Endoscopic retrograde cholangiopancreatography combined with extracorporeal shock wave lithotripsy for the removal of large gallbladder stones: a pilot study.

Patients who suffered from cholecystolithiasis (stone diameter ≥ 1 cm) complicated with choledocholithiasis and underwent ERCP combined with ESWL to remove common bile duct (CBD) stones and gallstones at the First Affiliated Hospital of Nanchang University from July 2022 to December 2022 were enrolled. The patients’ clinical characteristics, endoscopic treatment and follow-up data were analyzed. The inclusion criteria for this study were as follows: (1) aged 18–80 years, regardless of sex; (2) abdominal ultrasound, computed tomography (CT) or magnetic resonance cholangiopancreatography (MRCP) confirmed the diagnosis of cholecystolithiasis combined with choledocholithiasis, in which the gallbladder size and morphology were normal, the gallbladder stones were ≥ 1 cm, and the thickness of the gallbladder wall was ≤ 3 mm; (3) refused to choose surgery as the first option and had a strong desire to preserve the gallbladder after being fully informed of the risk of EGPC based on ERCP combined with ESWL and the need for surgery after EGPC failure; and (4) signed the informed consent form before the operation. The exclusion criteria were as follows: (1) history of previous ERCP or biliary surgery; (2) acute cholecystitis, gallbladder perforation or gangrene; (3) chronic cholecystitis; (4) fibrosis of the gallbladder wall or porcelain gallbladder; (5) gallbladder atrophy, gallbladder lumen disappearance or too small; (6) gallbladder duct obstruction or Mirrizzi syndrome; (7) preoperative imaging suspicion of gallbladder carcinoma; (8) diffuse gallbladder adenomyosis; and (9) pregnancy or lactation (Fig.  1 ). This study was approved by the Medical Research Ethics Committee of the First Affiliated Hospital of Nanchang University (2021048) and registered at the Clinical Trials Registration site in China [Registration number: ChiCTR2200060927 ( http://www.chictr.org.cn/ ); registration date: June 14, 2022]. All methods were performed in accordance with the relevant guidelines and regulations and were in accordance with the ethical standards described in the 1964 Declaration of Helsinki and its later amendments. Fig. 1 Flow chart of EGPC. Abbreviations: EGPC, endoscopic gallbladder-preserving cholecystolithotomy; ERCP, endoscopic retrograde cholangiopancreatography; ESWL, extracorporeal shock wave lithotripsy; CSEMS, covered self-expandable metal stent; PS, plastic stent; CBD, common bile duct Flow chart of EGPC. Abbreviations: EGPC, endoscopic gallbladder-preserving cholecystolithotomy; ERCP, endoscopic retrograde cholangiopancreatography; ESWL, extracorporeal shock wave lithotripsy; CSEMS, covered self-expandable metal stent; PS, plastic stent; CBD, common bile duct

This study included a total of six patients (Han ethnicity) who met the criteria, including three males and three females, with an average age of 50 years (23–72 years) and an average disease course of 12 days (7–17 days). The six patients had varying degrees of abdominal pain, of whom three patients had nausea and vomiting, three patients had jaundice, and two had fever. None of the patients had other comorbidities (Table  1 ). Table 1 Clinical characteristics of the six patients with cholecystolithiasis complicated with choledocholithiasis Case No. Age(y) /Sex Main symptoms Gallbladder size (cm) Number of gallbladder stones Size of gallbladder stones (cm) Number of common bile duct stones Size of common bile duct stones (cm) Diameter of common bile duct (cm) 1 63/F abdominal pain, nausea and vomiting 8.0 × 5.0 1 2.1 × 2.0 multiple 0.6 × 0.4 1.3 2 39/M abdominal pain, jaundice 6.3 × 2.3 1 3.9 × 1.2 multiple 2.0 × 1.5 1.7 3 23/F abdominal pain 8.3 × 3.3 multiple 2.0 × 0.7 multiple 1.0 × 1.0 1.0 4 67/F abdominal pain, jaundice, fever 6.6 × 3.2 1 1.7 × 1.0 1 2.6 × 1.3 1.4 5 33/M abdominal pain, jaundice, nausea and vomiting 7.3 × 2.7 1 1.2 × 1.2 multiple 1.2 × 1.0 0.9 6 72/M abdominal pain, fever, nausea and vomiting 7.0 × 2.6 multiple 1.1 × 0.9 2 0.6 × 0.6 1.0 Clinical characteristics of the six patients with cholecystolithiasis complicated with choledocholithiasis Both the technical success rate and clinical success rate of the six patients were 83.3% (5/6), and the incidence of adverse events was 16.7% (1/6). In total, 13 ERCP procedures were performed. In two patients, the gallbladder stones were not completely removed during the second ERCP, so a third ERCP was performed. The total number of ESWL operations was eight, and two patients failed to reach the condition after the first lithotripsy. Thus, a second lithotripsy was performed until the diameter of the gallbladder stones was less than 1 cm. The CSEMS was successfully placed in the cystic duct in all the cases, of which two were guided by an EyeMax choledochoscope, one was guided by a SpyGlass choledochoscope, and the remainder were guided by X-ray (Table  2 ). Table 2 ERCP combined with ESWL operation procedures and related adverse events Case No. Technical success Clinical success ERCP ESWL Times EPBD PS in the bile duct CSEMS in the cystic duct Cholangioscopy Adverse events Times Final Gallbladder stone size (cm) Adverse events 1 Yes Yes 2 1 cm, 3 atm for 0.5 min 9 cm/8.5 Fr 1.0 × 8.0 N/A No 1 0.8 × 0.8 No 2 Yes Yes 2 1.5 cm, 5 atm for 1 min 9 cm/8.5 Fr 1.0 × 8.0 N/A No 2 1.0 × 0.8 No 3 Yes Yes 2 N/A 9 cm/8.5 Fr 1.0 × 8.0 SpyGlass mild PEP 1 0.7 × 0.6 No 4 Yes Yes 3 1.0 cm, 3 atm for 1 min 7 cm/7 Fr 1.0 × 8.0 N/A No 2 sediment-like stones No 5 Yes Yes 3 1.0 cm, 5 atm for 1 min 7 cm/8.5 Fr 1.0 × 8.0 EyeMax No 1 0.7 × 0.6 No 6 No No 1 0.8 cm, 3 atm for 0.5 min 12 cm/8.5 Fr 1.0 × 8.0 EyeMax No 1 1.1 × 0.9 abdominal pain ERCP, endoscopic retrograde cholangiopancreatography; ESWL, extracorporeal shock wave lithotripsy; EPBD, endoscopic papillary balloon dilatation; PS, plastic stent; CSEMS, covered self-expandable metal stent; atm: atmospheric pressure; PEP, post-ERCP pancreatitis ERCP combined with ESWL operation procedures and related adverse events ERCP, endoscopic retrograde cholangiopancreatography; ESWL, extracorporeal shock wave lithotripsy; EPBD, endoscopic papillary balloon dilatation; PS, plastic stent; CSEMS, covered self-expandable metal stent; atm: atmospheric pressure; PEP, post-ERCP pancreatitis One 23-year-old female patient developed mild post-ERCP pancreatitis on the second day after the first ERCP and recovered after three days of medication. No other ERCP- or ESWL-related adverse events occurred in any of the patients. Five patients successfully completed ESWL, and one patient was transferred to laparoscopic cholecystectomy because of intolerable abdominal pain during ESWL (Table  2 ). The liver function of all patients improved significantly after EGPC ( P  < 0.05) (Table  3 ). Table 3 The liver function parameters of the patients before and after EGPC Case No. 1 2 3 4 5 6 Mean ± SD/ Median (IQR) * Difference between pre-and post-EGPC t ** P value ALT (U/L) Pre Post 486.3 32.3 576.5 309.3 271.1 113.3 50.7 31.6 194.0 100.4 511.6 65.4 348.37 ± 207.90 82.9 (130.2) 239.6 ± 182.23 3.221 0.023 AST (U/L) Pre Post 572.3 11.0 253.8 104.3 119.4 60.7 58.6 31.2 73.3 30.6 317.9 24.6 232.55 ± 195.75 43.73 ± 33.83 188.8 ± 207.63 2.228 0.076 TBIL (umol/L) Pre Post 35.6 12.8 71.5 40.1 142.0 24.3 39.8 29.5 112.3 38.9 110.2 23.4 85.23 ± 43.12 28.17 ± 10.33 57.07 ± 42.07 3.323 0.021 DBIL (umol/L) Pre Post 23.3 3.4 36.1 19.8 79.0 10.2 18.8 8.8 58.3 13.5 62.7 5.8 46.37 ± 23.96 10.25 ± 5.84 36.12 ± 24.14 3.665 0.015 γ-GT (U/L) Pre Post 1028.4 352.2 390.7 217.9 229.8 72.8 663.0 235.3 587.0 338.5 370.2 138.4 544.85 ± 283.93 225.85 ± 109.43 319.0 ± 199.80 3.911 0.011 ALP (U/L) Pre Post 368.0 135.4 328.1 198.7 167.2 113.3 783.5 430.4 191.0 162.6 160.8 107.7 259.55 (306.3) 149.0 (144.7) 141.7 ± 127.67 2.720 0.042 Mean ± SD, mean ± standard deviation; IQR, interquartile range; EGPC, endoscopic gallbladder-preserving cholecystolithotomy; WBC, white blood cell count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; DBIL, direct bilirubin; γGT, γglutamyl transferase; ALP, alkaline phosphatase * The normally distributed data were expressed as