Background: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III–IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. Results: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III–IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX. Conclusions: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.
A pancreatic fistula (PF) is the most relevant complication after a pancreaticoduodenectomy (PD). This retrospective multicentric study attempts to elucidate the risk factors and complications of a PF in a large cohort of patients undergoing a PD for ductal adenocarcinoma. Using a survey tool, clinical data of 1325 patients undergoing a PD for ductal adenocarcinoma at 37 institutions, between January 2004 and December 2009, were collected. Peri-operative risk factors associated with PF and its association with morbidity and mortality were assessed. Morbidity and PF were graded according to the ISGPF (International Study group for pancreatic fistula) definition and the Dindo-Clavien classification. Overall PF, mortality, morbidity and relaparotomy rates were 14.3%, 3.8%, 54.4% and 11.7%, respectively. PF occurred more frequently after a pancreaticojejunostomy (PJ) compared with a pancreaticogastrostomy (PG) (16.8% vs. 10.4%; P = 0.0012). Independent risk factors for PF by multivariate analysis were absence of pre-operative diabetes (P = 0.0014), PJ reconstruction (P = 0.0035), soft pancreatic parenchyma (P < 0.0001) and low-volume centre (P = 0.0286). Clinically relevant PF (grade B and C) and severe complications (Dindo-Clavien grade IIIB, IV, V) were significantly more frequent after PJ than PG (71.6% vs. 28.3%; P = 0.030 and 24.8% vs. 19.1%; P = 0.015, respectively). Overall mortality and relaparotomy rates were similar after PG and PJ. A soft pancreatic parenchyma, the absence of pre-operative diabetes, PJ and low-volume centre are independent risk factors for PF after PD for ductal adenocarcinoma. A significantly higher incidence and clinical severity of PF are associated with PJ.
Objective: This study assesses the safety and outcomes of the largest cohort of pancreatectomy with arterial resection (P-AR). Background: A high postoperative mortality rate and uncertain oncologic benefits have limited the use of P-AR for locally advanced pancreatic adenocarcinoma. Methods: We retrospectively reviewed a prospectively maintained database of patients who underwent P-AR between January 1990 and November 2017. Univariate and multivariate Cox analyses were used to assess prognostic factors for survival. Results: There were 118 consecutive resections (51 pancreaticoduodenectomies, 18 total pancreatectomies, and 49 distal splenopancreatectomies). Resected arterial segments included the coeliac trunk (50), hepatic artery (29), superior mesenteric artery (35), and other segments (4). The overall mortality and morbidity were 5.1% and 41.5%, respectively. There were 84 (75.4%) patients who received neoadjuvant chemotherapy, 105 (89%) simultaneous venous resections, and 101 (85.5%) arterial reconstructions. The rates of R0 resection and pathologic invasion of venous and arterial walls were 52.4%, 74.2%, and 58%, respectively. The overall survival was 59%, 13%, and 11.8% at 1, 3, and 5 years, respectively. The median overall survival after resection was 13.70 months (CI 95%:11–18.5 mo). In multivariate analysis, R0 resection (HR: 0.60; 95% CI: 0.38–0.96; P = 0.01) and venous invasion (HR: 1.67; 95% CI: 1.01–2.63; P = 0.04) were independent prognostic factors. Conclusion: In a specialized setting, P-AR for locally advanced pancreatic adenocarcinoma can be performed safely with limited mortality and morbidity. Negative resection margin and the absence of associated venous invasion might predict favorable long-term outcomes.