Scope: Dietary polyphenols may protect against breast cancer. However, it is unknown whether polyphenols reach human malignant breast tumors in molecular forms and(or) at concentrations likely to act against cancer. Methods and Results: Ninteen breast cancer patients consumed three capsules daily from biopsy-confirmed diagnosis to surgery (6 ± 2 days). The capsules contained pomegranate, orange, lemon, olive, cocoa, and grapeseed extracts plus resveratrol, providing 37 different phenolics (473.7 mg), theobromine and caffeine (19.7 mg). A total of 101 metabolites are identified in urine, 69 in plasma, 39 in normal (NT), and 33 in malignant (MT) tissues by UPLC-ESI-QTOF-MS. Eight control patients did not consume extracts. Phenolic-derived metabolites in MT and NT are mainly glucuronidated and(or) sulfated. Some representative metabolites detected in MT (median and range, pmol g −1 ) are urolithin-A-3-O-glucuronide (26.2; 3.2−66.5), 2,5-dihydroxybenzoic acid (40. 2; 27.7−52.2), resveratrol-3-O-sulfate (86.4; 7.8−224.4), dihydroresveratrol-3-O-glucuronide (109.9; 10.3−229.4), and theobromine (715.0; 153.9−3,216). Metabolites, as detected in breast tissues, do not exert antiproliferative or estrogenic/antiestrogenic activities in MCF-7 breast cancer cells. Conclusion: This is the first study that describes the metabolic profiling of dietary phenolics and methylxanthines in MT and NT comprehensively. Although phase-II conjugation might hamper a direct anticancer activity, long-term tumor-senescent chemoprevention cannot be discarded.

Scope Some polyphenol‐derived metabolites reach human breast cancer (BC) tissues at concentrations that induce cell senescence. However, this is unknown for isoflavones, curcuminoids, and lignans. Here, their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly‐diagnosed BC patients and the tissue‐occurring metabolites’ anticancer activity are evaluated. Methods and results Patients (n = 26) consumed 3 capsules/day (turmeric, red clover, and flaxseed extracts plus resveratrol; 296.4 mg phenolics/capsule) from biopsy‐confirmed diagnosis to surgery (5 ± 2 days) or did not consume capsules (n = 13). NT and MT, blood, and urine are analyzed by UPLC‐QTOF‐MS using targeted metabolomics. Anticancer activity was tested in MCF‐7 and MDA‐MB‐231 BC cells. Mainly phase‐II metabolites were detected (108, 84, 49, and 47 in urine, plasma, NT, and MT, respectively). Total metabolite concentrations reached 10.7 ± 11.1 and 2.5 ± 2.4 µmol L–1 in NT and MT, respectively. Free curcumin, but not its glucuronide, was detected in the tissues (1.1 ± 1.8 and 0.2 ± 0.2 µmol L–1 in NT and MT, respectively). Breast tissue‐occurring metabolites’ antiproliferation was mainly exerted in p53‐wild‐type MCF‐7 cells by curcuminoids through cell cycle arrest, senescence, and apoptosis induction via p53/p21 induction, while isoflavone‐derived metabolites exerted estrogenic‐like activity. Conclusion Curcuminoids could be coadjuvants that might help fight BC upon regular consumption.

Liver resection with HALS reproduces the low morbidity and mortality rates and effectiveness (3-year survival) of open surgery in SLTs when indicated selectively.

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Background: The potential benefit related to laparoscopic liver surgery (LLS) for colorectal liver metastases outcomes is not well known.Materials and Methods: Serum cytokines associated with Th1 (tumor necrosis factor-α) and Th2 [interleukin (IL)-10 and IL-6] phenotypes were measured in 36 patients operated on for colorectal liver metastases by open liver surgery (OLS) and LLS. Measurements were performed at 3 time points: 1 day before surgery, day 3 postoperative, and 1 month postoperative. We compared the postoperative inflammatory response influence between LLS and OLS on long-term outcomes.Results: In both groups, only IL-6 levels on day 3 postoperative were higher than those measured preoperatively and at 1 month. Comparing the tumor necrosis factor-α levels between the LLS and OLS groups, preoperative (7.28 vs. 2.36), day 3 (7.99 vs. 4.08) and 1 month (7.39 vs. 1.99) postoperative levels were higher in the OLS group (P < 0.01, <0.01, and <0.01, respectively). In contrast, IL-10 levels were higher in the LLS group preoperatively (7.51 vs. 4.57) and on day 3 postoperative (13.40 vs. 4.57) (P = 0.03 and 0.01, respectively). A cut-off IL-6 level of ≥ 4.41 in the first month was associated with a higher risk of recurrence (logrank = 4.8, P = 0.02).Conclusions: Both LLS and OLS induce an initial increase in IL-6 that normalizes one month after surgery, showing a similar pattern. In addition, a cut-off IL-6 value of 4.41 pg/mL was established, with a higher concentration at 1 month postoperative possibly related to a higher risk or recurrence.

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