Emergent biliary drainage is required for patients with acute cholangitis (AC). Acute biliary infection may lead to rapid development of sepsis, shock, multiple organ failure, disseminated intravascular coagulation syndrome, and death.¹ The duration of the procedure is important for patients with unstable vital signs. However, for obstructive jaundice in patients with surgically altered anatomy (SAA), the procedure is more challenging due to the use of balloon-assisted endoscope-guided endoscopic retrograde cholangiopancreatography (BAE-ERCP) and endoscopic ultrasonography-guided biliary drainage (EUS-BD) techniques, which are often performed in cases with stable vital signs.

BAE-ERCP is recommended for biliary drainage in patients with AC and SAA in the Tokyo Guideline 2018.² This is a highly intricate procedure that requires a significant amount of time and specialized equipment. The rates of biliary drainage success and adverse events (AEs) with BAE-ERCP with stable vital signs were reported to be 83.6% and 14.6%, respectively.³

Other biliary drainage techniques in patients with SAA are percutaneous transhepatic biliary drainage and EUS-BD.⁴ EUS-BD is reportedly a useful technique for patients with SAA. In EUS-BD, endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) and endoscopic ultrasonography-guided hepaticojejunostomy (EUS-HJS) are performed via the transintestinal approach to the left liver lobe.⁵ These techniques are useful for patients with SAA because it is not necessary to reach the papilla or biliary jejunal anastomosis, and successful drainage from the stomach or jejunum can be achieved if the intrahepatic bile ducts (IHBDs) are dilated. The technical and clinical success rates were reported to be 100%, with a rate of moderate AEs of 5.3%.⁶ EUS-BD is superior to percutaneous transhepatic biliary drainage in terms of the AE rate (18.2% vs. 70.6%, P < 0.001), the reintervention rate (80.4% vs. 15.7%, P < 0.001), and total cost ($9,072 ± $3,817 vs. $18,261 ± $16,021, P = 0.003).⁷

The outcomes of BAE-ERCP and EUS-BD for patients with SAA presenting with AC have been previously reported; however, no studies have compared the efficacies of BAE-ERCP and EUS-BD as an emergent primary treatment for AC in patients with SAA. The aim of this study was to evaluate and compare the efficacies of emergency BAE-ERCP and EUS-BD as a primary therapeutic intervention for AC in patients with SAA.

The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the Wakayama Medical University Ethical Review Committee (Approval No.: 4176).

This retrospective study was conducted at Wakayama Medical University Hospital between January 2020 and March 2024. The inclusion criteria were (i) age older than 20 years, (ii) patients with AC and SAA, and (iii) BAE-ERCP or EUS-BD performed within 24 hours after diagnosis in the hospital. The exclusion criteria were (i) percutaneous transhepatic biliary drainage performed prior to the procedure, (ii) esophageal SSA, (iii) distal gastrectomy with Billroth i reconstruction performed, and (iv) proximal gastrectomy performed. We diagnosed AC and determined its severity according to Tokyo Guideline 18,⁸ and analyzed clinical data, including primary disease, severity of cholangitis, anatomy, clinical success, technical success, AEs, performance status, diameter of the IHBD, and procedure time. The primary endpoint of this study was to compare the technical success rates of BAE-ERCP and EUS-BD. The secondary endpoints included the clinical success rate, procedure-related AE rate, and procedure time. Treatment was selected according to the discretion of endoscopists.

Definitions

Technical success was defined as successful biliary access with cholangiography, stent placement in the appropriate location, and stone removal determined endoscopically and radiographically. Clinical success was defined as improvement of symptoms caused by cholangitis, such as fever, organ failure, systemic inflammatory response syndrome, and jaundice, along with amelioration of laboratory findings, including the total white blood cell count and hepatobiliary enzyme levels, and reduction of the total bilirubin level by 50% or more from baseline at 2 weeks or a decrease to 3.0 mg/dL or less by 4 weeks. Procedure-related AEs were recorded and included peritonitis, pancreatitis, bleeding, and procedure-related death. AEs were graded according to the American Society for Gastrointestinal Endoscopy lexicon’s severity grading system.⁹

Technique

BAE-ERCP and EUS-BD were performed by experienced endoscopists within 24 hours after diagnosis of AC in the hospital. Patients received midazolam, dexmedetomidine, and pentazocine for conscious sedation and analgesia. BAE-ERCP was performed using a double-balloon endoscope (EI-580BT; Fujifilm Corp.). Advancement through the small bowel was achieved by the push-and-pull technique, which uses a balloon-fitted overtube with a second balloon inserted over the tip of a dedicated endoscope. Transparent cap usage, sphincterotomy, stricture dilation, stone removal, mechanical lithotripsy, and plastic or metal stent placement were performed as required (Fig. 1).

