The application of a new model for disease classification in minimally invasive treatment of concomitant cholecystolithiasis and choledocholithiasis

doi:10.21203/rs.3.rs-3779390/v1

Download PDF

Research Article

The application of a new model for disease classification in minimally invasive treatment of concomitant cholecystolithiasis and choledocholithiasis

https://doi.org/10.21203/rs.3.rs-3779390/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background: The optimal minimally invasive treatment of concomitant cholecystolithiasis and choledocholithiasis is still variable.

Materials and Methods: This Chinese retrospective single-center cohort study for patients with concomitant cholecystolithiasis and choledocholithiasiss undergoing different minimally invasive treatments. A new model for disease classification was developed and the optimal treatment was screened.

Results: Diameter of CBD, stone number, stone size was significantly correlated with choice of minimally invasive surgical procedures. All patients were sorted into Type I, II, III and Ⅳ respectively. Two invasive surgical methods was performed in patients with type I, IO-EPBD+LC was more suitable due to shorter surgical and hospital stay, and lower postoperative serum amylase levels. There are five surgical methods was performed in patients with type II. If cystic duct was unobstructed and enough big to pass slender choledochoscopy when the confluence of the cystic duct and the common bile duct was slightly incised, the LC+LTCBDE group is recommended as the preferred treatment. IO-EPBD+LCshould be used if cystic duct was not blocked up but the caliber was not enough big to pass slender choledochoscopy. Among the four minimally invasive surgical methods for patients with type III, the LC+LCCBDE+Gastroscope group has the advantage of shorter hospital stay and fewer postoperative complications. Among the three methods for the type IV, the stones are too more and bigger to completely removed during the surgery, LC+LTCD is more suitable.

Conclusion: A novel simple clinical classification system would benefit to induct selecting minimally invasive surgical model for concomitant cholecystolithiasis and choledocholithiasis.

laparoscopy

duodenoscopy

choledochoscopy

common bile duct stones

retrospective cohort study

Cholangiolithiasis is extremely common in western societies and Asia. Approximately 11% of the Chinese population has gallstones, and 10–15% of cases have concomitant common bile duct (CBD) stones. However, few cases of CBD stones in the absence of gallbladder (GB) stones have been reported in the western world(1–3). The management of concomitant GB and CBD stones has evolved significantly over the past 20 to 30 years. Before the advent of laparoscopy and endoscopic methods, open cholecystectomy and CBD exploration were the standard treatment for patients with CBD stones(4, 5). With the emergence of endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST), endoscopic stone removal became the treatment of choice before cholecystectomy for patients with CBD and GB stones(6, 7). However, this technique is associated with high complication (19%), failure (10–15%), and mortality (3%) rates(5, 8–11). It not only leads to postoperative complications such as pancreatitis, perforation, blood loss, sepsis, and death but can also disrupt the sphincter of Oddi, thus injuring the physiological barrier function of the sphincter that prevents cholangitis due to duodenobiliary reflux(10).

Due to the rapid expansion of skills in laparoscopic surgery, the laparoscopic one-stage approach to CBD stones has gained increasing attention. Laparoscopic common bile duct exploration (LCBDE) for CBD stones is substantially better than endoscopic and open surgery with regard to hospital stay, postoperative pain, and cosmesis (12, 13). However, LCBDE has especially high technical requirements and may involve extensive manipulation of instruments, such as balloon dilators, guidewires, catheters, and baskets, as well as laparoscopic suturing of the CBD. An argument against LCBDE is the potential risk of bile duct injury, postoperative bile leaks and strictures(2, 14).

The ideal treatment for choledocholithiasis should be simple, readily available, reliable, minimally invasive and cost-effective for patients. However, the optimal minimally invasive treatment for GB and CBD stones remains unknown, and no standard treatment protocol or clinical classification criteria have been established. There are six different minimally invasive techniques used to remove the stones until now, including two patterns for laparoscope combined with duodenoscope: two-stage preoperative ERCP/EST or EPBD + LC and one-stage intraoperative ERCP/EST or EPBD + LC; three patterns for Laparoscopy combined with intraoperative choledochoscopy (LTC-CBDE + LC, LCCBDE + primary duct-closure + LC, and LTCD + LC) and three mirror scheme (Laparoscopy and choledochoscopy combined with the intraoperative duodenoscope or gastroscopy ). The controversy has mainly focused on whether there is a need to place a T-tube for LCBDE(12). Which approach is more effective for one-stage versus two-stage management or for EST versus endoscopic papillary balloon dilatation (EPBD) remains undetermined. Furthermore, whether ERCP is preoperative and intraoperative must be determined. Advocates of the two-stage approach for ERCP stone removal followed by laparoscopic cholecystectomy (LC) argue that it is less invasive because surgical dissection of the CBD is unnecessary(15, 16). In contrast, advocates of the single stage approach for LCBDE argue that it is better for the patient because only a single procedure is necessary(17).

Because there is no consensus regarding the minimally invasive treatment mode, therapeutic guidelines should be suggested for each type of concomitant GB and CBD stones (6, 18, 19). Additionally, no universal classification of concomitant GB and CBD stones that is easy to apply in the clinic and useful in determining the best minimally invasive treatment mode has previously been reported. Therefore, we conducted a single-center retrospective cohort study of 1044 eligible patients with concomitant GB and CBD stones who were undergoing minimally invasive surgery. We developed a model for disease classification based on the inside diameter of the CBD, the maximum stone size and the stone number. This clinical classification and the clinical features and treatment strategies were analyzed to establish an optimal minimally invasive treatment mode for each patient type to reduce residual stones and relapse and improve therapeutic efficacy.

Study design and procedure

This was a single-center study. The sample consisted of 1044 consecutive patients with GB and CBD stones who were undergoing different minimally invasive surgical treatments at Zhongnan Hospital of Wuhan University in China and were enrolled from January 2014 to April 2021. The study excluded patients who had (1) acute cholecystitis, (2) acute cholangitis, (3) concurrent stones located in the third-order branch of the intrahepatic duct or smaller intrahepatic duct, (4) acute pancreatitis, (5) a history of upper abdominal surgery, (6) uncorrectable coagulopathy, (7) American Society of Anesthesiology (ASA) class 4 or 5 disease, or (8) open CBD exploration. Clinical data for all hospitalized patients were collected and analyzed, including age, gender, clinical presentation, ASA grade, the results of preoperative liver function tests, size and number of CBD stones, CBD diameter, imaging data, distribution of stones, type of surgery, stone clearance from CBD, postoperative morbidity, mortality, conversion to open surgery, operative time, duration of postoperative hospital stay, cost of surgical procedures, hospitalization charges, postoperative complications, and short-term therapeutic efficacy. This study protocol was designed in agreement with the Declaration of Helsinki and the corresponding Chinese regulations and was approved by the ethical committee of Zhongnan Hospital of Wuhan University. This trial was registered in the Chinese Clinical Trial Registry with registration No.ChiCTR1800017592. The full date of first registration is 15/08/2018.

The work has been reported in line with the STROCSS criteria(20).

Precise assessment of the distribution and size of the stones and CBD diameter

Doppler ultrasound (US), computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) were jointly used to assess the number and size of stones and the diameter of the CBD before the operation. The number and size of the stones would be determined by the intraoperative findings. A nutritional risk assessment and evaluation of liver function grade and reserve were performed routinely for each patient.

Surgical technique

Laparoscope combined with duodenoscope

There are two patterns for laparoscope combined with duodenoscope, including two-stage (preoperative ERCP/EST or EPBD + LC ) management and one-stage (intraoperative ERCP/EST or EPBD + LC) management. A detailed surgical plan was formed based on the preoperative evaluation, and the main consideration was how to remove the stones as completely as possible. For pre-ERCP/EST or EPBD + LC, LC was subsequently performed as soon as technically feasible after ERCP/EST or EPBD, normally 48 to 72 hours later. One-stage management was with simultaneous ERCP/EPBD with a guidewire via TC, and LC was performed in the IO-ERCP/EPBD + LC group. Intraoperative cholangiography (IOC) was used to determine that the stones had been removed from the CBD.

