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Marta Sandini*1, Katarina J Ruscic2, Cristina R. Ferrone1, Motaz Qadan1, Matthias Eikermann2, Andrew L. Warshaw1, Keith D. Lillemoe1, Carlos Fernandez-del Castillo1
1Department of Surgery, Massachusetts General Hospital, Boston, MA; 2Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA

Aim: To analyze whether major complications after surgical resection affect long-term survival in pancreatic cancer.
Background: Postoperative major morbidity has been associated with worse survival in most gastrointestinal tumors. The underlying mechanisms are incompletely understood, but seem to be related to impaired immune function, delayed recovery and reduced likelihood of receiving adjuvant therapy. This association remains controversial in pancreatic cancer.
Methods: Records of pancreatic cancer patients resected from 2007 to 2015 were retrospectively reviewed. Major morbidity was defined as any grade 3 or higher complication occurring the first 30 days postoperatively, according to the Clavien-Dindo classification.
Results: Of 616 patients, 81.7% underwent pancreatoduodenectomy (PD) and 18.3% distal pancreatectomy (DP). Major complications occurred in 18.5%; 19.1% after PD and 15.9% after DP (p=0.50). Patients who experienced major complications were less likely to receive adjuvant treatment (55.3% vs. 71.5%, p=0.005). Furthermore, those who received treatment experienced a 10-day median delay prior to receipt of adjuvant therapy compared with patients without major complications (median 60 days from the operation (50-72) vs. 50 days (40-60), respectively; p=0.001). Patients who died within 90-days after surgery (overall 21 patients, 3.4%, and out of these 13, 2.1%, for failure-to-rescue) were excluded from the survival analysis. On univariate analysis, major complications worsened long-term survival after PD (median OS 26 months vs. 15, p=0.008). In the multivariate Cox-proportional model for pancreatoduodenectomy, major postoperative complications remained independently associated with worse survival [HR 1.38, 95%CI (1.01-1.87), p=0.041], together with nodal involvement [HR 1.82, 95%CI (1.35-2.47), p<0.001], positive margins [HR 1.39, 95%CI (1.08-1.80), p=0.012], tumor size >3 cm [HR 1.43, 95%CI (1.11-1.85), p=0.006], and lack of adjuvant treatment [HR 1.85, 95%CI (1.42-2.39), p<0.001].
Conclusion: Major surgical complications after pancreatoduodenectomy are independently associated with worse long-term survival in pancreatic cancer. This effect is independent of the receipt of adjuvant treatment.

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