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Randomized Controlled Trial
. 2024 May 20;42(15):1799-1809.
doi: 10.1200/JCO.23.01019. Epub 2024 Apr 19.

Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial

Robert S Fichtinger  1   2 , Luca A Aldrighetti  3 , Mohammed Abu Hilal  4   5 , Roberto I Troisi  6   7 , Robert P Sutcliffe  8 , Marc G Besselink  9   10 , Somaiah Aroori  11 , Krishna V Menon  12 , Bjørn Edwin  13 , Mathieu D'Hondt  14 , Valerio Lucidi  15 , Tom F Ulmer  1   2 , Rafael Díaz-Nieto  16 , Zahir Soonawalla  17 , Steve White  18 , Gregory Sergeant  19 , Bram Olij  1   2   20 , Francesca Ratti  3 , Christoph Kuemmerli  4 , Vincenzo Scuderi  7 , Frederik Berrevoet  7 , Aude Vanlander  21 , Ravi Marudanayagam  8 , Pieter Tanis  9   10 , Maxime J L Dewulf  1 , Cornelis H C Dejong  1   2   22 , Zina Eminton  23 , Merel L Kimman  24 , Lloyd Brandts  24 , Ulf P Neumann  1   2   25 , Åsmund A Fretland  13 , Siân A Pugh  26 , Gerard J P van Breukelen  27 , John N Primrose  4 , Ronald M van Dam  1   2   20 ; ORANGE II PLUS Collaborative
Collaborators, Affiliations
Randomized Controlled Trial

Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial

Robert S Fichtinger et al. J Clin Oncol. .

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01441856.

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Conflict of interest statement

Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Marc G. Besselink

Research Funding: Intuitive Surgical, Medtronic, Ethicon/Johnson & Johnson, Oncosil, Viatris, Viatris

Zahir Soonawalla

Travel, Accommodations, Expenses: Ipsen

Steve White

Honoraria: Baxter, Medtronic, Johnson and Johnson

Research Funding: Intuitive Surgical

Travel, Accommodations, Expenses: Baxter, Medtronic

Gregory Sergeant

Travel, Accommodations, Expenses: Intuitive Surgical

Christoph Kuemmerli

Stock and Other Ownership Interests: Novartis

Pieter Tanis

Consulting or Advisory Role: Medtronic (Inst)

Research Funding: Novus Scientific (Inst)

Ulf P. Neumann

Honoraria: Merck Serono, AstraZeneca, Dr Falk Pharma UK Ltd

Åsmund A. Fretland

Honoraria: Olympus Medical Systems, Bayer Health

Research Funding: Siemens Healthineers (Inst)

Siân A. Pugh

Honoraria: Merck Serono, SERVIER

Travel, Accommodations, Expenses: Takeda

John N. Primrose

Honoraria: AstraZeneca

Travel, Accommodations, Expenses: Takeda

Ronald M. van Dam

Honoraria: Johnson & Johnson (Inst)

Research Funding: Abbott Laboratories (Inst), Guerbet (Inst)

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
CONSORT diagram of the ORANGE II PLUS trial. Surgical procedures that were converted from laparoscopy to hand-assisted or open surgery were considered a laparoscopic procedure in both the intention-to-treat analysis and the per-protocol analysis.
FIG 2.
FIG 2.
Global health status of the European Organization for Research and Treatment of cancer—Quality-of-Life Questionnaire C30.
FIG 3.
FIG 3.
Kaplan-Meier curves of probability of disease-free survival for laparoscopic hemihepatectomy versus open hemihepatectomy, (A) curtailed at a maximum follow-up time of 68 months for all malignancies (follow-up index 65%) (B) and for colorectal liver metastases at a maximal follow-up time of 62 months (follow-up index 67%). 99% CI in shadings.
FIG 4.
FIG 4.
Kaplan-Meier curves of probability of overall survival for laparoscopic hemihepatectomy versus open hemihepatectomy, (A) curtailed at a maximum of 68 months for all malignancies (follow-up index 43%) and (B) for colorectal liver metastases at a maximum follow-up time of 65 months (follow-up index 39%). 99% CI in shadings.
See this image and copyright information in PMC

References

    1. Kanas GP, Taylor A, Primrose JN, et al. Survival after liver resection in metastatic colorectal cancer: Review and meta-analysis of prognostic factors. Clin Epidemiol. 2012;4:283–301. - PMC - PubMed
    1. Cervantes A, Adam R, Rosello S, et al. Metastatic colorectal cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34:10–32. - PubMed
    1. Bridgewater J, Fletcher P, Palmer DH, et al. Long-term outcomes and exploratory analyses of the randomized phase III BILCAP study. J Clin Oncol. 2022;40:2048–2057. - PubMed
    1. Kehlet H. Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth. 1997;78:606–617. - PubMed
    1. Fretland AA, Sokolov A, Postriganova N, et al. Inflammatory response after laparoscopic versus open resection of colorectal liver metastases: Data from the Oslo-CoMet trial. Medicine (Baltimore) 2015;94:e1786. - PMC - PubMed

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