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Abstract

In Reply We appreciate the interest in our article and thank JAMA Surgery for the opportunity to reply to the letters to the editor. 1 Shi et al advised that combining patients without postoperative pancreatic fistula (POPF) and with biochemical leakage may have biased the analysis regarding long-term survival in patients receiving neoadjuvant therapy (NAT). While biochemical leakage may reflect a more preserved gland function, which has been associated with better survival in upfront resected pancreatic cancer, 2 a preliminary analysis had shown no significant differences between biochemical leakage and no pancreatic fistula in patients with NAT. The use, assessment, and prevalence of soft pancreatic texture faced criticism. Regarding the description of gland texture as assessed by the surgeon's manual palpation, this method has been recognized as noninferior to technical measurements. 3 The subjective approach is indeed widely used in most POPF prediction metrics. We agree with Trudeau and Vollmer that the soft pancreas has not been confirmed to be a determinant of POPF after distal pancreatectomy, and that a separate analysis of risk factors in proximal and distal resections would have been advisable. Owing to the overall low incidence of CR-POPF in patients with NAT, which was less than 5%, a specific analysis for distal resections was not feasible. Nonetheless, soft pancreatic texture was the only risk factor associated with the occurrence of CR-POPF after pancreatoduodenectomy in patients with NAT. Despite a lack of specific pathological assessment, our hypothesis of NAT-related fibrotic deposition and desmoplastic remodeling of the gland is based on previous strong pathologic evidence. 4 In their letter, Trudeau and Vollmer stressed how blood loss is a crucial determinant of surgical outcomes, and specifically CR-POPF. This appeared to be even more important in the setting of NAT, as they observed that preoperative systemic treatment was a major risk factor for increased intraoperative blood loss. 5 In their study with data from 17 institutions and more than 5300 patients, only 29 (1.8% of patients with cancer) received NAT, and therefore definite conclusions cannot be drawn. Furthermore, other large studies in patients undergoing pancreatoduodenectomy have failed to validate the association between blood loss and POPF, and in fact the Dutch group proposed an alternative fistula risk score that does not include blood loss. 6 In conclusion, no studies have specifically addressed the determinants of CR-POPF in the setting of NAT, and consequently the broad application of prediction metrics developed for treatment-naive patients might be misleading in this context. As well pointed in the last comment, our cohort of upfront resected patients included mainly resectable tumors, as well as some borderline resectable that underwent upfront resection and associated vascular resection. However, we believe that this aspect does not limit the observed adverse survival effect of CR-POPF in the NAT cohort nor the streng...