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The rise in the world's demand for fish is increasingly met by aquaculture. However, this sector still shows various criticalities in terms of sustainability of practices, first and foremost, that of feed availability. Nowadays, the use of insect meal represents one of the potential sustainable solutions, but consumption intention of fish fed with insect meal and the factors affecting it have not yet been adequately understood. This study investigates 318 Italian consumers' intentions to buy fish fed with insect meal using an extended version of the Theory of Planned Behavior, including consumers' moral attitude and sustainability consciousness as additional constructs. The results of structural equation models show that consumers' high sustainability consciousness (6.16 on a scale from 1 to 7) does not influence their consumption intention of this product. Also, the two moderating variables involved in the model, i.e., the country of origin and price sensitivity, do not significantly affect consumers' intentions. Since the analysis demonstrates that, for consumers, insect meal-fed fish conforms to their moral principles and a significant positive attitude toward this practice it could be argued that fish fed with insect meal can match the demand from consumers who feel responsible for their consumer behavior. Although the limited area of investigations and the high education of interviewed do not allow for generalizing of the results, this paper provides pivotal food for thought for companies, policymakers, and academics responding to previous research calls on understanding the role of some constructs of consumption intention and highlighting the levers on which to act to foster the consumption intention of insect-fed fish.

Growing Mediterranean seafood consumption, increasing consumers' awareness of food safety and quality, and changing food lifestyles are leading to the development of new food products. However, the majority of new food products launched on the market are expected to fail within the first year. One of the most effective ways to enhance new product success is by involving consumers during the first phases of New Product Development (NPD), using the so-called co-creation approach. Based on data collected through online discussion rooms, two new seafood product concepts-sardine fillets and sea burgers-were evaluated by a set of potential consumers in three Mediterranean countries-Italy, Spain, and Croatia. Textual information was analyzed by first using the topic modeling technique. Then, for each main topic identified, sentiment scores were calculated, followed by the identification of the main related emotions that were evoked. Overall, consumers seem to positively evaluate both proposed seafood product concepts, and three recurrent positive emotions (trust, anticipation, joy) were identified in relation to the main topics aroused during the discussions. The results of this study will be useful to guide future researchers and actors in this industry in the next development steps of the targeted seafood products in Mediterranean countries.

Background and Objectives : Jejunal artery (JA) and ileal artery (IA) aneurysms constitute less than 3% of all visceral artery aneurysms (VAAs), carrying a risk of rupture as high as 30%, and a mortality of 20%. Though many etiologies have been reported in the literature, no mention exists on a causal association between these aneurysms and inflammatory bowel diseases (IBD). We present the first case of a JA aneurysm related to Crohn's Disease (CD) together with a review of the literature. Materials and Methods : A 74-year-old male presenting with CD intestinal relapse and an incidental finding at the computed tomography enterography (CTE) of a 53 × 47 × 25mm apparently intact JA pseudoaneurysm, arising from the first and second jejunal branches, underwent coil embolization followed by small bowel resection, with an uneventful outcome. We also included the review of literature on JA and IA aneurysms, analyzing all reports published in PubMed and Scopus from 1943 to July 2022. Results : 60 manuscripts with 103 cases of JA and IA aneurysms in 100 patients were identified. Among cases with available data, 34 (33.0%) presented acutely with rupture, 45 (43.7%) were described as non-ruptured. 83 (80.6%), and 14 (13.6%) were JA and IA aneurysms, respectively, having a median size of 15 (range:3.5-52) mm. Atherosclerosis (16.5%), infections (10.7%), and vasculitides/connective tissue disorders (9.7%) represented the main causes mentioned. Mean age was 53.6 (±19.2) years, male patients being 59.4%. One third of patients (32.4%) were asymptomatic. Overall, treatment was indicated in 63% of patients, with surgery and endovascular procedures performed in 61.9% and 38.1% cases, respectively. The technical success rate of endovascular treatment (EVT) was 95.8%. The mortality rate was 11.8%, being higher (21.2%) in the rupture group. Conclusions : The prompt treatment accomplished in our case granted a successful outcome. JA and IA aneurysms should be included among local complications of IBD. Considering their high potential for rupture, regardless of size, a low threshold for endovascular or surgical treatment should be applied.

