In summary, our meta-analysis revealed that both single-stage (LC + LCBDE) and two-stage (LC + ERCP/EST) management achieved equivalent stone clearance from the CBD, but the former procedure was associated with fewer procedures per patient. In addition, there was no statistically difference between the two approaches in terms of postoperative morbidity, mortality, conversion to other procedures, length of hospital stay, total operative time and hospitalization charges.
Currently, the optimal treatment for concomitant gallstones and CBDS is still in dispute[24,30,31
]. In the laparoscopic era, the vast majority of patients who suffered from concomitant gallstones and CBDS were routinely managed by ERCP/EST, either preoperatively or postoperatively, prior to LC[25,26
]. Although this approach is effective and safe for removing the CBDS, it also has several drawbacks. First, it requires two periods of anesthesia and occasionally two hospital admissions, which may increase the length of hospital stay and hospitalization expenses. Furthermore, if patients still have CBDS detected by intraoperative cholangiography in LC after successful ERCP/EST, surgeons will face the dilemma of depending on LCBDE, postoperative ERCP/EST or traditional open choledochotomy. Most importantly, even in those patients with clinical, biochemical and imaging risk factors for CBDS, preoperative ERCP/EST can produce false-negative results, leading to the possibility of morbidity and mortality[26,32
]. Despite postoperative ERCP/EST can indeed avoid the risk inherent in preoperative ERCP/EST to patients without CBDS, it necessitates another surgical procedure when it fails to remove the CBDS[27
]. Both preoperative and postoperative ERCP/EST are likely to lead to some short-term and long-term complications. For instance, they may result in postoperative complications, including bleeding, perforation, pancreatitis and even death[14-17
]. Moreover, it is notable that the intact sphincter of Oddi is destroyed after EST so that biliary sphincter function is permanently lost, which damages the barrier of the sphincter that prevents duodenobiliary reflux[33
]. Reflux from the duodenum into the bile duct is responsible for the high rate of bacterobilia occurring after EST[34
], and chronic bacterobilia may even cause neoplastic changes in the biliary epithelium[35
]. Therefore, ERCP/EST should be adopted on a selective basis, i.e., in patients with acute obstructive suppurative cholangitis, severe biliary pancreatitis, ampullary stone impaction or severe comorbidity. If possible, MRCP should be used for preoperative diagnosis. According to a meta-analysis, MRCP achieved a high overall sensitivity of 95% and a speciﬁcity of 97% for detecting CBDS[36
With the improvement in laparoscopic equipment and skills, LCBDE has been increasingly used to remove the CBDS. It is considered to be a safe, efficient and cost-effective treatment for choledocholithiasis; it is associated with a high stone clearance rate ranging from 84%-97%, a postoperative morbidity rate of 4%-16%, and a mortality rate of approximately 0%-0.8%[26,37-39
]. However, to decompress the bile duct and decrease biliary complications, T-tube drainage has been routinely employed after choledochotomy[40,41
], which is inevitable with complications including bile leakage, bile infection and wound infection[41
]. Furthermore, the patients have to keep the bile drainage tube in place for several weeks before removal, causing great discomfort and delaying their return to work[42
Nevertheless, according to a recent meta-analysis[43
], primary closure might be as effective as T-tube drainage in the prevention of postoperative complications after choledochotomy. Consequently, it seems that LCBDE is a commendable alternative to the use of ERCP/EST.
Previously published trials have demonstrated that single-stage (LC + LCBDE) and two-stage (LC + ERCP/EST) management are equivalent with respect to stone clearance from the CBD, morbidity and mortality[5,24-26
]. However, most of the trials were limited by their small sample size. In 2006, Clayton et al[44
] reported a meta-analysis concerning endoscopy and surgery vs
surgery alone for CBDS with the gallbladder in situ
. In the subgroup analysis, they concluded that the endoscopic and laparoscopic surgery groups had similar outcomes; however, treatment should depend on local resources and expertise. Furthermore, the number of patients included was insufficient, and up-to-date trials were not included. Unlike previous studies, this meta-analysis took patients’ characteristics into consideration and gave suggestions for the optimum management of different patients.
