Long-duration EPBD vs EST for Removal of Biliary Stones

Study Overview
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Brief Summary
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Although EPBD has a lower risk of post-ERCP bleeding and long-term complications than EST and is easier to perform in altered/difficult anatomy, EPBD is reserved for patients with bleeding diathesis by current consensus because some studies reported a higher risk of pancreatitis. However, recent meta-analyses indicate that short EPBD duration increases the risk of post-ERCP pancreatitis, and EPBD with adequate duration has a similar pancreatitis risk and a lower overall complication rate compared with EST for choledocholithiasis. Therefore, this study aim to compare long-duration EPBD vs EST in the treatment of extrahepatic biliary stones.

Detailed Description
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Gallstones occur in 10%-15% of adults in the United States and are the most common and costly digestive disorder. Concomitant bile duct stones occur in up to 15% of persons with symptomatic gallstones. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy is the standard treatment for removal choledocholithiasis. The biliary sphincter is permanently ablated by sphincterotomy. Enteric-biliary reflux occurs with bacterial colonization, increased bile lithogenicity, contamination with cytotoxins, and chronic inflammation of the biliary system. Endoscopic papillary balloon dilation (EPBD) has become an option for removal of stones 1 cm or smaller in size. Advantages of EPBD over EST include a decreased risk of post-ERCP bleeding as well as a decreased risk of stone recurrence and cholangitis. Although a short dilation duration (≤1 minute) was previously advocated, a study that performed EPBD for 1 minute observed a 15.4% risk of post-ERCP pancreatitis with 2 cases of mortality. European Society of Gastrointestinal Endoscopy guideline recommends that the duration of EPBD should exceed 2 minutes because long-duration EPBD (>1 minute) is preferred over short-duration EPBD (≤1 minute) with better outcomes. A meta-analysis of RCTs showed that the duration of EPBD is inversely associated with the risk of PEP. Previous RCTs comparing outcome between EPBD and EST used short EPBD duration between 25 seconds and 1 minute, and there has been no comparison of outcome between EST and long-duration EPBD. The aim of this study was to compare the early and long term outcomes of patients treated with long duration balloon dilation or sphincterotomy for extraction of bile duct stones in a randomized, multicenter fashion involving a broad spectrum of practices.

Official Title
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Long-duration (3 Minutes) Endoscopic Papillary Balloon Dilation Versus Endoscopic Sphincterotomy in Patients With a Naive Major Papilla and Small- to Medium Sized Biliary Stones: Multicenter, Randomized, Controlled Trial

Conditions
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Cholangiopancreatography, Endoscopic Retrograde

Intervention / Treatment
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* Procedure: long duration EPBD
* Procedure: EST


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consecutive patients were invited to participate by the investigators or research staff if they were at least 18 years old, patients who had known or suspected choledocholithiasis Exclusion Criteria: active acute pancreatitis septic shock, coagulopathy (international normalized ratio >1.2, partial thromboplastic time greater than twice that of control), platelet count <50,000 x 103/uL, anticoagulation therapy within 48 hours of the procedure, stone diameter > 8 mm, bile duct diameter >15 mm, prior sphincterotomy, need for precut sphincterotomy for biliary access, biliary stricture, Billroth II or Roux-en-Y anatomy, periampullary malignancies, primary sclerosing cholangitis, pregnancy, and inability to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: long duration EPBD group<br>Balloon dilation was performed using wire-guided hydrostatic balloon catheters. An 8-mm dilatation balloon was used for EPBD. Balloons were gradually inflated to maximum pressure for 3 minute, and complete inflation was verified by fluoroscopy. Stones were removed by standard techniques, including balloon or basket catheters. | Procedure: long duration EPBD<br>* An 8-mm dilatation balloon was used for EPBD. Balloons were gradually inflated to maximum pressure for 3 minute, and complete inflation was verified by fluoroscopy.<br>Procedure: EST<br>* After deep cannulation was achieved, a complete sphincterotomy was performed with a 25-mm pull-type sphincterotome (Clever Cut 3; KD-V411M, Olympus, Tokyo, Japan) and the sphincter was divided up to the transverse duodenal fold.<br>|
| Active Comparator: endoscopic sphincterotomy (EST) group<br>After deep cannulation was achieved, a complete sphincterotomy was performed with a 25-mm pull-type sphincterotome (Clever Cut 3; KD-V411M, Olympus, Tokyo, Japan) and the sphincter was divided up to the transverse duodenal fold. A complete sphincterotomy was defined by the free passage of a fully bowed sphincterotome and the presence of spontaneous bile drainage. A complete sphincterotomy was defined by the free passage of a fully bowed sphincterotome and the presence of spontaneous bile drainage. | Procedure: long duration EPBD<br>* An 8-mm dilatation balloon was used for EPBD. Balloons were gradually inflated to maximum pressure for 3 minute, and complete inflation was verified by fluoroscopy.<br>Procedure: EST<br>* After deep cannulation was achieved, a complete sphincterotomy was performed with a 25-mm pull-type sphincterotome (Clever Cut 3; KD-V411M, Olympus, Tokyo, Japan) and the sphincter was divided up to the transverse duodenal fold.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of adverse event | Number of participants with treatment-related adverse events | up to 1 month after ERCP | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the stone clearance rate at the index ERCP | complete extraction of choledocholithiasis of all stones, fragments, and sludge at the initial procedure | during ERCP | 
| direct cost | The direct cost included the total cost for the entire admission, which comprised costs of hospital stay, performed procedures, and management of complications | within 30 day after ERCP | 
| recurrence of choledocholithiasis | recurrent choledocholithiasis or acute cholangitis either with or without bile duct stones, and overall hepatobiliary complications | more than 3 year follow-up | 
| adverse event (pancreatitis) | rate of pancreatitis | up to 1 month after ERCP | 
| adverse event (bleeding) | rate of bleeding | up to 1 month after ERCP | 
| adverse event (cholangitis) | rate of cholangitis | up to 1 month after ERCP | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholangiopancreatography, Endoscopic Retrograde