Detection and Inflammatory Characterization of Deep Infection After Surgery for Locally Advanced Rectal Cancer With Microdialysis Catheters

The intention of the study is to explore metabolic and inflammatory parameters in the pelvis after abdominoperineal resection for locally advanced rectal cancer in patients that have received radiation therapy before surgery.

Study Overview

• Status: Completed
• Conditions: Infection; 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. A very high rate of deep surgical site infections is reported in the APR group internationally, particularly in the patients that have received chemo-radiotherapy. The knowledge of why these patients have such a high rate of infections is scarce.

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, after extensive oncological surgery for LARC in patients that have undergone chemoradiotherapy before surgery. With the knowledge of how the normal biology is, the investigators hypothesize that infection can be readily detected by the biomarkers retrieved by microdialysis.

• Study Type: Observational
• Enrollment (Actual): 50

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 and older (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.
• have accepted and signed the consent form.

Exclusion Criteria:

• APR for other reasons

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
APR; Patients with locally advanced rectal cancer treated with neoadjuvant (chemo-) radiotherapy (CRT) and operated with abdominoperineal resection (APR)
APR with VRAM; Patients with locally advanced rectal cancer treated with neoadjuvant (chemo-) radiotherapy (CRT) and operated with abdominoperineal resection (APR) and subsequent reconstruction of the perineum with a vertical rectus abdominis myocutaneous flap (VRAM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monitoring intermediate metabolites in the remnant muscular tissue of the pelvis floor 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.	August 2023

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monitoring inflammatory mediators in the remnant muscular tissue of the pelvis floor with microdialysis catheters after neoadjuvant CRT and subsequent APR for LARC.	Microdialysis fluid will 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.	August 2023
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.	August 2023
Measure inflammatory mediators in pelvic drain fluid after neoadjuvant CRT and subsequent APR for LARC.	Pelvic drain fluid will 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.	August 2023
Measure the common innate immune defect MBL deficiency in blood in the study population.	Measure MBL (ng/mL) in serum by an enzyme immunoassay. Compare differences in the frequency of MBL-deficiency in patients with or without deep pelvic infections.	August 2023
Measure intermediate metabolites and inflammatory mediators after neoadjuvant CRT and subsequent APR for LARC with reconstruction of the perineum with VRAM.	Measure the above mentioned parameters and evaluate whether reconstruction with VRAM contribute to differences in these in patients after neoadjuvant CRT and subsequent APR for LARC, in comparison with patients without VRAM reconstruction.	August 2023

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): January 8, 2022

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: January 2, 2018
• First Posted (Actual): January 8, 2018

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: Locally advanced rectal cancer; Microdialysis; Surgical site infection; Deep infection
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Infections; Communicable Diseases; Rectal Neoplasms
• Other Study ID Numbers: 2016/865

Drug and device information, study documents

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