Figure 1. BAE-ERCP for acute cholangitis in a patient with surgically altered anatomy and an obstructing stone in the common bile duct. (A) Computed tomography image of the stone in the common bile duct. (B) The balloon-assisted endoscope was advanced into the papilla, and selective biliary cannulation was successful. (C) The balloon was dilated and the stone in the common bile duct was removed using a mechanical lithotripter. (D) Fluoroscopic image after selective biliary cannulation. BAE-ERCP, balloon-assisted endoscope-guided endoscopic retrograde cholangiopancreatography.

EUS-HGS/EUS-HJS was performed using an echoendoscope (GF-UCT260; Olympus Corp. and EG-580UT; Fujifilm Corp.) to achieve initial biliary access. Next, a 19- or 22-gauge needle (EZ Shot; Olympus Corp. and SonoTip ProControl; Medi-Globe) was used to puncture the biliary duct, and access was confirmed by aspiration of bile and a cholangiogram. Depending on the needle chosen, a 0.025- or 0.018-inch guidewire was then advanced into the bile duct. The biliary-enteric fistula was dilated with a catheter or balloon and a spiral dilator. A plastic or metal stent was placed using endoscopic and radiographic imaging. These devices were selected based on the patients’ anatomy and features of the obstructing structure (Fig. 2). In cases of HGS with antegrade stenting, an antegrade stent was deployed across the biliary structure and a HGS stent was placed between the IHBD and stomach.

Figure 2. EUS-BD with a plastic stent for acute cholangitis in a patient with surgically altered anatomy and an obstructing stone in the common bile duct. (A) Computed tomography image of the stone in the common bile duct. (B) Using a transgastric approach, the IHBD was punctured with a 19-gauge needle. (C) Fluoroscopic image showing cholangiography after the IHBD was punctured. (D) Fluoroscopic image showing insertion of the plastic biliary stent. EUS-BD, endoscopic ultrasonography-guided biliary drainage; IHBD, intrahepatic bile duct.

Statistical analysis

Continuous variables are presented as medians and interquartile ranges (IQR) and were compared using the Mann-Whitney U-test. Categorical variables are presented as numbers and proportions and were compared using Fisher’s exact test. Outcomes were compared between the BAE-ERCP and EUS-BD groups using the median test and Fisher’s exact test. Statistical significance was based on two-sided P-values and was set at P < 0.05. Statistical analysis was performed using JMP 16 (SAS Institute).

A flowchart of patients who underwent the BAE-ERCP and EUS-BD procedures is presented in Fig. 3. Of the 136 patients initially identified, 37 were considered eligible for inclusion in the study. Of the other cases, 96 were treated after 24 hours and three were excluded from further analysis because they underwent percutaneous transhepatic biliary drainage. Of the 37 patients who underwent emergent biliary drainage, 23 and 14 underwent BAE-ERCP and EUS-BD, respectively. Table 1 shows the baseline characteristics of the patients. The primary diseases of AC were classified as benign lesions (n = 25) and malignant lesions (n = 12). The severity of cholangitis was classified as grade 1 in nine, grade 2 in 17, and grade 3 in 11 patients. The types of SAA were as follows: 12 cases of pancreaticoduodenectomy, eight cases of total gastrectomy with Roux-en-Y reconstruction, ten cases of distal gastrectomy with Roux-en-Y reconstruction, three cases of Roux-en-Y hepaticojejunostomy, two cases of Billroth II distal gastrectomy, and two cases of gastrojejunal bypass. With regard to performance status, 18 cases had a value of 0 or 1, while 19 cases had a value of 2 or higher.

Figure 3. Patient flowchart and outcomes of BAE-ERCP and EUS-BD. BAE-ERCP, balloon-assisted endoscope-guided endoscopic retrograde cholangiopancreatography; EUS-BD, endoscopic ultrasonography-guided biliary drainage; AC, acute cholangitis; SAA, surgically altered anatomy.

