Introduction We aimed to evaluate the long-term outcomes of the association of neoadjuvant chemotherapy with pancreatectomy with vascular resection in patients with locally advanced pancreatic cancer. Methods Clinical data from patients who underwent pancreatic resection after neoadjuvant FOLFIRINOX were retrospectively reviewed. Cox analyses were used to identify factors prognostic of overall survival (OS). Results FOLFIRINOX protocol was administered pre-operatively with a median number of nine cycles (range 2–18) in 98 patients. Types of resections included pancreaticoduodenectomy ( n = 53), total pancreatectomy ( n = 17), and distal spleno-pancreatectomy ( n = 28). Venous resection and arterial resections were performed in 85 (86.7%) and 64 patients (65.3%), respectively. The overall 90-day mortality and morbidity rates were 6.1% ( n = 6) and 47% ( n = 47), respectively. The median OS was 31.08 months after surgery. OS rates at one, three, five, and 10 years were 82%, 47%, 28%, and 21%, respectively. According to the type of vascular resection, median OS and 5-year survival rates were exclusive venous resection (31.08 months; 23%) and arterial resections (24.7 months; 27%). Multivariate Cox analysis found lymph node involvement, venous invasion, and total pancreatectomy as independent prognostic factors for OS. According to the presence of 0 or 1–3 risk factors, 5-year survival (85% vs 16%) and median overall survival rates (not reached versus 24.7 months, respectively) were statistically significantly different ( p < 0.0001). Conclusions A multimodal treatment, including neoadjuvant FOLFIRINOX combined with pancreatectomy with venous and arterial resection, achieves long term survival rates in patients with locally advanced disease. Surgery, in experienced centers, should be integrated into the treatment of patients with locally advanced pancreatic adenocarcinomas.

Background: This study aimed to evaluate the results of synchronous liver resection for metastatic pancreatic ductal adenocarcinomas and to identify prognostic factors for overall survival. Methods: We retrospectively reviewed clinical data from patients who underwent the synchronous resection of pancreatic adenocarcinoma with liver metastases. Cox analyses were used to identify factors prognostic of overall survival. Results: Of the 92 patients included in this study, preoperative chemotherapy was administered to 52 patients. The median overall survival was 18.26 months (95% confidence interval: 14.7-22.7) (from diagnosis) and 12.68 months (95% confidence interval: 9.5-15.57) from surgery; overall survival at 1, 3, and 5 years was 70%, 10%, and 0%, respectively. Twenty-eight patients (30.4%) had median overall survival >18 months after surgery. The median overall survival from diagnosis was longer in patients undergoing preoperative treatment (22.7 vs 13.8 months; P =.01) but similar after surgery (12.6 vs 13.8 months; P =.86). Multivariate Cox analysis found CA19-9 levels <500 kU/L (hazard ratio: 0.35; 95% confidence interval: 0.17-0.70; P =.003), R0 resection (hazard ratio: 0.46; 95% confidence interval: 0.24-0.88; P =.020), and adjuvant chemotherapy (hazard ratio: 0.39; 95% confidence interval: 0.17-0.88; P =.024) as independent prognostic factors for overall survival. Conclusion: Survival after resection of oligometastatic liver disease remains limited, reflecting the dismal prognosis of metastatic disease even after aggressive treatment. Preresection CA19-9 serum levels represent a useful tool for patient selection, and administration of adjuvant chemotherapy has a major impact on overall survival. Large comparative studies with exclusive chemotherapy are needed to validate this approach and to identify optimal candidates. (c) 2022 Elsevier Inc. All rights reserved.

