scholarly journals Pancreatic ductal adenocarcinoma: Prognostic indicators of advanced disease

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262439
Author(s):  
Deirdré Kruger ◽  
Nicola Lahoud ◽  
Yandiswa Y. Yako ◽  
John Devar ◽  
Martin Smith
Keyword(s):  
Risk Factors ◽  
Platelet Count ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumour Marker ◽  
Tnm Staging ◽  
Prognostic Indicators ◽  
Ductal Adenocarcinoma ◽  
P Value ◽  
Gm Csf ◽  
Presenting Symptoms

Background/Objectives Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with high metastatic risk. Prognosis remains poor even after resection. Previously our group identified biomarkers that improved diagnostic accuracy in PDAC beyond the established diagnostic tumour marker, CA19-9. Risk factors, symptoms and circulating biomarkers associated with a PDAC diagnosis may differ from those that alter disease progression and metastasis. This study aimed at assessing the risk factors, presenting symptoms and potential prognostic biomarkers in PDAC and determine their relationship with PDAC stage and/or metastatic status. Methods Seventy-two PDAC patients with imaging available for TNM staging at presentation were enrolled following informed consent. Demographic and clinical data were captured. Blood was collected and 38 cytokines/angiogenic factors measured. Nonparametric association tests, univariate and multivariate logistic regression were performed using STATA version 14.2. A p-value≤0.05 was considered significant and odds ratios reported for effect size. Results Most risk factors and symptoms did not differ across the stages of cancer. Although male gender and smoking are risk factors for PDAC, the majority of study patients with metastatic PDAC were non-smoking females. In addition to CA19-9, the platelet count (p<0.01), IL-15 (p = 0.02) and GM-CSF (p<0.01) were significant, independent negative predictors of metastatic PDAC. Moreover, using specific cut-off values in a combined panel, the odds in a patient with all three biomarker levels below the cut-offs is 21 times more likely to have metastatic PDAC (p<0.0001). Conclusions Platelet count, IL-15 and GM-CSF are potential prognostic indicators of metastatic disease in PDAC patients from our local South African population.

scholarly journals Which Factors Are Associated with Positive Resection Margin in Pancreatic Ductal Adenocarcinoma for different surgical procedures? Results Based on a Standard Pathological Evaluation System-Retrospective Cohort Study

2021 ◽  
Author(s):  
Bo Li ◽  
Shiwei Guo ◽  
Xiaohan Shi ◽  
Chenming Ni ◽  
Suizhi Gao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Resection Margin ◽  
Tnm Staging ◽  
Ductal Adenocarcinoma ◽  
Pathological Examination ◽  
Multivariate Logistic Regression ◽  
R1 Resection ◽  
Independent Risk Factors

Abstract Background/Objectives: The present study identified the independent risk factors of R1 resection in pancreaticoduodenectomy (PD) and distal pancreatosplenectomy (DP) for patients with pancreatic ductal adenocarcinoma (PDAC).Methods：Consecutive patients who were operated from 1st December 2017 to 30th December 2018 with curative intent were analyzed retrospectively. A standardized pathological examination with digital whole-mount slide images (DWMSIs) was utilized for the resection margin status. R1 was defined as microscopic tumor infiltration within 1 mm to the resection margin. The potential risk factors of R1 resection for PD and DP were analyzed separately by univariate and multivariate logistic regression analyses. Results：For the 240 patients who underwent PD, and the 146 patients who underwent DP, the R1 resection rates were 30.8% and 35.6 %, respectively. Univariate analysis on risk factors of R1 resection for PD were tumor location, absence of tumor necrosis, N staging, and TNM staging; while those for DP were perineural invasion, T staging, and TNM staging. Multivariate logistic regression analysis showed the location of tumor in the neck and uncinate process, and N1/2 staging were independent risk factors of R1 resection for PD; while those for DP were T3/4 staging. Conclusions：The clarification of the risk factors of R1 resection might clearly make surgeons take better decisions on surgical strategies for different surgical precedures in patients with PDAC.

