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Background: Patients with single hepatocellular carcinoma (HCC) usually undergo transarterial chemoembolization (TACE) if they are not candidates for curative surgical or ablative therapy. The primary aim of the study was to assess the overall survival and clinical determinants of survival in patients with single HCC who underwent TACE. The secondary aims were tumor response, local and distant recurrence rates, time to recurrence and the impact of TACE on liver function., Methods: The outcomes of 148 consecutive patients with single HCC who underwent TACE from January 2004 to December 2009 were retrospectively analyzed., Results: Complete response (CR) was observed in 95/148 (64%) patients and a partial response (PR) in 39 (26%) patients. The recurrence rate was 27%, 42% and 65% at 6, 12 and 24 months, respectively. The day after TACE, 56 (38%) patients had a Child-Pugh increase ≥ 1 and 93 (63%) had a MELD increase ≥ 1. Median survival was 36.0 months with 1-, 3- and 5-year survival rates of 85%, 50% and 26%, respectively. Bland portal thrombosis was not seen to have any impact at univariate survival analysis; however, a slight impairment of PS (PS-1) in small tumors had some, although minor, impact on prognosis. Factors associated with shorter survival at multivariate analysis were tumor >5 cm, absence of CR, ascites, alpha-fetoprotein (AFP) ≥ 14.5 ng/mL and a MELD increase ≥ 1., Conclusions: Transarterial chemoembolization is a valid treatment option in patients with single HCC not suitable for curative treatment. Bland PVT has no major impact on survival and a slight impairment of PS attributable to cirrhosis in patients within the Milan criteria should not preclude the use of TACE.

Background: Transcatheter arterial chemoembolisation (TACE) is the treatment of choice for intermediate stage hepatocellular carcinoma (HCC). Doxorubicin-loaded drug-eluting beads (DEB)-TACE is expected to improve the performance of conventional TACE (cTACE). The aim of this study was to compare DEB-TACE with cTACE in terms of time-to-tumour progression (TTP), adverse events (AEs), and 2-year survival., Methods: Patients were randomised one-to-one to undergo cTACE or DEB-TACE and followed-up for at least 2 years or until death. Transcatheter arterial chemoembolisation was repeated 'on-demand'., Results: We enrolled 177 patients: 89 underwent DEB-TACE and 88 cTACE. The median number of procedures was 2 in each arm, and the in-hospital stay was 3 and 4 days, respectively (P=0.323). No differences were found in local and overall tumour response. The median TTP was 9 months in both arms. The AE incidence and severity did not differ between the arms, except for post-procedural pain, more frequent and severe after cTACE (P<0.001). The 1- and 2-year survival rates were 86.2% and 56.8% after DEB-TACE and 83.5% and 55.4% after cTACE (P=0.949). Eastern Cooperative Oncology Group (ECOG), serum albumin, and tumour number independently predicted survival (P<0.05)., Conclusions: The DEB-TACE and the cTACE are equally effective and safe, with the only advantage of DEB-TACE being less post-procedural abdominal pain.

Background: The ART score (a point score for the assessment of retreatment with transarterial chemoembolization, TACE) has been recently developed in Austria to differentiate patients who may benefit from multiple sessions of TACE for hepatocellular carcinoma (HCC) treatment. The primary aim of the study was to test the validity of the ART score in an Italian study cohort. The secondary aims were to evaluate overall survival (OS) and clinical determinants of improved survival in patients treated with multiple TACE sessions., Methods: The ART score and the clinical outcome of 51 consecutive patients with HCC submitted to multiple TACE sessions from April 2002 to December 2009 were retrospectively analyzed., Results: Median OS was 26.0 months (95% confidence interval 18.4-33.6) with 1-, 3- and 5-year survival rates of 75, 33 and 11%, respectively). Thirty-three patients had an ART score of 0-1.5 and in 18 it was ≥2.5, but in our patient series, the ART score was not found to be a predictor of survival (p = 0.173). At univariate analysis, tumor extent (uni- vs. bilobar: 34.0 vs. 9.0 months; p < 0.001), Child-Pugh score before the second TACE (A vs. B7 vs. B8-9: 26.0 vs. 16.0 vs. 5.0 months; p = 0.005) and Child-Pugh score increase between the first and second TACE (absent vs. + 1 point vs. + ≥2 points: 27.0 vs. 4.0 vs. 5.0 months; p < 0.001) were statistically related with survival. At multivariate analysis, only Child-Pugh score increase remained a significant predictor of worse survival (p = 0.001, hazard rate = 11.6)., Conclusions: The ART score was not found to work as an objective tool to guide TACE retreatment in our Italian patient series, only the Child-Pugh score increase was an independent predictor of a shorter survival.

