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BackgroundData on long-term actual survival in patients with surgically resected pancreatic ductal adenocarcinoma (PDAC) are limited. The aim of this study was to evaluate the actual 5-year disease-specific survival (DSS) and post-recurrence survival (PRS) in patients who underwent pancreatectomy for PDAC.MethodsData from patients who underwent upfront surgical resection for PDAC between 2009 and 2014 were analyzed. Exclusion criteria included PDAC arising in the background of an intraductal papillary mucinous neoplasm and patients undergoing neoadjuvant therapy. All alive patients had a minimum follow-up of 60 months. Independent predictors of PRS, DSS, and survival > 5 years were searched.ResultsOf the 176 patients included in this study, 48 (27%) were alive at 5 years, but only 20 (11%) had no recurrence. Median PRS was 12 months. In the 154 patients after disease recurrence, independent predictors of shorter PRS were total pancreatectomy, G3 tumors, early recurrence (< 12 months from surgery), and no treatment at recurrence. Median DSS was 36 months. Independent predictors of DSS were CA19-9 at diagnosis > 200 U/mL, total pancreatectomy, N + status, G3 tumors and perineural invasion. Only the absence of perineural invasion was a favorable independent predictor of survival > 5 years.ConclusionMore than one-quarter of patients who underwent upfront surgery for PDAC were alive after 5 years, although only 11% of the initial cohort were cancer-free. Long-term survival can also be achieved in tumors with more favorable biology in an upfront setting followed by adjuvant chemotherapy.

To evaluate the results of active surveillance beyond 5 years in patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) without worrisome features (WF) and high-risk stigmata (HRS) undergoing non-operative management. Patients with a minimum follow-up of 5 years who underwent surveillance with at least yearly magnetic resonance imaging were included. New onset of and predictors of WF/HRS during follow-up as well as long-term survival were analyzed. In all, 144 patients were followed for a median of 84 months. At diagnosis multifocal BD-IPMNs were found in 53% of cases and mean size of the largest cyst was 15.5 mm. Changes during follow-up were observed in 69 patients (48%). New onset of WF/HRS were observed in 26 patients (18%) but the rate of HRS was only 4%. WF and HRS developed after a median follow-up of 71 and 77.5 months from diagnosis, respectively, and without previous changes in 19/26 patients. Independent predictors of WF/HRS development were size at diagnosis>15 mm, increase in number of lesions, main pancreatic duct growth rate ≥0.2 mm/year, cyst growth rate >1 mm/year. Overall, the rate of pancreatic invasive malignancy was 2% and the 12-year disease-specific survival was 98.6%. Long-term nonoperative management is safe for BD-IPMNs without WF and HRS. Discontinuation of surveillance cannot be recommended since one out of six patients developed WF/HRS far beyond 5 years of surveillance and without previous relevant modifications. An intensification of follow-up should be considered after 5 years.

BackgroundThe prognostic role of resection margins in pancreatic ductal adenocarcinoma (PDAC) is debated. This study aimed to investigate the impact that global and individual resection margin status after pancreatic head resection for PDAC has on disease-free survival (DFS) and disease-specific survival (DSS).MethodsSurgical specimens of pancreaticoduodenectomy/total pancreatectomy performed for PDAC were examined with a standardized protocol. Surgical margin status (biliary, pancreatic neck, duodenal, anterior and posterior pancreatic, superior mesenteric vein groove and superior mesenteric artery margins) was classified as the presence of malignant cells (1) directly at the inked surface (R1 direct), (2) within less than 1 mm (R1 ≤ 1 mm), or (3) with a distance greater than 1 mm (R0). Patients with a positive neck margin at the final histology were excluded from the study.ResultsOf the 362 patients included in the study, 179 patients (49.4 %) had an R0 resection, 123 patients (34 %) had an R1 ≤ 1 mm resection, and 60 patients (16.6 %) had an R1 direct resection. The independent predictors of DFS were R1 direct resection (hazard ratio [HR], 1.49), R1 ≤ 1 mm resection (HR, 1.38), involvement of one margin (HR, 1.36), and involvement of two margins or more (HR, 1.55). When surgical margins were analyzed separately, only R1 ≤ 1 mm superior mesenteric vein margin (HR, 1.58) and R1 direct posterior margin (HR, 1.69) were independently associated with DFS.ConclusionsPositive R status is an independent predictor of DFS (R1 direct and R1 ≤ 1 mm definitions) and of DSS (R1 direct). The presence of multiple positive margins is a risk factor for cancer recurrence and poor survival. Different surgical margins could have different prognostic roles.

