Outcomes of endoscopic papillary large balloon dilatation combined with sphincterotomy for removing large common bile duct stones and risk factors for stone recurrence

Abstract

Background

To evaluate the outcomes of endoscopic sphincterotomy (EST) combined with endoscopic papillary large balloon dilation (EPLBD) for removing stones from large common bile duct (CBD) and identify the risk factors for stone recurrence.

Methods

After reviewing 69 patients with large CBD stones, 44 were included in the group treated with EST combined with EPLBD (ESLBD) and 25 patients were in included in the EPLBD group. The clinical data of both groups, including success rates of removing large CBD stones, complications, hospital stay and total costs of hospitalization were compared. In addition, the risk factors for stone recurrence were explored.

Results

The ESLBD and EPLBD groups showed similar success rates of stone clearance (97.27% vs 96.00%). However, the use of lithotripsy and the incidence of post-endoscopy pancreatitis (PEP) were higher in the EPLBD group. The recovery time and total costs of hospitalization were also lower in the ESLBD group. No serious complications were identified in our study, such as hemorrhage, perforation and death; and no significant differences in infection, procedural time, hospital stay and procedural costs of groups. Multiple logistic regression analysis showed that lithotripsy and maximum transverse diameter of the CBD stone were independent risk factors for stone recurrence.

Conclusions

ESLBD was superior to EPLBD alone for removing large CBD stones. In addition, the maximum transverse diameter of CBD stone and lithotripsy were independent risk factors for associated with stone recurrence.

Background

Endoscopic sphincterotomy (EST) for the treatment of gallstones was first reported by Kawai et al. in 1974^[1]. Endoscopic retrograde cholangiopancreatography (ERCP) gradually replaced surgery for the removal common bile duct (CBD) stones. However, this method was often used for clearing small stones in the past. Until 2003, EST combined with endoscopic papillary large balloon dilatation (EPLBD) (ESLBD)was first used to remove large CBD stones by Ersoz et al.^[2] with great success. Currently, ERCP is the most preferred treatment for removing CBD stones ^[3], and ESLBD is a standard treatment for removing large CBD stones. In general, EST is performed before EPLBD so as to create additional space for removing large CBD stones. Additional EST can damage the function of the sphincter of ampullar. However, EST increases the risk of bleeding theoretically. Studies reported that it may be not unnecessary to perform EST before EPLBD ^[4–6], which is not consistent with some guidelines^{[3, 7, 8]}. The study aimed to evaluate the outcomes of ESLBD for removing large CBD stones and compared the outcomes with EPLBD, in addition to exploring the risk factors for stone recurrence.

Methods

patients

In this retrospective study, we collected and analyzed the data of patients with large CBD stones (≥15mm) from April 1, 2017 to June 30, 2021. The incidence of stone recurrence was determined via calls. We defined inclusion criteria as follow: 1. Maximum CBD stone diameter ≥ 15 mm. 2. ERCP performed initially on the patient. 3. Balloon dilation diameter ≥ 12 mm. Exclusion criteria: 1. Gastrointestinal reconstruction. 2. Liver transplantation. 3. Severe abnormal coagulation. 4. Need for anticoagulant drugs within 7 days (Aspirin, Rivaroxaban and others). 5. Acute pancreatitis before the ERCP. 6. Age< 18 years. 7. Hospital stay < 48 hours. 

Endoscopic procedure:

ERCP was performed with a side-viewing duodenoscope (JF260V/240V, Olympus, Tokyo, Japan). Propofol was used for anesthesia. Duodenoscope was advanced into the descending portion of the duodenum and the papilla was cannulated. A 0.035-inch guidewire (Olympus, Tokyo, Japan) was inserted into the CBD cannulation, followed by the injection of 20mL loversol into the bile duct and a cholangiogram was obtained.

In the EPLBD group of patients, a large dilation balloon was advanced over the guidewire and positioned. The balloon was inflated gradually until the waist disappeared at 2.0-6.0 atm of balloon pressure and approximately 30-120 s of dilation time. In the ESLBD group of patients, the EST was performed first to cut the ampullary sphincter. The incision was performed in the direction of 11 to 12 o’clock, followed by EPLBD. A wire basket was used to remove the stone. Lithotripsy was used to crush stones if they could not be removed with EPLBD or ESLBD. After stone removal, cholangiogram was obtained again to confirm the clearance of CBD stones. A successful stone removal procedure was defined by no residual stones or need for further ERCP. A nasobiliary drainage or stent was used in every patient, along with antibiotic treatment after ERCP.

