Kaneko T, Kida M, Kurosu T, Kitahara G, Betto T, Saito Y, Koyama S, Nomura N, Kusano C. Early precut is useful for difficult bile duct cannulation, particularly in cases with long oral protrusion. World J Gastrointest Endosc 2025; 17(9): 108420 [DOI: 10.4253/wjge.v17.i9.108420]
Corresponding Author of This Article
Toru Kaneko, MD, PhD, Department of Gastroenterology, Kitasato University Medical Center, 1-1-15 Kitasato, Minami, Kitamoto 364-8501, Saitama, Japan. t.kaneko@kitasato-u.ac.jp
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Toru Kaneko, Mitsuhiro Kida, Takahiro Kurosu, Gen Kitahara, Tomohiro Betto, Yutaro Saito, Shiori Koyama, Nao Nomura, Department of Gastroenterology, Kitasato University Medical Center, Kitamoto 364-8501, Saitama, Japan
Toru Kaneko, Mitsuhiro Kida, Takahiro Kurosu, Gen Kitahara, Tomohiro Betto, Yutaro Saito, Shiori Koyama, Nao Nomura, Chika Kusano, Department of Gastroenterology, Kitasato University Hospital, Sagamihara 252-0375, Kanagawa, Japan
Author contributions: Kaneko T conducts conceptual research, data collation, formal analysis, investigation, is responsible for method and project management, validation, visualization, and writes the original draft; Kurosu T, Kitahara G, Betto T, Saito Y, Koyama S, and Nomura N were responsible for the resources; Kida M and Kusano C supervised the study; Kaneko T, Kida M, Kurosu T, Kitahara G, Betto T, Saito Y, Koyama S, Nomura N, and Kusano C have contributed to writing, commenting and editing; and all authors have read and approved the final manuscript.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Kitasato University Medical Center, approval No. 2024005.
Informed consent statement: This retrospective study was conducted using an opt-out approach in accordance with institutional and ethical guidelines. Details of the study and publication were disclosed in advance on our institution’s website, and participants were given the opportunity to refuse inclusion. Since no objections were raised, consent for publication was considered to have been obtained.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Toru Kaneko, MD, PhD, Department of Gastroenterology, Kitasato University Medical Center, 1-1-15 Kitasato, Minami, Kitamoto 364-8501, Saitama, Japan. t.kaneko@kitasato-u.ac.jp
Received: April 22, 2025 Revised: May 22, 2025 Accepted: August 21, 2025 Published online: September 16, 2025 Processing time: 143 Days and 23.3 Hours
Abstract
BACKGROUND
Endoscopic retrograde cholangiopancreatography involves selective bile duct cannulation, which is often challenging and associated with complications. In difficult cannulation cases, early precutting is frequently used. However, its efficacy and optimal indications require further evaluation.
AIM
To evaluate the efficacy and safety of early precut (EP) in difficult bile duct cannulation.
METHODS
This retrospective analysis of endoscopic retrograde cholangiopancreatography procedures was performed for bile duct cannulation in patients with naive papillae who required advanced cannulation techniques (ACTs). These patients were admitted between April 2020 and March 2024 and were analyzed for risk factors, success rates, and complications. Outcomes were compared between the EP group and the conventional other ACTs group, with a focus on cases with oral protrusion large (oral protrusion-L).
RESULTS
The need for ACTs was identified as an independent risk factor for complications [odds ratio (OR) = 5.4; 95% confidence interval: 1.887-15.53]. Malignant biliary strictures (OR = 2.58) and oral protrusion-L (OR = 2.77) were also identified as independent risk factors for requiring ACTs. The EP group had a significantly higher second-line cannulation success rate (97.9% vs 73.2%, P = 0.001) and lower complication rate (8.3% vs 39.0%, P = 0.001) than the other ACTs group. Additionally, similar benefits were observed in the oral protrusion-L cases.
CONCLUSION
This study provides compelling evidence that EP is a viable alternative and a superior strategy in cases requiring ACTs, particularly oral protrusion-L.
Core Tip: Early precut (EP) is a safe and effective alternative to conventional advanced cannulation techniques for difficult bile duct cannulation. This retrospective study demonstrates that EP significantly increases second-line cannulation success rates, shortens procedure time, and reduces complications, particularly in cases with prominent oral protrusion. These findings support EP as a first-line advanced cannulation technique after standard cannulation techniques fail in selected high-risk cases. This advocates for a strategic shift in endoscopic retrograde cholangiopancreatography practice.
Citation: Kaneko T, Kida M, Kurosu T, Kitahara G, Betto T, Saito Y, Koyama S, Nomura N, Kusano C. Early precut is useful for difficult bile duct cannulation, particularly in cases with long oral protrusion. World J Gastrointest Endosc 2025; 17(9): 108420
Endoscopic retrograde cholangiopancreatography (ERCP) is essential for diagnosing and managing biliary and pancreatic disorders[1-3]. Successful selective bile duct cannulation is fundamental to ensure proper access during ERCP. Selective bile duct cannulation can be challenging even for experts, with reports indicating that approximately 5%-20% of cases involving a naive papilla result in unsuccessful cannulation[4-7]. Factors contributing to the difficulty of selective bile duct cannulation include anatomical variations of the papilla and differences in the experience and skill levels of endoscopists and institutions[8-11]. Anatomical factors such as periampullary diverticula, the macroscopic shape of the papilla, and oral protrusion length have been reported as causes of difficulty[8-10]. Watanabe et al[10] focused on the impact of oral protrusions on bile duct cannulation. They reported that papillae with a large oral protrusion (oral protrusion-L) presented the greatest difficulty in bile duct cannulation and are more likely to lead to cannulation failure[10].
