Pancreatic Fat Infiltration Is Associated with a Higher Risk of Pancreatic Ductal Adenocarcinoma

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor survival rate, partly due to delayed diagnosis. Identifying high-risk individuals could lead to early detection and improve survival. A number of risk factors such as alcohol consumption and metabolic syndrome are associated with fatty infiltration of the pancreas. Experimental models show that a fatty pancreas promotes tissue inflammation and fibrosis, which could promote PDAC. Methods: We conducted a case-control study in a single-university tertiary hospital. Sixty-eight PDAC cases with recent non-contrast computed tomography (CT) and 235 controls were studied. The controls had no history of malignancy and underwent CT colonography for cancer screening in the same period. Pancreatic fat was estimated by calculating pancreatic (P) attenuation, corrected to splenic (S) attenuation, measured in three 1.0-cm² regions of the pancreas. The P.S100 value calculated was used to estimate fatty infiltration of the pancreas (FIP), with a lower P.S100 representing a higher FIP. Results: The PDAC patients had a lower BMI and a higher rate of type 2 diabetes mellitus. The P.S100 was lower in cases than in controls (86.452 vs. 92.414, p = 4.016e-06), suggesting that FIP is higher with PDAC. The risk of developing PDAC steadily increased significantly for the quartiles with a higher FIP compared to the low FIP quartile. No correlation between BMI and FIP (r = –0.1031179; 95% confidence interval [CI] –0.22267106 to 0.01949092) was found. Adjusting for confounders (age, sex, BMI, and DM), the risk of developing PDAC according to the FIP was estimated to be 3.75 (95% CI 1.9234408–7.993337; p = 0.000171). FIP was stable before and after the diagnosis of PDAC in 9 cases with prior CT scans when no pancreatic tumor was identifiable. Conclusion: Fatty pancreas is associated with an increased risk of pancreatic cancer. Once confirmed in larger-scale studies, these findings could help to identify at-risk individuals, particularly in high-risk groups such as chronic alcohol consumers

Focal Parenchymal Atrophy of the Pancreas Is Frequently Observed on Pre-Diagnostic Computed Tomography in Patients with Pancreatic Cancer: A Case-Control Study

“…This is an important topic for future research because fat replacement might result from, and be a predisposing factor for, pancreatic carcinogenesis. Pancreatic fat infiltration is involved in the development of PDAC [ 35 ] and is associated with a higher risk of PDAC [ 36 ].…”

Uniting epidemiology and experimental models: pancreatic steatosis and pancreatic cancer

“…32 There is no difference in degree of pancreatic steatosis before and after PDAC diagnosis on CT scans, suggesting that pancreatic steatosis, rather than resulting from cancerassociated inflammation, is a carcinogenic risk factor. 34 Furthermore, pancreatic fat content is significantly associated with cancer progression on MRI in low-risk branch duct IPMN. 30 Increased severity of pancreatic steatosis further correlates with increased risk of pancreatic cancer.…”

Type 2 Diabetes Mellitus Intersects With Pancreatic Cancer Diagnosis and Development

“…Inflammation may increase the risk of PC in patients with T2DM. In patients with T2DM, insulin resistance and hyperinsulinemia often occur, accompanied by abundant adipocytes and a large amount of inflammatory cell infiltrating the pancreas tissue (54)(55)(56). The high glucose and fat diet may accelerate the inflammatory response by increasing oxidative stress and activating transcription factors, such as nuclear factor kappa B (NF-kB) and activator protein 1, which leads to the development of genomic aberration and carcinogenesis (57)(58)(59).…”