Faculty Bibliography

BACKGROUND:Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer was previously categorized into tubular, colloid, and oncocytic subtypes. Intraductal oncocytic papillary neoplasms (IOPN) has long been associated with superior prognosis/indolent behavior, however, there is discordant emerging evidence. This study aimed to investigate this conflicting literature. METHODS:Patients with resected IOPN-derived and IPMN-derived pancreatic cancer were identified from six international centers. Log-rank tests compared time to (TtR) and survival after (SAR) recurrence and five-year overall survival (OS). A multivariable mixed model was used to determine hazard ratios (HR) with confidence intervals (95%CI) for five-year survival. RESULTS:Of 879 patients, 20 (2%) had IOPN-derived pancreatic cancer. Most patients had T1 (55%) or N0 (70%) disease. IOPN and colloid IPMN-derived pancreatic cancers had similar recurrence rates (25% vs. 24%), while recurrence was more common in tubular IPMN-derived pancreatic cancer (42%, p < 0.001). IOPN-derived pancreatic cancer displayed a longer TtR and SAR compared to colloid and tubular IPMN-derived pancreatic cancers. IOPN-derived and colloid IPMN-derived cancers demonstrated significantly lower 5-year mortality risks compared to tubular IPMN-derived cancers (74% and 27% risk reduction, respectively; p < 0.05). CONCLUSION/CONCLUSIONS:IOPN-derived pancreatic cancers have excellent OS. However, some patients have poor prognostic factors and are at risk for both local and systemic recurrence. Given more indolent disease progression given delayed TtR and prolonged SAR compared to colloid and tubular IPMN-derived pancreatic cancers, there may be a role for prolonged surveillance.

BACKGROUND:Antithrombotic therapy (AT) aims to strike a balance between preventing thromboembolic and hemorrhagic complications. However, evidence for AT management after pancreatectomy with vascular reconstruction is lacking. We aimed to provide an overview of the current use of AT for pancreatic surgery with vascular reconstructions. PATIENTS AND METHODS/METHODS:A web-based survey was distributed to 123 surgeons from high-volume pancreas centers (>50 pancreatic resections/year). AT management after different types of vascular reconstruction were investigated. An "aggressive" protocol was defined as the use of any AT protocol other than prophylactic heparin, aspirin, or their combination. RESULTS:The survey was completed by 80 surgeons (59% Europe, 30% USA, 11% Asia). In Europe/Asia, prophylactic heparin was the most commonly reported protocol after partial venous resection/end-to-end anastomosis/human graft (71%/65%/50%, respectively), and an "aggressive" protocol (86%) was the most frequently used after prosthetic graft reconstruction. Conversely, in the USA, prophylactic heparin + aspirin was the most commonly reported protocol after all types of venous reconstruction. Following arterial reconstruction, heparin + aspirin was the most commonly reported protocol, regardless of region. An "aggressive" protocol was more frequently used in Europe/Asia (odds ratio (OR) 1.28; p < 0.001) and following vein reconstruction with either human graft (OR 1.2; p = 0.007) or prosthetic graft (OR 1.56, p <0.001), while ultrasound (OR 1.65; p < 0.001) and arterial reconstruction (OR 1.64; p < 0.001) were significantly associated with antiplatelet use. CONCLUSIONS:In an international cohort of high-volume pancreas surgeons, significant variation in the use of AT following pancreatectomy with vascular reconstruction was observed. This variation was driven by geographical differences and the type of vascular reconstructions performed. In an international cohort of high-volume pancreas surgeons, this Worldwide Snapshot Survey analyzed the current use of antithrombotic therapy for pancreatic surgery with vascular reconstruction. A significant heterogeneity in antithrombotic practice was found and it was mainly driven by geographical differences and the type of vascular reconstructions performed.

INTRODUCTION/BACKGROUND:The management of intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer is extrapolated from pancreatic intraepithelial neoplasm (PanIN)-derived pancreatic cancer. However, these cancers are biologically and clinically distinct and evidence regarding the role of adjuvant therapy (AT) is unclear. The aim of this systematic review and meta-analysis was to consolidate current evidence regarding survival benefit of AT for IPMN-derived pancreatic cancer. METHODS:Systematic searches of the PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL databases were performed from inception to February 2nd, 2025. Studies that reported survival analyses comparing AT versus surgery alone for resected IPMN-derived pancreatic cancer were included. Risk of bias was assessed using the Newcastle-Ottawa scale. Hazard ratios were pooled using generic inverse-variance random-effects models. RESULTS:A total of 26 studies were included in this review. All studies were observational and 16 had low risk of bias while 10 had high risk of bias. AT was not associated with an OS benefit on pooled multivariable analysis (HR: 0.78 [0.47, 1.28]) in the total population. In subgroups of patients with pathology node-positive (pN1 or pN2) disease, advanced T-stage and overall AJCC tumor stage, elevated CA19-9 (>37 IU), and poor grade of differentiation, AT was associated with OS benefit. CONCLUSIONS:Current data suggests that routine AT after resection of IPMN-derived pancreatic cancer is not associated with an OS benefit and may constitute overtreatment. However, patients with high-risk features such as large or high-grade tumors, nodal disease, and elevated CA19-9 may benefit from AT.

Patients with pancreatic ductal adenocarcinoma (PDAC) frequently present with liver metastases, which severely limit treatment options and prognosis. In other cancers, treatment of liver disease can improve outcomes and similar approaches are being explored in PDAC. Clinical data for locoregional control of pancreatic cancer liver metastases (PCLM) are limited, and histotripsy offers a new noninvasive tool for disease control. This study evaluates the preliminary safety, efficacy, and imaging findings of histotripsy in patients with PCLM.