Complications occur in approximately 10% of ERCP procedures[12-14]. Notably, among these, post-ERCP pancreatitis (PEP) is recognized as one of the most serious and potentially fatal complications[13,14]. Difficulties in bile duct cannulation and multiple failed attempts increase the risk of developing PEP[14,15]. Overcoming the challenges of bile duct cannulation is expected to improve cannulation success rates and reduce the incidence of complications.
Advanced cannulation techniques (ACTs) have been developed and are widely used in clinical practice for difficult biliary cannulation. These techniques include precutting[16], the double-guidewire (GW) technique[17] in which a GW is securely placed in the pancreatic duct, the two-devices-in-one-channel method[18], and endoscopic ultrasound (EUS)-guided rendezvous techniques[19]. Additionally, among these, the precut technique involves making an incision in the major duodenal papilla with a needle knife or sphincterotome to expose the bile duct opening. It was originally employed as a salvage technique when other approaches to difficult biliary cannulation failed. Furthermore, precut has been reported as an independent risk factor for PEP[20-22].
Recent studies have highlighted the utility of an early precut (EP), which is performed at an earlier stage before prolonged cannulation attempts for difficult biliary cannulation cases[23-26]. Unlike traditional precuts, EPs have not increased the risk of PEP[23-25]. Moreover, reports suggest that the group undergoing EP surgery has a lower incidence of PEP than those who continue with conventional biliary cannulation attempts without an EP[26].
However, no study has compared the efficacy and safety of EP with other ACTs (OACTs) in difficult biliary cannulation cases. Additionally, there is no consensus on which difficult biliary cannulation cases are most suitable for early precutting. Therefore, we conducted a retrospective study to compare the efficacy and safety of EP with those of other techniques for biliary cannulation and identify the most relevant clinical characteristics of cases best suited for this approach.
MATERIALS AND METHODS
Study design
This study followed a single-center retrospective cohort study. It was conducted at Kitasato University Medical Center, Japan, and complied with the Declaration of Helsinki. This study was approved by our hospital’s Institutional Review Board, approval No. 2024005.
Target cases
We retrospectively reviewed the medical records of patients who underwent ERCP at Kitasato University Medical Center between April 2020 and March 2024. Of the 1048 ERCP cases during this period, we included those that met the inclusion criteria and those that did not meet any of the exclusion criteria. The inclusion criteria were as follows: (1) Cases in which ERCP was performed for biliary cannulation; and (2) Patients with a naive papilla at the initial attempt. The exclusion criteria includes: (1) Cases that had undergone endoscopic sphincterotomy or endoscopic biliary drainage; (2) Cases in which ERCP was performed for biliary cannulation; (3) Cases with a history of upper gastrointestinal surgery, excluding Billroth I procedure; (4) Cases with duodenal stenosis or other conditions that prevent the endoscope from reaching the duodenal papilla; and (5) Cases in which the duodenal papilla is not visible. In total, 403 cases met these criteria (Figure 1).
Figure 1 Flow chart of the inclusion process.
ERCP: Endoscopic retrograde cholangiopancreatography; B-I: Billroth I reconstruction.
Definitions
Biliary cannulation using contrast catheters, a papillotome knife for contrast injection, or wire-guided cannulation was defined as standard cannulation techniques (SCTs). Biliary cannulation using the double GW technique, precut, and two devices in the one-channel method was categorized as ACTs. Additionally, cannulation performed using SCTs was considered the first-line procedure. ACTs were considered a second-line procedure when biliary cannulation is difficult with SCTs. If biliary cannulation could not be achieved with the initial ACT, another ACT was employed, and cannulation with this technique was considered the third-line procedure.
Procedure time was measured from endoscope insertion to removal. In contrast, biliary cannulation time was recorded from the first frontal view of the duodenal papilla until biliary cannulation was successful. Biliary cannulation is considered successful when a catheter is inserted into the bile duct with subsequent cholangiography. Difficult biliary cannulation was defined according to the European Society of Gastrointestinal Endoscopy guidelines as any case in which biliary cannulation exceeded 5 minutes or five attempts, or at least one unintended pancreatic duct cannulation occurred[27]. Regarding EP, previous reports have described its use as 5-12 minutes after SCTs or following two to four unintended pancreatic duct cannulations[24-26]. The term “EP” in this study follows previous reports and refers to precutting performed within 10 minutes after unsuccessful standard cannulation attempts. Thus, representing a second-line ACTs rather than an initial or first-line approach[23-26].
Experts were defined as those who had performed more than 500 ERCP procedures. For cases performed by the trainees, an expert acted as a supervising assistant and guided them throughout the procedure. The length of the oral protrusion was classified as large if it was more than twice the horizontal diameter of the duodenal papilla[10]. The severity of adverse events (AEs) was classified based on the lexicon of the American Society of Gastrointestinal Endoscopy[28]. An elevated amylase level was defined as a serum amylase level exceeding three times the upper limit of normal in the absence of abdominal pain.