the means ± standard deviations and the nonnormally distributed data were expressed as medians and interquartile ranges (IQRs) ** The differences of parameters between pre-EGPC and post-EGPC (paired data) in all the six patients were normally distributed and were expressed as the means ± standard deviations, so a paired t test was performed The liver function parameters of the patients before and after EGPC Pre Post 486.3 32.3 576.5 309.3 271.1 113.3 50.7 31.6 194.0 100.4 511.6 65.4 348.37 ± 207.90 82.9 (130.2) Pre Post 572.3 11.0 253.8 104.3 119.4 60.7 58.6 31.2 73.3 30.6 317.9 24.6 232.55 ± 195.75 43.73 ± 33.83 Pre Post 35.6 12.8 71.5 40.1 142.0 24.3 39.8 29.5 112.3 38.9 110.2 23.4 85.23 ± 43.12 28.17 ± 10.33 Pre Post 23.3 3.4 36.1 19.8 79.0 10.2 18.8 8.8 58.3 13.5 62.7 5.8 46.37 ± 23.96 10.25 ± 5.84 Pre Post 1028.4 352.2 390.7 217.9 229.8 72.8 663.0 235.3 587.0 338.5 370.2 138.4 544.85 ± 283.93 225.85 ± 109.43 Pre Post 368.0 135.4 328.1 198.7 167.2 113.3 783.5 430.4 191.0 162.6 160.8 107.7 259.55 (306.3) 149.0 (144.7) Mean ± SD, mean ± standard deviation; IQR, interquartile range; EGPC, endoscopic gallbladder-preserving cholecystolithotomy; WBC, white blood cell count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; DBIL, direct bilirubin; γGT, γglutamyl transferase; ALP, alkaline phosphatase * The normally distributed data were expressed as the means ± standard deviations and the nonnormally distributed data were expressed as medians and interquartile ranges (IQRs) ** The differences of parameters between pre-EGPC and post-EGPC (paired data) in all the six patients were normally distributed and were expressed as the means ± standard deviations, so a paired t test was performed The follow-up rate of the six patients was 100%, with an average follow-up period of 24 months (21–26 months). Only one patient experienced gallbladder stone recurrence (0.3 cm in diameter) at the 3-month follow-up, but this patient did not experience any clinical symptoms. Interestingly, after continuing regular oral administration of UDCA, no gallbladder stone was found via abdominal ultrasound at her 6-month follow-up. None of the patients experienced digestive symptoms such as abdominal pain, dyspepsia, etc., or other adverse events during follow-up. In addition, abdominal ultrasound did not reveal stone recurrence in the gallbladder or bile duct at the 6-, 12-, 18- and 24-month follow-ups (Table  4 ). All the patients are still under follow-up. Table 4 Follow-up of patients after EGPC Case No. Follow-up time (months) Digestive symptoms Stones recurrence Gallbladder malignancy Other adverse events Transfer to surgery 1 26 No Yes No No No 2 26 No No No No No 3 26 No No No No No 4 24 No No No No No 5 23 No No No No No 6 21 No No No No Yes EGPC, endoscopic gallbladder-preserving cholecystolithotomy Follow-up of patients after EGPC EGPC, endoscopic gallbladder-preserving cholecystolithotomy

The instruments used in this study included a duodenoscope (TJF-240/TJF-260; Olympus Corporation, Tokyo, Japan), a SpyGlass™ peroral cholangioscopy (Boston Scientific Corporation, Massachusetts, U.S.A.), an EyeMax™ peroral cholangioscopy (Micro-Tech Corporation, Nanjing, China), a CSEMS (1.0 cm×8.0 cm, Micro-Tech Corporation, Nanjing, China), a biliary plastic stent (Leo Medical Corporation, Changzhou, China), a biliary dilation balloon (Micro-Tech Corporation, Nanjing, China), a nasobiliary tube (COOK Medical Corporation, Bloomington, USA), and a lithotripter (Shenzhen New Element Medical Technology Development Corporation, Shenzhen, China). The contrast agent used was ioversol.