The role of moderate alcohol consumption in the evolution of NAFLD is still debated. The aim of this study is to evaluate the impact of current and lifelong alcohol consumption in patients with NAFLD. From 2015 to 2020, we enrolled 276 consecutive patients fulfilling criteria of NAFLD (alcohol consumption up to 140 g/week for women and 210 g/week for men). According to their current alcohol intake per week, patients were divided in: abstainers, very low consumers (C1: <70 g/week) and moderate consumers (C2). We created a new tool, called LACU (Lifetime Alcohol Consuming Unit) to estimate the alcohol exposure across lifetime: 1 LACU was defined as 7 alcohol units per week for 1 drinking year. Patients were divided into lifelong abstainers and consumers and the latter furtherly divided into quartiles: Q1-Q4. Stratification according to alcohol intake, both current and cumulative as estimated by LACU, showed that very low consumers (C1 and Q1-Q3) displayed lower frequency of cirrhosis and hepatocellular carcinoma compared to abstainers and moderate consumers (C2 and Q4). We can speculate that up to one glass of wine daily in the context of a Mediterranean diet may be a long-term useful approach in selected NAFLD patients.

Background: Ultrasound-guided percutaneous liver biopsy is a standard procedure, but it might be burdened with serious adverse events, mainly hemorrhagic. Literature lacks recent studies taking into account new ultrasound machines, more sensitive to tiny vessels and the evolution of the bioptic technique, including ultrasound guidance in all instances. Hence, the primary aim of this study was to evaluate complication rates of ultrasound-guided percutaneous liver biopsy in a recent population. Secondary aims were to evaluate if the experience of operator is a determinant of risk of complication and to identify other potential risk factors., Methods: We evaluated 800 procedures carried out in one hospital in the period 2010-2018., Results: Complication rate resulted in 4%, with the occurrence of moderate hemorrhagic complications in 0.75%. No cases of severe events or death were registered. A higher risk of bleeding was found to be associated with less experienced operators, while the need to perform multiple needle insertions increased the probability of adverse events., Conclusion: The present findings confirmed ultrasound-guided percutaneous liver biopsy to be a substantially safe procedure with a low risk of overall adverse events and bleeding in particular, especially when performed by expert operators., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Hepatic epithelioid hemangioendothelioma (HEHE) and fibrolamellar hepatocellular carcinoma (HCC) are rare malignant neoplasms of the liver. Contrarily to HCC, no distinctive imaging criteria based on contrast enhancement pattern are known for these neoplasms, thus they are frequently misdiagnosed as other liver tumors. Due to their infrequency, very few data principally based on reports of few patients are currently available in literature. This results in several issues pending on the application of imaging in the diagnosis of these cancers, which absolutely needs pathological examination. Nevertheless, imaging techniques are fundamental in the diagnostic work-up and in the management of affected patient. This review summarizes the current evidence about imaging systems in the diagnosis of HEHE and fibrolamellar carcinoma (FLC), discussing the significance of the principal iconographic hallmarks and the prospective potentials of the most employed techniques., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2018.11.33). The series “Primary Liver Cancer” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2019 Translational Cancer Research. All rights reserved.)

Transarterial chemoembolization (TACE) is indicated in unresectable hepatocellular carcinoma and allows the delivery of embolics inside tumor vascularization to reduce blood supply and release gradually the drug. This lowers the systemic exposure to chemotherapeutics, while increasing their local concentration and tissue necrosis that is higher than conventional TACE. The technology of TACE has seen the introduction of several types of embolics that are made of different materials. Available embolics for TACE include: drug-eluting beads (DC beads), acrylic copolymer, tris-acrylic microspheres and polyethylene glycol (PEG) microspheres. Few studies are available on PEG embolics and their use for TACE. This review focuses on the efficacy and safety of TACE performed with PEG microspheres for the treatment of hepatocellular carcinoma and discusses future therapeutic advantages.

