Published online Aug 16, 2018. doi: 10.4253/wjge.v10.i8.130
Peer-review started: November 21, 2017
First decision: December 12, 2017
Revised: March 2, 2018
Accepted: March 28, 2018
Article in press: March 28, 2018
Published online: August 16, 2018
Endoscopic retrograde cholangiopancreatography (ERCP) has become one of the most important techniques for the treatment of choledocholithiasis, a pathology with an important prevalence in the population, which incidence increases with age, with an estimated 5% to 10% of patients with cholelithiasis at the time of cholecystectomy even without any predictive factors. The techniques and endoscopic instruments have evolved a lot in the last decades, with a significant improvement in effectiveness and safety, but we still have challenging situations (gallstones larger than 15 mm or in number greater than 10 or when there is a disproportion between stone size and the distal bile duct caliber). In this sense, we should seek solidified data in the available scientific literature to support our most appropriate therapeutic decision.
Endoscopic sphincterotomy as well as balloon dilation of duodenal major papilla are recognized endoscopic treatment approaches to choledocholithiasis. These two techniques, however, are associated with adverse events such as hemorrhage, perforation and pancreatitis. Additionally, gallstones cannot be removed in approximately 5% to 10% of patients, especially those with difficult duct biliary stones. Our initial motivation was to know if there is a preferential approach in choledocholithiasis with lower rates of adverse events while maintaining high effectiveness. From the literature review about the subject, we realized some characteristics that we interpreted as important limitations in the previous works. Thereafter, this study tried to remove these limitations and to follow a rigorous methodological approach in the selection and analysis of clinical trials in order to enhance the knowledge about safety and efficacy data.
We want to compare efficacy and safety data between the two most widespread endoscopic approach methods in choledocholithiasis: endoscopic sphincterotomy vs endoscopic sphincterotomy associated with large balloon dilation. It was possible to obtain in the literature a large sample of patients taken from properly conducted clinical trials. We believe that future systematic reviews on this issue can be based on our selection and analysis methodology and just add new trials which shall be published in order to update and to bring a greater dimension to the theme.
This systematic review was conducted according to the PRISMA Statement (Preferred reporting items for systematic reviews and meta-analyses). The search was performed in the electronic databases MedLine (via PubMed), Cochrane Library, LILACS, EMBASE, the CAPES database (Brazil), and gray literature. The incorporation of recent trials updates the understanding of the choledocholithiasis approach, and the sampling and selection of only randomized clinical trials provide greater magnitude and accuracy.
Eleven randomized controlled trials (RCTs) with 1824 patients were included. EST was associated with more post-ERCP bleeding (P = 0.05) and more need for mechanical lithotripsy in general (P = 0.002) and in subgroup analysis of stones greater than 15 mm (P = 0.003). Incidence of pancreatitis, cholangitis and perforation was similar between the groups as well as similar stone removal rates in general and in pooled analysis of stones greater than 15 mm. We obtained the largest sample already described in the literature that directly compares the EST vs sphincterotomy associated with balloon dilation (ESBD) methods in choledocholithiasis through data extracted from published randomized clinical trials. We were expecting that the primary outcome defined as stone removal rate have differentiated the methods efficacy about the balloon dilation association at least for the subgroup analysis of patients with stones greater than 15 mm, but, despite the tendency to favors the ESBD group, there was no statistical difference among the groups. Perhaps the subgroup sample (484 patients) was too small to evidence it. So it may be required more large-scale specific RCTs.
Through the direct meta-analysis of the largest sample ever pulled exclusively from randomized clinical trials addressing choledocholithiasis, we found that isolated sphincterotomy was associated with higher post-ERCP bleeding as well as an increased need for mechanical lithotripsy than when associated with balloon dilation. Regarding efficacy, stone removal rate tended to be better in ESBD than in EST, although the difference was not statistically significant. This study sought to remove the bias from the lack of methodological rigor applied in the selection and analysis of clinical trials identified in the previous reviews, thus obtaining more purified results, even though they are similar. We found that ESBD was a greater safety method compared to isolated sphincterotomy (ES) since ES group carried a higher risk of post-ERCP bleeding and required more frequent therapeutic complementation with use of mechanical lithotripsy, being exposed to a greater theoretical risk of bile duct injury, in addition to a potential longer procedure cost and time. In terms of efficacy, we obtained statistical similarity between groups, with tendency to superiority in stone removal rate for the ESBD group. This study proposes that the complement with balloon dilation after sphincterotomy of the papilla is associated with greater safety in ERCP for choledocholithiasis, since isolated sphincterotomy was associated with more post-ERCP bleeding. Taking into account the fact that mechanical lithotripsy (ML) was less needed in ESBD group both in general and in subgroup analysis with stones greater than 15 mm, this association should be part of the approach decision algorithm according to physician’s experience with one technique or another, since if he opts less often for dilation he will be more susceptible to the need for ML. This systematic review sought to homogenize the selection of randomized clinical trials and to compare the outcomes of the two most commonly used endoscopic methods in the extraction of gallstones from common bile duct: isolated sphincterotomy ES and ESBD, besides presenting the largest sample involved up to the present moment submitted to direct analysis. The incorporation of recent clinical trials updates the understanding of the choledocholithiasis approach, and the sampling and selection of only randomized clinical trials provide greater magnitude and accuracy. All the phenomena found had already occurred separately in previous studies, so, this study corroborates and reinforces with the findings of the literature. To achieve greater impact through direct analysis of the largest sample taken exclusively from the RCT so far, we can confirm some findings from the literature review as a higher risk of bleeding in the EST group compared to ESBD and less need for ML in the ESBD group when performing ERCP for choledocholithiasis resolution.
The legitimacy of comparing these two methods through meta-analyzes always seems to be influenced by the technical differences applied in each trial, such as the sphincterotomy length, once it shows an evident disturbance in the results of this study. Continuous assessment of efficacy and safety data for difficult cases of choledocholithiasis, focusing on compares the outcomes between partial vs total sphincterotomy, both associated to large balloon dilation. A pertinent study design to the theme would be a large multicentric randomized clinical trial with standardized techniques and assessments based on up-to-date consensus involving patients with complex gallstones (greater than 15 mm or in number greater than 10 or with size disproportion between stone and distal CBD) comparing small vs total sphincterotomy, both associated with large balloon dilation.