Hepatocellular carcinoma (HCC) is a major health concern, and early HCC diagnosis is a primary radiological concern. The goal of imaging liver cirrhosis is the early identification of high-grade dysplastic nodules/early HCC since their treatment is associated with a higher chance of radical cure and lower recurrence rates. The newly introduced MRI contrast agent gadoxetic acid (gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid, Gd-EOB-DTPA) has enabled the concurrent assessment of tumor vascularity and hepatocyte-specific contrast enhancement during the hepatobiliary phase (HBP), which can help to detect and characterize smaller HCCs and their precursors. HBP-EOB-MRI identifies hypovascular HCC nodules that are difficult to detect using ultrasonography or computed tomography, which do not show the diagnostic HCC hallmarks of arterial washin and portal/delayed washout. During the HBP, typical HCC and early HCC appear hypointense on EOB-MRI, whereas low-grade dysplastic or regenerative nodules appear as iso- or hyperintense lesions. The diagnostic accuracy of EOB-MRI for the diagnosis of early HCC is approximately 95-100%. One third of hypovascular hypointense nodules in HBP become hypervascular 'progressed' HCC, with a 1- and 3-year cumulative incidence of 25 and 41%, respectively. Therefore, these hypovascular nodules should be strictly followed up or definitely treated as typical HCC. Due to this capability of identifying the precursors and biological behavior of HCC, EOB-MRI has rapidly become a key imaging tool for the diagnosis of HCC and its precursors, despite the scarce MRI availability throughout Europe. With increasing experience, EOB-MRI may eventually be established as the diagnostic imaging modality of choice in this setting. Full recognition by the Western EASL-AASLD guidelines is expected.

We performed a molecular study aimed at identifying a gene expression profile (GEP) signature predictive of attainment of at least near complete response (CR) to thalidomide-dexamethasone (TD) as induction regimen in preparation for double autologous stem cell transplantation in 112 younger patients with newly diagnosed multiple myeloma. A GEP supervised analysis was performed on a training set of 32 patients, allowing to identify 157 probe sets differentially expressed in patients with CR versus those failing CR to TD. We then generated an eight-gene GEP signature whose performance was subsequently validated in a training set of 80 patients. A correct prediction of response to TD was found in 71 % of the cases analyzed. The eight genes were downregulated in patients who achieved CR to TD. Comparisons between post-autotransplantation outcomes of the 44 non-CR-predicted patients and of the 36 CR-predicted patients showed that this latter subgroup had a statistically significant benefit in terms of higher rate of CR after autotransplant(s) and longer time to progression, event-free survival, and overall survival. These results can be an important first step to identify at diagnosis those patients who will respond more favourably to a particular treatment strategy.

Aim: To evaluate the survival of patients with unresectable perihilar cholangiocarcinoma (PHC) treated with multimodal palliative approaches., Patients and Methods: thirty-two patients were enrolled in a multimodal protocol including: bilateral biliary drainage; Yridium-192 intraluminal brachytherapy (BT); metal biliary stenting; external-beam radiotherapy (EBRT); systemic chemotherapy (ChT). All patients underwent BT and biliary stenting: this was the only treatment for 14 patients, it was combined with EBRT in 11, and with EBRT and ChT in seven. Mean and median survival, complication rates and duration of hospital stay were calculated for each group., Results: BT with EBRT and ChT obtained the best median (15 months) and one year (71.42%) survival followed by BT with EBRT (14 months and 63.63%, respectively). BT with EBRT in a total dose of 54-60 Gy, with or without ChT, led to a significantly higher median survival rate (14 months) than that for BT alone (seven months)., Conclusion: BT with EBRT, with or without ChT, improves survival and should be considered as a suitable alternative to palliative surgery for patients with unresectable perihilar cholangiocarcinoma.

