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Cucchetti A.,University of Bologna | Trevisani F.,University of Bologna | Pecorelli A.,University of Bologna | Erroi V.,University of Bologna | And 17 more authors.
Journal of Hepatology

Background & Aims Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Methods One-thousand three-hundred and eighty Child-Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. Results The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p <0.001). In a 10-year follow-up perspective, the median lead-time calculated for all surveilled patients was 6.5 months (7.2 for semiannual and 4.1 for annual surveillance). Lead-time bias accounted for most of the surveillance benefit until the third year of follow-up after HCC diagnosis. However, even after lead-time adjustment, semiannual surveillance maintained a survival benefit over symptomatic diagnosis (number of patients needed to screen = 13), as did annual surveillance (18 patients). Conclusions Lead-time bias is the main determinant of the short-term benefit provided by surveillance for HCC, but this benefit becomes factual in a long-term perspective, confirming the clinical utility of an anticipated diagnosis of HCC. Source

Giannini E.G.,University of Genoa | Farinati F.,University of Padua | Ciccarese F.,Policlinico San Marco | Pecorelli A.,University of Bologna | And 7 more authors.

The prognosis of untreated patients with hepatocellular carcinoma (HCC) is heterogeneous, and survival data were mainly obtained from control arms of randomized studies. Clinical practice data on this topic are urgently needed, so as to help plan studies and counsel patients. We assessed the prognosis of 600 untreated patients with HCC managed by the Italian Liver Cancer Group. Prognosis was evaluated by subdividing patients according to the Barcelona Clinic Liver Cancer (BCLC) classification. We also assessed the main demographic, clinical, and oncological determinants of survival in the subgroup of patients with advanced HCC (BCLC C). Advanced (BCLC C: n=138; 23.0%) and end-stage HCC (BCLC D; n=210; 35.0%) represented the majority of patients. Overall median survival was 9 months, and the principal cause of death was tumor progression (n=279; 46.5%). Patients' median survival progressively and significantly decreased as BCLC stage worsened (BCLC 0: 38 months; BCLC A: 25 months; BCLC B: 10 months; BCLC C: 7 months; BCLC D: 6 months; P<0.0001). Female gender (hazard ratio [HR]=0.55; 95% confidence interval [CI]=0.33-0.90; P=0.018), ascites (HR=1.81; 95% CI=1.21-2.71; P=0.004), and multinodular (>3) HCC (HR=1.79; 95% CI=1.21-2.63; P=0.003) were independent predictors of survival in patients with advanced HCC (BCLC C). Conclusion: BCLC adequately predicts the prognosis of untreated HCC patients. In untreated patients with advanced HCC, female gender, clinical decompensation of cirrhosis, and multinodular tumor are independent prognostic predictors and should be taken into account for patient stratification in future therapeutic studies. © 2014 by the American Association for the Study of Liver Diseases. Source

Caturelli E.,Unita Operativa di Gastroenterologia | Ghittoni G.,Medicine VI Interventional Ultrasound | Ranalli T.V.,Unita Operativa di Anatomia Patologica | Gomes V.V.,Unita Operativa di Anatomia Patologica
British Journal of Radiology

Nodular regenerative hyperplasia (NRH) is an uncommon liver disease characterised histologically by numerous small hyperplastic nodules that are not separated by fibrotic tissue. It is thought to be the result of obliterative vasculopathy, and it has been associated with chronic use of medications, toxic substances and a wide variety of systemic diseases. Imaging diagnosis of early-stage NRH remains problematic. The nodules are rarely discerned and their appearance and behaviour before and after contrast medium administration are heterogeneous and not specific. A review of the literature shows that ultrasound has succeeded on occasion in revealing small focal liver lesions in patients with NRH. To our knowledge, there has been no published data on the performance in this setting of last-generation ultrasound scanners and techniques such as contrast-enhanced ultrasound (CEUS). The question is an important one because abdominal ultrasound is widely used as a first-line imaging technique for the evaluation of liver disease, and this makes it particularly suitable as a potential tool for the early diagnosis of NRH. Owing to the prolonged subclinical period and the limited help provided by imaging, the diagnosis in vivo of NRH is currently frequently missed, and it is still made exclusively on the basis of liver biopsy. In conclusion, this report describes 4 cases of biopsy-proven NRH that have been diagnosed over the past 2 years by our group. All were characterised by known comorbidities that confer a predisposition to NRH and by a peculiar parenchymal ultrasound pattern that we refer to as the "atoll sign". © 2011 The British Institute of Radiology. Source

Giannini E.G.,University of Genoa | Savarino V.,University of Genoa | Farinati F.,University of Padua | Ciccarese F.,Policlinico San Marco | And 7 more authors.
Liver International

Background: The role of clinically significant portal hypertension on the prognosis of cirrhotic patients undergoing hepatic resection for hepatocellular carcinoma (HCC) is debated. Aims: In this study, our aim was to assess the role of clinically significant portal hypertension after hepatic resection for HCC in patients with cirrhosis. Methods: We assessed the prognostic role of the presence of clinically significant portal hypertension (oesophageal/gastric varices/portal hypertensive gastropathy or a platelet count <100 × 109/L associated with splenomegaly) in 152 patients with compensated cirrhosis who underwent hepatic resection for HCC at the Italian Liver Cancer centres. Survival rates were assessed in the whole series, in the subgroup of Child-Pugh score 5 patients with uninodular HCC ≤5 cm, and in Child-Pugh score 5 patients with uninodular HCC ≤2 cm and normal bilirubin. Results: Median survival was similar in patients with and without clinically significant portal hypertension (79 vs 77 months, P = 0.686). Child-Pugh score 5 was the only variable significantly associated with survival by Cox multiple regression (P = 0.007). In Child-Pugh score 5 patients with single HCC ≤5 cm or in those with single HCC ≤2 cm and normal bilirubin, there was no survival difference between patients with and without clinically significant portal hypertension (median survival: 94 vs 78 months, P = 0.121 and >100 vs 86 months, P = 0.742). Conclusions: Presence of clinically significant portal hypertension has no influence on survival of patients with well-compensated cirrhosis undergoing hepatic resection for HCC. © 2013 John Wiley & Sons A/S. Source

Maglietta R.,CNR Institute of Intelligent Systems for Automation | Distaso A.,CNR Institute of Intelligent Systems for Automation | Piepoli A.,Unita Operativa di Gastroenterologia | Palumbo O.,Servizio di Genetica Medica | And 4 more authors.
Journal of Biomedical Informatics

One of the major problems in genomics and medicine is the identification of gene networks and pathways deregulated in complex and polygenic diseases, like cancer. In this paper, we address the problem of assessing the variability of results of pathways analysis identified in different and independent genome wide expression studies, in which the same phenotypic conditions are assayed. To this end, we assessed the deregulation of 1891 curated gene sets in four independent gene expression data sets of subjects affected by colorectal cancer (CRC). In this comparison we used two well-founded statistical models for evaluating deregulation of gene networks. We found that the results of pathway analysis in expression studies are highly reproducible. Our study revealed 53 pathways identified by the two methods in all the four data sets analyzed with high statistical significance and strong biological relevance with the pathology examined. This set of pathways associated to single markers as well as to whole biological processes altered constitutes a signature of the disease which sheds light on the genetics bases of CRC. © 2009 Elsevier Inc. All rights reserved. Source

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