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This multicenter retrospective study highlights the contrast-enhanced ultrasound (CEUS) findings in a series of histologically proven solitary necrotic nodules (SNN) of the liver, a poorly understood pathologic entity of uncertain origin that mimics malignancy. 22 patients (M/F 13/9; mean age 59.4 years, SD ± 10.7, range 35-81) with histological diagnosis of SNN and CEUS were selected from clinical, imaging, and pathological archives of 7 US interventional centers, each of which provided 1 to 6 cases (mean 2.8). Pathological diagnosis was made on 20 US-guided biopsies and 2 surgical specimens. 2 patients had 2 SNNs with identical CEUS findings so that imaging analysis was carried out on 24 nodules. SNN was an incidental finding in healthy people in 10 cases (45.5 %), and it was discovered during follow-up for either known extrahepatic malignancies (9 cases = 41 %) or chronic liver disease (3 cases = 13.5 %). SNNs had a mean size of 19.3 mm (SD ± 6.5, range 9-40). On B-mode US, SNNs appeared hypoechoic in 14 cases (66.7 %), "target-like" in 7 cases (29.2 %), and homogeneously hyperechoic in 1 case (4.1 %). On CEUS, all lesions appeared devoid of contrast enhancement ("punched out" aspect) in the arterial, portal venous, and late phases after US contrast agent injection. A uniformly thin, hyperenhancing ring in the early arterial phase and isoenhanced with the surrounding parenchyma in the portal venous and late phases was found in 10 nodules (41.6 %). Clinical and imaging follow-up (mean duration 42.2 months, SD ± 34.9, range 2-108) was available in 15 patients with 16 SNNs: no changes in size and echostructure were seen. CEUS can contribute to the diagnosis of SNN when a "punched out" appearance in all vascular phases with or without thin rim enhancement in the very early arterial phase is present in healthy subjects in whom a focal liver lesion is incidentally found. In patients with a history of chronic liver disease or malignancy, US-guided biopsy represents the unavoidable first-line diagnostic modality.ZIEL: Diese multizentrische retrospektive Studie beleuchtet die Befunde des kontrastverstärkten Ultraschalls (CEUS) bei histologisch nachgewiesenen solitären nekrotischen Knoten (SNN) der Leber, einer schlecht verstandenen pathologischen Entität ungewisser Entstehung 22 Patienten (M/F 13/9; mittleres Alter 59,4 Jahre, SD ± 10,7, Bereich 35–81) mit histologischer SNN-Diagnose und CEUS wurden aus den klinischen, bildgebenden und pathologischen Archiven von 7 US-amerikanischen Interventionszentren ausgewählt, von denen jedes Zentrum 1–6 Fälle (Mittelwert 2,8) zur Verfügung stellte SNN waren ein Zufallsbefund bei Gesunden in 10 Fällen (45,5 %), während sie bei der Nachsorge von bekannten extrahepatischen Malignomen in 9 Fällen (41 %) oder von chronischen Lebererkrankungen in 3 Fällen (13,5 %) entdeckt wurden. Die SNNs hatten eine mittlere Größe von 19,3 mm (SD ± 6,5, Bereich 9–40). Im Graustufen-Ultraschall zeigten sich die SNN in 14 Fällen (66,7 %) hypoechogen, in 7 Fällen (29,2 %) „zielähnlich“ und in einem Fall (4,1 %) homogen hyperechogen. Bei der CEUS-Untersuchung erschienen alle Läsionen ohne Kontrastanreicherung („ausgestanztes“ Aussehen) in der arteriellen, portalvenösen und späten Phase nach US-Kontrastmittelinjektion. Ein gleichmäßig dünner Ring mit Hyperenhancement in der frühen arteriellen Phase und Isoenhancement zum umgebenden Parenchym in der portalvenösen und späten Phase wurde bei 10 Knoten (41,6 %) gefunden.Eine klinische und bildgebende Nachbeobachtung (mittlere Dauer 42,2 Monate, SD ± 34,9, Bereich 2–108) stand bei 15 Patienten mit 16 SNNs zur Verfügung. Es wurden keine Veränderungen in Größe und Echostruktur festgestellt. CEUS kann zur Diagnose von SNN beitragen, wenn bei gesunden Probanden, bei denen zufällig eine fokale Leberläsion gefunden wird, ein „ausgestanztes“ Erscheinungsbild in allen vaskulären Phasen mit oder ohne dünnem Randsaum in der sehr frühen arteriellen Phase vorhanden ist. Bei Patienten mit chronischer Lebererkrankung oder einer Tumorerkrankung in der Anamnese ist die US-gestützte Biopsie unweigerlich die First-Line-Diagnostik.

The role of contrast-enhanced ultrasound (CEUS) in interventional ultrasound-guided procedures in the liver has been increasingly recognized. However, little is known about the capability of CEUS for diagnosing complications after liver biopsy and ablation with special regard to postprocedural hemorrhage. The aim of this Pictorial Essay is to present the CEUS features of a wide spectrum of vascular complications (with or without bleeding) and injuries of the surrounding abdominal and chest wall occurring after liver interventional procedures.

Background Portal vein aneurysm (PVA) is an uncommon vascular dilatation, showing no clear trend in sex or age predominance. Due to the low number of published cases and the lack of management guidelines, treatment of this condition remains a clinical challenge. Case summary We present three cases of asymptomatic PVA; the first and second involve an extrahepatic manifestation, of 48 mm and 42.3 mm diameter respectively, and the third involves an intrahepatic PVA of 27 mm. All were diagnosed incidentally during routine check-up, upon ultrasonography scan. Since all patients were asymptomatic, a conservative treatment strategy was chosen. Follow-up imaging demonstrated no progression in the aneurysm dimension for any case. Conclusion As PVA remains asymptomatic in many cases, recognition of its imaging features is key to favourable outcomes.

PURPOSE: Hepatocellular adenoma (HCA) is a rare benign monoclonal neoplasm, recently categorized on genetic and histopathological basis into four subtypes with different biological behaviors. Since contrast-enhanced ultrasonography (CEUS) is nowadays a well-established technique for liver nodule characterization, the aim of our study was to assess CEUS features of HCAs to identify criteria that correlate with different HCA subtypes as compared to histopathologic examination and other imaging modalities. METHODS: We retrospectively analyzed data of patients with histology-proven HCA who underwent CEUS, computed tomography or magnetic resonance imaging (MRI) in seven different Italian ultrasound units. RESULTS: The study enrolled 19 patients (16 females; 69% with concomitant/prior use of oral contraceptives): the mean size of all HCAs was 4.2 cm (range 1.6–7.1 cm); 14/19 had inflammatory HCAs (I-HCA), 1/19 β-catenin-activated HCA, and the others unclassified HCAs. On CEUS, during the arterial phase, all but one HCA displayed a rapid enhancement, with 89% of these showing centripetal and 11% centrifugal filling pattern, whereas during the portal and late venous phase 58% of HCA showed washout and the remaining 42% displayed persistent enhancement. In particular, among I-HCAs 7/14 showed no washout, 3/14 and 4/14 showed washout in the portal or late phase, respectively. CONCLUSIONS: This dataset represents one of the few published experiences on HCAs and CEUS in Italy and shows that HCAs are hypervascularized in the arterial phase usually with a centripetal flow pattern and have a heterogeneous behavior in portal and late phase. In particular, occurrence of delayed washout on CEUS but not on MRI is frequently observed in the subtype of I-HCA.

