A combined preoperative cardiorespiratory fitness and body composition phenotype is associated with major complications after pancreatoduodenectomy, independent of postoperative pancreatic fistula risk

Introduction: Major complication rates after pancreatoduodenectomy (PD) are high. Cardiorespiratory fitness and body composition are considered important determinants of postoperative outcomes. This study evaluated the association between a multimodal preoperative assessment of cardiorespiratory fitness and body composition as core patient phenotypes and the occurrence of major complications following PD. Methods: In this two-center retrospective cohort study (2022-2024), patients undergoing PD were included. Preoperative cardiorespiratory fitness was assessed using cardiopulmonary exercise testing (CPET) or the modified steep ramp test (mSRT). Poor cardiorespiratory fitness was defined as an oxygen uptake (VO2) at the ventilatory anaerobic threshold (AT) < 11.0 mL/kg/min or VO2 at peak exercise (VO2peak) < 18.0 mL/kg/min during CPET, or a work rate at peak exercise <2.1W/kg at the mSRT. Preoperative body composition parameters were derived from abdominal computed tomography scans. Low muscle mass based on skeletal muscle index (SMI) and myosteatosis (defined as low skeletal muscle radiation attenuation, SM-RA) were assessed. The primary outcome was 30-day major complications (Clavien-Dindo >= III). Logistic regression analyses identified predictors. Results: Among 175 eligible patients (mean +/- SD age 69.1 +/- 8.2 years, 44.6% female), 34.9% were unfit; 54.9% had low muscle mass and 35.4% had myosteatosis. Major complications occurred in 37.7% and 8.0% required unplanned intensive care unit (ICU) admission. Preoperative cardiorespiratory fitness correlated moderately with SM-RA (rho = 0.36-0.47; all p < 0.001). Poor cardiorespiratory fitness was associated with major complications in multivariable analysis (adjusted odds ratio [aOR] 2.54, 95% CI 1.17-5.54, p=0.02). Combined myosteatosis and poor cardiorespiratory fitness (n = 28, 16.0%) was associated with both major complications (aOR 3.40, 95% CI 1.25-9.28, p = 0.02) and unplanned ICU admission (aOR 4.62, 95% CI 1.06-20.16, p = 0.04). Conclusion: Myosteatosis correlates with lower cardiorespiratory fitness. The combination of preoperative myosteatosis and poor cardiorespiratory fitness is associated with major complications and postoperative ICU admission. In future preoperative assessment, these patient phenotypes may help to refine personalized risk assessment and guide inclusions for trials on targeted preventive interventions.