Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial
Authors: Fichtinger Robert S. , Aldrighetti Luca A. , Abu Hilal Mohammed , Troisi Roberto I. , Sutcliffe Robert P. , Besselink Marc G. , Aroori Somaiah , Menon Krishna V. , Edwin Bjørn , D'Hondt Mathieu , Lucidi Valerio , Ulmer Tom F. , Díaz-Nieto Rafael , Soonawalla Zahir , White Steve , Sergeant Gregory , Olij Bram , Ratti Francesca , Kuemmerli Christoph , Scuderi Vincenzo , Berrevoet Frederik , Vanlander Aude , Marudanayagam Ravi , Tanis Pieter , Dewulf Maxime J.L. , Dejong Cornelis H.C. , Eminton Zina , Kimman Merel L. , Brandts Lloyd , Neumann Ulf P. , Fretland Åsmund A. , Pugh Siân A. , van Breukelen Gerard J.P. , Primrose John N. , van Dam Ronald M. ,   for the ORANGE II PLUS Collaborative, Neumann Ulf , Ulmer Florian , Clausen Finja , Díaz-Nieto Rafael , Lintforth Michelle , Besselink Marc , Tanis Pieter , Gorçek Burak , van der Poel Marcel , Sutcliffe Robert , Marudanayagam Ravi , Rogers Penelope , Lucidi Valerio , van Laethem Viviane , Troisi Roberto , Berrevoet Frederik , Scuderi Vincenzo , Vanlander Aude , van Loo Betsy , Segers Kathleen , Sergeant Gregory , D'Hondt Mathieu , Demeyere Celine , Menon Krishna , Zamalloa Ane , van Dam Ronald , Dejong Cornelis , Dewulf Maxime , Brandts Lloyd , Fichtinger Robert , Olij Bram , Kimman Merel , van Breukelen Gerard , Aldrighetti Luca , Ratti Francesca , White Steve , Robinson Stuart , Brunton Caroline , Edwin Björn , Fretland Åsmund , Aghayan Davit , Soonawalla Zahir , Gordon-Quayle Katherine , Aroori Somaiah , Ward Tracy , Primrose John , Abu Hilal Mohammed , Kümmerli Christopher , Boxal Jess , Eminton Zina 
Published: April 2024

PURPOSE To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy. PATIENTS AND METHODS This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018. RESULTS Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, –17.5% [96% CI, –25.6 to –8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009). CONCLUSION Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.