Choledocholithiasis, or common bile duct (CBD) stone, affects up to 20% of patients with symptomatic gallstone disease [1]. Although CBD stones may pass spontaneously through the major duodenal papilla [2,3] without causing harm, some may lead to life-threatening conditions such as acute cholangitis and pancreatitis. Therefore, choledocholithiasis needs a planned, active intervention.

Over 90% of choledocholithiasis cases are linked to gallbladder stones, namely cholecystocholedocholithiasis (CCL) [4]. The management of CCL typically involves cholecystectomy combined with the removal of CBD stones. This can be achieved through a two-session or single-session approach. The two-session approach includes endoscopic retrograde cholangiopancreatography (ERCP) followed or preceded by laparoscopic cholecystectomy (LC), while the single-session approach involves LC with intraoperative ERCP and LC with laparoscopic common bile duct exploration (LCBDE).

For years, preoperative ERCP + LC has been the preferred approach for CCL in most centers and is recommended by the European Association for the Study of the Liver [5] and the British Society of Gastroenterology [1]. With the innovation of LCBDE, many surgeons have adopted this minimally invasive technique for managing CCL [6,7]. Furthermore, recent studies on single-stage ERCP + LC have demonstrated excellent results [8-10]. Given the distinct advantages and drawbacks of each approach, the optimal management strategy for CCL remains under debate.

To date, ERCP + LC remains the most widely employed strategy for CCL treatment in most centers, irrespective of the endoscopy timing (before, during, or after LC) [11]. Single-stage ERCP + LC is now favored by many surgeons, globally and nationally, for treating CCL owing to patient satisfaction and cost considerations [12]. However, the decision to start the procedure with ERCP or LC primarily depends on the surgeon’s preference and expertise. Therefore, clinical evidence is needed to establish the optimal single-stage ERCP + LC operative strategy. This study aims to compare the feasibility and efficacy of the two variants of single-stage ERCP + LC (initiating with ERCP followed by LC versus starting with LC followed by ERCP) for the treatment of CCL.

A total of 115 patients who underwent single-stage ERCP + LC for CCL between January 2021 and December 2023 were enrolled in a retrospective comparative cohort study. Patients were divided into two groups: Group A (ERCP-1st approach) and Group B (LC-1st approach).

The study protocol received approval from the Institutional Review Board of the Faculty of Medicine, Assiut University (IRB no. 04-2024-300368). This trial was registered at ClinicalTrials.gov (NCT06340594). The study was reported in accordance with the STROCSS 2021 criteria [13].

All patients underwent evaluation through history taking, clinical examination, liver function tests, and abdominal ultrasound. Preoperative diagnosis of choledocholithiasis was confirmed via ultrasound or magnetic resonance cholangiopancreatography (MRCP) if the ultrasound was inconclusive. Liver function tests and ultrasound were performed or repeated within 48 hours before surgery to prevent unnecessary ERCP for spontaneously passed stones.

Inclusion and exclusion criteria

Patients who underwent single-stage ERCP + LC for CCL were eligible for inclusion. Exclusion criteria included patients aged under 18 or over 80 years, those classified as American Society of Anesthesiologists (ASA) class IV and V, contraindications to ERCP or laparoscopy, liver cirrhosis with portal hypertension, pregnancy, previous cholecystectomy, prior upper abdominal surgery, acute cholangitis, acute pancreatitis, unsuccessful prior ERCP attempt, and multiple intrahepatic stones.

Surgical technique

Group A (ERCP 1st approach)

The patients initially underwent ERCP in a prone position followed by a standard 4-port LC in a supine position. If ERCP failed to clear the stones, an attempt was made with LC + LCBDE. Should LCBDE fail, the procedure was converted to open CBD exploration.

Group B (LC 1st approach)

The patients initially underwent LC, followed by ERCP in a prone position. If ERCP failed to clear the stones, the patient was re-positioned for laparoscopic or open CBD exploration.

Postoperative follow-up

Patients were admitted to the ward after recovery, beginning oral intake 6 to 12 hours postoperatively. Vital signs and drains were closely monitored. Patients were typically discharged between 24 and 48 hours postoperatively provided no complications developed.

Follow-up in the surgery outpatient clinic was conducted during the 1st and 2nd weeks post-discharge, and then 3 months later or whenever symptoms appeared. Ultrasound and liver function tests were generally performed on the second visit for CBD clearance assessment.

