Combined treatment of refractory ascites with an alfapump® plus hernia repair in the same surgical session: A retrospective, multicentre, European pilot study in cirrhotic patients.

INTRODUCTION: The treatment of symptomatic hernia in cirrhotic patients with refractory ascites is critical but challenging. The objective of this study was to assess the feasibility and safety of the implantation of alfapump® combined with concomitant hernia repair in cirrhotic patients with refractory ascites. METHODS: Using data from six European centres, we retrospectively compared patients treated with alfapump® system implantation and concomitant hernia repair [the combined treatment group (CT group, n=12)] or with intermittent paracentesis hernia repair [the standard treatment group (ST group, n=26)]. Some patients of the ST group had hernia repair in an elective setting (STel group) and others in emergency (STem group). The endpoints were requirement of peritoneal drainage, the rate of infectious complications, the in-hospital mortality, the length of stay, paracentesis-free survival. RESULTS: Postoperatively, none of the patients in the CT group and 21 patients (80%) in the ST group underwent peritoneal drainage for the evacuation of ascites fluid (P<0.0001). The overall incidence of infectious complications was not different between groups but there were fewer infections in the CT group than in the STem group (33% vs. 81%; P=0.01). There was no difference for in-hospital mortality. The length of stay was shorter in the CT group (P=0.03). Paracentesis-free survival was significantly better (P=0.0003) in the CT group than in the ST group. CONCLUSION: Implantation of alfapump combined with concomitant hernia repair seems feasible and safe in cirrhotic patients; however, larger and randomized study are required.

Endothelin 1 type a receptor antagonism prevents vascular dysfunction and hypertension induced by 11beta-hydroxysteroid dehydrogenase inhibition: role of nitric oxide.

BACKGROUND: The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) prevents inappropriate activation of the nonselective mineralocorticoid receptors by glucocorticoids. Renal activity of 11beta-HSD is decreased in patients with apparent mineralocorticoid excess (SAME), licorice-induced hypertension, and essential hypertension. Although expressed in vascular cells, the role of 11beta-HSD in the regulation of vascular tone remains to be determined. METHODS AND RESULTS: lycyrrhizic acid (GA; 50 mg/kg IP, twice daily for 7 days) caused a significant inhibition of 11beta-HSD activity and induced hypertension in Wistar-Kyoto rats (157 versus 127 mm Hg in controls; P<0.01). After 11beta-HSD inhibition, aortic endothelial nitric oxide (NO) synthase (eNOS) protein content, nitrate tissue levels, and acetylcholine-induced release of NO were blunted (all P<0.05 versus controls). In contrast, vascular prepro-endothelin (ET)-1 gene expression, ET-1 protein levels, and vascular reactivity to ET-1 were enhanced by GA treatment (P<0.05 versus controls). Chronic ET(A) receptor blockade with LU135252 (50 mg. kg(-1). d(-1)) normalized blood pressure, ET-1 tissue content, vascular reactivity to ET-1, vascular eNOS protein content, and nitrate tissue levels and improved NO-mediated endothelial function in GA-treated rats (P<0.05 to 0.01 versus untreated and verapamil-treated controls). In human endothelial cells, GA increased production of ET-1 in the presence of corticosterone, which indicates that activation of the vascular ET-1 system by 11beta-HSD inhibition can occur independently of changes in blood pressure but is dependent on the presence of glucocorticoids. CONCLUSIONS: Chronic ET(A) receptor blockade normalizes blood pressure, prevents upregulation of vascular ET-1, and improves endothelial dysfunction in 11beta-HSD inhibitor-induced hypertension and may emerge as a novel therapeutic approach in cardiovascular disease associated with reduced 11beta-HSD activity.