Viviana Neve

Serum ferritin as a new prognostic factor in hepatocellular carcinoma patients treated with radiofrequency ablation

Hepatic iron accumulation is considered to be a cofactor that influences liver injury and hepatocarcinogenesis. Aim of this study is to determine whether serum ferritin (SF) levels relate to overall survival (OS) and time to recurrence (TTR) in hepatocellular carcinoma (HCC) patients treated with percutaneous radiofrequency ablation (RFA).

Post-recurrence survival in hepatocellular carcinoma after percutaneous radiofrequency ablation

BACKGROUND Overall survival in hepatocellular carcinoma patients treated with percutaneous radiofrequency ablation is influenced by both recurrence and successive treatments. We investigated post-recurrence survival after radiofrequency ablation. METHODS Data on 103 early/intermediate patients initially treated with radiofrequency ablation and followed for a median of 78 months (range 68-82) were retrospectively analysed. If intrahepatic disease recurrence occurred within or contiguous to the previously treated area it was defined as local, otherwise as distant; recurrence classified as Barcelona Clinic Liver Cancer stage C was defined by neoplastic portal vein thrombosis or metastases. RESULTS A total of 103 patients were included (82.5% male; median age 70 years, range 39-86). During follow-up, 64 recurrences were observed. Median overall survival was 62 months (95% confidence interval: 54-78) and survival rates were 97%, 65% and 52% at 1, 4 and 5 years, respectively. Median post-recurrence survival was 22 months (95% confidence interval: 16-35). Child-Pugh score, performance status, sum of tumour diameters at recurrence and recurrence patterns were independent predictors of post-recurrence survival. CONCLUSIONS In patients with hepatocellular carcinoma after radiofrequency ablation, clinical and tumour parameters assessed at relapse, in particular the type of recurrence pattern, influence post-recurrence survival.

Conditional survival analysis of hepatocellular carcinoma patients treated with radiofrequency ablation

Survival estimates are commonly reported as survival from the first observation, but future survival probability changes based on the survival time already accumulated after therapy, otherwise known as conditional survival (CS). The aim of the study was to describe CS according to different prognostic variables in hepatocellular carcinoma (HCC) patients treated with radiofrequency ablation (RFA).

Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis

Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin (AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2 (vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phase-two studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients.

P085 Effect of phytoestrogenic dietary supplementation on the progression of chronic intestinal inflammation to cancer in an animal model

Background and aim : Colorectal cancer (CRC) is increased in inflammatory bowel diseases (IBD). Chemopreventive agents could minimize this risk. Estrogens exert prevention against CRC throught Estrogen Receptor β (ERβ) with an inverse relation with the tumor. ER β induction may be a target in CRC prevention. Phytoestrogens are dietary compounds with higher binding affinity for ERβ than Erα. A blend of the dietary phytoestrogens (silymarin and lignan) and non-starch insoluble fibers (Eviendep, CM&D Pharma) has been tested in an experimental mouse model of AOM/DSS induced colitis, to assess the anti-inflammatory and anti-carcinogenetic properties and to verify whether such effect is related to an increased ERβ expression. Material and methods : A known model of dextran sodium sulfate/azoxymethane induced CRC was used to obtain the best simulation of IBD-related CRC pathogenesis. Seventy-six C57BL/6J male mice were divided into three groups: 35 mice fed a Eviendepmodified diet during the whole carcinogenetic process, 35 fed a standard diet (positive control) and 6 mice with no treatment or modified diet (negative control). Monitoring of colitis and tumorigenesis was performed by a specific video-endoscopic system (Coloview Miniendoscopic System) at 21 weeks. Animals were sacrificed at 22 weeks for histogical and ERs immunohistochemical evaluation. Histological score was: 0 (no dysplasia), 1 (low grade dysplasia), 2 (high grade dysplasia) and 3 (carcinoma). Results : Mortality rate was of 40-50%. At sacrifice, treated animals showed a decrease in number/volume of polyps and in histological score (p,0.05 ANOVA-Bonferroni post hoc test). Only 30% of Eviendepsupplemented mice showed at least 1 CRC compared with the 100% of the positive controls. ERα expression was higher in neoplastic tissue than in normal mucosa both in treated and positive control groups, while ERβ labeling index (LI%) showed a higher value in nonneoplastic tissue of the Eviendep-supplemented group (63.8±4.7) than in positive control (46.6±6.4), resulting similar to the ERβ LI value of negative controls (54.9±7.9) (p,0.05 Fisher Exact Test) Conclusions : Our results suggest a chemopreventive effect of Eviendep on colonic carcinogenesis arising from inflamed tissue, and such an effect associates with an increase ERβ content in the tissue.

Sa1260 Non Invasive Evaluation of Endothelial Function in Inflammatory Bowel Diseases

In the last decades an ever-growing body of evidence has suggested the involvement of intestinal microvascular endothelial cells in development and maintenance of inflammatory bowel diseases (IBD). Changes in structure and function of endothelium, mediated by a multifaceted network of chemokines, cytokines and inflammatory growth factors, are a distinctive feature of active disease. In addition, human intestinal microvessels taken from inflamed mucosa exhibit consistent degrees of endothelial dysfunction, with significant impairment of acetylcholine-induced vasodilation based on decreased endothelial nitric oxide (NO) synthase (eNOS) activity. By “endothelial dysfunction” is comprehensively meant a condition in which the varied homeostatic functions of endothelium are impaired. Endothelial function can be measured through the flow-mediated dilation (FMD) technique, a wellestablished non invasive procedure in which changes in the calibre of the brachial artery induced by an increased vessel wall shear stress are measured ultrasonographically. AIM: The present study was designed to evaluate whether FMD at the brachial artery was impaired in a sample of patients with Crohns disease (CD) and ulcerative colitis (UC) in comparison to healthy control subjects. As a secondary measure of interest, intima-media thickness at the common carotid artery (ccIMT) was also calculated. MATERIALS AND METHOD: 49 patients (25 males; mean age, 41 yrs ± 16) with CD (26) and UC (23) in moderate-severe activity phase were included. Endothelial function was assessed through FMD and shear stress reactive hyperemia determination; moreover, ccIMT was measured ultrasonographically. Statistical analyses were made by using Statistica 6.1 software (StatSoft Inc.. Tulsa. OK. USA). RESULTS: In IBD patients FMD% values were significantly lower than in controls (6.3±3.3 vs 8.1±3.4, p=0.013). Such difference was not related to age, sex, disease duration, or comorbidity (such as, hypertension or diabetes). On the contrary, ccIMT measurements did not differ consistently between cases and controls. CONCLUSIONS: IBD group showed significant levels of endothelium dysfunction compared with controls. In our view, this result was more likely related to systemic inflammation than to traditional risk factors. By contrast, the lack of significant differences in ccIMT was possibly related to the low mean age and disease duration in our study population. Future studies of endothelial function are warranted comparing case series before and after remission obtained under elective treatments.