Effect of Immune-Enhancing Nutrition on Radical Cystectomy Outcomes- MERIT extension

免疫增强营养对根治性膀胱切除术结果的影响 - MERIT 扩展

• 批准号: 10517175
• 负责人: Jill Hamilton-Reeves
• 金额: $ 61.44万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10517175
• 关键词: Address; Amino Acids; Antibiotics; Arginine; Calories; Cancer Patient; Cancer Survivor; Caring; Cells; Clinical; Clinical Trials; Complication; Consumption; Cystectomy; Data; Death Rate; Dietary Intervention; Disease-Free Survival; Double-Blind Method; Dual-Energy X-Ray Absorptiometry; Fatty Acids; Future; Goals; Immune; Immune response; Immune system; Immunomodulators; Impairment; Infection; Infection prevention; Inflammation; Inflammatory; Inflammatory Response; Intake; Interleukin-6; Intervention; Intestines; Laboratories; Lymphocyte; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measures; Metabolism; Methods; Muscle; Muscular Atrophy; Myeloid-derived suppressor cells; National Cancer Institute; National Clinical Trials Network; Nitrogen; Nucleotides; Nutrient; Nutritional Support; Nutritional status; Omega-3 Fatty Acids; Operative Surgical Procedures; Oral; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Perioperative; Phase; Pilot Projects; Postoperative Complications; Postoperative Period; Procedures; Quality of life; Radical Cystectomy; Randomized; Research; Resistance to infection; Risk; Route; Running; Southwest Oncology Group; Supplementation; Surgical Oncology; Surgical complication; Testing; Translations; Urine; Urologic Oncology; Vitamin A; Work; arm; cancer surgery; cancer therapy; clinical practice; cost; cytokine; design; dietary; effectiveness evaluation; experience; fortification; healing; immune function; immunoregulation; improved; improved outcome; infection rate; innovation; microbiome; mortality; multi-site trial; neutrophil; nutrient metabolism; nutrition; operation; parent grant; pilot trial; preservation; readmission rates; reconstruction; restraint; skeletal muscle wasting; standard care; surgery outcome; wound healing

PROJECT SUMMARY/ABSTRACT Patients undergoing surgery to treat their bladder cancer experience persisting complications from their surgery. A lower resistance to infection and muscle wasting are common complications from the surgery. The radical cystectomy operation is not only extremely catabolic, but fraught with the highest complication rate of all the urologic oncology surgeries performed. Improve immune function, enhanced healing and reduced infections would offer significant benefit to bladder cancer. The overall goal of this project is to reduce post- operative complications from the surgical treatment of advanced bladder cancer and to better understand how specialized immunonutrition modulates the immune system to reduce infections and skeletal muscle wasting. The objective of this project is to assess the effectiveness of SIM intake before and after RC surgery compared to a calorie- and nitrogen-matched ONS to reduce post-operative complications. The central hypothesis is that SIM will reduce post-operative complications by restraining the expansion of MDSCs from RC surgery, preserving muscle, and reducing infections. This hypothesis has been formulated on the basis of preliminary data produced in the applicants’ laboratories and practice. The rationale is that surgery induces the expansion of immature immune cells called myeloid-derived suppressor cells, which lower the resistance to infection and may contribute to muscle wasting. SIM intake restrains the expansion of these cells, reduces infection rates, and appears to protect against overall complications and muscle wasting. Guided by strong preliminary data, the hypothesis will be tested in three specific aims: 1) To determine the impact of consuming SIM compared to ONS on post-operative complications from RC surgery; 2) To determine the impact of consuming SIM compared to ONS on infections and skeletal muscle wasting from RC surgery; 3) To evaluate the impact of consuming SIM compared to ONS for restraining MDSCs, decreasing inflammation, and modulating the immune landscape, nutrient metabolism, or the microbiome. The project is significant because there is currently no known means to prevent infections and muscle-wasting after RC surgery. This innovative approach could transform clinical practice to reduce post- operative complications, thereby diminishing the burden of bladder cancer surgery.

项目总结/摘要 接受手术治疗膀胱癌的患者会经历持续的并发症， 手术对感染的抵抗力较低和肌肉萎缩是手术的常见并发症。 根治性膀胱癌手术不仅是极端的分解代谢，但充满了最高的并发症发生率 所有泌尿肿瘤手术的记录提高免疫功能，增强愈合和减少 感染会给膀胱癌带来很大的好处。该项目的总体目标是减少后- 晚期膀胱癌手术治疗的手术并发症，并更好地了解 专门的免疫营养素如何调节免疫系统以减少感染和骨骼肌 浪费本研究的目的是评估在康复治疗前后SIM摄入的有效性 与卡路里和氮匹配的ONS相比，手术可以减少术后并发症。的 中心假设是，SIM将通过抑制扩张来减少术后并发症。 来自RC手术的MDSC，保留肌肉，减少感染。这一假设已经形成 根据申请人的实验室和实践中产生的初步数据。基本原理是 手术诱导称为髓源性抑制细胞的未成熟免疫细胞的扩增， 降低对感染的抵抗力，并可能导致肌肉萎缩。SIM进气抑制膨胀 这些细胞，降低感染率，似乎可以防止整体并发症和肌肉 浪费在强有力的初步数据的指导下，该假设将在三个具体目标中进行测试：1） 确定与ONS相比，使用SIM对RC术后并发症的影响 2）确定SIM与ONS相比对感染和骨骼肌的影响 RC手术导致的消瘦; 3）评价与ONS相比，使用SIM对抑制 MDSC，减少炎症，调节免疫景观，营养代谢，或 微生物组该项目意义重大，因为目前还没有已知的预防感染的方法， RC手术后肌肉萎缩这种创新的方法可以改变临床实践，以减少术后 手术并发症，从而减轻膀胱癌手术的负担。

项目成果

Current Therapeutic Targets in Cancer Cachexia: A Pathophysiologic Approach.

• DOI: 10.1200/edbk_389942
• 发表时间: 2023-06-01
• 期刊: American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting
• 作者: Kadakia, Kunal C;Hamilton-Reeves, Jill M;Baracos, Vickie E
• 通讯作者: Baracos, Vickie E

Optimizing Nutritional Status in Patients Undergoing Radical Cystectomy: A Systematic Scoping Review.

• DOI: 10.3233/blc-200428
• 发表时间: 2021
• 期刊: Bladder cancer (Amsterdam, Netherlands)
• 作者: Alam SM;Michel C;Robertson H;Camargo JT;Linares B;Holzbeierlein J;Hamilton-Reeves J
• 通讯作者: Hamilton-Reeves J