UNASSIGNED: Pancreatic ductal adenocarcinoma (PDAC) is 3rd most lethal cancer in the USA leading to a median survival of six months and less than 5% 5-year overall survival (OS). As the only potentially curative treatment, surgical resection is not suitable for up to 90% of the patients with PDAC due to late diagnosis. Highly fibrotic PDAC with an immunosuppressive tumor microenvironment restricts cytotoxic T lymphocyte (CTL) infiltration and functions causing limited success with systemic therapies like dendritic cell (DC)-based immunotherapy. In this study, we investigated the potential benefits of irreversible electroporation (IRE) ablation therapy in combination with DC vaccine therapy against PDAC.
UNASSIGNED: We performed a literature search to identify studies focused on DC vaccine therapy and IRE ablation to boost therapeutic response against PDAC indexed in PubMed, Web of Science, and Scopus until February 20th, 2023.
UNASSIGNED: IRE ablation destructs tumor structure while preserving extracellular matrix and blood vessels facilitating local inflammation. The studies demonstrated IRE ablation reduces tumor fibrosis and promotes CTL tumor infiltration to PDAC tumors in addition to boosting immune response in rodent models. The administration of the DC vaccine following IRE ablation synergistically enhances therapeutic response and extends OS rates compared to the use of DC vaccination or IRE alone. Moreover, the implementation of data-driven approaches further allows dynamic and longitudinal monitoring of therapeutic response and OS following IRE plus DC vaccine immunoablation.
UNASSIGNED: The combination of IRE ablation and DC vaccine immunotherapy is a potent strategy to enhance the therapeutic outcomes in patients with PDAC.

UNASSIGNED: Advancements in surgical techniques have improved outcomes in patients undergoing pancreatic surgery. To date there have been no meta-analyses comparing robotic and laparoscopic approaches for distal pancreatectomies (DP) in patients with pancreatic adenocarcinoma (PDAC). This systematic review and network meta-analysis aims to explore the oncological outcomes of laparoscopic distal pancreatectomy (LDP), robotic distal pancreatectomy (RDP) and open distal pancreatectomy (ODP).
UNASSIGNED: A systematic search was conducted for studies reporting laparoscopic, robotic or open surgery for DP. Frequentist network meta-analysis of oncological outcomes (overall survival, resection margins, tumor recurrence, examined lymph nodes, administration of adjuvant therapy) were performed.
UNASSIGNED: Fifteen studies totalling 9,301 patients were included in the network meta-analysis. 1,946, 605 and 6,750 patients underwent LDP, RDP and ODP respectively. LDP (HR: 0.761, 95% CI: 0.642-0.901, p = 0.002) and RDP (HR: 0.757, 95% CI: 0.617-0.928, p = 0.008) were associated with overall survival (OS) benefit when compared to ODP. LDP (HR: 1.00, 95% CI: 0.793-1.27, p = 0.968) was not associated with OS benefit when compared to RDP. There were no significant differences between LDP, RDP and ODP for resection margins, tumor recurrence, examined lymph nodes and administration of adjuvant therapy.
UNASSIGNED: This study highlights the longer OS in both LDP and RDP when compared to ODP for patients with PDAC.
UNASSIGNED: https://www.crd.york.ac.uk/, PROSPERO (CRD42022336417).

UNASSIGNED: Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death in the United States and is projected to become the second-leading cause of cancer-related death by 2030. Despite advances in systemic and radiation therapy, for patients with surgically resectable PDAC, complete surgical resection is the only potentially curative treatment option. The conduct of a safe, technically excellent pancreatectomy is essential to achieve optimal perioperative outcomes and long-term survival. In this narrative review, evidence from large, well-executed studies and clinical trials examining the technical aspects of pancreatectomy is reviewed.
UNASSIGNED: A search was conducted in PubMed, Medline, and Cochrane Review databases to identify English-language randomized clinical trials, meta-analyses, and systematic reviews assessing surgical aspects of pancreatectomy for PDAC published between 2010 to 2023.
UNASSIGNED: We identified retrospective and prospective studies evaluating the technical aspects of surgery for PDAC. In this review, we evaluate data on surgical techniques of pancreatectomy for PDAC, including the role of minimally invasive techniques, extent of lymphadenectomy, reconstruction options after pancreatoduodenectomy, and the role of surgical drainage.
UNASSIGNED: Surgical resection has a critical role in the treatment of operable PDAC. While pancreatic cancer surgery is an active area of research, conducting a technically excellent surgical resection maintains paramount importance for both oncological and perioperative outcomes. In this review, we summarize the latest evidence on surgical technique for operable PDAC.

