Energy Expenditure and Nutrition After Pancreatic Surgery (NUTRI-PD)

Resting Energy Expenditure, Nutritional Intake, and Postoperative Outcomes in Patients Undergoing Total or Partial Pancreatectomy for Pancreatic Tumors: A Prospective Observational Cohort Study

This prospective observational cohort study examines the energy requirements and nutritional care of patients undergoing total or partial pancreatectomy for pancreatic tumors. Patients undergoing pancreatectomy face major metabolic stress, a high burden of preoperative malnutrition, and frequent exocrine or endocrine insufficiency, yet procedure-specific nutritional guidance is limited. The study measures resting energy expenditure (REE) directly by indirect calorimetry during the early postoperative period and compares it with widely used predictive equations (Harris-Benedict, Schofield) and simplified weight-based targets (25 and 30 kcal/kg) to determine how accurately clinicians can estimate energy needs when calorimetry is unavailable. In the same patients, the study records the route of postoperative nutrition (enteral, parenteral, or combined), energy and protein intake relative to requirements, and diet-related symptoms, and follows postoperative complications, hospital readmission, mortality, and changes in body weight and body mass index through 3-6 months after surgery. By capturing measured energy expenditure and nutritional delivery in one cohort, the study aims to clarify whether adequacy of energy and protein intake, feeding route, or both influence recovery, and to provide primary data for developing individualized nutritional support protocols in this high-risk surgical population.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Neoplasms; Pancreatic Cancer; Pancreaticoduodenectomy; Whipple Procedures
• Intervention / Treatment: Procedure: Pancreatectomy; Diagnostic test: Indirect calorimetry

Detailed Description

Background and Rationale Patients undergoing pancreatic resection experience surgical stress, systemic inflammation, and frequent exocrine and endocrine insufficiency that together alter energy metabolism and place them at high risk of nutritional deterioration. Predictive equations and simplified weight-based targets are used routinely to prescribe nutrition when indirect calorimetry is unavailable, but their accuracy in this specific surgical population is poorly characterized, and the degree to which the route and adequacy of postoperative feeding influence recovery has not been examined alongside directly measured energy expenditure in the same patients. This study is designed to address both questions within a single prospective cohort, pairing calorimetry-based measurement of resting energy expenditure with structured documentation of nutritional delivery and clinical outcomes.

Design and Setting The study is a single-center prospective observational cohort study. Consecutive eligible adults undergoing total or partial pancreatectomy for pancreatic tumors are enrolled preoperatively after informed consent. Feeding route is not assigned by the protocol; it is determined case by case by the treating surgical and nutrition support teams according to clinical status and tolerance, and is recorded as an observed exposure. All measurements and data abstraction are performed by trained clinical dietitians and drawn from direct measurement and the medical record.

Indirect Calorimetry Procedure Measured resting energy expenditure (mREE) is determined using a Cosmed Q-NRG+ portable indirect calorimeter. The device is calibrated before each session per the manufacturer's automatic gas-calibration procedure. Measurements are obtained by canopy where feasible, with a face mask used only when a canopy cannot be applied, recording VO₂ and VCO₂. Patients are measured supine, awake, and motionless in the morning after an 8-10 hour fast, at a controlled room temperature of 22-24 °C, following a minimum 20-30 minutes of rest. The first five minutes of each recording are discarded, and steady state is defined as at least five consecutive minutes during which the coefficient of variation in VO₂ and VCO₂ does not exceed 10%. Caffeine and strenuous activity are avoided for at least 12 hours beforehand, and supplemental oxygen is suspended or accounted for where clinically feasible. mREE is derived using the abbreviated Weir equation, mREE = (3.94 × VO₂ + 1.11 × VCO₂) × 1.44, and the respiratory quotient is calculated as VCO₂/VO₂. To reduce the influence of single-timepoint sampling within a dynamic postoperative course, calorimetry is scheduled at more than one time point during the early recovery period where the patient's clinical stability permits, with the exact days recorded.

