Mesorectal Microbiome and Metabolome as a Prognostic Factor in Patients With Rectal Cancer

Mesorectal Microbiome and Metabolome as a Prognostic Factor in Patients With Rectal Cancer and Analysis of it's Applicability in Neoadjuvant Treatment

The equilibrium of intestinal microorganisms is essential for health an imbalance has been associated with an increased risk in the development of different pathologies; including colorectal cancer.

Rectal cancer is the third most common neoplasm worldwide and the complete excision of the mesorectum is a major prognostic factor.

The identification of microorganisms in the adipose tissue that surrounds the small intestine in inflammatory diseases, together with bacterial alterations found in colonic mucosa and feces in patients with rectal cancer in comparison with healthy individuals indicates that microbiome alteration plays an essential role in pathogenesis.

The mesorectal microbiome in rectal cancer patients stills unknown and given its importance in the prognostic of the disease the goal of this study is to identify microbial profiles that allow predicting rectal cancer patients with a poor prognosis.

The 5-year survival rate for patients with rectal cancer is 64%. Despite the development of personalized cancer treatments, the implantation of surgical approaches with more precise fields of vision and the current prognostic factors based on the quality of resection of the surgical specimen (intact margins and complete resection of the mesorectum), the long-term results for patients with rectal cancer remain grim.

Recently, it has been shown that dysfunctional fat tissue is characterized by tissue remodeling, grater lipids deposits and high adipokines secretion generates a pro inflammatory state, hypoxia and angiogenesis. These products generated by dysfunctional peritumoral adipose tissue create an ideal microenvironment for initiation and tumor progression.

The presence of microbiome in the mesentery of patients with colitis has confirmed the translocation of microorganisms from the intestine to adjacent tissues, together with the differences found in the bacterial composition in colonic mucosa and fecal samples between patients with rectal cancer and healthy individuals, and the prognosis value of the quality of mesorectum resection suggests that the microbiome present in lymph-fatty tissue in patients with rectal cancer may be a key element in mesorectum dysfunction, progression and dissemination of oncological disease.

Inclusion Criteria:

• Patients with colorectal cancer that will undergo elective surgery
• Patients diagnosed with non-oncological disease with an indication for elective surgery.
• Age ≥ 18 years
• Histology proven adenocarcinoma or adenoma with or without chemotherapy or neoadjuvant radiochemotherapy
• Tumoral stage equal or grater than T1
• Attempt to R0 resection
• Signed informed consent by the patient and by the researcher
• Dietary Questionnaire completed

Exclusion Criteria:

• Colorectal tumor with different histology to adenocarcinoma or adenoma
• History of colorectal cancer surgery different to the local excision
• Patients with psychiatric illness, addiction or disorder with inability to understand informed consent
• Inability to read or understand any of the languages of the informed consent and questionnaires (Catalan, spanish)
• Another synchronous malignancy
• Emergency Surgery
• Any patient that medical characteristics present an individual risk raised to be included and complete the study
• Severe kidney or liver disease
• Systemic disease with inflammatory activity, such as rheumatoid arthritis, Crohn's disease, asthma, chronic infection (HIV,TBC).
• Pregnancy and lactation
• Severe disorder of eating behaviour
• Clinical symptoms and sings of infection in the previous month
• Antibiotic, antifungal and antiviral treatment for the last 3 months
• Anti-inflammatory chronic treatment
• Major psychiatric antecedents
• Excessive alcohol intake or drug abuse