Outcomes

The primary outcome was the total operative time for ERCP + LC.

Secondary endpoints included CBD clearance rate, postoperative complications, conversion rate to open procedure, and length of hospital stay.

Data collection and statistical analysis

Basic demographic data and details such as operative time, hospital stay, success or failure of CBD clearance, and postoperative complications were retrospectively collected, tabulated, and analyzed using IBM SPSS Statistics ver. 24.0 (IBM Corp.). Data were reported as numbers and percentages for qualitative variables (compared using the chi-square test) and as mean ± standard deviation for quantitative variables (analyzed using the Mann–Whitney U test). Variables were considered significantly different at p < 0.05.

Patients’ demographic data

Over two years, a total of 115 patients were included in our study; 68 underwent the Group A and 47 the Group B. The mean age was 46 ± 16 years in Group A and 49 ± 14 years in Group B. In both groups, the majority were females, with 41 (60.3%) in Group A and 33 (70.2%) in Group B. The average number of CBD stones was 1.9 ± 0.78 in Group A and 2.24 ± 1.9 in Group B. The mean diameter of the largest stone was 7.51 ± 3.4 mm in Group A and 8.96 ± 2.7 mm in Group B. The mean diameter of the CBD was 11.39 ± 2.9 mm in Group A and 10.57 ± 3.1 mm in Group B.

There were no significant differences between the two groups in terms of mean age, gender distribution, ASA class, body mass index, average number of CBD stones, mean diameter of the largest stone, mean CBD diameter, and preoperative liver function tests as shown in Table 1.

Table 1 . Demographic data of the patients

	Group A (ERCP 1st approach) (n = 68)	Group B (LC 1st approach) (n = 47)	p-value
Age (yr)	46 ± 16 (21–72)	49 ± 14 (23–73)	0.301
Sex
Male	27 (39.7)	14 (29.8)	0.277
Female	41 (60.3)	33 (70.2)
BMI (kg/m2)	23.1 ± 2.6	23.8 ± 2.1	0.128
ASA score
ASA I and II	59 (86.8)	42 (89.4)	0.677
ASA III	9 (13.2)	5 (10.6)
Liver function test
TBil (μmol/L)	95.5 ± 13.7	91.3 ± 18.3	0.162
ALP (U/L)	695 ± 443	596 ± 378	0.204
ALT (U/L)	98.7 ± 16.8	102.5 ± 19.3	0.264
Clinical jaundice	48 (70.6)	39 (83.0)	0.129
Number CBD stones	1.9 ± 0.78 (1–9)	2.24 ± 1.9 (1–13)	0.188
Diameter of stones (mm)	7.51 ± 3.4 (5–13)	8.96 ± 2.7 (5–16)	0.307
Diameter of CBD (mm)	11.39 ± 2.9 (9–17)	10.57 ± 3.1 (8–15)	0.150

Values are presented as mean ± standard deviation (range) or number (%).

ERCP, endoscopic retrograde cholangiopancreatography; LC, laparoscopic cholecystectomy; BMI, body mass index; ASA, American Society of Anesthesiologists; TBil, total bilirubin; ALP, Alkaline phosphatase; ALT, alanine aminotransferase; CBD, common bile duct.

Perioperative data among the study population

Patients treated with the Group A had a CBD clearance rate of 88.2%, comparable to 95.7% in the Group B; p = 0.163. ERCP failed to clear CBD stones in only 6 (8.8%) cases in Group A and in 2 (4.3%) cases in Group B, with no significant difference between the groups (p = 0.346); see Table 2.

