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

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.

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Pancreatic ductal adenocarcinoma from a surgical perspective

International Journal of Cancer Research & Therapy ◽

10.33140/ijcrt.06.02.13 ◽

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.

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

10.21203/rs.2.20788/v1 ◽

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.

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