Laparoscopy combined with intraoperative choledochoscopy

One-stage (LC + LCBDE) management was performed under general anesthesia with the patient placed in a head-up, left-tilted supine position. LCBDE could be categorized into LTC-CBDE, which removed the stone via the transcystic (TC) route, and LCCBDE, which removed the stone via the transductal (TD) route. For LTC-CBDE, when the CBD had been adequately exposed, a longitudinal incision was made in the catchment area of the cystic duct afflux to the CBD. The initial incision was just sufficient to allow entry of the flexible choledochoscope and to extract the stones using a wire basket. IOC was performed to confirm complete clearance of the CBD, and primary closure of the incision was performed using interrupted absorbable sutures (4 − 0 Vicryl; Ethicon, Cincinnati, OH). LCCBDE consisted of stone extraction through laparoscopic choledochotomy with placement of a T-tube drainage (LCTD) and LCCBDE + primary duct closure according to whether the T-tube was used. For LCTD, complete clearance of the distal CBD was confirmed only when the wire basket passed into the duodenum through the ampulla of Vater. A T-tube of appropriate size was introduced through the epigastric port and placed in the choledochotomy. Saline was injected into the T tube to rule out leakage. The T-tube was commonly removed 4 to 6 weeks after a routine, scheduled cholangiography to confirm no evidence of residual stones in the CBD. For LCCBDE + primary duct closure, the incised CBD was primarily closed using an absorbable suture after confirmation of complete clearance of the distal CBD, simultaneous with the choledochotomy.

Laparoscopy and choledochoscopy combined with the intraoperative duodenoscope or gastroscopy

For LC + LCCBDE + IOC + duodenoscope or Gastroscope, conventional LC was completed; then, the CBD was dissected, and the stones were extracted with a basket under choledochoscopic control. After clearance of the stones, the guidewire was advanced until its end had entered the duodenum from the CBD. The endoscopist then inserted its flexible duodenoscope or gastroscope from the mouth to the back of the throat, and the endoscopic nasobiliary drain tube was inserted into the CBD using the railroad technique with a guidewire. Finally, a cholangiogram was conducted to confirm complete clearance of the bile duct via the nasobiliary drainage tube, and the CBD wound was primarily closed using an absorbable suture.

Follow-up

All patients were followed up with regular visits at 1 week, 6 weeks, 3 months, 6 months, and 1 year or at any time if symptoms developed after discharge. At the 6-week follow-up evaluation, overall satisfaction was assessed on a verbal rating scale with scores of 0 (not satisfied), 1 (partially satisfied), 2 (satisfied), or 3 (very satisfied). A transabdominal US and liver function tests were performed at the 3-month follow-up to assess the status of the CBD. Immediate stone clearance was defined as complete depletion of stones during the operation. Final stone clearance was defined as removal of residual stones after the operation using a stone basket under choledochoscopy or a holmium laser. Postoperative residual stones were defined as remaining stones that could not be removed by any nonoperative treatments and were confirmed by US, CT or MRCP 3 months postoperatively.

Statistical analysis

Patient demographics, stone number, size, location, treatment method, duration of surgery, post-hospital stay, and average expenses are presented as counts, and the differences among groups were compared with the Chi-square test or Fisher’s exact test. Continuous variables are expressed as the mean ± standard deviation (SD) or the median and were compared by ANOVA or the Kruskal-Wallis H test. Additionally, any two groups were compared using Student’s t test or the Mann-Whitney test. The associations of age, gender, weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin(TBIL), γ-glutamy transpeptidase(γ-GT), alkaline phosphatase (ALP) with clinical prognosis were compared using univariate and multivariate logistic regression analysis. Significance was determined by a p value less than 0.05. All analyses were conducted using Statistical Package for the Social Sciences (SPSS 24.0 for Windows, Chicago, United States).

Study selection and characteristics

A total of 1256 patients with concomitant GB and CBD stones were enrolled in the study. Of these patients, 212 were excluded for various reasons. We analyzed 1044 patients who had undergone 6 different minimally invasive treatments and met the inclusion criteria (Figure 1). These treatment management protocols were compared retrospectively. No significant differences were found among the 6 groups in terms of age, gender, ASA classification, BMI, clinical presentation, ALT, AST, TBIL, γ-GT or ALP (S-Table 1). Pre-ERCP/EST or EPBD followed by LC was performed in 336 patients, IO-ERCP/EPBD with a guidewire via TC and LC simultaneously was performed in 385 patients, LTC-CBDE+LC was performed in 48 patients, LC+LCCBDE+primary duct closure was performed in 86 patients, LCCBDE+IOC+Gastroscope+LC was performed in 94 patients, and LCTD+LC was performed in 95 patients (Figure 1).

The distribution of CBD stones

First, we examined the distribution of CBD stones. The results revealed 5 stone distribution types, with 75.5% of the stones located in the CBD and 0.2% of the stones located in the common hepatic duct. We found that 6.8% of the stones were located in the CBD together with the common hepatic duct and that 0.8% of the stones were located in the common hepatic duct together with the hepatic duct and/or second-order branches of the hepatic duct. Finally, 16.5% of the stones were located in the extrahepatic and hepatic duct (Figure 2A).

Stone characteristics of patients with different minimally invasive procedures

In this study, we assessed the stone characteristics of patients with different surgical procedures according to CBD diameter and the maximal stone size and stone number (Table 1). There were only five cases in the Post-ERCP/EST or EPBD + LC group,. In all 5 patients who underwent post-ERCP/EST or EPBD+LC, no stones were present in the CBD before surgery; these patients were not checked by MRCP due to fixation of the internal bone with a steel plate or other reasons. The patients who underwent LC returned to the hospital because of acute cholangitis and then accepted the post-ERCP/EST or EPBD treatment. Therefore, we excluded the data for the Post-ERCP/EST or EPBD + LC group from the analysis of the patient stone characteristics. The median CBD diameter and the maximal stone size were smaller in the Pre-ERCP/EST or EPBD+LC and Io-EPBD+LC group than in the other groups, and no differences were observed between the two groups. The median CBD diameter and the maximal stone size in the LC+LCTD group were large in all groups. There were no differences in the median CBD diameter or the maximal stone size between the LC+LCCBDE+Gastroscope group and the LC+LCCBDE+primary closure group or between the LC+LTC-CBDE group and the Io-EPBD+LC group. The median CBD diameter was more than 10 mm in all patients in the LC+LCCBDE+Gastroscope, LC+LTC-CBDE, LC+LCCBDE+primary closure and LC+LCTD groups. The maximal stone size was no more than 2.0 cm in all groups except the LC+LCTD group. Regarding stone number, there were no differences between the less than or equal to 5 subgroup and the more than 5 subgroup in the Pre-ERCP/EST or EPBD+LC group and the IO-EPBD+LC group. The stone number was typically more than 5 in the LC+LCTD group but more commonly less than or equal to 5 in the LC+LTC-CBDE, LC+LCCBDE+Gastroscope and LC+LCBDE+primary closure groups.

Classification of concomitant GB and CBD stones

To identify the main factor that influences the choice of different minimally invasive surgical procedures, logistic regression analysis was performed. The six different minimally invasive surgical procedures were the dependent variable (Post-ERCP/EST or EPBD +LC was exclude because of the case was too small ), and the clinical features and the stone characteristics of the patients, including gender, age, BMI, liver function, CBD diameter, and stone number and stone size were the independent variables. The univariate and multivariate logistic regression analysis revealed significant differences in the correlation between the CBD diameter, stone number, stone size were independent risk factors for the clinical prognosis of patients (Table 2). Therefore, we made the choice of different surgical procedures depending on the CBD diameter, stone number and maximal stone size. Therefore, we created a new clinical classification for patients with concomitant GB and CBD stones based on the CBD diameter and stone size and number (Figure 2B): Type I: CBD diameter <1.0 cm; Type II: CBD diameter ≥1.0 cm and maximal stone <1.0 cm; type III: CBD diameter ≥1.0 cm, maximal stone ≥1.0 cm, and stone number ≤5; type IV: CBD diameter ≥1.0 cm, maximal stone ≥1.0 cm, and stone number >5. According to this classification, 262 type I patients, 519 type II patients, 146 type III patients, and 117 type IV patients underwent 2, 5, 4, and 3 kinds of minimally invasive surgery, respectively (Figure 2C).