ERCP method
All procedures were performed under sedation with pethidine hydrochloride and midazolam. A duodenoscope (TJF290V, TJF260V, or JF260V; Olympus Medical Systems, Tokyo, Japan) was advanced into the duodenal papilla. Once the papillary opening was visualized, a contrast catheter (MTW ERCP catheter; MTW Endoscopy, Wesel, Germany, or FineJet Cannula; Gadelius Medical, Tokyo, Japan) or papillotomy knife (CleverCut3V KD-V411 M-0320; Olympus Medical Systems) with a GW (Visiglide2; Olympus Medical Systems, Filder25; Asahi Intech, Aichi, Japan) was inserted for biliary cannulation. The endoscopist initially determined the cannulation method, starting with SCT, using either contrast injection or wire-guided cannulation. Regarding cases of difficult biliary cannulation, ACT was performed using the specific method chosen by the endoscopist. For the precut techniques, either needle knife fistulotomy (NKF) or needle knife papillotomy (NKP) was performed using a Needle Knife (Needle Cut 3V KD-V451M; Olympus Medical Systems). Additionally, markings were made in the direction of the incision, and dissection was performed accordingly. Layer-by-layer dissection was performed to achieve a sufficiently long incision, allowing visualization of the Oddi muscle. NKF, which only involves an incision of the oral protrusion, was the first choice. However, if visualization of the Oddi muscle is difficult or a longer incision is required, NKP, which extends the incision to the papilla, was performed. After visualization, the Oddi muscle was incised to expose the bile duct opening. Either a contrast catheter or a GW was inserted to complete biliary cannulation (Video 1). In cases where a GW is placed in the pancreatic duct, the double GW technique is employed, typically with a detachable pancreatic duct stent placement. If biliary cannulation cannot be achieved using the double-GW technique and a precut is required (third-line precut), the procedure is performed with a Needle Knife while the detachable pancreatic duct stent remains in place. After successful biliary cannulation, additional procedures such as endoscopic sphincterotomy, endoscopic lithotomy, or endoscopic biliary drainage are performed depending on the case. If a trainee performs ERCP and encounters difficulty with biliary cannulation, an expert generally takes over the procedure after 5 minutes or five attempts.
Study protocol
Figure 2 illustrates this study protocol. We examined the treatment outcomes of patients in whom biliary cannulation was attempted using SCTs. Patients who required second-line ACTs due to failure of biliary cannulation with SCTs were divided into an EP and OACT groups. The treatment outcomes and incidence of AEs for both groups were compared.
The primary endpoint was the incidence of AEs. The secondary endpoints included investigating risk factors for AEs, assessing the success rate of biliary cannulation using ACTs, and analyzing underlying factors.
Statistical analysis
Based on previous studies[25,26,29], we assumed that the overall incidence of AEs in difficult cannulation cases would be 40% and that performing EP would reduce the incidence of AEs to 10%. With a significance level of 0.05 and a power of 0.80, the required sample size for each group was calculated to be 31. In this retrospective analysis, 48 patients and 41 patients were included in the EP and OACT group, respectively, which exceeded the required sample size.
Continuous variables were expressed as medians with interquartile ranges. Categorical variables were presented as percentages and absolute numbers. Continuous variables were compared using the Mann-Whitney U-test. Categorical variables were compared using Fisher’s exact test. Statistical significance was set at P < 0.05. Univariate logistic regression analyses were used to assess the association between each independent variable and the outcome. Some results are presented only from the univariate analysis. Variables with a P value < 0.05 in the univariate analysis were considered for multivariate logistic regression.
Additionally, variables identified as relevant in previous studies were also included in the multivariate logistic regression model, regardless of their univariate statistical significance. The final model was determined based on statistical significance and practical relevance. Results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). All authors had access to the study data, and they reviewed and approved the final manuscript. Statistical analyses were performed using EZR software (Saitama Medical Center, Jichi Medical University, Saitama, Japan).
RESULTS
Baseline characteristics and overall treatment outcomes
In total, 403 patients were identified using the database analysis. Baseline characteristics of all patients are shown in Table 1. The mean age was 78 years (range: 29-104 years), with 230 male patients (57.1%) and 173 female patients (42.9%). Regarding underlying diseases, 137 patients (34.0%) had malignant conditions, and 266 patients (66.0%) had benign conditions. Among the malignant conditions, cholangiocarcinoma was the most prevalent (72 patients, 17.9%). Conversely, among the benign conditions, bile duct stones were the most common (240 patients, 59.6%). Periampullary diverticula were present in 107 patients (26.6%), and oral protrusion-L was observed in 110 patients (27.3%). Experts performed the procedures on 214 patients (53.1%). Table 2 shows the overall treatment outcomes. The overall success rate of biliary cannulation was 99.2% (400/403). Notably, of the three cases in which biliary cannulation was unsuccessful, one underwent repeat ERCP, one required EUS-guided hepaticogastrostomy, and one was treated with the EUS-guided rendezvous technique (EUS-RZ) (Figure 2). Difficult cannulation was observed in 147 patients (36.5%). Biliary cannulation using SCT was successful in 314 patients (22.1%), while 89 patients (22.1%) required ACTs. Complications occurred in 37 patients (9.2%), and PEP was observed in 14 patients (3.5%). Of the 14 patients who developed PEP, 10 cases were mild, two were moderate, and one was severe.
