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// Filomena Morisco 1 , Silvia Camera 1 , Maria Guarino 1 , Raffaella Tortora 2 , Valentina Cossiga 1 , Anna Vitiello 1 , Gabriella Cordone 2 , Nicola Caporaso 1 , Giovan Giuseppe Di Costanzo 2 and Italian Liver Cancer (ITA.LI.CA) group 1 Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, Italy 2 Hepatology Unit, “Cardarelli” Hospital, Naples, Italy Correspondence to: Filomena Morisco, email: filomena.morisco@unina.it Keywords: large HCC; laser ablation; TACE Received: December 13, 2017 Accepted: February 27, 2018 Published: April 03, 2018 ABSTRACT Background: Limited therapies are available for large (≥40 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. Methods: Eighty-two patients with a single HCC nodule ≥40 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. Results: Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively ( p 60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively ( p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. Conclusions: LA is a more effective therapeutic option than TACE in patients with solitary large HCC.

The authors wish to inform readers of the below error: Section 2.2., right column, third line reads Esaote MyLab Twice (convex probe CA451, software version EVO 13.0 release 12.11) [pSWE]. It should read: Esaote MyLab Twice (convex probe CA541, software version EVO 13.0 release 12.11) [pSWE]. That is, the model number CA451 does not exist and should be replaced by CA541.

Background: Metabolic disorders are well-known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology. Methods: We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0-1, 2 and 3-5 metabolic features. Results: As compared with patients with 0-1 metabolic features, patients with 3-5 features showed lower percentage of HCC diagnosis on surveillance (P=.021), larger tumours (P=.038), better liver function (higher percentage of Child-Pugh class A [P=.007] and MELD&nbsp

The evolution of the magma plumbing system of the Pleistocene Apacheta-Aguilucho Volcanic Complex area (Altiplano-Puna Volcanic Complex, northern Chile) was investigated through petrographic, geochemical and isotopic studies of representative lavas and related enclaves. Updated available dates of these products, both from the Apacheta and Aguilucho stratovolcanoes and nearby domes, allow us to define the activity during the last 1 Ma. This investigation shows that the andesitic magmas were affected by processes of Assimilation plus Fractional Crystallization (AFC, with a significant role played by amphibole fractionation) during their ascent through the upper crust, presumably by the interaction with the Altiplano-Puna Magma Body (15–20 km). These andesitic magmas were erupted with no or minor additional contamination at shallower levels, or experienced plagioclase-dominated Fractional Crystallization (FC) to dacite within shallower crustal magma chambers (4–8 km depth). The constructional phase of the Apacheta and Aguilucho stratovolcanoes (≥1 to ca. 0.6 Ma) reflect a transition from high-flux (i.e. flare-ups) to steady state magmatism, as also documented in other Pleistocene volcanic complexes of the Altiplano-Puna Volcanic Complex. During this stage the mafic magma recharge was high enough to permit a large spectrum of hybridization of the resident magmas in the upper crust to form the abundant andesites and dacites lavas. In contrast, at ∼150–100 ka, the magmatism turned to a new stage of recharge (waning stage?) and the episodic intrusion of small-volumes of andesitic magmas permitted the remobilization of the crystal-rich dacites, triggering the extrusions of the Chanka, Chac-Inca and Cerro Pabellon domes. The andesitic enclaves in the domes studied here represent a snapshot of the magmatic processes of interaction that occurred in the shallower reservoir at the interface of the resident dacite with the ascending andesitic magma. Nevertheless, as there are no dated volcanic products from the area between 0.6 and 0.1 Ma, the youngest dacitic domes could also be interpreted as the beginning of a new magmatic pulse of the Altiplano-Puna Volcanic Complex. Independently from the significance of the mafic recharge at 150–100 ka (waning stage vs. new pulse) the youngest investigated domes share similar geochemical features and crustal depth constraints (4–8 km) with the ignimbrites of the Altiplano-Puna Volcanic Complex, therefore suggesting that the remobilized magmas erupted as the domes are possibly remains of older plumbing systems left over from the last magmatic flare-up of the Altiplano-Puna Volcanic Complex.

The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.

Background: Liver cancer is the second most common cause of cancer-related death, with hepatocellular carcinoma (HCC) accounting for most primary liver cancers and most commonly arising from a history of advanced chronic liver disease. Among the available therapies, transarterial chemoembolization (TACE) is the most widely utilized and is considered the first-line treatment recommended for patients staged as intermediate HCC (Barcelona Clinic Liver Cancer stage B). If applied correctly, TACE can produce survival benefits without adversely affecting hepatic functional reserve. Summary: The aim of this nonsystematic review is to evaluate the evidence supporting TACE, with a special interest in intermediate HCC, for which this treatment is recommended in first line. However, intermediate HCC represents a broad and heterogeneous group of patients, not all of whom will benefit from TACE. This review highlights the importance of appropriate patient selection for initial TACE and for retreatment. It also evaluates evidence for the treatment of patients who become refractory to TACE. Some patients may, in fact, benefit from early switch (i.e., after 1 or 2 TACE treatments) to systemic therapies rather than continuing retreatments with TACE in order to preserve liver function, thus allowing sequential first- and second-line drug therapies. Key Messages: Careful assessment of an individual patient's benefit/risk ratio is recommended before any TACE session is considered to ensure optimal long-term outcomes in intermediate HCC.

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle-based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (short version; the long version is published online).

Aim/Background: After the introduction of sorafenib in the treatment of advanced hepatocellular carcinoma (HCC), different studies tried to evaluate whether other systemic therapies can improve survival. To provide a comprehensive indirect treatment comparison of efficacy and safety of novel drugs, a network meta-analysis (NMA) of phase III randomized controlled trials was performed. Methods: After pertinent literature search up to November 1, 2016, 6 studies were eligible for the analysis including 4,812 individual patients with advanced HCC: 2,454 received sorafenib, 577 received brivanib, 530 received sunitinib, 514 received linifanib, 358 received sorafenib + erlotinib and 379 received placebo. Frequentist NMA was used to compare treatments within a single analytical framework. Results: NMA showed that sorafenib alone, regardless of combination with erlotinib, and linifanib provide a significant survival advantage over placebo (p < 0.05) but without any significant difference between each other. Conversely, all regimens significantly ameliorate progression-free survival versus placebo (p < 0.05). The rank order of efficacy was: sorafenib ± erlotinib, linifanib, brivanib, sunitinib, and placebo. Sorafenib ± erlotinib was the regimen with the fewest number of adverse events that required discontinuation of treatment, whereas linifanib and brivanib resulted in the most adverse events. The risk-benefit summary identified one cluster of therapies with a similar balance between efficacy and safety which included sorafenib alone or in combination with erlotinib, having, at the same time, the highest efficacy and safety. Conclusions: Sorafenib remains the best systemic treatment for advanced HCC; linifanib also resulted in survival advantages over placebo but with a lower safety profile.