Impact of Acute Inflammation on the Survival Outcomes of Patients with Resected Pancreatic Ductal Adenocarcinoma

2021 ◽  
pp. 1-9
Author(s):  
Mohamed Rabie Saad ◽  
Ho-Seong Han ◽  
Yoo-Seok Yoon ◽  
Jai Young Cho ◽  
Jun Suh Lee ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Predictive Factors ◽  
Acute Inflammation ◽  
Acute Cholangitis ◽  
Microvascular Invasion ◽  
Ductal Adenocarcinoma ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Positive Lymph Nodes

<b><i>Introduction:</i></b> The impact of acute inflammation on cancer progression is still not well elucidated. Pancreatic head cancer is occasionally associated with acute cholangitis. C-reactive protein (CRP) is a biomarker that indicates presence of acute inflammation. <b><i>Methods:</i></b> We reviewed the patients’ data with pancreatic ductal adenocarcinoma (PDAC) who underwent pancreaticoduodenectomy between 2004 and 2018. <b><i>Results:</i></b> Two hundred ninety-one patients were included. Median preoperative CRP was 0.45 mg/dL (0–18.9). Median follow-up duration was 22 months (4–152). The 1-, 3-, and 5-year overall survival (OS) rates were 76.4%, 32.2%, and 22.9%, respectively. Recurrence occurred in 168 cases (57.7%). The 1-, 3-, and 5-year disease-free survival (DFS) rates were 53.9%, 27.1%, and 21.9%, respectively. The median OS was higher in normal CRP patients (27 months) than those with elevated CRP (18 months) (log-rank 0.038). The median DFS was higher in normal CRP patients (17 months) than those with elevated CRP (9 months) (log-rank &#x3c; 0.001). Predictive factors for OS included BMI, CRP, adjuvant therapy, positive lymph nodes, and microvascular invasion. Predictive factors for DFS included CRP, positive lymph nodes, and microvascular invasion. <b><i>Conclusion:</i></b> Preoperative CRP was an independent poor prognostic factor for OS and DFS of patients with resected PDAC.

scholarly journals MicroRNA-Regulated Signaling Pathways: Potential Biomarkers for Pancreatic Ductal Adenocarcinoma

Stresses ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 30-47
Author(s):  
Maria Mortoglou ◽  
David Wallace ◽  
Aleksandra Buha Buha Djordjevic ◽  
Vladimir Djordjevic ◽  
E. Damla Arisan ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Metabolic Stress ◽  
Resistance Mechanisms ◽  
Current Data ◽  
Cellular Damage ◽  
Ductal Adenocarcinoma ◽  
Aberrant Expression ◽  
Metabolic Alterations ◽  
Limited Effectiveness ◽  
The Impact

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive and invasive type of pancreatic cancer (PCa) and is expected to be the second most common cause of cancer-associated deaths. The high mortality rate is due to the asymptomatic progression of the clinical features until the advanced stages of the disease and the limited effectiveness of the current therapeutics. Aberrant expression of several microRNAs (miRs/miRNAs) has been related to PDAC progression and thus they could be potential early diagnostic, prognostic, and/or therapeutic predictors for PDAC. miRs are small (18 to 24 nucleotides long) non-coding RNAs, which regulate the expression of key genes by targeting their 3′-untranslated mRNA region. Increased evidence has also suggested that the chemoresistance of PDAC cells is associated with metabolic alterations. Metabolic stress and the dysfunctionality of systems to compensate for the altered metabolic status of PDAC cells is the foundation for cellular damage. Current data have implicated multiple systems as hallmarks of PDAC development, such as glutamine redox imbalance, oxidative stress, and mitochondrial dysfunction. Hence, both the aberrant expression of miRs and dysregulation in metabolism can have unfavorable effects in several biological processes, such as apoptosis, cell proliferation, growth, survival, stress response, angiogenesis, chemoresistance, invasion, and migration. Therefore, due to these dismal statistics, it is crucial to develop beneficial therapeutic strategies based on an improved understanding of the biology of both miRs and metabolic mediators. This review focuses on miR-mediated pathways and therapeutic resistance mechanisms in PDAC and evaluates the impact of metabolic alterations in the progression of PDAC.

scholarly journals Repression of MUC1 promotes expansion and suppressive function of myeloid-derived suppressor cells in pancreatic ductal adenocarcinoma and breast cancer murine models

2020 ◽  
Author(s):  
S. Mahnaz ◽  
L. Das Roy ◽  
M. Bose ◽  
C. De ◽  
S. Nath ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathways ◽  
Suppressor Cells ◽  
Ductal Adenocarcinoma ◽  
Myeloid Derived Suppressor Cells ◽  
Mucin 1 ◽  
Transmembrane Glycoprotein ◽  
The Impact

