Comparison of LCBDE vs ERCP + LC for Choledocholithiasis

Study Overview
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Brief Summary
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Protection of Oddi's sphincter remains a huge argument especially in the long term complications like common bile duct stone recurrence or cholangitis after ERCP, which determined to destroy the sphincter of Oddi. The purpose of this study is to compare the long-term outcomes of ERCP sequential LC versus LCBDE for choledocholithiasis.

Detailed Description
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Cholelithiasis, a common etiology factor responsible for abdominal pain, is highly prevalent worldwide. According to data from general investigation, the morbidity of cholelithiasis differs from 2.36% to 42% in different areas, and about 5% to 29% (average 18%) of all cholelithiasis cases have both gallbladder stone and common bile duct stone. In the population with age above 70 years old, 30% of which suffers from gallbladder stone in China. A causal link between the development of gallbladder stone and common bile duct stone is that 10% to 15% of gallstone patients have high potential to develop secondary common bile duct stone. In 1987, the laparoscopic cholecystectomy (LC) came into being as a revolutionary surgical method. With minimally invasive effect and high safety, LC was soon accepted as a 'Golden standard' for the treatment of gallbladder stone. Endoscopic sphincterotomy (EST) was firstly reported by Kawai and Classen in 1970. As of now, the combination of EST with other endoscopic techniques, such as basket extraction, balloon dilation and lithotripsy, have significantly improved the stone removal rate from 85% up to 90%, and ERCP has been considered as the optimal method in regard to CBD stone treatment. In 1991, the laparoscopic common bile duct exploration (LCBDE) which reflected the advantage of rigid scopes had risen to be a very promising minimally invasive alternative for the treatment of common bile duct (CBD) stone. Currently, there are mainly two kinds of minimally invasive treatments for choledocholithiasis, which refers to the one-stage laparoscopic method, LCBDE and the sequential two-stage method, ERCP followed by LC. Both methods are able to achieve the same therapeutic purpose. However, there has always been a controversy about the advantages and disadvantages due to lack of evidence from long-term follow-ups, especially the difference of long-term complications related to Oddi's sphincter functional status, which importantly refers to stone recurrence rates and cholangitis. The potential long-term complications resulted from EST remains an issue now. It is believed that EST handles Oddi's sphincter stenosis, regurgitation cholangitis, and higher cholangiocarcinoma risks in a long run. By virtue of ERCP, multiple high stone clearance rates (87% 97%) were reported, but meanwhile high re-ERCP rates (around 25%) were also indicated because of stone residual, and whether great stone residual rates was linked to future stone recurrence and repeated cholangitis is not clear. Several randomized controlled trial (RCT) studies had compared ERCP plus LC and LCBDE, the results were similar to the aspects of stone removal rates, costs, and patient acceptance. However, the postoperative cholangitis rate of one single center study is quite different from another. Moreover, few studies have related the stone recurrence rate in the long term follow-up. Obviously, previous RCT studies were limited by few comparison of ERCP followed by LC versus LCBDE in long-term complications, especially stone recurrence and cholangitis. Therefore, this multicenter randomize control study is designed prospectively to compare the stone recurrence and cholangitis rates between ERCP plus LC and LCBDE which can reflects the valuable of Oddi's sphincter protection during the disease management, further dedicating the treatment of gallbladder and common duct stone.

Official Title
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A Long Term Complications Comparison of Laparoscopic Common Bile Duct Exploration and Cholecystectomy Versus Sequential ERCP Followed by Laparoscopic Cholecystectomy for Choledocholithiasis: a Multicenter Randomized Controlled Study

Conditions
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Choledocholithiasis