scholarly journals Moderate alcohol intake promotes pancreatic ductal adenocarcinoma development in mice expressing oncogenic Kras

2020 ◽  
Vol 318 (2) ◽  
pp. G265-G276
Author(s):  
Kinji Asahina ◽  
Steven Balog ◽  
Edward Hwang ◽  
Eugene Moon ◽  
Emily Wan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Alcohol Drinking ◽  
Calcium Binding ◽  
Alcohol Intake ◽  
Western Diet ◽  
Mutant Mice ◽  
Ductal Adenocarcinoma ◽  
Moderate Alcohol Intake

Kras mutations are associated with pancreatic ductal adenocarcinoma (PDAC). Although tobacco smoking, pancreatitis, and obesity are known environmental risk factors for PDAC, the contribution of moderate alcohol intake to PDAC remains elusive. In the present study, we tested whether a combination of risk factors or moderate alcohol intake induces PDAC development in mice. Control Pdx1Cre and Pdx1Cre;LSL- KrasG12D mutant mice were fed a Western alcohol diet containing high levels of cholesterol and saturated fat, 3.5% alcohol, and lipopolysaccharide for 5 mo. In addition, mice were treated with cerulein, for induction of pancreatitis, and nicotine every month. Treatment with all of these risk factors promoted development of advanced pancreatic neoplasia and PDAC in the Pdx1Cre;LSL- KrasG12D mice but not in the control Pdx1Cre mice. Moderate alcohol intake or Western diet feeding also significantly promoted advanced neoplasia and PDAC development in Pdx1Cre;LSL- KrasG12D mice compared with mice fed a regular chow. Alcohol, but not Western diet, increased tumor development in the liver in the Pdx1Cre;LSL- KrasG12D mice, but its origin remained elusive due to leakiness of Pdx1Cre in hepatocytes. RNA-seq analysis revealed that alcohol feeding increases expression of markers for tumors ( Epcam, Krt19, Prom1, Wt1, and Wwtr1), stroma ( Dcn, Fn1, and Tnc), and cytokines ( Tgfb1 and Tnf) and decreases expression of Fgf21 and Il6 in the pancreatic tumor tissues. Immunostaining showed heterogeneous expression of nephronectin, S100 calcium-binding protein A6, and vascular cell adhesion molecule 1 in pancreatic tumors surrounded by podoplanin-positive stromal cells. Our data indicate that moderate alcohol drinking is a risk factor for development of PDAC. NEW & NOTEWORTHY Heavy alcohol intake has been suspected to be a risk factor of pancreatic ductal adenocarcinoma (PDAC) in humans. However, the contribution of moderate alcohol intake to PDAC development remains elusive. In the present study, we experimentally show that moderate alcohol feeding significantly induces advanced stages of pancreatic intraepithelial neoplasia development and invasive PDAC in Pdx1Cre;LSL- KrasG12D mutant mice. Our data indicate that moderate alcohol drinking is a risk factor for PDAC.

scholarly journals A novel 20-gene prognostic score in pancreatic adenocarcinoma

2019 ◽  
Author(s):  
Secil Demirkol Canli ◽  
Ege Dedeoglu ◽  
Muhammad Waqas Akbar ◽  
Baris Kucukkaraduman ◽  
Murat Isbilen ◽  
...  
Keyword(s):  
Immune Cell ◽  
Prognostic Score ◽  
Performance Status ◽  
Cyclin B1 ◽  
Pancreatic Tissue ◽  
Tnm Staging ◽  
Prognostic Indicators ◽  
Ductal Adenocarcinoma ◽  
Primary Tumors ◽  
And Performance

