Endoscopic Ultrasound Finding of Diffuse Echogenicity in the Pancreas, Is It Relevant?

BACKGROUND/OBJECTIVES: Diffuse echogenicity of the pancreas, a commonly discovered finding on endoscopic ultrasound (EUS), is often of undetermined significance. The goal of this study was to characterize the clinical picture and pancreatic function in patients who incidentally present with this endosonographic finding. METHODS: This was a case-control study comparing consecutive adult patients with diffuse echogenicity of the pancreas found on EUS to those who did not have known pancreas disease. Demographic and clinical data were extracted from the electronic medical record. The primary endpoint was exocrine pancreatic insufficiency (EPI) defined as fecal elastase (FE-1) < 200 µg/g. RESULTS: A total of 166 patients were included in this study. There were 89 patients who had diffuse echogenicity of the pancreas on EUS and FE-1 testing. There were 77 control patients with chronic diarrhea who did not have known pancreas disease but did have FE-1 testing. EPI was significantly more likely in the fatty pancreas group compared to the control group (47% vs 6%, p < 0.001). There was also a significantly greater proportion of smokers in the fatty pancreas group compared to the control group (42% vs 17%, p = 0.002). There were no other differences in baseline characteristics between the two groups, including prevalence of chronic pancreatitis by Rosemont classification. On multiple logistic regression analysis controlling for multiple variables, smoking (OR 2.26, 95% CI 1.15-4.43) and NAFLD (OR 3.99, 95% CI 1.09-14.70) had significant associations with EPI. CONCLUSIONS: This study found a significantly greater amount of patients who had diffuse echogenicity of the pancreas on EUS to also have EPI. This is compared to a control group of patients without known pancreas disease. This prevalence was found in the absence of a significant association with chronic pancreatitis on EUS based on Rosemont classification. Future controlled studies are required to further investigate this relationship.

Secondary Causes of Hypertriglyceridemia are Prevalent Among Patients Presenting With Hypertriglyceridemia Induced Acute Pancreatitis.

BACKGROUND: Hypertriglyceridemia induced acute pancreatitis (HIAP) is the third common cause of acute pancreatitis. HIAP can result in recurrent attacks of severe AP with significant morbidity and mortality. Hypertriglyceridemia (HTG) could be primary or secondary. Although genetic causes of HTG are well studied, the prevalence of secondary causes of HTG in patients presenting with HIAP is not well characterized. This study aimed to identify the prevalence of risk factors for secondary hypertriglyceridemia among patients presenting with HIAP in a tertiary referral center in a large metropolitan area. METHODS: This is a retrospective analysis of all patients admitted with AP from August 2012-2017. A subgroup of patients with triglycerides >880 mg/dl were included for analysis. Secondary causes of HTG were identified. Secondary analysis evaluating the severity of pancreatitis was performed. RESULTS: There were 3,746 patients admitted for AP of which 57 patients had AP and HTG. Of these 57 patients, 70.2% had history of diabetes mellitus, 26.3% had history of heavy alcohol use, 22.8% had chronic kidney disease, 47.3% with obesity, and 21.1% with metabolic syndrome. Two patients were classified as unexplained HTG. Secondary analysis showed a total of 45.6% of patients requiring ICU admission. 26.3% of patients with severe inflammatory pancreatitis and 17.5% of patients with severe necrotizing pancreatitis. CONCLUSIONS: In our cohort of HIAP, 55 out of 57 patients had secondary causes for HTG. Identifying secondary causes of HTG during acute hospitalization is important to tailor outpatient treatment in order to prevent future admissions with HIAP.

Association between Toxoplasma gondii infection and coronary atherosclerosis.

BACKGROUND: Toxoplasma gondii is a worldwide protozoon that can infect all nucleated vertebrate cells. Little information is available about the association between T. gondii infection and coronary atherosclerosis. METHODS: A total of 320 cases were enrolled (160 patients with coronary atherosclerosis and 160 non-atherosclerotic individuals). Blood samples were collected to measure anti-T. gondii immunoglobulin G (IgG) antibodies using enzyme-linked immunosorbent assay (ELISA) and serum lipid profile. Coronary angiogram was also performed. RESULTS: The seroprevalence of anti-Toxoplasma antibodies in atherosclerotic and non-atherosclerotic individuals was 63.1% and 46.2%, respectively, with higher levels of anti-T. gondii IgG in atherosclerotic patients. Consumption of contaminated water, unwashed fruits and vegetables and raw meat and contact with soil were significant risk factors for Toxoplasma infection. Significant differences were detected in serum levels of low-density lipoproteins, triglycerides and cholesterol between both groups. Positive correlations were detected between ELISA titres and serum levels of low-density lipoproteins, triglycerides and cholesterol, disease severity and the number of affected vessels. Male gender and contact with soil had a significant association with positive T. gondii serology in atherosclerotic patients. CONCLUSIONS: Patients with coronary atherosclerosis have a high prevalence of T. gondii infection. More studies are crucial to elucidate the mechanisms underlying the effects of chronic toxoplasmosis on coronary atherosclerosis.

SETDB1 Inhibits p53-Mediated Apoptosis and Is Required for Formation of Pancreatic Ductal Adenocarcinomas in Mice.

BACKGROUND & AIMS: SETDB1, a histone methyltransferase that trimethylates histone H3 on lysine 9, promotes development of several tumor types. We investigated whether SETDB1 contributes to development of pancreatic ductal adenocarcinoma (PDAC). METHODS: We performed studies with Ptf1aCre; KrasG12D; Setdb1f/f, Ptf1aCre; KrasG12D; Trp53f/+; Setdb1f/f, and Ptf1aCre; KrasG12D; Trp53f/f; Setdb1f/f mice to investigate the effects of disruption of Setdb1 in mice with activated KRAS-induced pancreatic tumorigenesis, with heterozygous or homozygous disruption of Trp53. We performed microarray analyses of whole-pancreas tissues from Ptf1aCre; KrasG12D; Setdb1f/f, and Ptf1aCre; KrasG12D mice and compared their gene expression patterns. Chromatin immunoprecipitation assays were performed using acinar cells isolated from pancreata with and without disruption of Setdb1. We used human PDAC cells for SETDB1 knockdown and inhibitor experiments. RESULTS: Loss of SETDB1 from pancreas accelerated formation of premalignant lesions in mice with pancreata that express activated KRAS. Microarray analysis revealed up-regulated expression of genes in the apoptotic pathway and genes regulated by p53 in SETDB1-deficient pancreata. Deletion of Setdb1 from pancreas prevented formation of PDACs, concomitant with increased apoptosis and up-regulated expression of Trp53 in mice heterozygous for disruption of Trp53. In contrast, pancreata of mice with homozygous disruption of Trp53 had no increased apoptosis, and PDACs developed. Chromatin immunoprecipitation revealed that SETDB1 bound to the Trp53 promoter to regulate its expression. Expression of an inactivated form of SETDB1 in human PDAC cells with wild-type TP53 resulted in TP53-induced apoptosis. CONCLUSIONS: We found that the histone methyltransferase SETDB1 is required for development of PDACs, induced by activated KRAS, in mice. SETDB1 inhibits apoptosis by regulating expression of p53. SETDB1 might be a therapeutic target for PDACs that retain p53 function.