The present retrospective study was aimed at characterizing the clinical impact of contrast-enhanced ultrasound (CEUS) as a guidance technique for ablation of primary and secondary liver tumors at six interventional ultrasound centers. 148 patients (103M/45F, median age 74 yrs.) with 151 liver target lesions (median size 15 mm, 86.7% Hepatocellular Carcinomas) in whom CEUS guidance was used for Percutaneous Ethanol Injection (35.2%), Radiofrequency (46.3%) and Microwave (18.5%) were selected during the period 2008–2016. CEUS-guided ablations represented 7.3% (range 2.5%–13.8%) of 2015 ablative sessions performed at the participating centers. Indications to CEUS-guided ablation were: improvement of conspicuity of the target (28.5%), a target lesion undetectable on B-mode ultrasound (29.8%), detection of viable areas in nodules with either incomplete ablation or local tumor progression (41.7%). Overall, complete radiological ablation was obtained in 113/151 tumors (74.8%), with heat-based techniques (RF and MW) achieving higher rate of successful ablation (86.7%) than PEI (51%). Neither deaths nor major complications occurred after ablations. CEUS guidance demonstrates improved visibility and effectiveness in aiding ablation procedures that are otherwise technically difficult using only B-Mode US guidance.

To retrospectively characterize the prevalence and impact of contrast-enhanced ultrasound (CEUS) as a guidance technique for the biopsy of liver target lesions (LTLs) at six interventional ultrasound centers. The six participating centers retrospectively selected all patients in whom biopsy needles were positioned in LTLs during CEUS. The prevalence of CEUS-guided biopsies at each center between 2005 and 2016, contrast agent consumption, procedure indications, diagnostic yield and complications were assessed. Informed consent was obtained for all patients. CEUS-guided biopsy of LTLs was carried out in 103 patients (68 M/35 F, median age: 69 yrs) with 103 liver target lesions (median size: 20 mm) using cutting needles (18 - 20 g) in 94 cases (91.2 %). CEUS-guided biopsy represented 2.6 % (range: 0.8 - 7.7 %) of 3818 biopsies on LTLs carried out at the participating centers. Indications to CEUS-guided biopsy were: a target lesion not visible on non-enhanced US (27.2 %), improvement of conspicuity of the target (33 %), choice of non-necrotic area inside the target (39.8 %). 26 patients (25.2 %) had a previously non-diagnostic cyto-histological exam. The diagnostic accuracy of the technique was 99 %. No major complications followed infusion of contrast agent or biopsy performance. The indications for CEUS-guided biopsy for LTLs are limited, but CEUS can be useful in challenging clinical scenarios, e. g. poorly visualized or invisible lesions or sampling of non-necrotic areas in the target lesions. There is also a potential advantage in using CEUS to guide repeat biopsies after unsuccessful sampling performed using the standard ultrasound technique.ZIEL: Retrospektive Charakterisierung der Prävalenz und der Bedeutung des kontrastverstärkten Ultraschalls (CEUS) als Führungstechnik bei der Biopsie von Leber-Zielläsionen (LTL) in sechs interventionellen Ultraschallzentren. Die sechs teilnehmenden Zentren wählten retrospektiv alle Patienten aus, bei denen Biopsienadeln in den LTLs während des CEUS positioniert waren. Die Häufigkeit der CEUS-gestützten Biopsien an jedem Zentrum zwischen 2005 und 2016, der Kontrastmittelverbrauch, die Indikationen für den Eingriff, der diagnostische Gewinn und Komplikationen wurden beurteilt. Eine Einverständniserklärung wurde für alle Patienten eingeholt. Eine CEUS-gestützte Biopsie der LTL wurde bei 103 Patienten (68 M / 35 F, medianes Alter: 69 Jahre) mit 103 Leber-Zielläsionen (mediane Größe: 20 mm) durchgeführt, wobei in 94 Fällen (91,2 %) Biopsienadeln (18 – 20 g) zum Einsatz kamen. Die CEUS-gestützte Biopsie betrug 2,6 % (Bereich: 0,8 – 7,7 %) der 3818 LTL-Biopsien, die in den teilnehmenden Zentren durchgeführt wurden. Indikationen für eine CEUS-gestützte Biopsie waren: Eine im konventionellen US nicht sichtbare Zielläsion (27,2 %), eine Verbesserung der Auffälligkeit des Ziels (33 %), die Auswahl eines nicht-nekrotischen Bereichs im Ziel (39,8 %). Bei 26 Patienten (25,2 %) wurde zuvor eine nicht-diagnostische zytologische Untersuchung durchgeführt. Die diagnostische Genauigkeit der Methode betrug 99 %. Es traten keine größeren Komplikationen nach Infusion des Kontrastmittels oder bei Durchführung der Biopsie auf. Die Indikationen für die CEUS-gestützte Biopsie bei LTLs sind begrenzt, aber CEUS kann in schwierigen klinischen Szenarien nützlich sein, zum Beispiel bei schlecht darzustellenden oder unsichtbaren Läsionen oder bei Probenentnahme in nicht-nekrotischen Bereichen der Zielläsionen. Einen möglichen Nutzen besteht für den Einsatz von CEUS bei der Führung von Wiederholungsbiopsien, wenn die Probennahme bei Anwendung der Standard-Ultraschalltechnik erfolglos war.

Introduction An innovative method, known as sonoporation, was used to induce the expression of silenced genes, such as (but not restricted to) TRAIL and p53, in liver cancer cells (HepG2). The principal aim of the present study was the re-activation of silenced apoptotic pathways in liver cancer models, by using diagnostic synovial microbubble as plasmid gene delivery tools in combination with epigenetic treatments. Material and methods HepG2 cells were used as a liver cancer model. Microbubbles (Sonovue®) were chosen as gene deliver system in combination with the sonoporation approach. Plasmid pEGFP-TRAIL and pEGFP-p53 were selected and propagated in Escherichia coli grown in LB broth, in order to obtain the necessary amount. Results Sonoporation was induced by using transducer (Sonitron 2000) and, among the several conditions tested, 3 MHz, 51% Duty Cycle, and 5 W/cm2, 30 s resulted as the best parameters. Data collected showed a dose dependent effect in terms of output energy. A transfection efficacy of 30 – 50% was achieved and recombinant gene expression induced apoptotic effects. In order to increase efficacy, we used the histone deacetylase inhibitor (HDACi, entinostat) MS-275, able to activate TRAIL and thus inducing a stronger pro-apoptotic effect in combination with TRAIL-gene re-expression. Conclusion For the first time, it was shown the possibility to induce the exogenous expression of the pro-apoptotic gene TRAIL and p53 in a liver cancer HepG2 cells via a sonoporation procedure. The epigenetic treatment using HDACi was able to increase the pro-apoptotic effects of the gene therapy.