Estimation of Energy Requirements for Comparison Predicted resting energy expenditure is calculated for each patient using the Harris-Benedict and Schofield equations. Harris-Benedict is applied as: men, 66.47 + 13.75 × weight (kg) + 5.0 × height (cm) - 6.75 × age; women, 665.09 + 9.56 × weight (kg) + 1.84 × height (cm) - 4.67 × age. Schofield is applied by sex and age band. For overweight patients, ideal body weight is used in these equations; for obese patients, corrected weight [ideal body weight + 0.25 × (actual - ideal body weight)] is used. Total energy requirements are additionally estimated from the ESPEN weight-based targets of 25 and 30 kcal/kg of ideal body weight (adjusted using a BMI of 22 kg/m² for overweight and 24.9 kg/m² for obese patients) and compared with mREE adjusted by an activity/stress factor of 1.15. Because the two families of estimates target different quantities - basal/resting expenditure for the equations versus total requirements for the weight-based targets - equation comparisons use raw mREE while weight-based comparisons use mREE × 1.15, and this distinction is retained throughout analysis.

Nutritional Intake and Feeding-Route Documentation For each patient, the route of postoperative nutrition (enteral plus oral, parenteral only, or combined enteral and parenteral) is recorded, together with the formulation used, the daily administered volume, and the delivery rate. Daily energy and protein delivery are quantified and expressed relative to individually calculated requirements to derive an energy deficit and a protein deficit for the early postoperative period. Diet-related symptoms (including diarrhea and abdominal pain) are recorded prospectively. These data support the planned subgroup comparison of outcomes across feeding routes and across strata of energy and protein deficit.

Anthropometry and Body Composition Body weight is measured on a calibrated electronic scale to the nearest 0.1 kg. Height is measured with the patient standing upright, unshod and bare-headed, using the Frankfort horizontal plane for head alignment. BMI is calculated as weight (kg) divided by height squared (m²). Weight and BMI are recorded at the preoperative assessment, at discharge, and at the 3-6 month follow-up, and recent percentage weight change is documented. Because body weight in the early postoperative period is confounded by fluid shifts, third-spacing, and edema, preoperative weight is used as the reference exposure in modeling, and objective body composition assessment (bioelectrical impedance or CT-derived skeletal muscle measurement, where available) is incorporated to distinguish loss of fat mass from loss of lean mass.

Nutritional Risk Screening and Biochemical Markers Preoperative nutritional risk is screened using the Perioperative Nutrition Screen (PONS), which weights recent weight loss, reduced intake or anorexia, low BMI, and the presence of a high-metabolic-risk underlying disease. Serum albumin (as a surrogate marker of visceral protein status) and C-reactive protein (as a marker of systemic inflammation) are recorded as exploratory variables at defined time points around the calorimetry measurement, per the hospital's standard laboratory procedures. Clinical variables including comorbidities, tumor site and surgical procedure, postoperative complications, length of stay, and readmissions are abstracted from the medical record.

Follow-up Schedule Assessments are anchored to the perioperative pathway: a preoperative baseline (anthropometry, screening, biochemistry), early postoperative calorimetry and intake documentation during the index admission, a discharge assessment, and a follow-up contact at 3-6 months after discharge for anthropometry and outcome ascertainment. Complication, readmission, and mortality windows follow the postoperative course as specified in the outcome measures.

Statistical Analysis Plan Analyses will be conducted in Jamovi with two-tailed tests at α = 0.05. Distributional normality is assessed by the Shapiro-Wilk test; normally distributed continuous variables are summarized as mean (SD) and non-normal variables as median (interquartile range), with categorical variables as counts and percentages. Agreement between mREE and each estimation method is evaluated by Bland-Altman analysis, reporting mean bias, 95% limits of agreement, and tests for proportional bias, complemented by accuracy indices (percentage within ±10% and ±20%, mean absolute percentage error, and root mean square error) and by linear regression of estimates against mREE. Determinants of mREE are examined using multiple linear regression with prespecified adjustment sets (unadjusted; age and sex; and additionally CRP and albumin). Changes in weight, BMI, and laboratory markers across time points are analyzed with repeated-measures ANOVA or Friedman's test as appropriate, with pairwise comparisons. Where repeated calorimetry measurements are obtained, longitudinal trajectories are analyzed using linear mixed-effects models to accommodate within-patient correlation and variable measurement timing. Feeding route and deficit strata are compared for complications, readmission, and mortality. The single-center design and anticipated sample size are recognized as constraints on power and generalizability, and subgroup analyses (including by surgical type) are treated as exploratory.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Dimitrios Karagiannis, PhD; Phone Number: +30 2132045035; Email: jimkar_d@yahoo.com
• Study Contact Backup: Name: Ζοι Bouloubassi, MSc; Phone Number: +30 2132041685; Email: zoippp@yahoo.com