Endpoints

Primary outcomes included success rates of stone clearance, complications associated with ERCP (pancreatitis, hemorrhage and infection), the use of lithotripsy, recovery time, hospital stay and total costs of hospitalization. Secondary outcomes were risk factors for stone recurrence.

Definitions

Procedure time: The time starting from successful cannulation of the bile duct up to nasobiliary insertion. 

Postoperative recovery time: The time from the completion of ERCP until patient discharge. If ERCP was performed more than once, the recovery time was calculated from the completion of the last ERCP. 

Pancreatitis: Patients with abdominal pain accompanied by serum lipase or amylase, which was more than three times the upper limit of normal after more than 24 h after post-ERCP. Pancreatitis was graded using the modified Cotton standard^{[9, 10]}.    

Infection: The criteria for infection were: 1. Positive test results of bile, blood or sputum microbiological culture. 2. Fever (>38℃) or abdominal pain accompanied by significant increase in white blood cells (≥12×10⁹). 

Hemorrhage: Bleeding during the procedure or a 20% decreased in hemoglobin level.

Statistical analysis

Data were analyzed with SPSS26.0 for windows (Armonk, NY, IBM Corp). Continuous variables were expressed as medians and interquartile ranges [M (P25, P75)] and data were compared using Mann-Whitney-U test. Categorical variables were expressed as numbers. Percentages [n (%)] and data were compared via c2 test or Fisher’s exact test. The risk factors for stone recurrence were analyzed via multiple logistic regression. The stone recurrence in both groups was compared via Kaplan-Meier (Log-Rank test).  A two-sided P value of less than 0.05 was considered statistically significant.

Results

Baseline characteristics of the patients

No significant differences in baseline characteristics were found between the groups (Table 1).

Outcomes of the EPLBD and ESLBD groups

There were no significant differences in success rates at first session of stone removal (77.27% vs. 68.00%, p = 0.399), and overall success rates (97.27% vs. 96.00%, p = 1.000). However, the EPLBD group reported higher rates of lithotripsy use (27.27% vs. 56.00%, p = 0.018) and incidence of post-endoscopy pancreatitis (PEP) (11.36% vs. 36.00%, p = 0.014). The ESLBD group reported lower recovery time [115.00 (90.25 vs. 163.75) vs. 141.00 (115.00, 213.00) h, p = 0.046] and total costs of hospitalization [37 219.325 (30 437.325, 45 961.055) vs. 42 932.31 (37 447.25, 50164.11) yuan, p = 0.029]. In the ESLBD group, the CBD stones were not removed from a patient although mechanical and extracorporeal shock wave lithotripsy was performed due to the hard stone. Another patient in the EPLBD group had an incarceration of gallstone, which was therefore not removed (Table 2).

Stone recurrence and risk factors

The follow-up duration of all patients was 20 (7.00-35.00) months, which was not significantly between the EPLBD and ESLBD groups (p = 0.236) (Table 2).  No significant difference in stone recurrence was detected between the groups based on the Kaplan-Meier method (13.64% vs. 20.00%, p = 0.306). (Fig.1). In the multivariate analysis, the lithotripsy (OR = 14.628, 95%CI =1.337-160.064, p = 0.028) and maximum transverse diameter of stone (OR = 1.567, 95%CI =1.046-2.348, p = 0.029) were independent risk factors for stone recurrence after adjusting for clinical confounders, including the maximum transverse diameter of stone, maximum diameter of stone, age, procedure time, balloon dilation time, balloon dilation pressure, cholecystectomy, gallbladder stones, lithotripsy, diverticulum, bile duct expansion, and gender.

Discussion

CBD stone is a common condition globally, with a prevalence of 10–20% in patients with gallstones. The main clinical symptoms include abdominal pain, nausea, vomiting and jaundice. EPLBD and ESLBD can be used for the endoscopic removal of large CBD stones, whether EST should be performed before EPLBD is still disputed.

Kuo et al. reported that additional EST prior to EPLBD increased the success rate of stone removal during the first session^[11]. Although we found that the ESLBD group reported a higher rate of lithotripsy usage in stone removal during the first session, no significant difference was detected between both groups. The usage of lithotripsy and EPLBD with EST was often in the range of 1.0–29.0% ^{[4, 12, 13]}. However, we found higher use rates of lithotripsy used in our study, suggesting insufficient balloon dilation. Hwang et al. advised that the diameter of balloon dilation should be larger than the maximum transverse diameter of the stone^[6], but the diameter of EPLBD did not exceed the stone diameter in our study.

