Sage Journals: Discover world-class research

Abstract

Background:

Endoscopic papillary balloon dilation (EPBD) has been recommended as a potential alternative to endoscopic sphincterotomy for common bile duct stones (CBDS), due to protecting the sphincter function.

Objectives:

This retrospective study aims to evaluate the safety and efficacy of endoscopic nasobiliary drainage (ENBD) versus endoscopic retrograde biliary drainage (ERBD) after EPBD for CBDS.

Design:

This study is a retrospective analysis of patients with CBDS who underwent EPBD followed by either ENBD or ERBD. It enrolled 283 patients, who underwent slow dilation and long-duration EPBD for CBDS with ENBD (eNbd group, n = 154) or ERBD (eRbd group, n = 129) from January 2022 to September 2023.

Methods:

Propensity score matching (PSM) was used to balance preoperative baselines and intraoperative specifics, resulting in 220 matched patients (110 patients per group). The incidence rate of post-ERCP pancreatitis (PEP) was compared between the two groups, and risk factors for PEP were analyzed.

Results:

After PSM, there were no significant differences in the baseline between the eNbd group and the eRbd group. The eNbd group exhibited significantly greater reduction in serum bilirubin levels compared to the eRbd group. Before PSM, the incidence rate of PEP was 2.6% (4/154) in the eNbd group and 8.5% (11/129) in the eRbd group (p = 0.027). After PSM, the incidence rate of PEP was 2.7% (3/110) in the eNbd group and 9.1% (10/110) in the eRbd group (p = 0.045). In addition, subgroup analysis revealed that patients with multiple stones may have a higher likelihood of developing PEP.

Conclusion:

ENBD may be an optimal choice for patients with CBDS undergoing EPBD, and the presence of multiple stones may be particularly relevant when considering the risk of PEP.

Plain language summary

A study comparing two methods to prevent pancreatitis after a specific type of bile duct procedure

Why was the study done? Sometimes, people have stones in their bile ducts, which can cause problems. Doctors use a procedure called endoscopic papillary balloon dilation (EPBD) to remove these stones. After this procedure, doctors need to decide whether to use a tube called endoscopic nasobiliary drainage (ENBD) or to place a small tube called a biliary stent (ERBD) to help with drainage. We wanted to find out which method is better at preventing a serious complication called pancreatitis, which is inflammation of the pancreas.

What did the researchers do? We looked at 283 patients who had EPBD for bile duct stones. Half of them had ENBD, and the other half had ERBD. We used a special method called propensity score matching to make sure the groups were similar in important ways before we compared them. We then checked how many people in each group got pancreatitis after the procedure.

What did the researchers find? Before matching, 2.6% of people with ENBD got pancreatitis, while 8.5% of those with ERBD did. After matching, the numbers were 2.7% for ENBD and 9.1% for ERBD. This means that fewer people got pancreatitis with ENBD. We also found that patients with multiple stones might be more likely to get pancreatitis.

What do the findings mean? Our study shows that using ENBD is a better choice for patients having EPBD to remove bile duct stones, as it helps prevent pancreatitis. Doctors should consider this when deciding on the best treatment, especially for patients with multiple stones.

Keywords

common bile duct stones (CBDS)endoscopic nasobiliary drainage (ENBD)endoscopic retrograde biliary drainage (ERBD)ERCP post-ERCP pancreatitis (PEP)

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is currently the gold standard in the diagnosis of pancreaticobiliary disease, and is considered the first choice in the treatment of common bile duct stones (CBDS).^1–3 In 1974, Classen and Demling⁴ and Kawai et al.⁵ performed the endoscopic duodenal papillary sphincterotomy (EST), significantly improving the success rate and accomplishing a complete removal of CBDS. However, EST has a relatively high risk of short- and long-term complications. Besides bleeding and perforation, EST-induced destruction of the Oddi’s sphincter results in cholangitis, cholecystitis, the recurrence of bile duct stones, and even the occurrence of cholangiocarcinoma.^6,7 In 1983, Staritz et al.⁸ first introduced endoscopic papillary balloon dilation (EPBD) for the removal of CBDS while protecting sphincter function and reducing the probability of bleeding, perforation. Thus, EPBD is recognized as a potential alternative for EST.

However, EPBD is always thought to be associated with post-ERCP pancreatitis (PEP),^9–11 though Fujisawa et al.⁹ reviewed 13 randomized controlled trials (RCTs) comparing EPBD and EST, and found that there was no significant difference of PEP in 10 RCTs, indicated that the lower maximum pressure and shorter ballooning time might be related to PEP. Therefore, it is usually concerned to reduce the risk of PEP after EPBD. Endoscopic nasobiliary drainage (ENBD) is a simple and rapid method for biliary decompression; moreover, several studies indicated that ENBD prevented the occurrence of PEP, especially post-EPBD pancreatitis.^12–15 However, the catheter of ENBD is easy to be dislodged or removed by some patients,¹⁶ and make the patients feel nasopharyngeal discomfort, which can affect the patient’s quality of life. In contrast, indwelling stents by endoscopic retrograde biliary drainage (ERBD) cannot be removed by the patient and are relatively more comfortable than ENBD. Furthermore, ERBD is equally effective for patients with acute suppurative cholangitis caused by bile duct stones like ENBD, thus gaining application.¹⁷ However, it is unclear the role of ERBD on preventing post-EPBD pancreatitis.

Therefore, the aim of this study is to retrospectively compare the efficacy and safety of the efficacy of ENBD versus ERBD in preventing post-EPBD PEP for CBDS.