Concerning stone clearance from the CBD, this meta-analysis demonstrated that single-stage (LC + LCBDE) management was as effective as two-stage (LC + ERCP/EST) management (P
= 0.17), but one trial[29
] was more strongly in favor of the single-stage (LC + LCBDE) management than any other included studies. One possible reason was that they abandoned ERCP/EST at an earlier stage when they detected multiple and large stones in the CBD, and they favored a transductal approach if the bile duct diameter was large or if the stones were large and multiple. Another reason might be the use of intention-to-treat analysis. Our meta-analysis showed that the difference in the length of hospital stay between the two groups was not statistically significant (P
= 0.45). Two of the included trials reported that the length of hospital stay was shorter for the single-stage (LC + LCBDE) approach with a statistically significant difference compared with the two-stage (LC + ERCP/EST) management[24,25
]. Other studies showed that there was no significant difference between the two groups, but a recent review suggested that single-stage management had the potential merit of a shorter hospital stay[45
]. One probable reason was that the definitions of hospital stay varied, which had an impact on the validity of the data. Some trials defined it as the duration from the last finished procedure to discharge, while other trials defined it as the entire duration from hospital admission to discharge. Another explanation for the discrepancy in the studies might be the use of data conversions to produce estimates. In our meta-analysis, only one trial reported hospitalization charges, and there was no significant difference in total hospitalization charges and hospital service charges between the two groups. However, the charges for single-stage (LC + LCBDE) management were lower than those for two-stage (LC + ERCP/EST) management[24
]. Other studies[46,47
] showed that single-stage management is a cost-effective method compared to two-stage management.
The postoperative morbidity, mortality and total operating time were similar between the two-stage (LC + ERCP/EST) and single-stage (LC + LCBDE) management with no statistically significant difference in this meta-analysis (P = 0.16, P = 0.42 and P = 0.09, respectively). When considering preoperative ERCP/EST + LC vs LC + LCBDE and postoperative ERCP/EST + LC vs LC + LCBDE separately in the subgroup analysis, the outcomes, as stated, remained consistent.
This meta-analysis was subject to some limitations. First, the funnel plot analysis detected publication bias, which results in over-representation of significant or positive studies. However, the random effects model was utilized for this analysis, and this model is known to enlarge the presence of publication bias by attributing heavier weighting to smaller trials compared to the fixed effects models. Second, the different methodological quality and the heterogeneity of the effect after intervention could also account for the asymmetry in the funnel plot. A second potential limitation was the presence of significant heterogeneity for three outcomes, including stone clearance from the CBD, conversion to other procedures and length of hospital stay, which might influence the reliability and validity of the conclusions to some extent. Finally, the restriction of only including studies published in English was another possible limitation.
For future research studies on this topic, the following suggestions may be helpful (1) hospitalization expenses data were available in only one included trial, which was far from sufficient, and future studies should evaluate this significant endpoint; (2) follow-up was poorly reported in most of the included trials, and long-term outcomes, which largely rely on the follow-up, are as yet unknown. Future trials should strengthen the work of follow-up; (3) future studies need to assess outcomes such as pain scores, health economics, patients satisfaction and quality of life scores because it is more practical for patients to choose their optimal treatment; (4) blinded outcome assessment should be employed in future trials to better reduce bias; and (5) as a result of the different data types provided by the included trials, the outcomes, including the length of hospital stay and total operative time were weakened. Thus, future researchers should use unified data types.
In conclusion, single-stage (LC + LCBDE) management is not only as effective as two-stage (LC + ERCP/EST) management and equivalent in terms of postoperative morbidity, mortality and conversion, but it also reduces the number of procedures used per patient and potentially shortens the length of hospital stay. In addition, single-stage (LC + LCBDE) management also eliminates the underlying risk of ERCP/EST and keeps the sphincter of Oddi intact. It is likely that as laparoscopic expertise and operators’ experience improve, the need for two-stage (LC + ERCP/EST) management will decrease, and single-stage (LC + LCBDE) management should be ultimately available for most patients. However, the optimal management of patients with CBDS should depend on the condition of patients, the expertise of operators and local resources.