All patients were administered with intravenous drip of lactated Ringer’s solution and resumed a normal diet as early as possible after endoscopic procedures if no adverse events occurred. In addition, the pateints took ursodeoxycholic acid (UDCA) tablets 500 mg once a day for 6 consecutive months, and adjusted their lifestyle if necessary. All the patients were subjected to regular clinical follow-up at 3, 6, 12, 18 and 24 months after EGPC. Abdominal ultrasound was performed at each follow-up to detect the recurrence of gallbladder stones, changes in gallbladder size, morphology and wall thickness or other lesions of the gallbladder. The statistical analysis was performed using SPSS 25.0 statistical software. The normally distributed data were expressed as the means ± standard deviations, and the nonnormally distributed data were expressed as medians and interquartile ranges (IQRs). A paired t test was performed if the differences between paired data were normally distributed; otherwise, a nonparametric test was performed. P  < 0.05 was considered statistically significant.

Cholecystolithiasis is a common benign disorder of the gallbladder in clinical practice, and their prevalence increases with age [ 3 ]. In some conditions, patients with asymptomatic cholecystolithiasis need only follow-up, and prophylactic cholecystectomy is not recommended. Symptomatic cholecystolithiasis is usually characterized by biliary colic attacks or cholecystitis, and alternative treatment options generally include cholecystectomy, pharmacological stone litholysis (≤ 5 mm cholesterol stones), and gallbladder-preserving cholecystolithotomy [ 4 ]. Currently, cholecystectomy is still the main treatment for symptomatic gallbladder stones, especially for large stones. Although laparoscopic cholecystectomy is considered as a relatively safe and less invasive procedure, the mortality rate is approximately 0.3–0.5% [ 3 ], and the risk of bile duct injury is still up to 4% [ 3 , 15 ]. As a digestive organ, the gallbladder not only stores, concentrates, and excretes bile and regulates bile duct internal pressure but also has important immune and secretory functions [ 16 ]. Moreover, an increasing number of studies have shown that although cholecystectomy can prevent gallbladder stone recurrence and malignancy, the lack of gallbladder function after cholecystectomy might lead to a variety of short-term and long-term adverse effects. It has been reported that 5–40% of patients may develop postcholecystectomy syndrome, including abdominal pain, diarrhea, and dyspeptic symptoms, as well as bile reflux gastritis, which is associated with an increased risk of functional gastrointestinal and psychological conditions [ 15 , 17 – 20 ]. Additionally, previous studies suggested a slightly increased risk for gastrointestinal tract tumors, such as colorectal cancer, gastric cancer, pancreatic cancer, and esophageal adenocarcinomas, with evidence indicating that this risk might be more significant 10 years after cholecystectomy [ 21 – 27 ]. With the development of peroral direct visualization techniques such as cholangioscopy, the problem of incomplete removal of gallbladder stones due to the inability of traditional cholecystostomy to explore the interior of the gallbladder has been solved. Because the gallbladder is preserved after EGPC, the risk of subsequent stone recurrence remains [ 15 ]. However, 80% of gallbladder stones are cholesterol stones, and the recurrence of these stones can be prevented by pharmacological litholysis, such as UDCA after EGPC [ 4 ]. In addition, if patients with stone recurrence still intend to preserve the gallbladder and high-risk factors for recurrence are not present, a second EGPC can also be performed [ 8 ]. At present, there are two main approaches for EGPC: laparoscopy combined with choledochoscopic small-incision stone extraction [ 9 – 11 ] and endoscopic stone extraction via NOTES [ 12 , 13 ]. Although these two approaches preserve the gallbladder, they both require an incision in the gallbladder, which might increase the risk of bile leakage, lead to scar formation in the gallbladder wall, and cause adhesions around the gallbladder, potentially affecting its function to some extent. To preserve the gallbladder with the gallbladder wall intact, our team recently reported EGPC based on ERCP for cholecystolithiasis without a gallbladder incision [ 14 ]. The technical success rate was 91.67%, and the clinical success rate was 77.27%. The incidence of post-EGPC adverse events was 6.25%, including 4.17% pancreatitis and 2.08% cholangitis, with no perforation or