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%; P<.001). The LRR was 23%:20% in small, 27% in intermediate, and 67% in large HCCs (P<.05). The median TTnP of large HCCs was 4 months versus 7-9 months for small and intermediate HCCs. The second superselective transarterial chemoembolization achieved a higher CR (63% in LR, 52% in PR) than the third superselective transarterial chemoembolization (32%). Median TTnP after the second superselective transarterial chemoembolization for LR and PR (8 months and 6 months) was longer than after the third superselective transarterial chemoembolization (3.5 months). Nodules ≤ 5 cm had a CR after the first superselective transarterial chemoembolization (66%) and the second superselective transarterial chemoembolization for LR (64%) or PR (55%) higher than after the third superselective transarterial chemoembolization (40%); nodules>5 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., (Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Gadoxetic acid (Gd-EOB-DTPA) is a 'hepatocyte-specific' contrast agent for magnetic resonance (MR) in both the vascular and the hepatobiliary phases., Aim: To evaluate the contribution of the hepatobiliary phase of Gd-EOB-DTPA MR in the diagnosis of small hepatocellular carcinoma (HCC) in cirrhotic patients under surveillance., Methods: Between 2008 and 2011, 48 consecutive small (10-30 mm) liver nodules were detected in 33 patients, who prospectively underwent contrast-enhanced ultrasound (CEUS), Gd-EOB-DTPA-enhanced MR and helical-computed tomography (CT) in a blind study. The diagnosis of HCC was established according to AASLD 2005 criteria., Results: Of the 48 nodules, 38 (79%) were diagnosed as HCC, 24 (63%) of them based on AASLD non-invasive criteria, 11 diagnosed at histology and 3 during follow-up. The typical vascular pattern (arterial hypervascularisation and venous/late washout) was detected in 30 (79%) HCC nodules by MR, in 22 (58%) by CT and in 17 (45%) by CEUS. Hypointensity during the MR hepatobiliary phase was observed in all HCC nodules and in 3 nonmalignant nodules (sensitivity 100%, specificity 70%, positive predictive value 93%, negative predictive value 100%, positive likelihood ratio 3.33, negative likelihood ratio 0). Eight (21%) of the 38 HCC nodules, 7 of which lacked the typical vascular features at any of the imaging modalities, showed washout in the portal/venous phase and hypointensity in the hepatobiliary phase at MRI, while this pattern was not detected in any nonmalignant lesion., Conclusions: Gadoxetic acid magnetic resonance may enhance the sensitivity of the non-invasive diagnosis of small hepatocellular carcinoma nodules in cirrhotic patients under surveillance. Double hypointensity in the portal/venous and hepatobiliary phases could be considered a new magnetic resonance pattern, highly suggestive of hypovascular hepatocellular carcinoma., (© 2012 Blackwell Publishing Ltd.)

Background: The presence of refractory ascites is a common indication for transjugular intrahepatic portosystemic shunt (TIPS). Different models have been proposed for the prediction of survival after TIPS. The aim of this study was to evaluate the predictive factors associated with patients' survival after TIPS placement for refractory ascites., Methods: Data from all consecutive patients undergoing TIPS placement in our center for refractory ascites between February 2003 and January 2008 were prospectively recorded., Results: Seventy-three patients (52M/21F; 57 ± 10 years) met the inclusion criteria; mean follow-up was 17 ± 2 months. Mean MELD value, before TIPS placement, was 15.7 ± 5.3. TIPS placement led to an effective resolution of refractory ascites in 54% of patients (n = 40) with no significant increase in severe portosystemic encephalopathy. The 1-year survival rate observed was 65.7%, while the overall mortality was 23.3% (n = 17) with a mean survival of 17 ± 14 months. MELD score (B = 0.161, p = 0.042), basal AST (B = 0.020, p = 0.090), and pre-TIPS HVPG (B = 0.016, p = 0.093) were independent predictors of overall mortality, while MELD (B = 0.419, p = 0.018) and HVPG (B = 0.223, p = 0.060) independently predicted 1-year survival. ROC curves identified MELD ≥ 19 and HVPG ≥ 25 mmHg as the best cut-off points for the prediction of 1-year mortality., Conclusions: TIPS is an effective treatment for refractory ascites in cirrhotic patients, leading to an effective ascites control in more than half patients. Improvement in patients' selection criteria could lead to better outcome and survival after this procedure. Liver function (MELD), presence of active necroinflammation (AST), and portal hypertension (HVPG) are independent predictors of patients' outcome after TIPS.

