Effect of Immune-Enhancing Nutrition on Radical Cystectomy Outcomes

项目摘要/摘要 接受手术治疗膀胱癌的患者面临着非常高的并发症和死亡率。 在所有泌尿外科肿瘤中，根治性膀胱切除术的并发症发生率最高。 手术进行的，也是非常分解代谢的。正如国家癌症研究所在其 挑衅性的问题2和11，免疫功能的变化和营养干预影响 对癌症治疗的反应。根治性膀胱切除术将继续挽救生命，但在以下方面代价高昂 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 旨在改善癌症患者预后、生存率和生活质量的干预措施。这个项目的目标是 是确定一种特殊形式的营养支持对手术结果的影响，并更好地 了解它的行动机制。假说是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更有效地减少术后 手术并发症。这一假设是在已公布的初步数据的基础上提出的 由申请者的实验室和专家指南提出，呼吁对此进行更严格的研究 接近。其基本原理是专门的免疫营养素(SIM)是用营养物质(L-精氨酸， Omega-3脂肪酸、饮食核苷酸和维生素A)，这些物质对免疫和 手术后的炎症反应、肌肉保护和伤口愈合。以强劲的前期工作为指导 数据，这一假设将在三个具体目标上进行检验：1)确定围手术期SIM的影响 与相同的术后缺乏免疫调节剂的口服营养支持(ONS)相比 RC并发症：2)比较SIM和ONS对RC术后二次临床结局的影响 手术；3)评价服用SIM和ONS对抑制髓系来源的影响 抑制细胞(MDSCs)，减少炎症，调节营养代谢。该项目是 意义重大，因为它提供了一种高收益、低风险、低成本的策略来改善患者的预后 接受RC的膀胱癌患者。我们的创新方法可以改变临床实践，以减少 手术并发症，从而减轻了膀胱癌手术的负担，增加了 有可能帮助许多其他手术患者超越膀胱切除术。

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.