Background: Neoadjuvant treatment before resection for pancreatic adenocarcinoma having contact with the splenomesentericoportal venous axis could improve the results of extended pancreatectomies. We compared the outcomes of upfront (UR) and resection after neoadjuvant chemotherapy (NAC) for pancreatic adenocarcinoma. Methods: We retrospectively reviewed clinical data of patients who underwent pancreaticoduodenectomy with venous resection for pancreatic adenocarcinoma between January 1, 2006, and December 31, 2020. Operative, pathologic, and survival outcomes were compared between upfront and resection after neoadjuvant chemotherapy. Results: Of the 169 patients, 55 patients underwent preoperative chemotherapy and 114 underwent upfront. No differences were found in operative time, morbidity, and mortality between the 2 groups. At pathologic examination, patients who underwent resection after neoadjuvant chemotherapy had a significantly smaller tumor size, higher rate of RO resection, less lymph node involvement, and a lower rate of pathologic venous invasion (P < .05). The median overall survival was 27.96 months, and the overall survival rates at 1, 3, 5, and 10 years were 82%, 39%, 22%, and 11%, respectively. Multivariate Cox analysis found neoadjuvant treatment (hazard ratio: 0.60; 95% confidence interval: 0.38-0.97; P = .03), and intraoperative transfusion (hazard ratio: 2.25; 95% confidence interval: 1.47-3.46; P = .0002) as independent prognostic factors for overall survival. A dose-dependent effect of perioperative transfusion on overall survival was found (no transfusion, = 2 red blood cells, >2 red blood cells; median overall survival 41.1 months vs 27.01 months vs 19.4 months; P = .0003). Conclusion: Neoadjuvant chemotherapy improves the pathologic and survival outcomes of pancreaticoduodenectomy with venous resection for pancreatic adenocarcinomas. The dose-dependent effect of perioperative transfusion on overall survival warrants further investigation. (C) 2022 Elsevier Inc. All rights reserved.

Background: The current study aimed to identify histological prognostic factors after resection of locally advanced (LA) and borderline (BL) pancreatic adenocarcinomas treated by neoadjuvant chemo-therapy (NC). Methods: A retrospective review was performed of patients with LA and BL adenocarcinomas operated after NC between January 2010 and April 2018. Prognostic factors for survival were assessed by multivariate Cox analysis. Results: Of the 84 patients, 29 had BL and 55 had LA pancreatic adenocarcinomas. Seventy-five patients underwent synchronous venous resection and 57 underwent arterial resection. The median overall survival from surgery was 21.10 months (BL 23-LA 21) (95% CI: 14.8-30.3) with 1-, 3-, and 5-year overall survival rates of 73%, 32%, and 20%, respectively. Multivariate analysis identified lymphovas-cular invasion (LVI) as an independent prognostic factor for overall survival (HR: 2.32, 95% CI: 1.28-4.22; p = 0.004). Patients without LVI (n = 37) had superior median overall and 5-year survival rates (31.0 months [40 from diagnosis]; 39%) compared to patients with LVI (n = 47; 14.4 months [22 from diag-nosis]; 7%). The absence of residual LVI was associated with major pathologic response rates (p < 0.05). Conclusion: The persistence of LVI at pathology after resection of LA and BL treated by neoadjuvant chemotherapy predicts poor response and limited long-term survival.

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.

Background: The ligation of the splenic vein during pancreaticoduodenectomy with synchronous resection of the spleno-mesenteric-portal venous confluence has been associated with the development of left portal hypertension despite preservation of the natural confluence with the inferior mesenteric vein. This study aimed to assess whether a left splenorenal venous shunt might mitigate clinical signs of left portal hypertension associated with splenic vein ligation. Methods: We retrospectively evaluated the presence of left portal hypertension based on biologic and radiologic parameters in patients undergoing pancreaticoduodenectomy with synchronous resection of the spleno-mesentericoportal confluence between January 1, 2012, and December 31, 2018. We compared several parameters between patients undergoing splenic vein ligation with preservation of the inferior mesenteric vein confluence and a splenorenal venous shunt: the early and late spleen volumes and spleen volume ratios, an early and late platelet count, the presence of thrombocytopenia, the presence of varices, and digestive bleeding in the long-term. Results: There were 114 consecutive patients: 36 with splenic vein ligation and 78 with splenorenal venous shunt. All had a pancreaticogastrostomy. Patients with splenic vein ligation had a comparable baseline and early and late platelet counts. Although baseline splenic volumes were comparable between the 2 groups (242 +/- 115 mL vs 261 +/- 138 mL; P = .51), patients with splenic vein ligation showed a statistically significant greater splenic volume beyond the 6th postoperative months (334 +/- 160 mL vs 241 +/- 111 mL; P = .004), higher early and late spleen volume ratios (1.42 +/- 0.67 vs 1.10 +/- 0.3; P = .001 and 1.38 +/- 0.38 vs 0.97 +/- 0.4; P = .0001) than patients with splenorenal venous shunt. Splenic vein ligation was also associated with a higher rate of varices (81% vs 50%; P = .002) and more frequent varices with a caliber greater than 1 cm (57% vs 36%; P = .05) and more colonic varices (33% vs 12%; P = .01). Only 1 patient had long-term digestive bleeding (splenic vein ligation). Conclusion: The left splenorenal shunt decreases clinical signs of left portal hypertension associated with splenic vein ligation and inferior mesenteric vein confluence preservation. (C) 2020 Elsevier Inc. All rights reserved.

