Estrogen Receptor Beta Agonists (Eviendep) and Polyp Recurrence (CRC)

• Expression of ERβ, ERα, TUNEL, Caspase-3, Ki-67 in bioptic samples of non adenomatous mucosa in sporadic adenopolyposis [ Time Frame: 60 days following dietary oral supplementation, in advance of the screening colonoscopy as per the planning of the surveillance program ] [ Designated as safety issue: Yes ]
  ERβ and ERα protein content (Elisa), mRNA and immunohistochemically stained cells (% over the total number of cells/field,ICH); TUNEL (%,ICH); caspase-3 (%,ICH), Ki-67 (%ICH), and comparison (mean, median, %ICH) between study groups. Safety assessed by no induction of ERα expression.
  
  

• Safety assessed by unchanged hematochemistry [ Time Frame: 30 and 60 days following dietary oral supplementation ] [ Designated as safety issue: Yes ]
  Hemoglobin ≥ 12.0 g/dL; platelets ≥ 120,000/mm3; INR ≤ 1.5; AST or ALT ≤ 1.5 times the upper limit of normal values (ULN); Alkaline Phosphatase ≤ 1.5 times ULN; Bilirubin ≤ 1.5 times ULN; BUN ≤ 40 mg/dL; normal blood pressure or controlled hypertension
  
  
• Urinary lignans [ Time Frame: baseline (T0, 30 (T30) and 60 (T60) days during the study period ] [ Designated as safety issue: No ]
  To verify comparability of phytoestrogens contributed from the common diet in the two arms at baseline, and to assess compliance to the active comparator during the study period.
  
  

Enrolled patients were actively ongoing the surveillance program for the follow up of polyp recurrence and progression to CRC. Eligible patients should have undergone a polypectomy since 2003, affected by multiple polyps < 10 mm or one-two adenomas < 10 mm and/or with a grade of dysplasia to make them classified at intermediate risk for CRC, and scheduled to screening colonoscopy each 3-5 years. Patients were sequentially 1:1 randomly allocated to placebo or Eviendep at baseline (T0). The dietary supplements were administered twice a day for 60 days in advance of the screening colonoscopy, thus covering approximately eight complete colon epithelial turnover to occur. Five days in advance of T60 colonoscopy, patients refrained from fresh and cooked fruit and vegetable intake. Bowel cleansing was achieved by PEG 4000 oral administration (1120 g/4 L water solution). N=8 biopsy samples/patient were collected from the non adenomatous mucosa in the sigmoidal colon. Small polyps (diameter less or equal 0.5 cm) were topically electrocoagulated, whereas villous and tubulovillous polyps (diameter equal or higher than 0.5 cm) were submitted to the histological assessment.