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Background & Aims The Pre-TACE-Predict model was devised to assess prognosis of patients treated with trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). However, before entering clinical practice, a model should demonstrate that it performs a useful role. Methods We performed an independent external validation of the Pre-TACE model in a cohort that differs in setting and time period from the one that generated the original model. Data from 826 patients treated with TACE for naïve HCC (2008-2018) were used to assess calibration and discrimination of the Pre-TACE-Predict model. Results The four risk-categories identified by the Pre-TACE-Predict model had gradient monotonicity, with median survivals of 52.0, 36.2, 29.9, and 14.1 months respectively. However, predicted survivals systematically underestimated observed survivals (R2: 0.667). A recalibration was adopted maintaining fixed the prognostic index and modifying the baseline survival function. This resulted in an almost perfect calibration (R2: 0.995) in all the four risk categories. Cox regressions showed that aetiology and macrovascular invasion, included in the Pre-TACE-Predict model, had no prognostic impact in the present study population, and that coefficients for tumour size and multiplicity were overestimated. The c-index was similar to that of the m-HAP-III, but higher than those of HAP, m-HAP-II and the six-and-twelve models. Conclusions The recalibration of Pre-TACE-Predict model improved the estimation of survival probabilities of HCC patients treated with TACE. The highest discriminatory ability of the Pre-TACE-model in comparison to other available models, together with risk stratification and recalibration, makes it the best prognostic tool currently available for these patients.

Additional file 1. Supplementary Tables.

Additional file 2. Supplementary Figures.

The history of the European Federation of Societies in Ultrasound in Medicine and Biology (EFSUMB) is closely related to the general history of ultrasound. In the presented paper the physical background and history of technologies including A-mode, Time motion or M-mode, 2D Imaging (B-mode) are summarized. In addition, ultrasound tissue characterization, Doppler ultrasound, 3D and 4D ultrasound, intracavitary and endoscopic ultrasound, interventional ultrasound, ultrasonic therapy, contrast enhanced ultrasound (CEUS) and key developments in echocardiography are discussed.

This file includes additional results such as figures and tables. (DOCX 60 kb)

Contains fulltext : 220051.pdf (Publisher’s version ) (Closed access) Congenital extrahepatic portosystemic shunt (CEPS) or Abernethy malformation is a rare condition in which splanchnic venous blood bypasses the liver draining directly into systemic circulation through a congenital shunt. Patients may develop hepatic encephalopathy (HE), pulmonary hypertension (PaHT), or liver tumors, among other complications. However, the actual incidence of such complications is unknown, mainly because of the lack of a protocolized approach to these patients. This study characterizes the clinical manifestations and outcome of a large cohort of CEPS patients with the aim of proposing a guide for their management. This is an observational, multicenter, international study. Sixty-six patients were included; median age at the end of follow-up was 30 years. Nineteen patients (28%) presented HE. Ten-, 20-, and 30-year HE incidence rates were 13%, 24%, and 28%, respectively. No clinical factors predicted HE. Twenty-five patients had benign nodular lesions. Ten patients developed adenomas (median age, 18 years), and another 8 developed HCC (median age, 39 years). Of 10 patients with dyspnea, PaHT was diagnosed in 8 and hepatopulmonary syndrome in 2. Pulmonary complications were only screened for in 19 asymptomatic patients, and PaHT was identified in 2. Six patients underwent liver transplantation for hepatocellular carcinoma or adenoma. Shunt closure was performed in 15 patients with improvement/stability/cure of CEPS manifestations. Conclusion: CEPS patients may develop severe complications. Screening for asymptomatic complications and close surveillance is needed. Shunt closure should be considered both as a therapeutic and prophylactic approach.