Materials and methods

Patients

This study retrospectively analyzed the data of 283 patients who underwent ERCP with EPBD for the management of CBDS and received either ENBD or ERBD at the First Affiliated Hospital of Sun Yat-sen University from January 2022 to September 2023. According to biliary drainage, the patients were divided into two groups, eNbd group (n = 154) and eRbd group (n = 129). Patients with concurrent malignant biliary tumors or missing group variables were excluded. We collected the data on patient demographics, preoperative baseline conditions, procedure details, and postoperative complications. The baseline variables of patients were matched and imputed using k-Nearest Neighbor Imputation. After propensity score matching (PSM), 220 patients remained, including 110 per group.

The diagnosis of CBDS was based on the results of abdominal CT, hepatobiliary ultrasound, or magnetic resonance cholangiopancreatography. Coagulation disorders were corrected before ERCP, and antibiotics were administered postoperatively if evidence of infection were present. According to our center’s clinical experience and relevant literature,¹⁸ antibiotics or somatostatin are not routinely used prophylactically in the postoperative period; these medications are only administered when a patient is diagnosed with cholangitis or pancreatitis. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.¹⁹

Endoscopic procedure

Patients signed informed consent forms, then were placed in the prone position, were given intravenous conscious sedation and local pharyngeal anesthesia. ERCP was performed with a side-viewing duodenoscope (TJF-240, JF-260V; Olympus Co. Ltd, Tokyo, Japan) by experienced endoscopists (>1000 ERCP procedures). A duodenoscope was inserted through the mouth to the descending part of the duodenum. After cannulating the common bile duct via the duodenal papilla, cholangiography was performed to record the location, diameter, and presence of stones. Then, slow dilation and long-duration EPBD alone were performed. The balloon (Boston Scientific Corp., Natick, MA, USA) was inflated using dilute contrast and gradually expanded slowly from the smallest diameter (6–7–8 mm dilation balloon), increasing 1 ATM every 15 s. After reaching the 8 mm diameter, the larger dilation balloon (8–9–10 mm dilation balloon) was replaced until the specified size was reached according to the size of stones. After the final ATM was maintained for more than 2 min, the balloon was deflated immediately. Based on the patient’s condition, selective dilation of the stenotic segment and stone extraction using a balloon or basket were performed. After assessing the location, diameter, and length of the biliary stricture, the decision to place a plastic stent (8.5 Fr × 12 cm, or 8.5 Fr × 10 cm, or 8.5 Fr × 7 cm; Boston Scientific Corporation, Marlborough, MA, USA) or nasobiliary drainage tube (8.5 Fr × 250 cm; Boston Scientific Corporation) was made according to the physician’s experience. Following the placement of the plastic stent or nasobiliary drainage tube, another cholangiography was conducted to ensure the patency of the drainage. For patients with ENBD, daily drainage volume and symptoms were monitored, and the tube was typically removed 3–14 days after ERCP. However, for patients with ERBD, they were suggested to remove the plastic stent 1–6 months after ERCP.

Evaluation parameters and complications

Multiple stones are defined as the presence of ⩾2 stones in the common bile duct, as detected by preoperative imaging or intraoperative X-ray cholangiography.²⁰ The European Society of Gastrointestinal Endoscopy 2016 guidelines suggest that difficult biliary cannulation is defined as one or more of the following situations: more than five contacts with the major duodenal papilla, or attempts at cannulation exceeding 5 min after contrast injection, or more than one accidental pancreatic duct cannulation or contrast injection.²¹ Those with a total procedural volume exceeding 1000 cases are considered experts, while the rest are considered fellows. A small papilla is often flat, with a diameter not bigger than 3 mm. Literature indicates that patients with small papillae have a higher incidence of postoperative complications. Therefore, our study categorized papilla types into small papilla and other papilla.²²

PEP is diagnosed when there is a new onset (or increase) of pain in the upper abdomen, an elevation in pancreatic enzymes to at least three times the upper limit of normal 24 h after the procedure, and a hospital stay of at least two nights.^23–25 The severity of PEP is classified as mild, moderate, or severe. If serum amylase levels are elevated without abdominal pain after ERCP, it is diagnosed as hyperamylasemia. Post-ERCP cholangitis is defined by fever (>38°C), leukocytosis, and abdominal pain attributed to biliary causes, in the absence of evidence for acute cholecystitis. Post-ERCP bleeding is defined as the occurrence of melena or hematemesis accompanied by a hemoglobin (Hb) decrease of at least 2 g/dL or requiring transfusion. Perforations include retroperitoneal or intestinal wall perforations documented by any radiological technique. The incidence of ERCP-related complications, including PEP, hyperamylasemia, perforation, bleeding, and cholangitis, was closely monitored.

Propensity score-matched analysis

To minimize potential confounders, we employed PSM using logistic regression on demographic and clinical characteristics. We performed 1:1 greedy nearest neighbor matching with the caliper of 0.45, using the R package MatchIt. This method assigned control units one by one without optimizing an overall criterion, ensuring that observed differences were attributable to the treatments rather than confounding factors. Each row corresponds to a specific covariate, with columns showing the mean or proportion values for each group, as well as the p-value before and after matching. The notable change in p-value after matching indicates that PSM effectively improved the covariate balance between the two treatment groups. This improvement allows for a more reliable comparison of treatment effectiveness by minimizing the potential influence of confounding factors.

Laboratory parameters

Key indicators, including red blood cell count (RBC), Hb, white blood cell count (WBC), platelet count (PLT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), as well as amylase and lipase, were analyzed in the comparison between the two groups. Pre-ERCP test indicators were derived from the most recent blood test before ERCP, while post-ERCP test indicators were taken from the first blood test on the day following ERCP.

Statistical analysis

Statistical analyses were conducted using SPSS (version 26.0; SPSS, Chicago, IL, USA) and R (version 4.2.2; R Foundation, Vienna, Austria). PSM was employed to address potential biases introduced by baseline characteristics. Categorical data were analyzed using Chi-squared tests or Fisher’s exact tests, while continuous data were assessed with Student’s t tests or Mann–Whitney U tests. For continuous variables with a normal distribution, means ± standard deviations (SD) were reported, whereas median (interquartile range) was used for skewed distributions.