UNASSIGNED: Pancreatic adenocarcinoma remains a dismal disease and is expected to become an even greater burden in the near future. This review focuses on the different surgical aspects for pancreaticoduodenectomy (PD), distal and total pancreatectomy (TP), incorporating lessons from both the western and eastern visions in treating pancreatic cancer.
UNASSIGNED: We conducted an extensive literature review through PubMed, prioritizing papers published in the last 5 years, but older emblematic papers were also included. We included articles that explored the treatment of pancreatic adenocarcinoma, with focus on the surgical aspect and strategies to improve outcomes. References of selected articles were also reviewed to identify any missed studies. Only papers in English were included.
UNASSIGNED: As evidence continues to build, it is clear that both systemic and surgical therapies have a fundamental and complementary role. State of art surgical treatment encompasses complete mesopancreas excision for radical lymphadenectomy. Preoperative planning of dissection planes, extensive knowledge of vascular anatomic variations, oncological principles and expertise for vascular resections are mandatory to perform a more radical operation, in pursuit of improved outcomes.
UNASSIGNED: Based on current data, patient selection remains key and a more radical surgical approach brings more accomplishing results bringing as to believe that more is better.

Pancreatic mixed neoplasms are very rare. We herein report a unique case of pancreatic mixed acinar-neuroendocrine-ductal carcinoma with trilineage differentiation. The patient was an 83-year-old woman referred to our hospital due to anemia and a pancreatic mass. Contrast-enhanced computed tomography revealed a 60-mm mass in the pancreas. Subtotal stomach-preserving pancreaticoduodenectomy was performed. The postoperative pathological diagnosis was mixed acinar-neuroendocrine-ductal carcinoma. Postoperative chemotherapy was conducted according to the adenocarcinoma and neuroendocrine carcinoma protocols. The patient died 26 months postoperatively. Choosing appropriate chemotherapy for mixed neoplasms is difficult. Cancer gene panel testing, if possible, may support the choice of therapeutic agents.

BACKGROUND: The aim of this review was to characterize the second- and later-line (≥2L) treatment landscape for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).
METHODS: This systematic literature review (PROSPERO: CRD42021279753) involved searches of MEDLINE® and Embase to identify results from prospective studies of ≥2L treatment options for metastatic pancreatic cancer published from 2016 to 2021. Publications were screened according to predetermined eligibility criteria; population-level data were extracted using standardized data fields. Publication quality was assessed according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The data were analyzed descriptively, grouped by drug class.
RESULTS: Sixty publications were identified, including 23 relating to comparative trials. GRADE assessment found that, of these 23 trials, 83% reported high or moderate-quality evidence. Of the publications relating to comparative trials, nine (three trials) reported favorable results: the pivotal phase 3 NAPOLI-1 trial for liposomal irinotecan; a phase 3 trial of non-liposomal irinotecan within the FOLFIRINOX regimen; and a phase 2 trial of eryaspase plus chemotherapy.
CONCLUSIONS: The level of unmet need for ≥2L treatment options for mPDAC remains high. Irinotecan-based regimens currently offer the greatest promise. Investigations into paradigm-changing agents and combination approaches continue.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of solid tumors, associated with a high prevalence of cachexia (~80%). PDAC-derived cachexia (PDAC-CC) is a systemic disease involving the complex interplay between the tumor and multiple organs. The endocrine organ-like tumor (EOLT) hypothesis may explain the systemic crosstalk underlying the deleterious homeostatic shifts that occur in PDAC-CC. Several studies have reported a markedly heterogeneous collection of cachectic mediators, signaling mechanisms, and metabolic pathways, including exocrine pancreatic insufficiency, hormonal disturbance, pro-inflammatory cytokine storm, digestive and tumor-derived factors, and PDAC progression. The complexities of PDAC-CC necessitate a careful review of recent literature summarizing cachectic mediators, corresponding metabolic functions, and the collateral impacts on wasting organs. The EOLT hypothesis suggests that metabolites, genetic instability, and epigenetic changes (microRNAs) are involved in cachexia development. Both tumors and host tissues can secrete multiple cachectic factors (beyond only inflammatory mediators). Some regulatory molecules, metabolites, and microRNAs are tissue-specific, resulting in insufficient energy production to support tumor/cachexia development. Due to these complexities, changes in a single factor can trigger bi-directional feedback circuits that exacerbate PDAC and result in the development of irreversible cachexia. We provide an integrated review based on 267 papers and 20 clinical trials from PubMed and ClinicalTrials.gov database proposed under the EOLT hypothesis that may provide a fundamental understanding of cachexia development and response to current treatments.

