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

Sponsor

Oslo University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03392584

Collaborator

University of Oslo (Other)

Enrollment

Location

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Rectal Cancer Abdominoperineal Resection Infection

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 Design

Study Type:

Observational

Anticipated Enrollment :

50 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Oct 1, 2016

Actual Primary Completion Date :

Mar 1, 2021

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
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)

Outcome Measures

Primary Outcome Measures

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

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.
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 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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Norwegian Radium Hospital Oslo University Hospital	Oslo		Norway	0379

Sponsors and Collaborators

Oslo University Hospital
University of Oslo

Investigators

Principal Investigator: Ebbe B Thorgersen, MD PhD, Surgeon, The Department of Gastroenterological Surgery, The Norwegian Radium Hospital, Oslo University Hospital