl transpeptidase was significantly elevated in the DBBSG, the median remained within the normal range, and no subject developed clinical cholestasis or liver dysfunction, indicating that this rise was subclinical and likely related to transient procedural factors. DBBSG patients had slightly longer hospital stays (P = 0.039), likely reflecting greater procedural complexity rather than complications. This suggests that intra-biliary cleansing at the time of biliary stent removal is a safe and effective prophylactic measure, especially in patients who have had a stent in place for a long time or who are at high risk for stones. Unlike the European Society of Gastrointestinal Endoscopy guidelines, which prioritize timely stent replacement, our findings advocate intra-biliary cleansing as a standard step during removal, particularly for DBBS, to prevent late complications like cholangitis[29,33]—a practice shift supported by our low adverse event rates and significant risk reduction. The long-term safety of biliary stenting depends on its type and management, particularly in complex cases or those requiring prolonged stent drainage. By comparing different stent types, this study further refined the relationship between stent type, chyme reflux into the bile duct, and CBDS, providing new evidence for the choice of stent type in practice.

Although this study provides new insights into the optimization of biliary stent use, some limitations remain. This study did not investigate the long-term effects of different types of stents on the biliary micro-ecosystem, which may play an important role in the development of biliary complications[29,34]. In addition, future studies should focus on exploring the long-term effects of different stent types on the biliary microbial community and biofilm formation to provide more robust evidence for clinical decision-making[27,30,31,33]. This study’s single-center, retrospective design may have introduced potential selection bias and limited generalizability. Although comprehensive multivariable adjustment was applied, residual confounding by unmeasured variables remains possible. Furthermore, the findings may not be fully representative of outcomes in other geographic or healthcare contexts.

CONCLUSION

In summary, our study identified DBBS as a risk factor for enterobiliary reflux. Intra-biliary cleansing during secondary stent removal was associated with improved short-term outcomes in our cohort; however, additional long-term studies are required to determine sustained benefits and impacts on patient prognosis. Based on the results of this study, it is recommended that routine bile duct irrigation be performed during each planned stent replacement or removal procedure. For patients with temporary stents, irrigation should typically be performed every 3 months. Irrigation should include balloon or basket-based cleaning of the bile duct, with confirmation of clearance via cholangiography.