bleeding. The recurrence rates of gallbladder stones at 12, 18, 24, 30, and 36 months after EGPC were 0%, 3.23%, 6.45%, 12.9%, and 16.13%, respectively [ 14 ]. In terms of recurrence, different studies have reported that the gallbladder stone recurrence rate of EGPC varies greatly from 4.92 to 40.0%, and the results of our previous studies were roughly similar or even lower [ 9 ]. The above results showed that EGPC based on ERCP was safe and effective. This technique not only removed gallbladder stones and reduced the risk of secondary bile duct stones but also ensured the integrity of the gallbladder structure, maximized the possibility of preserving the normal physiological function of the gallbladder, and avoided adverse events such as bile duct injury and bile leakage after cholecystectomy [ 14 ]. Restricted by the diameter of the CSEMS, our previous study involved only gallbladder stones with a diameter less than 1.0 cm, and reasonable lithotripsy methods are needed to remove gallbladder stones with a diameter > 1.0 cm. Owing to the sharp angle between the cystic duct and the body of the gallbladder and the pouch-like structure of the gallbladder, mechanical lithotripsy and laser lithotripsy based on ERCP are difficult to perform for gallbladder stones. As a minimally invasive, simple, safe and effective technique, ESWL used to be widely applied for the treatment of gallbladder stones in the 1980s [ 28 – 30 ], but its role has dramatically declined since then. One of the reasons was that the concept of cholecystectomy predominated, which marginalized the concept of EGPC. Another important reason was that the ERCP technique was immature at that time. In many cases, gallbladder stones fell into the CBD after ESWL, causing secondary CBD stones and even leading to acute cholangitis and pancreatitis, which might be life-threatening. However, with the development of ERCP since the 21st century, ESWL is expected to regain good prospects for the treatment of gallbladder stones. This preliminary study revealed that ERCP combined with ESWL has a high technical success rate and clinical success rate and might be a safe, effective, and promising alternative treatment option for large gallbladder stones (≥ 1.0 cm in diameter). To our knowledge, this study is the first report on the use of ERCP combined with ESWL for the treatment of large gallbladder stones (diameter ≥ 1.0 cm). This study differed from previous studies in the following ways. First, the previous EGPC required an incision in the gallbladder, which might damage the gallbladder wall to varying degrees and affect gallbladder function to some extent. In this study, the first ERCP was performed to remove bile duct stones and place a CSEMS into the cystic duct. ESWL was performed after the first ERCP to crush the gallbladder stones into smaller pieces (diameter < 1.0 cm), and the gallbladder stones were removed using a stone retrieval basket through the CSEMS in the following ERCP. This new route, which is more physiological, does not require an incision in the gallbladder; thus, it ensures the integrity of the gallbladder structure and preserves the normal physiological function of the gallbladder. Second, previous EGPC was mostly applied to patients with gallbladder stones alone. However, the conditions of all patients in this study were complicated with CBD stones, so it was more reasonable to use the ERCP-based EGPC pathway, which removed both CBD stones and gallbladder stones. Thus, an additional ERCP or surgery specially designed for CBD stones was not needed after gallbladder stone removal. However, this study also had several limitations. First, this study was a single-center pilot study with a small sample size, which inevitably caused bias. Second, stone recurrence is an important issue after EGPC. The follow-up period of this study was relatively short, and long-term follow-up is needed for further evaluation of EGPC based on ERCP. Third, the majority of gallstones are clinically silent. That means patients might experience a silent recurrence of gallstones within the interval of follow-up, and the gallstones might have passed out of the gallbladder before the next follow-up, leading to a false negative results of no recurrence. Therefore, some follow-up results might be skewed.

