Preoperative bilirubin normalization and outcomes after pancreaticoduodenectomy in patients with predominantly mild-to-moderate obstructive jaundice due to periampullary tumors

Aims: Pancreaticoduodenectomy remains the cornerstone of curative treatment for periampullary tumors but is associated with substantial postoperative morbidity. Obstructive jaundice is common in this setting and has traditionally been regarded as a risk factor warranting delay of surgery until biochemical normalization of bilirubin. However, evidence supporting this strategy remains conflicting, particularly in patients with mild to moderate hyperbilirubinemia.Methods: This retrospective single-center cohort study screened 295 consecutive patients who underwent pancreaticoduodenectomy for suspected periampullary tumors between June 2020 and August 2025. To specifically evaluate the impact of cholestasis, patients without preoperative hyperbilirubinemia were excluded. The final study cohort comprised 197 patients with cholestasis-associated periampullary tumors, including patients operated on with elevated bilirubin levels and those who underwent preoperative biliary drainage due to bilirubin elevation. Preoperative total bilirubin, C-reactive protein (CRP), and white blood cell count were recorded within 72 hours prior to surgery. Postoperative morbidity was assessed using the Clavien–Dindo classification, with overall morbidity defined as Clavien–Dindo grade ≥1 and major morbidity as Clavien Dindo grade ≥3. Bilirubin was evaluated both as a continuous variable and using clinically relevant cut-off values. Multivariable analyses were performed to identify independent associations with postoperative outcomes.Results: The mean preoperative total bilirubin level was 3.01±2.91 mg/dl. Preoperative bilirubin levels were not independently associated with overall morbidity, major morbidity, or postoperative mortality across multiple thresholds (≥2 mg/dl, >5 mg/dl, and >10 mg/dl). Similarly, the combined elevation of bilirubin and CRP did not predict increased postoperative morbidity or mortality. However, a more selective inflammatory cholestasis phenotype (bilirubin >5 mg/dl and CRP ≥10 mg/L) was independently associated with prolonged hospital stay after adjustment for age and American Society of Anesthesiologists (ASA) physical status.Conclusion: In this cohort of patients with cholestasis-associated periampullary tumors, preoperative hyperbilirubinemia—alone or combined with inflammatory markers—was not associated with increased postoperative morbidity or mortality after pancreaticoduodenectomy. These findings suggest that, in clinically stable patients with mild to moderate obstructive jaundice, delaying surgery solely to achieve biochemical normalization of bilirubin may not be necessary. Preoperative cholestasis and inflammation may be more informative for anticipating postoperative recovery patterns than for determining surgical eligibility.