Io-ERCP/EPBD+LC should be the first treatment choice option for type I

To screen the optimal minimally invasive treatments, we evaluated the surgical results, postoperative complications and follow-up complication for each type. First, we will consider the incidence rate of serious complications, residual stones, relapse, surgical success rate, average expense and postoperative hospital stay as assessment indicators when screening for the optimal procedure. For type I, two minimally invasive treatments were performed. 103 patients underwent a Pre-ERCP/EST or EPBD+LC, of whom 96 patients had a successful ERCP followed by cholecystectomy after a median duration of 3 days (range 1–8 days), 7 patients underwent unsuccessful ERCP , of which 4 patients converted to IO-ERCP/EPBD+LC after 4-6 days, 3 patients had to accept open surgery because of duodenum perforation. In addition,1 patient who had to convert to open surgery due to severe gallbladder inflammation. 159 patients underwent a IO-EPBD+LC, of which 135 patients who had a successful intraoperative EPBD with insertion of the wire through the cystic duct from the CBD to the duodenum and simultaneous LC. 22 patients completed surgery through changing surgical method because of the anatomical variation or obstruction of the gallbladder duct, we dissected the gallbladder duct and cut it at the confluence of the gallbladder neck duct and the common bile duct, and then to insert the wire through the confluence of the gallbladder neck duct and the common bile to the duodenum; 2 patients had to accept open surgery because of severe gallbladder inflammation. The CBD stone clearance, conversion to open surgery, mortality, and intra-operative blood loss were not significantly different between the Pre-ERCP/EST or EPBD+LC and IO-ERCP/EPBD+LC groups (Table 3). However, the average cost was cheaper and the postoperative hospitalization time was shorter in the IO-EPBD+LC group than in the Pre-ERCP/EST or EPBD+LC group, and the level of postoperative serum amylase and total complications in the IO-EPBD+LC group were significantly lower than those in the Pre-ERCP/EST or EPBD+LC group. In this study, most of Pre-ERCP/EST or EPBD+LC were performed in early stage. Recently, more IO-ERCP/EPBD+LC were performed. These results suggest that IO-ERCP/EPBD+LC is more suitable for the treatment of type I due to shorter surgical and hospital stay, and lower postoperative serum amylase levels.

LTC-CBDE+LC is more suitable for the treatment of patients with type II

Five minimally invasive treatments were performed for patients with type II (Figure 2C). 217 patients underwent Pre-ERCP/EST or EPBD+LC, of whom 5 patients had a failed ERCP and were converted to open surgery due to duodenum perforation or bleeding, and 3 patients were converted to open surgery due to severe inflammation and adhesion during laparoscopic cholecystectomy. The mean postoperative hospital stay was 7 days and the stone-free rate was 97.8% in this group. 168 patients had compilcations including postoperative uprising serum amylase, stone recurrence, reflux cholangitis, among which the postoperative serum amylase was uprise in 137 patients, 19 patients experienced recurrent bile duct stones at least 1 year after surgery. IO-ERCP/EPBD+LC was performed in 226 patients, of whom 5 patients were converted to LC+LCCBDE+IOC+Gastroscope due to cystic duct blockage, 4 patients were converted to open surgery due to severe inflammation and adhesion during laparoscopic cholecystectomy. The mean postoperative hospital stay was 3.5 days and the stone-free rate was 96.3% in this group. The postoperative serum amylase was uprise in 49 patients, 23 patients experienced recurrent bile duct stones at least 1 year after surgery. LTC-CBDE+LC was conducted in 48 patients, of whom 8 patients were converted to LC+LCCBDE+IOC+Gastroscope or LC+LCBDE +primary closure because the cystic duct was too small for passage of the 2.8 mm flexible choledochoscope. The mean postoperative hospital stay was 2.6 days and the stone-free rate was 100% in this group. 3 patients experienced recurrent bile duct stones at least 1 year after surgery, the total complication was 10.4%. 14 patients underwent LC+LCCBDE+primary duct closure, and 14 patients underwent LC+LCCBDE+IOC+Gastroscope. The CBD stone clearance, conversion to open surgery, mortality, stone recurrence and intraoperative blood loss were not significantly different among these minimally invasive treatments (Table 4). Postoperative hospital stay, increases in serum amylase and total complications were higher in the Pre-ERCP/EST or EPBD+LC group than in the other groups, which indicates that Pre-ERCP/EST or EPBD should be carefully selected. The total complications, operative time and average cost were lowest in the LTC-CBDE+LC group in all groups, however we should be careful for many patients who were change the treatment to LC+LCCBDE+IOC+Gastroscope or LC+LCBDE +primary closure because of the cystic duct was too small or was blocked for choledochoscope passage. The results for the IO-ERCP/EPBD+LC group were similar to those of the LC+LTC-CBDE group with respect to surgical success rate, operative time and total complications, but the average cost and the postoperative hospital stay were higher than that in the LC+LTC-CBDE group. Taken together, these results suggest that LTC-CBDE+LC should be the first choice for patients with type II, and those who fail due to cystic duct blockage preventing passage of the flexible choledochoscope should undergo LC+LCCBDE+IOC+Gastroscope or LC+LCBDE +primary closure as a replacement. In this study, mostly Pre-ERCP/EST or EPBD+LC and IO-ERCP/EPBD+LC were performed before 2020, however LTC-CBDE+LC were completed after 2020.

LC+LCCBDE+IOC+Gastroscope or duodenoscope is more appropriate for treating patients with type III

Four minimally invasive treatments were conducted for patients with type III. Successful completion of ERCP followed by cholecystectomy was achieved for 11 (68.8%) of the 16 patients in the Pre-ERCP/EST +LC group. Three cases (18.7%) were converted to open CBD exploration because of duodenal injury (2 patients) and injury to the posterior wall of the CBD (1 patient). Two cases (12.5%)were converted to LC+LCCBDE+IOC+Gastroscope because of an inability to identify the papilla (1 patient) and unsuccessful cannulation (1 patient). There are a patient died of serious complications (severe necrotizing pancreatitis due to ERCP secondary damage). All patients have varying degrees of complications including postoperative uprising serum amylase, stone recurrence, reflux cholangitis, and the mean postoperative hospital stay was longest in all groups. Laparoscopic surgery for CBD stones in various surgical groups, including LC+LCCBDE+primary duct closure, LC+LCCBDE+IOC+Gastroscope and LC+LCTD, have demonstrated a higher success rate and fewer complications. 57 patients underwent treatment using LC+LCCBDE+primary duct closure, 11 patients underwent LC+LCTD, and 62 patients underwent LC+LCCBDE+IOC+Gastroscope. The CBD stone clearance, conversion to open surgery, blood loss, operation time, and mortality did not significantly differ among the 3 laparoscopic surgery CBD stone groups (Table 5). The postoperative hospital stay and average costs were higher in the LC+LCTD group than in the LC+LCCBDE+IOC+Gastroscope and LC+LCCBDE+primary duct closure groups. Similar surgical results and complications, with the exception of an increasing trend associated with the risk of bile leakage, stenosis and recurrent cholangitis, were observed between the LC+LCCBDE+primary duct closure group and the LC+LCCBDE+IOC+Gastroscope group. Total complications were lowest in the LC+LCCBDE+IOC+Gastroscope group among the 4 minimally invasive treatments. These results suggest that LC+LCCBDE+IOC+Gastroscopeis more appropriate for the treatment of patients with type III.

LC+LCTD should be a first-line treatment for patients with type IV

Three minimally invasive treatments were performed for patients with type IV. 18 patients underwent LC+LCCBDE+IOC+Gastroscope, of whom 3 patients was converted to open surgery due to difficulty clearing the stone. LC+LCCBDE+primary duct closure was completed in 15 patients, of whom 2 patients was converted to LCTD and 3 patients were converted to open surgery due to difficulty clearing the stone. 84 patients underwent LC+LCTD, of whom 5 patients were converted to open surgery due to difficulty clearing the stone. Average cost, blood loss, operation time, and mortality did not significantly differ among the 3 groups (Table 6). However, the LC+LCTD group demonstrated lower CBD stone clearance and longer postoperative hospitalization durations than the other groups. The reason lies in that the CBD stone number was more and size was larger , the surgery often chose to the LC+LCTD. In this study, the stone number was more and the size was larger in the LC+LCTD group than the LC+LCCBDE+IOC+Gastroscope and LC+LCCBDE+primary duct closure groups. The maximum stone size was less than 1.5 cm in the LC+LCCBDE+IOC+Gastroscope and LC+LCCBDE+primary duct closure groups, however the maximum stone size was often more than 2.0 cm and the stone number was more in the LC+LCTD group . Most importantly, the total complications were lower in the LC+LCTD group than in the LC+LCCBDE+IOC+Gastroscope and LC+LCCBDE+primary duct closure groups. Therefore, LC+LCTD is more appropriate for the treatment of type IV.

The optimal minimally invasive management protocol for concomitant GB and CBD stones is controversial, and several different approaches are used to remove such stones(6). The selected approach is influenced by multiple factors, such as the nature of the presentation, surgeon preference and expertise, and the availability of appropriate facilities(5, 21). In this study, we summarized six surgical options for the treatment of concomitant GB and CBD stones (Fig. 1). The main techniques included the single stage approach of LCBDE + LC and the two-stage approach of ERCP stone removal followed by LC. The concrete methods are currently as follows. 1) Laparoscopy combined with intraoperative choledochoscopy: LC/LCBDE + IOC; LCBDE consists of stone removal via a TC or TD route. For LCBDE via TD, there are two options based on whether T-tube placement is required; T-tube placement is not required for LC + LCCBDE + primary duct closure but is required for LCTD. 2) Laparoscopy combined with duodenoscopy (three patterns): a preoperative ERCP with EST or EPBD followed by LC (Pre-ERCP/EST or EPBD + LC); LC with intraoperative ERCP and EST or EPBD according to the rendezvous technique (IO-ERCP/EST or EPBD + LC); or LC followed by postoperative ERCP (Post-ERCP/EST or EPBD + LC). 3) Laparoscopy and choledochoscopy combined with intraoperative gastroscopy (LC + LCCBDE + IOC + Gastroscope or duodenoscope). This study evaluated the advantages and disadvantages of each treatment option and to establish an optimal minimally invasive treatment mode as clear future guidelines.

First, we determined the main factor that influenced the choice of different minimally invasive surgical produces using logistic regression analysis. Because there were only 5 cases of post-ERCP/EST or EPBD + LC, this treatment was performed as a remedial measure because no stones were present in the CBD before surgery. Thus, post-ERCP/EST or EPBD + LC was not an ideal treatment model for CBD stones and was excluded. Thus, we chose the six different minimally invasive surgical procedures, excluding post-ERCP/EST or EPBD + LC, as the dependent variable, and the clinical features (including stone characteristics) of the patients served as the independent variables. We found that the choice of different surgical produces depended on the CBD diameter, stone number and stone size. Initially, we predicted that the choice of different surgical procedures was also associated with the bilirubin level; however, the bilirubin level was closely related to whether the stone was incarcerated, and incarcerated CBD stones were often accompanied by acute cholangitis, which was excluded from the analysis. This exclusion provides a possible explanation for why the choice of different surgical procedures was independent of bilirubin level. We also found that the choice of different surgical procedures was independent of the stone location within the CBD. Therefore, we developed a model for disease classification based on the inside CBD diameter, the maximum stone size and the stone number. All patients with concomitant GB and CBD stones were sorted into four types(Fig. 2B).

To establish an optimal minimally invasive treatment mode for concomitant GB and CBD stones, we compared the benefits and drawbacks of different minimally invasive treatment approaches for CBD stone removal in four different types according to the classification. We first considered the incidence rate of serious complications, residual stones, relapse, surgical success rate, average expense and postoperative hospital stay as assessment indicators when screening the optimal procedures. For type I, two minimally invasive treatment approaches, including Pre-ERCP/EST or EPBD + LC and IO-EPBD + LC were utilized. IO-EPBD with a guidewire via TC + LC was the best strategy for type I patients due to shorter surgical and hospital stay, and lower postoperative serum amylase levels. For type II, 5 minimally invasive treatment approaches were utilized. The optimal surgical method depends on whether the gallbladder neck canal is unobstructed and whether it can pass through slender choledochoscopy when the confluence of the cystic duct and the common bile duct was slightly incised. If cystic duct was unobstructed and enough big to pass slender choledochoscopy, the LC + LTCBDE group is recommended as the preferred treatment method, due to its lowest average cost and shortest hospital stay. IO-ERCP/EPBD + LC should be used if cystic duct was not blocked up but the caliber was not enough big to pass slender choledochoscopy; LC + LCCBDE + primary duct-closure should be better way to clear stones if cystic duct was blocked. For type III, 4 kinds of treatments were selected. LC + LCCBDE + IOC + Gastroscope was more appropriate treatment. For type IV, 3 kinds of minimally invasive treatment approaches were utilized, and LC + LCTD was an ideal treatment method.

For patients with a maximum stone size less than 1.0 cm and CBD less than 1.0 cm, whether Pre-ERCP/EST or EPBD + LC and IO-ERCP/EPBD with a guidewire via TC + LC is the better option has been highly controversial. Pre-ERCP/EST was previously the most common routine therapeutic procedure used. It is safe and effective, but severe perforation or massive bleeding and permanent destruction of the Oddi sphincter are the main causes of mortality(8, 22). Permanent and long-term complications, such as intestinal content reflux, biliary tract inflammation and stone recurrence, are the basis of the argument against the use of EST(23–25). However, limited EST + EPBD appears to be a more reasonable alternative procedure. In this real-world study, EPBD was only performed in selected patients, i.e., patients with an altered anatomy or coagulopathy because of a higher incidence of post-ERCP pancreatitis in the Pre-ERCP/EST or EPBD + LC group. In addition, Pre-ERCP/EST or EPBD has many drawbacks: during LC, 12.9% of patients who had undergone preoperative endoscopic clearance of the CBD still had CBD stones(26). These stones may either be retained (due to false-negative ERCP or incomplete stone extraction) or new stones (due to passage of stones from the GB into the CBD during the interval before LC). This option also requires two periods of anesthesia and sometimes two hospital admissions. Therefore, current evidence tends to support IO-ERCP/EPBD with a guidewire via TC + LC as superior to Pre-ERCP/EST or EPBD. No post-EPBD pancreatitis was observed in patients who underwent IO-ERCP/EPBD with a guidewire via TC + LC. This technology has the advantage of being an ideal management protocol compared with Pre-ERCP/EST or EPBD + LC. First, Pre-ERCP/EST or EPBD + LC requires two interventions and occasionally two hospital admissions, which prolongs the hospital stay and increases costs. IO-ERCP/EPBD with a guidewire via TC + LC has the advantage of being a one stage procedure, could avoid cutting the sphincter of Oddi and appears to be more cost-effective than Pre-ERCP/EST or EPBD + LC. Second, IO-ERCP/EPBD with a guidewire via TC is easier to perform because of the wire guidance. The success rate of ERCP in our study of IO-ERCP/EPBD with a guidewire via TC was 100%, which was comparable to the rate of 91.3% for Pre-ERCP/EST or EPBD + LC. However, 3 patients with ERCP failure in the Pre-ERCP/EST or EPBD group successfully underwent IO-ERCP/EPBD with a guidewire via TC. Moreover, the incidence and severity of complications was higher for Pre-ERCP/EST or EPBD. If failure occurred in the Pre-ERCP/EST or EPBD group, most cases were converted to open surgery because of serious complications. We think the 100% ERCP success rate for IO-ERCP/EPBD with a guidewire via TC resulted from the clear cystic duct when the internal CBD diameter was less than 1.0 cm and there was no chronic inflammation. These results suggest that IO-ERCP/EPBD with a guidewire via TC is preferable for patients with a maximal stone size less than 1.0 cm and CBD less than 1.0 cm. In addition, Pre-ERCP/EST or EPBD + LC should be chosen with great caution as the treatment mode for type III patients. In this study, there are a patient died of serious complications (severe necrotizing pancreatitis due to ERCP secondary damage). All patients have varying degrees of complications including postoperative uprising serum amylase, stone recurrence, reflux cholangitis, and the mean postoperative hospital stay was longest longer.