Results

In this study, we retrospectively analyzed the medical records of 283 patients who underwent ERCP and EPBD with ENBD or ERBD for CBDS. The overall baseline characteristics of these 283 patients were presented in Table 1, including the eNbd group with ENBD (n = 154) and eRbd group with ERBD (n = 129). We found that some parameters showed imbalance between the two groups, such as gender, preoperative laboratory parameters (WBC, TB, DB, and PT), and acute cholangitis. To enhance baseline comparability and reduce confounding factors, we applied PSM. After matching, the balanced baseline characteristics were achieved (p > 0.05), and the sample size was reduced to 220 patients, with 110 patients per group, as shown in Figure 1.

Table 1.

Baseline characteristics of the eNbd and eRbd groups before and after PSM.

Characteristics	Unmatched			Matched
Characteristics	eNbd, N = 154	eRbd, N = 129	p-Value	eNbd, N = 110	eRbd, N = 110	p-Value
Age			0.050			0.828
Mean ± SD	57 ± 16	61 ± 15		60 ± 15	60 ± 15
Gender, n (%)			0.041			0.890
Female	71 (46%)	44 (34%)		43 (39%)	42 (38%)
Male	83 (54%)	85 (66%)		67 (61%)	68 (62%)
Diabetes, n (%)			0.740			0.676
No	138 (90%)	114 (88%)		96 (87%)	98 (89%)
Yes	16 (10%)	15 (12%)		14 (13%)	12 (11%)
BMI			0.813			0.903
Mean ± SD	23.0 ± 3.7	22.9 ± 3.2		23.0 ± 3.6	22.9 ± 3.2
RBC (×10⁹/L)			0.223			0.726
Mean ± SD	4.37 ± 0.72	4.27 ± 0.70		4.31 ± 0.72	4.27 ± 0.69
Hb (g/L)			0.305			0.688
Mean ± SD	128 ± 19	125 ± 23		126 ± 20	125 ± 23
WBC (×10⁹/L)			0.020			0.165
Mean ± SD	7.1 ± 3.0	8.2 ± 4.5		7.2 ± 3.1	7.9 ± 4.3
PLT (×10⁹/L)			0.699			0.851
Mean ± SD	237 ± 77	233 ± 77		235 ± 84	233 ± 77
ALT (U/L)			0.055			0.996
Mean ± SD	164 ± 207	126 ± 123		128 ± 186	128 ± 127
AST (U/L)			0.128			0.678
Mean ± SD	121 ± 167	95 ± 113		90 ± 136	97 ± 120
TB (µmol/L)			0.004			0.078
Mean ± SD	50 ± 67	77 ± 84		56 ± 75	75 ± 86
DB (µmol/L)			0.009			0.105
Mean ± SD	25 ± 55	45 ± 72		28 ± 64	44 ± 76
PT(s)			0.018			0.181
Mean ± SD	12.13 ± 1.22	12.63 ± 2.10		12.21 ± 1.31	12.52 ± 2.10
Acute cholangitis			0.014			0.575
No	111 (72%)	75 (58%)		72 (65%)	68 (62%)
Yes	43 (28%)	54 (42%)		38 (35%)	42 (38%)
Acute pancreatitis			0.271			0.676
No	139 (90%)	111 (86%)		98 (89%)	96 (87%)
Yes	15 (10%)	18 (14%)		12 (11%)	14 (13%)
Acute cholecystitis			0.126			0.550
No	126 (82%)	114 (88%)		94 (85%)	97 (88%)
Yes	28 (18%)	15 (12%)		16 (15%)	13 (12%)
Chronic cholecystitis			0.067			0.377
No	99 (64%)	96 (74%)		74 (67%)	80 (73%)
Yes	55 (36%)	33 (26%)		36 (33%)	30 (27%)

ALT, alanine aminotransferase; AST, aspartate aminotransferase; DB, direct bilirubin; eNbd, endoscopic nasobiliary drainage; eRbd, endoscopic retrobiliary drainage; Hb, hemoglobin; PLT, platelet count; PSM, propensity score matching; RBC, red blood cell count; SD, standard deviation; TB, total bilirubin; WBC, white blood cell count.

Figure 1.

The enrolled patients’ demographics.

Intraoperative details of ERCP were meticulously documented, incorporating several indicators identified in guidelines as potential risk factors for ERCP-related complications, such as stone size, procedure time, intubation time, multiple stones, difficult cannulation, guidewire insertion into the pancreatic duct, balloon dilatation size, mechanical lithotripsy, with gallbladder stones, operator experience, papilla type, the presence with diverticulum and incomplete stones extraction, as shown in Table 2. The results demonstrated similar intraoperative conditions between the two groups before or after PSM.

Table 2.

ERCP procedure details of the eNbd and eRbd groups before and after PSM.

