Long-term effectiveness of Radiofrequency Ablation for solitary small Hepatocellular Carcinoma: A retrospective analysis of 363 patients

BackgroundRadiofrequency Ablation is the most widely performed percutaneous treatment for Hepatocellular Carcinoma. This multicentre study was aimed at assessing the complication, overall survival and disease-free survival rates in cirrhotic patients with single Hepatocellular Carcinoma nodule ≤3 cm undergoing Radiofrequency Ablation.MethodsData of 365 patients (59% males; mean age 67 ± 8 years), Child–Pugh A/B, with single Hepatocellular Carcinoma nodule ≤3 cm (tumours >2–3 cm = 127/236), showing complete necrosis after Radiofrequency Ablation between 1998 and 2010 in 7 Italian Centers were retrospectively reviewed. Complication, overall survival and disease-free survival rates were analyzed as main clinical end-points.ResultsMajor complications were observed in 8 patients (2.2%) and minor complications in 23 patients (6.3%). The 3-, and 5-year overall survival rates were 80% and 64%. One hundred and seven patients (29.5%) died, being 41 deaths (38.3%) Hepatocellular Carcinoma-related. At multivariate analysis only age (p = 0.04; OR 2.29), ascites (p < 0.001; OR 3.74) and Child–Pugh class ≥B8 (p = 0.003; OR 2.42) were confirmed as independent predictors for overall survival. The disease-free survival rates at 3- and 5-year were 50%, and 41.8%.ConclusionsRadiofrequency Ablation is an effective and safe tool for the treatment of single Hepatocellular Carcinoma ≤3 cm providing excellent 5-year overall survival and disease-free survival rates. Patient's age and liver status appeared as main determinants of outcome.     

Phospholipase inhibition and prostacyclin generation by gastric muscularis and mucosa layers

The effects of drugs which interfere with arachidonate metabolism as well as glucocorticoid-induced anti-phospholipase proteins (APP) have been studied on PGI₂ generation by rat stomach tissue. Indomethacin inhibited PGI₂ generation bothin vitro andex vivo while dexamethasone was ineffective in both instances. APP inhibited PGI₂ generationin vitro. The results are discussed in the light of the possible mode of action of glucocorticoids.Prostacyclin (PGI₂) is the major cyclo oxygenase metabolite in the rat gastric mucosa [1] and exerts gastroprotective actions [2]. Therefore a correlation between the inhibition of PGI₂ synthesis and the induction of gastric damage has been suggested for the non-steroidal anti-inflammatory drugs [3].Glucocorticoids inhibit phospholipase A₂ (PLA₂) by inducing in the target cells the synthesis of inhibitory proteins, the lipocortins, [4] and consequently reduce the release of eicosanoids in a number of cells and tissues (for review of this topic, see Ref. 5). However, there is a surprising paucity of information on the effect of glucocorticoids on arachidonic acid (AA) metabolism in the gastro-intestinal tract. Moreover, the relationship between steroid administration and gastic damage is still controversial [6].The present work was undertaken to investigate the effect of drugs which interfere with AA metabolism on the synthesis of PGI₂ by rat stomach mucosa and by the underlying muscularis layer bothin vitro andex vivo.     

Arachidonic acid and its metabolites are involved in the expression of morphine dependence in guinea-pig isolated ileum

The effects of phospholipase A₂, cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase inhibitors were investigated on the naloxone-precipitated withdrawal contracture of the acute morphine-dependent guinea-pig ileum in vitro. Mepacrine (a phospholipase A₂ inhibitor), tolmetin (selective cyclooxygenase-1 inhibitor) and meloxicam (selective cyclooxygenase-2 inhibitor) treatment before or after morphine was able to both prevent and reverse the naloxone-induced contracture after exposure to morphine in a concentration-dependent fashion. Also, nordihydroguaiaretic acid (5-lipooxygenase inhibitor) was able to block the naloxone-induced contracture following exposure to morphine when injected before or after the opioid agonist. The results of the present study suggest that arachidonic acid and its metabolites (prostaglandins and leukotrienes) are involved in the development of opioid withdrawal.     

Retinoic acid modulates the cell‐cycle in fetal rat hepatocytes and HepG2 cells by regulating cyclin‐cdk activities

Abstract: Retinoic acid (RA), the most biologically active metabolite of vitamin A, is known to modulate cell proliferation, apoptosis and differentiation, with different effects depending on the cellular context. Retinoic acid can exert its effects by directly or indirectly influencing the expression of genes involved in the control of cell proliferation. In the present report we investigate the possible correlation between the antiproliferative, differentiative and apoptotic effects previously observed on rat hepatocytes and HepG2 cells, with a possible modulation of cell‐cycle regulators. We demonstrate that RA induces growth arrest and differentiation in HepG2 cells by influencing the activities of cyclin‐cdk complexes involved in the regulation of G1/S transition and S‐phase progression, in particular by modifying the binding of these complexes to p21 and p27 inhibitors. In fetal cells, however, the induction of apoptosis and differentiation by RA was obtained via inhibition of cyclin D1‐cdk4 activity, as result of an increased binding to the p16 inhibitor. Retinoic acid also modulates c‐myc and Bcl‐2 expression. In conclusion, our data suggest that RA could be useful to regulate the reversion of transformed phenotype and could also be utilized as a chemiopreventive agent in cells of hepatic origin.     

One-year follow-up of tension-free vaginal tape (TVT) and trans-obturator suburethral tape from inside to outside (TVT-O) for surgical treatment of female stress urinary incontinence: a prospective randomised trial

OBJECTIVES: To compare tension-free vaginal tape (TVT) and trans-obturator suburethral tape from inside to outside (TVT-O) for surgical treatment of stress urinary incontinence (SUI) for complications (primary end point) and success rate (secondary end point). METHODS: Seventy-two consecutive patients, with a mean age of 53.2 yr (range: 38-69 yr) and affected by SUI, were included in this randomised controlled trial. After preoperative assessment, patients were randomly allocated to the TVT or TVT-O procedure. Operative time, perioperative complications, and hospital stay were prospectively recorded. Cure of SUI was defined as no leakage of urine during the stress test at urodynamic testing at the 12-mo evaluation. The Wilcoxon signed rank sum test, Mann-Whitney U test, McNemar test, and Fisher exact test were used to verify statistical significance, set at p<0.05. RESULTS: All patients were evaluable at the 12-mo follow-up. The characteristics of patients were well balanced between groups after randomisation. The mean operative time was significantly shorter in the TVT-O group. Perioperative complications were significantly more common after the retropubic approach (5% and 27% in TVT-O and TVT groups, respectively, p<0.04). The groups did not differ significantly in intraoperative blood loss, hospital stays, and time to return to normal activities. Sixty-five patients (90%) were successfully treated for SUI 12 mo after the operation (89% and 91% for TVT-O and TVT groups, respectively). CONCLUSIONS: Both techniques appear to be equally effective in the surgical treatment of SUI. However, TVT-O had a shorter operative time and lower overall perioperative complication rate.