Background: Hepatitis C virus (HCV) infection represents one of the most important causes of chronic liver damage. The development of new therapeutic approaches based on the use of direct-acting antivirals allowed reaching the high rates of sustained virological response and on the other hand, the low rates of drug side effects. Objectives: The study aimed to evaluate the efficacy and safety of multiple direct-acting antiviral (DAA) therapies against the major HCV genotypes in Campania. Methods: We enrolled, in this monocentric observational study, 518 adult patients (> 18-years-old) affected by HCV who received a DAA anti-HCV-based therapy in the routine clinical practice. We collected direct data registered by the Hepatogastroenterology Division of the University of Campania “L. Vanvitelli”, which covers a catchment area from the entire Campania region. Results: A great number (98.2 %) of the 518 enrolled patients was naive to the antiviral treatment and genotype distribution was 1a = 32 (6.2%), 1b = 252 (48.7%), 2 = 146 (28.2%), 3 = 52 (10.1%), and 4 = 36 (6.9%). 300 patients were cirrhotic (57.9%) and most of them had a Child-Pugh A5 score. 79.56 % of the patients belonging to the population of our study were classified as fibrosis Metavir F3 or F4 by Fibroscan. All the enrolled patients completed the treatment with the exception of five (n = 5; 0.96%) who interrupted it due to adverse events. We observed a relapse of infection in three patients treated with Sofosbuvir and Simeprevir for 12 weeks (0.57%). Intention to treat analysis showed an overall rate of 98.46% (n = 510/518) sustained virological response. Six of the eight failure patients had a second line anti-HCV treatment and four of them obtained SVR (two patients are waiting for resistance test results). Conclusions: New antiviral regimens of DAA-based for HCV represent one of the greatest innovations in the scientific context in the last few years. Our prospective observational study confirms the elevated efficacy in terms of SVR12, independently from HCV genotype and disease stage, when these treatments are used as the methods of a good clinical practice.

// Luca Rinaldi 1 , Veronica Folliero 2 , Luciana Palomba 2 , Carla Zannella 2 , Rachele Isticato 3 , Raffaele Di Francia 4 , Massimiliano Berretta 5 , Ilario de Sio 6 , Luigi E. Adinolfi 1 , Giancarlo Morelli 7 , Secondo Lastoria 8 , Lucia Altucci 6 , Carlo Pedone 7 , Massimiliano Galdiero 2 and Gianluigi Franci 2 1 Department of Medical, Surgical, Neurological, Metabolic and Aging Science, University of Campania “Luigi Vanvitelli”, Naples, Italy 2 Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy 3 Department of Biology, Federico II University, Naples, Italy 4 Department of Hematology, National Cancer Institute, Foundation G. Pascale IRCCS, Naples, Italy 5 Department of Medical Oncology, National Cancer Institute IRCCS, Aviano, Italy 6 Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy 7 Department of Pharmacology, Federico II University, Naples, Italy 8 Department of Diagnostic Imaging, Radiation and Metabolic Therapy, National Cancer Institute, Foundation G. Pascale IRCCS, Naples, Italy Correspondence to: Luca Rinaldi, email: luca.rinaldi@unicampania.it Keywords: microbubbles; sonoporation; ultrasound; liver cancer; gene therapy Received: June 05, 2018 Accepted: July 13, 2018 Published: August 14, 2018 ABSTRACT Introduction: An innovative method, known as sonoporation, was used to induce the expression of silenced genes, such as (but not restricted to) TRAIL and p53, in liver cancer cells (HepG2). The principal aim of the present study was the re-activation of silenced apoptotic pathways in liver cancer models, by using diagnostic synovial microbubble as plasmid gene delivery tools in combination with epigenetic treatments. Material and methods: HepG2 cells were used as a liver cancer model. Microbubbles (Sonovue®) were chosen as gene deliver system in combination with the sonoporation approach. Plasmid pEGFP-TRAIL and pEGFP-p53 were selected and propagated in Escherichia coli grown in LB broth, in order to obtain the necessary amount. Results: Sonoporation was induced by using transducer (Sonitron 2000) and, among the several conditions tested, 3 MHz, 51% Duty Cycle, and 5 W/cm2, 30 s resulted as the best parameters. Data collected showed a dose dependent effect in terms of output energy. A transfection efficacy of 30 – 50% was achieved and recombinant gene expression induced apoptotic effects. In order to increase efficacy, we used the histone deacetylase inhibitor (HDACi, entinostat) MS-275, able to activate TRAIL and thus inducing a stronger pro-apoptotic effect in combination with TRAIL-gene re-expression. Conclusion: For the first time, it was shown the possibility to induce the exogenous expression of the pro-apoptotic gene TRAIL and p53 in a liver cancer HepG2 cells via a sonoporation procedure. The epigenetic treatment using HDACi was able to increase the pro-apoptotic effects of the gene therapy.

Background/Aim: A reduction in portal vein inflow velocity seems to predispose to the emergence of portal vein thrombosis (PVT). Nonselective β-blockers (NSBBs), used to prevent variceal bleeding, may increase the development of PVT by reducing portal vein inflow velocity. In this retrospective case-control study, we evaluated the risk factors and clinical features of a first event of PVT in 130 cirrhotics, 19 (15%) with (PVT group) and 111 (85%) without PVT (non-PVT group). Patients and Methods: Patient evaluation and NNBB treatment were carried out according to the AASLD guidelines. Results: PVT was prevalently partial (84%) and asymptomatic (84%). Patients with PVT were treated with different regimens, and resolution of thrombosis was observed in about 50% of the cases. In both groups, HCV was the most frequent cause of cirrhosis and Child-Pugh score A was prevalent. Ascites and esophageal varices were more frequent in the PVT group (P = 0.05 and

Introduction: An innovative method, known as sonoporation, was used to induce the expression of silenced genes, such as (but not restricted to) TRAIL and p53, in liver cancer cells (HepG2). The principal aim of the present study was the reactivation of silenced apoptotic pathways in liver cancer models, by using diagnostic synovial microbubble as plasmid gene delivery tools in combination with epigenetic treatments. Material and methods: HepG2 cells were used as a liver cancer model. Microbubbles (Sonovue®) were chosen as gene deliver system in combination with the sonoporation approach. Plasmid pEGFP-TRAIL and pEGFP-p53 were selected and propagated in Escherichia coli grown in LB broth, in order to obtain the necessary amount. Results: Sonoporation was induced by using transducer (Sonitron 2000) and, among the several conditions tested, 3 MHz, 51% Duty Cycle, and 5 W/cm2, 30 s resulted as the best parameters. Data collected showed a dose dependent effect in terms of output energy. A transfection efficacy of 30 – 50% was achieved and recombinant gene expression induced apoptotic effects. In order to increase efficacy, we used the histone deacetylase inhibitor (HDACi, entinostat) MS-275, able to activate TRAIL and thus inducing a stronger pro-apoptotic effect in combination with TRAILgene re-expression. Conclusion: For the first time, it was shown the possibility to induce the exogenous expression of the pro-apoptotic gene TRAIL and p53 in a liver cancer HepG2 cells via a sonoporation procedure. The epigenetic treatment using HDACi was able to increase the pro-apoptotic effects of the gene therapy.

BACKGROUND & AIMS: The aim of this study was to compare liver resection and radiofrequency ablation in patients with single hepatocellular carcinoma ≤3 cm and compensated cirrhosis. METHODS: The study involved 544 Child-Pugh A cirrhotic patients (246 in the resection group and 298 in the radiofrequency group) observed in 15 Italian centers. Overall survival and tumor recurrence rates were analyzed using the Kaplan Meier method before and after propensity score matching. Cox regression models were used to identify factors associated with overall survival and tumor recurrence. RESULTS: Two cases of perioperative mortality were observed in the resection group and the rate of major complications was 4.5% in the resection group and 2.0% in the radiofrequency group (p=0.101). Four-year overall survival rates were 74.4% in the resection group and 66.2% in the radiofrequency group (p=0.353). Four-year cumulative HCC recurrence rates were 56% in the resection group and 57.1% in the radiofrequency group (p=0.765). Local tumor progression was detected in 20.5% of ablated patients and in one resected patient (p

Sorafenib confers a survival benefit for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) A liver cirrhosis. At present, limited data exists with regard to the safety and efficacy of sorafenib in treating CP-B HCC patients. The present study describes the use of sorafenib in patients with HCC and CP-A or -B cirrhosis. Clinical data was obtained from patients with HCC who were treated with sorafenib at the Department of Clinical and Experimental Medicine, Second University of Naples (Naples, Italy) and were analyzed retrospectively in terms of tumor response, tolerance and survival. The treatment outcomes were analyzed according to the respective CP status. The adverse events (AEs) were graded using the Common Terminology Criteria for Adverse Events, version 3.0, and the tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.2. In total, 26 patients received sorafenib at 400 mg twice daily. The median age was 69 years (range, 58-81 years) and the ratio of males to females was 18:8. Overall, 15 patients were infected with the hepatitis C virus (HCV), eight with HBV and three were co-infected with HCV/HBV. In total, 20 (77%) patients presented with an underlying CP-A (CP-A5 and CP-A6) cirrhosis and six (23%) with CP-B (CP-B7). Previous treatments included surgery (n=4), transarterial chemoembolization (n=5) and percutaneous ethanol injection or radiofrequency interstitial thermal ablation (n=12). A partial response was observed in three patients (12%), a stable disease lasting at least 12 weeks in 13 patients (50%) and a progression of disease in 10 patients (38%). The median overall survival (OS) time was 7.4 months [95% confidence interval (CI), 3.2-11.6) and the median progression-free survival (PFS) time was 3.7 months (95% CI, 1.9-5.5). The median OS and PFS times differed between patients with CP-A and CP-B, with a trend (P=0.06) toward a worse outcome in those with CP-B, although this was not statistically significant. The CP-A and CP-B groups experienced a similar incidence in the majority of AEs. A reduction in dose was required in 59% of the patients. The CP-A5, CP-A6 and CP-B7 patients tolerated sorafenib similarly, and derived comparable clinical and survival benefits.

AIMS This multicentre cohort study evaluated the role of ageing on clinical characteristics, treatment allocation and outcome of new hepatocellular carcinomas (HCCs), in clinical practice. MATERIAL & METHODS From September 2008, 541 patients >70 years old (elderly group), and 527 ≤70 years old (non-elderly group) with newly diagnosed HCC were consecutively enrolled in 30 Italian centres. Differences in clinical characteristics and treatment allocation between groups were described by a multivariable logistic regression model measuring the inverse probability weight to meet the elderly group. Survival differences were measured by unadjusted and adjusted (by inverse probability weight) survival analysis. RESULTS Elderly patients were mainly females, hepatitis C virus infected and with better conserved liver function (P

Background: Hepatocellular carcinoma (HCC) is the leading cause of death amongst cirrhotic patients. Its diagnosis and discrimination from non-HCC malignant lesions in cirrhosis includes contrast enhanced computed tomography (CECT), contrast enhanced magnetic resonance imaging (CEMRI), or, in selected cases, liver biopsy. The role of contrast-enhanced ultrasonography (CEUS) is still controversial. Aims: To evaluate whether, by selecting an appropriate ‘time to wash-out’ cut-off value, CEUS capability of discriminating between HCC and non-HCC malignancies in cirrhotic patients may be enhanced. Methods: We enrolled 282 cirrhotic patients who underwent CEUS at our institute, from January 2008 to January 2012, for focal liver lesions (FLLs) detected at ultrasound (US). We used liver biopsy and subsequent histological evaluation as the gold standard for correct classification of FLLs. We calculated the area under receiver operator characteristic curves for CEUS to distinguish patients with HCC from those with non-HCC malignancies. The best ‘time to wash-out’ cut-off values were selected. Results: Histological diagnosis of FLLs was as follows: 34 benign lesions (i.e. 25 regenerative nodules and 9 dysplastic nodules) and 248 malignant lesions (223 well-to-moderately differentiated HCCs; 7 poorly-differentiated HCCs; 5 intrahepatic colangiocellular carcinomas (ICCs); 5 primary non-Hodgkin B-cell lymphomas (NHBLs); and 8 metastatic liver tumors). A time to wash-out >55s identified patients with HCC with the highest level of accuracy (92.7%). Similarly, a time to washout � 55s correctly identified the vast majority of the non-HCC malignancies (100% sensitivity, 98.2% specificity and diagnostic accuracy of 98.3%). Conclusions: CEUS is an accurate and safe procedure for discriminating FLLs in cirrhotic patients, especially when a cut-off time to wash-out of 55s is chosen as a reference value.

