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

Completed

• Conditions: Locally Advanced Rectal Cancer; Abdominoperineal Resection; Infection

• Registration Number: NCT03392584
• Lead Sponsor: Oslo University Hospital

Brief Summary

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.

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 Timeline

• Study Start: 2016-10-01
• Study First Submitted: 2017-12-18
• Study First Submitted QC: 2018-01-02
• Study First Posted: 2018-01-08
• Primary Completion: 2021-03-01
• Study Completion: 2022-01-08
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-31
• Last Update Posted: 2023-04-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Monitoring intermediate metabolites in the remnant muscular tissue of the pelvis floor with microdialysis catheters after neoadjuvant CRT and subsequent APR for LARC.	August 2023	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.

Secondary Outcome Measures

Name	Time	Method
Monitoring inflammatory mediators in the remnant muscular tissue of the pelvis floor with microdialysis catheters after neoadjuvant CRT and subsequent APR for LARC.	August 2023	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.
Measure the common innate immune defect MBL deficiency in blood in the study population.	August 2023	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.
Monitoring inflammatory mediators in blood after neoadjuvant CRT and subsequent APR for LARC.	August 2023	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.
Measure inflammatory mediators in pelvic drain fluid after neoadjuvant CRT and subsequent APR for LARC.	August 2023	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.
Measure intermediate metabolites and inflammatory mediators after neoadjuvant CRT and subsequent APR for LARC with reconstruction of the perineum with VRAM.	August 2023	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.

Trial Locations

Locations (1)

The Norwegian Radium Hospital Oslo University Hospital; 🇳🇴 Oslo, Norway