Background & Aims The role of hepatic resection for hepatocellular carcinoma (HCC) in different Barcelona Clinic Liver Cancer (BCLC) stages is controversial. We aimed at measuring the survival benefit of resection vs. non-surgical-therapies in each BCLC stage. Methods Using the ITA.LI.CA database, we identified 2090 BCLC A, B, and C HCC patients observed between 2000 and 2012: 550 underwent resection, 1046 loco-regional therapy (LRT), and 494 best supportive care (BSC). A multivariate log-logistic model was chosen to predict median survival (MS) after resection vs. MS after LRT or BSC. The results were expressed as net survival benefit of resection: (MS resection - MS LRT)/MS BSC. Results After stratifying for BCLC stage, the median net survival benefit of resection over LRT was: BCLC 0 = 62% (40%, 82%), A = 45% (13%, 65%), B = 46% (9%, 76%), C = -16% (-55%, 33%). Model for end-stage liver disease (MELD) score >9, Child B class, and performance status (PST) = 2 were the main risk factors for liver resection. 1181 Child A patients (57%) with MELD ≤9 and PST 9 or PST = 2 or Child B class), resection did not prove any survival benefit over LRT. Conclusions Resection could result in survival benefit over LRT for HCC patients regardless of their BCLC stage, provided that liver dysfunction (Child B or MELD >9) and PST >1 are absent.

This is the first part of the Guidelines on Interventional Ultrasound of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and covers all general aspects of ultrasound-guided procedures (short version; the long version is published online).

Summary Background Hepatitis C virus (HCV) and alcohol abuse are the main risk factors for hepatocellular carcinoma (HCC) in Western countries. Aim To investigate the role of alcoholic aetiology on clinical presentation, treatment and outcome of HCC as well as on each Barcelona Clinic Liver Cancer (BCLC) stage, as compared to HCV-related HCCs. Methods A total of 1642 HCV and 573 alcoholic patients from the Italian Liver Cancer (ITA.LI.CA) database, diagnosed with HCC between January 2000 and December 2012 were compared for age, gender, type of diagnosis, tumour burden, portal vein thrombosis (PVT), oesophageal varices, liver function tests, alpha-fetoprotein, BCLC, treatment and survival. Aetiology was tested as predictor of survival in multivariate Cox regression models and according to HCC stages. Results Cirrhosis was present in 96% of cases in both groups. Alcoholic patients were younger, more likely male, with HCC diagnosed outside surveillance, in intermediate/terminal BCLC stage and had worse liver function. After adjustment for the lead-time, median (95% CI) overall survival (OS) was 27.4 months (21.5–33.2) in alcoholic and 33.6 months (30.7–36.5) in HCV patients (P = 0.021). The prognostic role of aetiology disappeared when survival was assessed in each BCLC stage and in the Cox regression multivariate models. Conclusions Alcoholic aetiology affects survival of HCC patients through its negative effects on secondary prevention and cancer presentation but not through a greater cancer aggressiveness or worse treatment result. In fact, survival adjusted for confounding factors was similar in alcoholic and HCV patients.

PURPOSE: To evaluate the per-nodule efficacy of superselective transarterial chemoembolization of hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: From 2006-2009, 271 cirrhotic patients with 635 nodules underwent a first superselective transarterial chemoembolization, repeated "on demand" after local recurrences (LR) or partial responses (PR). Complete response (CR), time to nodule progression (TTnP), and local recurrence rate (LRR), according to three size classes (≤ 2 cm, 2.1-5 cm, and>5 cm) were evaluated. RESULTS: After the first superselective transarterial chemoembolization, the CR was 64%, sustained over time in 77%, higher in small (68%) and intermediate-size (64%) nodules than in large nodules (25%; P5 cm had a CR of 25% after the first superselective transarterial chemoembolization, LR of 50% and PR of 25%, and after the second and third superselective transarterial chemoembolizations, PR of 0%. CONCLUSIONS: Effectiveness of superselective transarterial chemoembolization has a clear cutoff above and below 5-cm nodules, with better results in smaller nodules. In HCCs ≤ 5 cm, the efficacy of the first and second superselective transarterial chemoembolizations performed for LR was higher than the second superselective transarterial chemoembolization for PR and the third superselective transarterial chemoembolization. For HCCs>5 cm, retreatment of PR is of little value, and the third cycle is ineffective.

