Faculty Bibliography

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.

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.

BACKGROUND/PURPOSE/OBJECTIVE:Intraductal papillary mucinous neoplasms (IPMNs) progress from low-grade dysplasia to high-grade dysplasia (HGD) or invasive carcinoma (IC). High diagnostic accuracy is critical for surgical decision-making. METHODS:We searched Medline, Embase, and Cochrane Library from January 1, 2015, to January 27, 2025. Eligible studies reported on resected IPMNs, assessing diagnostic features for HGD/IC. Two reviewers screened articles, extracted data, and assessed bias using the Newcastle-Ottawa scale. Descriptive statistics summarized outcomes. The performance of worrisome features (WFs) and high-risk stigmata (HRS) based on International Association of Pancreatology guidelines were evaluated. RESULTS:In the 53 studies, 12 953 patients were included. HRS including obstructive jaundice and enhancing mural nodules ≥5mm showed robust specificity for HGD/IC, while main pancreatic duct size ≥10mm showed variable diagnostic accuracy. WFs such as cyst size ≥3 cm performed poorly, while cyst growth rate >3.5 mm/year demonstrated higher sensitivity (88%) and specificity (91%). Although rare, abrupt caliber change with distal atrophy was a robust predictor of malignancy (median odds ratio: 3.01). Acute pancreatitis and lymphadenopathy displayed variable value. Incremental improvement in diagnostic accuracy was observed with additional HRS or WFs. CONCLUSIONS:Current diagnostic markers are valuable but provide limited guidance for surgical decision-making in IPMNs, highlighting the need for further refinement of diagnostic tools.

OBJECTIVE:To establish a novel method for evaluating carbohydrate antigen 19-9 (CA19-9) during neoadjuvant therapy (NAT) and assess its role in predicting overall (OS) and disease-free (DFS) survival in borderline resectable pancreatic adenocarcinoma (BR-PC). SUMMARY BACKGROUND DATA/BACKGROUND:Static CA19-9 values or percentage changes often fail to capture therapeutic responses in patients with BR-PC undergoing NAT. Improved evaluation methods are essential for guiding the treatment. METHODS:This was a retrospective multicenter study of patients who underwent BR-PC surgery. Two parameters were developed: slope coefficient (SC, change in CA19-9 divided by therapy duration) and mean δf (mδf, calculated as the sum of CA19-9 values over therapy intervals divided by the number of 15-day periods). The main objective was to correlate mδf with OS thresholds derived using a maximally selected log-rank statistic and validated in independent cohorts. RESULTS:Overall, 991 patients (median age 65 [59-71] years; 49% male) were included. The thresholds for mδf were defined as U.mL-1. month-1 (negative SC) and U.mL-1. month-1 (positive SC). Patients with mδf below these thresholds had significantly better prognoses, with hazard ratios (HR) for OS (95% CI) of 0.6 (0.4-0.8; P<0.01) and 0.4 (0.2-0.9; P=0.04) for negative and positive SC, respectively. Both thresholds were validated for mOS, with 29 vs 22 months (P=0.015) and 32 vs 16 months (P=0.0034) for negative and positive SC, respectively. Similarly, the mDFS was 13 vs 10 months (P=0.011) and 12 vs 7 months (P=0.0018), respectively. CONCLUSION/CONCLUSIONS:This CA19-9 evaluation approach accurately predicts survival outcomes, offering a valuable tool for optimizing treatment strategies. An mδf calculator is available at https://www.pancpals.com/tools.

BACKGROUND:The National Comprehensive Cancer Network guidelines consider pancreatic cancer with celiac axis (CA), proper hepatic artery (PHA), and superior mesenteric artery (SMA) involvement unresectable. Thus, technical reports and video illustrations of these operations are rare. We report the stepwise management of multivascular reconstruction for Mayo Clinic class IIIb CA resections at New York University Langone Health, a dedicated center of excellence in pancreatic surgery. METHODS:We illustrated the management of a 56-year-old patient with biopsy-confirmed pancreatic ductal adenocarcinoma arising from the pancreatic body and involving the CA, PHA, SMA, and mesentericoportal venous axis. PERIOPERATIVE MANAGEMENT/UNASSIGNED:The preoperative stepwise considerations include: 1) mandatory patient selection; 2) planning vascular reconstructability; 3) tailoring risk assessment while carefully considering the need for total pancreatectomy, total gastrectomy, and mesenteric/hepatic revascularization; and 4) 3D-reconstruction for arterial evaluation. The key intraoperative considerations include: 1) selective and sequential clamping for vascular reconstruction in a "domino" fashion, to minimize warm ischemic time 2) a combined multi-surgeon approach to comprehensively tackle vascular reconstructions; 3) a low threshold for total pancreatectomy to avoid pancreatic leak; and 4) two-stage surgery to reassess the blood supply to the liver and stomach for on-demand gastric preservation instead of a theoretically advised total gastrectomy. CONCLUSION/CONCLUSIONS:Liver, stomach, and bowel vascularization present life-threatening risks that require an extensive preoperative evaluation and a multidisciplinary approach. Our stepwise management for these extensive operations includes total pancreatectomy, "domino" vascular reconstruction, and two-stage surgery.