Prospective Cohort Study of Nutritional, Metabolic, Molecular, and Volumetric Assessment of the Remnant Pancreas in Patients With Periampullary Malignancies Undergoing Pancreaticoduodenectomy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Resting Energy Expenditure (REE) in kcal/day
研究概览
简要总结
Periampullary malignant neoplasms are among the most lethal gastrointestinal tumors. They are usually diagnosed at advanced stages and require complex surgical treatment. Pancreaticoduodenectomy, the standard procedure for resectable cases, significantly impacts nutritional status, pancreatic function, and the structural integrity of the remaining pancreas. However, there are still significant knowledge gaps regarding the volumetric and molecular changes that occur postoperatively and how these changes interact with body composition, resting energy expenditure, and biochemical markers.
This prospective, controlled, cohort study aims to integrate clinical, nutritional, metabolic, molecular, and imaging data to investigate changes in the remnant pancreas and their associations with postoperative outcomes. The study is expected to provide novel insights to support personalized, evidence-based nutritional and metabolic care for patients undergoing pancreaticoduodenectomy.
详细描述
Periampullary malignant neoplasms are lethal gastrointestinal tumors that are often diagnosed at advanced stages and require complex surgical intervention. Pancreaticoduodenectomy, the gold standard for resectable disease, has profound effects on nutritional status, exocrine pancreatic function, and the structural integrity of the remaining pancreas. Despite recent advances, significant gaps remain in our understanding of the volumetric and molecular alterations that occur postoperatively and how these alterations interact with body composition, resting energy expenditure, and biochemical markers.
This is a prospective, longitudinal, controlled, clinical-translational cohort study. Data on clinical, nutritional, biochemical, and plasma parameters will be collected at three time points for the experimental group (preoperatively and 3 and 6 months after hospital discharge) and one time point for the control group. Plasma samples will be stored at -80 °C and analyzed using validated techniques, including multiplex assays, spectrophotometry, ELISA, and tandem mass spectrometry (LC-MS/MS) to detect inflammatory biomarkers (IL-1β, , IL-6, TNF-α, and MCP-1; oxidative markers (MDA, GSH, TAC, and FRAP); proteomic targets (HSP70, fibronectin, and laminin); and lipidomic profiles (ceramides, sphingolipids, and cardiolipins). Abdominal imaging (CT and/or MRI) will be processed using 3D Slicer software to estimate the volume of the remnant pancreas via three-dimensional segmentation.
Statistical analyses will be conducted in RStudio. We will apply mixed linear models (MLM and MLMG), incorporating fixed and random effects to account for intra- and inter-individual variability. Missing not-at-random data will be addressed using multiple imputation by chained equations (MICE), and pooled estimates will be calculated according to Rubin's rules. We will set statistical significance at p < 0.05 with Holm-Bonferroni correction for multiple comparisons.
This integrative approach ensures methodological rigor, bias control, and robust inference. It has the potential to guide personalized, evidence-based nutritional strategies in the context of pancreatic cancer.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults aged between 18 and 80 years;
- •Histologically or radiologically confirmed diagnosis of resectable periampullary malignant neoplasms (e.g., pancreatic head adenocarcinoma, ampullary carcinoma, distal cholangiocarcinoma, duodenal adenocarcinoma);
- •Candidates for elective pancreaticoduodenectomy (either classic Whipple or pylorus-preserving technique), performed by the institutional surgical team following standardized protocols;
- •ECOG Performance Status ≤2;
- •Adequate cardiopulmonary function to undergo major surgery, as assessed preoperatively;
- •Ability and willingness to provide written informed consent.
排除标准
- •Previous pancreatic surgery;
- •Pancreaticoduodenectomy performed outside the study institution;
- •Evidence of unresectable disease, distant metastases, or local tumor recurrence at baseline imaging or intraoperative assessment;
- •Active inflammatory or autoimmune diseases (e.g., rheumatoid arthritis, lupus, inflammatory bowel disease);
- •Active malignancy other than periampullary cancer, or history of non-pancreatic cancer within the past 5 years;
- •Use of systemic immunosuppressive therapy (e.g., corticosteroids >10 mg/day prednisone equivalent, chemotherapy, biologics);
- •Diagnosed malabsorption syndromes unrelated to pancreatic disease;
- •Severe hepatic dysfunction or severe renal impairment (eGFR <30 mL/min/1.73m²);
- •Pregnancy or breastfeeding;
- •Refusal or inability to attend scheduled follow-up visits within 6 months;
结局指标
主要结局
Resting Energy Expenditure (REE) in kcal/day
时间窗: Day 0 (preoperative), 3 months post-discharge, and 6 months post-discharge
Resting energy expenditure will be measured using indirect calorimetry (Quark RMR®) following standardized protocols. Results will be expressed in kcal/day, and normalized to body weight and fat-free mass. Results will be compared with predictive equations (Harris-Benedict, Mifflin-St Jeor, FAO/WHO).
次要结局
- Fat-Free Mass (kg) measured by multifrequency bioimpedance analysis(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Fasting Glucose (mg/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- ALT (U/L)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Serum Albumin (g/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Hydration Status (%) assessed by bioimpedance analysis(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Serum C-Reactive Protein - CRP (mg/L)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Fat Mass (kg) measured by multifrequency bioimpedance analysis(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Phase Angle (°) assessed by bioimpedance analys(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Total Serum Protein (g/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Hemoglobin (g/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Absolute Lymphocyte Count (×10³/mm³)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Serum Ferritin (ng/mL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Latent Iron-Binding Capacity - LIBC (µg/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Serum Transferrin (mg/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Transferrin Saturation (%)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Serum Urea (mg/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Serum Creatinine (mg/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- AST (U/L)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Serum Iron (µg/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Serum Folate - Vitamin B9 (ng/mL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Serum Vitamin B12 (pg/mL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Vitamin A - Retinol (µg/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Vitamin E - Alpha-tocopherol (mg/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Plasma Copper (µg/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Interleukin 1 beta (IL-1β), pg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Plasma Zinc (µg/dL)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Sudan III Stool Test (qualitative)(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Interleukin 4 (IL-4), pg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Interleukin 6 (IL-6), pg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Interleukin 8 (IL-8), pg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Interleukin 10 (IL-10), pg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Tumor Necrosis Factor Alpha (TNF-α), pg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Interferon Gamma (INF-γ), pg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Vascular Endothelial Growth Factor (VEGF), pg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Monocyte Chemoattractant Protein 1 (MCP-1), pg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Free Plasma Amino Acids (HPLC), nmol/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Malondialdehyde (MDA), nmol/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Reduced Glutathione (GSH), µmol/L(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Total Hydroperoxides (FOX), µmol/L(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Total Antioxidant Capacity (TAC), mmol/L(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Ferric Reducing Ability of Plasma (FRAP), mmol/L(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Heat Shock Protein 70 (HSP70), ng/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Fibronectin, µg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Laminin, µg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Plasma Ceramides, ng/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Plasma Sphingolipids, ng/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Plasma Cardiolipins, ng/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Plasma Prostaglandins, pg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Plasma Leukotrienes, pg/mL(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
- Pancreatic Remnant Volume, cm³(Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge)
研究者
Marco Aurélio Ribeiro, PhD
Principal Investigator
University of Sao Paulo