Characteristics	Unmatched			Matched
Characteristics	eNbd, N = 154	eRbd, N = 129	p-Value	eNbd, N = 110	eRbd, N = 110	p-Value
Stone size (mm)			0.285			0.959
Mean ± SD	7.8 ± 3.8	8.4 ± 4.6		8.3 ± 3.8	8.3 ± 4.8
Procedure time (min)			0.685			0.779
Mean ± SD	42 ± 17	42 ± 19		44 ± 17	43 ± 20
Intubation time (min)			0.947			0.764
Mean ± SD	5.6 ± 7.2	5.6 ± 5.4		6.1 ± 8.3	5.8 ± 5.7
Multiple stones			0.140			0.415
No	78 (51%)	54 (42%)		51 (46%)	45 (41%)
Yes	76 (49%)	75 (58%)		59 (54%)	65 (59%)
Difficult cannulation			0.359			>0.999
No	107 (69%)	83 (64%)		73 (66%)	73 (66%)
Yes	47 (31%)	46 (36%)		37 (34%)	37 (34%)
Guidewire insertion into the pancreatic duct			0.168			>0.999
No	124 (81%)	95 (74%)		84 (76%)	84 (76%)
Yes	30 (19%)	34 (26%)		26 (24%)	26 (24%)
Balloon dilatation size (mm)			0.099			0.762
Mean ± SD	8.15 ± 1.29	8.41 ± 1.33		8.41 ± 1.28	8.35 ± 1.29
Mechanical lithotripsy			0.274			0.665
No	142 (92%)	114 (88%)		99 (90%)	97 (88%)
Yes	12 (8%)	15 (12%)		11 (10%)	13 (12%)
With gallbladder stones			0.866			>0.999
No	94 (61%)	80 (62%)		69 (63%)	69 (63%)
Yes	60 (39%)	49 (38%)		41 (37%)	41 (37%)
Operator experience			0.876			0.538
Expert	137 (89%)	114 (88%)		98 (89%)	95 (86%)
Fellow	17 (11%)	15 (12%)		12 (11%)	15 (14%)
Papilla type			0.870			0.767
Other	110 (71%)	91 (71%)		79 (72%)	77 (70%)
Small	44 (29%)	38 (29%)		31 (28%)	33 (30%)
Diverticulum			0.713			0.748
No	121 (79%)	99 (77%)		86 (78%)	84 (76%)
Yes	33 (21%)	30 (23%)		24 (22%)	26 (24%)
Incomplete stones extraction			0.090			0.499
No	143 (93%)	112 (87%)		107 (97.3%)	104 (94.5%)
Yes	11 (7%)	17 (13%)		3 (2.7%)	6 (5.5%)

ERCP, endoscopic retrograde cholangiopancreatography; eNbd, endoscopic nasobiliary drainage; eRbd, endoscopic retrobiliary drainage; PSM, propensity score matching; SD, standard deviation.

On the first postoperative day, laboratory parameters were collected, including ALT, AST, TB, and DB, as shown in Table 3. We calculated the change in values by subtracting the preoperative levels from the postoperative levels in two groups, and analyzed their significant differences to evaluate the efficacy of these two drainage methods for the recovery of patients. Interestingly, we observed that the reduction level of serum TB in the eNbd group was significantly greater than that in the eRbd group (−17.0 ± 66.34 vs −7.4 ± 61.58 µmol/L, p = 0.008). Similarly, the change in DB of eNbd group was also remarkably greater than that of ERBD DB levels (−13.6 ± 67.97 vs −12.1 ± 77.02 µmol/L, p = 0.021). Moreover, the length of total hospital stay and post-ERCP hospital stay in the eNbd group were both shorter than those in the eRbd group (6.6 ± 4.42 vs 7.6 ± 4.58 days, p = 0.136; 3.6 ± 3.05 vs 4.2 ± 3.60 days, p = 0.251); however, no marked difference was found. In addition, the changes in ALT (eNbd −48.2 ± 128.29 U/L vs eRbd −37.8 ± 83.04 U/L, p = 0.507), AST (eNbd −45.2 ± 133.93 U/L vs eRbd −34.2 ± 78.99 U/L, p = 0.482) also showed no significant differences between the two groups.

Table 3.

Comparison of laboratory parameters measured on day 1 after ERCP between the eNbd and eRbd groups.

Characteristics	Final		Change from baseline		eRbd − eNbd
Characteristics	eNbd	eRbd	eNbd	eRbd	Difference in LS mean (95% CI)	p-Value
ALT (U/L)	83.5 (115.59)	86.3 (97.32)	−48.2 (128.29)	−37.8 (83.04)	6.63 (−12.90, 26.17)	0.507
AST (U/L)	49.9 (55.39)	53.3 (44.29)	−45.2 (133.93)	−34.2 (78.99)	4.70 (−8.39, 17.80)	0.482
TB (µmol/L)	38.3 (32.89)	63.0 (74.13)	−17.0 (66.34)	−7.4 (61.58)	18.05 (4.78, 31.31)	0.008*
DB (µmol/L)	17.0 (20.33)	31.4 (47.93)	−13.6 (67.97)	−12.1 (77.02)	12.66 (2.00, 23.33)	0.021*
Total hospital stay (days)	6.6 (4.42)	7.6 (4.58)			0.92 (−0.29, 2.13)	0.136
Hospital stay after ERCP (days)	3.6 (3.05)	4.2 (3.60)			0.53 (−0.37, 1.42)	0.251

Data are expressed as mean (SD).

p < 0.05.

ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval; DB, direct bilirubin; ERCP, endoscopic retrograde cholangiopancreatography; eNbd, endoscopic nasobiliary drainage; eRbd, endoscopic retrobiliary drainage; LS, least squares; TB, total bilirubin.

In the assessment of ERCP-related postoperative complications, as shown in Table 4, we present the results before and after PSM. Before PSM, among the 283 ERCP procedures, 15 patients (5.30%, 15/283) underwent PEP, including 4 cases (2.6%, 4/154) in the eNbd group and 11 cases (8.5%, 11/129) in the eRbd group. The difference between two groups was remarkable, p = 0.027. In addition, all cases belonged to mild pancreatitis. No significant differences were observed in other complications, such as hyperamylasemia, cholangitis, bleeding, and perforation. After PSM, there were 13 cases of PEP (5.91%, 13/220) among the 220 ERCP procedures, including 3 cases (2.7%, 3/110) in the eNbd group and 10 cases (9.1%, 10/110) in the eRbd group. The difference in PEP incidence between the two groups remained significant (p = 0.045). Similarly, other complications still showed no significant differences.

Table 4.

Incidence of ERCP-related adverse events between the eNbd and eRbd groups.

	Unmatched			Matched
	eNbd, N = 154	eRbd, N = 129	p-Value	eNbd, N = 110	eRbd, N = 110	p-Value
PEP	4 (2.6%)	11 (8.5%)	0.027*	3 (2.7%)	10 (9.1%)	0.045*
Hyperamylasemia	26 (17%)	14 (11%)	0.15	20 (18%)	13 (12%)	0.19
Cholangitis	5 (3.2%)	6 (4.7%)	0.54	5 (4.5%)	4 (3.6%)	>0.99
Bleeding	2 (1.3%)	3 (2.3%)	0.66	2 (1.8%)	3 (2.7%)	>0.99
Perforation	0(0%)	0(0%)	>0.99	0 (0%)	0 (0%)	>0.99

p < 0.05.

eNbd, endoscopic nasobiliary drainage; eRbd, endoscopic retrobiliary drainage; ERCP, endoscopic retrograde cholangiopancreatography; PEP, postendoscopic retrograde cholangiopancreatography pancreatitis.

The exploratory subgroup analyses for PEP occurrence, as shown in Table 5, reveal significant differences in ERBD and the presence of multiple stones. Specifically, ERBD and the presence of multiple stones was associated with a significantly higher risk of PEP in the eRbd group compared to the eNbd group, with an odds ratio (OR) of 3.50 (95% confidence interval (CI): 1.09–11.26, p = 0.036) and 2.12 (95% CI: 0.21–20.94, p = 0.043). Other factors such as gender, diabetes, acute cholangitis, acute pancreatitis, acute cholecystitis, chronic cholecystitis, difficult cannulation, guidewire insertion into the pancreatic duct, gallbladder stones, mechanical lithotripsy, operator experience, and incomplete stone extraction did not show significant differences in PEP occurrence between the two groups. These findings suggest that ERBD and the presence of multiple stones may be particularly relevant when considering the risk of PEP after EPBD for CBDS. Subsequently, we conducted a multivariate regression analysis and found that ERBD was still significantly associated with an increased risk of PEP, with an OR of 3.29 (95% CI: 1.02–10.66, p = 0.047), while the presence of multiple stones did not show a significant difference.

Table 5.

Exploratory subgroup analyses and multivariate analyses for PEP occurrence.

Subgroup	eRbd	eNbd	Univariate analysis		Multivariable analysis
Subgroup	eRbd	eNbd	Crude OR (95% CI)	p-Value	Crude OR (95% CI)	p-Value
Drainage method	11/129 (8.5)	4/154 (2.6)	3.50 (1.09–11.26)	0.036*	3.29 (1.02–10.66)	0.047*
Gender				0.121
Female	2/44 (4.5)	3/71 (4.2)	0.93 (0.15–5.78)
Male	9/85 (10.6)	1/83 (1.2)	0.10 (0.01–0.83)
Diabetes				0.992
No	9/114 (7.9)	4/138 (2.9)	0.35 (0.10–1.16)
Yes	2/15 (13.3)	0/16 (0.0)	0.00 (0.00–Inf)
Acute cholangitis				0.992
No	6/75 (8.0)	4/111 (3.6)	0.43 (0.12–1.58)
Yes	5/54 (9.3)	0/43 (0.0)	0.00 (0.00–Inf)
Acute pancreatitis				0.568
No	9/111 (8.1)	3/139 (2.2)	0.25 (0.07–0.95)
Yes	2/18 (11.1)	1/15 (6.7)	0.57 (0.05–7.00)
Acute cholecystitis				1
No	11/114 (9.6)	4/126 (3.2)	0.31 (0.09–0.99)
Yes	0/15 (0.0)	0/28 (0.0)	1.00 (0.00–Inf)
Chronic cholecystitis				0.989
No	11/96 (11.5)	3/99 (3.0)	0.24 (0.07–0.89)
Yes	0/33 (0.0)	1/55 (1.8)	43016076.48 (0.00–Inf)
Multiple stones				0.043*
No	1/54 (1.9)	3/78 (3.8)	2.12 (0.21–20.94)		2.304(0.709–7.487)	0.165
Yes	10/75 (13.3)	1/76 (1.3)	0.09 (0.01–0.70)
Difficult cannulation				0.501
No	7/83 (8.4)	2/107 (1.9)	0.21 (0.04–1.02)
Yes	4/46 (8.7)	2/47 (4.3)	0.47 (0.08–2.68)
Guidewire insertion into the pancreatic duct				0.253
No	8/95 (8.4)	2/124 (1.6)	0.18 (0.04–0.86)
Yes	3/34 (8.8)	2/30 (6.7)	0.74 (0.11–4.74)
With gallbladder stones				0.923
No	8/80 (10.0)	3/94 (3.2)	0.30 (0.08–1.16)
Yes	3/49 (6.1)	1/60 (1.7)	0.26 (0.03–2.58)
Mechanical lithotripsy				0.99
No	9/114 (7.9)	4/142 (2.8)	0.34 (0.10–1.13)
Yes	2/15 (13.3)	0/12 (0.0)	0.00 (0.00–Inf)
Operator experience				0.993
Expert	10/114 (8.8)	4/137 (2.9)	0.31 (0.10–1.03)
Fellow	1/15 (6.7)	0/17 (0.0)	0.00 (0.00–Inf)
Papilla type				0.959
Other	8/91 (8.8)	3/110 (2.7)	0.29 (0.07–1.13)
Small	3/38 (7.9)	1/44 (2.3)	0.27 (0.03–2.72)
Diverticulum				0.703
No	9/99 (9.1)	3/121 (2.5)	0.25 (0.07–0.97)
Yes	2/30 (6.7)	1/33 (3.0)	0.44 (0.04–5.09)
Incomplete stones extraction				0.99
No	9/112 (8.0)	4/143 (2.8)	0.33 (0.10–1.10)
Yes	2/17 (11.8)	0/11 (0.0)	0.00 (0.00–Inf)

p < 0.05.

