Laparoscopic intracorporeal rectus aponeuroplasty (LIRA) technique versus intraperitoneal onlay mesh (IPOM plus) for ventral hernia repair: a comparative analysis.

PURPOSE: Primary aim of this study is to compare the postoperative outcomes of the laparoscopic intracorporeal rectus aponeuroplasty (LIRA) technique to the intraperitoneal onlay mesh closing the defect (IPOM plus), in terms of recurrence and bulging rates at one-year follow-up; secondary aim is to compare the postoperative complications, seroma and pain at 30 days and one-year after surgery. METHODS: Patients with midline ventral hernia of 4-10 cm in width were included. Computed tomography scan was performed before, 1 and 12 months after surgery. Pain was evaluated using the visual analogue scale. RESULTS: Forty-five and forty-seven consecutive patients underwent LIRA and IPOM plus, respectively. Preoperatively, smoke habits and chronic obstructive pulmonary disease rates were statistically significantly higher in the LIRA group (p = 0.0001 and p = 0.012, respectively). Two bulgings (4.4%) occurred in the LIRA group, while in the IPOM plus group occurred 10 bulgings (21.3%) and three recurrences (6.4%) (p = 0.017 and p = 0.085, respectively). Postoperatively, seven (15.6%, Clavien-Dindo I) and four complications (8.5%, two Clavien-Dindo I, two Clavien-Dindo III-b) occurred in the LIRA and in the IPOM plus group, respectively (p = 0.298). One month after surgery, clinical seroma, occurred in five (11.1%) and eight patients (17%) in the LIRA and in the IPOM plus group, respectively (p = 0.416). During follow-up, pain reduction occurred, without statistically significant differences. CONCLUSIONS: In this study, even if we analysed a small series, LIRA showed lower bulging and recurrence rates in comparison to IPOM plus at one-year follow-up. Further prospective studies, with a large sample of patients and longer follow-up are required to draw definitive conclusions.

Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells.

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.