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Objectives: We followed The Cancer Genome Atlas (TCGA) grouping criteria and conducted a clinicopathological cohort study in a unique patient population to gain insight into the pathobiology of esophageal adenocarcinoma (EAC) and adenocarcinoma of the gastroesophageal junction (AGEJ). Methods: We studied and statistically compared the clinicopathological and prognostic features of both cancers in 303 consecutive patients treated at the Veterans Affairs Boston Healthcare System over a 20‐year period using uniform criteria and standardized routines. Results: Over 99% of patients were white men with a mean age of 69.1 years and an average body mass index (BMI) of 28.0 kg/m2. No significant differences were detected in age, gender, ethnicity, BMI, and history of tobacco abuse between the two groups. Compared to AGEJ patients, a significantly higher proportion of EAC patients had gastroesophageal reflux disease, long‐segment Barrett's esophagus, common adenocarcinoma type, smaller tumor size, better differentiation, more stages I or II but fewer stages III or IV diseases, scarcer lymph node invasion, fewer distant metastases, and better overall, disease‐free, and relapse‐free survival. The 5‐year overall survival rate was significantly higher in EAC patients than in AGEJ patients (41.3% vs 17.2%, P < 0.001). This improved survival among EAC patients remained significant after censoring all cases detected during endoscopic surveillance, suggesting different pathogenesis mechanisms between EAC and AGEJ. Conclusions: EAC patients showed significantly better outcomes than AGEJ patients. Our results require validation in other patient populations. [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose We sought to determine the incidence and risks for severe thrombocytopenia (platelets < 50 000/μL) in United States Veteran patients treated with pegylated interferon (PEG-IFN) plus ribavirin for hepatitis C virus-positive (HCV) chronic liver disease (CLD). Methods Using a retrospective, observational cohort study design to analyze databases from the New England Veterans Healthcare System, we identified 979 patients diagnosed with HCV-positive CLD treated solely with PEG-IFN plus ribavirin. The cohort was stratified by pre-treatment platelet counts of 50 000-100 000/μL ( N = 90), >100 000-150 000/μL ( N = 162), and >150000μL ( N = 727). The cumulative incidence of severe thrombocytopenia and major bleeding events were determined for each baseline platelet group for 48 weeks following treatment initiation. Multivariable Cox regression was used to identify risk factors for incident severe thrombocytopenia. Results Overall, severe thrombocytopenia occurred in 6.1% ( N = 60), but in 41.1% of patients with pre-treatment platelet counts 50 000-100 000/μL compared with 11.7% ( p < 0.001) and 0.55% ( p < 0.001) in the two higher pre-treatment platelet groups. Most episodes occurred within the first 12 weeks of treatment. Median nadir count for these 60 patients was 35 000/μL (inter-quartile range 28 000, 44 000). Baseline platelet counts of 50 000-100 000/μL [adjusted hazard ratio (HR) = 3.81; 95%CI = 2.07-7.00] and hemoglobin <10 g/dL (adjusted HR = 3.39; 95%CI = 1.45-7.960) associated with severe thrombocytopenia. Major bleeding events during the 48-week observation period were rare ( N = 5, 0.51%). Conclusions The incidence of severe thrombocytopenia in a large, observational cohort of veteran patients with HCV CLD treated with PEG-IFN plus ribavirin was 6.1%. Low pre-treatment platelet counts and hemoglobin levels associated with early, incident severe thrombocytopenia. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The G protein-coupled human gastrin-releasing peptide receptor (hGRP-R) is frequently found aberrantly expressed in human cancers of the colon, stomach, and lung, and its ligand-specific activation has been implicated in cell proliferation and differentiation. Here, we demonstrated hGRP-R activation stimulated sustained cyclic AMP response element binding protein (CREB) phosphorylation and transactivation in duodenal cancer cells through a protein kinase C and partially p38 mitogen-activated protein kinase-dependent pathway. In contrast, intracellular calcium, ERK1/2, protein kinase A, and PI3 kinase were not involved. This novel signaling mechanism might be of importance for regulation of CREB-dependent gene expression in human cancer expressing functional hGRP-R. [Copyright &y& Elsevier]