Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge—conventional TACE. Recently, a drug-eluting bead (DC Bead®) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.

Criteria to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) are based on tumor size and number of nodules rather than on tumor biology. The present study was undertaken to assess the role of transarterial chemoembolization (TACE) in selecting patients with tumors suitable for LT. Ninety-six consecutive patients with HCC were treated by repeatedly performed TACE, 62 of them exceeding the Milan criteria. Patients meeting the Milan criteria were immediately listed, and patients beyond the listing criteria were listed upon downstaging of the tumor following successful TACE. Fifty patients were finally transplanted. Of these 50 patients, 34 exceeded the Milan criteria. In these 96 patients, overall 5-year survival was 51.9%. However, it was 80.9% for patients undergoing LT and 0% for patients without transplantation (P Ͻ 0.0001). Tumor recurrence was primarily influenced by the control of the disease through continued TACE during the waiting time. Freedom from recurrence after 5 years was 94.5% in patients (n ϭ 39) with progression-free TACE during the waiting time. Tumor recurrence was significantly higher in patients (n ϭ 11) who after initial response to TACE progressed again before LT (freedom from recurrence 35.4%; P ϭ 0.0017). Progression-free course of TACE during the waiting time (P ϭ 0.006; risk ratio, 8.95), and a limited number of tumor nodules as assessed in the surgical specimen (P ϭ 0.025; risk ratio, 0.116) proved to be significant predictors for freedom from recurrence in the multivariate analysis. Milan criteria were without impact on recurrence. Our data suggest that sustained response to TACE is a better selection criterion for LT than the initial assessment of tumor size or number.

ObjectivesTo evaluate the incidence, management, and outcome of visceral artery aneurysms (VAA) over one decade.Methods233 patients with 253 VAA were analyzed according to location, diameter, aneurysm type, aetiology, rupture, management, and outcome.ResultsVAA were localized at the splenic artery, coeliac trunk, renal artery, hepatic artery, superior mesenteric artery, and other locations. The aetiology was degenerative, iatrogenic after medical procedures, connective tissue disease, and others. The rate of rupture was much higher in pseudoaneurysms than true aneurysms (76.3 % vs.3.1 %). Fifty-nine VAA were treated by intervention (n = 45) or surgery (n = 14). Interventions included embolization with coils or glue, covered stents, or combinations of these. Thirty-five cases with ruptured VAA were treated on an emergency basis. There was no difference in size between ruptured and non-ruptured VAA. After interventional treatment, the 30-day mortality was 6.7 % in ruptured VAA compared to no mortality in non-ruptured cases. Follow-up included CT and/or MRI after a mean period of 18.0 ± 26.8 months. The current status of the patient was obtained by a structured telephone survey.ConclusionsPseudoaneurysms of visceral arteries have a high risk for rupture. Aneurysm size seems to be no reliable predictor for rupture. Interventional treatment is safe and effective for management of VAA.Key Points• Diagnosis of visceral artery aneurysms is increasing due to CT and MRI.• Diameter of visceral arterial aneurysms is no reliable predictor for rupture.• False aneurysms/pseudoaneurysms and symptomatic cases need emergency treatment.• Interventional treatment is safe and effective.

Locoregional therapy (LRT) is being increasingly used for the management of hepatocellular cancer (HCC) in patients listed for liver transplantation (LT). Although several selection criteria have been developed, stratifications of survival according to the pathology of explanted livers and pre-LT LRT are lacking. Radiological progression according to the modified Response Evaluation Criteria in Additional Supporting Information may be found in the online version of this article.

Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g., Calleman et al., 1978] years essentially for three purposes: (a) as passive monitors of the mean level of individual exposure to specific chemicals, either endogenously present in the human body or to which the subject is exposed through food or environmental contamination; (b) as quantitative indicators of the mean extent of the individual metabolic processing which converts a non-reactive chemical substance into its toxic products able to damage DNA (en route to cancer induction through genotoxic mechanisms) or key proteins (as in the case of several drugs, pesticides or otherwise biologically active substances); (c) to relate the extent of protein modification to that of biological function impairment (such as enzyme inhibition) finally causing the specific health damage. This review describes the role that contemporary mass spectrometry-based approaches employed in the qualitative and quantitative study of protein-electrophile adducts play in the discovery of the (bio)chemical mechanisms of toxic substances and highlights the future directions of research in this field. A particular emphasis is given to the measurement of often high levels of the protein adducts of several industrial and environmental pollutants in unexposed human populations, a phenomenon which highlights the possibility that a number of small organic molecules are generated in the human organism through minor metabolic processes, the imbalance of which may be the cause of "spontaneous" cases of cancer and of other degenerative diseases of still uncharacterized etiology. With all this in mind, it is foreseen that a holistic description of cellular functions will take advantage of new analytical methods based on time-integrated metabolomic measurements of a new biological compartment, the "adductome," aimed at better understanding integrated organism response to environmental and endogenous stressors.

Breath-hold MR imaging techniques enable morphologic and semiquantitative functional assessment of patients with CTEPH.

Ischemic-type biliary lesions (ITBL) belong to a group of biliary disorders that are regarded as the major complication in patients with orthotopic liver transplantation (OLT). We performed histological evaluation of donor common bile ducts received during OLT to find morphological clues to the pathomechanisms of ITBL. We investigated 93 grafts of 92 patients (recipients: mean age, 56.5 years; underlying disease: hepatocellular carcinoma (n = 45), alcoholic cirrhosis (n = 16), viral hepatitis with cirrhosis (n = 9), retransplantations (n = 9), others (n = 14); donors: mean age, 53.2 years). Donor common bile ducts were received after recirculation of the hepatic artery prior to biliary end-to-end anastomosis and routinely processed. Statistical evaluation was performed by chi-square analysis and multivariate analysis using a logistic regression model. With regard to ITBL (observed in 19.4 %), the following phenomena were found to be statistically relevant: necrosis of the bile duct wall, arteriolonecrosis, vascular lesions (such as subintimal edema), and intramural bleeding (P < 0.001, P < 0.001, P = 0.029, and P = 0.031, respectively). In logistic regression analysis, arteriolonecrosis was the only parameter with significance (P = 0.001). Based on these results on the morphology of the donor common bile duct, we conclude that these phenomena of vascular damage, reflecting microangiopathy, play a major role in the pathogenesis of ITBL.

• A prospective single-centre study evaluated ECG-gated MDCTA, ce-MRA and DSA in CTEPH patients. • ECG-gated MD-CT angiography outperformed DSA and ce-MRA. • Right heart catheterisation should be reserved only for assessment of pulmonary haemodynamics.