Transarterial chemoembolization is an effective, minimally invasive therapy that is widely used for treatment of unresectable colorectal cancer liver metastases (CRC-LM). However, chemoembolization induces a hypoxic microenvironment, which increases neoangiogenesis and may promote early progression. For this reason, transarterial chemoembolization efficacy may be improved by combining it with an angiogenesis inhibitor, such as bevacizumab. This report shows that transarterial chemoembolization with irinotecan-loaded polyethylene glycol embolics and bevacizumab therapy was effective and well tolerated by 6 patients with CRC-LM, resulting in a disease control rate of 83% and an overall improvement in quality of life., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study is to determine the efficacy and tolerability of transarterial chemoembolization (TACE) using polyethylene glycol (PEG) drug-elutable microspheres loaded with doxorubicin for treatment of hepatocellular carcinoma (HCC)., Subjects and Methods: Forty-two patients with unresectable HCC, as determined by a tumor board, were assigned to undergo TACE and were treated with PEG drug-elutable embolics loaded with doxorubicin. Patients were prospectively enrolled and included 32 (76%) men and 10 (24%) women. Their median age was 65 years (range, 42-83 years). Patients were treated with 50 mg of doxorubicin loaded in 2 mL of PEG embolics (mean [± SD] diameter, 100 ± 25 µm) that were infused via a chemoembolization method. Data collected included previous cancer therapy, tumor size, number of lesions, history of TACE, tumor response (at 1, 3, and 6 months), type and intensity of adverse events, and quality of life (QOL) analysis., Results: One month after TACE, the overall tumor response rate was 79% (50% complete response, 29% partial response, 17% stable disease, and 5% progressive disease). At 3 months, the rates were 48% for complete response, 24% for partial response, 24% for stable disease, and 3% for progressive disease. At 6 months, the rates were 43% for complete response, 19% for partial response, 29% for stable disease, and 10% for progressive disease. TACE was well tolerated by all patients, with no evidence of procedure-related complications or systemic drug-related adverse events. Fever (33%), increase in transaminase level (17%), and pain (33%) were the most frequent adverse events, and their intensity was mostly mild (grades 1 and 2). The QOL scores were 80 at 1 month, 81 at 3 months, and 82 at 6 months after TACE., Conclusion: These data suggest that PEG embolics are efficacious and safe for the treatment of HCC, as indicated by their good tolerability, QOL scores, and high tumor response.

Background and Aims: Whether Fibroscan thresholds can be immediately adopted for none, some or all other shear wave elastography techniques has not been tested. The aim of the present study was to test the concordance of the findings obtained from 7 of the most recent ultrasound elastography machines with respect to Fibroscan., Methods: Sixteen hepatitis C virus-related patients with fibrosis ≥2 and having reliable results at Fibroscan were investigated in two intercostal spaces using 7 different elastography machines. Coefficients of both precision (an index of data dispersion) and accuracy (an index of bias correction factors expressing different magnitudes of changes in comparison to the reference) were calculated., Results: Median stiffness values differed among the different machines as did coefficients of both precision (range 0.54-0.72) and accuracy (range 0.28-0.87). When the average of the measurements of two intercostal spaces was considered, coefficients of precision significantly increased with all machines (range 0.72-0.90) whereas of accuracy improved more scatteredly and by a smaller degree (range 0.40-0.99)., Conclusions: The present results showed only moderate concordance of the majority of elastography machines with the Fibroscan results, preventing the possibility of the immediate universal adoption of Fibroscan thresholds for defining liver fibrosis staging for all new machines., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aim: The aim is to report clinical outcomes of hepatic intra-arterial (IACHT) and systemic chemotherapy (SCHT), followed by gemcitabine-based maintenance therapy (maintenance), for the treatment of relapsed or unresectable