Natural course and management of common bile duct stones

<p dir="ltr">Introduction</p><p dir="ltr">Common bile duct stones (CBDS) represent a frequent and clinically important complication of gallstone disease, yet their optimal management remains debated. While symptomatic CBDS require prompt intervention, the natural course and appropriate treatment of incidentally detected or asymptomatic stones-particularly small ones-are less well defined. This thesis aimed to investigate the natural history of CBDS and evaluate the effectiveness and safety of different management strategies using nationwide data from the Swedish registry for gallstone surgery and ERCP (GallRiks).</p><p dir="ltr">Aims </p><p dir="ltr">Paper 1 aimed to investigate if ERCP with a CBDS registered in GallRiks after a cholecystectomy is valid as a proxy for clinically significant retained CBDS.</p><p dir="ltr">Paper 2 aimed to describe the rate of retained CBDS that need reintervention when left to their natural course after identification at intraoperative cholangiography (IOC) and compare it to active intervention.</p><p dir="ltr">Paper 3 aimed to describe the safety and effectiveness of management strategies for CBDS compared to the natural course, even for the smallest most inconspicuous stones.</p><p dir="ltr">Paper 4 aimed to investigate the rate of retained CBDS after ERCP for stone removal depending on the sedation level used for the procedure.</p><p dir="ltr">Methods</p><p dir="ltr">All studies in this thesis were made possible by GallRiks. Because GallRiks is maintained as a prospectively collected database the studies are considered observational cohort studies on prospectively collected data.</p><p dir="ltr">Paper 1 used GallRiks to identify patients with preoperative suspicion of CBDS who had a cholecystectomy at Södersjukhuset between 2015 and 2020. The medical records were systematically reviewed to identify retained CBDS according to predefined criteria and the findings were compared to the rates of ERCP with a retained stones in GallRiks, evaluated as a proxy using sensitivity and specificity.</p><p dir="ltr">Paper 2 is a population-based observational cohort study where data on all cholecystectomies in GallRiks from 2009 to 2019 were included and rates of retained CBDS were compared between those that completed IOC and those that did not. Rates of retained CBDS were further evaluated among those with CBDS on IOC that underwent active intervention and compared to those that were left untreated. A separate subgroup of the smallest asymptomatic stones was evaluated comparing natural course to active intervention.</p><p dir="ltr">Paper 3 is a population-based observational cohort study where all cholecystectomies from 2009 to 2023 where CBDS was identified on IOC were evaluated to determine the safety and effectiveness of CBDS management strategies. Short term Textbook Outcome completion as well as long-term freedom from retained CBDS were evaluated. A subset of the smallest, most inconspicuous stones under favourable clinical conditions were evaluated separately.</p><p dir="ltr">Paper 4 is a population-based observational cohort study where all ERCP procedures that were not part of a one-stage cholecystectomy-intraoperative ERCP where a CBDS was identified. Rates of retained CBDS at twelve months were compared depending on the sedation level used for the procedure.</p><p dir="ltr">Results</p><p dir="ltr">Paper 1 found that for 182 patients with a CBDS on IOC, an ERCP with a CBDS after a cholecystectomy had approximately 73% sensitivity and 100% specificity for a clinically significant retained CBDS as identified by medical records. In nine cases a retained CBDS was diagnosed but was not identified in GallRiks. Four patients had spontaneous passage, and five patients had an ERCP not correctly registered with CBDS.</p><p dir="ltr">Paper 2 found that among more than 134,419 patients included, active intervention was associated with a substantially lower risk of retained CBDS compared with surveillance. This benefit persisted even in patients with small (<4 mm), asymptomatic stones, indicating that the natural course is less favourable. The group that did not complete IOC had an approximately 40% higher risk of retained CBDS than when IOC was performed.</p><p dir="ltr">Paper 3 compared outcomes among 25,073 patients with CBDS on IOC between flushing, transcystic extraction, rendezvous and non-rendezvous ERCP, and choledochotomy as management strategies, compared to leaving the stone in- situ. Management outcomes varied by technique. Rendezvous ERCP and transcystic extraction were associated with favourable balances of safety and effectiveness, while standard ERCP without rendezvous, particularly when performed postoperatively, was associated with less favourable outcome profiles with a trade-off between stone clearance and more complications. In patients with small, asymptomatic stones in favourable clinical settings, no invasive strategy improved overall outcomes compared with surveillance, and transcystic flushing was the only strategy associated with a reduced hazard of retained stones without a corresponding increase in short-term adverse outcomes.</p><p dir="ltr">Paper 4 evaluated 28,709 patients undergoing ERCP for CBDS. Deeper sedation, including propofol-based sedation and general anaesthesia, was associated with lower rates of retained CBDS with a marginally favourable association for general anaesthesia compared to propofol sedation.</p><p dir="ltr">Conclusion</p><p dir="ltr">Paper 1 concludes that postoperative ERCP with confirmed CBDS is a valid and clinically meaningful proxy for retained stones in registry-based research. The proxy captures cases requiring intervention with high specificity, supporting its use as a robust outcome measure in population-based studies.</p><p dir="ltr">Paper 2 concludes that both completion of IOC and active intervention when a stone was identified was associated with fewer retained CBDS. Active intervention was superior to surveillance even for the smallest asymptomatic CBDS, indicating a less favourable natural course.</p><p dir="ltr">Paper 3 concluded that active intervention beyond transcystic flushing was not associated with improved rates of retained CBDS or Textbook Outcome for the most inconspicuous stones. For CBDS in general, the Rendezvous technique was superior to standard ERCP while transcystic extraction was safe and effective as single stage option to intraoperative ERCP. The findings support a tailored, context-dependent approach to CBDS management.</p><p dir="ltr">Paper 4 concluded that deeper sedation is associated with procedural effectiveness of ERCP and that level of sedation should be considered when planning ERCP for stone extraction.</p><h3 dir="ltr">List of scientific papers</h3><p dir="ltr">I. Postoperative ERCP as proxy for clinically significant retained stones in a population-based cohort? <b>Liljegren E</b>, Hedestig L, Sverden E, Österberg J, Enochsson L, Sandblom G Surg Open Sci. 2026 Jan 31;30:36-40. <a href="https://doi.org/10.1016/j.sopen.2026.01.007" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.sopen.2026.01.007</a></p><p dir="ltr">II. Intervention versus surveillance in patients with common bile duct stones detected by intraoperative cholangiography: a population-based registry study.<b> </b><b>Johansson E,</b> Österberg J, Sverden E, Enochsson L, Sandblom G. Br J Surg. 2021 Dec 1;108(12):1506-1512. <a href="https://doi.org/10.1093/bjs/znab324" rel="noreferrer" target="_blank">https://doi.org/10.1093/bjs/znab324</a></p><p dir="ltr">III. Management of common bile duct stones identified at intraoperative cholangiography during cholecystectomy: a population-based cohort study with analysis of small asymptomatic stones <b>Liljegren E</b>, Sverden E, Österberg J, Enochsson L, Sandblom G [Manuscript]</p><p dir="ltr">IV. Deeper sedation during ERCP is associated with fewer retained common bile duct stones: a prospective population-based registry study. <b>Liljegren E</b>, Sverden E, Österberg J, Enochsson L, Sandblom G. BMC Gastroenterol. 2026 Mar 21. E-publication ahead of print <a href="https://doi.org/10.1186/s12876-026-04742-4" rel="noreferrer" target="_blank">https://doi.org/10.1186/s12876-026-04742-4</a></p>