Multiplex gene expression profile in inflamed mucosa of patients with Crohn’s disease ileal localization: A pilot study

BACKGROUND Crohn’s disease (CD) is a complex disorder resulting from the interaction of genetic,environmental,and microbial factors.The pathogenic process may potentially affect any segment of the gastrointestinal tract,but a selective location in the terminal ileum was reported in 50% of patients.AIM To characterize clinical sub-phenotypes (colonic and/or ileal) within the same disease,in order to identify new therapeutic targets.METHODS 14 consecutive patients undergoing surgery for ileal CD were recruited for this study.Peripheral blood samples from each patient were collected and the main polymorphisms of the gene Card15/Nod2 (R702W,G908R,and 1007fs) were analyzed in each sample.In addition,tissue samples were taken from both the tract affected by CD and from the apparently healthy and disease-free margins (internal controls).We used a multiplex gene assay in specimens obtained from patients with ileal localization of CD to evaluate the simultaneous expression of 24 genes involved in the pathogenesis of the disease.We also processed surgery gut samples with routine light microscopy (LM) and transmission electron microscopy (TEM) techniques to evaluate their structural and ultrastructural features.RESULTS We found a significant increase of Th17 (IL17A and IL17F,IL 23R and CCR6) and Th1 (IFN-γ) gene expression in inflamed mucosa compared to non-inflamed sites of 14 CD patients.DEFB4 and HAMP,two genes coding for antimicrobial peptides,were also strongly activated in inflamed ileal mucosa,suggesting the overwhelming stimulation of epithelial cells by commensal microbiota.IFN-γ and CCR6 were more expressed in inflamed mucosa of CD patients with ileal localization compared with patients with colonic localization suggesting a more aggressive inflammation process in this site.Morphological analysis of the epithelial lining of Lieberkün crypts disclosed enhanced release activity from goblet mucocytes,whereas the lamina propria contained numerous cells pertaining to various lines.CONCLUSION We observed that the expression of ileal genes related to Th1 and Th17 activity is strongly activated as well as the expression of genes involved in microbiota regulation.

Vascular Invasion, Satellite Nodules and Absence of Tumor Capsule Strongly Correlate with Disease-Free Survival and Long-Term Outcome in Patients Resected for Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most common cancer in the world. Liver resection (LR) is the most used therapy in well compensated liver cirrhosis and maybe used as a first-line treatment. Aim of the study is to evaluate survival rates in patients who underwent LR for HCC and to identify risk factors able to influence the prognosis. Material/Method: A retrospective study was carried out in 115 patients whounderwent LR for HCC. We evaluated overall and disease-free survival rates at 1, 3 and 5years (y) and a series of variables included: type of resection, clamping, blood loss, transfusions, tumor size, presence of capsule, satellite nodules and vascular invasion. Results: The 1-, 3-, 5-y survival rates were 90.2%, 67% and 52.7%, and disease-free survival rates were 75.3%, 44.7% and 28.4%, respectively. We have found presence/ absence of capsulated tumor (p = 0.05), satellite nodules (p = 0.004) and vascular invasion (p = 0.001) as factors able to influence the overall survival and the disease-free survival (p = 0.04 for capsulated tumor, p = 0.01 for satellite nodules and p = 0.006 for vascular invasion). Conclusion: LR is the best therapeutic option for HCC when liver transplantation is contraindicated, with good survival rates. Presence of capsule, satellite nodules and vascular invasion are the most important factors able to influence the prognosis.