BACKGROUND:Neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) is increasingly being used. The aim of this study was to evaluate the association between type, duration, and sequencing of adjuvant therapy (AT) after NAT and overall survival (OS) in patients with resected PDAC. METHODS:Patients receiving NAT and resection for PDAC (2010-2019) at two high-volume pancreatic surgery centers were included and stratified into groups on the basis of NAT regimen: gemcitabine-based NAT, 5-fluorouracil (5FU)-based NAT, or switched NAT regimen. The maximally selected rank statistic was used to determine the optimal NAT duration. Univariate and multivariable Cox proportional hazards models were used to assess the association between NAT regimen and OS, and between AT and OS. RESULTS:Of 651 patients, 200 (30.7%) received gemcitabine-based NAT, 362 (56%) received 5FU-based NAT, and 89 (13.7%) switched NAT regimen. Median OS in patients receiving gemcitabine-based NAT was 19 months (95% confidence interval (CI) 17-25 months), compared with 26 months (95% CI 24-31 months) in patients receiving 5FU-based NAT (hazard ratio (HR) 0.81, 95% CI 0.66-0.99, p = 0.04) and 21 months (95% CI 16-26 months) in patients who switched NAT regimen (HR 0.98, 95% CI 0.73-1.29, p = 0.86). Optimal NAT duration was 3.6 months in the complete cohort. Receiving AT was associated with improved survival (HR 0.61, 95% CI 0.43-0.86, p < 0.001), but its association was reduced after a NAT duration of ≥5 months (adjuvant chemotherapy × NAT duration ≥ 5 months: HR 1.50, 95% CI 1.00-2.24, p = 0.048). CONCLUSIONS:Patients receiving 5FU-based NAT showed improved survival compared with patients receiving gemcitabine-based NAT before surgery for PDAC. Adjuvant therapy improved survival, particularly in patients with shorter NAT duration.

OBJECTIVE:Identify how surgical resection of pancreatic ductal adenocarcinoma (PDAC) affects systemic minimal residual disease (MRD). METHODS:Pancreatic tumors were generated by orthotopic implantation of tumor cells into the pancreas of immunocompetent mice. Tumor resection was carried out via distal pancreatectomy and splenectomy. Liver metastases and microenvironment immune changes were analyzed in resected vs. non-resected mice. RESULTS:Resection was accompanied by proliferative expansion of liver metastases and an increase in hepatic metastatic burden. Postoperative immune changes predominantly manifested as a time-dependent increase in eosinophils and decrease in neutrophils. The postoperative hepatic eosinophilia was protective of further metastatic progression. The parenchymal findings were detectable in the circulation, and the trends observed in the mouse model modeled those seen in PDAC patients postoperatively. CONCLUSION/CONCLUSIONS:Collectively, we describe a preclinical resection model that offers a means to investigate MRD. Using this model, we delineated effects of surgical resection on metastatic outgrowth and uncovered a protective link between the postoperative hepatic eosinophilia and further metastatic progression.

BACKGROUND:The introduction of (m)FOLFIRINOX and gemcitabine-nab-paclitaxel has changed the perspective for patients with locally advanced pancreatic cancer (LAPC). Consequently, in experienced centres 23% of patients with LAPC undergo a resection with 5-year overall survival (OS) rates of up to 25%. In the Netherlands, the nationwide resection rate for LAPC remains low at 8%. The PREOPANC-4 program aims for a nationwide implementation of the international multidisciplinary best-practice to improve patient outcome. METHODS:Nationwide program implementing the international multidisciplinary best-practice for LAPC. In the training phase, multidisciplinary and surgical webinars are given by 4 international experts, leading to a clinical protocol, followed by surgical off-site and on-site proctoring sessions. In the implementation phase, the clinical protocol will be implemented in all centres, including a nationwide expert panel (2022-2024). Healthcare professionals will be trained in shared decision-making. Consecutive patients diagnosed with pathology-proven LAPC (i.e., arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion [DPCG criteria]) are eligible. Primary outcomes are median and 5-year OS from diagnosis, resection rate, in-hospital/30-day mortality and major morbidity (i.e., Clavien-Dindo grade ≥ IIIa), and radical resection (R0) rate. Secondary outcomes include quality of life, functioning, side effects, and patients' healthcare satisfaction in all included patients. Outcomes will be compared with patients with borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX in the PREOPANC-2 trial (EudraCT: 2017-002036-17) and a historical cohort of patients with LAPC from the PACAP registry (NCT03513705). The existing prospective LAPC Registry and PACAP PROMs (NCT03513705) will be used for data collection. In qualitative interviews, treatment preferences, values, and experiences of LAPC patients, their relatives, and healthcare professionals will be assessed for the development of shared decision-making supportive tools. It is hypothesized that the program will double the nationwide LAPC resection rate to 16% with major morbidity < 50% and mortality ≤ 5%, and OS following resection similar to that observed in patients with BRPC. DISCUSSION/CONCLUSIONS:The PREOPANC-4 program aims to safely implement the international multidisciplinary best-practice for LAPC leading to benchmark outcomes for both short-term morbidity, mortality, and OS. TRIAL REGISTRATION/BACKGROUND:PREOPANC-4 program was registered at ClinicalTrials.gov (NCT05524090) on September 1, 2022.