Table 1 Baseline characteristics of all patients, n (%).
The risk factors for AEs are listed in Table 3. In the univariate analysis, 59.5% of the difficult cannulation cases had AEs compared to 34.2% of cases without it, with a statistically significant difference (P = 0.004). Notably, among patients requiring ACTs, 54.1% experienced AEs, while 20.5% did not, showing a significantly higher incidence of AEs (P < 0.001). Multivariate analysis using logistic regression revealed that requiring ACT (OR = 5.4; 95%CI: 1.887-15.53) was an independent risk factor for AEs.
Table 3 Investigation of the occurrence of complications, n (%).
Comparison of treatment outcomes between ACT and SCT, risk factors for cases requiring ACT, and breakdown of cannulation methods used in ACT cases
The treatment outcomes for SCTs and ACTs are compared in Table 4. The biliary cannulation rates were 99.7% and 97.8% in the SCT and ACT groups, respectively, with no significant intergroup difference (P = 0.68). In contrast, the incidence of complications was significantly higher in ACT-required cases (22.5%) than in SCT cases where cannulation was successful (5.4%) (P < 0.001). Additionally, the incidence of PEP was also significantly higher in the ACTs-required cases (10.1%) than in the SCTs cases where cannulation was successful (1.6%) (P < 0.001). Notably, all cases of PEP in the SCT group were mild, whereas the ACT group included two moderate and one severe case. The cases in which cannulation was successful with SCTs and those requiring ACTs are shown in Table 5. In the univariate analysis, bile duct malignancy was found to be significantly more common in the ACTs group (53.9%) than in the SCTs group (28.3%) (P < 0.001). Similarly, oral protrusion-L was significantly more frequent in the ACTs group (65.2%) than in the SCTs group (16.6%) (P < 0.001). In the multivariate analysis using logistic regression, malignancy of the bile duct (OR = 2.58, 95%CI: 1.53-4.34) and oral protrusion-L (OR = 2.77, 95%CI: 1.65-4.65) were identified as independent factors requiring ACT.
Table 4 Comparison of treatment outcomes between standard and advanced cannulation techniques, n (%).
Table 6 shows a breakdown of the cannulation methods for the ACT. In the second-line procedures, the double-GW technique was used in 31 cases (34.8%), and precut was used in 57 cases (64.0%), with 48 of these cases (53.9%) involving EP. Third-line procedures were performed in all 11 cases, following the failure of the double-GW technique used in second-line procedures. A precut was performed in these cases while a detachable pancreatic duct stent was placed.
Table 6 Details of the advanced cannulation technique, n (%).
Comparison of patient backgrounds and treatment outcomes between the EP group and OACT group
Table 7 shows a comparison of patient backgrounds between the EP group and the OACT group in second-line procedures. Malignant biliary strictures were significantly more frequent in the EP group (70.8%) (P = 0.001) compared to the OACT group (34.1%) (P = 0.001). Pancreatic duct stents were not placed on any patients in the EP group, while 29 patients (70.1%) in the OACT group received a pancreatic duct stent (P < 0.001). However, no significant differences were found in age, sex, frequency of oral protrusion-L cases, frequency of periampullary diverticulum cases, or the proportion of procedures performed by expert endoscopists. A comparison of the treatment outcomes is presented in Table 8. The overall biliary cannulation rates were similar between both groups, with 97.9% and 97.6% of patients in the EP and OACT groups, respectively (P = 1.00). However, the success rate of biliary cannulation up to second-line procedures was significantly higher in the EP group (97.9%) than in the OACT group (73.2%) (P = 0.001). Furthermore, the biliary cannulation time was significantly shorter in the EP group [837 seconds (242-2085 seconds)] than in the OACT group [1287.5 seconds (194-4526 seconds)] (P < 0.001). Additionally, the number of biliary cannulation attempts was significantly lower in the EP group (seven attempts[2-15]) compared to the OACT group (eight attempts[3-20]) (P < 0.001). The procedure time was shorter in the EP group [31 minutes (10-102 minutes)] than in the OACT group [43 minutes (13-135 minutes)] (P < 0.001).
Table 7 Comparison of patient backgrounds between the early precut and the other advanced cannulation technique groups, n (%).
The overall incidence of AEs was significantly lower in the EP group (8.3%) than in the OACT group (39.0%) (P = 0.001). The incidences of PEP were 4.2% and 17.1% in the EP and OACT groups, respectively, with no significant differences observed. However, there was a trend toward a lower incidence of PEP in the EP group (P = 0.075). All AEs, including PEP, were mild in the EP group. In contrast, the OACT group included two moderate cases and one severe case of PEP, indicating a trend toward more severe complications in this group.