The allocation rules for patients with hepatocellular carcinoma (HCC) who are awaiting liver transplantation (LT) are a difficult issue and are continually evolving. To reduce tumor progression or down-stage advanced disease, most transplant centers have adopted the practice of treating HCC candidates with resection or locoregional therapies. This study was designed to assess the effectiveness of bridge therapy in preventing removal from the waiting list for death/sickness severity or tumor progression beyond the Milan criteria and in determining posttransplant outcomes. The removal rates for 315 adult patients with HCC who were listed for LT were analyzed and were correlated to responses to bridge therapy with a competing risk analysis. The 3-, 6-, and 12-month dropout rates were 3.5%, 6.5%, and 19.9%, respectively, and they were significantly affected by the Model for End-Stage Liver Disease score (P = 0.032), the tumor stage at diagnosis (P = 0.041), and the response to bridge therapy (P < 0.001). The stratification of candidates by the tumor stage and the response to bridge therapy showed that patients with T2 tumors who achieved only a partial response or no response to bridge therapy had the highest dropout rates, and they were followed by patients with successfully down-staged T3-T4a tumors (P = 0.037). Patients with T2 tumors who had a complete response and patients with T1 tumors had similar dropout rates (P = 0.964). The response to bridge therapy significantly affected both the recurrence rate of 176 transplant patients (P = 0.017) and the overall intention-to-treat survival rate (P = 0.001). In conclusion, the response to therapy is a potentially effective tool for prioritizing HCC patients for LT as well as select cases with different risks of tumor recurrence after transplantation.

Factors associated with sustained virological response (SVR) in patients treated for hepatitis C virus (HCV) recurrence after liver transplantation (LT) are unclear. Ninety-nine HCV-positive/hepatitis B surface antigen-negative patients received antiviral treatment (AVT) with interferon/peginterferon plus ribavirin for HCV recurrence after LT. Cyclosporine (CyA) or tacrolimus (TAC) was used as the main immunosuppressor in 37 (37%) and 62 (63%) patients, respectively. Twenty-five patients (25%) achieved an SVR. Twenty-seven donor-related, recipient-related, HCV-related, and immunosuppression-related variables were investigated for their association with SVR. In logistic regression analysis, donor age < 60 years (odds ratio = 4.45, 95% confidence interval = 1.39-14.19, P = 0.01), viral genotype other than 1 (odds ratio = 4.97, 95% confidence interval = 1.59-15.48, P = 0.006), and the use of CyA during treatment (odds ratio = 6.85, 95% confidence interval = 2.15-21.73, P = 0.001) were predictors of SVR. Patients treated with CyA (SVR rate: 43%) and those treated with TAC (SVR rate: 14%) were comparable for all variables, except for a shorter ischemia time and shorter timing of AVT initiation in the TAC group (P = 0.02 and P = 0.005, respectively) and a greater use of anti-CD25 antibodies, azathioprine, and mycophenolate mofetil in the CyA group (P = 0.03, P < 0.001, and P = 0.001, respectively). The rate of AVT discontinuation due to side effects was similar between groups (16% versus 8%, P = 0.3). In conclusion, the type of immunosuppression during AVT may predict SVR in patients treated for HCV recurrence after LT.

AIM: To evaluate the acute effect of treatment with the molecular adsorbent recirculating system (MARS) on splanchnic, renal and systemic haemodynamics in patients with end-stage cirrhosis. METHODS: Twelve patients with end-stage cirrhosis, undergoing MARS treatment, were enrolled. The following haemodynamic parameters were measured by means of Doppler ultrasonography and thoracic electrical bioimpedance, before and after each session: portal velocity, renal and splenic resistance indices, cardiac output, cardiac stroke volume, heart rate, mean arterial pressure, systemic vascular resistance. RESULTS: Median portal velocity increased significantly after treatment (23.7 vs. 20.3 cm/s, P < 0.05) while renal resistance index (0.72 vs. 0.75, P < 0.05) and splenic resistance index (0.60 vs. 0.65, P < 0.05) decreased significantly. Mean arterial pressure (83 vs. 81 mmHg, P < 0.05) and vascular resistance (899 vs. 749 dyne. s/cm5, P < 0.05) increased significantly, while cardiac output and stroke volume showed no significant changes. CONCLUSIONS: Data emerging from this investigation suggest that MARS treatment improves significantly various haemodynamic alterations in cirrhotic patients in the short term. The observed decrease in renal vascular resistance and improvement in splenic resistance index, a parameter related to portal resistance, which leads us to hypothesize that these haemodynamic effects are probably mediated by clearance of vasoactive substances during MARS treatment.