Table 1 . Patients Characteristics.

Characteristic	Value (n = 37)
Age (yr)	76 [73–81]
Sex
Male	31
Female	6
Primary disease
Benign	25
Stones	24
Biliary structure	1
Malignancy	12
Pancreatic cancer	2
Biliary duct cancer	7
Metastatic cancer	3
Severity of cholangitis
Grade 1	9
Grade 2	17
Grade 3	11
Anatomy
Pancreaticoduodenectomy with child reconstruction	12
Total gastrectomy with Roux-en-Y reconstruction	8
Distal gastrectomy with Roux-en-Y reconstruction	10
Distal gastrectomy with Billroth II reconstruction	2
Hepaticojejunostomy with Roux-en-Y reconstruction	3
Gastrojejunal bypass	2
Performance status
0 or 1	18
Over 2	19

Values are presented as median [interquartile range] or number only.

Table 2 shows comparison of characteristics between the BAE-ERCP and the EUS-BD groups. The rates of benign lesions and grade 1 cholangitis were significantly higher in the BAE-ERCP group than in the EUS-BD group (P < 0.01 and P = 0.01, respectively). The diameter of the IHBD was significantly larger in the EUS-BD group than in the BAE-ERCP group (6.7 mm vs. 5.3 mm, P = 0.02). The choice of treatment was determined by the endoscopists. The choice of treatment was determined by the endoscopists. Among patients with mild AC, eight benign and one malignant case were observed. For the eight benign cases, choledocholithotomy was performed in six cases, leading to a preference for BAE-ERCP in these cases to facilitate stone removal. Conversely, EUS-BD was more commonly selected for cases of moderate or severe AC caused by malignant bile duct strictures.

Table 2 . Comparison of Characteristics Between BAE-ERCP and EUS-BD Groups.

	BAE-ERCP (n = 23)	EUS-BD (n = 14)	P-value
Age (yr)	77 [74.0–81.0]	75 [68.5–83.3]	0.57
Sex			> 0.999
Male	19	12
Female	4	2
Primary disease			< 0.01
Benign	21	5
Malignant	2	9
Severity of cholangitis			0.01
Grade 1	9	0
Grade 2 or 3	14	14
Anatomy			0.15
Pancreaticoduodenectomy	9	3
Others	14	11
Performance status			0.09
0 or 1	14	4
Over 2	9	10
Diameter of IHBD (mm)	5.3 [2.8–6.4]	6.7 [5.3–9.6]	0.02

Values are presented as median [interquartile range] or number only.

BAE-ERCP, balloon-assisted endoscope-guided endoscopic retrograde cholangiopancreatography; EUS-BD, endoscopic ultrasonography-guided biliary drainage; IHBD, intrahepatic bile duct.

Table 3 shows outcomes in the BAE-ERCP and EUS-BD groups. Technical success and clinical success rates did not significantly differ between the two groups. The rate of choledocholithotomy was significantly higher in the BAE-ERCP group than in the EUS-BD group (52% vs. 0%, P < 0.01). The median procedure time was significantly shorter in the EUS-BD group than in the BAE-ERCP group (32.5 [IQR, 28.8–52.5] minutes vs. 70.0 [IQR, 60.0–90.0] minutes, P < 0.01). In only stent placement cases, the procedure time was significantly shorter in the EUS-BD group than in the BAE-ERCP group (32.5 [IQR, 28.8–52.5] minutes vs. 80.0 [IQR, 60.0–90.0] minutes, P < 0.01). Although procedure-related AEs did not significantly differ between the two groups, they were observed in three patients and included mild pancreatitis (n = 1) in the BAE-ERCP group and mild peritonitis (n = 2) in the EUS-BD group. One case of technical failure was managed conservative therapy and another was treated with EUS-BD as an alternative, and clinical success was not achieved in one patient in each group (Fig. 3). In the EUS-BD group, one case of clinical failure subsequently required BAE-ERCP. Among the five benign cases, EUS-guided antegrade stone removal was successfully performed in two cases approximately 1–2 months following EUS-BD.

Table 3 . Comparison of Outcomes Between BAE-ERCP and EUS-BD.

	BAE-ERCP (n = 23)	EUS-BD (n = 14)	P-value
Technical success rate	21/23 (91)	14/14 (100)	0.51
Clinical success rate	20/21 (95)	13/14 (93)	0.66
Drainage methods			< 0.01
Choledocholithotomyto	12	0
Stent placement	9	14
Technique			-
DB-ERCP	23	0
HGS	0	9
HJS	0	3
HGS + AG	0	2
Procedure time (min)	70.0 [60.0–90.0]	32.5 [28.8–52.5]	< 0.01
Stent placement case	80.0 [60.0–90.0]	32.5 [28.8–52.5]	< 0.01
Adverse event	1 (4)	2 (14)	0.54
Pancreatitis	1 (4)	0 (0)
Bleeding	0 (0)	0 (0)
Peritonitis	0 (0)	2 (14)

Values are presented as number (%), number only, or median [interquartile range].

BAE-ERCP, balloon-assisted endoscope-guided endoscopic retrograde cholangiopancreatography; EUS-BD, endoscopic ultrasonography-guided biliary drainage; DB-ERCP, double balloon endoscope-guided endoscopic retrograde cholangiopancreatography; HGS, EUS-guided hepaticogastrostomy; HJS, EUSguided jejunogastrostomy; HGS + AGS, EUS-guided hepaticogastrostomy with antegrade stenting.

Table 4 shows the characteristics and outcomes of patients with grade 2 or higher cholangitis. Of these patients, 14 and 14 underwent BAE-ERCP and EUS-BD, respectively. With the exception of benign lesions, the characteristics of the patients did not significantly differ between the two groups. The technical and clinical success rates did not significantly differ between the two groups. The rate of choledocholithotomy was significantly higher in the BAE-ERCP group than in the EUS-BD group (50% vs. 0%, P < 0.01). The median procedure time was significantly shorter in the EUS-BD group than in the BAE-ERCP group (32.5 [IQR, 28.8–52.5] minutes vs. 70 [IQR, 56.3–90.0] minutes, P < 0.01). In only stent placement cases, the procedure time was significantly shorter in the EUS-BD group than in the BAE-ERCP group (32.5 [IQR, 28.8–52.5] minutes vs. 80.0 [IQR, 50.0–105.0] minutes, P = 0.05).

Table 4 . Severity of Cholangitis Grade Over 2 Characteristics and Outcomes.

	BAE-ERCP (n = 14)	EUS-BD (n = 14)	P-value
Age (yr)	78.5 [75.0–81.0]	75.0 [68.5–83.3]	0.46
Sex			> 0.999
Male	12	12
Female	2	2
Primary disease			< 0.01
Benign	13	5
Malignant	1	9
Anatomy			0.42
Pancreaticoduodenectomy	6	3
Others	8	11
Performance status			0.44
0 or 1	7	4
Over 2	7	4
Diameter of IHBD (mm)	5.4 [3.7–7.1]	6.7 [5.3–9.6]	0.25
Technical success rate	12/14 (86)	13/14 (100)	0.48
Clinical success rate	12/12 (100)	13/14 (93)	> 0.999
Drainage methods			< 0.01
Choledocholithotomy	6	0
Stent placement	6	14
Procedure time (min)	70.0 [56.3–90.0]	32.5 [28.8–52.5]	< 0.01
Stent placement case	80.0 [50.0–105.0]	32.5 [28.8–52.5]	0.05

Values are presented as median [interquartile range], number only, or number (%).

BAE-ERCP, balloon-assisted endoscope-guided endoscopic retrograde cholangiopancreatography; EUS-BD, endoscopic ultrasonography-guided biliary drainage; IHBD, intrahepatic bile duct.

In the absence of an appropriate therapy, AC has the potential to progress to a fatal state. This is the first study to compare BAE-ERCP and EUS-BD for treatment of AC in patients with SAA in an emergency setting. Although the rates of technical success, clinical success, and AEs did not significantly differ between the two groups, the procedure time was significantly shorter in the EUS-BD group than in the BAE-ERCP group. In subgroup analyses, the results were similar in patients with severe cholangitis and receiving stent placement.