Study Locations

• Greece
  • Attica
    • Athens, Attica, Greece, 10676
      • Recruiting
      • Evaggelismos General Hospital
      • Contact: Dimitrios Karagiannis; Phone Number: 6937158640; Email: jimkar_d@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Consecutive adult patients admitted for total or partial pancreatectomy - including pancreaticoduodenectomy (Whipple procedure) and distal pancreatectomy - for a pancreatic tumor at the participating surgical center. The cohort reflects the real-world case mix referred for pancreatic resection and therefore includes both malignant tumors and premalignant or benign lesions (such as intraductal papillary mucinous neoplasm and ampullary tumors), spanning the head, body, and tail of the pancreas. Participants are enrolled preoperatively and followed through the early postoperative period and to 3-6 months after discharge. Within this single cohort, the postoperative feeding route (enteral with oral intake, parenteral, or combined) is observed rather than assigned and is analyzed as an exposure of interest.

Description

Inclusion Criteria:

• Age 18 years or older
• Scheduled to undergo total or partial pancreatectomy (including pancreaticoduodenectomy/Whipple procedure or distal pancreatectomy) for a pancreatic tumor
• Able to complete indirect calorimetry measurement by canopy or face mask for the required duration
• Able to provide written informed consent

Exclusion Criteria:

• Age under 18 years, greater than 75 years
• Pregnancy
• Inability to tolerate the calorimetry canopy or mask for the duration required for a valid measurement
• Unable or unwilling to provide informed consent
• patients already on preoperative enteral nutrition or unable to feed orally preoperatively

