Clinical practice lacks biomarkers to predict the severity of acute pancreatitis (AP). We studied if intracellular signaling of circulating leukocytes could predict persistent organ dysfunction (OD) and secondary infections in AP.

A venous blood sample was taken from 174 patients with AP 72 hours or less from onset of symptoms and 31 healthy controls. Phosphorylation levels (p) of appropriately stimulated signal transducer and activator of transcription 1 (STAT1), STAT6, nuclear factor-κB (NF-κB), Akt, and nonstimulated STAT3 in monocytes, neutrophils, and lymphocytes was measured using phosphospecific flow cytometry.

The patients showed higher pSTAT3 and lower pSTAT1, pSTAT6, pNF-κB, and pAkt than healthy controls. pSTAT3 in all leukocyte subtypes studied increased, and pSTAT1 in monocytes and T cells decreased in an AP severity-wise manner. In patients without OD at sampling, high pSTAT3 in monocytes and T lymphocytes were associated with development of persistent OD. In patients with OD, low interleukin-4-stimulated pSTAT6 in monocytes and neutrophils and Escherichia coli-stimulated pNF-κB in neutrophils predicted OD persistence. click here High pSTAT3 in monocytes, CD8+ T cells, and neutrophils; low pSTAT1 in monocytes and T cells; and low pNF-κB in lymphocytes predicted secondary infections.

Leukocyte STAT3, STAT1, STAT6, and NF-κΒ phosphorylations are potential predictors of AP severity.

Leukocyte STAT3, STAT1, STAT6, and NF-κΒ phosphorylations are potential predictors of AP severity.

This study aimed to quantify the prevalence of venous thromboembolic (VTE) events in patients with pancreatitis requiring hospitalization and its impact on outcomes.

Adult patients admitted from 2011 to 2018 for pancreatitis were identified. Every admission for pancreatitis in the first year after diagnosis was evaluated for a VTE (pulmonary embolism, deep vein thrombosis, or mesenteric vessel thrombosis) within 30 days of discharge. Characteristics of patients who developed a thromboembolic event were compared with those who did not.

There were 4613 patients with pancreatitis identified, 301 of whom developed a VTE (6.5%). Patients who developed a VTE were more likely to be male (P < 0.01), older (P = 0.03), and have an underlying coagulopathy (P < 0.01). Those with VTEs were more likely to die (27% vs 13%, P < 0.01), have more readmissions for pancreatitis (1.7 vs 1.3, P < 0.01), longer length of stay (16 vs 5.5 days, P < 0.01), and be discharged to acute or long-term rehabilitation rather than home (P < 0.01).

Acute pancreatitis requiring hospitalization is associated with high risk of VTE in the first year after diagnosis. Thromboembolic disease is associated with worse morbidity and mortality.

Acute pancreatitis requiring hospitalization is associated with high risk of VTE in the first year after diagnosis. Thromboembolic disease is associated with worse morbidity and mortality.

This study aimed to investigate the effect and mechanism of hypoxia on pancreatic cancer (PC) cell dedifferentiation and tumorigenic potential.

Inhibition of hypoxia-inducible factor 1α (HIF-1α) and overexpression of Notch1 in PC HS766T cell lines were by lentiviral transfection. The expression of stem cell-specific markers C-X-C motif chemokine receptor 4, CD44, and Nestin was detected by immunofluorescence and Western blot assays. Cell invasion capacity was examined by Transwell assay. Tumorigenic potential was measured in an in situ tumor transplantation experiment. The expression of HIF-1α, Notch signals, and apoptosis signals was examined by Western blot assay.

Hypoxia promoted PC cells to dedifferentiate into stem-like cells by upregulating HIF-1α and activating Notch signals. Silencing of HIF-1α significantly repressed cell dedifferentiation and invasion, whereas overexpression of Notch1 reversed the effect of HIF-1α repression. In situ tumor transplantation experiment further confirmed that hypoxia promoted tumorigenic ability through upregulating HIF-1α. Moreover, the expression of HIF-1α and Notch1 was significantly increased in human PC tissues, and high expression of HIF-1α was correlated with poor survival rate.

Hypoxia promoted PC cell dedifferentiation to stem-like cell phenotypes with high tumorigenic potential by activating HIF-1α/Notch signaling pathway, indicating a novel role in regulating PC progression.

Hypoxia promoted PC cell dedifferentiation to stem-like cell phenotypes with high tumorigenic potential by activating HIF-1α/Notch signaling pathway, indicating a novel role in regulating PC progression.

The aim of this study was to assess sex-based differences in prognosis of a contemporary cohort of gastroenteropancreatic-neuroendocrine neoplasm (GEP-NEN) patients.

Surveillance, Epidemiology, and End Results database was accessed, and cases with GEP-NENs were selected. Rates of GEP-NEN diagnosis from 1975 to 2016 for both male patients and female patients were reviewed. Survival outcomes of GEP-NEN patients diagnosed from 2010 to 2014 were determined through Kaplan-Meier estimates and multivariable Cox regression analysis. Overall survival analyses were stratified by stage and histology.

A total of 20,836 GEP-NEN patients were diagnosed from 2010 to 2014, and they were included in the current analysis. These include 10,336 male patients and 10,500 female patients. Annual percent change for the age-adjusted rate for GEP-NENs in the United States (1975-2016) is 5.0 (95% confidence interval [CI], 4.8-5.2). When stratified by sex, annual percent change for male patients was 4.8 (95% CI, 4.6-5.1), whereas for female patients, it was 5.0 (95% CI, 4.8-5.3). Female patients have better overall survival compared with male patients among all substrata of patients (according to stage, histology, and differentiation) (P for all comparisons <0.01).

Female sex seems to be associated with better overall survival among patients with GEP-NENs. It is unclear if this is the result of differences in noncancer mortality or is the result of inherent biological differences.

Female sex seems to be associated with better overall survival among patients with GEP-NENs. It is unclear if this is the result of differences in noncancer mortality or is the result of inherent biological differences.