Cholecysto-choledocholithiasis refers to the simultaneous presence of stones in the gallbladder and the common bile duct (CBD). The prevalence of concomitant choledocholithiasis in patients with symptomatic gallstone disease varies from approximately 10 to 18% [1]. While laparoscopic cholecystectomy (LC) is considered the “gold standard” for the treatment of cholecystolithiasis, the preferred therapy for cholecysto-choledocholithiasis is still controversial.

In the past, open CBD exploration combined with cholecystectomy was a conventional method for treating patients with cholecysto-choledocholithiasis. Along with the improvement of laparoscopic and endoscopic techniques, the surgical management of concomitant gallstones with CBD stones encompasses a variety of strategies, including simultaneous or sequential approaches [2]. Currently, the most commonly applied procedure is preoperative endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) and stone extraction followed by LC, the so-called sequential two-stage intervention, which was also recommended by the 2016 EASL (the European Association for the Study of the Liver) clinical practice guidelines for the prevention, diagnosis, and treatment of gallstones [3]. Nevertheless, accumulated evidence suggests that ERCP/EST may lead to unpredictable severe complications, such as post-ERCP pancreatitis (PEP), perforation, and hemorrhage [4, 5]. It is reported that ERCP/EST is associated with a failure to cannulate the ampulla of Vater, with a rate ranging from 4 to 18% [6]. Meanwhile, PEP is a major concern that can result from prolonged and repeated pancreatic duct cannulation and inadvertent contrast injection.

Considering the above disadvantages of ERCP/EST, a fascinating alternative approach could be the laparoendoscopic rendezvous technique (LERV), the so-called simultaneous one-stage intervention, which was first described by Deslandres in 1993 and completed by Feretis in 1994 [7]. LERV involves a combined laparoendoscopic procedure in which cholecystectomy is performed laparoscopically while choledocholithiasis is cleared endoscopically via the simultaneous application of biliary cannulation over the papilla of Vater. In the rendezvous cannulation, the guide wire goes through the cystic duct into the duodenum under laparoscopy. This method might theoretically achieve immediate bile duct cannulation and prevent inadvertent pancreatic cannulation [8]. Moreover, it does not require additional equipment apart from what is usually employed in ERCP/EST and LC procedures.

Previously, limited data have indicated that LERV is associated with a lower incidence of PEP than preoperative ERCP/EST and LC [9]. However, whether the combination of rendezvous cannulation with the ERCP strategy has better or worse results than the preoperative ERCP/EST approach for choledocholithiasis complicated with cholecystolithiasis remains controversial. A number of studies have suggested that both methods are equivalent in terms of efficacy, morbidity, and mortality [10,11,12]. Therefore, we performed a retrospective cohort analysis to determine the effectiveness and safety of the simultaneous intervention (LERV) versus sequential management (pre-ERCP/EST + LC) in patients with cholecysto-choledocholithiasis.

Materials and methods

Patients and selection

From January 2013 to December 2018, 528 consecutive patients with concomitant cholecysto-choledocholithiasis (CCL) were enrolled in the Department of Hepato-Biliary Pancreatic Surgery, Zhongnan Hospital of Wuhan University, P. R. China. We retrospectively analyzed the medical records of 260 patients with CCL who were scheduled for either a single-stage or two-stage procedure. A total of 123 of these patients were treated with the one-stage procedure, and 137 patients were managed with the two-stage procedure. The flow chart of patients is presented in Fig. 1. Ethical approval for this study was granted by the Medical Ethics Committee of the Zhongnan Hospital of Wuhan University, and informed consent from the retrospective patient cohort was waived. The exclusion criteria of this study included the following: (i) previous biliary tract surgical history, (ii) American Society of Anesthesiologists (ASA) score ≥ 4, (iii) suppurative cholangitis, (iv) acute pancreatitis, (v) decompensated cirrhosis, and (vi) pregnancy. All patients received reasonable treatment before surgery. A preoperative diagnosis of CCL was routinely determined based on clinical presentation, abdominal ultrasonography, and magnetic resonance cholangiopancreatography (MRCP).

Fig. 1
figure 1

Flow chart of patients with cholecysto-choledocholithiasis (CCL)

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Surgical and endoscopic techniques

The techniques of the two-stage procedure (ERCP/EST followed by LC) have been described in previous studies [13, 14]. All ERCP/EST procedures were performed by experienced endoscopic physicians, and all LC procedures were performed by skilled laparoscopic surgeons. Before proceeding to LC, a waiting period was mandatory. The median interval period was 3 days in this study.

Currently, there are many described techniques for performing LERV. Miscusi G et al. presented a procedure with traditional LERV [15]. During LC, a catheter was introduced into the cystic duct, and then intraoperative cholangiography was performed. Subsequently, ERCP/EST was performed by an endoscopist. Finally, LC was completed after the stones were completely removed. An LERV approach with technical adjustments may be more commonly performed due to its simplicity. In our study, a slightly modified LERV technique was applied. A guide wire was inserted into the cystic duct and out through the duodenal papilla. The guide wire was further endoscopically gripped with a polypectomy loop or a snare and retrieved through the mouth. Sequently a water balloon catheter dilator was inserted over the wire and selective CBD cannulation was performed followed by intraoperative ERCP and clearance of CBD stones. It should be noted that all LERV procedures were performed by the authors in the absence of endoscopic physicians.

Outcome measures

The primary outcome measure was the incidence of early surgical complications, including bile leakage, postoperative bleeding, perforation, and post-ERCP pancreatitis. The secondary outcome measures were the success of the stone clearance, operation time, length of hospital stay, cost, and rate of later biliary complications.

Statistical analysis

All statistical analyses were performed using the SPSS software package (version 19.0, SPSS Inc., Chicago IL, United States). Quantitative data are presented as the mean ± SD. Statistical comparisons between the two groups were analyzed by Student’s t test, ANOVA, Mann–Whitney U test, or the Chi-square test, when appropriate. A P value < 0.05 was considered statistically significant.

Results

Demographic characteristics of patients with CCL

In this study, a total of 260 patients with CCL (128 females and 132 males) were included and retrospectively analyzed. Among them, 137 patients were treated with the two-stage procedure (ERCP + LC), and 123 patients underwent one-stage management (LERV). The ERCP + LC group consisted of 73 females and 64 males with a median age of 58.2 years, whereas the LERV group was composed of 55 females and 68 males with a median age of 56.3 years. The relevant preoperative characteristics of CCL patients are shown in Table 1. There were no significant differences between the two groups in terms of sample size, gender, median age, BMI, ASA score, clinical presentation, mean diameter of CBD stones, serum levels of total bilirubin, and alkaline phosphatase (P > 0.05 for each).

Table 1 Demographic of patients with concomitant gallstones and common bile duct stones
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Clinical outcomes for one-stage and two-stage management

The intraoperative and postoperative parameters of the patients with CCL who underwent different management were measured and are depicted in Table 2. There was no death of patients in our study. We found no difference in the rate of stone clearance between the LERV approach and the conventional one-stage procedure group (97.5% vs. 96.3%, P > 0.05). The overall operation time, including the preoperative time of ERCP/EST and LC, was 107.7 ± 40.6 min in the two-stage group and 139.8 ± 46.8 min in the one-stage group. This difference may exist because with the LERV technique it is difficult to perform selective cannulation during LC. Moreover, the mean duration of endoscopic part of the procedure did differ between the two groups (one-stage: 60.5 ± 16.2 min; two-stage: 41.4 ± 20.7 min, P < 0.01).

Table 2 Clinical outcomes after LERV and ERCP + LC management
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The incidence of complications in the two groups was further investigated. The incidence of PEP in the single-stage group was 2.4% (3/123); in the two-stage group, it was 8.8% (12/137); and there was a significant difference between the two groups (P < 0.05). Consistent with the PEP rate, the level of serum amylasemia was lower post-LERV than post-ERCP. The incidences of bile leakage, bleeding, and perforation did not differ significantly between the two groups. All patients with early complications were managed successfully with timely treatment. Nevertheless, the occurrence rates of later biliary complications, including cholangitis (2.2% vs. 0%, P < 0.05), recurrence of CBD stones (16.8% vs. 3.3%, P < 0.01), and papillary stenosis (4.4% vs. 0%, P < 0.01) in the two-stage group were higher than in the one-stage group. The later biliary complication incidence in the two-stage management group was in accordance with previous publications concerned with ERCP/EST.

The patients’ duration of hospital stay and economic expenses were important clinical outcomes. The median hospital stay of the one-stage group was significantly shorter than that of the two-stage group (12 days vs. 18 days, P < 0.01). Meanwhile, the total cost in the one-stage group was 53591.4 ± 11361.2 RMB and 60089.2 ± 11311.3 RMB. There was a significant difference between the two groups (P < 0.01). Several factors may have contributed to the prolonged length of hospital stay and increased cost. In the present series, the median interval from ERCP/EST to LC was 3 days, and this seems to be the main reason for the differences in hospital stay and total cost.

All patients were followed up for a median of 9 months (2–30 months). Laboratory tests, ultrasonography, and MRCP were employed for postoperative review. Patients with residual or recurrent stones were treated successfully with repeat ERCP.

Discussion

The treatment of concomitant choledocholithiasis in patients with gallstones aims to remove the stones thoroughly. However, there is still no consensus regarding which strategy is optimal for cholecysto-choledocholithiasis. Although the risk of complications, including acute pancreatitis, hemobilia, and cholangitis, has been reported in many studies, preoperative ERCP/EST followed by LC, the so-called two-stage approach, remains the most frequently applied approach worldwide [16, 17]. In recent years, improvements in laparoscopic surgery techniques have made it possible to manage cholecysto-choledocholithiasis with traditional one-stage procedures, including laparoscopic CBD exploration (LCBDE) and laparoscopic trans-cystic bile duct exploration (LTCBDE) [18]. The traditional one-stage approach is associated with fewer procedures, shorter hospital stays, and lower costs compared to the one-stage strategy [19]. Furthermore, accumulating evidence has suggested that there are no significant differences in outcomes between these two procedures [20, 21].

Laparoendoscopic rendezvous (LERV), a novel and feasible one-stage technique, is a combined laparoscopic and endoscopic approach for removing stones in the gallbladder and common bile duct [22]. It is regarded as safe, effective, and economical in theory. The procedure facilitates the identification and cannulation of the papilla because a guide wire is inserted through the cystic duct, which allows the catheter to be grasped and avoids cannulation of the pancreas and the creation of a false passage. In the past, most patients with CCL were firstly treated by ERCP in department of Gastroenterology in our hospital. Subsequently, the patients were transferred to our department of Hepato-Biliary Pancreatic Surgery for performing LC. In recent years, the LERV was found by many experts to be safety, effective, and less expensive single-session management. Moreover, with the progress of our endoscopy skills, we switched to perform LERV by ourselves. In this study, we showed equivalent feasibility (one-stage, 97.5%; two-stage, 96.3%) between the two management options. These results were in accordance with previous published literature [23, 24]. Furthermore, we compared the complications and outcomes between the sequential two-step procedure and single-stage management. As our findings show, the incidence rate of post-ERCP pancreatitis was 2.4% in the LERV group and 8.8% in the ERCP/EST + LC group. Moreover, the average level of serum amylase in the one-stage procedure was significantly lower than that in the two-stage approach. Several studies have indicated that post-ERCP pancreatitis ranges between 1 and 14% [25, 26]. Currently, the pathogenic factors related to post-ERCP pancreatitis are considered to be associated with inadvertent cannulation, contrast injection into the pancreatic duct, and multiple attempts to cannulate the ampulla of Vater [27]. The LERV technique may avoid these complications to a large extent, especially in cases of anatomically difficult endoscopic intubation. Thus, we concluded that the one-stage approach can reduce the incidence of post-ERCP pancreatitis for patients with cholecysto-choledocholithiasis.