Comparison of EP group and OACT group in cases with oral protrusion-L
In cases with oral protrusion-L, the treatment outcomes of the EP group and the OACT group were compared. The results are summarized in Table 9. The overall biliary cannulation rates were 97.1% and 100% in the EP and OACT groups, respectively, with no significant difference (P = 1.00). However, the biliary cannulation success rate up to the second-line procedure was significantly higher in the EP group (97.1%) than in the OACT group (65.2%; P = 0.001). Additionally, biliary cannulation time was significantly shorter in the EP group [757.5 seconds (242-2085 seconds)] than in the OACT group [1764 seconds (305-3437 seconds)] (P < 0.001). The number of biliary cannulation attempts was also lower in the EP group (seven attempts[2-15]) than in the OACT group (10 attempts[3-20]) (P < 0.001). Finally, the procedure time was shorter in the EP group [30 minutes (10-69 minutes)] than in the OACT group [58 minutes (30-135 minutes)] (P = 0.007).
Table 9 Comparison of treatment outcomes between the early precut and other advanced cannulation technique groups, limited to cases of oral protrusion-large, n (%).
The overall incidence of AEs was significantly lower in the EP group (8.6%) than in the OACT group (43.5%) (P = 0.003). The incidences of PEP were 2.9% and 17.4% in the EP and OACT groups, respectively, with no significant differences observed. However, there was a trend toward a lower incidence of PEP in the EP group (P = 0.075). All AEs, including PEP, were mild in the EP group. In contrast, the OACT group included one moderate and one severe PEP case, indicating a trend toward more severe complications in this group.
Subgroup analysis of EP techniques: NKF vs NKP
For subgroup analysis within the EP group, we compared the clinical outcomes between patients who underwent NKF and those who underwent NKP, as shown in Table 10. NKF was performed in 29 patients (60.4%), while NKP was performed in 19 patients (39.6%). The proportion of cases with oral protrusion-L was significantly higher in the NKF group (89.7%) compared to the NKP group (47.4%) (P = 0.002). Cannulation success rates up to the second-line procedure were 100% in the NKF group and 94.7% in the NKP group, with no statistically significant difference (P = 0.40). Moreover, no statistically significant differences were observed in cannulation time, number of attempts, or overall procedure time between the two groups. Regarding safety, the incidence of complications tended to be lower in the NKF group (3.4%) compared to the NKP group (15.8%), although no statistically significant difference was observed (P = 0.29). Notably, there were no cases of bleeding in either group. One case of mild PEP occurred in each group, and no moderate or severe PEP was observed. Elevated serum amylase was reported in two patients who underwent NKP. However, none was observed in the NKF group.
Table 10 Comparison of treatment outcomes between the needle knife fistulotomy group and the needle knife papillotomy within the early precut group, n (%).
This study evaluated the efficacy and safety of early precutting for difficult bile duct cannulation in patients with naive papillae. Our results showed that patients requiring ACTs had a significantly higher incidence of complications, with malignant biliary strictures and oral protrusion-L identified as independent risk factors for ACTs. Moreover, early precutting demonstrated a higher success rate in biliary cannulation, shorter cannulation and procedure times, and a lower incidence of complications than OACTs. These benefits were particularly pronounced in patients with oral protrusion-L.
This study identified the need for ACTs as an independent risk factor for AEs during ERCP in patients with naive papillae. The association between the ACTs and AEs is consistent with previous reports. This indicates that difficult biliary cannulation is associated with an increased risk of AEs, particularly PEP, due to the greater burden on the papilla[13,14]. However, in this study, difficult biliary cannulation was not an independent risk factor for AEs. One potential explanation is that approximately half of the procedures were performed by trainees. Biliary cannulation typically takes longer in trainee-performed procedures and requires more attempts than those performed by experts. This may lead to cases being more frequently classified as difficult to cannulate. However, trainees generally perform procedures under the supervision of an expert who guides them to ensure that excessive force is not applied and that the procedure is carried out cautiously. Consequently, the burden on the papilla may not be significant in these cases, and some reports suggest that the definition of difficult biliary cannulation can be broadened in the context of trainee-performed procedures[30]. Difficult biliary cannulation has previously been evaluated based on criteria such as the number of attempts (five or more) or the time taken to cannulate (5 minutes or more)[27,30]. However, cases in which biliary cannulation proves challenging using standard techniques and requires advanced methods could also be considered indicators of the burden on the papilla. This aspect has not been previously addressed in the existing literature, which highlights the value of this study.
Malignant biliary obstruction and oral protrusion-L were independent risk factors for procedures requiring ACTs. This finding aligns with previously reported risk factors for difficult cannulation[10,31]. In malignant biliary obstruction cases, obstruction of the bile duct leads to reduced bile secretion, narrowing of the duct, and makes catheter or GW passage difficult. Additionally, tumor infiltration may lead to duodenum and papilla deformation, making it difficult to visualize the opening. Bile duct infiltration may also cause deviation, complicating the alignment and advancement of the catheter or GW, thus altering successful biliary cannulation[31]. Furthermore, in cases of oral protrusion-L, the acute angle of the bile duct and long narrow distal segment (NDS) may cause the bile duct to change, which is thought to result in difficulties aligning the catheter or GW in the direction of the bile duct[10]. These cases are challenging for biliary cannulation, leading to a higher frequency of complications; therefore, appropriate management strategies should be considered.
