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"PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT.METHODS: Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i.p. for 2 days), and the CPT-11 and TU-100 co-treated group (1000 mg/kg, p.o. for 5 days). All of the rats were sacrificed on day 6 and their tissues were collected.RESULTS: CPT-11 and TU-100 co-treatment improved CPT-11 the related cytotoxicity in vitro. All CPT-11-treated rats developed different grades of diarrhea and BT was observed in 80% of the rats. CPT-11 caused a significant increase in the expression of TLR4, IL-6, TNF-α, IL-1β and caspase-3 mRNAs in the large intestine. The expression of tight junction (TJ) marker mRNAs (occludin, claudin-1 and 4, and ZO-1) was significantly decreased in comparison to the control group. TU-100 co-treatment significantly reversed diarrhea, BT, and the expression of TLR2, IL-6, TNF-α, IL-1β and caspase-3, and improved the expression of occludin, claudin-4 and ZO-1.CONCLUSIONS: TU-100 can suppress the adverse effects associated with CPT-11 and improve the function of the TJ. It is possible that this occurs through the TLR pathway."

"ABSTRACTPurposes This study compared the effectiveness of 1 day vs 3 days antibiotic regimen to prevent surgical site infection (SSI) in open liver resection.MethodWe performed a randomized controlled non inferiority trial in 480 patients at 39 hospitals across Japan (registered as UMIN000002852). Patients with hepatocellular carcinoma scheduled to undergo resection were randomly assigned to receive either a 1 day regimen for antimicrobial prophylaxis, or a 3 day regimen. The primary endpoint was the incidence of SSI.ResultsAmong 480 randomized patients, 232 assigned to the 1 day regimen and 235 to the 3 day regimen were included in the full analysis set. Baseline characteristics of the two groups were well balanced. SSI was diagnosed in 22 patients (9,5%) in the 1 day group vs 23 patients (9,8%) in the 3 day group (difference, -0,30; 90% CI -4,80 to 4,19% (95% CI -5,66% to 5,05%); one sided P = 0,001 for non inferiority), meeting the non inferiority hypothesis. In both groups, remote site infection (16 (6,9%) vs 22 (9,4%), P 0,001 for non inferiority) and drain-related infection (5 (2,2%) vs 4 (1,7%), P 0.001 for non inferiority) were comparable.ConclusionTo prevent SSI in liver cancer surgery, a 1 day regimen of flomoxef sodium is recommended for antimicrobial prophylaxis because of confirming the non-inferiority to longer usage."