Inflammation After Laparoscopic Robot-assisted Surgery for Locally Advanced Rectal Cancer (APR-IMM)

The intention of the study is to explore metabolic and inflammatory parameters in the pelvis and systemically after abdominoperineal resection (APR) for locally advanced rectal cancer (LARC) in patients that have received radiation therapy before surgery. In this study the inflammatory response after laparoscopic robot-assisted APR for LARC will be compared to results obtained in a recent cohort of patients operated with open APR for LARC, which will serve as the control population.

Study Overview

• Status: Completed
• Conditions: Abdominoperineal Resection; Locally Advanced Rectal Cancer

Detailed Description

Locally advanced rectal cancers (LARC) threaten the normal surgical margins and therefore needs neoadjuvant (chemo-) radiotherapy to down-stage the tumor before surgery. The Norwegian Radium Hospital Oslo University Hospital is a regional center for treatment of LARC in the south-eastern part of Norway and treat approximately 80-100 patients in this category annually. About 50 of these patients receive abdominoperineal resection (APR) as the main surgical treatment.

Laparoscopic surgery in LARC has been limited because of difficult dissection with straight instruments outside the normal anatomical planes in the confined space of the pelvis. However, recent papers report on better feasibility and good results in robot-assisted surgery for LARC. In respect to shorter postoperative length of stay for minimally invasive compared to open surgery, reduced inflammation may be the explanation, however, results are not conclusive. Most studies comparing open to minimally invasive surgery in colorectal cancer have had conventional laparoscopy as the minimally invasive group, including studies comparing inflammation after surgery. A study on inflammation after laparoscopic robot-assisted major surgery for bladder cancer has recently been published, but to our knowledge no comprehensive studies have been done with patients with rectal cancer resections. Additionally, there are claims that excessive and/or dysregulated inflammatory response after cancer surgery, worsen oncologic outcome. The need to characterize the inflammatory response after laparoscopic robot-assisted surgery of rectal cancer is thus highly relevant and needed.

The investigators want to analyse inflammatory parameters in plasma and peritoneal fluid in patients undergoing robot-assisted and open surgery for LARC.

Microdialysis is a technique which enables close to real-time monitoring of the tissues and organs of interest. The investigators want to utilize the microdialysis method to describe and monitor metabolic and inflammatory parameters in some patients after extensive robot-assisted oncological surgery for LARC.

The investigators hypothesize inflammatory response differ between patients undergoing open versus robot-assisted surgery.

• Study Type: Observational
• Enrollment (Actual): 55

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0379
    • The Norwegian Radium Hospital Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with locally advanced rectal cancer who receive radiotherapy >25 Gy prior to surgery.

Description

Inclusion Criteria:

• Patients with primary rectal adenocarcinoma that have received radiation ≥25 Gy to the pelvis.
• operation with APR with laparoscopic robot assisted technique.
• have accepted and signed the consent form.

Exclusion Criteria:

• APR for other reasons

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
APR-open; Patients with locally advanced rectal cancer treated with neoadjuvant (chemo-) radiotherapy (CRT) and operated with abdominoperineal resection (APR) with laparotomy.
APR-robot; Patients with locally advanced rectal cancer treated with neoadjuvant (chemo-) radiotherapy (CRT) and operated with abdominoperineal resection (APR) with laparoscopic robot assisted technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak value of surgically induced C-reactive protein (CRP), expected to occur 1-3 days after surgery	CRP will be measured prior to surgery as well as on a daily basis the first 4 postoperative days. Peak values of CRP will be compared between patients undergoing open versus robot-assisted surgery.	December 2022

