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

Not Applicable
Active, not recruiting
Conditions
Liver Surgery
Interventions
Procedure: Parenchymal preserving postero-superior liver segment resection
Registration Number
NCT03270917
Lead Sponsor
Maastricht University Medical Center
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
250
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
OpenParenchymal preserving postero-superior liver segment resectionOpen liver surgery
LaparoscopyParenchymal preserving postero-superior liver segment resectionLaparoscopic liver surgery
Primary Outcome Measures
NameTimeMethod
Time to functional recoveryexpected average of 4-10 days

Time until a patient is functionally recovered

Secondary Outcome Measures
NameTimeMethod
Incisional herniation1 year

Cicatricial hernia

Overall five-year survival5 years

Five-year survival

Intraoperative blood lossduring procedure

Net intraoperative blood loss

Operating timesurgical time from incision until closure
Body image and cosmesis1 year

The aesthetic appearance of the scars associated with the operation and its influence on the patient self-view

Reasons for delay of discharge after functional recovery1 year

All reasons that may cause delay in discharge after the patient has recovered functionally, such as administrative reasons, patient confidence, logistics problems, etc.

Time to adjuvant chemotherapy initiation1 year

The time it takes to start adjuvant chemotherapy after the patient has been operated

Hospital length of stay30 days

Total length of hospital stay

Readmission percentage1 year

Total percentage of patients being readmitted

Resection margin1 year

Residual tumor cells in resection border

Quality of life1 year

The physical, social and emotional well-being of the patient

Hospital and societal costs1 year

All costs that are associated with the operation, including in-hospital costs and out of hospital costs, such as home care, work absence, etc.

(Liver specific) morbidity1 year

Composite endpoint of liver specific morbidity (intra-abdominal bleeding, intra-abdominal abcess, ascites, postresectional liver failure, intra-operative mortality, bile leakage)

Trial Locations

Locations (16)

Aintree University Hospital

🇬🇧

Aintree, United Kingdom

Manchester Royal Infirmary

🇬🇧

Manchester, United Kingdom

Queen Elizabeth Hospital

🇬🇧

Birmingham, United Kingdom

General Hospital Groeninge

🇧🇪

Kortrijk, Belgium

Freeman Hospital

🇬🇧

Newcastle, United Kingdom

Derriford Hospital

🇬🇧

Plymouth, United Kingdom

King's College Hospital

🇬🇧

London, United Kingdom

Oxford University Hospitals

🇬🇧

Oxford, United Kingdom

University Hospital Southampton

🇬🇧

Southampton, United Kingdom

Academic Medical Center

🇳🇱

Amsterdam, Netherlands

Moscow Clinical Scientific Center

🇷🇺

Moscow, Russian Federation

Poliambulanza Hospital

🇮🇹

Brescia, Italy

San Raffaele Hospital

🇮🇹

Milan, Italy

San Camillo-Forlanini Hospital

🇮🇹

Rome, Italy

University Hospital Oslo

🇳🇴

Oslo, Norway

Maastricht University Medical Center+

🇳🇱

Maastricht, Netherlands

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