Laparoscopic versus open resections in the posterosuperior liver segments within an enhanced recovery programme (ORANGE Segments): study protocol for a multicentre randomised controlled trial

Christoph Kuemmerli; Robert S Fichtinger; Alma Moekotte; Luca A Aldrighetti; Somaiah Aroori; Marc G H Besselink; Mathieu D'Hondt; Rafael Díaz-Nieto; Bjørn Edwin; Mikhail Efanov; Giuseppe M Ettorre; Krishna V Menon; Aali J Sheen; Zahir Soonawalla; Robert Sutcliffe; Roberto I Troisi; Steven A White; Lloyd Brandts; Gerard J P van Breukelen; Jasper Sijberden; Siân A Pugh; Zina Eminton; John N Primrose; Ronald van Dam; Mohammed Abu Hilal; ORANGE trials collaborative

doi:10.1186/s13063-022-06112-3

Laparoscopic versus open resections in the posterosuperior liver segments within an enhanced recovery programme (ORANGE Segments): study protocol for a multicentre randomised controlled trial

Trials. 2022 Mar 9;23(1):206. doi: 10.1186/s13063-022-06112-3.

Authors

Christoph Kuemmerli^#^{1

2}, Robert S Fichtinger^#^{3

4}, Alma Moekotte¹, Luca A Aldrighetti⁵, Somaiah Aroori⁶, Marc G H Besselink⁷, Mathieu D'Hondt⁸, Rafael Díaz-Nieto⁹, Bjørn Edwin¹⁰, Mikhail Efanov¹¹, Giuseppe M Ettorre¹², Krishna V Menon¹³, Aali J Sheen¹⁴, Zahir Soonawalla¹⁵, Robert Sutcliffe¹⁶, Roberto I Troisi¹⁷, Steven A White¹⁸, Lloyd Brandts¹⁹, Gerard J P van Breukelen²⁰, Jasper Sijberden^{2

7}, Siân A Pugh²¹, Zina Eminton²², John N Primrose²³, Ronald van Dam^{3

4

24}, Mohammed Abu Hilal^{25

26}; ORANGE trials collaborative

Affiliations

¹ Hepatobiliary and Pancreatic Surgical Unit, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK.
² Department of Surgery, Foundation Poliambulanza, Via Bissolati, Brescia, Italy.
³ Department of Surgery, Maastricht University Medical Centre+, 6202 AZ, Maastricht, The Netherlands.
⁴ Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
⁵ Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy.
⁶ Peninsula HPB Unit, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth, UK.
⁷ Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
⁸ Department of Digestive and Hepatobiliary/Pancreatic Surgery, Groeninge Hospital, Kortrijk, Belgium.
⁹ Hepatobiliary Surgery Unit, Aintree University Hospital, Liverpool, UK.
¹⁰ Department of HPB Surgery, Oslo University Hospital, Oslo, Norway.
¹¹ Department of Hepato-Pancreato-Biliary Surgery, Moscow Clinical Research Centre, Moscow, Russia.
¹² Division of General Surgery and Liver Transplantation, San Camillo Hospital, Rome, Italy.
¹³ Institute of Liver Studies, Kings College Hospital, London, UK.
¹⁴ Department of Surgery, Manchester University Foundation Trust, Manchester, UK.
¹⁵ Department of Surgery, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
¹⁶ Department of Hepatobiliary and Pancreatic Surgery, University Hospitals Birmingham, NHS Foundation Trust, Birmingham, UK.
¹⁷ Division of HPB, Minimally Invasive and Robotic Surgery, Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy.
¹⁸ Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK.
¹⁹ Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht UMC+, Maastricht, The Netherlands.
²⁰ Department of Methodology and Statistics, Maastricht University Medical Centre, Maastricht, The Netherlands.
²¹ Department of Oncology, Addenbrooke's Hospital, Cambridge, UK.
²² Southampton Clinical Trials Unit, University of Southampton, Southampton, UK.
²³ Department of Surgery, University of Southampton, Southampton, UK.
²⁴ GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
²⁵ Hepatobiliary and Pancreatic Surgical Unit, University Hospital Southampton NHS Foundation Trust, Southampton, SO16 6YD, UK. abuhilal9@gmail.com.
²⁶ Department of Surgery, Foundation Poliambulanza, Via Bissolati, Brescia, Italy. abuhilal9@gmail.com.

^# Contributed equally.

Abstract

Background: A shift towards parenchymal-sparing liver resections in open and laparoscopic surgery emerged in the last few years. Laparoscopic liver resection is technically feasible and safe, and consensus guidelines acknowledge the laparoscopic approach in the posterosuperior segments. Lesions situated in these segments are considered the most challenging for the laparoscopic approach. The aim of this trial is to compare the postoperative time to functional recovery, complications, oncological safety, quality of life, survival and costs after laparoscopic versus open parenchymal-sparing liver resections in the posterosuperior liver segments within an enhanced recovery setting.

Methods: The ORANGE Segments trial is an international multicentre randomised controlled superiority trial conducted in centres experienced in laparoscopic liver resection. Eligible patients for minor resections in the posterosuperior segments will be randomised in a 1:1 ratio to undergo laparoscopic or open resections in an enhanced recovery setting. Patients and ward personnel are blinded to the treatment allocation until postoperative day 4 using a large abdominal dressing. The primary endpoint is time to functional recovery. Secondary endpoints include intraoperative outcomes, length of stay, resection margin, postoperative complications, 90-day mortality, time to adjuvant chemotherapy initiation, quality of life and overall survival. Laparoscopic liver surgery of the posterosuperior segments is hypothesised to reduce time to functional recovery by 2 days in comparison with open surgery. With a power of 80% and alpha of 0.04 to adjust for interim analysis halfway the trial, a total of 250 patients are required to be randomised.

Discussion: The ORANGE Segments trial is the first multicentre international randomised controlled study to compare short- and long-term surgical and oncological outcomes of laparoscopic and open resections in the posterosuperior segments within an enhanced recovery programme.

Trial registration: ClinicalTrials.gov NCT03270917 . Registered on September 1, 2017. Before start of inclusion.

Protocol version: version 12, May 9, 2017.

Keywords: Enhanced recovery; Laparoscopy; Liver surgery; Posterosuperior segments; Randomised controlled trial.

Publication types

Clinical Trial Protocol

MeSH terms

Hepatectomy* / adverse effects
Hepatectomy* / methods
Humans
Laparoscopy* / adverse effects
Laparoscopy* / methods
Length of Stay
Liver Neoplasms* / surgery
Multicenter Studies as Topic
Quality of Life
Randomized Controlled Trials as Topic
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT03270917

Abstract

Publication types

MeSH terms

Associated data

Grants and funding