Background The value of ultrasound (US) in assessing gastrointestinal diseases is well documented, but its demand in clinical practice is unknown. This survey evaluated the demand for bowel US in Italy. Methods Twelve sonographers of the Gastroenterology Section of the Italian Society of Ultrasound participated in a 1-month survey; they compiled a questionnaire assessing total number of patients referred for abdominal US and for gastrointestinal tract US, type of referring physician, indications and results of examinations. Results The survey included 2424 examinations, 586 of which (24%) investigated the gastrointestinal tract: 280 for signs or symptoms and 268 for follow-up of pre-existing gastrointestinal diseases. Referring physicians were mainly gastroenterologists (78%) and general practitioners (13%). Organic lesions were found or suspected in 292 examinations. Conclusions Bowel US is used in Italy in routine practice, mainly by gastroenterologists and general practitioners, both for follow-up of pre-existing diseases and for gastrointestinal complaints.

Obesity is a chronic complex disease, consequence of an unbalance between energy intake and expenditure and of the interaction between predisposing genotype and facilitating environmental factors. The aim of the study was to evaluate body composition, abdominal fat, and metabolic changes in a group of severely obese patients before and after laparoscopic gastric bypass (LGBP) at standardized (10% and 25%) total weight loss.Twenty-eight patients (14 M, 14 F; age 41.71 +/- 6.9 years; body mass index (BMI) 49.76 +/- 5.8 kg/m(2)) were treated with laparoscopic gastric bypass. All evaluations before surgery and after achieving ~10% and ~25% weight loss (WL). Body composition was assessed by bioimpedance analysis; resting metabolic rate (RMR) was measured by indirect calorimetry.Body weight, BMI, and waist circumference significantly decreased at 10% and 25% WL. We observed a significant reduction of both RMR (2,492 +/- 388 at entry vs. 2,098 +/- 346.6 at 10% WL vs. 2,035 +/- 312 kcal per 24 h at 25% WL, p = 0.001 vs. baseline) as well as of RMR corrected for fat-free mass (FFM; 35.7 +/- 6.7 vs. 34.9 +/- 9.0 at 10% WL vs. 33.5 +/- 5.4 at 25% WL kilocalorie per kilogram FFM x 24 h, p = 0.041 vs. baseline). Body composition analysis showed a relative increase in FFM and a reduction of fat mass at 25% WL. A significant reduction in blood glucose, insulin, homeostasis model assessment index was observed. Ultrasonography showed a marked decrease in the signs of hepatic steatosis.In conclusion, our study confirms that LGBP is a safe procedure in well-selected severely obese patients and has early favorable effects on both metabolic parameters and body composition. Longer-term observations are required for in-depth evaluation of body composition changes.

Oxidative stress leads to chronic liver damage. Silybin has been conjugated with vitamin E and phospholipids to improve its antioxidant activity. Eighty-five patients were divided into 2 groups: those affected by nonalcoholic fatty liver disease (group A) and those with HCV-related chronic hepatitis associated with nonalcoholic fatty liver disease (group B), nonresponders to treatment. The treatment consisted of silybin/vitamin E/phospholipids. After treatment, group A showed a significant reduction in ultrasonographic scores for liver steatosis. Liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis showed an improvement in treated individuals. A significant correlation among indexes of fibrosis, body mass index, insulinemia, plasma levels of transforming growth factor-beta, tumor necrosis factor-alpha, degree of steatosis, and gamma-glutamyl transpeptidase was observed. Our data suggest that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage.

Aims and objectives: If the integration of the study of diaphragmatic motility(dm) with bedside ultrasound (BUS) is useful in patients(pz) with ARF Methods: 32 pz with ARF referred to our ED were studied (T0,T1..T24)with BUS (heart,ICV, lung and diaphragm) with 3.5 MHz convex probe. For the study of dm probe was positioned in the right subcostal region between the midclavicular and anterior axillary using the acoustic window of the liver between the gallbladder and ICV. Were evaluated in M-Mode: Excursion E (cm), Inspiration time Ti (sec) Expiratory time Te (sec) Total time Ttot (sec) Dome (cm) Results: Compared with controls homogeneous for clinical features and severity (SOFA) pz with E Moreover a good increase of E during NIV (3.63 ± 0:32cm vs 2.3 ± 0:29) coincided with time of NIV shorter (media 27 hours vs 44).(p Conclusions: BUS with integration of the study of dm showed the adoption of more appropriate therapeutic measures and allowed to improve our pz outcome.

Objectives Direct puncture of subcapsular hepatocellular carcinoma (HCC) for tumor ablation has been considered high risk due to a perceived increased incidence of hemorrhage or tumor seeding. The purpose of this retrospective multicenter study was to identify the rate of tumor seeding, hemorrhage and local tumor progression (LTP) associated with direct puncture radiofrequency (RF) and microwave (MW) ablation of subcapsular HCC. Methods A multicenter, retrospective review of direct-puncture RF and MW performed on subcapsular HCC was conducted. Complications and local tumor progression were documented. Data was analyzed using Kaplan–Meier and log-rank tests. Results The study group consisted of 60 cirrhotic patients (M/F = 43/17; mean age 69.6 years) with 67 subcapsular HCC (mean diameter 2.3 cm ± 1.0 cm) that were directly punctured for RF (n = 40) or MW (n = 27) under ultrasound (US) guidance. The mean follow-up period was 30.8 months. There were no hemorrhagic complications. The overall LTP rate was 13.4%. There was one case of tumor tract seeding in a patient who had undergone a percutaneous biopsy two weeks prior to RF. Conclusions Thermal ablation of HCC by direct puncture appears safe and effective. There were no cases of intraperitoneal hemorrhage, and tumor seeding was seen in a single case in which a preceding percutaneous biopsy had been performed.

Purpose To describe the characteristics at presentation and the outcome of elderly patients (≥70 years old) with HCC, a retrospective analysis using a CLIP database was performed. Patients and methods The database included 650 patients. χ 2-test, logistic and Cox model were applied. Results Baseline characteristics and stage were similarly among elderly ( n =158) and non-elderly ( n =492) patients. More elderly patients did not receive any local treatment (56% versus 38%, p Conclusion Elderly patients with HCC have a worse prognosis compared to non-elderly ones. Such difference seems the consequence of undertreatment.

Patients with persistently normal ALT affected with HCV-related chronic hepatitis exist. The natural history of liver disease in these patients was demonstrated to be very slow and progression to cirrhosis likely absent. The case we report describes the occurrence of hepatocellular carcinoma (HCC) in a patient with persistently normal ALT affected with mild chronic hepatitis. This observation suggests that asymptomatic carriers of HCV may develop HCC that is not related to underlying liver cirrhosis.