Background: Inflammation is a long-established hallmark of liver fibrosis and carcinogenesis. Eosinophils are emerging as crucial components of the inflammatory process influencing cancer development. The role of blood eosinophils in patients with hepatocellular carcinoma receiving systemic treatment is an unexplored field. Objective: The objective of this study was to analyse the prognostic role of the baseline eosinophil count in patients with sorafenib-treated hepatocellular carcinoma. Patients and Methods: A training cohort of 92 patients with advanced- or intermediate-stage sorafenib-treated hepatocellular carcinoma and two validation cohorts of 65 and 180 patients were analysed. Overall survival and progression-free survival in relation to baseline eosinophil counts were estimated by the Kaplan–Meier method. Univariate and multivariate analyses were performed. Results: A negative prognostic impact of low baseline eosinophil counts (< 50*109/L) was demonstrated in all cohorts (training cohort: hazard ratio = 50.1, 95% confidence interval 11.6–216.5, p < 0.0001 for low vs high eosinophil counts; first validation cohort: hazard ratio = 4.55, 95% confidence interval 1.24–16.65, p = 0.022; second validation cohort: hazard ratio = 3.21, 95% confidence interval 1.83–5.64, p < 0.0001). Moreover, low eosinophil counts had a negative prognostic role in patients progressing on or intolerant to sorafenib who received second-line regorafenib, but not capecitabine or best supportive care. Conclusions: Our analysis identified baseline blood eosinophil counts as a new prognostic factor in patients with sorafenib-treated hepatocellular carcinoma. Concerning second-line therapies, eosinophil counts were associated with survival outcomes only in regorafenib-treated patients, suggesting a possible predictive role in this setting.

This mono-institutional observational study was conducted to determine incidence, severity, risk factors, and outcome of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in high-risk Ewing sarcoma (ES) patients treated with intravenous busulfan and melphalan (BU-MEL) followed by autologous stem cell transplantation (ASCT). During the past 10 years, 75 consecutive ES patients resulted evaluable for the analysis. After diagnosis of SOS/VOD, defibrotide therapy was started as soon as the medication was available. The variables analyzed as potential risk factors were: gender, patient's age at diagnosis, primary tumor site, disease stage, and prior radiation therapy (RT) given, focusing on RT liver exposure. The median age at diagnosis was 18.8 years. Five patients developed moderate to severe SOS/VOD (cumulative incidence, 6.67%). None of 32 pediatric patients (≤17 years) developed SOS/VOD (p = 0.0674). In univariate analysis, prior RT liver exposure resulted statistically significant (p = 0.0496). There was one death due to severe SOS/VOD. This study reports the largest series of high-risk ES patients treated with intravenous BU-MEL before ASCT. The incidence of SOS/VOD was lower when compared with other studies that used oral busulfan. Any prior RT liver exposure should be avoided. Earlier defibrotide treatment confirms to be effective.