Intervention / Treatment
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* Procedure: Laparoscopy
* Procedure: Endoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years old Choledocholithiasis patient did not perform any operation Common bile duct stone less than 2cm in maximum diameter Exclusion Criteria: Unwillingness or inability to consent for the study Coagulation dysfunction (INR> 1.3) and low peripheral blood platelet count (<50×109 / L) or using anti-coagulation drugs Previous EST, EPBD or percutaneous transhepatic biliary drainage (PTBD) Prior surgery of Bismuth Ⅱ and Roux-en-Y Benign or malignant CBD stricture Preoperative coexistent diseases: acute pancreatitis, GI tract hemorrhage, severe liver disease, primary sclerosing cholangitis (PSC), septic shock Combined with Mirizzi syndrome and intrahepatic bile duct stones Malignancies Biliary-duodenal fistula confirmed during ERCP Pregnant women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LCBDE group (single step)<br>Choledocholithiasis patient, after Laparoscopic Cholecystectomy (LC) to remove the gallbladder, Laparoscopic Common Bile Duct Exploration (LCBDE) was performed for removing the bile duct stone(s) in laparoscopy. Choledochoscope detection or cholangiograms should be chosen as a method of obtain stone clearance. T-tube was acceptable if needed. | Procedure: Laparoscopy<br>* After removing the gallbladder, Laparoscopic common bile duct exploration (LCBDE) was performed by one fulltime attending in laparoscopy in a routine fashion. Access from the opening of the anterior wall of common bile duct or from the dilated cystic duct was acceptable, removed stone(s) and irrigated the duct followed by choledochoscope detection simultaneously. Cholangiograms were also can be a alternative method to obtain stone clearance. If needed, all fluoroscopy was performed by the principal author in the presence of and concurrence with the ERCP endoscopist. Once the LCBDE was completed, the incision of the bile duct was sewed intermittently by absorbed threads, or ligated cystic duct. T-tube was acceptable if needed.<br>* Other names: Laparoscopic common bile duct exploration (LCBDE);|
| Active Comparator: ERCP group (sequential step)<br>Choledocholithiasis patient, Endoscopic Retrograde cholangiopancreatography (ERCP) was performed for removing the bile duct stone(s) in endoscopy prior to Laparoscopic Cholecystectomy (LC). Sphincterotomy (EST) and Endoscopic papillary balloon dilatation (EPBD) can be chosen accordingly. The laparoscopic cholecystectomy was subsequently performed as soon as technically feasible following the ERCP in one month. | Procedure: Endoscopy<br>* Initially endoscopic retrograde cholangiopancreatography (ERCP) was performed by a fulltime attending and concurrence of the principal author in endoscopy. Patients randomized to ERCP+ LC group were scheduled to undergo the endoscopic procedure using fluoroscopy in the endoscopy center under moderate sedation (principally intravenous midazolam and meperidine) prior to the intended laparoscopy. Gastric intestinal atony during ERCP was routinely achieved using scopolamine butylbromide injection. Sphincterotomy (EST) and Endoscopic papillary balloon dilatation (EPBD) can be choose accordingly. The laparoscopic cholecystectomy was subsequently performed as soon as technically feasible following the ERCP in one month.<br>* Other names: Endoscopic Retrograde cholangiopancreatography (ERCP);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Common bile duct stone recurrence | Stone was diagnosed by MRI or CT whenever be confirmed after 3 months after procedures. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with all stones removed |  | Up to 8 hours | 
| Operation time | For arm1 (LCBED): the whole process of the operation; for arm2 (LC+ERCP): the total of the two procedures, LC and ERCP | Up to 8 hours | 
| Length of stay in hospital |  | Up to 60 days | 
| The total hospitalization costs |  | Up to 60 days | 
| Upper abdominal pain after each procedure by Numerical Rating Scale |  | Up to 60 days | 
| Hemorrhage | Maintained positive fecal occult blood test appears or Hb decreased by 10g/l | Up to 60 days | 
| Perforation | CT scan shows retroperitoneal space fluid or gas | Up to 7 days | 
| Acute cholangitis | Intermittent chills and fever after procedures | Up to 5 years | 
| Bile leakage | Any bile juice aspirated from the abdominal cavity after procedures | Up to 60 days | 
| Stricture of the bile duct | Any stricture appears after the procedures | Up to 5 years | 
| Number of Death connected with the procedures and complications |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholangiopancreatography, Endoscopic, Common bile duct, Complication, Recurrence, Laparoscopic