Neoadjuvant Treatment is a Risk Factor for Clinically Relevant Chyle Leak (ISGPS Grade B/C) After Pancreatic Cancer Resection: A Retrospective Cohort Study

Background Chyle leak is a relevant complication after surgery for pancreatic ductal adenocarcinoma (PDAC). Increasing use of multimodal neoadjuvant therapy (NAT) and extended resections may contribute to a higher incidence. This study aimed to describe the incidence of clinically relevant chyle leak and identify its risk factors in patients with PDAC treated with NAT and surgery versus upfront surgery. Patients and Methods Patients undergoing PDAC resection between 2014 and 2019 were identified from a prospective institutional database. Clinicopathologic and demographic data were extracted. The primary outcome was clinically relevant chyle leak according to the International Study Group of Pancreatic Surgery (ISGPS). Univariable and multivariable logistic regression were performed to identify associated factors. Results A total of 1402 patients were included: 1090 (77.7%) underwent upfront surgery, and 312 (22.3%) received NAT. Pancreatic head resections were performed in 718 (51.2%), distal pancreatectomies in 317 (22.6%), and total pancreatectomies in 367 (26.2%) individuals. Overall, 108 (7.7%) developed clinically relevant chyle leak: 88 (6.3%) grade B and 20 (1.4%) grade C. NAT (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.10–1.91), T stage (pT2/3/4 versus pT0/1, OR 1.53, 95% CI 1.03–2.34), and total pancreatectomy (OR 2.29, 95% CI 1.78–2.96) were associated with any chyle leak. For grade B/C, only NAT was an independent risk factor (OR 2.63, 95% CI 1.74–3.94). Age, resection type, and nodal status were not independent risk factors. Conclusions NAT is an independent risk factor for clinically relevant chyle leak following PDAC resection. These findings highlight the need for risk-adapted postoperative management and warrant prospective validation.