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

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

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.

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