CI, confidence interval; eNbd, endoscopic nasobiliary drainage; eRbd, endoscopic retrobiliary drainage; Inf, infinity; PEP, postendoscopic retrograde cholangiopancreatography pancreatitis.

Discussion

This is the largest sample size study to date that evaluates and reveals the safety and efficacy of nasobiliary drainage versus stent drainage in patients with CBDS. Although this is a retrospective study, the preoperative patient baseline and intraoperative details were well-balanced and comparable after PSM. Upon comparison, we found no significant differences between the two groups in terms of liver function indicators, hospital stay duration, or complications such as hyperamylasemia, cholangitis, and bleeding. However, a significant difference in the incidence of PEP was observed. This finding may help enhance endoscopists’ understanding of drainage method selection after EPBD for CBDS and potentially promote further contemplation and advancement in endoscopic practice.

Based on our center’s clinical experience, papillary edema may occur after EPBD, which can promote the occurrence of postoperative complications. Moreover, the study by Zhang et al.²⁶ suggests that endoscopic biliary drainage by nasobiliary tube or biliary stent insertion is a simple and quick method for biliary decompression, especially for ENBD. In addition, with the continuous development of stents and delivery systems and advancements in technology, the placement of nasobiliary drainage tubes or biliary stents under ERCP has become a common method for biliary drainage after CBDS extraction.²⁷ ENBD is a surgical procedure for draining bile and relieving biliary obstruction, facilitating bile cytology examination and cholangiography.²⁸ Zhang et al.²⁹ indicated that preoperative ENBD effectively reduced hospital stay and prevented from postoperative bile leakage and duodenal papilla damage after laparoscopic cholecystectomy. However, throat discomfort can hinder ENBD as an initial drainage method. Compared to ENBD, biliary stents are easier to replace and can significantly improve patient comfort and adherence, thus are widely used. Additionally, some reports indicate that long-term stent placement can effectively reduce the size of difficult stones, facilitating mechanical lithotripsy.^30,31 However, it is undeniable that patients with plastic stents placed during ERCP generally require another ERCP or gastroscopy procedure for stent removal after 3–6 months. This can lead to a higher incidence of complications and decreased patient comfort. The primary drawbacks of plastic stents also include poor biocompatibility, small diameter, and a propensity for blockage, leading to recurrent jaundice and pruritus.³² Thus, the two procedures are both very effective biliary drainage with their own shortcomings.

In terms of efficacy, we found that there were significant differences in the reduction of the TB (eNbd −17.0 ± 66.34 vs eRbd −7.4 ± 61.58 µmol/L, p = 0.008), and DB (eNbd −13.6 ± 67.97 vs eRbd −12.1 ± 77.02 µmol/L, p = 0.021). However, no significant differences were observed between the two groups in terms of the reduction of AST, ALT, and length of hospital stay, or complications such as hyperamylasemia, cholangitis, and bleeding. The role of ENBD in emergency biliary drainage has been recognized. A retrospective study by Huang et al.¹⁵ found that ENBD was superior to ERBD in terms of biliary drainage effectiveness, and the incidence of drainage tube occlusion associated with cholangitis was significantly higher in the eRbd group than in the eNbd group. This is consistent with our study results. Considering that ENBD drains through a nasobiliary tube, it may be more effective in dealing with bile that is highly viscous or infected, which could be the reason for its better performance in reducing the obstruction of drainage tubes. Furthermore, the eNbd group can undergo flushing through the nasobiliary drainage tube, diluting and aspirating the obstructions, thus resolving most cases of tube occlusion, whereas patients in the eRbd group may require additional ERCP procedures to replace the drainage tube or even emergency surgery.

In terms of safety, PEP is one of the most severe and common complications after ERCP, particularly after EPBD for CBDS.^33,34 In terms of preventing PEP, ENBD is reported to block the occurrence of PEP effectively, while there is no ERBD-related literature for PEP after CBDS extraction. In a retrospective study comparing biliary strictures caused by benign and malignant diseases involving 1136 patients, plastic biliary stent placement was superior to self-expandable metallic stents in preventing PEP,^35,36 because the latter might impede pancreatic juice outflow. Hence, we focus on the safety and efficacy of ENBD versus ERBD in preventing PEP after EPBD in patients with CBDS. In this study, we utilized the maximum sample size of data among single-center studies to analyze, and found that the total incidence of PEP was only 5.30% after simple slow dilation and long duration EPBD, which is lower than that in the current reported data. The results may be related to our experience: no sphincterotomy, slow dilation, and long duration EPBD, and biliary drainage. We further compared eNbd group with eRbd group, noticed that ENBD decreased the incidence of PEP from 8.5% to 2.6%, the difference was significant, p = 0.027. Then, we applied PSM to enhance baseline comparability and reduce confounding factors, and still observed that ENBD decreased the incidence of PEP from 9.1% to 2.7%; the difference was still significant, p = 0.045. The results supported that ENBD is superior to ERBD in preventing PEP after EPBD for CBDS.

To explore whether there are independent risk factors for the difference in the incidence of PEP between the eRbd group and the eNbd group, we conducted a subgroup analysis. Our subgroup analysis revealed that ERBD and multiple stones may be independent risk factors for PEP, with an OR of 3.50 (95% CI: 1.09–11.26, p = 0.036) and 2.12 (95% CI: 0.21–20.94, p = 0.043), respectively. Biliary stones have long been recognized as a risk factor for pancreatitis.³⁷ A study by Niels G Venneman et al.³⁸ found that patients with pancreatitis more frequently had sludge-like stones and multiple stones, which is consistent with our findings. The reason may be that the greater the number of stones, the higher the chance of them becoming impacted in the ampulla. In addition, the regular passage of stones can cause damage to the common channel and increase the pressure in the pancreatic and biliary ducts, further promoting the occurrence of pancreatitis. To further control for potential confounding factors, we conducted a multivariate regression analysis. The results indicated that ERBD remains an independent risk factor for the occurrence of PEP (multivariate analysis OR = 3.29, p = 0.047), while multiple stones did not show significant differences in the multivariate analysis. Our findings underscore the importance of ERBD or ENBD in the occurrence of PEP in patients with CBDS. Although multiple stones did not show significant differences in the multivariate analysis, their significance in the univariate analysis suggests that we cannot ignore their potential impact. This may imply that, in certain situations, multiple stones might influence the risk of PEP through other confounding factors that are not fully controlled by the multivariate model.

To analyze the reasons for better safety and efficacy of ENBD, we speculated that there were several factors. First, ENBD can more effectively drain bile, reducing bile accumulation in the bile ducts and thereby decreasing the chance of pancreatic irritation. Second, continuous drainage reduces bacterial growth in the bile ducts, helping maintain a low-pressure state in the biliary system and lowering the risk of bile reflux into the pancreas due to increased biliary pressure. In addition, the placement of ENBD is relatively simple and is less prone to blockage compared to biliary stents. Besides, ENBD can be combined with negative-pressure drainage, which can more effectively drain bile, alleviate biliary inflammation, reduce the damage and spasm of the pancreaticobiliary sphincter that may trigger PEP, and thereby decrease the incidence of PEP. Biliary stents may become obstructed due to biliary sludge or bacterial biofilm formation, leading to recurrent obstruction and subsequent inflammation and pancreatitis. Furthermore, biliary stents can exert continuous mechanical irritation on the bile duct walls, whereas ENBD tubes are typically thinner and softer, causing less irritation to the bile duct walls and thus reducing the risk of pancreatitis. Moreover, Sato et al.¹² speculated that ENBD may prevent pancreatic duct obstruction caused by residual stones or papillary edema.

This study primarily investigates the safety and efficacy of ENBD versus ERBD after EPBD in patients with CBDS. Compared to other studies, our study boasts the largest sample size among single-center studies. Moreover, our study incorporated factors that may increase the risk of pancreatitis or other complications during the procedure, as outlined in guidelines and literature, which many other studies have not included. This reduces the impact of confounding factors and allows for a more accurate focus on the differences between ENBD and ERBD. However, it is undeniable that this is a single-center retrospective study, and its results may be influenced by the specific medical environment, technical expertise, and patient population of the center, potentially limiting the generalizability to other medical settings. Therefore, multicenter, prospective RCTs are necessary to validate the generalizability and robustness of our findings.

In summary, the results of this study indicate that ENBD not only prevents post-EPBD pancreatitis but also provides better biliary drainage. Therefore, it is recommended to routinely place an ENBD catheter, rather than a plastic stent, after EPBD for CBDS extraction.

Conclusion

ENBD results in a significantly lower incidence of PEP after EPBD for CBDS, with a remarkably greater reduction of bilirubin, compared to ERBD. Therefore, ENBD may be an optimal choice for patients with CBDS undergoing EPBD.

Supplemental Material

sj-docx-1-tag-10.1177_17562848251365025 – Supplemental material for Endoscopic nasobiliary drainage is superior to biliary stent placement in preventing postendoscopic papillary balloon dilation pancreatitis

Supplemental material, sj-docx-1-tag-10.1177_17562848251365025 for Endoscopic nasobiliary drainage is superior to biliary stent placement in preventing postendoscopic papillary balloon dilation pancreatitis by Junlong Lin, Baifeng Qian, Zhichao Li, Jialin Chen, Kai Gao, Jianpeng Cai and Yunpeng Hua in Therapeutic Advances in Gastroenterology

Footnotes

Appendix

Acknowledgements

None.

Declarations

ORCID iD

Yunpeng Hua

Supplemental material

Supplemental material for this article is available online.

References

Syren

Sandblom

Enochsson

, et al. Outcome of ERCP related to case-volume. Surg Endosc 2022; 36(7): 5339–5347.

Saito

Kadono

Shono

, et al. Remaining issues of recommended management in current guidelines for asymptomatic common bile duct stones. World J Gastroenterol 2021; 27(18): 2131–2140.

Williams

Beckingham

El Sayed

, et al. Updated guideline on the management of common bile duct stones (CBDS). Gut 2017; 66(5): 765–782.

Classen

Demling

[Endoscopic sphincterotomy of the papilla of vater and extraction of stones from the choledochal duct (author’s transl)]. Dtsch Med Wochenschr 1974; 99(11): 496–497.

Kawai

Akasaka

Murakami

, et al. Endoscopic sphincterotomy of the ampulla of Vater. Gastrointest Endosc 1974; 20(4): 148–151.

Hakuta

Hamada

Nakai

, et al. Multicenter retrospective and comparative study of 5-minute versus 15-second endoscopic papillary balloon dilation for removal of bile duct stones. Endosc Int Open 2017; 5(11): E1027–E1034.

Gloor

Minder

Schnell

, et al. Antegrade balloon dilatation of the duodenal papilla during laparoscopic cholecystectomy versus endoscopic retrograde cholangiography in patients with acute choledocholithiasis: a case control matched study. Surg Endosc 2024; 38(7): 3810–3818.

Staritz

Ewe

Meyer

ZBK

. Endoscopic papillary dilation (EPD) for the treatment of common bile duct stones and papillary stenosis. Endoscopy 1983; 15(Suppl. 1): 197–198.

Fujisawa

Kagawa

Hisatomi

, et al. Is endoscopic papillary balloon dilatation really a risk factor for post-ERCP pancreatitis? World J Gastroenterol 2016; 22(26): 5909–5916.

10.