(1) ERCP for common bile duct (CBD) stone removal (the first ERCP): All patients without contraindications for nonsteroidal anti-inflammatory drugs (NSAIDs) received routine rectal administration of 100 mg of diclofenac 30 min before ERCP. The patient was placed in the prone position under general anesthesia. After successful bile duct cannulation, cholangiography was performed to locate CBD stones. Depending on the size of the stones, an incision of the papillary sphincter or a dilatation of the papillary sphincter with a dilatation balloon or a combination of both was performed to facilitate the removal of CBD stones. Under X-ray guidance or peroral cholangioscopy direct vision, the guidewire was delivered into the gallbladder lumen through the cystic duct, and a CSEMS (1.0 cm×8.0 cm) was placed along the guidewire through the cystic duct, with the proximal end of the stent in the gallbladder lumen and the distal end in the lower part of the CBD. To ensure effective drainage of both the bile duct and gallbladder to prevent post-ERCP biliary infection, we placed a nasobiliary tube in the gallbladder and a plastic stent in the CBD using the dual wire technique. Gallbladder stone removal was not performed during this session of ERCP because the CSEMS needed time for complete expansion (Figs.  2 and 3 ). Fig. 2 Removal of common bile duct stones by ERCP. ( A ) Intact duodenal papilla; ( B ) cannulation and radiography; ( C ) endoscopic sphincterotomy; ( D , E ) balloon dilatation of the duodenal papilla; ( F ) removal of bile duct stones Removal of common bile duct stones by ERCP. ( A ) Intact duodenal papilla; ( B ) cannulation and radiography; ( C ) endoscopic sphincterotomy; ( D , E ) balloon dilatation of the duodenal papilla; ( F ) removal of bile duct stones Fig. 3 Placement of a CSMES in the cystic duct, a plastic stent in the bile duct, and a nasobiliary tube in the gallbladder through the CSEMS. ( A ) A guidewire was successfully passed through the cystic duct guided by the peroral cholangioscopy direct vision. ( B ) Cholecystography indicated multiple gallbladder stones. ( C ) A CSEMS (1.0 cm × 8.0 cm) was placed through the guidewire in the cystic duct, with the proximal end of the stent in the gallbladder lumen and the distal end in the distal common bile duct. ( D ) A plastic stent was placed in the bile duct, and a nasobiliary tube was placed in the gallbladder through the CSEMS Placement of a CSMES in the cystic duct, a plastic stent in the bile duct, and a nasobiliary tube in the gallbladder through the CSEMS. ( A ) A guidewire was successfully passed through the cystic duct guided by the peroral cholangioscopy direct vision. ( B ) Cholecystography indicated multiple gallbladder stones. ( C ) A CSEMS (1.0 cm × 8.0 cm) was placed through the guidewire in the cystic duct, with the proximal end of the stent in the gallbladder lumen and the distal end in the distal common bile duct. ( D ) A plastic stent was placed in the bile duct, and a nasobiliary tube was placed in the gallbladder through the CSEMS (2) ESWL: Given that the gallbladder stones in our study were relatively large, with a diameter larger than that of the CSEMS (1.0 cm in diameter), we used ESWL to perform extracorporeal gallbladder stone lithotripsy on the patient to fragment the gallbladder stones into pieces with a maximum diameter less than 1.0 cm. If there are no adverse events after the first ERCP, ESWL will be performed on the second day. The patient was placed in the supine position and administered intravenous remifentanil for analgesia and propofol for sedation. Localization of the gallbladder stones was performed via cholecystography through a nasobiliary tube. Then, the shock waves were focused on the stones. The treatment voltage was set at 14.5 kV, the trigger count was 2000, and the shock wave frequency was 90 times/min (Fig.  4 ). After ESWL, abdominal ultrasound was performed