ORANGE SEGMENTS: Open Versus Laparoscopic Parenchymal Preserving Postero-Superior Liver Segment Resection

NCT ID: NCT03270917

Last Updated: 2025-05-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-01
• Study Completion Date: 2026-11-01

Brief Summary

The international and multicentre ORANGE SEGMENTS - Trial is a prospective, double blinded, randomized controlled study comparing patients undergoing parenchymal preserving resection of postero-superior liver segments (involving one or two of segments 4a, 7, 8). All patients will be participating in an enhanced recovery programme.

Primary outcome is time to functional recovery. Secondary study parameters include hospital length of stay, intraoperative blood loss, operation time, liver specific morbidity, readmission percentage, resection margin, quality of life, body image and cosmesis , reasons for delay of discharge after functional recovery, long term incidence of incisional hernias, hospital and societal costs during one year, time to adjuvant chemotherapy initiation, overall five-year survival.

Detailed Description

Liver resection for colorectal metastasis is a potential curative therapy and has become the standard of care in appropriately staged patients, offering five-year survival rates ranging from 38 up to 61% in selected cases, with approximately 30% of patients surviving ten years or more, compared to five-year survival rates of less than 5% for patients not amenable to resection. Liver surgery is also a widely accepted treatment for symptomatic benign lesions and those of uncertain nature or large size. Whilst the figures are a vast improvement on the past, there is still a need to refine the treatment of these patients, including surgical technique.

Open hepatectomy is the current standard of care for the management of primary and secondary tumours. The open postero-superior liver segment resection requires a large incision to achieve adequate access and proper control during resection. This has a significant impact on patient's recovery and, in cases of small resections, this access may represent the major component of surgical trauma. Advances in surgical technique and expertise now permit these operations to be performed with minor incisions by using the laparoscopic approach. Although the feasibility of laparoscopic hepatectomy has been established, only select centres use this technique as their primary modality.

Laparoscopic liver resection was first reported in 1991. Over the past decades, the method has gained wide acceptance for various liver resection procedures. Multiple retrospective case series, patient cohorts, systematic reviews and meta-analyses have compared open with laparoscopic liver surgery and indicate the laparoscopic approach to be safely applicable for the resection of both malignant and benign liver lesions. Laparoscopic liver resection has been associated with shorter hospital length of stay, reduced intraoperative blood loss, less postoperative pain and earlier recovery. Despite this, concerns remain over operative times, the ability to control haemorrhage laparascopically and long-term oncological outcomes.

Initially, the left lateral segments of the liver were chosen for anatomic laparoscopic resection, with good results. Many liver centres worldwide currently use laparoscopy for resection of the anterior liver segments. Whilst case control studies would now seem sufficient to allay such concerns in the context of minor liver resections and left lateral sectionectomies, the adoption and dissemination of laparoscopy by hepatobiliary oncologic surgeons for major hepatectomies and resections of postero-superior segments has been restricted. Besides the relatively low volume of patients, major laparoscopic liver resections are technically demanding, have a significant learning curve, are time consuming, are thought to hold an increased morbidity risk and lack in evidence.

Nevertheless, a new impulse for the laparoscopic management of major liver lesions came after the first reports of laparoscopic hemihepatectomies, which demonstrated that in expert hands major anatomical laparoscopic liver resections are feasible with good efficacy and safety. When comparing surgical procedures, one of the easiest to measure and often used outcomes is the length of hospital stay; the time it takes for a patient to be discharged from the hospital after an operation. On the whole, a median hospital length of stay of 6.0 to 13.1 days and 3.5 to 10.0 days have been observed after open and laparoscopic hepatic resections in European centres respectively. For major surgery in expert centres, median duration of hospital admission varied between 6 to 12.5 days for open surgery and 4 to 8.2 days for laparoscopic resections. Concentrating on postero-superior liver segment resections, the median hospital stay is 6 days (3-44 days) for those undergoing open compared with 4 days (1-11 days) for those having laparoscopic resections.

Besides the immediate benefits to the patient, such as decreased intraoperative blood loss, diminished postoperative pain, earlier recovery and reduced hospital length of stay, laparoscopic liver surgery may also have the potential to improve outcomes in the longer term by reducing complications, enhancing quality of life, improving cosmesis, ensuring early commencement and completion of adjuvant therapies. However, level-1 evidence on all outcomes is still to be presented.

Within the framework of optimized perioperative care, broader indications for hepatic surgery and further adoption of laparoscopic liver resections, there is a clear need for a randomized trial. Therefore, the multicentre and international ORANGE SEGMENTS - Trial has been designed to provide evidence on the merits of laparoscopic versus open parenchymal preserving postero-superior liver segment resection within an enhanced recovery programme in terms of time to functional recovery, hospital length of stay, intraoperative blood loss, operation time, resection margin, time to adjuvant chemotherapy initiation, readmission percentage, (liver specific) morbidity, quality of life, body image, reasons for delay of discharge after functional recovery, long term incidence of incisional hernias, hospital and societal costs during one year and overall five-year survival.

Conditions

Liver Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Open

Open liver surgery

Group Type: OTHER

Parenchymal preserving postero-superior liver segment resection

Intervention Type: PROCEDURE

Parenchymal preserving liver segment resection of one or two of the postero-superior liver segments (4A, 7 or 8).

Laparoscopy

Laparoscopic liver surgery

Group Type: OTHER

Parenchymal preserving postero-superior liver segment resection

Intervention Type: PROCEDURE

Parenchymal preserving liver segment resection of one or two of the postero-superior liver segments (4A, 7 or 8).

Interventions

Parenchymal preserving postero-superior liver segment resection

Parenchymal preserving liver segment resection of one or two of the postero-superior liver segments (4A, 7 or 8).

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Patients requiring a parenchymal sparing liver resection (including wedge resections and full segmentectomies) involving one or two of segments 4a/7/8 for accepted indications . A segment 6/7 resection would also be eligible.
• Able to understand the nature of the study and what will be required of them.
• Men and non-pregnant, non-lactating women, aged 18 years and older.
• BMI between and including 18-35 kg/m2
• Patients with ASA physical status I-II-III.

Exclusion Criteria

• Inability to give (written) informed consent.
• Patients requiring other liver surgery than a parenchymal sparing resection involving one or two of segments 4a, 7, 8.
• Patients requiring parenchymal sparing liver resection involving segment 1. This is due to the high level of technical difficulty.
• Patients with hepatic lesion(s), that are located with insufficient margin from vascular or biliary structures to be operated laparoscopically.
• Patients with ASA physical status IV-V.
• Repeat hepatectomy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

The Queen Elizabeth Hospital

OTHER

Sponsor Role: collaborator

General Hospital Groeninge

OTHER

Sponsor Role: collaborator

Liverpool University Hospitals NHS Foundation Trust

OTHER_GOV

Sponsor Role: collaborator

King's College Hospital NHS Trust

OTHER

Sponsor Role: collaborator

San Raffaele University Hospital, Italy

OTHER

Sponsor Role: collaborator

Newcastle-upon-Tyne Hospitals NHS Trust

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: collaborator

Oxford University Hospitals NHS Trust

OTHER

Sponsor Role: collaborator

Derriford Hospital

OTHER

Sponsor Role: collaborator

University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Manchester University NHS Foundation Trust

OTHER_GOV

Sponsor Role: collaborator

Moscow Clinical Scientific Center

OTHER

Sponsor Role: collaborator

San Camillo Hospital, Rome

OTHER

Sponsor Role: collaborator

Fondazione Poliambulanza Istituto Ospedaliero

OTHER

Sponsor Role: collaborator

Federico II University

OTHER

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohammed Abu Hilal, Prof.

Role: STUDY_CHAIR

University Hospital Southampton NHS Foundation Trust

John Primrose, Prof.

Role: STUDY_CHAIR

University Hospital Southampton NHS Foundation Trust

Locations

General Hospital Groeninge

Kortrijk, , Belgium

Poliambulanza Hospital

Brescia, , Italy

San Raffaele Hospital

Milan, , Italy

San Camillo-Forlanini Hospital

Rome, , Italy

Academic Medical Center

Amsterdam, , Netherlands

Maastricht University Medical Center+

Maastricht, , Netherlands

University Hospital Oslo

Oslo, , Norway

Moscow Clinical Scientific Center

Moscow, , Russia

Aintree University Hospital

Aintree, , United Kingdom

Queen Elizabeth Hospital

Birmingham, , United Kingdom

King's College Hospital

London, , United Kingdom

Manchester Royal Infirmary

Manchester, , United Kingdom

Freeman Hospital

Newcastle, , United Kingdom

Oxford University Hospitals

Oxford, , United Kingdom

Derriford Hospital

Plymouth, , United Kingdom

University Hospital Southampton

Southampton, , United Kingdom

Countries

Belgium; Italy; Netherlands; Norway; Russia; United Kingdom

References

Coles SR, Besselink MG, Serin KR, Alsaati H, Di Gioia P, Samim M, Pearce NW, Abu Hilal M. Total laparoscopic management of lesions involving liver segment 7. Surg Endosc. 2015 Nov;29(11):3190-5. doi: 10.1007/s00464-014-4052-2. Epub 2015 Jan 13.

Reference Type: BACKGROUND

PMID: 25582963 (View on PubMed)

Cipriani F, Shelat VG, Rawashdeh M, Francone E, Aldrighetti L, Takhar A, Armstrong T, Pearce NW, Abu Hilal M. Laparoscopic Parenchymal-Sparing Resections for Nonperipheral Liver Lesions, the Diamond Technique: Technical Aspects, Clinical Outcomes, and Oncologic Efficiency. J Am Coll Surg. 2015 Aug;221(2):265-72. doi: 10.1016/j.jamcollsurg.2015.03.029. Epub 2015 Mar 27.

Reference Type: BACKGROUND

PMID: 25899733 (View on PubMed)

Scuderi V, Barkhatov L, Montalti R, Ratti F, Cipriani F, Pardo F, Tranchart H, Dagher I, Rotellar F, Abu Hilal M, Edwin B, Vivarelli M, Aldrighetti L, Troisi RI. Outcome after laparoscopic and open resections of posterosuperior segments of the liver. Br J Surg. 2017 May;104(6):751-759. doi: 10.1002/bjs.10489. Epub 2017 Feb 13.

Reference Type: BACKGROUND

PMID: 28194774 (View on PubMed)

Zheng B, Zhao R, Li X, Li B. Comparison of laparoscopic liver resection for lesions located in anterolateral and posterosuperior segments: a meta-analysis. Surg Endosc. 2017 Nov;31(11):4641-4648. doi: 10.1007/s00464-017-5527-8. Epub 2017 Apr 7.

Reference Type: BACKGROUND

PMID: 28389796 (View on PubMed)

Sijberden JP, Kuemmerli C, Ratti F, D'Hondt M, Sutcliffe RP, Troisi RI, Efanov M, Fichtinger RS, Diaz-Nieto R, Ettorre GM, Sheen AJ, Menon KV, Besselink MG, Soonawalla Z, Aroori S, Marino R, De Meyere C, Marudanayagam R, Zimmitti G, Olij B, Eminton Z, Brandts L, Ferrari C, M van Dam R, Aldrighetti LA, Pugh S, Primrose JN, Abu Hilal M. Laparoscopic versus open parenchymal preserving liver resections in the posterosuperior segments (ORANGE Segments): a multicentre, single-blind, randomised controlled trial. Lancet Reg Health Eur. 2025 Feb 20;51:101228. doi: 10.1016/j.lanepe.2025.101228. eCollection 2025 Apr.

Reference Type: DERIVED

PMID: 40060302 (View on PubMed)

Kuemmerli C, Fichtinger RS, Moekotte A, Aldrighetti LA, Aroori S, Besselink MGH, D'Hondt M, Diaz-Nieto R, Edwin B, Efanov M, Ettorre GM, Menon KV, Sheen AJ, Soonawalla Z, Sutcliffe R, Troisi RI, White SA, Brandts L, van Breukelen GJP, Sijberden J, Pugh SA, Eminton Z, Primrose JN, van Dam R, Hilal MA; ORANGE trials collaborative. 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.

Reference Type: DERIVED

PMID: 35264216 (View on PubMed)

Other Identifiers

NL36215.068.11*

Identifier Type: -

Identifier Source: org_study_id