Objectives Clinically significant pancreatic fistula (POPF) has been established as a well-known risk factor for late and severe postpancreatectomy hemorrhage after pancreaticoduodenectomy (PD) (postpancreatectomy pancreatic fistula–associated hemorrhage [PPFH]). Our aim was to assess whether contrast-enhanced CT scan after PD is an effective tool for early prediction of PPFH. Methods From a prospectively acquired database, all consecutive patients who underwent PD between January 2013 and May 2019 were identified; within this database, all patients who were evaluated, for clinical suspicion of POPF, with at least one contrast-enhanced CT scan examination, were enrolled in this retrospective study. The selected CT findings included perianastomotic fluid collections and air bubbles; pancreaticojejunostomy (PJ) was analyzed in terms of dehiscence and defect. Results One hundred seventy-eight out of 953 PD patients (18.7%) suffered from clinically significant POPF; after exclusions, 166 patients were enrolled. Among this subset, 33 patients (19.9%) had at least one PPFH episode. In multivariable analysis, PPFH was associated with postoperative CT evidence of fluid collections ( p = 0.046), air bubbles ( p = 0.046), and posterior PJ defect ( p < 0.001). Based on these findings, a practical 4-point prediction score was developed (AUC: 0.904, Se: 76%, Sp: 93.8%): patients with a score ≥ 3 demonstrated a significantly higher risk of PPFH development (OR = 45.6, 95% CI: 13.0–159.3). Conclusions Postoperative CT scan permits early stratification of PPFH risk, thus providing an actual aid for patients’ management. Key Points • Postpancreatectomy hemorrhage (PPH) is a dramatic, clinically unpredictable occurrence. • After pancreaticoduodenectomy (PD), early identification of posterior pancreaticojejunostomy defect, perianastomotic air bubbles, and retroperitoneal fluid collections enables effective PPH risk stratification by means of a practical CT-based 4-point scoring system. • CT scan after PD allows a paradigm shift in the management PPH, from a conventional “wait and see” approach, to a more proactive one that relies on early anticipation and timely prevention.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related death in the USA. A wealth of evidence has demonstrated the chemopreventive activity of aspirin, statins, and metformin against PDAC. The aim of this study is to investigate the effect of aspirin, statins, and metformin on disease-free survival (DFS) and disease-specific survival (DSS) in a large population of PDAC patients undergoing pancreatic resection.Patients and MethodsAll patients who underwent pancreatic resections between January 2015 and September 2018 were retrospectively reviewed. The potentially “chemopreventive agents” considered for the analysis were aspirin, statins, and metformin. Drug use was defined in case of regular assumption at least 6 months before diagnosis and regularly after surgery along the follow-up period.ResultsA total of 430 patients were enrolled in this study, with median DFS and DSS of 21 months (IQR 13–30) months and 34 (IQR 26–52) months, respectively. On multivariable analysis, use of aspirin was associated with better DFS (HR: 0.62; p = 0.038). Metformin was associated with better DFS, without reaching statistical significance (p = 0.083). Use of statins did not influence DFS in the studied population. Aspirin, metformin, and statins were not associated with better DSS on multivariable analysis. Factors influencing DSS were pT3/pT4, N1, N2, no adjuvant treatment, G3, and ASA score > 3.ConclusionsThe results suggest that chronic use of aspirin is associated with increased DFS but not with better DSS after surgical resection in patients with PDAC.

