Effect of the Laparoscopic Approach in Reducing Postoperative Severe Complications Following Hepatectomy for Colorectal Liver Metastases

Study Overview
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Brief Summary
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The objective of this study is to demonstrate the superiority of the laparoscopic approach over the open approach in the resection of colorectal liver metastases, by examining the reduction of postoperative complications (including mortality), measured using the Comprehensive Complication Index (CCI) within 90 days of the procedure or regardless of the date during the hospital stay.

Detailed Description
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While laparotomy is still the standard approach of resectable colorectal liver mestastases, its associated morbidity remains non-negligible with reported mortality and complications rates ranging from 2 to 8% and 30 to 70%, respectively (1). Besides the underlying liver disease together with the comorbidities of the patients, this high morbidity is also related to the type of surgical approach. Since less than 15% of liver resections are currently performed using the laparoscopic approach in France, a trial showing the superiority of the laparoscopic approach in comparison to the open approach for patients with colorectal liver metastases qualifying for both approaches would allow improving management of patients, reducing the length of stay, maybe decreasing the global cost and changing current practices on a national scale. In order to demonstrate the superiority of the laparoscopic approach over the laparotomy approach, patients with colorectal hepatic metastasis will be randomly assigned to either the laparoscopy or laparotomy groups. Post-operative complications (including mortality) will be measured using the Comprehensive Complication Index (CCI) within 90 days postoperatively or at any time during hospitalization. The participation time for each patient in the study is 3 years, the patient will be followed at 1, 3, 6, 9, 9, 12, 15, 18, 21, 24, 30 and 36 months.

Official Title
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Effect of the Laparoscopic Approach in Reducing Postoperative Severe Complications Following Hepatectomy for Colorectal Liver Metastases: Prospective, Randomized, Controlled Study

Conditions
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Liver Metastasis Colon Cancer, Postoperative Complications

Intervention / Treatment
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* Procedure: hepatectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presenting with colorectal liver metastases requiring liver resection ± concomitant radiofrequency ablation. Qualifying for both a laparoscopic approach and an open approach. Informed written consent. Affiliated to health insurance regimen. Exclusion Criteria: Hybrid liver resection (including both laparoscopic and open resection). Liver resection requiring an associated vascular or biliary reconstruction. Contraindication to surgery. Contraindication to laparoscopy (pneumoperitoneum). ASA (American Society of Anesthesiologists) score IV or V or life expectancy < 3 months. Poor comprehension of French language or cognitive impairment Pregnancy or breastfeeding. Patient under guardianship or unable to give consent People particularly protected by French law.

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: Prospective multicenter, open-label and pragmatic, controlled randomized (minimization procedure) superiority trial in 2 parallel groups comparing the rates of 90 days postoperative complications between patients undergoing laparoscopic and open liver resection for colorectal liver metastases.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: laparoscopic liver resection<br>Laparoscopy allows some surgical procedures to be performed through small incisions that enable the operator to access the abdominal cavity, often at the pubic area, and surgical instruments are introduced through these small incisions. This technique avoids large abdominal incisions and significantly reduces the duration of hospitalization. | Procedure: hepatectomy<br>* Resection colorectal liver metastases using a laparoscopic approach or an open approach.<br>|
| Other: open liver resection<br>standard of care | Procedure: hepatectomy<br>* Resection colorectal liver metastases using a laparoscopic approach or an open approach.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of overall complications using the comprehensive complication Index (CCI) | CCI is calculated using the burden of postoperative complications weighted with a measure of the severity according to the widely accepted Dindo-Clavien classification of postoperative complications and a dedicated CCI calculator. | Within 90 days postoperatively or at any time during hospitalization. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients presenting severe postoperative complications | Proportion of patients presenting severe postoperative complications rate as defined by the Clavien-Dindo classification ≥ grade 3 (including mortality) between patients treated with laparoscopic liver resection and those treated with open liver surgery | Within 90 days postoperatively or at any time during hospitalization. | 
| Rate of conversion from laparoscopy liver resection to open liver surgery | Conversion is defined as the requirement for laparotomy at any time of the procedure with the exception of the extraction of the resected specimen. Specific data regarding conversion will be noticed from the operative reports. These included the reasons for conversion, the timing of conversion and the type of conversion. | during surgery. | 
| Length of hospital stay | Length of hospital stay and occurrence of unplanned readmission after discharge,assessed by hospitalization reports | Within 90 days postoperatively or at any time during hospitalization. | 
| Delay of recovery before resuming professional activities. | Delay of recovery before resuming professional activities assessed by PQRS (Postoperative Quality Recovery Scale) including nociceptive domain, emotional domain, cognition domain and day-to-day activities at D-1, D1, D7, D30 and D90. | Within 90 days postoperatively | 
| Postoperative quality of life using quality of life questionnaries. | Patient-reported outcome measures were assessed with the validated European Organisation for Research and Treatment of Cancer (EORTC) score questionnaire, EORTC Quality of Life Questionnaire (QLQ) -C30 (version 3.0), and the module dedicated to colorectal liver metastases (EORTC QLQ-LMC21). EQ5D-5L is a standardised measure of health status that provides a simple descriptive profile and a single index value suitable for the economic evaluation of health. It will be used to calculate the QALYs of each enrolled patient, by valuing health. | At the inclusion (before surgery), at 1 month postintervention, 3 months, 6 months and then every 6 months during 3 years. | 
| Health economics analysis | A cost-effectiveness study will be performed and completed by a cost-utility analysis to identify the efficient therapeutic strategy (laparoscopic approach) ompared to the reference (open surgery). Only direct costs will be considered for treatments, management of side effects, medical transports, rehabilitation procedures and medical consultations. Out of hospital resources are valued from the Social Health Insurance (SHI) tariffs and hospital stays the Diagnosis-Related group (DRG) tariff taking into account additional daily fixed prices for ICU stay, if any. | During the full participation period (3 years). | 
| Oncologic quality of the resection using the pathological report. | Mean surgical margin widths (in millimeters). Percentages of microscopically complete (R0), microscopically incomplete (R1) and macroscopically incomplete (R2) resections as stated in the pathological report. | During surgery | 
| Disease-free and overall survival at 3 years. | Percentage of patients with intrahepatic or extrahepatic recurrence three years after the operation. Median disease-free survival time (in months). Percentage of patients who died at 1, 2 and 3 years after the procedure. Median overall survival time (in months). | During the full participation period (3 years). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver resection, Laparoscopy