Effect of Immune-Enhancing Nutrition on Radical Cystectomy Outcomes

项目概要/摘要 接受手术治疗膀胱癌的患者面临非常高的并发症和死亡率。 根治性膀胱癌手术是所有泌尿系肿瘤中并发症发生率最高的手术 进行手术，也是非常分解代谢。正如国家癌症研究所在其 挑衅性的问题2和11，免疫功能和营养干预的变化会影响 对癌症治疗的反应。激进的化学疗法将继续拯救生命，但在这方面的代价很高。 持续的手术并发症这个项目的长期目标是释放营养的潜力 干预措施，以改善癌症患者的预后，生存和生活质量。本项目的目标 是为了确定一种特殊形式的营养支持对手术结果的影响， 了解它的作用机制。假设围手术期使用一种特殊形式的 营养支持将比标准形式的营养支持具有更大的功效， 手术并发症这一假设是根据已发表的初步数据提出的 在申请人的实验室和专家指南中产生，要求对此进行更严格的研究。 approach.基本原理是专门的免疫营养素（SIM）用营养素（L-精氨酸， ω-3脂肪酸，饮食核苷酸和维生素A），对免疫和 炎症反应、肌肉保护和手术后伤口愈合。以强有力的初步指导 数据，该假设将在三个具体目标进行测试：1）确定围手术期SIM的影响 与术后缺乏免疫调节剂的相同口服营养支持（ONS）相比， RC并发症; 2）比较SIM与ONS对RC后次要临床结局的影响 3）评价与ONS相比，使用SIM对抑制骨髓源性 抑制细胞（MDSC），减少炎症，调节营养代谢。该项目 意义重大，因为它提供了一个高收益，低风险，低成本的策略，以改善患者的结果， 膀胱癌患者接受RC。我们的创新方法可以改变临床实践，以减少术后 手术并发症，从而减少膀胱癌手术的负担，并增加了 有可能帮助许多其他手术患者超越cyberspace。

PROJECT SUMMARY/ABSTRACT Patients undergoing surgery to treat their bladder cancer face very high rates of complications and mortality. The radical cystectomy operation is fraught with the highest complication rates of all urologic oncology surgeries performed and is also extremely catabolic. As the National Cancer Institute has identified in its provocative questions 2 & 11, variations in immune function and nutritional interventions affect the response to cancer treatment. Radical cystectomy will continue to save lives, but there is a high cost in terms of persistent surgical complications. The long-term goal of this project is to unlock the potential of nutrition interventions to improve outcomes, survival, and quality of life in cancer patients. The objective of this project is to determine the impact of a specialized form of nutritional support on surgical outcomes and to better understand the mechanisms by which it acts. The hypothesis is that perioperative use of a specialized form of nutritional support will have greater efficacy than a standard form of nutritional support to reduce post- operative complications. This hypothesis has been formulated on the basis of published preliminary data produced in the applicants' laboratories and expert guidelines calling for more rigorous study of this approach. The rationale is that Specialized IMmunonutrition (SIM) is fortified with nutrients (L-arginine, omega-3 fatty acids, dietary nucleotides, and vitamin A) that have immediate effects on immune and inflammatory responses, muscle sparing, and wound healing after surgery. Guided by strong preliminary data, the hypothesis will be tested in three specific aims: 1) To determine the impact of perioperative SIM versus an identical Oral Nutrition Support (ONS) lacking the immuno-modulators on post-operative complications from RC; 2) To compare the impact of SIM to ONS on secondary clinical outcomes after RC surgery; 3) To evaluate the impact of consuming SIM compared to ONS for restraining myeloid-derived suppressor cells (MDSCs), decreasing inflammation, and modulating nutrient metabolism. The project is significant because it offers a high yield, low-risk, low-cost strategy to improve the outcome of patients with bladder cancer who undergo RC. Our innovative approach could transform clinical practice to reduce post- operative complications, thereby diminishing the burden of bladder cancer surgery and has the added potential to help many other surgical patients beyond cystectomy.