Table 2 . Perioperative data of the patients

	Group A (ERCP 1st approach) (n= 68)	Group B (LC 1st approach) (n = 47)	p-value
CBD clearance	60 (88.2)	45 (95.7)	0.163
ERCP failure	6 (8.8)	2 (4.3)	0.346
Failed cannulation	4 (5.9)	1 (2.1)	0.334
Incomplete stone extraction	2 (2.9)	1 (2.1)	0.789
Pre-cut	3 (4.4)	4 (8.5)	0.368
ERCP stenting	2 (2.94)	0	0.238
Conversion to OS	1 (1.5)	1 (2.1)	0.792
Conversion to LCBE	5 (7.4)	1 (2.1)	0.217
ERCP duration (min)	43.3 ± 11.8 (25–65)	39.5 ± 13.5 (20–80)	0.112
LC duration (min)	41.2 ± 8.98 (30–105)	37.2 ± 12.2 (20–75)	0.045
Total operative time (min)	81.9 ± 16.7 (55–160)	75.1 ± 19.3 (45–165)	0.046
Postoperative complication	6 (8.8)	2 (4.3)	0.346
Pancreatitis	4 (5.9)	2 (4.3)	0.701
Bile leak	1 (1.47)	0	0.406
Hemorrhage	1 (1.47)	0	0.406
Perforation	0	0	NA
Cholangitis	0	0	NA
Missed stones	2 (2.9)	0	0.238
Hospital stay (day)	2.1 ± 0.6 (1–6)	1.9 ± 0.5 (1–7)	0.063

Values are presented as number (%) or mean ± standard deviation (range).

LC, laparoscopic cholecystectomy; ERCP, endoscopic retrograde cholangiopancreatography; CBD, common bile duct; OS, open surgery; LCBDE, laparoscopic common bile duct exploration.

Conversion to LCBE occurred in 5 patients in Group A due to failed cannulation in 4 cases and incomplete stone clearance by ERCP in one patient. Another patient in the same group underwent conversion to laparotomy due to incomplete stone clearance. Two patients underwent ERCP stenting after extraction of stones due to incidentally diagnosed distal benign-featuring CBD stricture. Two cases were diagnosed with missed stones and managed with another session of ERCP. In Group B, one patient required conversion to LCBE due to failed cannulation, while another patient needed conversion to open CBD exploration due to incomplete stone removal by ERCP.

The mean duration of the ERCP procedure was comparable between the two groups (43.3 ± 11.8 vs 39.5 ± 13.5 minutes; p = 0.112). In contrast, the mean duration of the LC procedure in Group A was significantly longer than in Group B (41.2 ± 8.98 vs 37.2 ± 12.2 minutes; p = 0.045). Moreover, the mean total operative time for combined ERCP + LC was significantly greater in Group A than in Group B (81.9 ± 16.7 vs 75.1 ± 19.3 minutes; p = 0.046).

Postoperative complications included post-ERCP pancreatitis in four patients from Group A and two from Group B (p = 0.701). A single case of bile leak in Group A was detected via the abdominal drain and managed conservatively. Postoperative bleeding occurred in one patient in Group A as well. No significant differences were observed in perioperative complications between the two groups (p = 0.346). The length of hospital stay was also comparable between both groups (p = 0.063).

Since the introduction of laparoscopy for gallbladder removal in the early 1990s, LC has largely replaced the open approach and has become the standard procedure for gallbladder stones [14]. Additionally, the increased adoption of ERCP has established it as the preferred method for removing CBD stones in most centers [15-17]. Thus, the traditional management for CCL has been preoperative ERCP with extraction of CBD stones followed by LC [9,18-20]. However, the wide adoption of this two-session strategy was changed by the innovation of laparoscopic CBD exploration, which offers a single-session minimally invasive solution for both gallbladder and CBD stones. However, this approach requires advanced surgical expertise and specialized equipment, such as a choledochoscope, limiting its availability in most hospitals [21].

Single-stage ERCP + LC has become increasingly popular in recent years [10,19]. This popularity stems from its ability to circumvent the disadvantages associated with the two-stage procedure, such as repeated hospitalizations and prolonged hospital stays, which reduce patient satisfaction and escalate overall medical costs [22-24]. Additionally, the two-stage procedure exposes the patient to the risk of repeated anesthesia. Also, the delay between preoperative ERCP and LC can increase the risk of stone migration to the CBD, or recurrence of cholecystitis [25]. This delay may be exacerbated by complications such as post-ERCP pancreatitis or cholangitis. Some authors believe that contrast injection and sphincterotomy during ERCP can lead to bacterial colonization of the bile duct, potentially causing inflammation and adhesions in Calot’s triangle, thereby increasing the likelihood of converting LC to laparotomy [26,27]. Another advantage of single-stage ERCP + LC is the ability to verify the presence of CBD stones through transcystic intraoperative cholangiography, thus avoiding an unnecessary ERCP.

