Postoperative pancreatic fistula affects recurrence-free survival of pancreatic cancer patients

Abstract

Purpose Postoperative pancreatic fistula (POPF) with reported incidence rates up to 45% contributes substantially to overall morbidity. In this study, we conducted a retrospective evaluation of POPF along with its potential perioperative clinical risk factors and its effect on tumor recurrence. Methods Clinical data on patients who had received pancreatoduodenectomy (PD), distal pancreatectomy (DP), or duodenum-preserving pancreatic head resection (DPPHR) were prospectively collected between 2007 and 2016. A Picrosirius red staining score was developed to enable morphological classification of the resection margin of the pancreatic stump. The primary end point was the development of major complications. The secondary end points were overall and recurrence-free survival. Results 340 patients underwent pancreatic resection including 222 (65.3%) PD, 87 (25.6%) DP, and 31 (9.1%) DPPHR. Postoperative major complications were observed in 74 patients (21.8%). In multivariable logistic regression analysis, POPF correlated with body mass index (BMI) (p = 0.025), prolonged stay in hospital (p<0.001), high Picrosirius red staining score (p = 0.049), and elevated postoperative levels of amylase or lipase in drain fluid (p≤0.001). Multivariable Cox regression analysis identified UICC stage (p<0.001), tumor differentiation (p<0.001), depth of invasion (p = 0.001), nodal invasion (p = 0.001), and the incidence of POPF grades B and C (p = 0.006) as independent prognostic markers of recurrence-free survival. Conclusion Besides the known clinicopathological risk factors BMI and amylase in the drain fluid, the incidence of POPF correlates with high Picrosirius red staining score in the resection margins of the pancreatic stumps of curatively resected pancreatic ductal adenocarcinoma (PDAC). Furthermore, clinically relevant POPF seems to be a prognostic factor for tumor recurrence in PDAC.

Does Pancreatic Fistula Affect Long-Term Survival after Resection for Pancreatic Cancer? A Systematic Review and Meta-Analysis

“…The MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library searches yielded a total of 4045 citations ( Figure 1 ), and a consensus among all investigators led to 16 studies being judged as eligible for our meta-analysis [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Screening the references of the full-text articles assessed for eligibility revealed no further studies potentially suitable for inclusion.…”

“…Screening the references of the full-text articles assessed for eligibility revealed no further studies potentially suitable for inclusion. Eleven studies reporting DFS data (n = 3375 patients) [ 15 , 17 , 19 , 21 , 22 , 23 , 25 , 26 , 27 , 28 , 29 ] and sixteen studies containing information about OS (n = 5019 patients) were included in the meta-analysis [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ] ( Figure 1 ). Correlation between long-term survival and POPF was assessed as the primary endpoint in 14 studied [ 14 , 15 , 16 , 17 , 18 , 19 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]; only two studies considered all complications [ 21 ] and the analysis of prognostic factors [ 20 ] as primary endpoints, and POPF impact as a secondary endpoint.…”

“…Of the 16 retrospective cohort studies analyzed [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], 2 [ 19 , 29 ] were multicentric, and concerned a total of 5019 patients with an overall POPF rate of 20.78% (n = 1043 patients) and a CR-POPF rate of 12.63% (n = 634 patients). Table 1 and Supplementary Table S2 show the main characteristics of these studies.…”

“…Eleven studies [ 15 , 17 , 19 , 21 , 22 , 23 , 25 , 26 , 27 , 28 , 29 ] provided DFS data for patients with POPF or CR-POPF, as shown in Table 2 and Supplementary Table S3 . The median DFS rates of whole cohorts, reported in only three studies [ 17 , 21 , 29 ], ranged from 12.2 [ 17 ] to 19 months [ 29 ].…”

“…Four studies described the impact of POPF (grades A–C) on DFS [ 17 , 22 , 23 , 25 ]: DFS was significantly shorter in the POPF group in the study by Dundar et al [ 22 ], while no significant difference was seen in the other three studies [ 17 , 23 , 25 ]. Six studies reported the impact of CR-POPF (grades B and C) on DFS [ 15 , 21 , 25 , 27 , 28 , 29 ], with only Watanabe et al and Nagai et al reporting a significantly shorter DFS in their CR-POPF groups [ 15 , 21 , 28 ]. The one study that considered subgroups of patients with grade-C POPF [ 19 ] found no significant differences in DFS via multivariate analysis.…”