to confirm the size of the stones. If the stones are still larger than 1.0 cm, ESWL will be performed again the next day. Fig. 4 ESWL for crushing gallbladder stones into pieces with a diameter less than 1.0 cm. The patient was placed in the supine position and given intravenous remifentanil for analgesia and combined with propofol sedation. Localization of the gallbladder stones was performed via cholecystography through a nasobiliary tube, and then the shock waves were focused on the stones. The treatment voltage was set at 14.5 kV, the trigger count was 2000 times and the shock wave frequency was 90 times/min ESWL for crushing gallbladder stones into pieces with a diameter less than 1.0 cm. The patient was placed in the supine position and given intravenous remifentanil for analgesia and combined with propofol sedation. Localization of the gallbladder stones was performed via cholecystography through a nasobiliary tube, and then the shock waves were focused on the stones. The treatment voltage was set at 14.5 kV, the trigger count was 2000 times and the shock wave frequency was 90 times/min (3) ERCP for gallbladder stone removal (the second ERCP): The pre-ERCP radiograph confirmed that the CSEMS in the cystic duct, the nasobiliary tube in the gallbladder and the plastic stent in the CBD were all in place. Cholecystography through a nasobiliary tube confirmed the existence and suitable diameter (< 1.0 cm) of the gallbladder stones. Afterwards, the nasobiliary tube was removed. The plastic stent of the CBD was also removed with a snare, and a stone retrieval basket was inserted into the gallbladder through the CSEMS to remove the gallbladder stones from the duodenal papilla until no residual stones were found in the gallbladder by the last cholecystography using the retrieval basket. A third ERCP will be performed if the gallbladder stones are not completely removed during the second ERCP. After confirming that the gallbladder stones were completely removed, the residual contrast agent in the gallbladder was aspirated by the retrieval basket to avoid secondary cholecystitis. Finally, the CSEMS was removed with endoscopic forceps under X-ray guidance, and the CBD residual small stones were completely removed with the retrieval basket (Fig.  5 ). Fig. 5 Gallbladder-preserving removal of gallbladder stones by ERCP. ( A ) The pre-ERCP radiographs revealed that the CSEMS through the cystic duct, the nasobiliary tube in the gallbladder and the plastic stent in the common bile duct were all in place. ( B ) Cholecystography through a nasobiliary tube revealed multiple gallbladder stones with a maximum diameter of less than 1.0 cm. ( C , D ) Removal of gallbladder stones with a retrieval basket through the CSEMS. ( E ) Cholecystography revealed no residual gallbladder stones. ( F , G ) Removal of the CSEMS with forceps under X-ray guidance. ( H )Cholangiography revealed no residual stones in the common bile duct. ( I )Final radiography of ERCP Gallbladder-preserving removal of gallbladder stones by ERCP. ( A ) The pre-ERCP radiographs revealed that the CSEMS through the cystic duct, the nasobiliary tube in the gallbladder and the plastic stent in the common bile duct were all in place. ( B ) Cholecystography through a nasobiliary tube revealed multiple gallbladder stones with a maximum diameter of less than 1.0 cm. ( C , D ) Removal of gallbladder stones with a retrieval basket through the CSEMS. ( E ) Cholecystography revealed no residual gallbladder stones. ( F , G ) Removal of the CSEMS with forceps under X-ray guidance. ( H )Cholangiography revealed no residual stones in the common bile duct. ( I )Final radiography of ERCP

In conclusion, ERCP combined with ESWL potentially represents a safe and effective treatment for large gallbladder stones (diameter ≥ 1.0 cm) complicated with CBD stones and could be beneficial for patients with good gallbladder function and a desire for gallbladder preservation. More prospective, multicenter, large-sample randomized controlled trials are needed to confirm the efficacy and safety of this novel technique in the future.