It is worth noting that not all patients with CCL are suitable for single-stage ERCP + LC. Thus, exclusion criteria should be considered when employing this approach for treating CCL. These criteria include conditions that are not suitable or challenging for ERCP, such as altered gastroduodenal anatomy from prior surgeries (e.g. Billroth II gastrectomy), previously failed ERCP, and multiple intrahepatic stones. Additionally, challenging cases of LC with a high conversion rate (e.g. liver cirrhosis with portal hypertension, previous upper abdominal surgery, cholangitis, and pancreatitis) should be excluded. Moreover, patients with advanced age, or with poor general health who cannot tolerate prolonged anesthesia are better managed with a two-session approach.

When performing ERCP in single-stage ERCP + LC, consideration of patient positioning is essential. Generally, most endoscopists prefer the prone position for ERCP as it facilitates papilla cannulation and helps prevent pulmonary aspiration. Some authors advocate for the supine position during general anesthesia to ensure adequate airway protection [28]. However, performing ERCP in the supine position can be inconvenient and more challenging for the endoscopist [29,30]. A meta-analysis has found that prone ERCP has a higher technical success rate and slightly shorter operative time, but is associated with a greater rate of cardiopulmonary complications [31].To enhance ERCP feasibility and minimize bias, we decided to conduct the ERCP in the classic prone position for both study groups (variants).

The stone clearance rate is the primary metric for evaluating the therapeutic efficacy of the single-stage approach for choledocholithiasis treatment. In our study, the CBD clearance rate was higher in Group B than in Group A (95.7% vs 88.2%), though this difference was not statistically significant (p = 0.163). This success rate aligns with previous reports. A study by Selimah et al. [32] reported that CBD clearance was 82.5% in the two-stage group compared to 80% in the single-stage group. Similarly, a meta-analysis by Liao et al. [19] comparing intra-ERCP + LC and pre-ERCP + LC revealed CBD clearance rates of 93.3% and 89.4%, respectively. We observed a high success rate for single-stage ERCP + LC irrespective of the technique utilized, indicating that both procedural variations are highly effective for treating CCL. Furthermore, we hypothesized that performing ERCP after clipping the cystic duct in Group B allowed retrieval of stones that may have migrated from the cystic duct into the CBD during manipulation of Hartmann’s pouch, thereby reducing the rate of missed stones. Missed stones in both groups were effectively treated with postoperative ERCP, which was successful in all cases.

Another important aspect of success to be considered in single-stage strategy is completing the procedure using minimally invasive techniques. For the two-session approach, a 2-week interval between ERCP and LC is recommended to reduce the conversion rate of LC to open surgery [5]. While many surgeons do not consider the conversion of LC to open cholecystectomy a failure, it is associated with increased morbidity and reduced patient satisfaction, and therefore should only be performed when other strategies have failed [33,34]. Conversion in single-stage ERCP + LC may occur due to inability to complete cholecystectomy laparoscopically or failure to extract CBD via endoscopy. In the first case, converting to open surgery is mandatory, while in the second, conversion can be either to LCBDE to remain a minimally invasive procedure, or to open CBDE depending on operative conditions and availability of surgical expertise. In our study, LC was successfully accomplished in all attempted cases, whereas ERCP failed to extract CBD stones in 6 cases in Group A and 2 cases in Group B (p = 0.346). This resulted in 6 conversions to LCBDE and two conversions to open CBDE, one in each group.

In our study, the operative time for ERCP was comparable between both groups (p = 0.112), while the operative time for LC was significantly shorter in the LC 1st group compared to the ERCP 1st group (37.2 ± 12.2 vs 41.2 ± 8.98, p = 0.045). Consequently, the total operative time favored the LC-1st approach (75.1 ± 19.3 vs 81.9 ± 16.7, p = 0.046). Both LC and ERCP were performed by the same team throughout the study, minimizing the potential for surgical confounders. It was found that bowel distention that occurred with intraoperative endoscopic insufflation can make the LC more challenging in the ERCP-1st approach. This phenomenon also noted by several authors [21,30,35,36].

