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Completed

NCT Number: NCT07159672

Cohort Study on Nutritional, Metabolic, and Volumetric Assessment After Pancreaticoduodenectomy

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.

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Key information

Conditions

Periampullary Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Neoplasms Neoplasms by Site Pancreatic Cancer Pancreatic Diseases Pancreatic Neoplasms Pancreaticoduodenectomy

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Ribeirão Preto Medical School University of São Paulo

Ribeirão Preto, São Paulo, 14.048-900, Brazil

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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;

Treatment and study plan

Pancreaticoduodenectomy

Procedure

Pancreaticoduodenectomy (classic Whipple or pylorus-preserving) performed as part of standard clinical care for patients with periampullary malignant neoplasms. This procedure is not assigned by the study protocol, but is the exposure of interest. The study observes nutritional, metabolic, molecular, and imaging outcomes at baseline (preoperative), and at 3 and 6 months after hospital discharge.

Other names: Whipple procedure, Pylorus-preserving pancreaticoduodenectomy

Primary outcomes

  1. Resting Energy Expenditure (REE) in kcal/day

    Time frame: 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).

Secondary outcomes

  1. Fat-Free Mass (kg) measured by multifrequency bioimpedance analysis

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Fat-free mass will be assessed using multifrequency bioimpedance (SECA mBCA 525®). Values will be reported in kilograms and normalized by body surface area.

  2. Fat Mass (kg) measured by multifrequency bioimpedance analysis

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Fat mass will be measured using SECA mBCA 525® bioimpedance. Results will be expressed in kilograms and monitored across study visits.

  3. Hydration Status (%) assessed by bioimpedance analysis

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Percentage of total body water will be determined by SECA mBCA 525® device using multifrequency bioimpedance.

  4. Phase Angle (°) assessed by bioimpedance analys

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Phase angle will be derived from resistance and reactance using multifrequency BIA with SECA mBCA 525®, as a proxy of cell membrane integrity.

  5. Total Serum Protein (g/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Measured using colorimetric assay with spectrophotometric reading at 540 nm. Reference range: 6.0-8.3 g/dL.

  6. Serum Albumin (g/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Quantified using specific colorimetric method with reading at 625 nm. Normal range: 3.5-5.0 g/dL.

  7. Serum C-Reactive Protein - CRP (mg/L)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Systemic inflammation marker measured via immunoturbidimetric assay with latex particles. Reference value: <3 mg/L.

  8. Fasting Glucose (mg/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Measured by enzymatic colorimetric method. Reference range: 70-99 mg/dL.

  9. Hemoglobin (g/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Determined by automated hematology analyzer (ABX Pentra DX120), using impedance, photometry, and fluorescence. Reference: 13-17.5 g/dL (men), 12-15.5 g/dL (women).

  10. Absolute Lymphocyte Count (×10³/mm³)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Analyzed using automated hematology analyzer. Normal range: 1.0-4.0 ×10³/mm³.

  11. Serum Iron (µg/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Determined by direct colorimetric method. Normal range: 65-175 µg/dL (men), 50-170 µg/dL (women).

  12. Serum Ferritin (ng/mL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Measured by chemiluminescence (Immulite 2000). Normal: 30-300 ng/mL (men), 15-150 ng/mL (women).

  13. Latent Iron-Binding Capacity - LIBC (µg/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Assessed via direct colorimetric method. Reference: 240-450 µg/dL.

  14. Serum Transferrin (mg/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Calculated using Vannucchi et al. (1996): Transferrin = ((LIBC + Iron) × 0.8) - 43. Reference: 200-360 mg/dL.

  15. Transferrin Saturation (%)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Calculated by serum iron / LIBC ratio. Normal range: 20-50%.

  16. Serum Urea (mg/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Measured using kinetic method and spectrophotometric reading at 340 nm. Reference: 10-40 mg/dL.

  17. Serum Creatinine (mg/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Quantified by kinetic method with reading at 500 nm. Reference: 0.7-1.3 mg/dL (men), 0.6-1.1 mg/dL (women).

  18. AST (U/L)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Aspartate aminotransferase assessed via optimized UV method. Normal range: 10-40 U/L.

  19. ALT (U/L)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Alanine aminotransferase determined by UV method at 340 nm. Reference: 7-56 U/L.

  20. Serum Folate - Vitamin B9 (ng/mL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Measured by chemiluminescence (Immulite 2000). Reference: 3.0-17.0 ng/mL.

  21. Serum Vitamin B12 (pg/mL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Cobalamin levels determined by chemiluminescence. Normal range: 200-900 pg/mL.

  22. Vitamin A - Retinol (µg/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Determined by HPLC. Reference: 30-80 µg/dL.

  23. Vitamin E - Alpha-tocopherol (mg/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Assessed by HPLC. Normal range: 0.5-2.0 mg/dL.

  24. Plasma Copper (µg/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Measured by atomic absorption spectroscopy at 327.4 nm. Reference: 70-140 µg/dL (men), 80-155 µg/dL (women).

  25. Plasma Zinc (µg/dL)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Determined via atomic absorption spectroscopy at 213.9 nm. Reference: 60-120 µg/dL.

