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Principal Investigator: Jill Reeves Hamilton-Reeves
Organization: UNIVERSITY OF KANSAS MEDICAL CENTER
Fiscal Year: 2024
Award: $557,517
Funding agency: National Cancer Institute
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.
Terms: <Address><Amino Acids><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Arginine><B cell differentiation factor><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Stimulatory Factor-2><BCDF><BSF-2><BSF2><Bladder Cancer><Bladder removal><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Calories><Cancer Patient><Cancer Treatment><Cancers><Caring><Cell Body><Cells><Cellular Immune Function><Clinical><Clinical Trials><Complication><Consumption><Cystectomy><DEXA><DXA><Data><Death Rate><Dietary Intervention><Disease-Free Survival><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><Dual-Energy X-Ray Absorptiometry><Dual-Energy Xray Absorptiometry><Event-Free Survival><Fatty Acids><Fortification><Future><Goals><HPGF><Hepatocyte-Stimulating Factor><Hybridoma Growth Factor><IFN-beta 2><IFNB2><IL-6><IL6 Protein><Immune><Immune response><Immune system><Immunes><Immunological response><Immunomodulation><Immunomodulators><Impairment><Infection><Infection prevention><Inflammation><Inflammatory><Inflammatory Response><Intake><Interleukin-6><Intermediary Metabolism><Intervention><Intervention Strategies><Intestinal><Intestines><L-Arginine><Laboratories><Lymphatic cell><Lymphocyte><Lymphocytic><MGI-2><Malignant Bladder Neoplasm><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Tumor><Malignant Tumor of the Bladder><Malignant neoplasm of urinary bladder><Marrow Neutrophil><Measures><Metabolic Processes><Metabolism><Methods><Miscellaneous Antibiotic><Muscle><Muscle Atrophy><Muscle Tissue><Muscular Atrophy><Myeloid Differentiation-Inducing Protein><Myeloid-derived suppressor cells><NCI Organization><National Cancer Institute><National Clinical Trials Network><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Nitrogen><Nucleotides><Nutrient><Nutrition Interventions><Nutritional Interventions><Nutritional Support><Nutritional status><Omega-3 Fatty Acids><Omega-3 PUFA><Omega-3 Polyunsaturated Fatty Acid><Omega3><Operative Procedures><Operative Surgical Procedures><Oral><Outcome><Pathway interactions><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Perioperative><Phase><Pilot Projects><Plasmacytoma Growth Factor><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Post-Operative><Postoperative><Postoperative Complications><Postoperative Period><Prevent infection><Procedures><QOL><Quality of life><Radical Cystectomy><Randomized><Research><Resistance to infection><Risk><Route><Running><SWOG><Southwest Oncology Group><Supplementation><Surgical><Surgical Interventions><Surgical Oncology><Surgical Procedure><Surgical complication><Testing><Translations><Urinary Bladder Cancer><Urinary Bladder Malignant Tumor><Urine><Urologic Oncology><Vitamin A><Work><Wound Repair><aminoacid><anti-cancer therapy><arm><assess effectiveness><bowel><cancer surgery><cancer therapy><cancer-directed therapy><clinical practice><cost><cytokine><design><designing><determine effectiveness><diet intervention><dietary><effectiveness assessment><effectiveness evaluation><evaluate effectiveness><examine effectiveness><experience><healing><hospital re-admission rates><hospital readmission rate><host response><immune function><immune modulation><immune modulators><immune regulation><immune system response><immunologic reactivity control><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><immunosuppressive myeloid cells><improved><improved outcome><infection rate><infection resistance><innovate><innovation><innovative><interferon beta 2><interventional strategy><lymph cell><malignancy><microbiome><mortality><mortality rate><mortality ratio><multi-site trial><multisite trial><muscle breakdown><muscle degradation><muscle deterioration><muscle loss><muscle wasting><muscular><myeloid suppressor cells><myeloid-derived suppressive cells><n-3 Fatty Acids><neoplasm/cancer><neutrophil><nutrient metabolism><nutrition><nutritional care><nutritional therapy><omega-3><oncologic surgery><operation><operations><parent grant><pathway><patient oriented outcomes><pilot study><pilot trial><post-operative complications><preservation><quality of life and care for cancer survivors><quality of life for cancer survivors><randomisation><randomization><randomly assigned><rate of infection><re-admission rates><re-hospitalization rate><readmission rates><reconstruction><rehospitalization rate><restraint><skeletal muscle atrophy><skeletal muscle breakdown><skeletal muscle loss><skeletal muscle protein loss><skeletal muscle wasting><standard care><standard treatment><suppressive myeloid cells><surgery><surgery complication><surgery outcome><surgical outcome><translation><wound healing><wound recovery><wound resolution><ω-3 fatty acids>