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in Western countries and is increasingly being recognized in developing nations. Fatty liver disease encompasses a spectrum of hepatic pathology, ranging from simple steatosis to non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and end-stage liver disease. Moreover, NAFLD is often associated with other metabolic conditions, such as diabetes mellitus type 2, dyslipidemia and visceral obesity. The most recent guidelines suggest the management and treatment of patients with NAFLD considering both the liver disease and the associated metabolic co-morbidities. Diet and physical exercise are considered the first line of treatment for patients with NAFLD, but their results on therapeutic efficacy are often contrasting. Behavior therapy is necessary most of the time to achieve a sufficient result. Pharmacological therapy includes a wide variety of classes of molecules with different therapeutic targets and, often, little evidence supporting the real efficacy. Despite the abundance of clinical trials, NAFLD therapy remains a challenge for the scientific community, and there are no licensed therapies for NAFLD. Urgently, new pharmacological approaches are needed. Here, we will focus on the challenges facing actual therapeutic strategies and the most recent investigated molecules.

Background/Aims : Studies on non-alcoholic fatty liver disease (NAFLD) have included chronic liver damage attributed to various causes. Our investigation was held to observe the main clinical, histological, and pathophysiological aspects of NAFLD in patients not exposed to any known cause of chronic liver disease. Methods : We evaluated, in 84 in-patients (male/female, 66/18; median age, 36 years), the clinical and biochemical characteristics of NAFLD, and particularly its association with diabetes, dyslipidemia, hyperinsulinemia and/or with the increase of parameters of oxidative stress (blood levels of malonyldialdehyde, 4-hydroxynonenal and total plasma antioxidant capacity). Results : Ninety percent of patients had an increased body mass index (BMI), 35% had dyslipidemia, 40% had sub-clinical diabetes (only 3% had overt diabetes), 60% had hyperinsulinemia, and more than 90% had enhanced levels of lipid peroxidation markers. In 48 patients who had consented to liver biopsy, we found: 14 with simple steatosis, 32 with steatohepatitis, and two with cirrhosis. Conclusions : Our data indicate that in our country, NAFLD may occur in young males with an increased BMI, with or without hyperinsulinemia, dyslipidemia and diabetes, generally associated with disorders of redox status, and that it may be differentiated from steatosis to steatohepatitis or cirrhosis only with a liver biopsy.

The aim of this study was to evaluate the clinical efficacy and safety of the ultrasound-guided fine needle biopsy (UG-FNB) of the spleen in a large population of patients. We collected retrospectively the findings concerning the application of UG-FNB of the spleen from eight Italian clinical centers that utilized this technique for at least ten years. A data schedule was sent to all centers to collect information about techniques, results, and complications of UG-FNB of the spleen. We analyzed 398 biopsy procedures both on focal lesions (257 cases) and on splenic parenchyma (141 cases). The overall accuracy was 90.9% for the series as a whole, 84.9% for cytological sampling, 88.3% for microhistological sampling, and 90.3% for both cytological and histological sampling (double biopsy). Tissue core biopsy yielded better overall accuracy in patients with suspected splenic involvement by lymphoma (90.9% vs. 68.5% for cytology). The complication rate was low (no death cases, less than 1% for major complications, and 5.2% for all complications). No predictive factors were able to detect high-risk situations. The operator's skill (higher number of performed procedures) was significantly related to better overall accuracy. Conversely, the complication rate was not affected. UG-FNB of the spleen is a very effective diagnostic procedure with low risk for the patient. Aspiration cytology and core needle biopsy showed similar diagnostic yields, except for the diagnosis of splenic lymphoma, in which core needle biopsy obtained better results.

Aim: Adherence to and the applicability of practice guidelines for the management of hepatocellular carcinoma (HCC) in field practice have not been fully addressed. We designed a multicenter field practice prospective study to evaluate the adherence to the 2005 American Association for the Study of Liver Diseases guidelines in Italy. Materials & methods: The study began in September 2008 and consecutively enrolled cirrhotic patients with newly diagnosed HCC from 30 local, nonreference centers in Italy. Patients were stratified according to Child–Pugh, the model for end-stage liver disease, tumor-node metastasis, performance status and the Barcelona Clinic Liver Cancer (BCLC) classifications. The diagnostic and therapeutic strategies adopted in each individual patient were recorded. Statistical analysis was carried out on 536 patients using all of the valuable data. Results: A total of 286 (54.5%) patients were ≥70 years old. Comorbidities, recorded in 397 (74%) patients, were classified as moderate to severe in 170 patients (43%). Overall, 174 (59%) patients with early-stage BCLC were ≥70 years; 104 (35%) of these had moderate-to-severe comorbidities and 54% were under a regular US surveillance program. Diagnosis was performed by computed tomography in 93% of patients, contrast-enhanced ultrasound in 62% and MRI in 17%. In patients with nodules of ≤2 cm, adherence to noninvasive diagnostic criteria was 56%. Adherence to the BCLC classification was shown to be suboptimal overall, particularly regarding allocation to surgical procedures, and a total of 119 patients (40%) with BCLC stage A did not receive curative therapies. Conclusions: This multicenter survey showed that, in the ‘real world’, adherence to the both the diagnostic and therapeutic American Association for the Study of Liver Diseases 2005 algorithms was low, particularly in patients with early-stage HCC. Difficulties in applying the algorithms in routine clinical practice and the high prevalence of older patients with relevant comorbidities may account for our findings. Strategies to help improve adherence to international guidelines for HCC in field practice are required.

“Wait and see” policy for early hepatocellular carcinomaGiampiero Francica, Ilario de Sio, Maurizio Pompili, Tito LivraghiPII: S0168-8278(13)00367-XDOI: http://dx.doi.org/10.1016/j.jhep.2013.04.039Reference: JHEPAT 4739To appear in: Journal of HepatologyReceived Date: 18 March 2013Revised Date: 25 April 2013Accepted Date: 26 April 2013Please cite this article as: Francica, G., Sio, I.d., Pompili, M., Livraghi, T., “Wait and see” policy for earlyhepatocellular carcinoma, Journal of Hepatology (2013), doi: http://dx.doi.org/10.1016/j.jhep.2013.04.039This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customerswe are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, andreview of the resulting proof before it is published in its final form. Please note that during the production processerrors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Background & Aims: The aim of this study was to compare liver resection and radiofrequency ablation in patients with single hepatocellular carcinoma

Sixteen cases of focal nodular hyperplasia (FNH) of the liver were followed by ultrasound (US) for a mean of 33 months (range 6-81). In 69% of the cases, the diagnosis was incidental. On US the lesions were single in 75% of the cases, localized in the right lobe in 75%, and subcapsular in 50%. No specific US-pattern could be identified. A central scar was found in 19% of the patients. At the end of the follow-up, the size was reduced in 7/16 cases, and in 1/16 the lesion disappeared. The spontaneous reduction of nodules in FNH must be considered in the management of this pseudotumor.