OBJECTIVE: The concept of neoadjuvant approach for patients with locally advanced pancreatic cancer (LAPC) has been evolving with the advancement in therapeutic modalities. In this narrative review, we aimed to discuss the updates and future perspectives on the treatment of LAPC.
METHODS: We discussed the recent literature and up-to-date evidence along with the future perspectives for the treatment of LAPC using the neoadjuvant approach. Reviewed literatures were searched by systematic search of PubMed and Google Scholar, including articles published in English between January 1st, 2013, and October 31st, 2021.
UNASSIGNED: We aimed to review the efficacy outcomes of modern-era chemotherapy regimens and chemoradiation therapy for LAPC based on the results of up-to-date clinical trials and pivotal observational studies. Moreover, we aimed to discuss the role of conversion surgery and studies on the prediction of resectability after neoadjuvant therapy along with the necessity of adjuvant therapy for patients who have received neoadjuvant systemic treatments. Finally, we have addressed several unanswered questions regarding the optimal management of patients with LAPC and determined the future directions by introducing some ongoing trials.
CONCLUSIONS: Current chemotherapy and chemoradiation therapy has improved clinical outcomes and the conversion surgery rate in patients with LAPC. Future randomized clinical trials and biomarker studies are needed to provide better evidence that can aid in the selection of optimal treatment modalities for individual patients.

OBJECTIVE: Preoperative neoadjuvant therapy (NAT) is increasingly used in the treatment of patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Because NAT often induces heterogeneous tumor response and extensive fibrosis both in tumor and adjacent pancreatic tissue, pathologic assessment of posttherapy pancreatectomy specimens is challenging. A limited number of studies examined the optimal grossing and sampling methods, tumor response grading (TRG), and the prognostic value of posttherapy tumor (ypT) and lymph node (ypN) stages of treated PDAC patients. In this review, we will provide an overview of the current status and critical issues in pathologic evaluation of PDAC resected after NAT.
METHODS: In PubMed, Google Scholar and Web of Science, we reviewed existing English literature (published up to December 2021) highlighting the most recent ones using electronic databases and authors\' experience to outline the challenging aspects and new perspectives on pathologic assessment of the treated PDAC.
UNASSIGNED: The recent recommendations from the Pancreatobiliary Pathology Society (PBPS) provide the much-needed guidelines for systematic and standardized pathologic evaluation and reporting of treated PDAC for optimal patient care. For treated PDAC, tumor size measured by gross and radiology is not reliable. Histologic validation of tumor size on consecutive mapping sections is recommended for accurate ypT stage. A tumor size of 1.0 cm seems to be a better cutoff for ypT2 for treated PDACs. The published data suggested that the MD Anderson Cancer Center (MDA) TRG system is easy to use, has a better interobserver agreement and better correlation with patient prognosis compared to the College of American Pathologists (CAP) and Evans grading systems and may be used as an alternative TRG system for the CAP cancer protocol.
CONCLUSIONS: Systemic and standardized grossing and sampling are essential for accurate pathologic evaluation and reporting for optimal care of PDAC patients who received NAT. Future studies on optimal sampling and integration of histopathology with artificial intelligence (AI), molecular and immunohistochemical markers are needed for better and personalized care of treated PDAC patients.

BACKGROUND: Pancreatic cancer represents a systemic disease, and its treatment ideally includes the administration of systemic therapy regardless of its anatomical stage.
METHODS: In this brief narrative review, the most recent literature will be highlighted, together with updates, new perspectives on the topic, and the authors own personal view.
RESULTS: While preoperative therapy has recently become the new standard for borderline resectable stages, adjuvant therapy after surgery remains the current standard of care for resectable disease. However, to deliver systemic therapy in the postoperative setting implies that a significant subset of patients, not fully recovering after a pancreatectomy, will never receive appropriate treatment. Administration of chemotherapy before pancreatectomy may represent the only way to assure optimal treatment, simultaneously selecting patients for surgery according to tumor biology. For these reasons, many high-volume centers for pancreatic surgical oncology are increasingly considering this strategy also for patients with resectable disease.
CONCLUSIONS: Nonetheless, available data to support this paradigm shift are still germinal, and the optimal modalities and timing of preoperative therapy are eagerly debated as well.