Factors Associated with the Success Rate of Endoscopic Retrograde Cholangiopancreatography with Standard Technique followed by Laparoscopic Cholecystectomy in the Management of Choledocholithiasis: A Single-Center Experience

Background Choledocholithiasis is the most common benign biliary disease. Endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC) has been the first-line therapy in recent years, although laparoscopic common bile duct exploration has promising results. This retrospective study aimed to define the factors associated with biliary clearance by standard ERCP technique and conversion rate of LC. Materials and Methods We retrospectively evaluated the records of 217 choledocholithiasis patients who had undergone ERCP with stone removal by the standard technique from 2010 to 2018. A failed ERCP was defined when the first ERCP session could not remove the stones . The number of patients who later underwent open cholecystectomy or LC was also recorded. Conversion was defined when LC had to be converted OC. Statistical Analysis Student’s t-test was used for the comparison of continuous variables. Nominal variables were analyzed using Pearson’s chi-square test or Fisher’s exact test. Binary logistic regression was performed for multivariate analysis. Results The rate of successful biliary clearance was 81.1%. Of the patients, 109 (50.2%) had difficult stones. Increasing age (p = 0.004), increasing number (p = 0.001), and increasing size of stone (p < 0.001) were the three significant factors that were associated with the failure of biliary clearance. The difficult stone group had a higher failure rate of ERCP and a higher conversion rate of LC compared with the easy stone group (p = 0.001 and p = 0.027, respectively). Conclusions ERCP with the standard technique is a highly effective and safe management option for patients with common bile duct (CBD) stones. The difficult stone group was found to be an independent risk factor that affected the success rate of both ERCP and the following LC. Difficult stone criteria should be assessed to identify a patient who might benefit from laparoscopic CBD exploration.

A Change in Bile Flow: Looking Beyond Transporter Inhibition in the Development of Drug-induced Cholestasis

Background:Drug-induced Liver Injury (DILI) has received increasing attention over the past decades, as it represents the leading cause of drug failure and attrition. One of the most prevalent and severe forms of DILI involves the toxic accumulation of bile acids in the liver, known as Drug-induced Cholestasis (DIC). Traditionally, DIC is studied by exploring the inhibition of hepatic transporters such as Bile Salt Export Pump (BSEP) and multidrug resistance-associated proteins, predominantly through vesicular transport assays. Although this approach has identified numerous drugs that alter bile flow, many DIC drugs do not demonstrate prototypical transporter inhibition, but rather are associated with alternative mechanisms.Methods:We undertook a focused literature search on DIC and biliary transporters and analyzed peer-reviewed publications over the past two decades or so.Results:We have summarized the current perception regarding DIC, biliary transporters, and transcriptional regulation of bile acid homeostasis. A growing body of literature aimed to identify alternative mechanisms in the development of DIC has been evaluated. This review also highlights current in vitro approaches used for prediction of DIC.Conclusion:Efforts have continued to focus on BSEP, as it is the primary route for hepatic biliary clearance. In addition to inhibition, drug-induced BSEP repression or the combination of these two has emerged as important alternative mechanisms leading to DIC. Furthermore, there has been an evolution in the approaches to studying DIC including 3D cell cultures and computational modeling.

Modified laparoscopic Janeway gastrostomy: a novel adjunct for the management of choledocholithiasis in Roux-en-Y patients

A 76-year-old woman with surgical history of Roux-en-Y gastric bypass presented with recurrent choledocholithiasis. Double balloon enteroscopy was unsuccessful in cannulating the biliary tree, thus, requiring surgically assisted endoscopic retrograde cholangiopancreaticogram (ERCP) access. Due to her stable clinical status, the non-urgent indication and multiple anticipated ERCPs for definitive biliary clearance, a more durable port of access to the ampulla was desired. A modified laparoscopic Janeway gastrostomy of the gastric remnant was performed and served as access for multiple subsequent endoscopic procedures with successful clearance of the biliary tree.

Oxidative Stress Status in Patients with Choledocholithiasis: Before and After Endoscopic Sphincterotomy and Biliary Clearance

Choledocholithiasis may cause biliary obstruction which leads to hepatocellular injury. Oxidative stress has been proposed as a possible mechanism involved in this disorder. This study evaluates the oxidative stress burden in patients with choledocholithiasis and secondary cholestasis, before and after endoscopic sphincterotomy. Experimental part: Patients diagnosed with choledocholithiasis and secondary extrahepatic cholestasis were included in the study between January 1st 2016 and October 31st 2016. In all patients oxidative stress markers were collected within 2 hours before and 48 hours after therapeutic ERCP. Selected markers were superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA). The results were compared to those from a group of 40 healthy subjects. Significantly lower concentrations of SOD (p = 0.03) and GPX (p [ 0.0001) activities, associated with an increased level of MDA level (p [ 0.0001) were shown in patients before biliary clearance compared with the healthy control group. After ERCP the only oxidative stress parameter which showed improvement was the SOD specific activity (p = 0.037). This study shows that extrahepatic cholestasis secondary to choledocholithiasis is associated with increased oxidative stress status. After biliary clearance one oxidative stress marker was significantly improved (SOD), suggesting a possible antioxidant effect of such procedure.

Pharmacokinetics of Boldine in Control and Mrp2-Deficient Rats

The aim of the present study was to describe the currently poorly understood pharmacokinetics (PK) of boldine in control rats (LW, Lewis rats), and Mrp2 transporter-deficient rats (TR-). Animals from the LW and TR- groups underwent a bolus dose study with 10 mg/kg of boldine applied either orally or intravenously in order to evaluate the major PK parameters. The TR- rats demonstrated significantly reduced total clearance with prolonged biological half-life (LW 12±4.6 versus TR- 20±4.4 min), decreased volume of distribution (LW 3.2±0.4 l/kg versus TR- 2.4±0.4 l/kg) and reduced bioavailability (LW 7 % versus TR- 4.5 %). Another set of LW and TR- rats were used for a clearance study with continuous intravenous administration of boldine. The LW rats showed that biliary and renal clearance formed less than 2 % of the total clearance of boldine. The treatment of samples with β glucuronidase showed at least a 38 % contribution of conjugation reactions to the overall clearance of boldine. The TR- rats demonstrated reduced biliary clearance of boldine and its conjugates, which was partly compensated by their increased renal clearance. In conclusion, this study presents the PK parameters of boldine and shows the importance of the Mrp2 transporter and conjugation reactions in the elimination of the compound.

Endoscopic Management of the Difficult Bile Duct Stones: A Single Tertiary Center Experience

Background. Most common bile duct (CBD) stones can be removed with standard techniques using endoscopic retrograde cholangiopancreatography (ERCP), but in some cases additional methods are needed. In this study we aimed to investigate the management of patients with difficult stones and the factors that affect the outcome of patients that have undergone periodic endobiliary stenting. Materials and Methods. Data of 1529 patients with naive papilla who had undergone ERCP with an indication of CBD stones was evaluated retrospectively. Stones that could not be removed with standard techniques were defined as “difficult stones.” Cholangiograms of patients who had difficult stones were revised prospectively. Results. Two hundred and eight patients (13.6%) had difficult stones; 150 of these patients were followed up with periodic endobiliary stenting and successful biliary clearance was achieved in 85.3% of them. Both CBD (p<0.001) and largest stone size (p<0.001) were observed to be significantly reduced between the first and the last procedure. This difference was even more significant in successfully treated patients. Conclusions. Periodic endobiliary stenting can be used as an effective treatment for patients with difficult stones. Sizes of the CBD and of the largest stone are independent risk factors that affect the success rate.