In addition, the overall complication occurrence rate was not significantly different between groups, and no patient died in either group, similar to previous publications. These results suggest that the LERV technique provides the same safety and efficacy as ERCP/EST followed by LC for the treatment of cholecysto-choledocholithiasis. Interestingly, late recurrent biliary complications were found in only four cases in the one-stage procedure group but in 34 cases in the two-stage approach group. The rate of recurrent biliary problems such as stenosis of the ampulla in the management of traditional ERCP + LC procedures is reported to range from 11 to 24% [28]. The lower incidence of later biliary complications was attributable to the LERV technique, which decreased the risk of the destruction of the sphincter of Oddi. Further research found that the median hospital stay and cost were both much lower in the group that underwent the one-stage approach. Longer hospital stays obviously contributed to the high cost of the group that underwent the two-stage approach. However, the surgical time was significantly longer for the one-stage procedure. The interval between ERCP and LC seems extended hospitalization time and increased costs. Recent studies have shown that it is extremely difficult to reduce this time interval [29, 30]. Twenty-four hours is the minimal waiting period to ensure that no post-ERCP complications have occurred before proceeding to LC, and this is an obvious disadvantage of two-stage management.

Although the LERV technique has many benefits, its application is still limited in many medical centers. This is largely because it is difficult to ensure the presence of an experienced endoscopist and a skilled laparoscopic surgeon [31, 32]. Close cooperation between the surgeon and the endoscopist is essential for this approach. However, the performance of LERV by surgeons alone without an endoscopic team has been reported [33]. In this article, 123 patients with cholecysto-choledocholithiasis who underwent LERV were treated by the authors. The median operation time was much lower in our series than that indicated in other studies following the LERV technique, which took minutes [34, 35]. This is likely because we did not have to wait for the endoscopist during the operation.

Recently, a few studies have demonstrated that the traditional LERV technique is an optimal approach for patients with cholecysto-choledocholithiasis [36, 37]. Nevertheless, the applied strategy has presented some technical problems [38, 39]: (a) the supine position is inconvenient for performing ERCP; (b) the guide wire is difficult to manipulate when passing across the Oddi sphincter under certain conditions, such as in cases of impacted stones, an excessive diameter of stones, or cystic duct stenosis; (c) the pushing and pulling of the guide wire out of the endoscope for papillary cannulation increases the operation time; (d) the intraoperative endoscopic insufflation can cause bowel distention, which reduces the operating space for LC and causes difficulty with cannulation. Hence, several technical solutions have been presented to ease these difficulties, including changing to the left lateral position and using a bowel desufflator or an atraumatic laparoscopic clamp to avoid bowel distention [40]. Additionally, some aspects of the LERV technique were modified during our study. We first changed the patient’s position from supine to left lateral. In the left lateral position, it was easy to grasp the guide wire and cannulate the ampulla of Vater when the endoscope passes into the descending duodenum. Subsequently, to prevent problems arising from bowel loop distention induced by endoscopic insufflations, Calot’s triangle was completely dissected before ERCP. These experiences improved the success rate of the LERV procedure in patients with cholecysto-choledocholithiasis.

In conclusion, our data further confirmed that one-stage management is a safe and effective approach for patients with cholecysto-choledocholithiasis. In comparison with conventional two-stage procedures, it could lead to a shorter median hospital stay, lower costs, a lower incidence of pancreatitis, and fewer late biliary complications. However, a limitation of the current research was the fact that it was a single-center retrospective study with small sample sizes. Selection bias may have been introduced by the retrospective nature of the study. Further prospective investigations should be conducted to determine the best treatment option for cholecysto-choledocholithiasis.