Amylase value in drains (AVD) is a predictor of pancreatic fistula (PF). We evaluated the accuracy of an AVD-based model. Two hundred thirty-one patients underwent pancreatoduodenectomy with pancreaticojejunostomy (PDPJ) or pancreatoduodenectomy with duct-to-mucosa (PDDTM) and distal pancreatectomy (DP). Patients with AVD greater than 5,000 U/L on postoperative day (POD) 1 underwent AVD measurement on POD5. Sensitivity and specificity of POD1 AVD greater than 5,000 in predicting PF were 71% and 90%, respectively. The sensitivity and specificity of POD5 AVD greater than 200 were 90% and 83%, respectively. AVD greater than 1,000 (for PDPJ) and 2,000 U/L (PDDTM and DP) represented the most accurate cutoffs on POD1. AVD greater than 200 (PDPJ), 300 (PDDTM), and 50 U/L (DP) represented the cutoffs with the highest sensitivity in predicting PF on POD5. AVD-based model for predicting PF after pancreatic resection is an accurate tool, although AVD cutoffs should be evaluated for each type of operation.

Objectives Malignant double obstruction, defined as the simultaneous presence of biliary and gastric outlet obstruction, represents a challenging clinical scenario. Previous retrospective experiences have demonstrated shorter dysfunction‐free survival (DyFS) of endoscopic ultrasound‐guided choledochoduodenostomy (EUS‐CDS) versus EUS‐hepaticogastrostomy (EUS‐HGS) in this setting, but no prospective evidence is available. Methods Twenty consecutive patients with malignant double obstruction, treated with EUS‐gastroenterostomy (and EUS‐guided biliary drainage, following a previously failed ERCP, were enrolled in a prospective observational study (ClinicalTrials.gov NCT04813055) comparing EUS‐CDS versus EUS‐HGS. Efficacy and safety were evaluated, with Biliary Dysfunctions as the primary outcome and DyFS using Kaplan‐Meier estimates as a primary measure. Results Twenty patients (75% with pancreatic cancer, 50% with metastatic disease) with EUS‐gastroenterostomy were included (seven EUS‐CDS and 13 EUS‐HGS). No significant difference was detected at baseline. Technical success was 100% in both groups. EUS‐CDS compared to EUS‐HGS showed similar clinical success (100% vs. 92.3%, p = 0.5), a higher rate of post‐procedural adverse events (42.9% vs. 7.7%, p = 0.067, mostly related to severe/fatal cholangitis in the EUS‐CDS group) and a higher rate of biliary dysfunctions during follow‐up (71.4% vs. 16.7%, p = 0.002). DyFS was significantly shorter in the EUS‐CDS group (39 [15–62] vs. 268 [192–344] days, p = 0.0023), with a 30‐days DyFS probability of 57.1% vs. 100% (hazard ratio = 7.8 [1.4–44.2]). Conclusions In this prospective comparison of patients with malignant double obstruction undergoing EUS‐gastroenterostomy, treating jaundice with EUS‐CDS versus EUS‐HGS resulted in a reduced probability of survival without biliary events and an increased risk of biliary dysfunctions (number needed to harm = 1.8), with detection of severe/fatal cholangitis.

Purpose of ReviewThe aim of this review was to discuss how to select patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) for surgery.Recent FindingsSurgical resection represents the mainstay for the curative treatment of GEP-NENs. Conservative strategies, such as endoscopic resection and active surveillance, have been recently advocated for the management of patients with small and asymptomatic GEP-NENs. On the other hand, patients with GEP-NENs showing features of aggressiveness should be managed by surgical resection with lymphadenectomy, when the surgical risk is considered acceptable. An accurate selection is important also in the setting of advanced disease, where surgery can provide a survival benefit in the context of a multimodal treatment strategy.SummarySurgical and oncological risk should be always assessed in order to define indications for surgery in patients with GEP-NENs. Given the variety of available treatment options, surgical indication should be always shared with a dedicated multidisciplinary team.