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

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ClinicalTrials.gov Identifier: NCT03392584
Recruitment Status : Recruiting
First Posted : January 8, 2018
Last Update Posted : January 8, 2018
Sponsor:
Collaborator:
University of Oslo
Information provided by (Responsible Party):
Ebbe Billmann Thorgersen, 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.

Condition or disease
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 Type : Observational
Estimated Enrollment : 40 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 : October 1, 2016
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2018

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)



Primary Outcome Measures :
  1. Monitoring intermediate metabolites in the remnant muscular tissue of the pelvis floor with microdialysis catheters after neoadjuvant CRT and subsequent APR for LARC. [ Time Frame: 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 :
  1. Monitoring inflammatory mediators in the remnant muscular tissue of the pelvis floor with microdialysis catheters after neoadjuvant CRT and subsequent APR for LARC. [ Time Frame: 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.

  2. Monitoring inflammatory mediators in blood after neoadjuvant CRT and subsequent APR for LARC. [ Time Frame: 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.

  3. Measure inflammatory mediators in pelvic drain fluid after neoadjuvant CRT and subsequent APR for LARC. [ Time Frame: 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.

  4. Measure the common innate immune defect MBL deficiency in blood in the study population. [ Time Frame: 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.

  5. Measure intermediate metabolites and inflammatory mediators after neoadjuvant CRT and subsequent APR for LARC with reconstruction of the perineum with VRAM. [ Time Frame: 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.


Biospecimen Retention:   Samples Without DNA
Microdialysis samples 6-10 times every day. Regularly standard blood samples. Daily samples from pelvic drain. EDTA plasma 3 times a week.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with locally advanced rectal cancer who receive radiotherapy >25 Gy prior to surgery.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03392584


Contacts
Contact: Ebbe B Thorgersen, MD PhD +4722934001 Ebbe.Billmann.Thorgersen@rr-research.no
Contact: Jørund Asvall, MD +4722935608 joeasv@ous-hf.no

Locations
Norway
The Norwegian Radium Hospital Oslo University Hospital Recruiting
Oslo, Norway, 0379
Contact: Ebbe B Thorgersen, MD PhD    +4722934615    Ebbe.Billmann.Thorgersen@rr-research.no   
Contact: Stein G Larsen, MD PhD    +4722934052    STL@ous-hf.no   
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

Responsible Party: Ebbe Billmann Thorgersen, Principal Investigator, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT03392584     History of Changes
Other Study ID Numbers: 2016/865
First Posted: January 8, 2018    Key Record Dates
Last Update Posted: January 8, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ebbe Billmann Thorgersen, Oslo University Hospital:
Locally advanced rectal cancer
Deep infection
Microdialysis
Surgical site infection

Additional relevant MeSH terms:
Infection
Communicable Diseases
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases