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Mesorectal Microbiome as a Prognostic Factor in Patients With Rectal Cancer

Recruiting
Conditions
Rectal Cancer
Interventions
Procedure: Stool sample
Procedure: Rectal mucosa sample
Procedure: Mesorectal adipose tissue sample
Procedure: Subcutaneous adipose tissue sample
Procedure: Visceral adipose tissue sample
Behavioral: Dietary assessment
Registration Number
NCT04804956
Lead Sponsor
University Hospital of Girona Dr.Josep Trueta
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
Inclusion Criteria
  • Patients with rectal cancer that will undergo anterior resection for rectal cancer.
  • 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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Advanced-rectal cancerStool sampleThe patients to be included in this group will be those with Stages II and III, that is, advanced tumors at the time of preoperative diagnosis. Tumors included in this group invade the perirectal fat and / or the surface of the visceral peritoneum and / or invade or adhere to adjacent organs or structures. In addition, any tumor stage with lymph nodes without distant metastases will be included in this group.
Advanced-rectal cancerMesorectal adipose tissue sampleThe patients to be included in this group will be those with Stages II and III, that is, advanced tumors at the time of preoperative diagnosis. Tumors included in this group invade the perirectal fat and / or the surface of the visceral peritoneum and / or invade or adhere to adjacent organs or structures. In addition, any tumor stage with lymph nodes without distant metastases will be included in this group.
Advanced-rectal cancerSubcutaneous adipose tissue sampleThe patients to be included in this group will be those with Stages II and III, that is, advanced tumors at the time of preoperative diagnosis. Tumors included in this group invade the perirectal fat and / or the surface of the visceral peritoneum and / or invade or adhere to adjacent organs or structures. In addition, any tumor stage with lymph nodes without distant metastases will be included in this group.
Early-rectal cancerSubcutaneous adipose tissue sampleThe patients to be included in this group will be those with Stage I (initial tumor stage). The tumors classified in stage I will be tumors in which the invasion of the submucosa and / or the invasion of the muscularis propria occur. This group will include patients diagnosed preoperatively with tumor stage T1-T2 N0.
Advanced-rectal cancerRectal mucosa sampleThe patients to be included in this group will be those with Stages II and III, that is, advanced tumors at the time of preoperative diagnosis. Tumors included in this group invade the perirectal fat and / or the surface of the visceral peritoneum and / or invade or adhere to adjacent organs or structures. In addition, any tumor stage with lymph nodes without distant metastases will be included in this group.
Advanced-rectal cancerVisceral adipose tissue sampleThe patients to be included in this group will be those with Stages II and III, that is, advanced tumors at the time of preoperative diagnosis. Tumors included in this group invade the perirectal fat and / or the surface of the visceral peritoneum and / or invade or adhere to adjacent organs or structures. In addition, any tumor stage with lymph nodes without distant metastases will be included in this group.
Synchronous metastasis -rectal cancerRectal mucosa sampleThe patients to be included in this group will be those with Stage IV (disseminated tumor stage) in the initial study of the disease. Patients with distant metastases in one organ or more than one organ will be included.
Advanced-rectal cancerDietary assessmentThe patients to be included in this group will be those with Stages II and III, that is, advanced tumors at the time of preoperative diagnosis. Tumors included in this group invade the perirectal fat and / or the surface of the visceral peritoneum and / or invade or adhere to adjacent organs or structures. In addition, any tumor stage with lymph nodes without distant metastases will be included in this group.
Synchronous metastasis -rectal cancerMesorectal adipose tissue sampleThe patients to be included in this group will be those with Stage IV (disseminated tumor stage) in the initial study of the disease. Patients with distant metastases in one organ or more than one organ will be included.
Synchronous metastasis -rectal cancerDietary assessmentThe patients to be included in this group will be those with Stage IV (disseminated tumor stage) in the initial study of the disease. Patients with distant metastases in one organ or more than one organ will be included.
Synchronous metastasis -rectal cancerSubcutaneous adipose tissue sampleThe patients to be included in this group will be those with Stage IV (disseminated tumor stage) in the initial study of the disease. Patients with distant metastases in one organ or more than one organ will be included.
Early-rectal cancerStool sampleThe patients to be included in this group will be those with Stage I (initial tumor stage). The tumors classified in stage I will be tumors in which the invasion of the submucosa and / or the invasion of the muscularis propria occur. This group will include patients diagnosed preoperatively with tumor stage T1-T2 N0.
Early-rectal cancerDietary assessmentThe patients to be included in this group will be those with Stage I (initial tumor stage). The tumors classified in stage I will be tumors in which the invasion of the submucosa and / or the invasion of the muscularis propria occur. This group will include patients diagnosed preoperatively with tumor stage T1-T2 N0.
Synchronous metastasis -rectal cancerStool sampleThe patients to be included in this group will be those with Stage IV (disseminated tumor stage) in the initial study of the disease. Patients with distant metastases in one organ or more than one organ will be included.
Synchronous metastasis -rectal cancerVisceral adipose tissue sampleThe patients to be included in this group will be those with Stage IV (disseminated tumor stage) in the initial study of the disease. Patients with distant metastases in one organ or more than one organ will be included.
Early-rectal cancerRectal mucosa sampleThe patients to be included in this group will be those with Stage I (initial tumor stage). The tumors classified in stage I will be tumors in which the invasion of the submucosa and / or the invasion of the muscularis propria occur. This group will include patients diagnosed preoperatively with tumor stage T1-T2 N0.
Early-rectal cancerMesorectal adipose tissue sampleThe patients to be included in this group will be those with Stage I (initial tumor stage). The tumors classified in stage I will be tumors in which the invasion of the submucosa and / or the invasion of the muscularis propria occur. This group will include patients diagnosed preoperatively with tumor stage T1-T2 N0.
Early-rectal cancerVisceral adipose tissue sampleThe patients to be included in this group will be those with Stage I (initial tumor stage). The tumors classified in stage I will be tumors in which the invasion of the submucosa and / or the invasion of the muscularis propria occur. This group will include patients diagnosed preoperatively with tumor stage T1-T2 N0.
Primary Outcome Measures
NameTimeMethod
Identification of mesorectal microbial biomarkers as prognostic factor for rectal cancerUp to 5 years after rectal cancer surgery

Correlation between mesorectal microbial signatures and survival

Secondary Outcome Measures
NameTimeMethod
Mesorectal microbiome evaluationUp to 1 month after rectal cancer surgery

Qualitative and quantitative analysis of the mesorectal microbiome in patients with rectal cancer

Evaluation of mesorectal dysfunctionality and dysbiosis on tumor progressionUp to 1 month after rectal cancer surgery

Correlation between mesorectal dysfunction and response to neoadjuvant treatment

Evaluation of mesorectal dysfunctionality and its correlation with microbial dysbiosisUp to 1 month after rectal cancer surgery

Analysis of mesorectal tissue inflammation, angiogenesis and hypoxia and its correlation with microbial dysbiosis

Trial Locations

Locations (1)

Hospital Universitari Dr. Josep Trueta de Girona

🇪🇸

Girona, Spain

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