Technical success refers to successful entrance into the gallbladder lumen by the guidewire, the placement of a covered self-expandable metal stent (CSEMS) through the cystic duct, and successful lithotripsy of gallbladder stones by ESWL. Clinical success refers to the successful removal of common bile duct stones and gallbladder stones, confirmed by abdominal ultrasound and MRCP before discharge.

Gallstones are among the most prevalent digestive system disorders in the world and are estimated to afflict 10–15% of the population in America and other developed countries, as well as approximately 5–10% of Chinese adults [ 1 – 2 ]. Most patients have no apparent symptoms, and > 20% of people with gallstones develop biliary colic, gastrointestinal symptoms, or concurrent infections [ 3 ]. Cholecystolithiasis refers to the formation of solid calculi in gallbladder bile. On the basis of their composition, gallbladder stones are classified as cholesterol stones (if > 50% cholesterol) or black pigment stones (predominantly polymerized calcium bilirubinate if < 30% cholesterol). Many risk factors are associated with the development of gallstones, including age over 40 years, obesity, female sex, family history, fertility, race and lifestyle-related diseases [ 4 ]. Approximately 15% of cholecystolithiasis are complicated with choledocholithiasis, which can lead to complications such as cholecystitis, biliary obstruction, cholangitis, pancreatitis, gallbladder cancer and even life-threatening conditions [ 5 ]. Cholecystectomy is surgery to remove your gallbladder. It is the only treatment option to cure symptomatic gallstones and the treatment of choice for both uncomplicated symptomatic gallbladder stones and proven gallbladder sludge with characteristic biliary pain. Cholecystectomy should be performed in time when gallbladder stone-related complications occur or when high-risk factors for gallbladder cancer exist [ 5 – 7 ]. However, given that gallbladder function and post-cholecystectomy adverse events have been increasingly emphasized, endoscopic gallbladder-preserving cholecystectomy (EGPC) has become an alternative option for cholecystectomy [ 8 ]. Traditional EGPC methods for gallbladder stones can be divided into laparoscopy combined with choledochoscopy and natural orifice transluminal endoscopic surgery (NOTES) [ 9 – 13 ]. However, both methods above inevitably damage the gallbladder wall to varying degrees and increase the risk of postoperative bile leakage. Furthermore, traditional EGPC might cause postoperative scar formation in the gallbladder wall and adhesion around the gallbladder, which might impair gallbladder function. Therefore, it is particularly important to identify a more physiologic route for the EGPC. Our team’s previous studies revealed that a new EGPC called transcystic gallbladder-preserving cholecystolithotomy based on endoscopic retrograde cholangiopancreatography (ERCP) is safe and effective for removing gallbladder stones smaller than 1 cm [ 14 ]. In this study, we aimed to expand the indications and conducted a pilot study on the feasibility and safety of ERCP combined with extracorporeal shock wave lithotripsy ( ESWL) in the treatment of larger gallbladder stones (diameter ≥ 1 cm) to maximize the preservation of the physiological function of the gallbladder.