{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T07:21:18Z","timestamp":1771485678595,"version":"3.50.1"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n The first-line treatment for common bile duct stones (CBDS) is endoscopic transpapillary stone removal, typically performed using either endoscopic sphincterotomy (EST) or endoscopic papillary balloon dilation (EPBD). However, EST is associated with risks of bleeding and perforation, while EPBD carries a significant risk of post-procedural pancreatitis. Recently, a combined approach involving minimal EST followed by EPBD (ESBD) has been reported to mitigate these drawbacks, offering potentially safer and more effective outcomes. Nevertheless, no prospective study has adequately evaluated the utility of ESBD, as prior studies were mainly observational or limited by small sample sizes. Therefore, we designed a randomized controlled trial to investigate whether ESBD is superior to EST for the treatment of small CBDS.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This study is a multicenter, randomized, open-label, parallel-group trial; outcome assessors will not be blinded, but objective predefined criteria will be used to minimize bias. Eligible participants will include patients aged 18\u00a0years or older diagnosed with CBDS who require endoscopic stone removal, with eligibility confirmed via imaging modalities. After confirming eligibility, patients will be randomly assigned in a 1:1 ratio to either the ESBD group or the EST group. In the ESBD group, a minimal sphincterotomy will first be performed, followed by balloon dilation for stone extraction. In the EST group, a medium incision extending beyond the hooding fold will be performed prior to stone extraction. The primary endpoint is the incidence of procedure-related adverse events, including pancreatitis, bleeding, and perforation. Secondary endpoints include technical success rate, clinical success rate, procedure time, need for lithotripsy, and stone recurrence rate.<\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n This study is the first multicenter, randomized controlled trial to prospectively evaluate the efficacy and safety of ESBD for the treatment of small CBDS. The findings are expected to determine whether ESBD can serve as a new standard therapeutic option compared with conventional EST.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n Japan Registry of Clinical Trials: jRCT1040250008. Registered on 21 April 2025. (https:\/\/jrct.mhlw.go.jp\/en-latest-detail\/jRCT1040250008<\/jats:ext-link>).<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s13063-025-09076-2","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T07:37:30Z","timestamp":1756193850000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Minimal endoscopic sphincterotomy with papillary balloon dilation versus endoscopic sphincterotomy for the treatment of common bile duct stones (MARBLE Trial): study protocol for a multicenter randomized controlled trial"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0718-9099","authenticated-orcid":false,"given":"Tadahisa","family":"Inoue","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akinori","family":"Maruta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junichi","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toji","family":"Murabayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Okuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Yano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rena","family":"Kitano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Uemura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shota","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun","family":"Futagami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Koizumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoya","family":"Kitada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"TTSG Consortium and Collaborators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"9076_CR1","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1055\/a-0862-0346","volume":"51","author":"G Manes","year":"2019","unstructured":"Manes G, Paspatis G, Aabakken L, et al. Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2019;51:472\u201391.","journal-title":"Endoscopy"},{"key":"9076_CR2","doi-asserted-by":"publisher","first-page":"3808","DOI":"10.3390\/jcm9123808","volume":"9","author":"S Ishii","year":"2020","unstructured":"Ishii S, Isayama H, Ushio M, et al. Best procedure for the management of common bile duct stones via the papilla: literature review and analysis of procedural efficacy and safety. J Clin Med. 2020;9:3808.","journal-title":"J Clin Med"},{"key":"9076_CR3","doi-asserted-by":"publisher","unstructured":"Ishii S, Fujisawa T, Ushio M, et al. Evaluation of the safety and efficacy of minimal endoscopic sphincterotomy followed by papillary balloon dilation for the removal of common bile duct stones.\u00a0Saudi J Gastroenterol. Published online July 21, 2020. https:\/\/doi.org\/10.4103\/sjg.SJG_162_20","DOI":"10.4103\/sjg.SJG_162_20"},{"key":"9076_CR4","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1002\/jhbp.12097","volume":"32","author":"Y Ishida","year":"2025","unstructured":"Ishida Y, Hisa T, Matsumoto R, et al. Utility and safety of endoscopic papillary balloon dilation with small-incision sphincterotomy for small bile duct stones: a randomized controlled trial. J Hepatobiliary Pancreat Sci. 2025;32:160\u20137.","journal-title":"J Hepatobiliary Pancreat Sci"},{"key":"9076_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/den.12183","volume":"26","author":"K Fujimoto","year":"2014","unstructured":"Fujimoto K, Fujishiro M, Kato M, et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc. 2014;26:1\u201314.","journal-title":"Dig Endosc"},{"key":"9076_CR6","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1111\/den.13184","volume":"30","author":"M Kato","year":"2018","unstructured":"Kato M, Uedo N, Hokimoto S, et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment: 2017 appendix on anticoagulants including direct oral anticoagulants. Dig Endosc. 2018;30:433\u201340.","journal-title":"Dig Endosc"},{"key":"9076_CR7","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.gie.2009.10.027","volume":"71","author":"PB Cotton","year":"2010","unstructured":"Cotton PB, Eisen GM, Aabakken L, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc. 2010;71:446\u201354.","journal-title":"Gastrointest Endosc"},{"key":"9076_CR8","doi-asserted-by":"publisher","unstructured":"Mukai S, Takeyama Y, Itoi T, et al. Clinical practice guidelines for post-ERCP pancreatitis 2023.\u00a0Dig Endosc. Published online March 25, 2025. https:\/\/doi.org\/10.1111\/den.15004","DOI":"10.1111\/den.15004"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-025-09076-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-025-09076-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-025-09076-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T06:13:13Z","timestamp":1757484793000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-025-09076-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":8,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["9076"],"URL":"https:\/\/doi.org\/10.1186\/s13063-025-09076-2","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]},"assertion":[{"value":"19 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Ethics Committee of Aichi Medical University School of Medicine (Approval No. 2024\u2013295) in accordance with the principles of the Declaration of Helsinki, and subsequently, the approved protocol was approved at the institutional review board at each participating center. Written, informed consent to participate will be obtained from all participants prior to enrollment.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {24}"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"307"}}