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival at 1 year follow up after surgery	Differences between patients undergoing open versus robot-assisted surgery will be registered.	December 2024
Progression-free survival at 1 year follow up after surgery	Differences between patients undergoing open versus robot-assisted surgery will be registered	December 2024
Operating time in minutes	Differences between patients undergoing open versus robot-assisted surgery will be registered	December 2023
Hospital length of stay in days after primary surgery	Differences between patients undergoing open versus robot-assisted surgery will be registered	December 2023
Postoperative deep pelvic surgical site infection within 30 days after primary surgery	Differences between patients undergoing open versus robot-assisted surgery will be registered. Clinical diagnose (yes/no) supported by CT-scan	December 2023
Superficial wound infection within 30 days after primary surgery	Differences between patients undergoing open versus robot-assisted surgery will be registered. Clinical diagnose (yes/no)	December 2023
Dehiscence of the perineal wound at 3 months follow-up	Differences between patients undergoing open versus robot-assisted surgery will be registered. Clinical diagnose (yes/no)	December 2023

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monitoring inflammatory mediators in blood after neoadjuvant CRT and subsequent APR for LARC.	Blood be analysed using a multiplex cytokine assay (Bio-Plex Human Cytokine 27-Plex Panel, Bio-Rad Laboratories Inc., Hercules, CA). The following cytokines, chemokines and growth factors will be measured (all in pg/mL): Activated complement component 5 (C5a) Interleukin (IL) 1 beta (IL-1β), IL-1 receptor antagonist (IL-1Ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8 (CXCL8), IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17, Eotaxin (CCL11), basic fibroblast growth factor (bFGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFNG), interferon gamma inducible protein-10 (IP-10 or CXCL10), monocyte chemoattractant protein-1 (MCP-1 or CCL2), macrophage inflammatory protein-1-alpha (MIP-1α or CCL3), macrophage inflammatory protein-1-beta (MIP-1β or CCL4), platelet-derived growth factor-BB (PDGF-BB), regulated upon activation, normal T cell expressed and secreted (RANTES or CCL5), TNF-α and VEGF.	December 2023
Monitoring inflammatory mediators in pelvic drain fluid after neoadjuvant CRT and subsequent APR for LARC.	Blood be analysed using a multiplex cytokine assay (Bio-Plex Human Cytokine 27-Plex Panel, Bio-Rad Laboratories Inc., Hercules, CA). The following cytokines, chemokines and growth factors will be measured (all in pg/mL): Activated complement component 5 (C5a) Interleukin (IL) 1 beta (IL-1β), IL-1 receptor antagonist (IL-1Ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8 (CXCL8), IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17, Eotaxin (CCL11), basic fibroblast growth factor (bFGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFNG), interferon gamma inducible protein-10 (IP-10 or CXCL10), monocyte chemoattractant protein-1 (MCP-1 or CCL2), macrophage inflammatory protein-1-alpha (MIP-1α or CCL3), macrophage inflammatory protein-1-beta (MIP-1β or CCL4), platelet-derived growth factor-BB (PDGF-BB), regulated upon activation, normal T cell expressed and secreted (RANTES or CCL5), TNF-α and VEGF.	December 2023
Monitoring intermediate metabolites in the remnant muscular tissue of the pelvis floor in up to 10 patients with microdialysis catheters after neoadjuvant CRT and subsequent APR for LARC.	Lactate (mM), pyruvate (µM), lactate/pyruvate ratio, glycerol (µM) and glucose (mM) will be measured in microdialysis fluid from catheters inserted in the remnant muscular tissue of the pelvis floor after neoadjuvant CRT and subsequent APR for LARC to detect deep pelvic surgical site infection. The results will be compared to current standard monitoring. The measures will be done bedside on Iscus analyzer, M Dialysis AB, Stockholm, Sweden. The Iscus analyzer will calculate the lactate/pyruvate ratio.	December 2023

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: University of Oslo

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2019
• Primary Completion (Actual): March 5, 2022
• Study Completion (Actual): March 5, 2022

Study Registration Dates

• First Submitted: March 5, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (Actual): March 27, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Microdialysis; Inflammatory Response
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Inflammation; Rectal Neoplasms
• Other Study ID Numbers: 2019/810

Drug and device information, study documents

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