Regarding treatment outcomes, this study found that EP had a higher cannulation rate, shorter time to cannulation, and lower incidence of complications than OACTs. The higher cannulation rate with EP as the second-line approach may be attributed to the fact that EP reduces the likelihood of pancreatic duct misplacement, alleviates papillary edema, and preserves papilla anatomical structure. This allows for a better determination of the direction of the incision, and its easy performance. As a result, it becomes easier to visualize the bile duct opening, and further incision shortens its NDS, making it easier to advance the catheter or GW along the bile duct axis. This is considered the reason for the higher success rate of the procedure. Regarding complications, cases where an EP was performed showed less pancreatic duct stimulation. In contrast, OACTs, such as the double-GW method, often involve pancreatic duct stimulation. There have been reports that excessive GW insertion into the pancreatic duct increases the risk of PEP[32]. Reduced pancreatic duct stimulation with an EP is, therefore, believed to be the reason for the lower incidence of complications, including PEP. Precut has been identified as an independent risk factor for PEP[20-22]. However, it is believed that the increase in complications is due to repeated attempts at biliary cannulation before performing the precut rather than the precut itself, which elevates the risk of complications. This incidence aligns with previous reports on EP[23-26]. Reducing pancreatic duct stimulation and achieving easier cannulation are important for minimizing complications, including PEP, in ERCP. Additionally, early precutting is performed under favorable conditions without papillary oedema or inflammation. Reports have suggested that bleeding may decrease the success rate[33] and that the absence of oedema and inflammation reduces the risk of bleeding. This likely makes the precut easier to perform, which, in turn, contributes to the higher cannulation and lower complication rates. In this study, pancreatic duct stents were used exclusively in the OACT group, while none were placed in the EP group. Nevertheless, the EP group exhibited a lower incidence of PEP. This indicates that EP may reduce pancreatic duct irritation and lower the risk of pancreatitis without additional prophylactic interventions. This finding supports prior reports suggesting that EP performed before repeated pancreatic duct cannulation minimizes trauma to the papilla.
Given that oral protrusion-L cases are independent risk factors for ACTs, we extracted and analyzed these cases among those requiring ACTs. In the analysis of oral protrusion-L cases alone, EP showed a higher second-line cannulation rate. It also showed a lower incidence of complications, including PEP, compared to OACTs, indicating that EP is a more effective approach. Biliary cannulation is often challenging in cases of oral protrusion L[10], and the results suggest that early precutting is beneficial in these cases. Previous reports have shown that many cases of oral protrusion L require precutting[31]. One of the technical difficulties in performing a precut is visualizing the Oddi muscle. A longer incision improves the visualization of the Oddi muscle, making it critical for the success of the precut procedure. In cases of oral protrusion, a longer incision is anatomically feasible, making the precut more effective. Furthermore, oral protrusion-L cases are characterized by a steep bile duct angle and long NDS, which complicate cannulation. However, precutting reduces the length of the NDS and flattens the bile duct angle, thereby enhancing its effectiveness. Therefore, an EP is considered a valuable technique in oral protrusion-L cases.
Precut techniques such as NKF, NKP, and transpancreatic sphincterotomy (TPS) have been previously reported[27,34,35]. In this study, NKF or NKP was performed on all patients using a needle knife, while TPS was not performed. In the TPS, the GW is inserted into the pancreatic duct and used to facilitate the incision. This allows a more stable incision, which reduces the risk of bleeding and perforation. Additionally, placing a pancreatic duct stent can help manage the risk of PEP[35]. However, GW insertion into the pancreatic duct can cause irritation, which is believed to increase the risk of PEP[32]. In contrast, this study used NKF only to incise oral-side papillary protrusions. NKF places minimal stress on the pancreatic duct and is considered the safest technique[27,34]. By performing an EP, pancreatic duct stimulation is minimized, and using NKF further reduces pancreatic duct irritation. These factors contribute to the lower incidence of complications in EP cases. In our subgroup analysis, both NKF and NKP showed high procedural success and acceptable safety profiles. However, NKF tended to be associated with fewer complications. Importantly, NKF was more frequently chosen in cases of oral protrusion-L, likely due to its technical feasibility in these anatomically elongated papillae. In oral protrusion-L cases, the oral-side protrusion is sufficiently long such that an incision in this portion alone provides sufficient length, making NKF anatomically easier to perform. Therefore, early precutting is considered an effective technique for treating oral protrusion-L (Figure 3).
Figure 3 Stepwise endoscopic images of early precut needle knife fistulotomy in a case with a large oral protrusion.
A: Papilla with a long oral protrusion (oral protrusion-L); the incision line is marked at the apex of the protrusion prior to precutting; B: The initial incision is made using a needle knife, limited to the oral protrusion only, avoiding the papillary orifice characteristic of needle knife fistulotomy; C: Exposure of the sphincter of the Oddi muscle layer (highlighted with a blue circle). The extended oral protrusion allows for a wide incision plane, facilitating clear visualization of the muscle layer; D: Identification of the artificially created bile duct opening after further dissection (blue arrow); E: Successful bile duct cannulation with a guidewire through the exposed opening.