  26. Sudan III Stool Test (qualitative)

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Microscopic evaluation of Sudan III-stained stool samples for detection of steatorrhea. Reported as positive or negative.

  27. Interleukin 1 beta (IL-1β), pg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Plasma concentrations will be quantified using a multiplex immunoassay with magnetic beads (MagPix®, Luminex Corporation), following manufacturer's specifications.

  28. Interleukin 4 (IL-4), pg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Quantified via bead-based multiplex fluorescence assay using the MagPix® system (Luminex®), allowing simultaneous detection of multiple cytokines.

  29. Interleukin 6 (IL-6), pg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Measured by high-sensitivity magnetic bead-based immunoassay (Luminex® MagPix®), using standard calibration curves.

  30. Interleukin 8 (IL-8), pg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Determined using multiplex fluorescence-based immunoassay with magnetic bead differentiation and spectral laser detection.

  31. Interleukin 10 (IL-10), pg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Plasma levels will be assessed using a validated multiplex Luminex® panel, enabling parallel cytokine detection.

  32. Tumor Necrosis Factor Alpha (TNF-α), pg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Measured by multiplex immunoassay with magnetic beads on the Luminex® platform; assay sensitivity <1 pg/mL.

  33. Interferon Gamma (INF-γ), pg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Quantified using bead-based multiplex immunoassay with MagPix® system and fluorophore-labeled secondary antibodies.

  34. Vascular Endothelial Growth Factor (VEGF), pg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Determined by multiplex immunoassay using magnetic beads, with detection by Luminex® MagPix® laser-based fluorescence reader.

  35. Monocyte Chemoattractant Protein 1 (MCP-1), pg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Assessed using a Luminex®-based multiplex immunoassay with internal controls and duplicate sampling.

  36. Free Plasma Amino Acids (HPLC), nmol/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Quantified by high-performance liquid chromatography (HPLC) with pre-column derivatization using o-phthaldialdehyde (OPA) and fluorescence detection (excitation: 340 nm; emission: 450 nm).

  37. Malondialdehyde (MDA), nmol/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Measured by the thiobarbituric acid reactive substances (TBARS) assay, with spectrophotometric reading at 532 nm.

  38. Reduced Glutathione (GSH), µmol/L

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Quantified by spectrophotometric method using DTNB (5,5'-dithiobis-(2-nitrobenzoic acid)), with absorbance measured at 412 nm.

  39. Total Hydroperoxides (FOX), µmol/L

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Measured using the Ferrous Oxidation-Xylenol Orange (FOX) method with absorbance at 560 nm.

  40. Total Antioxidant Capacity (TAC), mmol/L

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Assessed using the ABTS+ radical cation decolorization assay with spectrophotometric analysis.

  41. Ferric Reducing Ability of Plasma (FRAP), mmol/L

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Quantified using the FRAP assay, based on the reduction of Fe3+ to Fe2+, measured at 593 nm.

  42. Heat Shock Protein 70 (HSP70), ng/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Plasma concentrations will be measured using sandwich-type enzyme-linked immunosorbent assay (ELISA), with detection at 450 nm after chromogenic substrate reaction.

  43. Fibronectin, µg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Quantified by high-sensitivity ELISA using monoclonal antibodies specific for fibronectin. Detection will be performed at 450 nm, using manufacturer-calibrated standard curves.

  44. Laminin, µg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Determined by validated ELISA sandwich assay with photometric quantification at 450 nm. Assay will be conducted in duplicate with quality controls and external calibrators.

  45. Plasma Ceramides, ng/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) after lipid extraction via the Folch method. Identification and quantification will be based on retention times and certified external standards.

  46. Plasma Sphingolipids, ng/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Plasma concentrations will be determined using validated LC-MS/MS protocols with external calibrators, after sample preparation by chloroform/methanol extraction.

  47. Plasma Cardiolipins, ng/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Quantified by LC-MS/MS using C18 chromatographic separation and tandem MS detection, with identification based on spectral patterns and standard curves.

  48. Plasma Prostaglandins, pg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Determined by LC-MS/MS with high-sensitivity detection and external calibration for absolute quantification. Sample preparation follows established lipidomic protocols.

  49. Plasma Leukotrienes, pg/mL

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    Measured using targeted LC-MS/MS following Folch lipid extraction. Identification and quantification will be conducted against authentic leukotriene standards.

  50. Pancreatic Remnant Volume, cm³

    Time frame: Day 0 (preoperative), 3 months post-discharge, 6 months post-discharge

    The remnant pancreatic volume will be measured using computed tomography (CT) and/or magnetic resonance imaging (MRI). Volumetric analysis will be performed through three-dimensional segmentation using 3D Slicer software.

Sponsors and collaborators

Lead sponsor

Marco Aurélio Ribeiro, PhD

Other

Collaborators

  • University of Sao Paulo

Registry information

Official study title

Prospective Cohort Study of Nutritional, Metabolic, Molecular, and Volumetric Assessment of the Remnant Pancreas in Patients With Periampullary Malignancies Undergoing Pancreaticoduodenectomy

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Sep 8, 2025
Registry last updated
Sep 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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