When the maximal stone size was less than 1.0 cm and the CBD was greater than 1.0 cm, LTC-CBDE showed advantages in terms of cost compared with IO-ERCP/EPBD with a guidewire via TC. Additionally, there were no differences between the two groups with respect to hospital stay, operation time, CBD stone clearance, surgical success rate and complications(11). Currently, LCBDE can be categorized into the TC (LTC-CBDE) and choledochotomy (LCCBDE) approaches. For LCCBDE, the CBD integrity is lost due to the incision over the CBD. In contrast, the cystic duct is used for LTC-CBDE, thus minimizing the size of the incision over the CBD. Moreover, application of a separate laparoscopic suture over the stump of the cystic duct dramatically decreases the postoperative incidence of bile leakage(27, 28). Therefore, it may be a preferred technique over a choledochotomy incision. An important advantage of the TC approach is that it leaves intact both the CBD and the sphincter of the duodenal papilla(27). As confirmed by our results, LTC-CBDE is certainly the least invasive, safest, and most efficient option, with low morbidity rates observed in this study. LTC-CBDE avoids choledochotomy and eliminates the subsequent requirement for a T-tube, thus avoiding T-tube prolapse or displacement, CBD stricture, electrolyte imbalance, acid-base balance disorders, and complications caused by bile drainage and invasive treatments. These results were also supported by other studies(28–30). Additionally, the cystic duct itself functions like a sphincter and can coordinate GB filling. The diameter of the confluence between the cystic and hepatic ducts is wider than the diameter of the CBD. The diameter of the cystic duct can expand to 1 cm or more when the CBD is obstructed, and the expansion is more apparent at the confluence. The anatomical features of the cystic duct and CBD create favorable conditions for LTC-CBDE. However, the success of the TC approach depends on whether the choledochoscope can enter the CBD. The success of LTC-CBDE depends on the anatomy of the cystic duct (duct diameter, bifurcation angle of the cystic and hepatic ducts). If the stone bulk was large or the cystic duct was blocked, complete clearance of the CBD cannot be completed via TC exploration(11, 28). Additionally, many patients had stones in the supracystic portion of the CBD, and these would be difficult to remove via the TC route. A success rate of 88.5% was demonstrated among all patients for LTC-CBDE in the present study. Therefore, we chose LCCBDE + IOC + Gastroscope as a reasonable alternative. Compared with LTC-CBDE, LCCBDE + IOC + Gastroscope has the disadvantage of the incision over the CBD and the need for more equipment and higher costs. However, LCCBDE + IOC + Gastroscope has the advantage of a higher success rate compared with LTC-CBDE and avoids the use of the T-tube compared with LCTD. LCCBDE + primary duct closure was similar to LCCBDE + IOC + Gastroscope. The greatest problem with the former strategy was the delayed bile leakage compared with LCCBDE + IOC + Gastroscope. Therefore, LTC-CBDE is the ideal treatment for CBD stones in patients with a maximum stone size less than 1.0 cm and CBD greater than 1.0 cm. LCCBDE + IOC + Gastroscope could be a reasonable alternative when LTC-CBDE fails. However, LTC-CBDE is not recommended when the internal CBD diameter is less than 1.0 cm because of the stricture risk of CBD.

For patients with a maximum stone size of greater than 1.0 cm and stone number less than 5, LTC-CBDE has several technical limitations, and the factors that contribute to the failure of this approach included an unfavorable cystic duct anatomy, the presence of stones with a diameter > 0.6 cm, or a large number of stones. In the present study, we modified this approach: we slit the cystic duct, and the confluence part was cut open 3–5 mm at the superior and inferior margins. Using this approach, it was easy to insert the choledochoscope into the cystic duct without balloon dilation. Clearing of the CBD using this approach, as described herein, allowed us to remove CBD stones larger than 6 mm in diameter with a single procedure. However, if the CBD stones were larger than 10 mm, it was difficult to remove them even when crushing the stones and utilizing a prolonged operative time(28). The complementary advantages of the three endoscopes, gastroscope, laparoscope and choledochoscope, in a single-stage approach rendered an effective, feasible and safe procedure with fewer complications than using the other treatments for this kind of patient(31). The guidewire traveled to the CBD via choledochoscopy, passed the ampulla of Vater and arrived at the lumen of the descending duodenum. The guidewire was directed with ease under a gastroscope. An ENBD tube was then inserted under the guidance of the guidewire to the CBD. This method not only avoided the risk of post-ERCP pancreatitis but also preserved the function of the sphincter of Oddi. The combined tri-endoscopic approach has the advantage of a higher success rate than LTC-CBDE and avoids the use of the T-tube compared with LCTD. LCCBDE + primary duct closure was similar to LCCBDE + IOC + Gastroscope. The greatest problem with the former strategy was the delayed bile leakage compared with that observed in LCCBDE + IOC + Gastroscope. Therefore, the combined tri-endoscopic approach is the ideal treatment for CBD stones in patients with a maximum stone size of more than 1.0 cm and fewer than 5 stones.

However, it is difficult to achieve complete clearance of the CBD by LTC-CBDE, LC + LCCBDE + primary closure and LC + LCCBDE + IOC + Gastroscope when the maximum stone size is greater than 2.0 cm and the stone number is more than 5. Long tortuous cystic ducts with low insertions will likely make LTC-CBDE challenging if not impossible. Similarly, multiple large stones in a dilated CBD will be difficult and time-consuming to remove using LTC-CBDE, with a significant risk of displacing some of the stones into the proximal CBD, which then cannot be retrieved. Our results confirmed that the retained stones were larger in the LC + LCCBDE + primary closure and LC + LCCBDE + IOC + Gastroscope groups compared with the LCTD group. All these factors must be considered when determining the best approach. LCTD results have shown that this laparoscopic procedure is superior to LC + LCCBDE + primary closure and LC + LCCBDE + IOC + Gastroscope with regard to a reduced postoperative stone retention rate. Although LCTD requires use of the T-tube, complete removal of the stone and prevention of stone retention were key to the success or failure of the operation. Therefore, a suggested algorithm is to use LCTD for patients with type IV, especially for patients with a maximum stone size larger than 2.0 cm or the stone number was more than 5.

In summary, we have developed a novel simple clinical classification system based on the CBD diameter, stone size and stone number. This classification system can be used to guide surgeons to choose an optimal minimally invasive treatment mode for each patient type to reduce residual stones and relapse and to improve the therapeutic efficacy. Further prospective studies with larger subject numbers are needed to validate the applicability of this clinical classification system.

LC, laparoscopic cholecystectomy; IOC, intraoperative cholangiography; CBD, common bile duct; GB, gallbladder; LCBDE, laparoscopic common bile duct exploration; ERCP, endoscopic retrograde cholangiopancreatography; pre-ERCP, preoperative ERCP; EPBD, endoscopic papillary balloon dilatation; EST, endoscopic sphincterotomy; ENBD, endoscopic nasobiliary drainage; LCTD, laparoscopic choledochotomy stone extraction with T-tube drainage; OCBDE, open common bile duct exploration; LCCBDE, laparoscopic choledochotomy for common bile duct exploration; LTC-CBDE, laparoscopic transcystic common bile duct exploration; ATP, adenosine triphosphate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma glutamyl transpeptidase; DBIL, direct bilirubin; TBIL, total bilirubin; ALP, alkaline phosphatase; γ-GT, γ-glutamy transpeptidase

Declaration of Interest Statement

All authors disclosed no relevant relationships.

Ethical approval

This study protocol was designed in agreement with the Declaration of Helsinki and the corresponding Chinese regulations and was approved by the ethical committee of Zhongnan Hospital of Wuhan University (Scientific Ethics Quick Review Number: 2017134).

Availability of data and materials

Not applicable.

Consent for publication

Not applicable.

Competing interests

None of the authors have any competing interests.

Hungness ES, Soper NJ. Management of common bile duct stones. J Gastrointest Surg. 2006;10(4):612–9.
Tsukamoto T, Nobori C, Kunimoto T, Kaizaki R, Inoue T, Nishiguchi Y. Laparoscopic lithotripsy and lithotomy of impacted stone at the terminal end of the common bile duct using a laparotomy biliary lithotomy spoon: A case report. Int J Surg Case Rep. 2022;90:106753.
Simon M, Hassan IN, Ramasamy D, Wilson D. Primary Choledocholithiasis 15 Years Postcholecystectomy. Case Rep Med. 2020;2020:3265010.
Zheng YM, Liu DB, Wang YH, Liu JF, Liu LW, Bai XS, et al. [Operative method choice and strategy of laparoscopic surgery therapy for gallbladder stones and common bile duct stones]. Zhonghua Wai Ke Za Zhi. 2019;57(4):282–7.
Nassar AHM, Ng HJ, Katbeh T, Cannings E. Conventional Surgical Management of Bile Duct Stones: A Service Model and Outcomes of 1318 Laparoscopic Explorations. Ann Surg. 2022;276(5):e493–e501.
Barreras Gonzalez JE, Torres Pena R, Ruiz Torres J, Martinez Alfonso MA, Brizuela Quintanilla R, Morera Perez M. Endoscopic versus laparoscopic treatment for choledocholithiasis: a prospective randomized controlled trial. Endoscopy Int open. 2016;4(11):E1188–E93.
Mallick R, Rank K, Ronstrom C, Amateau SK, Arain M, Attam R, et al. Single-session laparoscopic cholecystectomy and ERCP: a valid option for the management of choledocholithiasis. Gastrointest Endosc. 2016;84(4):639–45.
Barakat MT, Banerjee S. Sequential endoscopist-driven phone calls improve the capture rate of adverse events after ERCP: a prospective study. Gastrointest Endosc. 2021;93(4):902–10. e1.
Medhioub M, Khsiba A, Mahmoudi M, Ben Mohamed A, Hamzaoui L, Azouz MM. Preoperative endoscopic treatment for the management of concomitant gallstones and common bile duct stones. Tunis Med. 2021;99(2):233–7.
Talukdar R. Complications of ERCP. Best Pract Res Clin Gastroenterol. 2016;30(5):793–805.
Fugazza A, Fabbri C, Di Mitri R, Petrone MC, Colombo M, Cugia L, et al. EUS-guided choledochoduodenostomy for malignant distal biliary obstruction after failed ERCP: a retrospective nationwide analysis. Gastrointest Endosc. 2022;95(5):896–904e1.
Xu Y, Dong C, Ma K, Long F, Jiang K, Shao P, et al. Spontaneously removed biliary stent drainage versus T-tube drainage after laparoscopic common bile duct exploration. Medicine. 2016;95(39):e5011.
Shively EH, Richardson M, Romines R, Englund G, Watkins J. Laparoscopic common duct exploration in 90-bed rural hospital. Am Surg. 2010;76(6):626–9.
Martin IJ, Bailey IS, Rhodes M, O'Rourke N, Nathanson L, Fielding G. Towards T-tube free laparoscopic bile duct exploration: a methodologic evolution during 300 consecutive procedures. Ann Surg. 1998;228(1):29–34.
Lu J, Xiong XZ, Cheng Y, Lin YX, Zhou RX, You Z, et al. One-stage versus two-stage management for concomitant gallbladder stones and common bile duct stones in patients with obstructive jaundice. Am Surg. 2013;79(11):1142–8.
Bansal VK, Misra MC, Rajan K, Kilambi R, Kumar S, Krishna A, et al. Single-stage laparoscopic common bile duct exploration and cholecystectomy versus two-stage endoscopic stone extraction followed by laparoscopic cholecystectomy for patients with concomitant gallbladder stones and common bile duct stones: a randomized controlled trial. Surg Endosc. 2014;28(3):875–85.
Tranter SE, Thompson MH. Comparison of endoscopic sphincterotomy and laparoscopic exploration of the common bile duct. Br J Surg. 2002;89(12):1495–504.
Nilsson E, Sandzen B. Meta-analysis of endoscopy and surgery versus surgery alone for common bile duct stones with the gallbladder in situ (Br J Surg. 2006; 93; 1185–1191). The British journal of surgery. 2007;94(2):249 – 50.
Rabago LR, Chico I, Collado D, Olivares A, Ortega A, Quintanilla E, et al. Single-stage treatment with intraoperative ERCP: management of patients with possible choledocholithiasis and gallbladder in situ in a non-tertiary Spanish hospital. Surg Endosc. 2012;26(4):1028–34.
Mathew G, Agha R, Group SSTROCSS. 2021: Strengthening the reporting of cohort, cross-sectional and case-control studies in surgery. Ann Med Surg (Lond). 2021;72:103026.
Dasari BV, Tan CJ, Gurusamy KS, Martin DJ, Kirk G, McKie L, et al. Surgical versus endoscopic treatment of bile duct stones. Cochrane Database Syst Rev. 2013;2013(12):CD003327.
Facciorusso A, Gkolfakis P, Ramai D, Tziatzios G, Lester J, Crino SF et al. Endoscopic Treatment of Large Bile Duct Stones: A Systematic Review and Network Meta-Analysis. Clin Gastroenterol Hepatol. 2021.
Beltz S, Sarkar A, Loren DE, Andrel J, Kowalski T, Siddiqui AA. Risk stratification for the development of post-ERCP pancreatitis by sphincter of Oddi dysfunction classification. South Med J. 2013;106(5):298–302.
Murray WR. Reducing the incidence and severity of post ERCP pancreatitis. Scand J Surg. 2005;94(2):112–6.
Sotoudehmanesh R, Eloubeidi MA, Asgari AA, Farsinejad M, Khatibian M. A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis. Am J Gastroenterol. 2014;109(6):903–9.
Nair MS, Re. Preoperative versus intraoperative endoscopic sphincterotomy for management of common bile duct stones. Surg Endosc. 2011;25(8):2758. author reply 9.
Lee SE. One-stage versus two-stage approach for concomitant gallbladder and common bile duct stones: which one is more proper in patients over 80 years old? J Minim Invasive Surg. 2022;25(1):7–8.
Otani T, Yokoyama N, Sato D, Kobayashi K, Iwaya A, Kuwabara S, et al. Safety and efficacy of a novel continuous incision technique for laparoscopic transcystic choledocholithotomy. Asian J Endosc Surg. 2017;10(3):282–8.
Hanif F, Ahmed Z, Samie MA, Nassar AH. Laparoscopic transcystic bile duct exploration: the treatment of first choice for common bile duct stones. Surg Endosc. 2010;24(7):1552–6.
Al-Ardah M, Barnett RE, Morris S, Abdelrahman T, Nutt M, Boyce T, et al. Lessons learnt from the first 200 unselected consecutive cases of laparoscopic exploration of common bile duct stones at a district general hospital. Surg Endosc. 2021;35(11):6268–77.
Lv F, Zhang S, Ji M, Wang Y, Li P, Han W. Single-stage management with combined tri-endoscopic approach for concomitant cholecystolithiasis and choledocholithiasis. Surg Endosc. 2016;30(12):5615–20.

Table 1 Stone characteristics of the patients with different surgical produces

Operative tactics	Cases	Diameter of CBD(mm)	Maximal stone size(mm)	Number of stones
Operative tactics	Cases	Diameter of CBD(mm)	Maximal stone size(mm)	≤5	> 5
Pre-ERCP+LC	336	10.0(8.0, 13.0)b,c,d,e	8.0(5.0, 12.0)b,c,d,e	209(62.2%)	127(37.8%)c,d,e
Io-ERCP+LC	385	11.0(9.0, 14.0)f,g,h,i	8.5(5.0, 12.0)f,g,h,i	273(70.9%)	112(29. 1%)g,h,i
LC+LCCBDE+	94	14.0(13.0, 16.0)j	11.0(8.0, 14.0)j	55(58.5%)	39(41.5%)j,k,l
Gastroscope
LC+LCTD	95	18.0(14.7,20.3)m,n	15.5(14.3, 18.5)m,n	10(10.5%)	85(89.5%)m,n
LC+LTC-CBDE	48	12.5(11.0, 14.5)o	10.5(9.0, 12.0)o	37(77. 1%)	11 (22.9%)
LC+LCCBDE+
primary closure	86	14.5(14.0, 16.0)	13. 0(10.5, 15.0)	64(74.4%)	22(25.6%)
p value		<0.001	0.002		0.013

a. Pre-ERCP+LC vs Io-ERCP+LC p＜0.05;
b. Pre-ERCP+LC vs LC+LCCBDE+Gastroscope p＜0.05;
c. Pre-ERCP+LC vs LC+LCTD, p＜0.05;
d. Pre-ERCP+LC vs LC+LTC-CBDE p＜0.05;

e. Pre-ERCP+LC vs LC+LCCBDE+primary closure, p＜0.05;

f. Io-ERCP+LC vs LC+LCCBDE+Gastroscope, p＜0.05;
g. Io-ERCP+LC vs LC+ LCTD, p＜0.05;

h. Io-ERCP+LC vs LC+LCCBDE;

i. Io-ERCP+LC vs LC+LCCBDE+primary closure, p＜0.05;

j. LC+LCCBDE+Gastroscope vs LC+LCTD;

k. LC+LCCBDE+Gastroscope vs LC+LTCBDE;

l. LC+LCCBDE+Gastroscope vs LC+LCCBDE+primary closure, p＜0.05;

m. LC+ LCTD vs LC+LTC-CBDE, p＜0.05;
n. LC+ LCTD vs LC+LCCBDE+primary closure p＜0.05;

o. LC+LTC-CBDE vs LC+LCCBDE+primary closure, p＜0.05

Table 2 Logistics Regression Analysis between surgical procedures and clinical data

Characteristics	Univariate analysis		Multivariate analysis
Characteristics	Odds Ratio (95% CI)	P value	Odds Ratio (95% CI)	P value
Gender
female	Reference
male	1.190 (0.724 - 1.958)	0.493
Age	1.010 (0.992 - 1.028)	0.269
Diameter of CBDS(mm)	1.285 (1.206 - 1.370)	< 0.001	1.142 (1.048 - 1.243)	0.002
Stone size(mm)	1.371 (1.260 - 1.491)	< 0.001	1.201 (1.083 - 1.333)	< 0.001
Stone number
single	Reference		Reference
multiple	6.825 (2.423 - 19.219)	< 0.001	4.614 (1.576 - 13.508)	0.005
Weight(kg)	0.999 (0.976 - 1.021)	0.903
ALT（U/L）	0.999 (0.997 - 1.001)	0.322
AST（U/L）	0.999 (0.996 - 1.001)	0.274
TBIL(mmol/L)	1.000 (0.996 - 1.003)	0.959
ALP（U/L)	1.001 (0.999 - 1.002)	0.254
γ-GT(U/L)	1.000 (0.999 - 1.001)	0.711