The mean operative time for single-stage ERCP + LC ranges from 94.2 to 142 minutes, according to a recent meta-analysis of 9 randomized controlled trials (RCTs) by Nie et al. [10], which compared single-stage and two-stage treatments for CCL. In a retrospective study, Qian et al. [30] found that the total operative time for the intraoperative ERCP + LC group exceeded that of the preoperative ERCP + LC group (139.8 ± 46.8 minutes vs 107.7 ± 40.6 minutes, p < 0.05). The wide range in the reported mean operative time of single-stage ERCP + LC across studies can be attributed to differences in surgical and endoscopic experience, as well as technical variations. These variations include the use of the ‘‘laparoendoscopic rendezvous’’ (LERV) technique. Some authors used this technique routinely in all study cases [23]; some applied it selectively in challenging cases involving difficult cannulation of the papilla [36], while others omitted its use in single-stage ERCP + LC [37], as in our study. Although the LERV technique has a potential benefit of decreasing post-ERCP pancreatitis, it has two main disadvantages. Firstly, performing selective cannulation may be challenging in cases where the cystic duct or CBD is obstructed by stones [21]. Secondly, LERV requires returning to the surgical field after completing the ERCP procedure to clip the cystic duct and dissect the gallbladder, which can be time-consuming, particularly if ERCP is done in the prone position.

Post-ERCP pancreatitis is one of the leading complications of ERCP and, by extension, of single-stage ERCP + LC. Although it typically resolves with conservative treatment, it delays patient recovery and prolongs the hospital stay. LCBDE has shown superiority over ERCP + LC regarding this problem. A recent meta-analysis comparing pre-ERCP + LC and LCBDE + LC for CCL revealed that the former had a higher CBD stone clearance rate and a higher incidence of pancreatitis [38]. In our study, 4 patients in Group A and 2 in Group B developed pancreatitis, with no significant difference between the two groups (p = 0.701). The rate of post-ERCP pancreatitis (5.2%) aligns with the range reported in previous studies, which can reach up to 9.7% [39].

Post-ERCP bile leak is a very rare complication that typically occurs during endoscopic management of bile duct strictures [40,41]. We recorded one case of bile leak in the ERCP 1st group, which resolved spontaneously with conservative management. There were no cases of bile leak in the LC 1st group, suggesting that the potential risk of bile leakage from the cystic duct stump is minimal when performing ERCP after cystic duct clipping during LC. Therefore, we suggest that bile leak after single-stage ERCP + LC is more likely related to the LC procedure rather than ERCP.

The lack of significant difference between the two groups regarding complications, including post-ERCP pancreatitis, is understandable since the technique of ERCP was consistent between the groups. If LC was performed first, the LERV technique might help identify the duodenal papilla, facilitate selective biliary catheterization, and consequently reduce the risk of post-ERCP pancreatitis by preventing inadvertent catheterization of the pancreatic duct. However, the LERV technique was not used in our cases. In the meta-analysis by Nie et al. [10] of 8 RCTs, intra-ERCP + LC was superior to pre-ERCP + LC in reducing postoperative pancreatitis (p = 0.004). In subgroup analysis, they found that in the LERV group, the incidence of pancreatitis in the one-stage approach was lower than in the two-stage approach (p = 0.002), while in the non-LERV group, the incidence of pancreatitis was similar between the intra-ERCP + LC and the pre-ERCP + LC groups (p = 0.97). It can be hypothesized that if LERV was applied in the LC 1st group, a difference between the two groups regarding ERCP failure and post-ERCP pancreatitis might occur.

The hospital stay between the two groups in our study were similar (p = 0.063), with comparable postoperative morbidity rates (8.8% vs 4.3%; p = 0.346). Typically, the hospital stay ranged from 24 to 48 hours, a period during which complications such as pancreatitis and bile leak could be detected.

The main limitation of this study is its retrospective nature and single-center scope, which might subjected to selection and recall biases with a lack of strict follow-up. Additionally, the sample size could be considered small. Therefore, large prospective randomized trials are required to further validate these findings.

In conclusion, both the LC-1st approach and ERCP-1st approach are feasible and highly effective for treating CCL through single-stage ERCP + LC. However, the LC-1st approach has the advantage of a shorter operative time.

None.

No potential conflict of interest relevant to this article was reported.

Conceptualization: MMS. Data analysis and interpretation: MMS, MR. Writing - original draft: MMS, MR, ASA, IB. Writing - review & editing: MMS, MR, ASA, IB. All authors approved the final version of the manuscript.