BAE-ERCP has been commonly used to treat benign and malignant cholangial diseases in patients with SAA.¹⁰ The advantage of BAE-ERCP for patients with SAA is that it can remove the biliary stone in a single procedure. The present study showed that stone removal in a single procedure was an effective therapeutic intervention in 60% of cases of cholangitis in which stones were identified as the underlying cause. The disadvantages of BAE-ERCP are that it is necessary to reach the papilla and there is a high risk of procedure-related pancreatitis. The incidence of pancreatitis was 4% following BAE-ERCP in the present study. On the other hand, since the initial report of EUS-BD,¹¹ numerous reports have published findings on its efficacy as a valuable alternative drainage technique after failed ERCP.^12–15 Although EUS-BD is more frequently performed to treat malignant obstruction in patients with SAA,^16,17 it was recently performed to remove stones in such patients.^18,19 If the left IHBDs are dilated, EUS-BD can be performed. EUS-BD does not require access to the papilla, which is beneficial in cases where anatomical changes prevent the papilla from being reached. EUS-BD allows direct access to the bile duct through the stomach or duodenum, bypassing anatomical obstacles such as duodenal stenosis.²⁰ However, the disadvantages of EUS-BD are bleeding and leakage of bile into the abdominal cavity related to penetrated liver tissue. In a study of the efficacy of BAE-ERCP for AC in patients with SAA, the rates of clinical success and AEs were 87.7% and 4.4%, respectively.⁴ In a study of EUS-BD for AC in patients with SAA, the rates of clinical success and AEs were 84.9% and 9.1%, respectively.²¹ In the present study, the technical and clinical success rates did not significantly differ between the two groups (88% vs. 100%, P = 0.51 and 95% vs. 93%, P = 0.66, respectively). The rate of AEs also did not significantly differ between the two groups (4% vs. 14%, P = 0.54).

AC develops with infection in biliary stasis, and can lead to organ failure or coagulopathy due to sepsis, which requires respiratory and circulatory management due to cholangiovenous and cholangio-lymphatic reflux, in which increased biliary pressure causes bacteria and endotoxins in bile to migrate into blood and lymphocytes.¹ Emergent biliary drainage is essential for patients as soon as possible. In the present study, the procedure time was significantly shorter in the EUS-BD group than in the BAE-ERCP group, and the technical success rate was as high as in the BAE-ERCP group. The results were similar in subgroup analysis of severe cholangitis and stent placement cases. A shortened procedure time is essential to minimize the burden for patients with severe AC; therefore, EUS-BD may be more suitable for the patients with moderate or severe cholangitis with SAA than BAE-ERCP. On the other hand, BAE-ERCP is able to remove biliary stone at single term procedure. In the present study, BAE-ERCP was performed in nine cases of mild, benign cholangitis, of which six underwent choledocholithotomy. BAE-ERCP may be suitable for the patients with mild AC caused by benign disease than EUS-BD. SAA includes various anatomical variations: EUS-HGS drainage is effective in distal gastrectomy, while EUS-HJS drainage is feasible in total gastrectomy if the elevated jejunum is in contact with the liver. However, EUS-BD is unsuitable in cases of post-left lobectomy of the liver and a non-dilated bile duct.

This study has limitations. First, technical bias could not be completely avoided because it was a retrospective single-center study. Second, the numbers of patients in the two groups were insufficient, which may have biased the results. Third, the baseline characteristics of the patients in terms of primary disease, severity of cholangitis, and diameter of the IHBD differed between the two groups. There was a particular bias, especially regarding the choice of the two procedures, with BAE-ERCP being selected for mild benign AC and EUS-BD for moderate to severe malignant AC.

In conclusion, while both BAE-ERCP and EUS-BD can be performed safely and effectively in patients with AC and SAA, the procedure time is significantly shorter with EUS-BD than with BAE-ERCP. A shortened procedure time is essential to minimize the burden for patients with severe AC; therefore, EUS-BD may be more appropriate for these patients. Conversely, BAE-ERCP has the advantage of removing biliary stones in a single session, making it a more suitable option for patients with mild AC caused by benign diseases.

None.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Masayuki Kitano has received honoraria from Olympus Corporation for delivering lectures at conferences and grants from Boston Scientific, Zeon Medical Inc., and Medicos Hirata Inc. Takahiro Shishimoto, Masahiro Itonaga, Reiko Ashida, Yasunobu Yamashita, Yuki Kawaji, Takashi Tamura, Hiromu Morishita, Akiya Nakahata, Yuto Sugihara, and Tomokazu Ishihara have no conflicts of interest or financial ties to disclose.