Disario

Freeman

Bjorkman

, et al. Endoscopic balloon dilation compared with sphincterotomy for extraction of bile duct stones. Gastroenterology 2004; 127(5): 1291–1299.

11.

Ishii

Fujisawa

Ushio

, et al. Evaluation of the safety and efficacy of minimal endoscopic sphincterotomy followed by papillary balloon dilation for the removal of common bile duct stones. Saudi J Gastroenterol 2020; 26(6): 344–350.

12.

Sato

Shibahara

Miyazaki

, et al. Efficacy of endoscopic nasobiliary drainage for the prevention of pancreatitis after papillary balloon dilatation: a pilot study. Pancreas 2005; 31(1): 93–97.

13.

Dai

Qian

, et al. Prevention of pancreatitis after papillary balloon dilatation by nasobiliary drainage: a randomized controlled trial. Dig Dis Sci 2015; 60(4): 1087–1091.

14.

Dai

Qian

, et al. Nasobiliary drainage after endoscopic papillary balloon dilatation may prevent postoperative pancreatitis. World J Gastroenterol 2015; 21(8): 2443–2449.

15.

Huang

Shao

Wang

, et al. Nasobiliary drainage can reduce the incidence of post-ERCP pancreatitis after papillary large balloon dilation plus endoscopic biliary sphincterotomy: a randomized controlled trial. Scand J Gastroenterol 2018; 53(1): 114–119.

16.

Leung

Cotton

PB.

Endoscopic nasobiliary catheter drainage in biliary and pancreatic disease. Am J Gastroenterol 1991; 86(4): 389–394.

17.

Lee

Chan

Lam

, et al. Biliary decompression by nasobiliary catheter or biliary stent in acute suppurative cholangitis: a prospective randomized trial. Gastrointest Endosc 2002; 56(3): 361–365.

18.

Mukai

Takeyama

Itoi

, et al. Clinical practice guidelines for post-ERCP pancreatitis 2023. Dig Endosc 2025; 37(6): 573–587.

19.

von Elm

Altman

Egger

, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ 2007; 335(7624): 806–808.

20.

Yang

Peng

Pang

, et al. Efficacy of endoscopic nasobiliary drainage for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis and cholangitis after repeated clearance of common bile duct stones: experience from a Chinese center. Dig Endosc 2013; 25(4): 453–458.

21.

Testoni

Mariani

Aabakken

, et al. Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2016; 48(7): 657–683.

22.

Chen

Tung

Peng

, et al. Duodenal major papilla morphology can affect biliary cannulation and complications during ERCP, an observational study. BMC Gastroenterol 2020; 20(1): 310.

23.

Park

Cho

, et al. The safety and effectiveness of endoscopic biliary decompression by plastic stent placement in acute suppurative cholangitis compared with nasobiliary drainage. Gastrointest Endosc 2008; 68(6): 1076–1080.

24.

Elmunzer

Foster

Serrano

, et al. Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial. Lancet 2024; 403(10425): 450–458.

25.

Cotton

Lehman

Vennes

, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991; 37(3): 383–393.

26.

Zhang

Cheng

Cai

, et al. Comparison of the safety and effectiveness of endoscopic biliary decompression by nasobiliary catheter and plastic stent placement in acute obstructive cholangitis. Swiss Med Wkly 2013; 143: w13823.

27.

Dumonceau

Tringali

Papanikolaou

, et al. Endoscopic biliary stenting: indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline—Updated October 2017. Endoscopy 2018; 50(9): 910–930.

28.

Yagioka

Hirano

Isayama

, et al. Clinical significance of bile cytology via an endoscopic nasobiliary drainage tube for pathological diagnosis of malignant biliary strictures. J Hepatobiliary Pancreat Sci 2011; 18(2): 211–215.

29.

Zhang

Shao

, et al. Efficacy and safety of laparoscopic common bile duct exploration with primary closure and intraoperative endoscopic nasobiliary drainage for choledocholithiasis combined with cholecystolithiasis. Surg Endosc 2023; 37(3): 1700–1709.

30.

Fan

Hawes

Lawrence

, et al. Analysis of plastic stents in the treatment of large common bile duct stones in 45 patients. Dig Endosc 2011; 23(1): 86–90.

31.

Pisello

Geraci

Li Volsi

, et al. Permanent stenting in “unextractable” common bile duct stones in high risk patients. A prospective randomized study comparing two different stents. Langenbecks Arch Surg 2008; 393(6): 857–863.

32.

Kwon

Lehman

GA.

Mechanisms of biliary plastic stent occlusion and efforts at prevention. Clin Endosc 2016; 49(2): 139–146.

33.

Saito

Kakuma

Kadono

, et al. Increased risk and severity of ERCP-related complications associated with asymptomatic common bile duct stones. Endosc Int Open 2017; 5(9): E809–E817.

34.

Tse

Yuan

Moayyedi

, et al. Guide wire-assisted cannulation for the prevention of post-ERCP pancreatitis: a systematic review and meta-analysis. Endoscopy 2013; 45(8): 605–618.

35.

Martinez

Inamdar

Firoozan

, et al. Evaluation of post-ERCP pancreatitis after biliary stenting with self-expandable metal stents vs. Plastic stents in benign and malignant obstructions. Endosc Int Open 2021; 9(6): E888–E894.

36.

Cote

Kumar

Ansstas

, et al. Risk of post-ERCP pancreatitis with placement of self-expandable metallic stents. Gastrointest Endosc 2010; 72(4): 748–754.

37.

Dai

Zhao

, et al. Comparison of early and delayed cholecystectomy for biliary pancreatitis: a meta-analysis. Surgeon 2021; 19(5): 257–262.

38.

Venneman

Renooij

Rehfeld

, et al. Small gallstones, preserved gallbladder motility, and fast crystallization are associated with pancreatitis. Hepatology 2005; 41(4): 738–746.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.03 MB