The Inflammatory Response to Stress and Angiogenesis in Liver Resection

The Inflammatory Response to Stress and Angiogenesis in Open Versus Laparoscopic Liver Resection for Colorectal Liver Metastases

Patients with resectable liver metastases of colorectal origin will be assigned to laparoscopic liver resection or conventional open liver surgery.

Blood samples will be drawn preoperatively and 24 hours after resection. Determination of Interleukin-6 (IL-6) and IL-8 will be done to assess the stress response between open and laparoscopic liver resection (Elisa test).

The Messenger Ribonucleic Acid (mRNA) of inflammation related factors (cyclooxygenase-2 (COX-2) and Matrix metalloproteinase (MMP-9)), angiogenesis related factor (vascular endothelial growth factor (VEGF) and hypoxia induced factor-1 (HIF-1)) in tumor tissue and normal liver parenchyma will be detected by real-time real time-Polymerase Chain Reaction (RT-PCR).

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Metastatic Cancer; Liver Metastases; Liver Cancer
• Intervention / Treatment: Procedure: Liver resection

Detailed Description

According to the null hypothesis, no difference in the IL6 postoperative value, between the two groups would be expected. To calculate sample size, a IL6 postoperative value of 100±40 pg/mL in the laparoscopic group and 60±40 mL/m pg/mL in the open group was hypothesized. Considering a two-sided α=0.05 and β=0.1, the minimal sample size required to achieve statistical significance was 17 subjects in both groups in a 1:1 randomization. Laparoscopic group was increased by 20% of patients considering a conversion rate of 20% accordingly. Randomization will be performed using computer-generated random numbers the day before operation and stopped when 20 patients per group will be reached.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18-80 years old
2. Patients with colorectal liver metastases
3. Colorectal liver metastases ≤10 cm in size -

Exclusion Criteria:

1. Patients not fit for laparoscopic surgery due to comorbidities
2. Patients with tumors close or infiltrating the major vessels -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Open Liver Resection; Conventional open liver resection trough subcostal incision	Procedure: Liver resection; liver resections for colorectal liver metastases
EXPERIMENTAL: Laparoscopic Liver Resection; Pure laparoscopic liver resection without hand assistance	Procedure: Liver resection; liver resections for colorectal liver metastases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in inflammatory response	Differences in POD 1 levels of IL6 and IL8	Preoperative and postoperative day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in tumor stimulating factors	Differences in levels of VEGF, HIF-1α, MMP-9 and COX2 in both humoral and normal liver tissue	One week after surgery
Overall Survival	From surgery to date of death or last follow up. Data will be reported in months	1-3-5 years
Recurrence free survival	From surgery to recurrence either in the liver or elsewhere. Data will be reported in months	1-3-5 years

Collaborators and Investigators

• Sponsor: University Hospital, Ghent

Publications and helpful links

General Publications

• Fretland AA, Sokolov A, Postriganova N, Kazaryan AM, Pischke SE, Nilsson PH, Rognes IN, Bjornbeth BA, Fagerland MW, Mollnes TE, Edwin B. Inflammatory Response After Laparoscopic Versus Open Resection of Colorectal Liver Metastases: Data From the Oslo-CoMet Trial. Medicine (Baltimore). 2015 Oct;94(42):e1786. doi: 10.1097/MD.0000000000001786. Erratum In: Medicine (Baltimore). 2016 Mar;95(10):e367e.
• Ueda K, Turner P, Gagner M. Stress response to laparoscopic liver resection. HPB (Oxford). 2004;6(4):247-52. doi: 10.1080/13651820410023987.
• Buunen M, Gholghesaei M, Veldkamp R, Meijer DW, Bonjer HJ, Bouvy ND. Stress response to laparoscopic surgery: a review. Surg Endosc. 2004 Jul;18(7):1022-8. doi: 10.1007/s00464-003-9169-7. Epub 2004 May 12.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2010
• Primary Completion (ACTUAL): June 30, 2011
• Study Completion (ACTUAL): June 30, 2011

Study Registration Dates

• First Submitted: April 20, 2017
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (ACTUAL): April 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 1, 2017
• Last Update Submitted That Met QC Criteria: April 27, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: 2006/048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No