cholangiocarcinoma., Patients & Methods: In this retrospective observational study, 145 cholangiocarcinoma patients were treated with Epirubicin-Cisplatin as IACHT associated with Capecitabine or 5-fluorouracil as SCHT. Maintenance was performed with gemcitabine-based schedule. Toxicity was assessed with NCI-CTCAE and tumor response with RECIST 1.1., Results: Tumor response was complete in 1%, partial in 20%, stable disease in 48% and progression in 31% of patients (3 months after therapy). The most frequent adverse events were: anemia (24%), nausea and vomiting (33%), alopecia (60%)., Conclusion: Cholangiocarcinoma patients may benefit from IAHCT-SCHT. Maintenance may prolong clinical benefits. ClinicalTrials.gov registry Identifier: NCT01920503., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Aim: To report clinical outcomes of transarterial chemoembolization (TACE) using drug-eluting beads (DEBs) loaded with doxorubicin for the treatment of unresectable intrahepatic cholangiocarcinoma (CCA)., Patients and Methods: We treated 127 patients with doxorubicin via TACE. Inclusion criteria were: diagnosis of unresectable CCA; indication for TACE, performance status (PS) 0-2, >3 months of life expectancy, >18 years old, written consent. TACE was performed using DEBs for 109 (86%) patients and polythylene glycol drug-elutable microspheres (PEG) loaded with doxorubicin for 18 (14%) patients., Results: Tumor response of the whole sample of 127 patients was partial response (PR) in 19 (15%) patients, stable disease (SD) in 101 (80%) and progressive disease (PD) in seven (5%) 3 months after therapy, with no complete responses. There were differences between type of embolics: PR was 7% and 77%, SD was 88% and 8%, and PD was 5% and 15%, and the disease control rate was 95% and 85% in the DEB and PEG groups, respectively. Most frequent side-effects were: abdominal pain, fever, nausea, and transaminase rise., Conclusion: TACE was effective and safe for CCA treatment, with a high disease control rate. The best response of PEG-TACE was PR, whereas it was SD for DEB-TACE., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Recently, there has been the launch of the new Polyethylene glycol (PEG) drug-eluting beads (LifePearl®) for transarterial chemoembolization. Their innovation is that PEG guarantees more compressibility, elasticity and maximizes beads' suspension time. We applied these beads for hepatic intra-arterial infusion of irinotecan or doxorubicin for the therapy of primary and metastatic liver cancer., Patients and Methods: We treated 20 consecutive patients, affected by unresectable primary liver cancer (PLC) or hepatic metastases (refractory to chemotherapy) using chemoembolization with doxorubicin or irinotecan pre-loaded Lifepearls., Results: Tumor response rate was >80% in most patients with 63% of complete and 37% of partial response. We observed no complications during the chemoembolization and no severe general drug-related side-effects., Conclusion: Our data suggest that chemoembolization with LifePearl® is efficacious and safe for the treatment of liver cancer as indicated by good tolerability, quality of life and high tumor response., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To analyze contrast-enhanced ultrasound (CEUS) features of histologically proven hepatic epithelioid hemangioendothelioma (HEHE) in comparison to other multilocular benign focal liver lesions (FLL)., Methods: Twenty-five patients with histologically proven HEHE and 45 patients with histologically proven multilocular benign FLL were retrospectively reviewed. Four radiologists assessed the CEUS enhancement pattern in consensus., Results: HEHE manifested as a single (n = 3) or multinodular (n = 22) FLL. On CEUS, HEHE showed rim-like (18/25, 72%) or heterogeneous hyperenhancement (7/25, 28%) in the arterial phase and hypoenhancement (25/25, 100%) in the portal venous and late phases (PVLP), a sign of malignancy. Eighteen patients showed central unenhanced areas (18/25, 72%); in seven patients (7/25, 28%), more lesions were detected in the PVLP. In contrast, all patients with hemangioma and focal nodular hyperplasia showed hyperenhancement as the most distinctive feature (P < 0.01)., Conclusion: CEUS allows for characterization of unequivocal FLL. By analyzing the hypoenhancement in the PVLP, CEUS can determine the malignant nature of HEHE.

