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An in-depth healthcare utilization and cost-effectiveness analysis of the international multicenter ORANGE II PLUS randomized controlled trial comparing LH and OH was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Patients were randomly assigned to LH or OH in 16 European centers from October 2013 to January 2019. Costs were determined as a product of unit costs using patient-level, clinician-reported resource utilization up to 90\u00a0days. Item-specific resource use per country was presented. The measure of effect was quality-adjusted life year (QALY). Cost and effect differences were compared between treatment arms using nonparametric bootstrapping, from a Dutch healthcare cost perspective. A cost-effectiveness analysis was performed to establish the incremental cost-effectiveness ratio (ICER), i.e., costs per QALY gained, for LH compared with OH 1 year postoperatively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 332 patients randomized to LH (\n                      <jats:italic>n<\/jats:italic>\n                      = 166) and OH (\n                      <jats:italic>n<\/jats:italic>\n                      = 166), intraoperative costs were higher for LH (LH 13,208 \u20ac versus OH 9437 \u20ac), while postoperative costs were lower for LH (LH 5774 \u20ac versus OH 7703 \u20ac). Longer operative time and greater instrument use contributed to higher intraoperative costs, while shorter hospital stays contributed to lower postoperative costs. Mean overall costs per patient were higher in LH (LH 18,982 \u20ac versus OH 17,141 \u20ac). The QALYs gained over 1 year postoperative were mean (standard deviation [SD]) 0.834 (0.218) for LH and mean 0.795 (0.237) for OH. The ICER was 36,677 \u20ac per additional QALY gained, and uncertainty analyses showed that LH had a 77% probability of being cost-effective compared with OH at a willingness-to-pay (WTP) threshold of 80,000 \u20ac.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although LH was more costly than OH, in a multicenter randomized trial, its clinical advantages translated into more QALYs gained over the first postoperative year and high probability of cost-effectiveness. These findings suggest that, where resources allow, LH may be preferred over OH for selected patients, offering both clinical benefits and acceptable economic value.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1245\/s10434-025-18779-4","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:02:52Z","timestamp":1765544572000},"page":"2882-2898","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Healthcare Utilization, Costs, and Cost-Effectiveness of Patients Undergoing Laparoscopic and Open Hemihepatectomy: A Secondary Analysis of the ORANGE II PLUS Randomized Controlled, Phase 3, Superiority Trial"],"prefix":"10.1245","volume":"33","clinical-trial-number":[{"clinical-trial-number":"nct01441856","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1027-8685","authenticated-orcid":false,"given":"Bram","family":"Olij","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Pilz da Cunha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merel","family":"Kimman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Ratti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Abu Hilal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto I.","family":"Troisi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Sutcliffe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc G.","family":"Besselink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Somaiah","family":"Aroori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishna V.","family":"Menon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f8rn","family":"Edwin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"D\u2019Hondt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerio","family":"Lucidi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom F.","family":"Ulmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"D\u00edaz-Nieto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahir","family":"Soonawalla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Sergeant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari\u00eblle M. 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