Background Recent reports indicate that numerical assessment of B-lines during transthoracic ultrasound may aid the differential diagnosis of acute diffuse pleuropulmonary disorders. Purpose To determine whether B-lines are different in normal and diseased lungs and whether they can be used to discriminate between different types of pulmonary disorders in acutely ill patients. Material and Methods In this multicenter study, transthoracic ultrasonography was performed on 193 patients with acute dyspnea, 193 healthy non-smokers, and 58 patients who had undergone pneumonectomy for lung cancer. Examinations were done with a low–medium frequency (3.5–5.0 MHz) convex probe and a high-frequency (8–12.5 MHz) linear probe. Video recordings were re-examined by a second set of examiners. In each participant, we measured the number of B-lines observed per scan. Results B-lines counts were higher in dyspnoic patients (means: 3.11 per scan per linear probe scan vs. 1.93 in healthy controls and 1.86 in pneumonectomized patients; P < 0.001 for all); all counts were higher when convex probes were used (5.4 in dyspnoic patients and 2 in healthy controls; P < 0.001 vs. the linear probe). Subgroups of dyspnoic patients defined by cause of dyspnea displayed no significant differences in the number of B-lines. Conclusion Our results demonstrate that there are a significant higher number of B-lines in the lungs of patients with dyspnea compared to healthy subjects and to pneumonectomized patients. Nevertheless, the quantification of B-lines does not make any significant contribution to the differential diagnosis of dyspnea.

Evidence of relative effectiveness of local treatments for hepatocellular carcinoma (HCC) is scanty. We investigated, in a retrospective cohort study, whether surgical resection, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial embolization with (TACE) or without (TAE) chemotherapy resulted in different survival in clinical practice. All patients first diagnosed with HCC and treated with any locoregional therapy from 1998 to 2002 in twelve Italian hospitals were eligible. Overall survival (OS) was the unique endpoint. Three main comparisons were planned: RFA versus PEI, surgical resection versus RFA/PEI (combined), TACE/TAE versus RFA/PEI (combined). Propensity score method was used to minimize bias related to non random treatment assignment. Overall 425 subjects were analyzed, with 385 (91%) deaths after a median followup of 7.7 years. OS did not significantly differ between RFA and PEI (HR 1.11, 95% CI 0.79–1.57), between surgery and RFA/PEI (HR 0.95, 95% CI 0.64–1.41) and between TACE/TAE and RFA/PEI (HR 0.88, 95% CI 0.66–1.17). 5-year OS probabilities were 0.14 for RFA, 0.18 for PEI, 0.27 for surgery, and 0.15 for TACE/TAE. No locoregional treatment for HCC was found to be more effective than the comparator. Adequately powered randomized clinical trials are still needed to definitely assess relative effectiveness of locoregional HCC treatment.

Gastrointestinal tract lesions, both inflammatory and/ or neoplastic, may be visualized at ultrasound as "a target" or "bull's eye" lesion, or as a "pseudokidney" mass. Although the diagnosis of nature of gastrointestinal tract lesion is conventionally based on endoscopic biopsies, since 1981 many authors have reported the possibility to reach the diagnosis of gastrointestinal neoplasia by using an ultrasound-guided biopsy. This procedure has been performed using fine needles (i.e., Needles with an outer diameter

The natural history of nonalcoholic steatohepatitis (NASH) includes the passage through steatosis.To retrospectively evaluate the usefulness of sonographic parameters compared to histological diagnosis when differentiating steatosis from NASH.This retrospective study reviewed records of patients with steatosis from databases of our Departments, selecting only those who had been diagnosed by sonography and liver biopsy [64 males (63.82%); 30 females (36.18%)].Attenuation of the echo amplitude (P0.05; odds ratio (OR): 3.43; confidence interval (CI): 1.02-11.57), focal fat sparing (P0.05; OR: 3; CI: 1.02-11.88) and splenic diameter (P0.05; OR: 1.66; CI: 1.04-3.26) were independent predictors of NASH. A significantly higher association of attenuation of the echo amplitude, enlarged splenic diameter, and presence of focal fat sparing was observed in NASH patients (P0.01).It is very difficult to build a predictive system to distinguish NASH from steatosis based on sonographic scores. However, it is already possible to differentiate NASH from steatosis by combining 3 simple sonographic parameters: attenuation of the echo amplitude, enlarged splenic diameter, and presence of focal fat sparing.

Polycystic ovary syndrome (PCOS) is considered a sex-specific form of the metabolic syndrome (MetS). Visceral obesity is one of the main diagnostic criteria for the MetS. Patients with MetS have a significantly higher risk for cardiovascular disease (CVD). PCOS is the most common endocrine-metabolic disease of reproductive-age women and PCOS patients are predisposed to an androgen adiposity phenotype, characterized by a prevalent fat accumulation in the abdominal area, and by insulin resistance. PCOS women are exposed to a cluster of metabolic abnormalities and cardiovascular risk factors from a young age, and therefore PCOS patients might represent a high-risk group for developing early-onset CVD. Early signs of CVD have been reported in PCOS patients and correlated to the amount of visceral fat. Visceral fat might represent a new prognostic and therapeutic target to define the cardiovascular risk profile and prevent CVD in PCOS patients.