In the last 12 - 18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan(®) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by transient elastography, performed with Fibroscan(®), a technology dedicated exclusively to liver elastography. Since then, more than 1300 articles dealing with transient elastography have been listed in PubMed, some describing results with more than 10,000 patients 5. The technique has been tested in nearly all liver disease etiologies, with histology as the reference standard. Meta-analysis of data, available in many etiologies 6, showed good performance and reproducibility as well as some situations limiting reliability 5. Thresholds for the different fibrosis stages (F0 to F4) have been provided by many large-scale studies utilizing histology as the reference standard 7. Transient elastography tracks the velocity of shear waves generated by the gentle hit of a piston on the skin, with the resulting compression wave traveling in the liver along its longitudinal axis. The measurement is made in a 4 cm long section of the liver, thus able to average slightly inhomogeneous fibrotic deposition.In 2008 a new modality became available, Acoustic Radiation Force Impulse (ARFI) quantification, and classified by EFSUMB 1 as point shear wave elastography (pSWE), since the speed of the shear wave (perpendicular to the longitudinal axis) is measured in a small region (a "point", few millimeters) at a freely-choosen depth within 8 cm from the skin. This technology was the first to be implemented in a conventional ultrasound scanner by Siemens(®) 8. Several articles have been published regarding this technology, most with the best reference standards 9, some including findings on more than 1000 hepatitis C patients 10 or reporting meta-analysis of data 11. Although the correlation between Siemens pSWE and transient elastography appeared high 12 13, the calculated thresholds for the different fibrosis stages and the stiffness ranges between the two techniques are not superimposable.Interestingly, pSWE appears to provide greater applicability than transient elastography for measuring both liver 13 and spleen stiffness, which is a new application of elastography 14, of interest for the prediction of the degree of portal hypertension 15 16.Nowadays other companies have started producing equipment with pSWE technology, but only very few articles have been published so far, for instance describing the use of Philips(®) equipment, which was the second to provide pSWE. These articles show preliminary good results also in comparison with TE 17 18. Not enough evidence is currently available in the literature about the elastographic performance of the products most recently introduced to the market. Furthermore, with some products the shear wave velocities generated by a single ultrasound acoustic push pulse can be measured in a bidimensional area (a box in the range of 2 - 3 cm per side) rather than in a single small point, producing a so-called bidimensional 2D-SWE 1. The stiffness is depicted in color within the area and refreshing of the measurement occurs every 1 - 2 seconds. Once the best image is acquired, the operator chooses a Region Of Interest (ROI) within the color box, where the mean stiffness is then calculated. 2D-SWE can be performed as a "one shot" technique or as a semi-"real-time" technique for a few seconds (at about 1 frame per second) in order to obtain a stable elastogram. With either technique, there should be no motion/breathing during image acquisition. A bidimensional averaged area should overcome the limitation of pSWE to inadvertently investigate small regions of greater or lesser stiffness than average. A shear wave quality indicator could be useful to provide real-time feedback and optimize placement of the sampling ROIs, a technology recently presented by Toshiba(®), but which is still awaiting validation in the literature.Supersonic Imagine by Aixplorer(®) which works with a different modality of insonation and video analysis compared to the the previously-mentioned three techniques (i. e., transient elastography, pSWE and 2D-SWE), leading to a bidimensional assessment of liver stiffness in real time up to 5 Hz and in larger regions; thus this technique is also termed real-time 2 D SWE. It has been available on the market for a few years 19 20, and many articles have been published showing stiffness values quite similar to those of Fibroscan(®) 21; likewise, defined thresholds based on histological findings have appeared in several articles 19 20 21.After this brief summary of the technological state of the art we would like to mention the following critical issues that we believe every user should note prior to providing liver stiffness reports. · The thresholds obtained from the "oldest" techniques for the various fibrosis stages based on hundreds of patients with histology as reference standard cannot be straightforwardly applied to the new ultrasound elastography techniques, even if based on the same principle (e. g. pSWE). In fact, the different manufacturers apply proprietary patented calculation modes, which might result in slightly to moderately different values. It should be kept in mind that the range for intermediate fibrosis stages (F1 to F3) is quite narrow, in the order of 2 - 3 kilopascal (over a total range spanning 2 to 75 kPa with Fibroscan), so that slightly different differences in outputs could shift the assessment of patients from one stage to another. Comparative studies using phantoms and healthy volunteers, as well as patients, are eagerly awaited. In fact, the equipment might not produce linear correlations of measurements at different degrees of severity of fibrosis. As a theoretical example, some equipment might well correlate in their values with an older technique, such as transient elastography, at low levels of liver fibrosis, but not as well in cases of more advanced fibrosis or vice versa. Consequentely, when elastography data are included in a report, the equipment utilized for the measurement should be clearly specified, and conclusions about the fibrosis stage should be withheld if an insufficient number of comparative studies with solid reference standards are available for that specific equipment.. · Future studies using histology as a reference might be biased in comparison to previous studies, since nowadays fewer patients with chronic hepatitis C or hepatitis B undergo biopsy. In fact, due to wide availability of effective drugs as well as the use of established elastography methods for patients with viral hepatitis, most cases submitted to biopsy today have uncertain etiology or inconsistent and inconclusive clinical data. Therefore, extrapolated thresholds from such inhomogeneous populations applied to more ordinary patients with viral hepatitis might become problematic in the future, although no better solution is currently anticipated. This situation might lead to the adoption of a standard validated elastographic method as reference, but this has to be agreed-upon at an international level.. · Ultrasound elastography embedded in conventional scanners usually allows the choice of where to place the ROI within the color stiffness box and whether to confirm or exclude each single measurement when determining the final value. Thus, the operator has a greater potential to influence the final findings than with Fibroscan®, where these choices are not available. This has to be kept in mind to avoid the possibility that an operator could, even inadvertently, tend to confirm an assumption about that specific patient or to confirm the patient's expectations.. · Quality criteria for the new technologies following transient elastography are absent (depending on the manufacturer) or have not been satisfactorily defined, so that the information potentially inserted in a report cannot currently be judged for its reliability by the clinician.. (ABSTRACT TRUNCATED), (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: To better define the efficacy and the safety of intra-arterial infusion performed with or without hemofiltration for recurrent limb melanoma., Methods: Patients with the following characteristics were included in the study: recurrent limb melanoma not indicated for surgical resection, measurable disease in the extremity, > 18 years, performances status (Eastern Cooperative Oncology Group ) was 0-1 and life expectancy of at least 6 mo. Twenty nine consecutive patients were enrolled in the study. Patients underwent fluoroscopic placement of angiographic arterial and venous catheters to infuse the drug in the artery [isolated limb infusion (ILI)], and to stop the out flow (venous). Melphalan was rapidly infused into the isolated limb via the arterial catheter after the inflation of venous balloon catheter. Then the circulation of the limb was completely blocked with a pneumatic cuff at the root of the limb. Haemofiltration (HF) was available only in the main center, and was performed with an extracorporeal perfusion system, in order to reduce high systemic toxic peaks of drug., Results: Thirty seven ILI were done in 29 cases (31 ILI-HF and 6 ILI) between 2001 and 2014 at Ancona and Pesaro Hospitals, Italy. Clinical outcomes were monitored 30 d after treatment. Eleven patients (38%) received infusion of melphalan alone, 7 (24%) melphalan associated to mitomicin C and 7 (24%) melphalan associated to cisplatin, the remaining 4 were treated with cisplatin, melphalan and epirubicin or cisplatin and mitomicin C. The overall response rate was 66%, in particular, 3 patients (10%) were complete responders and 16 (56%) were partial responders; whereas 7 patients (24%) had stable disease, and 3 (10%) showed progressive disease. Limb toxicity was assessed adopting Wieberdink scale, with evidence of 90% of low grade (I and II) toxicity., Conclusion: ILI-HF and ILI are effective and safe treatments for recurrent non-resectable limb melanoma. They present evidence of favorable clinical benefit and is effective in delaying progression.

