Impact of Biliary Fungal Contamination on Outcomes after Pancreaticoduodenectomy for Pancreatic Cancer

Jeremy Chang¹Sophia Xiao¹Yutao Su¹Scott K. Sherman^1,2James Howe V^1,2James P. De Andrade^1,2Hisakazu Hoshi¹Carlos H. F. Chan^1,2*

• ¹Department of Surgery, University of Iowa Health Care, Iowa City, United States
• ²The University of Iowa Holden Comprehensive Cancer Center, Iowa City, United States

Introduction: Many patients with cancer of the pancreatic head will have biliary stenting to relieve malignant obstruction. Biliary stenting is associated with increased rates of bacterial and fungal biliary contamination. Little is known regarding the impact of fungal biliary contamination on postoperative and oncologic outcomes of pancreatic cancer. This study aims to evaluate the effects of fungal biliary contamination on postoperative and oncologic outcomes in patients receiving pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). Methods: A retrospective study of a prospectively maintained single tertiary institutional database was performed identifying patients with the diagnosis of PDAC from 2015 to 2022 who underwent curative-intent resection and had intraoperative biliary fungal cultures. Primary outcome measures assessed included overall survival (OS) and recurrence free survival (RFS). Secondary outcome measure was postoperative complication rate. Kaplan method estimated OS and RFS and survival curves were compared with log rank test. Clinicopathologic variables were assessed for association with multivariable Cox hazard ratio. Results: Among 82 patients included, 87.8% had preoperative stenting. In stented patients, bacterial and fungal contamination had an incidence of 98.7% and 48.6%, respectively. Patients with positive fungal cultures had higher rates of neoadjuvant chemotherapy utilization than those with negative intraoperative fungal bile cultures (p=0.05). Positive biliary fungal cultures were not independently associated with risk for postoperative complications nor RFS but were associated with worse OS (HR = 2.11 [1.04 – 4.26], p=0.04). In the subgroup of patients who received neoadjuvant chemotherapy, positive fungal bile culture was associated with worse OS (HR = 2.70 [1.11 – 6.60], p=0.03), but without more pronounced hematological evidence of systemic immunosuppression before and after chemotherapy. Conclusion: Biliary fungal contamination was not associated with increased risk of postoperative complications in pancreatic cancer patients but was associated with worse OS, particularly in patients who received neoadjuvant therapy. Investigations regarding the causal relationship between biliary fungus and treatment response and outcome in PDAC patients are warranted.