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INTRODUCTION: Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion. AIM: This study explores the efficacy of multisite intratumoral injections in improving a drug's distribution while minimizing its side effects. METHODS AND RESULTS: In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (p < 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (p < 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (p = 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (p = 0.007). CONCLUSIONS: Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC.
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BACKGROUND: Reducing postprandial blood glucose concentrations in diabetic patients might contribute to optimal glycemic control. Gastrointestinal electrical stimulation has been proposed as a novel therapy for both gastrointestinal motility disorders and obesity. The present study investigated the effects and underlying mechanisms of intestinal electrical stimulation (IES) on postprandial blood glucose levels in rats. METHODS: Electrical stimulation electrodes were implanted into the duodenal wall of 33 male Sprague-Dawley rats. The blood glucose and insulin levels were measured before and after a glucose tolerance test both with and without electrical stimulation. In addition, the gastric emptying and intestinal flow rates were measured. RESULTS: IES applied immediately after the glucose tolerance test caused a significant decrease in the rising phase slope and the maximal serum blood glucose level. Additionally, the area under the curve of the blood glucose levels was reduced by approximately 50%. Insulin secretion decreased by 21%. The main reduction in insulin secretion was during the first 30 minutes after the glucose tolerance test. IES also caused a nearly 80% decrease of the gastric emptying rate and a 40% increase in the flow rate of nutrients inside the intestine. The effect was immediate after IES activation and reversible. CONCLUSION: These results suggest that IES applied to the duodenum can reduce postprandial blood glucose levels. The possible etiology is the modulating of gastric emptying and intestinal flow rate.