Recently, EUS-guided biliary drainage and EUS-RZ have become more widespread in cases of difficult ERCP. The treatment outcomes have been favorable, with results comparable to those of ERCP[36,37]. Additionally, reports have compared the treatment outcomes of EUS-RZ and Precut, demonstrating the effectiveness of EUS-RZ[38]. However, these results were compared with the conventional precut method rather than the EP method. Additionally, EUS-guided biliary drainage may not be feasible in cases where the bile ducts are extremely narrow or when there is a significant amount of ascites. Therefore, enhancing the success rate of ERCP remains a crucial objective. In this study, the use of EP demonstrated an improvement in the second-line biliary cannulation rate compared to OACTs, with a reduction in cannulation and procedure time and a decrease in complications, including PEP. Since there have been no similar reports, this study was considered significant.
Our study has several limitations. First, this was a retrospective single-center study with a small sample size, which may limit the generalizability of the findings. Second, although the sample size was sufficient for statistical analysis, the number of patients who underwent EP was relatively limited. Third, the presence of multiple operators means that the choice of the ERCP technique was not standardized and may have been subject to operator bias. Additionally, variations in patient backgrounds may have influenced outcomes. Lastly, as some procedures were initiated by trainees and completed by expert endoscopists, operator switching may have influenced cannulation time and complication rates. This procedural variability should be considered when interpreting the results. Therefore, future studies should be prospective, involve larger sample sizes, and standardize these factors.
CONCLUSION
This study provides compelling evidence that EP is a viable alternative and superior strategy in cases requiring ACTs, particularly oral protrusion-L. Our findings showed that EP significantly improves procedural success rates, reduces cannulation time, and minimizes complications in difficult cases. Overall, our results highlight the need for a shift in ERCP strategy, moving away from prolonged conventional cannulation attempts toward an early decision to perform precut in high-risk cases such as oral protrusion-L. Future research should focus on validating these findings in multicenter trials and integrating EP into ERCP guidelines, particularly as a first-choice ACT after SCT fails in oral protrusion-L cases.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: Japan
Peer-review report’s classification
Scientific Quality: Grade B, Grade B, Grade D
Novelty: Grade B, Grade B, Grade D
Creativity or Innovation: Grade B, Grade B, Grade D
Scientific Significance: Grade B, Grade B, Grade D
P-Reviewer: Chisthi MM, MD, Professor, India; Fan Z, MD, PhD, Professor, China; Li H, PhD, China S-Editor: Bai Y L-Editor: A P-Editor: Lei YY
Adler DG, Baron TH, Davila RE, Egan J, Hirota WK, Leighton JA, Qureshi W, Rajan E, Zuckerman MJ, Fanelli R, Wheeler-Harbaugh J, Faigel DO; Standards of Practice Committee of American Society for Gastrointestinal Endoscopy. ASGE guideline: the role of ERCP in diseases of the biliary tract and the pancreas.Gastrointest Endosc. 2005;62:1-8.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 292][Cited by in RCA: 287][Article Influence: 14.4][Reference Citation Analysis (0)]
Mukai S, Itoi T, Baron TH, Takada T, Strasberg SM, Pitt HA, Ukai T, Shikata S, Teoh AYB, Kim MH, Kiriyama S, Mori Y, Miura F, Chen MF, Lau WY, Wada K, Supe AN, Giménez ME, Yoshida M, Mayumi T, Hirata K, Sumiyama Y, Inui K, Yamamoto M. Indications and techniques of biliary drainage for acute cholangitis in updated Tokyo Guidelines 2018.J Hepatobiliary Pancreat Sci. 2017;24:537-549.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 87][Cited by in RCA: 120][Article Influence: 15.0][Reference Citation Analysis (0)]
Pécsi D, Farkas N, Hegyi P, Balaskó M, Czimmer J, Garami A, Illés A, Mosztbacher D, Pár G, Párniczky A, Sarlós P, Szabó I, Szemes K, Szűcs Á, Vincze Á. Transpancreatic sphincterotomy has a higher cannulation success rate than needle-knife precut papillotomy - a meta-analysis.Endoscopy. 2017;49:874-887.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 25][Cited by in RCA: 26][Article Influence: 3.3][Reference Citation Analysis (0)]
Williams EJ, Taylor S, Fairclough P, Hamlyn A, Logan RF, Martin D, Riley SA, Veitch P, Wilkinson M, Williamson PR, Lombard M; BSG Audit of ERCP. Are we meeting the standards set for endoscopy? Results of a large-scale prospective survey of endoscopic retrograde cholangio-pancreatograph practice.Gut. 2007;56:821-829.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 160][Cited by in RCA: 179][Article Influence: 9.9][Reference Citation Analysis (0)]
Haraldsson E, Kylänpää L, Grönroos J, Saarela A, Toth E, Qvigstad G, Hult M, Lindström O, Laine S, Karjula H, Hauge T, Sadik R, Arnelo U. Macroscopic appearance of the major duodenal papilla influences bile duct cannulation: a prospective multicenter study by the Scandinavian Association for Digestive Endoscopy Study Group for ERCP.Gastrointest Endosc. 2019;90:957-963.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 75][Cited by in RCA: 66][Article Influence: 11.0][Reference Citation Analysis (0)]
Shi HX, Ye YQ, Zhao HW, Kong DC, Huang SZ, Yan Q, Chen YB, Zhang P, Chen S, Hou BH, Zhang CZ. A new classification of periampullary diverticulum: cannulation of papilla on the inner margins of the diverticulum (Type IIa) is more challenging.BMC Gastroenterol. 2023;23:252.
