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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Liver Surgery

Intervention / Treatment
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* Procedure: Parenchymal preserving postero-superior liver segment resection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomised to either the open or the laparoscopic treatment arm.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Open<br>Open liver surgery | Procedure: Parenchymal preserving postero-superior liver segment resection<br>* Parenchymal preserving liver segment resection of one or two of the postero-superior liver segments (4A, 7 or 8).<br>|
| Other: Laparoscopy<br>Laparoscopic liver surgery | Procedure: Parenchymal preserving postero-superior liver segment resection<br>* Parenchymal preserving liver segment resection of one or two of the postero-superior liver segments (4A, 7 or 8).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to functional recovery | Time until a patient is functionally recovered | expected average of 4-10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital length of stay | Total length of hospital stay | 30 days | 
| Intraoperative blood loss | Net intraoperative blood loss | during procedure | 
| Operating time |  | surgical time from incision until closure | 
| (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 | 
| Readmission percentage | Total percentage of patients being readmitted | 1 year | 
| Resection margin | Residual tumor cells in resection border | 1 year | 
| Quality of life | The physical, social and emotional well-being of the patient | 1 year | 
| Body image and cosmesis | The aesthetic appearance of the scars associated with the operation and its influence on the patient self-view | 1 year | 
| 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 | 
| Incisional herniation | Cicatricial hernia | 1 year | 
| 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 | 
| Time to adjuvant chemotherapy initiation | The time it takes to start adjuvant chemotherapy after the patient has been operated | 1 year | 
| Overall five-year survival | Five-year survival | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parenchymal preserving, Postero-superior, Laparoscopy, Hepatectomy