Table 3 Comparison of Surgical Results and complications in patients with Type Ⅰ

	Pre-ERCP+LC	Io-ERCP+LC	p value
	(n=103)	(n=159)	p value
Preoperative indicators
Age	56.6±10.4	57.4±14.2	0.623
Gender (female)	51(49.5%)	81(50.9%)	0.139
ASA grade	2.3±0.2	2.2±0.5	0.055
Body mass index	21.9±2.8	22.7±3.8	0.067
Medical history
Diabetes	18(17.5%)	16(10.1%)	0.081
Hypertension	17(16.5%)	27(17.0%)	0.920
Liver function
TBIL (µmol/L)	43.3±35.6	50.2±40.6	0.160
ALT level (U/L)	143.2±116.7	133.8±114.1	0.519
AST level (U/L)	115.3±65.1	130.8±62.9	0.056
γ-GT (U/L)	242.2±157.4	280.9±204.1	0.103
ALP (U/L)	199.7±136.8	211.3±147.7	0.523
Surgical Results
Average expenses	36132.1±4804.9	30850.8±2069.7	0.015
Postoperative hospital stay (days)	6.0(5.0,9.0)	3.0(2.00,5.0)	＜0.001
Intra-operative blood loss(ml)	10.0(5.0,20.0)	10.0(5.0,20.0)	0.834
Operative time (minutes)	116.5±18.9	88.4±25.2	＜0.001
CBDS clearance	101(98.0%)	157(98.7%)	1.000
Conversion to open surgery	4 (3.9%)	2(1.3%)	0.547

ERCP failure	7（6.8%）	2(1.3%)	＜0.001
Mortality	0(0.0%)	0(0.0%)
Postoperative complications
Uprising serum amylase	82(75.2%)	31(19.4%)	＜0.001
Bile leakage	0(0.0%)	0(0.0%)
Bleeding	2(1.9%)	0(0.0%)
Perforation	1(0.9%)	0(0.0%)
Cholangitis	0(0.0%)	0(0.0%)
Pleural effusion	1(0.9%)	0(0.0%)
Pneumonia	1(0.9%)	0(0.0%)
T-tube displacement	0(0.0%)	0(0.0%)
Multiple organ failure	0(0.0%)	0(0.0%)
Follow-up complications
Stone recurrence	5(4.9%)	6(3.8%)	1.000
Stricture of CBD	0(0.0%)	0(0.0%)
Reflux cholangitis	1(0.9%)	1(0.1%)
Total Complication	93(85.3%)	37(23.2%)	＜0.001

Table 4 Comparison of Surgical Results and complications in patients with Type Ⅱ

	Pre-ERCP+LC	Io-ERCP+LC	LC+LCCBDE+ Gastroscope		LC+LTCBDE	LC+LCBDE +primary closure	p value
	(n=217)	(n=226)		(n=14)	(n=48)	(n=14)	p value
Preoperative indicators
Age	55.9±13.2	61.1±16.8		51.9±11.8	50.9±14.3	53.9±13.1	0.573
Gender (female)	98(45.2%)	145(64.2%)		6(42.9%)	23(47.9%)	4(28.6%)	0.489
ASA grade	2.2±0.5	2.0±0.4		1.9±0.4	1.6±0.3	1.8±0.2	0.218
Body mass index	20.8±3.7	21.3±4.0		22.3±2.8	22.7±2.2	23.1±3.6	0.192
Medical history
Diabetes	31(14.3%)	25(11.1%)		2(14.3%)	6(12.5%)	2(14.3%)	0.731
Hypertension	34(15.7%)	41(18.1%)		1(7.1%)	8(16.7%)	3(21.4%)	0.943
Liver function
TBIL (µmol/L)	44.8±39.6	50.6±41.8		53.4±42.9	57.6±40.7	62.9±58.0	0.381
ALT level (U/L)	147.3±143.5	134.2±110.2		131.7±130.4	139.7±97.1	141.5±130.3	0.139
AST level (U/L)	100.7±68.9	153.2±80.9		169.2±99.7	113.7±71.2	133.5±111.5	0.097
γ-GT (U/L)	209.3±191.0	288.5±261.3		272.1±195.4	258.6±149.3	269.3±217.5	0.328
ALP (U/L)	220.7±172.5	210.4±183.1		176.9±142.8	215.1±159.4	222.9±173.6	0.069
Surgical results
Average expenses	37304.4±4497.1	30611.7±1671.4^a		34704.6±3624.6	22185.7±3480.3^cfhj	33657.3±2990.9^d	<0.001
Postoperative hospital stay(d)	7.0(6.0,9.5)	3.5(3.0,5.5)^a		3.5(3.0,6.0)^b	2.6(2.0,5.0)^c	4.0(4.3, 7.9)^d	0.021
Intra-operative blood loss(ml)	20.0(10.0,30.0)	20.0(20.00,62.5)		50.0(10.0,80.0)	20.0(10.0,50.0)	50.0(25.0,95.0)	0.329
Operation time(min)	122.8±18.1	98.4±28.6^a,e,g		127.7±45.9	104.1±33.5^c,h,j	133.0±56.4	0.029
CBDS clearance	214(97.8%)	218(96.3%)		14(100%)	47(97.4%)	13(92.9%)	0.661
Conversion to open surgery	8(3.7%)	4(1.8%)		1(7.1%)	1(2.1%)	1(7.1%)	0.310
Mortality	0(0.0%)	0(0.0%)		0(0.0%)	0(0.0%)	0(0.0%)
Postoperative complications
Uprising serum amylase	137(63.1%)^a,b,c,d	49(21.7%)^f,g		2(14.3%)	0(0.0%)	0(0.0%)	<0.001
Bile leakage	0(0.0%)	0(0.0%)		0(0.0%)	2(4.2%)	1(7.1%)
Bleeding	4(1.8%)	0(0.0%)		0(0.0%)	0(0.0%)	1(7.1%)
Perforation	1(0.5%)	0(0.0%)		0(0.0%)	0(0.0%)	0(0.0%)
Cholangitis	0(0.0%)	0(0.0%)		1(6.3%)	0(0.0%)	1(8.3%)
Pleural effusion	0(0.0%)	0(0.0%)		0(0.0%)	0(0.0%)	0(0.0%)
Pneumonia	0(0.0%)	0(0.0%)		0(0.0%)	0(0.0%)	0(0.0%)
T-tube displacement	0(0.0%)	0(0.0%)		0(0.0%)	0(0.0%)	00.0%)
Multiple organ failure	0(0.0%)	0(0.0%)		0(0.0%)	0(0.0%)	0(0.0%)
Follow-up complications
Stone recurrence	19(8.8%)	23(10.2%)		2(14.2%)	3(6.3%)	1(7.1%)	0.458
Stricture of CBD	0(0.0%)	0(0.0%)		0(0.0%)	0(0.0%)	0(0.0%)
Reflux cholangitis	2(0.9%)	1(0.04%)		0(0.0%)	0(0.0%)	0(0.0%)
Total complication	168(77.7%)^a,b,c,	73(32.3%)^f,		5(35.7%)^h	5(10.4%)^j	4(28.6%)	<0.001

a. PreERCP+LC vs Io-ERCP+LC, p＜0.05; b: Pre-ERCP+LC vs LC+LTCBDE+ Gastroscope , p＜0.05;

c. Pre-ERCP+LC vs LC+LTCBDE, p＜0.05; d: Pre-ERCP+LC vs LC+LCBDE +primary closure, p＜0.05;

e. Io-ERCP+LC vs LC+LTCBDE+ Gastroscope , p＜0.05; f: Io-ERCP+LC vs LC+LTCBDE, p＜0.05;

g. Io-ERCP+LC vs LC+LCBDE +primary closure, p＜0.05;

h. LC+LTCBDE+ Gastroscope vs LC+LTCBDE , p＜0.05;

i. LC+LTCBDE+ Gastroscope vs LC+LCBDE +primary closure, p＜0.05;

j. LC+LTCBDE vs LC+LCBDE +primary closure, p＜0.05

Table 5 Comparison of Surgical Results and complications in patients with Type Ⅲ

	Pre-ERCP+LC	LC+LCCBDE+	LC+LCTD	LC+LCBDE+	p
	(n=16)	Gastroscope (n=62)	(n=11)	primary closure (n=57)	value
Preoperative indicators
Age	57.6±11.2	59.7±16.1	52.9±10.7	56.4±12.3	0.358
Gender (female)	11(68.8%)	30(48.4%)	5(45.5%)	25(43.9%)	0.339
ASA grade	2.1±0.2	2.0±0.5	2.0±0.1	1.8±0.5	0.419
Body mass index	21.7±1.9	23.2±2.4	20.7±2.7	21.8±2.1	0.267
Medical history
Diabetes	2(12.5%)	7(11.3%)	1(9.1%)	8(14.0%)	0.482
Hypertension	3(18.8%)	9(14.5%)	1(9.1%)	11(19.3%)	0.872
Liver function
TBIL (µmol/L)	52.8±39.3	57.9±45.6	60.2±28.2	64.4±55.6	0.216
ALT level (U/L)	159.8±113.4	145.5±112.8	151.8±102.7	130.2±114.3	0.117
AST level (U/L)	116.2±76.7	180.6±111.7	120.4±89.3	153.7±96.4	0.103
γ-GT (U/L)	251.4±150.3	247.6±181.0	299.2±224.3	293.5±162.7	0.149
ALP (U/L)	219.7±161.9	205.4±108.8	211.3±158.7	221.5±155.0	0.058
Surgical result
Average expenses	41766.3±7383.6	39129.1±2105.1	42490.4±4758.9	34185.7±4480.3		0.238
Postoperative hospital stay(d)	8.8(5.7,12.1)	4.2(3.5,5.8)^a,d	9.5(7.6,14.8)^f	5.5(4.5,7.2)^c		0.001
Intra-operative blood loss(ml)	15.0(8.8,32.3)	30.0(10.0,52.0)	40.0(11.5,85.0)	20.0(10.0,42.6)		0.250
Operation time(min)	152.2±15.6	132.0±37.8	121.4±33.8	134.1±33.6		0.152
CBDS clearance	15(93.8%)	54(94.7%)	10(90.9%)	58(93.5%)		0.304
Conversion to open surgery	3 (18.7%)	1(1.8%)	1(9.0%)	0(1.6%)		0.100
Mortality	1(6.3%)	0(0.0%)	0(0.0%)	0(0.0%)
Postoperative complications
Uprising serum amylase	15(93.8%)^a,b,c	7(11.8%)	0(0.0%)	0(0.0%)		＜0.001
Bile leakage	0(0.0%)	0(0.0%)	1(9.0%)	2(3.2%)		0.082
Bleeding	2(12.5%)	0(0.0%)	0(0.0%)	1(1.6%)
Perforation	1(6.2%)	0(0.0%)	0(0.0%)	0(0.0%)
Cholangitis	0(0.0%)	0(0.0%)	1(4.8%)	1(6.7%)
Pleural effusion	0(0.0%)	0(0.0%)	0(0.0%)	0(0.0%)
Pneumonia	0(0.0%)	0(0.0%)	0(0.0%)	0(0.0%)
T-tube displacement	0(0.0%)	0(0.0%)	2(9.5%)	0(0.0%)
Multiple organ failure	0(0.0%)	0(0.0%)	0(0.0%)	0(0.0%)
Follow-up complications
Stone recurrence	3(18.7%)	3(5.2%)	1(9.0%)	3(4.8%)		0.637
Stricture of CBD	0(0.0%)	0(0.0%)	0(0.0%)	1(6.7%)
Reflux cholangitis	4(25.0%)	0(0.0%)	0(0.0%)	0(0.0%)		0.019
Total complication	25(156.2%)^abc	13(22.8%)^de	6(54.5%)	8(12.9%)		＜0.001

a. PreERCP+LC vs LC+LTCBDE+ Gastroscope, p＜0.05;
b. Pre-ERCP+LC vs LC+LTCD, p＜0.05;
c. Pre-ERCP+LC vs LC+LCBDE+primary closure, p＜0.05;
d. LC+LTCBDE+ Gastroscope vs LC+LTCD, p＜0.05;
e. LC+LTCBDE+ Gastroscope vs LC+LCBDE+primary closure, p＜0.05;
f. LC+LTCD vs LC+LCBDE+primary closure, p＜0.05.

Table 6 Comparison of Surgical Results and complications in patients with Type Ⅳ

	LC+LCBDE+ primary closure	LC+LCCBDE+ Gastroscope	LC+LCTD	P value
	(n=15)	(n=18)	(n=84)	P value
Preoperative indicators
Age	58.1±13.6	56.9±15.2	51.3±13.9	0.162
Gender (female)	9(60.0%)	8(44.4%)	39(46.4%)	0.217
ASA grade	1.8±0.4	2.0±0.6	1.9±0.4	0.374
Body mass index	23.1±2.2	22.8±3.1	22.0±3.8	0.089
Medical history
Diabetes	2(13.3%)	2(11.1%)	9(10.7%)	0.169
Hypertension	3(20.0%)	3(16.7%)	10(11.9%)	0.927
Liver function
TBIL (µmol/L)	60.1±65.4	54.5±47.6	57.6±39.6	0.074
ALT level (U/L)	139.9±114.5	143.3±108.3	149.0±118.1	0.092
AST level (U/L)	133.2±109.8	180.9±102.8	109.2±90.3	0.061
γ-GT (U/L)	280.7±216.4	255.2±204.3	344.2±239.7	0.158
ALP (U/L)	234.6±163.7	213.9±115.2	223.8±165.6	0.124
Surgical result
Average expenses	40135±3201.8	42315.5±3598.6	39650.8±4153.6	0.238
Post-hospitalization time(d)	4.5(3.7,6.3)^b	5.0(4.2,7.5)^c	9.8(8.5,14.7)	0.003
Intra-operative blood loss(ml)	30.0(10.0,50.0)	20.0(10.0,30.0)	30.0(20.0,50.0)	0.471
Operation time(min)	135.1±17.1	144±21.7	139±25.4	0.172
CBDS clearance	13(86.7%)^b	17(94.4%)^c	65(77.4%)	0.037
Conversion to open surgery	2(13.3%)	3(16.7%)	5(5.9%)	0.153
Mortality	0(0.0%)	0(0.0%)	0(0.0%)
Postoperative complications
Uprising serum amylase	0(0.0%)	3(16.7%)	0(0.0%)
Bile leakage	1(6.7%)	0(0.0%)	4(4.8%)	0.182
Bleeding	0(0.0%)	1(5.6%)	1(1.1%)	0.626
Perforation	0(0.0%)	0(0.0%)	0(0.0%)
Cholangitis	1(6.7%)	0(0.0%)	0(0.0%)
Pleural effusion	0(0.0%)	0(0.0%)	0(0.0%)
Pneumonia	0(0.0%)	0(0.0%)	1(1.1%)
T-tube displacement	0(0.0%)	0(0.0%)	2(2.4%)	1.000
Multiple organ failure	0(0.0%)	0(0.0%)	0(0.0%)
Follow-up complications
Stone recurrence	2(13.3%)	3(16.7%)	6(7.1%)	0.445
Stricture of CBD	0(0.0%)	0(0.0%)	0(0.0%)
Reflux cholangitis	0(0.0%)	1(5.6%)	0(0.0%)
Total complication	4(26.7%)	8(44.4%)	14(16.7%)	0.08

a. LC+LTCBDE+Gastroscope vs LC+LCTD, p＜0.05;

b. LC+LTCBDE+Gastroscope vs LC+LCBDE+primary closure, p＜0.05;

c. LC+ LCTD vs LC+LCBDE+primary closure, p＜0.05

No competing interests reported.

9STable1.docx

Download PDF

Version 1

posted

You are reading this latest preprint version

The application of a new model for disease classification in minimally invasive treatment of concomitant cholecystolithiasis and choledocholithiasis

Status:

Version 1

Abstract

Figures

Introduction

MATERIALS AND METHODS

Study design and procedure

Precise assessment of the distribution and size of the stones and CBD diameter

Surgical technique

Laparoscope combined with duodenoscope

Laparoscopy combined with intraoperative choledochoscopy

Laparoscopy and choledochoscopy combined with the intraoperative duodenoscope or gastroscopy

Follow-up

Statistical analysis

Results

Discussion

Conclusions

Abbreviations

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1