Previous studies showed no significant differences in the incidence of PEP between EPLBD and ESLBD groups ^{[4–6, 11, 13, 14]}. Conversely, we found that the EPLBD group had a higher risk of PEP, suggesting insufficient dilatation to increase the incidence of PEP based on the higher frequency of lithotripsy, because lithotripsy was performed more frequently and increased the risk of papillary edema. The mechanisms of PEP require additional studies for confirmation in the current study. Further, we found that the ESLBD group showed a lower recovery time and total costs of hospitalization. Thus, ESLBD reduced patients’ recovery time and cost. Excluding PEP, the EPLBD and ESLBD groups reported similar complications after ERCP, which was consistent with two recent meta-analysis ^{[15, 16]}.

According to the conventional view, EPBD is considered as a treatment to preserve the function of ampullary sphincter, compared with EST, which destroyed the function of ampullar sphincter papillary muscle during incision^[17]. Kim et al.^[18] reported that EPLBD alone preserved sphincter function. A prospective randomized clinical trial conducted by Cheon et al^[19], evaluated the recovery of papillary muscle function in a year following EPLBD or ESLBD, suggested similar function of the papillary muscle based on endoscopic manometric testing of the bile duct in both groups. Stone recurrence is associated with functional impairment of ampullary sphincter. We did not find significant differences s in stone recurrence between the groups^{[11, 20]}. The finding suggested that the long-term function of ampullary sphincter could not be preserved after ESLBD or EPLBD. Further, multiple logistic regression analysis revealed that the maximum transverse diameter of CBD stone and lithotripsy were independent risk factors for stone recurrence^[21].

The study has several limitations. First, the diameters of the balloon dilation ranged from 10 to 14 mm. Lee et al.^[22] reported that a larger EPLBD (> 15mm) was associated with severe-to-fatal adverse events when compared with a smaller EPLBD (12–15mm) as short-term outcomes. Therefore, the efficacy of balloons larger than 15 mm for removal of large CBD stones needs further investigation. Second, the patients involved in our study were mainly older individuals. Finally, the study was limited by the small sample size and retrospective nature, which may increase the risk of bias. The results of our study need to be corroborated via, multi-center prospective studies with large samples and longer follow-up periods.

Conclusions

ESLBD is superior to EPLBD alone for removing large CBD stones. In addition, lithotripsy and maximum transverse diameter of CBD stone were risk factors for stone recurrence.

Abbreviations

Declarations

Ethical approval and consent to participate

The retrospective study was conducted in compliance with the Helsinki Declaration and in accordance with local legislation, was approved by the ethics committee of Zhongnan Hospital, Wuhan University. (Approval No. 2021028K). All patients proved their written informed consent before endoscopic interventions.

Consent for publication

Not applicable. 

Availability of supporting data

The datasets generated during the the current study are available in the manuscript. 

Conflicts of Interest and Source of Funding

The authors report no conflicts of interest or funding information to declare.

Author’s contribution statements

Sanyang Yu made contribution to the data collection, analysis and writing. Yan Fan revised it critically for important intellectual content. Shouquan Dong made contribution to the data collection and ethics approval. Hongling Wang designed the work. Qiu Zhao approved the version to be published.

Acknowledgements

The authors appreciate the linguistic assistance provided by TopEdit (www.topeditsci.com) during the preparation of this manuscript.

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Tables

Table 1. Baseline characteristics of the ESLBD and EPLBD groups.

n (%): number(percentage); M (P₂₅, P₇₅): median (interquartile ranges); EPLBD: endoscopic papillary large balloon dilatation; ESLBD:  endoscopic sphincterotomy (EST) combined with endoscopic papillary large balloon dilation (EPLBD). 

Table 2. Outcomes of ERCP: ESLBD vs. EPLBD

n (%): number (percentage); M (P₂₅, P₇₅): median (interquartile ranges); EPLBD: endoscopic papillary large balloon dilatation; ESLBD:  endoscopic sphincterotomy (EST) combined with endoscopic papillary large balloon dilation (EPLBD).  ERCP: Endoscopic retrograde cholangiopancreatography. Yuan: Chinese yuan. *: P < 0.05 between the groups