[RCA] [PubMed] [DOI] [Full Text][Cited by in RCA: 5][Reference Citation Analysis (0)]
Watanabe M, Okuwaki K, Kida M, Imaizumi H, Yamauchi H, Kaneko T, Iwai T, Hasegawa R, Miyata E, Masutani H, Tadehara M, Adachi K, Koizumi W. Transpapillary Biliary Cannulation is Difficult in Cases with Large Oral Protrusion of the Duodenal Papilla.Dig Dis Sci. 2019;64:2291-2299.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 14][Cited by in RCA: 26][Article Influence: 4.3][Reference Citation Analysis (0)]
Dumonceau JM, Kapral C, Aabakken L, Papanikolaou IS, Tringali A, Vanbiervliet G, Beyna T, Dinis-Ribeiro M, Hritz I, Mariani A, Paspatis G, Radaelli F, Lakhtakia S, Veitch AM, van Hooft JE. ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.Endoscopy. 2020;52:127-149.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 249][Cited by in RCA: 505][Article Influence: 101.0][Reference Citation Analysis (1)]
Ikeda Y, Ono M, Ohmori G, Ameda S, Arihara Y, Yamada M, Abe T, Maeda M. Clinical benefit of early precut sphincintroterotomy for difficult biliary cannulation during endoscopic retrograde cholangiopancreatography.Surg Endosc. 2023;37:120-126.
[RCA] [PubMed] [DOI] [Full Text][Cited by in RCA: 3][Reference Citation Analysis (0)]
Mariani A, Di Leo M, Giardullo N, Giussani A, Marini M, Buffoli F, Cipolletta L, Radaelli F, Ravelli P, Lombardi G, D'Onofrio V, Macchiarelli R, Iiritano E, Le Grazie M, Pantaleo G, Testoni PA. Early precut sphincterotomy for difficult biliary access to reduce post-ERCP pancreatitis: a randomized trial.Endoscopy. 2016;48:530-535.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 35][Cited by in RCA: 54][Article Influence: 6.0][Reference Citation Analysis (0)]
Testoni PA, Mariani A, Aabakken L, Arvanitakis M, Bories E, Costamagna G, Devière J, Dinis-Ribeiro M, Dumonceau JM, Giovannini M, Gyokeres T, Hafner M, Halttunen J, Hassan C, Lopes L, Papanikolaou IS, Tham TC, Tringali A, van Hooft J, Williams EJ. Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.Endoscopy. 2016;48:657-683.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 290][Cited by in RCA: 386][Article Influence: 42.9][Reference Citation Analysis (1)]
Han S, Zhang J, Durkalski-Mauldin V, Foster LD, Serrano J, Coté GA, Bang JY, Varadarajulu S, Singh VK, Khashab M, Kwon RS, Scheiman JM, Willingham FF, Keilin SA, Groce JR, Lee PJ, Krishna SG, Chak A, Slivka A, Mullady D, Kushnir V, Buxbaum J, Keswani R, Gardner TB, Wani S, Edmundowicz SA, Shah RJ, Forbes N, Rastogi A, Ross A, Law J, Yachimski P, Chen YI, Barkun A, Smith ZL, Petersen BT, Wang AY, Saltzman JR, Spitzer RL, Spino C, Elmunzer BJ, Papachristou GI; SVI Study Group. Impact of difficult biliary cannulation on post-ERCP pancreatitis: secondary analysis of the stent versus indomethacin trial dataset.Gastrointest Endosc. 2025;101:617-628.
[RCA] [PubMed] [DOI] [Full Text][Cited by in RCA: 3][Reference Citation Analysis (0)]
Maruta S, Sugiyama H, Ogasawara S, Sugihara C, Ouchi M, Kan M, Yamada T, Miura Y, Nagashima H, Takahashi K, Kusakabe Y, Ohyama H, Okitsu K, Ohno I, Mikata R, Sakai Y, Tsuyuguchi T, Kato J, Kato N. "Salvage techniques" are the key to overcome difficult biliary cannulation in endoscopic retrograde cholangiopancreatography.Sci Rep. 2022;12:13627.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in RCA: 6][Reference Citation Analysis (0)]
Goenka MK, Akshintala VS, Kamal A, Bhullar FA, Bush N, Kumar V, Chakraborty M, Gurakar M, Lakhtakia S, Talukdar R, Trikudanathan G, Khashab MA, Kalloo AN, Reddy DN, Sinha SK, Singh VK, Kochhar R. Frequent guidewire passage into the pancreatic duct is an independent risk factor for postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among high-risk individuals: A post-hoc analysis of a randomized controlled trial data.J Dig Dis. 2023;24:427-433.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 2][Reference Citation Analysis (0)]
Dhir V, Singh VK, Dalal A, Patil GK, Maydeo A. Randomized comparison of precut papillotomy versus an endoscopic ultrasound-guided rendezvous procedure for difficult biliary access in malignant distal biliary obstruction.Endoscopy. 2025.
[RCA] [PubMed] [DOI] [Full Text][Cited by in RCA: 1][Reference Citation Analysis (0)]