Abstract Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Known risk factors for this disease are currently insufficient in predicting mortality. The only FDA approved prognostic biomarker for PDAC patients is CA19-9. This, along with AJCC TNM staging and performance status, are considered important prognostic indicators in clinical practice. In order to better prognosticate patients with PDAC, we identified a novel panel of genes by utilizing publically available microarray and RNAseq data of PDAC tumors from GEO and TCGA. Expression of 20 genes were significantly associated with overall survival in four datasets and event-free survival in TCGA. A score generated based on the expression matrix of these genes could be validated in two independent cohorts. We find that this “Pancreatic cancer prognostic score 20 – PPS20” is dramatically elevated in metastatic tissue compared to primary tumor, and is higher in primary tumors compared to normal pancreatic tissue. Transcriptomic analyses show that tumors with low PPS20 have overall more immune cell infiltration and a higher CD8 T cell/Treg ratio when compared to those with high PPS20. Analyses of proteomic data from TCGA PAAD indicated higher levels of Cyclin B1, RAD51, EGFR and a lower E-cadherin/Fibronectin ratio in tumors with high PPS20. The PPS20 score defines not only prognostic and biological sub-groups but can predict response to targeted therapy options as well. Overall, PPS20 is a stronger and more robust transcriptomic signature when compared to similar, previously published gene lists.

scholarly journals Pancreatic ductal adenocarcinoma from a surgical perspective

2021 ◽  
Vol 6 (2) ◽  
Keyword(s):  
Risk Factors ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Adjuvant Treatment ◽  
Locally Advanced ◽  
Historical Background ◽  
Ductal Adenocarcinoma ◽  
Curative Intent ◽  
Pancreatic Cancers ◽  
Operative Care ◽  
Histological Staging

Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of pancreatic cancers. Whilst most patients present with locally advanced or metastatic disease, a minority are candidates for curative-intent resection. This review covers the aspects of PDAC which are relevant to the surgeon. Firstly, an up-to-date overview of epidemiology, risk factors and pathogenesis are provided. Secondly, presentation, diagnosis and staging are covered, including a summary of the most recent staging guidelines. The review will then focus on the historical background of the pancreatico-duodenectomy (PD), the modern procedure and post-operative care. Finally, short sections provide the reader with an update on histological staging and adjuvant treatment.

scholarly journals Liver Metastases in Newly Diagnosed Pancreatic Ductal Adenocarcinoma: A Population Based Analysis

2020 ◽  
Author(s):  
Guoyi Wu ◽  
Xiaoben Pan ◽  
Baohua Wang ◽  
Xiaolei Zhu ◽  
Jing Wu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Metastases ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Size ◽  
Cox Regression ◽  
Population Based ◽  
The Body ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Factors Associated

Abstract Background Estimates of the incidence and prognosis of developing liver metastases at the pancreatic ductal adenocarcinoma (PDAC) diagnosis are lacking.Methods In this study, we analyzed the association of liver metastases and the PDAC patients outcome. The risk factors associated with liver metastases in PDAC patients were analyzed using multivariable logistic regression analysis. The overall survival (OS) was estimated using Kaplan-Meier curves and log-rank test. Cox regression was performed to identify factors associated with OS.Results Patients with primary PDAC in the tail of the pancreas had a higher incidence of liver metastases (62.2%) than those with PDAC in the head (28.6%). Female gender, younger age, primary PDAC in the body or tail of the pancreas, and larger primary PDAC tumor size were positively associated with the occurrence of liver metastases. The median survival of patients with liver metastases was significantly shorter than that of patients without liver metastases. Older age, unmarried status, primary PDAC in the tail of the pancreas, and tumor size ≥4 cm were risk factors for OS in the liver metastases cohort.Conclusions Population-based estimates of the incidence and prognosis of PDAC with liver metastases may help decide whether diffusion-weighted magnetic resonance imaging should be performed in patients with primary PDAC in the tail or body of the pancreas. The location of primary PDAC should be considered during the diagnosis and treatment of primary PDAC.

scholarly journals 1553P Incidence of and risk factors for venous thromboembolism in patients with pancreatic ductal adenocarcinoma

2020 ◽  
Vol 31 ◽  
pp. S950
Author(s):  
B. Mathilde ◽  
K. Maoui ◽  
M. Fovet ◽  
B. Le Roy ◽  
X. Roblin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma
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