ABSTRACTMyeloid-derived suppressor cells (MDSCs) are immature myeloid cells that are responsible for immunosuppression in tumor microenvironment. Here we report the impact of mucin 1 (MUC1), a transmembrane glycoprotein, on proliferation and functional activity of MDSCs. To determine the role of MUC1 in MDSC phenotype, we analyzed MDSCs derived from wild type (WT) and MUC1-knockout (MUC1KO) mice bearing pancreatic ductal adenocarcinoma KCKO and breast cancer C57MG xenografts. We observed enhanced tumor growth in MUC1KO mice compared to WT mice in both pancreatic KCKO and breast C57MG cancer models due to increased MDSC population and enrichment of Tregs in tumor microenvironment. Our current study shows that knockdown of MUC1 in MDSCs promotes proliferation and immature suppressive phenotype indicated by increased level of iNOS, ARG1 activity and TGF-β secretion under cancer conditions. Increased activity of MDSCs leads to repression of IL-2 and IFN-ɣ production by T-cells. We were able to find that MDSCs from MUC1KO mice have higher levels of c-Myc and activated pSTAT3 as compared to MUC1 WT mice, that are signaling pathways leading to increased survival, proliferation and prevention of maturation. In summary, MUC1 regulates signaling pathways that maintain immunosuppressive properties of MDSCs. Thus, immunotherapy must target only tumor associated MUC1 on epithelial cells and not MUC1 on hematopoietic cells to avoid expansion and suppressive functions of MDSC.

P-P13 Long-term outcome after portal vein resection during pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a propensity score matched analysis

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
James Russell ◽  
Claire Stevens ◽  
Rahul Bhome ◽  
Dimitrios Karavias ◽  
Ali Arshad ◽  
...  
Keyword(s):  
Propensity Score ◽  
Portal Vein ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Perineural Invasion ◽  
Nodal Metastasis ◽  
Ductal Adenocarcinoma ◽  
Safe Procedure ◽  
Portal Vein Resection ◽  
Vein Resection ◽  
The Impact

Abstract Background Portal vein resection (PVR) with pancreaticoduodenectomy (PD) is often performed to achieve clear margins for patients with vascular involvement in pancreatic ductal adenocarcinoma (PDAC). However, there is evidence to suggest that patients undergoing PVR often have more advanced cancers, therefore the impact of PVR on survival and recurrence remains unclear. The aim of this study is to assess overall (OS) and recurrence free (RFS) survival in patients who underwent PVR during PD, with particular attention to margin positivity. Methods A retrospective analysis was performed on 638 patients who underwent PD during a 12-year period. Exclusion criteria included PD for non-PDAC tumours, neoadjuvant chemotherapy or intra-operative radiotherapy. 374 patients were included in the study (90 PVR and 284 non-PVR). Patient characteristics and histopathological factors associated with OS and RFS were then evaluated using univariate and multivariate Cox regression analyses. 270 patients (90 PVR and 180 non-PVR), were matched by propensity score based on perineural invasion, pT and pN staging. The Kaplan-Meier method was used to calculate survival and log-rank tests. Results Resection margin positivity was associated with shorter OS and RFS (p &lt; 0.0001), and the superior mesenteric vein (SMV) margin was the most significant risk factor for survival on competing risks analysis. Absent adjuvant chemotherapy, nodal metastasis and margin positivity were independent risk factors for OS and RFS on multivariate analysis. PVR was associated with higher intra-operative blood loss (p = 0.009), but was not associated with increased length of stay, complications or readmissions. PVR patients had increased pT staging, nodal metastasis and perineural invasion, however, there was no difference in OS (p = 0.551) or RFS (p = 0.256) between PVR and non-PVR after propensity matching. Conclusions Positive resection margins are associated with shorter survival times, and the SMV margin is the most significant prognostic indicator for overall survival and recurrence compared to other margins. PVR is a relatively safe procedure, however, it does not achieve the intended survival benefits of complete margin clearance. The impact on survival for margin positivity, particularly the SMV margin, and nodal metastasis should be considered when making decisions with regards to vein resection and adjuvant treatments.

scholarly journals The Emerging Role of Microbiota and Microbiome in Pancreatic Ductal Adenocarcinoma

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 565
Author(s):  
Sona Ciernikova ◽  
Maria Novisedlakova ◽  
Danka Cholujova ◽  
Viola Stevurkova ◽  
Michal Mego
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Early Stage ◽  
Poor Response ◽  
Response To Therapy ◽  
Oral Microbiome ◽  
Ductal Adenocarcinoma ◽  
The Impact

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors due to the absence of biomarkers for early-stage detection and poor response to therapy. Since mounting evidence supports the role of microbiota composition in tumorigenesis and cancer treatment, the link between microbiome and PDAC has been described. In this review, we summarize the current knowledge regarding the impact of the gut and oral microbiome on the risk of PDAC development. Microenvironment-driven therapy and immune system interactions are also discussed. More importantly, we provide an overview of the clinical trials evaluating the microbiota role in the risk, prognosis, and treatment of patients suffering from PDAC and solid tumors. According to the research findings, immune tolerance might result from the microbiota-derived remodeling of pancreatic tumor microenvironment. Thus, microbiome profiling and targeting represent the potential trend to enhance antitumor immunity and improve the efficacy of PDAC treatment.

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