Objective: To report the outcomes of surgical resection of borderline resectable (BL) and locally advanced (LA) ‘unresectable' pancreatic cancer after neoadjuvant chemotherapy. Methods: A review of a prospectively maintained database for pancreatic resections was undertaken to identify patients undergoing resection for BL and LA pancreatic cancer after neoadjuvant chemotherapy between January 2007 and December 2012. Clinicopathological, surgical and survival outcomes were analyzed. Results: A total of 45 patients with LA (n = 34) or BL cancer (n = 11) underwent surgery after a mean (± SD) of 7 ± 4 preoperative chemotherapy cycles. Ninety-day mortality was 6.7%, and overall morbidity was 33.3%. An R0 resection was achieved in 34 patients, and 4 patients showed a complete pathological response. Overall median postoperative survival was 17 months (21 after the start of neoadjuvant treatment). Overall and disease-free survival was 74.9 and 43.6% at 1 year and 21.2 and 10.3% at 3 years, respectively. In BL cancer patients, the 3-year survival was significantly higher compared to that of LA cancer patients (p = 0.02). Conclusions: Curative intent resection in BL and LA cancer patients after neoadjuvant chemotherapy can be achieved with reasonable mortality and morbidity and an encouraging 3-year survival. After neoadjuvant therapy, resection provides a better overall survival for BL compared to LA cancer patients.

BACKGROUND:Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy.METHODS/DESIGN:This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m(2)) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m(2), oxaliplatin 100 mg/m(2)) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and representative histological sections will be centrally reviewed by a dedicated pathologist.DISCUSSION:The NEOPAC study will determine the efficacy of neoadjuvant chemotherapy in pancreatic cancer for the first time and offers a unique potential for translational research. Furthermore, this trial will provide the unbiased overall survival of all patients undergoing surgery for resectable cancer of the pancreatic head.TRIAL REGISTRATION:clinicalTrials.gov NCT01314027.

OBJECTIVE:To investigate whether sinusoidal injury (SI) was associated with a worse outcome after hepatectomy in patients with colorectal liver metastases (CRLM).BACKGROUND:Correlation between SI and oxaliplatin-based chemotherapy (OBC) was recently shown in patients with CRLM. However, it has yet to be fully clarified whether SI affects liver functional reserve and outcome after hepatectomy.PATIENTS AND METHODS:Between 2003 and 2005, 90 patients with CRLM who underwent an elective hepatectomy after preoperative chemotherapies were included. Diagnosis of SI was established pathologically in the nontumoral liver parenchyma of the resected specimens, and perioperative data were assessed in these patients.RESULTS:OBC was significantly associated with a higher incidence of SI. Preoperative indocyanine green retention rate at 15 minutes (ICG-R15) and postoperative value of total-bilirubin were significantly higher, and hospital stay was significantly longer in patients presenting with SI. Multivariate analysis showed that female gender, administration of 6 cycles or more of OBC, abnormal value of preoperative aspartate aminotransferase >36 IU/L, or abnormal value of preoperative ICG-R15 (>10%) were preoperative factors significantly associated with SI. Among patients undergoing a major hepatectomy, SI was significantly associated with higher morbidity and longer hospital stay.CONCLUSION:The present study suggests that SI resulted in a poorer liver functional reserve and in a higher complication rate after major hepatectomy. Therefore, female patients who received 6 cycles or more of OBC, or presenting with abnormal preoperative aspartate aminotransferase and ICG-R15 values should be carefully selected before deciding to undertake a major hepatectomy.