Laparoscopic versus open parenchymal preserving liver resections in the posterosuperior segments (ORANGE Segments): a multicentre, single-blind, randomised controlled trial

Background: An increasing number of liver resections are performed laparoscopically, while laparoscopic resection of lesions in the posterosuperior segments is technically challenging. We aimed to assess the outcomes of laparoscopic and open parenchymal preserving resection of lesions in the posterosuperior segments in a randomised controlled trial. Methods: In this multicentre, patient-blinded, superiority randomised controlled trial, patients requiring parenchymal preserving liver resection for tumours in segment 4a, 7, or 8 were enrolled at 17 centres and randomised 1:1 to laparoscopic or open surgery using a minimisation scheme stratifying for centre and lesion size. The primary endpoint was time to functional recovery measured in postoperative days. To detect a difference in time to functional recovery of two days the sample size needed 250 patients, an interim analysis was planned with 125 patients. Patients and outcome assessors were blinded to the allocation. The study was registered on clinicaltrials.gov, NCT03270917. Findings: Between November 2017 and November 2021, 251 patients were randomised to laparoscopic (n = 125) or open (n = 126) surgery. The majority of patients had a preoperative diagnosis of cancer (225/246 = 91.5%). Time to functional recovery was 3 days (IQR 3–5) in the laparoscopic group compared to 4 days (IQR 3–5) in the open group (difference −19.2%, 96% CI −28.8% to −8.4%; p < 0.001). Hospital stay was similarly shorter in the laparoscopic group (4 days, IQR 3–5 versus 5 days, IQR 4–7; p < 0.001). There were three deaths in the laparoscopic group (3/122 = 2.5%) and one in the open group (1/124 = 0.8%) within 90 days of resection (p = 0.336). Overall postoperative morbidity, severe morbidity, liver-specific morbidity, and readmission were not statistically significant different between the groups. The radical resection (R0) rate in patients with cancer was comparable (laparoscopic 93/106 = 87.7% versus open 97/113 = 85.8%, p = 0.539). Interpretation: For patients with lesions in the posterosuperior segments of the liver, laparoscopic surgery, as compared to open surgery, reduces time to functional recovery. However, this reduction in time to functional recovery did not meet the hypothesized difference in time to functional recovery of two days. Funding: This investigator-initiated trial was funded by Ethicon ( Johnson & Johnson), Cancer Research United Kingdom, and Maastricht University Medical Centre+.