Clinical trial NCT04005118: Human Intestinal Microbiome and Surgical Outcomes in Patients Undergoing Colorectal Cancer Surgery
Official title: Human Intestinal Microbiome and Surgical Outcomes in Patients Undergoing Colorectal Cancer Surgery
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Adenocarcinoma of the Colon
Adenocarcinoma of the Rectum
Keywords: Intestinal microbiome
colorectal cancer
mechanical bowel preparation
postoperative complications
anastomotic leakage
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-07-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient with rectal or left colon adenocarcinoma

Brief summary: Intro: Recent studies on colorectal cancer surgery have been focusing on the role of intestinal microbiome on surgical outcomes. Standard perioperative cares, like mechanic bowel preparation (MBP), administration of antibiotics (ABT) and surgery-related stress and injury influence the microbiome composition and possibly induce a shift toward a microbiome dysbiotic state, which predisposes to complicated postoperative course. Microbiome composition changes and enhanced virulence factors may increase the risk of postoperative complications, such as anastomotic leakage (AL), surgical site infection (SSI), and postoperative ileus (PI), which are known to impact on patient's overall survival and cancer recurrence.

Objective: The primary objective is to investigate if a significant association might exist between the microbiome composition and the occurrence of postoperative complications at 90 days.

Methods: 3 different microbiome samples will be taken from all patients. Two fresh fecal samples for detection of LM and fecal water preparation: a) a day before the surgery before MBP and/or ABT (LM1), b) postoperatively after first bowel movement (LM2). One sample will be taken intra-operatively from the stapled resection lines of circular stapler used for forming a colorectal anastomosis, to detect the MAM and to perform immunohistochemistry staining for detection of HACE1 expression.

DNA analysis will be performed for all samples. IHC will be performed for detecting HACE1 expression in the tumor and colorectal anastomosis tissues using anti-HACE1 antibodies. .

For proliferation assessment, human colon carcinoma cell lines HT29 will be plated in monolayers and scratched with a single scratch. Monolayers will be incubated for 24 hours with fecal water from patients with surgical complications and matched control patients without complications.

Descriptive statistics will be performed to describe the study population. This project aim to describe microbiome composition and its impact on postoperative complications.


Eligibility criteria: Inclusion Criteria:

* Adult ≥ 18 years old
* With histologically confirmed rectal or left colon adenocarcinoma by biopsy material from colonoscopy
* Having elective colorectal surgery after standardized bowel preparation
* Affiliated to a social security system
* Signature of informed consent

Exclusion Criteria:

* Major surgery 30 days before scheduled colorectal surgery
* Administration of systemic antibiotic therapy within 30 days prior to planned colorectal surgery
* Presenting a contraindication to elective colorectal surgery
* Patient protected by law
* Pregnant or breastfeeding woman

Primary outcomes:
measure: Rate of anastomotic leakage
timeFrame: 90 days after surgery
measure: Rate of surgical site infection
timeFrame: 90 days after surgery
measure: Rate of prolonged postoperative ileuss
timeFrame: 90 days after surgery
Secondary outcomes:
measure: microbiome composition
timeFrame: 3 months after study start date
measure: microbiome composition
timeFrame: 6 months after study start date
measure: impact of microbiome composition on length of hospitalization
timeFrame: at the time of patient's discharge of the hospital
measure: Correlation between detected bacterial OTUs (Operation Taxonomic Units) and the event of reintervention
timeFrame: 90 days after surgery
measure: impact of microbiome metabolites on intestinal epithelial cell proliferation and wound healing
timeFrame: 6 months after study start date
measure: Expression intensity in cytoplasm of protein ligase HACE1 in tumoral and non-tumoral tissues
timeFrame: 6 months after study start date
measure: Expression intensity in cytoplasm of protein ligase HACE1 in tumoral and non-tumoral tissues
timeFrame: 3 months after study start date
Other outcomes:
Locations:
city: Créteil
country: France
facility: Dr Lelde Lauka
Study officials:
affiliation: APHP
name: Lelde Lauka, PHD
role: PRINCIPAL_INVESTIGATOR
References: