While primarily unresectable locally advanced pancreatic cancer (LAPC) used to be an indication for palliative therapy, a strategy of neoadjuvant therapy (NAT) and conversion surgery is being increasingly used after more effective chemotherapy regimens have become available for pancreatic ductal adenocarcinoma. While high-level evidence from prospective studies is still sparse, several large retrospective studies have recently reported their experience with NAT and conversion surgery for LAPC. This review aims to provide a current overview about different NAT regimens, conversion rates, survival outcomes and determinants of post-resection outcomes, as well as surgical strategies in the context of conversion surgery after NAT. FOLFIRINOX is the predominant regimen used and associated with the highest reported conversion rates. Conversion rates considerably vary between less than 5% and more than half of the study population with heterogeneous long-term outcomes, owing to a lack of intention-to-treat analyses in most studies and a high heterogeneity in resectability criteria, treatment strategies, and reporting among studies. Since radiological criteria of local resectability are no longer applicable after NAT, patients without progressive disease should undergo surgical exploration. Surgery after NAT has to be aimed at local radicality around the peripancreatic vessels and should be performed in expert centers. Future studies in this rapidly evolving field need to be prospective, analyze intention-to-treat populations, report stringent and objective inclusion criteria and criteria for resection. Innovative regimens for NAT in combination with a radical surgical approach hold high promise for patients with LAPC in the future.

Objective: Our investigation on in-hospital mortality after 4474 pancreatoduodenectomies aimed to identify time-dependent risks as well as windows of opportunity to rescue patients from complications. Background: Pancreatoduodenectomy is generally considered a safe procedure with a 1% to 10% perioperative mortality based on complexity and surgical volume. Yet, patients are susceptible to life-threatening complications particularly with extended resections. Recognition of distinct vulnerabilities over time while patients recover is required to permit focused monitoring, sophisticated resource allocation, and the greatest surgical safety. Methods: Patients who deceased in-hospital after pancreatoduodenectomy between 2003 and 2021 were retrieved from the institutional pancreatectomy registry and analyzed in detail with respect to their postoperative course. Results: Among 4474 pancreatoduodenectomies, 156 patients deceased in-hospital (3.5%). When assessing root causes of mortality, we observed 3 different clusters of complications, which were postpancreatectomy-specific (51.9%), visceral vasculature–associated (25.6%), or cardiopulmonary in origin (17.9%). The median times of root cause onset in the 3 categories were postoperative day (POD) 9, POD 4.5 ( P =0.008), and POD 3 ( P <0.001), respectively. Medians of in-hospital mortality were POD 31, POD 18 ( P =0.009), and POD 8 ( P <0.001). Intervals between root cause onset and mortality varied with medians of 23 days, 11 days ( P =0.017), and 1 day ( P <0.001). The 3 categories were similarly distributed between different types of surgical complexity. Conclusions: Postpancreatectomy-specific complications prompt almost half of the in-hospital mortalities after pancreatoduodenectomy, with rather long intervals for interventions to prevent failure to rescue. In contrast, visceral vasculature-related events and cardiopulmonary complications dominate early in-hospital mortalities with short intervals until mortality, demanding rigorous management of such events or preoperative conditioning. These data externally validate a previous high-volume initiative and highlight distinct windows of opportunity to optimize perioperative safety.

In the last decade there has been increasing interest in defining pancreatic steatosis (PS) and establishing its association with pancreatic ductal adenocarcinoma (PDAC). However, no consensus guidelines have yet been published on the management of PS. In this systematic review and meta-analysis performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we investigated the association between PS and PDAC. Medical literature between 2007 and 2023 was reviewed for eligible trials investigating the prevalence of PS in patients with PDAC. Eligible studies reporting on PS, assessed via imaging or histology, were included. The primary objective was to determine the association between PDAC and PS by comparing the prevalence of PS in individuals with- and without PDAC. Secondary, an evaluation was conducted to establish whether the method of assessment correlated with the association of PDAC and PS, and the prevalence of PDAC in individuals with PS. Measures of effect size were determined using odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CI). The systematic review identified a total of 23 studies, of which seventeen studies examined PS prevalence among PDAC patients and were included in the meta-analysis. Overall, the pooled prevalence of PS in patients with PDAC was 53.6 % (95 % CI 40.9-66.2). No significant difference in PS prevalence was observed across various diagnostic methods or geographical regions. Overall, the pooled OR for PS in patients with PDAC compared to controls was 3.23 (95 % CI 1.86-5.60). PDAC patients have a high prevalence of PS, and they are significantly more likely to have PS compared to controls. These findings emphasize the need to prioritize a standardized approach to the diagnosis, follow-up, and treatment of PS, with future studies focusing on identifying patients who would benefit from PDAC surveillance programs.

Objective: To compare short-term outcomes and survival in patients undergoing pancreatic head resection after preoperative endoscopic stenting (ES) versus preoperative surgical drainage (SD) through T-tube insertion. Background: Patients with pancreatic cancer and obstructive jaundice routinely undergo ES placement. It is well known that ES causes bacterial contamination and infectious complications after pancreatic resection. Methods: Patients with obstructive jaundice who underwent SD or ES from 2016 to 2022 were identified from a prospective database. Outcome analyses included microbiological bile contamination, overall morbidity, and assessment of the overall complication burden using the Comprehensive Complication Index. Overall survival was investigated by Kaplan-Meier analysis. Results: A total of 55 patients who underwent SD were identified and matched with 110 patients who underwent ES. After the primary intervention, patients who underwent ES experienced more complications (ES: 17.3% vs SD: 3.6%; P = 0.013). The overall complication burden after pancreatic resection was higher in patients who underwent ES than in patients who underwent SD (Comprehensive Complication Index: 27.2 vs 19.9; P = 0.022). In addition, bacterial contamination of the bile was more frequent in patients who underwent ES compared with individuals who underwent SD (94.3% vs 7.1%; P < 0.001) with similar bacteria in 83.3% of postoperative abdominal infections in patients who underwent ES. While overall survival did not differ between the two groups, patients with postinterventional complications after ES had impaired survival compared with those without complications (11.3 vs 20.4 mo; P = 0.03). Conclusions: SD for obstructive jaundice in resectable pancreatic cancer is associated with a lower overall complication burden. In addition, patients with complications after ES experience worse overall survival. These findings indicate a rethink of our standards of treatment of obstructive jaundice in patients with pancreatic cancer.

Objective: To validate the prognostic value of the PAncreatic NeoAdjuvant MAssachusetts (PANAMA) score and to determine its predictive ability for survival benefit derived from adjuvant treatment in patients after resection of pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant FOLFIRINOX. Background: The PANAMA score was developed to guide prognostication in patients after neoadjuvant therapy and resection for PDAC. As this score focuses on the risk for residual disease after resection, it might also be able to select patients who benefit from adjuvant after neoadjuvant therapy. Methods: This retrospective international multicenter study is endorsed by the European-African Hepato-Pancreato-Biliary Association. Patients with PDAC who underwent resection after neoadjuvant FOLFIRINOX were included. Mantel-Cox regression with interaction analysis was performed to assess the impact of adjuvant chemotherapy. Results: Overall, 383 patients after resection of PDAC following neoadjuvant FOLFIRINOX were included of whom 187 (49%), 137 (36%), and 59 (15%) had a low-risk, intermediate-risk, and high-risk PANAMA-score, respectively. Discrimination in median overall survival (OS) was observed stratified by risk groups (48.5, 27.6, and 22.3 months, log-rank P _{low-intermediate} = 0.004, log-rank P _{intermediate-high} = 0.027). Adjuvant therapy was not associated with an OS difference in the low-risk group [hazard ratio (HR): 1.50, 95% CI: 0.92–2.50], whereas improved OS was observed in the intermediate (HR: 0.58, 95% CI: 0.34–0.97) and high-risk groups (HR: 0.47, 95% CI: 0.24–0.94; P interaction = 0.008). Conclusions: The PANAMA 3-tier risk groups (low-risk, intermediate-risk, and high-risk, available through pancreascalculator.com) correspond with differential survival in patients with resected PDAC following neoadjuvant FOLFIRINOX. The risk groups also differentiate between survival benefits associated with adjuvant treatment, with only the intermediate- and high-risk groups associated with improved OS.

Sarcopenia and altered body composition are increasingly recognized as prognostic markers in oncology. In pancreatic ductal adenocarcinoma (PDAC), their time-dependent impact on survival remains unclear. Patients with PDAC who underwent resection at Heidelberg University Hospital between 2013 and 2018 were included. Preoperative CT scans were assessed at the L3 level using the automated Body and Organ Analysis (BOA) tool. Sarcopenia Index (SI) and Myosteatosis Fat Index (MFI) were calculated. Multivariable Cox regression was performed for overall survival at predefined postoperative time points. A total of 723 patients were included. Some 140 patients (19.4%) underwent neoadjuvant therapy, while 583 (80.6%) received upfront surgical resection. The median OS for the entire cohort was 26.0 months (95% CI, 23.4 - 28.3). Patients with a low SI exhibited markedly reduced overall survival compared to those with a high SI (p < 0.001). In multivariate Cox regression analyses, a lower SI was independently associated with increased mortality at 90 days (HR: 0.44, 95% CI: 0.24-0.81) and at 1 year (HR: 0.71, 95% CI: 0.56-0.90). A similar prognostic pattern was observed for the MFI, which also showed independent associations with early mortality. Beyond the first postoperative year, this effect diminished and nodal status, resection margin and CA19-9 levels became the predominant predictors of overall survival. Preoperative sarcopenia and myosteatosis are strong predictors of early mortality after PDAC resection, whereas tumor biology determines long-term outcomes. Automated CT-based body composition analysis may support perioperative risk stratification and targeted prehabilitation strategies.