none 7 no Background & Aims: Pain management in cirrhosis is a clinical challenge. Most analgesics are metabolized in the liver and cirrhosis may deeply alter their concentration, favouring the appearance of side effects. We aimed to assess the efficacy and safety of oral prolonged-release association of oxycodone/naloxone tablets (OXN) in the treatment of moderate/severe cancer pain in cirrhotic patients with metastatic hepatocellular carcinoma (HCC). Methods: We enrolled n = 32 HCC patients with moderate/severe cancer pain unresponsive to paracetamol alone or associated with codeine or tramadol. All patients received an initial OXN dose of 5 mg bid to be gradually increased in case of insufficient analgesia. At baseline and follow-up visits, we evaluated: pain intensity (using the Numerical Rating Scale, NRS), patients' autonomy in daily activities (Barthel Functioning Index); bowel dysfunction (Bowel Function Index, BFI), signs of hepatic encephalopathy (HE) and other opioid-induced side effects. Results: No clinically significant adverse effects were reported (median follow-up 122 days). No significant worsening of the BFI score was noted and no cases of HE were detected. Two patients (6.3%) discontinued treatment before T14 because of mild nausea and dizziness. The remaining n = 30 patients were assessed for efficacy. Treatment led to a significant reduction in the mean of pain scores both at T14 (-37.1 ± 16.3%, P < .001) and at T28 (-55.6 ± 21.5%, P < .001); Barthel scores showed gradual and significant increase from T0 (81.6 ± 13.0) to T14 (86.5 ± 11.4, P = .001) and to T28 (88.3 ± 13.6, P = .009). Conclusions: OXN may be considered a safe and effective option in the fragile population of cirrhotic patients. Tovoli, Francesco; De Lorenzo, Stefania; Samolsky Dekel, Boaz G.; Piscaglia, Fabio; Benevento, Francesca; Brandi, Giovanni; Bolondi, Luigi Tovoli, Francesco; De Lorenzo, Stefania; Samolsky Dekel, Boaz G.; Piscaglia, Fabio; Benevento, Francesca; Brandi, Giovanni; Bolondi, Luigi

Purpose: Different shear wave elastography (SWE) machines able to quantify liver stiffness (LS) have been recently introduced by various companies. The aim of this study was to investigate the agreement between point SWE with Esaote MyLab Twice (pSWE.ESA) and 2D SWE with Aixplorer SuperSonic (2D SWE.SSI). Moreover, we assessed the correlation of these machines with Fibroscan in a subgroup of patients. Methods: A total of 81 liver disease patients and 27 subjects without liver disease accessing the ultrasound lab were considered. Exclusion criteria were liver nodules, BMI >35, and severe comorbidities. LS was sampled from the same intercostal space with both pSWE.ESA and 2D SWE.SSI and values were tested with Lin’s analysis and Bland–Altman analysis (B&A). Agreement between each SWE machine and Fibroscan was assessed in 26 liver disease patients with Spearman correlation. Results: Precision and accuracy between pSWE.ESA and 2D SWE.SSI were, respectively, 0.839 and 0.999. B&A showed a mean of only −0.2 kPa, with no systematic deviation between the techniques and limits of agreement at −11.6 and 11.3 kPa. Spearman’s rho correlation versus Fibroscan was 0.849 for pSWE.ESA and 0.878 for 2D SWE.SSI. The relationship became less strict in the higher range of LS (≥15.2 kPa), corresponding to cirrhosis. Conclusion: The overall degree of concordance of pSWE.ESA and 2D SWE.SSI in measuring LS resulted remarkable, also when compared with Fibroscan. The less strict correlation for patients with LS in the higher range would not affect the staging of disease as such patients are anyhow classified as cirrhotic.

Contrast-enhanced ultrasound (CEUS) is a specialized form of ultrasound (US) performed with an intravenous injection of microbubble contrast agents. It has been successfully used for a variety of applications including characterization of liver tumors. In April 2014, the American College of Radiology (ACR) convened a working group of international experts to develop ACR CEUS Liver Imaging Reporting and Data System (CEUS LI-RADS). An initial version of CEUS LI-RADS was published in August 2016. Although the CEUS LI-RADS concept and principles for liver lesion characterization, using dynamic contrast enhancement features, are similar to those for CT or MRI, there are significant differences between CT/MRI and CEUS LI-RADS. Therefore, CEUS LI-RADS has different diagnostic features and a unique characterization algorithm. The size of a lesion, the type and degree of arterial phase enhancement, the presence of washout, and the timing and degree of washout are the major features used for categorization. This paper describes key differences between CT/MRI and CEUS, and provides a diagnostic algorithm of CEUS LI-RADS with detailed, step-by-step instructions and imaging examples of CEUS LI-RADS categories.

