Human Intestinal Microbiome and Surgical Outcomes in Patients Undergoing Colorectal Cancer Surgery (Microbiota)

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.

Study Overview

• Status: Unknown
• Conditions: Adenocarcinoma of the Rectum; Adenocarcinoma of the Colon

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

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94000
    • Recruiting
    • Dr Lelde Lauka
    • Contact: Lauka Lelde, PhD

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

Patient with rectal or left colon adenocarcinoma

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
preoperative preparation on microbiome composition; Mechanical Bowel Preparation + oral antibiotics group: receiving mechanical bowel preparation only MBP will be prepared with 4 liters of Polyethylene glycol (PEG) solution to be started 24 hours before the planned surgery. 500mg of Metronidazole will be administrated 3 times one day before the surgery at 2 pm, 3 pm and 10 pm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of anastomotic leakage	detected by imaging techiques (CT scan or MRI)	90 days after surgery
Rate of surgical site infection	1)superficial and deep infection:clinical observation of purulent discharge from the wound and/or bacterial staining from the wound 2)organ or deep space infection: imaging techniques (CT, MRI, USS)	90 days after surgery
Rate of prolonged postoperative ileuss	detected by clinical observation of the first bowel movement after the surgery	90 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
microbiome composition	The composition of luminal microbiome and mucosal-associated microbiome will be studied by DNA analyses from fresh fecal samples and surgical anastomosis material, accordingly	3 months after study start date
microbiome composition	The composition of luminal microbiome and mucosal-associated microbiome will be studied by DNA analyses from fresh fecal samples and surgical anastomosis material, accordingly	6 months after study start date
impact of microbiome composition on length of hospitalization	length of hospitalization will be detected and analyzed in association with microbiome composition	at the time of patient's discharge of the hospital
Correlation between detected bacterial OTUs (Operation Taxonomic Units) and the event of reintervention	In the patient group with the event of reintervention, an abundance of specific OTUs will be analysed in compare with patients with no event of reintervention.	90 days after surgery
impact of microbiome metabolites on intestinal epithelial cell proliferation and wound healing	Monolayers of human colon cancer cell lines HT29 will be incubated for 24 hours with fecal water from patients with surgical complications and matched control patients without complications. Proliferation will be calculated in two manners: 1) The time of the closure of the scratch defect will be evaluated and compared in the two group., 2)Proliferation rate will be analyzed by immunohistochemistry marker Ki 67, expression of Ki 67 will be evaluated in cells at the borders of the scratch defect	6 months after study start date
Expression intensity in cytoplasm of protein ligase HACE1 in tumoral and non-tumoral tissues	Immunohistochemistry with anti-HACE1 antibodies will be used to detect expression levels in tumoral (colorectal cancer) and non-tumoral (anastomotic sample) tissues. In a case of decreased expression, tissues will be analyzed by methylation PCR to detect an aberrant methylation of HACE1 and its hypermethylation	6 months after study start date
Expression intensity in cytoplasm of protein ligase HACE1 in tumoral and non-tumoral tissues	Immunohistochemistry with anti-HACE1 antibodies will be used to detect expression levels in tumoral (colorectal cancer) and non-tumoral (anastomotic sample) tissues. In a case of decreased expression, tissues will be analyzed by methylation PCR to detect an aberrant methylation of HACE1 and its hypermethylation	3 months after study start date

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Lelde Lauka, PHD, APHP

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 28, 2019
• Primary Completion (ANTICIPATED): April 1, 2020
• Study Completion (ANTICIPATED): April 1, 2020

Study Registration Dates

• First Submitted: March 15, 2019
• First Submitted That Met QC Criteria: July 1, 2019
• First Posted (ACTUAL): July 2, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 2, 2019
• Last Update Submitted That Met QC Criteria: July 1, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: colorectal cancer; mechanical bowel preparation; postoperative complications; anastomotic leakage; Intestinal microbiome
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Adenocarcinoma
• Other Study ID Numbers: APHP190088

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

Drug and device information, study documents

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