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

Liver Surgery Clinical Trial

Official title:

The ORANGE SEGMENTS - Trial: an International Multicentre Randomized Controlled Trial of Open Versus Laparoscopic Parenchymal Preserving Postero-superior Liver Segment Resection

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03270917
• Other study ID #: NL36215.068.11*
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 1, 2017
• Est. completion date: December 1, 2026

Study information

• Verified date: December 2021
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 250
• Est. completion date: December 1, 2026
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Liver Surgery

Intervention

Procedure:
• 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).

Locations

Country	Name	City	State
Belgium	General Hospital Groeninge	Kortrijk
Italy	Poliambulanza Hospital	Brescia
Italy	San Raffaele Hospital	Milan
Italy	San Camillo-Forlanini Hospital	Rome
Netherlands	Academic Medical Center	Amsterdam
Netherlands	Maastricht University Medical Center+	Maastricht
Norway	University Hospital Oslo	Oslo
Russian Federation	Moscow Clinical Scientific Center	Moscow
United Kingdom	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

Sponsors (17)

Lead Sponsor

Collaborator

Maastricht University Medical Center

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Derriford Hospital, Federico II University, Fondazione Poliambulanza Istituto Ospedaliero, General Hospital Groeninge, King's College Hospital NHS Trust, Liverpool University Hospitals NHS Foundation Trust, Manchester University NHS Foundation Trust, Moscow Clinical Scientific Center, Newcastle-upon-Tyne Hospitals NHS Trust, Oslo University Hospital, Oxford University Hospitals NHS Trust, Queen Elizabeth Hospital Birmingham, San Camillo Hospital, Rome, San Raffaele University Hospital, Italy, University Hospital Southampton NHS Foundation Trust

Countries where clinical trial is conducted

Belgium,  Italy,  Netherlands,  Norway,  Russian Federation,  United Kingdom, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to functional recovery	Time until a patient is functionally recovered	expected average of 4-10 days
Secondary	Hospital length of stay	Total length of hospital stay	30 days
Secondary	Intraoperative blood loss	Net intraoperative blood loss	during procedure
Secondary	Operating time		surgical time from incision until closure
Secondary	(Liver specific) morbidity	Composite endpoint of liver specific morbidity (intra-abdominal bleeding, intra-abdominal abcess, ascites, postresectional liver failure, intra-operative mortality, bile leakage)	1 year
Secondary	Readmission percentage	Total percentage of patients being readmitted	1 year
Secondary	Resection margin	Residual tumor cells in resection border	1 year
Secondary	Quality of life	The physical, social and emotional well-being of the patient	1 year
Secondary	Body image and cosmesis	The aesthetic appearance of the scars associated with the operation and its influence on the patient self-view	1 year
Secondary	Reasons for delay of discharge after functional recovery	All reasons that may cause delay in discharge after the patient has recovered functionally, such as administrative reasons, patient confidence, logistics problems, etc.	1 year
Secondary	Incisional herniation	Cicatricial hernia	1 year
Secondary	Hospital and societal costs	All costs that are associated with the operation, including in-hospital costs and out of hospital costs, such as home care, work absence, etc.	1 year
Secondary	Time to adjuvant chemotherapy initiation	The time it takes to start adjuvant chemotherapy after the patient has been operated	1 year
Secondary	Overall five-year survival	Five-year survival	5 years

External Links

•   The ORANGE - Trials consortium webpage