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Enteral and oral nutrition; Participants undergoing total or partial pancreatectomy for a pancreatic tumor whose postoperative nutrition is delivered by the enteral route together with oral intake. Feeding route is not assigned by the study; it is determined by the treating surgical and nutrition support teams according to clinical status and tolerance, and recorded as an observed exposure. All participants in this cohort undergo indirect calorimetry and structured documentation of energy and protein intake during the early postoperative period.	Procedure: Pancreatectomy; Total or partial pancreatectomy (including pancreaticoduodenectomy / Whipple procedure and distal pancreatectomy) performed for a pancreatic tumor. This is the qualifying surgical exposure common to all participants. Applies to: Cohort 1, Cohort 2, Cohort 3.; Other Names: Indirect calorimetry; Diagnostic test: Indirect calorimetry; Measurement of resting energy expenditure by indirect calorimetry (Cosmed Q-NRG+), performed under standardized fasting and steady-state conditions during the early postoperative period. This is the reference measurement against which predictive equations and weight-based targets are compared.
Parenteral nutrition; Participants undergoing total or partial pancreatectomy for a pancreatic tumor whose postoperative nutrition is delivered exclusively by the parenteral route, as determined clinically by the treating teams. As in the other cohorts, participants undergo indirect calorimetry and documentation of nutritional delivery, complications, and follow-up outcomes.	Procedure: Pancreatectomy; Total or partial pancreatectomy (including pancreaticoduodenectomy / Whipple procedure and distal pancreatectomy) performed for a pancreatic tumor. This is the qualifying surgical exposure common to all participants. Applies to: Cohort 1, Cohort 2, Cohort 3.; Other Names: Indirect calorimetry; Diagnostic test: Indirect calorimetry; Measurement of resting energy expenditure by indirect calorimetry (Cosmed Q-NRG+), performed under standardized fasting and steady-state conditions during the early postoperative period. This is the reference measurement against which predictive equations and weight-based targets are compared.
Combined enteral and parenteral nutrition; Participants undergoing total or partial pancreatectomy for a pancreatic tumor who receive combined enteral and parenteral nutrition, as determined clinically by the treating teams. Participants undergo the same calorimetry, intake documentation, and follow-up assessments as the other cohorts.	Procedure: Pancreatectomy; Total or partial pancreatectomy (including pancreaticoduodenectomy / Whipple procedure and distal pancreatectomy) performed for a pancreatic tumor. This is the qualifying surgical exposure common to all participants. Applies to: Cohort 1, Cohort 2, Cohort 3.; Other Names: Indirect calorimetry; Diagnostic test: Indirect calorimetry; Measurement of resting energy expenditure by indirect calorimetry (Cosmed Q-NRG+), performed under standardized fasting and steady-state conditions during the early postoperative period. This is the reference measurement against which predictive equations and weight-based targets are compared.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospital Stay	Total duration of the index hospitalization, in days.	From surgery through hospital discharge (up to approximately 30 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Agreement Between Measured and Predicted Resting Energy Expenditure	Agreement between mREE and each estimation method (Harris-Benedict, Schofield, 25 kcal/kg, 30 kcal/kg), assessed by Bland-Altman mean bias and 95% limits of agreement, mean absolute percentage error (MAPE), and root mean square error (RMSE). Equations are compared with raw mREE; weight-based targets with activity-adjusted mREE × 1.15.	Within 14 days after surgery.
Measured Resting Energy Expenditure (mREE)	Resting energy expenditure measured by indirect calorimetry (Cosmed Q-NRG+) and derived using the abbreviated Weir equation, expressed in kcal/day.	Within 14 days after surgery.
. Energy Intake as Percentage of Requirements	Daily energy delivery as a percentage of individually calculated energy requirements, reported overall and by feeding-route group (enteral+oral, parenteral only, combined). Unit of Measure: Percentage of estimated requirements (%)	Postoperative days 2, 4, and 8, and up to 30 days (hospital discharge)
Incidence of Postoperative Complications	Proportion of participants with delayed gastric emptying, postoperative pancreatic fistula, or infectious complications, recorded per standard clinical definitions.	From surgery through 90 days postoperatively.
All-Cause Mortality	Proportion of participants who died from any cause.	At 30, 90, and 180 days after surgery.
Protein Intake as Percentage of Requirements	Daily protein delivery as a percentage of individually calculated protein requirements, reported overall and by feeding-route group (enteral+oral, parenteral only, combined). Unit of Measure: Percentage of estimated requirements (%)	Postoperative days 2, 4, and 8, and up to 30 days (hospital discharge)

Collaborators and Investigators

• Sponsor: Evangelismos Hospital
• Collaborators: Agricultural University of Athens; University of Peloponnese
• Investigators: Study Chair: Kalliopi Anna Poulia, PhD, School of Food and Nutritional Sciences, Agricultural University of Athens; Study Chair: Melina Dimitriou, PhD, m.dimitriou@go.uop.gr

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2017
• Primary Completion (Estimated): January 10, 2028
• Study Completion (Estimated): November 10, 2028

Study Registration Dates

• First Submitted: July 4, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Nutrition; Pancreaticoduodenectomy; Nutrition support; Indirect calorimetry; Surgical oncology nutrition; Postoperative nutrition
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Investigative Techniques; Surgical Procedures, Operative; Digestive System Surgical Procedures; Chemistry Techniques, Analytical; Calorimetry; Calorimetry, Indirect; Pancreatectomy
• Other Study ID Numbers: 484/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying published results will be made available to qualified researchers whose proposed use has been approved by an independent review committee. Requests must include a methodologically sound proposal and a signed data-access agreement, and data will be shared only after the necessary approvals from the sponsoring institution and the ethics committee, and only to the extent permitted by the participants' informed consent and applicable data-protection law (including the EU General Data Protection Regulation). Given the single-center design and limited sample size, data will be released in de-identified form with any potentially identifying variables removed or aggregated to minimize re-identification risk.
• IPD Sharing Time Frame: Beginning 6 months after publication of the primary results and ending 36 months after publication.
• IPD Sharing Access Criteria: Access is granted to qualified researchers who submit a written request with a scientifically justified proposal to the corresponding author. Requests are evaluated by the sponsor/institution and require ethics-committee approval and execution of a data-access/data-transfer agreement before any data are released. Data are provided in de-identified form for the approved analysis only and may not be redistributed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No