BACKGROUND We investigated whether several different inflammatory markers including C-reactive protein (CRP) and fibrinogen and white blood cells (WBCs) count, are associated with maximal oxygen consumption (VO(2 max)) in women with polycystic ovary syndrome (PCOS). METHODS In PCOS women (n = 124, 24.1 +/- 4.5 year-old) VO(2 max) was measured during symptom-limited cardiopulmonary exercise test. Abdominal fat distribution was determined by ultrasound. Physical activity level was assessed by a standardized questionnaire. CRP was measured by immunoassays, fibrinogen by the Clauss method, and WBCs count with a Coulter counter. RESULTS Pearson's analysis showed a significant correlation between VO(2 max) and logCRP (r = -0.437, P < 0.001), fibrinogen (r = -0.479, P < 0.001), and WBCs count (r = -0.438, P < 0.001). Multivariable logistic regression model showed that age (beta = -0.127, P = 0.005), AUC(INS )(beta = -0.335, P < 0.001), HDL-C (beta = 0.390, P < 0.001), physical activity score (beta = 0.238, P = 0.002), visceral fat (beta =-0.184), P = 0.023), FAI (beta = -0.291, P = 0.028); CRP (beta = -0.216, P = 0.011), fibrinogen (beta = -0.113, P = 0.008) and WBCs count (beta = -0.177, P < 0.001) were significantly associated with VO(2 max). CONCLUSIONS Acute-phase reactants, such as CRP and fibrinogen, and WBCs count were independently and inversely associated with a direct measure of cardiorespiratory fitness (VO(2 max)) in women with PCOS, even after adjustment for physical activity level and other potential confounding factors. These findings add to the growing body of evidence linking inflammation to cardiorespiratory fitness in PCOS women.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have been reported to have subclinical cardiovascular disease (CVD) and increased abdominal fat. The aim of this study was to evaluate the relationship between visceral fat (VF) and early markers of CVD in PCOS women. METHODS: Two hundred overweight PCOS women [(mean +/- SD) age 24.6 +/- 3.2 years, body mass index (BMI) 28.5 +/- 2.8 kg/m2] and 100 healthy age- and BMI-matched volunteer controls entered this cross-sectional study. In all subjects, the amount of VF was measured by ultrasonography. Anthropometric measurements [BMI and waist circumference (WC)], complete hormonal and metabolic pattern, carotid intima-media thickness (IMT), brachial arterial flow-mediated dilation (FMD) and inflammatory biomarkers [C-reactive protein (CRP), fibrinogen, white blood cells count and plasminogen activated inhibitor-1] were also obtained from all subjects. A stepwise linear regression model was used in PCOS patients to verify if IMT or FMD as dependent variables are affected by other independent variables. RESULTS: VF amount was significantly (P < 0.001) higher in PCOS subjects than in healthy controls [31.4 +/- 7.3 versus 28.0 +/- 6.1 (mean+/-SD) mm, respectively] and directly related to insulin resistance: HOMA (r = 0.918, P < 0.001) and AUC(INS) (r = 0.879, P < 0.001), and to WC (r = 0.658; P < 0.001). In PCOS, the two linear regression analyses showed that IMT is positively affected by VF and CRP, whereas FMD is positively affected by IMT and negatively by VF and CRP. CONCLUSIONS: VF amount is associated with subclinical CVD in PCOS patients.

To describe the characteristics at presentation and the outcome of elderly patients (or =70 years old) with HCC, a retrospective analysis using a CLIP database was performed.The database included 650 patients. Chi2-test, logistic and Cox model were applied.Baseline characteristics and stage were similarly among elderly (n=158) and non-elderly (n=492) patients. More elderly patients did not receive any local treatment (56% versus 38%, p0.0001). Age and CLIP score were independently predictive of the odds of locoregional treatment. Prognosis was worse for elderly patients with a hazard ratio of death of 1.49 (95% CI 1.20-1.86) at multivariable analysis. The survival difference disappeared when patients were compared within each treatment group, suggesting a close link between undertreatment and shorter survival.Elderly patients with HCC have a worse prognosis compared to non-elderly ones. Such difference seems the consequence of undertreatment.

For "early" hepatocellular carcinoma (HCC), surgery, orthotopic liver transplantation (OLT) and percutaneous ethanol injection (PEI) improve the natural history of the disease. We performed a retrospective study to evaluate the outcome of patients with cirrhosis and early HCC treated by PEI (n = 417) or OLT (n = 172). Overall, 589 patients with cirrhosis were studied. The proportion of patients in Child-Turcotte-Pugh (CTP) classes A, B, and C was 52.5%, 33.6%, and 13.9%, respectively. Most patients (78.9%) had solitary HCC. Overall 5-year and 10-year cumulative survival rates were 36.1% and 15.5% after PEI, and 66.3% and 49.1% after OLT, respectively (P < .0001). Overall 5-year and 10-year cumulative tumor-free survival rates were 25.3% and 18.0% after PEI, and 84.6% and 82.2% after OLT, respectively (P < .0001). When patients were sorted according to the severity of cirrhosis, mean survival times in PEI and OLT patients were 67 and 80 months in CTP class A (P = .05), 38 and 90 months in class B (P < .0001), and 31 and 95 months in class C (P = .0004). Similarly, mean tumor-free survival times in the 2 series of patients were 49 and 98 months in CTP class A (P < .0001), 39 and 121 months in class B (P < .0001), and 35 and 139 months in class C (P < .0001). In conclusion, this study challenges the therapeutic efficacy of PEI for patients with cirrhosis and early HCC, when compared to OLT: the proportion of both long-term survivors and tumor-free survivors was increased by OLT over PEI. The benefit of OLT extends to all patients, regardless of the degree of liver impairment. Copyright © 2004 by the American Association for the Study of Liver Diseases

To determine the prevalence of the coarse nodular ultrasonographic (US) pattern and its prognostic importance in terms of hepatocellular carcinoma (HCC) risk in hepatic cirrhosis caused by hepatitis B virus (HBV); HBV with hepatitis D virus (HDV), formerly known as hepatitis delta virus; hepatitis C virus (HCV); and alcoholic cirrhosis (ALC) or primary biliary disease (primary biliary cirrhosis [PBC]).Four hundred two cases of hepatic cirrhosis caused by HBV (94 patients), HDV (100 patients), HCV (100 patients), ALC (63 patients), or PBC (45 patients) were retrospectively reviewed to identify the US pattern present at diagnosis and its possible association with the cause of the disease and subsequent development of HCC during a mean follow-up of 43.9 months +/- 29.9 (SD). Data were analyzed with the chi2, Fisher exact, and log-rank tests and with the Kaplan-Meier method (all two-tailed).The coarse nodular pattern was found in a significantly higher percentage of patients with HDV-related cirrhosis (51%) compared with those with HBV (9%), HCV (9%), ALC (11%), or PBC (9%) (P.001). This pattern was associated with a significantly increased risk for HCC in patients with cirrhosis and HBV-, HCV-, and ALC-related disease but not in those with HDV-related disease and PBC.The coarse nodular pattern is more often seen in patients with HDV-related cirrhosis, and, in this setting (in contrast to HBV-, HCV-, and ALC-related cirrhosis, as well as in PBC), it does not represent an added risk factor for HCC.

Patients with small hepatocellular carcinoma (HCC) are usually treated with hepatic resection or percutaneous ethanol injection (PEI).To compare the effects of hepatic resection versus PEI on survival in a matched case-control study. STUDY Patients with single-nodule HCC (or=5 cm) who were treated with hepatic resection (cases) or PEI (controls) were eligible. Matching criteria were date of diagnosis, Child-Pugh stage, and age at diagnosis. Kaplan-Meier survival curve of the control group was drawn weighing each stratum by the inverse of its size. Treatments were compared by a stratified Cox's model, adjusted by CLIP score.Of 912 patients, 197 were eligible and 82 (17 cases and 65 controls) were matched, creating 17 strata. Nine (53%) cases and 41 (63%) controls died. Cox model showed no survival difference between the two groups; hazard ratio of PEI versus hepatic resection was 1.04 (95% CI = 0.43-2.52). One- and 3-year survival rates in the hepatic resection and PEI groups were 82% versus 91% and 63% versus 65%, respectively.Patients with small HCC treated with hepatic resection or PEI have similar survival rates. In view of the higher cost and morbidity of hepatic resection, a prospective randomized study is warranted.