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography with a focus on the assessment of diffuse liver disease. The short version provides clinical information about the practical use of elastography equipment and interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users.Dies ist die erste Überarbeitung der 2013 publizierten EFSUMB-Leitlinien zur klinischen Anwendung der Elastografie und konzentriert sich auf die diffusen Lebererkrankungen. Der klinische Teil dieser Leitlinien erläutert die praktische Anwendung der Elastografie bei der Beurteilung diffuser Lebererkrankungen unter Berücksichtigung der Geräteausstattung und Interpretation der Ergebnisse. Die aktuelle Literatur wurde analysiert unter besonderer Beachtung von Metaanalysen. Die klinische Anwendung der Elastografie wird unter Reflexion unterschiedlicher klinischer Szenarien und der unterschiedlichen Ätiologien diffuser Lebererkrankungen erläutert. Alle Empfehlungen erfolgten gemäß der Evidenz basierten Methodik der Oxford-Klassifikation. Das hier vorgestellte Update soll dem Anfänger und fortgeschrittenen Nutzer eine praktische Hilfe darstellen.

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EUS

Author(s): Kono, Yuko; Lyshchik, Andrej; Cosgrove, David; Dietrich, Christoph F; Jang, Hyun-Jung; Kim, Tae Kyoung; Piscaglia, Fabio; Willmann, Juergen K; Wilson, Stephanie R; Santillan, Cynthia; Kambadakone, Avinash; Mitchell, Donald; Vezeridis, Alexander; Sirlin, Claude B

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.

Patients with cirrhosis present with hemostatic alterations secondary to reduced availability of pro-coagulant and anti-coagulant factors. The net effect of these changes is a rebalanced hemostatic system. The Italian Association of the Study of the Liver (AISF) and the Italian Society of Internal Medicine (SIMI) promoted a consensus conference on the hemostatic balance in patients with cirrhosis. The consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Rome in December 2014. The statements were graded according to quality of evidence and strength of recommendations, and approved by an independent jury. The statements presented here highlight strengths and weaknesses of current laboratory tests to assess bleeding and thrombotic risk in cirrhotic patients, the pathophysiology of hemostatic perturbations in this condition, and outline the optimal management of bleeding and thrombosis in patients with liver cirrhosis.

In 2001, the European Association for the Study of the Liver (EASL) endorsed the possibility of achieving a non-invasive diagnosis of Hepatocellular Carcinoma (HCC) for the first time. Since then, various refinements of the criteria and techniques capable of achieving this diagnosis and the role of plasma and tissue oncomarkers have been reported in the literature and have been accepted to different extents in various geographical areas. Such tools can also potentially imply prognostic significance. The present article critically discusses some of the most relevant and debated challenges which have emerged in this field, including the role of contrast-enhanced ultrasound, and of hepatocyte-specific magnetic resonance contrast agents, the pitfall of transient hepatic attenuation differences, the reliability of biopsy and the status of biomarkers.

The impact of radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) on survival in patients with small hepatocellular carcinoma (HCC) is unclear. We compared their efficacy in cirrhotics with single HCC ≤2 cm.Two hundred forty-four cirrhotics with single HCC ≤2 cm treated with PEI (108 cases) or RFA (136 cases) were enrolled in the study. Eighty-one patients in each group were selected for propensity score matching analysis.The five-year survival was not significantly different (64.7% in PEI and 72.9% in RFA group) but the 5-year recurrence (73.3% in PEI and 49% in RFA group, p=0.023) and local tumor progression (49% in PEI and 30.1% in RFA group, p=0.018) were higher in the PEI group.PEI and RFA are equally effective in treating HCCs smaller than 2 cm in terms of 5-year survival, despite higher cumulative and local recurrence rates, in patients treated with PEI.

Background No standard second-line treatments are available for hepatocellular carcinoma patients who fail sorafenib therapy. We assessed the safety and efficacy of metronomic capecitabine after first-line sorafenib failure. Methods Retrospective analysis of consecutive hepatocellular carcinoma patients receiving metronomic capecitabine between January 2012 and November 2014. The primary end-point was safety, secondary end-point was efficacy, including time-to-progression and overall survival. Results Twenty-six patients (80% Child–Pugh A, 80% Barcelona Clinic Liver Cancer stage C) received metronomic capecitabine (500 mg/bid). Median treatment duration was 3.2 months (range 0.6–31). Fourteen (53%) patients experienced at least one adverse event. The most frequent drug-related adverse events were bilirubin elevation (23%), fatigue (15%), anaemia (11%), lymphoedema (11%), and hand–foot syndrome (7.6%). Treatment was interrupted in 19 (73%) for disease progression, in 4 (15%) for liver deterioration, and in 1 (3.8%) for adverse event. Disease control was achieved in 6 (23%) patients. Median time-to-progression was 4 months (95% confidence interval 3.2–4.7). Median overall survival was 8 months (95% confidence interval 3.7–12.3). Conclusions Metronomic capecitabine was well tolerated in hepatocellular carcinoma patients who had been treated with sorafenib. Preliminary data show potential anti-tumour activity with long-lasting disease control in a subgroup of patients that warrants further evaluation in a phase III study.