Aim: To investigate efficacy and safety of second-line treatment with irinotecan-loaded drug-eluting beads (DEBIRI) and cetuximab (DEBIRITUX) of unresectable colorectal liver metastases., Methods: Patients with the following characteristics were included in the study: unresectable hepatic metastases from colorectal carcinoma (CRC-LM), progression after first line chemotherapy (any type of chemotherapeutic drug and combination was allowed), second line treatment (mandatory), which included for each patient (unregarding the KRas status) two cycles of DEBIRI (using 100-300 μm beads loaded with irinotecan at a total dose 200 mg) followed by 12 cycles of cetuximab that was administered weekly at a first dose of 400 mg/m(2) and then 250 mg/m(2); good performance status (0-2) and liver functionality (alanine aminotransferase and gamma-glutamyl transferase not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/mL). Data were collected retrospectively and included: tumor response (evaluated monthly for 6 mo then every 3 mo), overall response rate (ORR), KRas status, type and intensity of adverse events (G according to the Common Terminology Criteria for Adverse Events v3.0, CTCAE), overall survival (OS) and progression free survival (PFS)., Results: Forty consecutive cases of CRC hepatic metastases were included in the study. Median duration of DEBIRITUX was 4.4 mo (range, 4.0-6.5). Sixteen patients (40%) received the planned 2 cycles of DEBIRI and an average of 10 cetuximab cycles. ORR of the whole sample was 50%, in particular 4 patients were complete responders (10%) and 16 (40%) partial responders. The most observed side effects (G2) were: post-embolization syndrome (30%), diarrhea (25%), skin rushes (38%) and asthenia (35%). The retrospective evaluation of KRas status (24 wild type, 16 mutated) showed that the group of patients with wild type KRas had ORR significantly higher than mutant KRas. Median follow-up was 29 mo (8-48 range); median PFS was 9.8 mo and OS was 20.4 mo. Future randomized trials are required in this setting to establish a role for DEBIRITUX compared with systemic chemotherapy., Conclusion: DEBIRITUX seems to be efficacious after first line chemotherapy for the treatment of unresectable CRC-LM.

Currently image-guided trans-arterial chemoembolization (TACE) has a significant role in the therapy of patients with hepatocellular carcinoma and liver metastases. This endovascular hepatic-directed therapy offers the dual benefit of true local neoplastic control and reduction of side-effects. As a result, it has been included in the guidelines for primary liver cancer and is often considered as salvage therapy for patients liver metastases from neuroendocrine and chemorefractory colorectal tumors. The development of new embolizing agents, such as DC beads loaded with doxorubicin and irinotecan, permits better standardization and definition of protocols, making the procedures less linked to criteria of different hospitals and personal experiences of interventional radiologists. The understanding that hypoxia induces vessel re-growth will open a new avenue for clinical research and a rebirth for TACE. Chemoembolization followed by target therapy (bevacizumab, aflibercept and regorafenib) could increase quality, duration of responses and better quality of life.

Background: Metastases to the liver receive most of their blood supply from the arterial route, therefore for patients with hepatic metastases from large bowel cancer, hepatic arterial infusion adopting drug-eluting beads preloaded with irinotecan (DEBIRI) may offer a chance of cure., Patients and Methods: In a multi-institutional study, 74 patients were randomly assigned to receive DEBIRI (36) versus systemic irinotecan, fluorouracil and leucovorin (FOLFIRI, 38). The primary end-point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost and influence of molecular markers., Results: At 50 months, overall survival was significantly longer for patients treated with DEBIRI than for those treated with FOLFIRI (p=0.031, log-rank). Median survival was 22 (95% Confidence Interval CI=21-23) months, for DEBIRI and 15 (95% CI=12-18) months for FOLFIRI. Progression-free survival was 7 (95% CI=3-11) months in the DEBIRI group compared to 4 (95% CI=3-5) months in the FOLFIRI group and the difference between groups was statistically significant (p=0.006, log-rank). Extrahepatic progression had occurred in all patients by the end of the study, at a median time of 13 (95% CI=10-16) months in the DEBIRI group compared to 9 (95% CI 5-13) months in the FOLFIRI group. A statistically significant difference between groups was not observed (p=0.064, log-rank).The median time for duration of improvement to quality of life was 8 (95% CI=3-13) months in the DEBIRI group and 3 (95% CI=2-4) months in the FOLFIRI group. The difference in duration of improvement was statistically significant (p=0.00002, log-rank)., Conclusion: This study showed a statistically significant difference between DEBIRI and FOLFIRI for overall survival (7 months), progression-free survival (3 months) and quality of life (5 months). In addition, a clinically significant improvement in time to extrahepatic progression (4 months) was observed for DEBIRI, a reversal of the expectation for a regional treatment. This suggests a benefit of DEBIRI treatment over standard chemotherapy and serves to establish the expected difference between these two treatment options for planning future large randomized studies.