Faculty Bibliography
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656
Surgical Resection of Murine PDAC Alters Hepatic Metastases and Immune Microenvironment
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.
PMID: 40403285
ISSN: 1536-4828
CID: 5853432
Adjuvant therapy after resection of intraductal papillary mucinous neoplasm-derived pancreatic cancer: A systematic review and meta-analysis
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.
PMID: 40450826
ISSN: 1532-1967
CID: 5861832
Clinical and radiological predictive features for high-grade and invasive carcinoma in intraductal papillary mucinous neoplasms: A systematic review
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.
PMID: 40320724
ISSN: 1868-6982
CID: 5838852
Decisional Control Preferences in Managing Intraductal Papillary Mucinous Neoplasms of the Pancreas
OBJECTIVES/OBJECTIVE:To evaluate patient preferences for decision-making role in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and to identify individual characteristics associated with those preferences. BACKGROUND:Management of IPMNs is rooted in uncertainty with current guidelines failing to incorporate patients' preferences and values. METHODS:A representative sample of participants aged 40-70 were recruited to evaluate a clinical vignette where they were given the option to undergo surveillance or surgical resection of their IPMN. Their preferred role in the decision-making process for the vignette was evaluated using the Control Preference Scale. The relationship between control preference and variables including cancer anxiety, health literacy, and education level was analyzed. RESULTS:Of the 520 participants in the study, most preferred an active role (65%), followed by shared (29%), and passive roles (6%) in the decision-making process. Lower health literacy was significantly associated with a more passive control preference (p = 0.003). Non-active preference was significantly associated with Latino race compared to White race (odds ratio = 0.52, p = 0.009) in multivariate analysis. We found no significant association between control preference and education level or cancer anxiety. CONCLUSIONS:Most patients preferred an active role in IPMN treatment decisions. Lower health literacy and Latino race were associated with a preference for non-active decision roles. Clinicians should strive to align patient involvement in IPMN treatment decisions with their patient's preferred role.
PMID: 39626203
ISSN: 1536-4828
CID: 5804402
Recognizing IPMN-derived pancreatic cancer as a specific entity requiring prospective clinical studies: a call for international collaboration
PMID: 39945800
ISSN: 1460-2105
CID: 5793802
Prognostic factors in localized pancreatic ductal adenocarcinoma after neoadjuvant therapy and resection: a systematic review and Meta-Analysis
INTRODUCTION/BACKGROUND:Prognostic markers for overall survival (OS) in resected pancreatic ductal adenocarcinoma (PDAC) are well-established but remain unclear following neoadjuvant therapy (NAT). This systematic review and meta-analysis aimed to determine factors associated with OS following NAT in resected PDAC. METHODS:The PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL databases were systematically searched from inception till May 2024. Studies that reported univariable and multivariable hazard ratios (HRs) were included if patients underwent NAT and resection for localized PDAC. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was performed using generic inverse-variance random-effects models. RESULTS:Among 2,208 unique articles identified by the search, 92 were included in the meta-analysis. Eighty-five of these were of 'good' and 7 of 'poor' quality. The NAT regimen was described in 84 studies, of which 62 included patients treated with FOLFIRINOX (FFX). Margin status, nodal disease, AJCC T-stage, and normalization of CA19-9 after NAT were prognostic for OS, while age, sex, perineural invasion, baseline tumor size, and baseline CA19-9 were not. The test for subgroup differences between ypN-substages was not significant in the multivariable model. Neoadjuvant FFX was associated with better survival than other regimens. CONCLUSIONS:This meta-analysis identified margin status, nodal disease, AJCC T-stage, and normalization of CA19-9 after NAT as prognostic factors for OS in patients with resected localized PDAC following NAT.
PMID: 39563429
ISSN: 1460-2105
CID: 5758522
The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study
PURPOSE/OBJECTIVE:To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery. BACKGROUND:Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC. METHODS:International multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). Primary endpoint is OS from diagnosis. Time-dependent Cox regression analysis was performed to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at time of diagnosis. Adjusted OS probabilities were calculated. RESULTS:=0.96) involvement. CONCLUSIONS:Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared to upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.
PMID: 39814200
ISSN: 1569-8041
CID: 5776932
ASO Author Reflections: The Robotic Evolution-Transforming Pancreatic Surgery
PMID: 39994166
ISSN: 1534-4681
CID: 5800642
Robotic Distal Pancreatectomy with Celiac Axis Resection and SMA Divestment: A Step-by-Step Educational Video
INTRODUCTION/BACKGROUND:En-bloc celiac axis resection (CAR) was first proposed by Lyon H. Appleby in 1952 for gastric cancer and later modified for pancreatic resections with gastric preservation by Nimura et al. in 1976. CAR remains uncommon, performed in fewer than 0.2 cases annually. Advancements in preoperative imaging and anatomy understanding, ischemic complication management, and centralization of care have improved outcomes. This report presents a robotic distal pancreatectomy (DP) with CAR and superior mesenteric artery (SMA) divestment. CASE REPORT/METHODS:A 65-year-old woman presented with back pain. Imaging revealed biopsy-proven pancreatic adenocarcinoma in the pancreatic body, encasing the celiac, splenic, and common hepatic arteries with SMA abutment. Following four cycles of neoadjuvant FOLFIRINOX, follow-up imaging demonstrated stable disease without metastasis. The need for hepatic artery reconstruction was assessed intraoperatively, with alternative strategies detailed in the accompanying video. OPERATIVE TECHNIQUE/METHODS:The patient underwent a distal pancreatectomy and splenectomy with class Ia CAR. Surgery was conducted in a caudal approach, lasted 420 minutes with minimal blood loss (100 ml). Laparoscopic ultrasound (lapUS) and indocyanine green (ICG) perfusion were used to assess resectability, vascular perfusion, and targeted blood vessels. The postoperative course was uneventful, except for a Grade B chyle leak managed conservatively. No liver or gastric ischemia occurred. Adjuvant chemotherapy was initiated two months postoperatively. CONCLUSION/CONCLUSIONS:Enhanced visualization, improved dexterity, and adjuncts including lapUS and ICG are potential benefits that are available to surgeons with the robotic platform when performing arterial divestment and CAR via a caudal approach.
PMID: 39918751
ISSN: 1534-4681
CID: 5784382
Carbohydrate Antigen 19-9 Delta Function for Survival Prediction in Borderline Pancreatic Cancer. A PANC-PALS Consortium International Multicenter Derivation and Validation Study
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.
PMID: 40235433
ISSN: 1528-1140
CID: 5827952