We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography, focused on the assessment of diffuse liver disease. The first part (long version) of these Guidelines and Recommendations deals with the basic principles of elastography and provides an update of how the technology has changed. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided regarding optimization of scanning technique, image display, image interpretation, reporting of data and some of the known image artefacts. The second part provides clinical information about the practical use of elastography equipment and the interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users.Dies ist die erste Überarbeitung der 2013 publizierten EFSUMB-Leitlinien zur klinischen Anwendung der Elastographie und konzentriert sich auf die diffusen Lebererkrankungen. Der erste Teil dieser Leitlinien und Empfehlungen handelt von den Grundlagen der Elastografie und erläutert die Weiterentwicklungen der Technologie während dieses Zeitraumes. Die praktischen Vor- und Nachteile der verschiedenen Techniken werden beschrieben. Auch die Optimierung der Untersuchungstechnik, Bilddarstellung, Bildinterpretation und die Befundbeschreibung sowie Artefakte werden dargelegt. Der klinische Teil dieser Leitlinien erläutert die praktische Anwendung der Elastografie bei der Beurteilung diffuser Lebererkrankungen unter Berücksichtigung der Geräteausstattung und Interpretation der Ergebnisse. Die aktuelle Literatur wurde analysiert unter besonderer Beachtung von Metaanalysen. Die klinische Anwendung der Elastografie wird unter Reflexion unterschiedlicher klinischer Szenarien und der unterschiedlichen Ätiologien diffuser Lebererkrankungen erläutert. Alle Empfehlungen erfolgten gemäß der Evidenz basierten Methodik der Oxford-Klassifikation. Das hier vorgestellte Update soll dem Anfänger und fortgeschrittenen Nutzer eine praktische Hilfe darstellen.

Gangrenous cholecystitis and perforation are severe complications of acute cholecystitis, which have a challenging preoperative diagnosis. Early identification allows better surgical management. Contrast-enhanced computed tomography (ceCT) is the current diagnostic gold standard. Contrast-enhanced ultrasonography (CEUS) is a promising tool for the diagnosis of gallbladder perforation, but data from the literature concerning efficacy are sparse. The aim of the study was to evaluate CEUS findings in pathologically proven complicated cholecystitis (gangrenous, perforated gallbladder, pericholecystic abscess). A total of 8 patients submitted to preoperative CEUS, and with subsequent proven acute complicated cholecystitis at surgical inspection and pathological analysis, were retrospectively identified. The final diagnosis was gangrenous/phlegmonous cholecystitis (n. 2), phlegmonous/ulcerative changes plus pericholecystic abscess (n. 2), perforated plus pericholecystic abscess (n. 3), or perforated plus pericholecystic biliary collection (n. 1). Conventional US findings revealed irregularly thickened gallbladder walls in all 8 patients, with vaguely defined walls in 7 patients, four of whom also had striated wall thickening. CEUS revealed irregular enhancing gallbladder walls in all patients. A distinct wall defect was seen in six patients, confirmed as gangrenous/phlegmonous cholecystitis at pathology in all six, and in four as perforation at macroscopic surgical inspection. CEUS is a non-invasive easily repeatable technique that can be performed at the bedside, and is able to accurately diagnose complicated/perforated cholecystitis. Despite the limited sample size in the present case series, CEUS appears as a promising tool for the management of patients with the clinical possibility of having an acute complicated cholecystitis.

Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Background & Aims: Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Methods: One-thousand three-hundred and eighty Child–Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. Results: The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p