Background & Aims: Aim of the study was to assess the clinical impact of conventional transarterial chemoembolization (cTACE) repeated "on demand" on HCC outcome. Outcome measures were: response rate to first and repeated cTACE, recurrence rates and overall survival., Methods: The outcome of 151 consecutive HCC patients submitted to a first cTACE from January 2004 to December 2005 was retrospectively analyzed., Results: Complete radiological response (CR) was observed in 72/151 (48%), 34/60 (52%) and 12/22 (55%) patients after first, second and third cTACE, respectively. Recurrence rates at 6 and 12months were 37% and 61% after the first cTACE, and 40% and 59% after the second cTACE, respectively. Patients not achieving CR or with a recurrence after CR not treated with curative therapies were 94 and 84 after first and second cTACE, respectively. Of these, 60/94 (64%) and 22/84 (26%) were submitted to a second and third cTACE, respectively. Median overall survival was 32.0months but 25.0months excluding transplanted patients. Factors at the time of first cTACE associated with overall shorter survival at multivariate analysis were higher bilirubin, higher AFP and not achieving CR., Conclusions: CR and recurrence rates after first and second cTACE were similar. About 64% of patients were submitted to second cTACE, while only few patients (26%) were submitted to third cTACE using an "on demand" policy. These figures may be also useful for planning trials for the evaluation of the efficacy of repeated TACE vs. TACE combined with adjuvant treatments or vs. systemic treatments., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate whether the malignancy of atypical nodules in cirrhosis can be identified at gadoxetic-acid-disodium(Gd-EOB-DTPA)-MRI by their hypointensity in the hepatobiliary(HB)-phase alone or combined with any other MR imaging features., Materials and Methods: One hundred eleven atypical nodules detected in 77 consecutive Gd-EOB-DTPA-MRIs were divided, based on arterial-phase behavior, into: Class I, isovascular (n = 82), and Class II, hypervascular without portal/delayed washout (n = 29). The two classes were further grouped based on HB-phase intensity (A/B/C hypo/iso/hyperintensity). Portal/venous/equilibrium-phase behavior and T2w features were also collected. Histology was the gold standard. Per-nodule sensitivity, specificity, negative and positive predictive values (NPV/PPV), and diagnostic accuracy were calculated for HB-phase hypointensity alone, and combined with vascular patterns and T2w hyperintensity., Results: Histology detected 60 benign and 51 malignant/premalignant nodules [10 overt hepatocellular carcinomas (HCCs) and 41 high-grade dysplastic nodules (HGDN)/early HCC]. Class IA contained 31 (94%) malignancies, IB one (3%), and IC only benign lesions. Class IIA had 100% malignancies, IIB three (37.5%) and IIC only two (28.5%). HB-phase hypointensity alone (Classes I-IIA) had 88% sensitivity, 91% NPV, and 93% diagnostic accuracy, superior (P < 0.05, P < 0.006, and P < 0.05, respectively) to any other MR imaging feature alone or combined., Conclusion: In atypical cirrhotic nodules, HB-phase hypointensity by itself is the strongest marker of malignancy., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: To provide dose-area-product (DAP) to effective dose (E) conversion factors for complete interventional procedures, based on in-the-field clinical measurements of DAP values and using tabulated E/DAP conversion factors for single projections available from the literature., Methods: Nine types of interventional procedures were performed on 84 patients with two angiographic systems. Different calibration curves (with and without patient table attenuation) were calculated for each DAP meter. Clinical and dosimetric parameters were recorded in-the-field for each projection and for all patients, and a conversion factor linking DAP and effective doses was derived for each complete procedure making use of published, Monte Carlo calculated conversion factors for single static projections., Results: Fluoroscopy time and DAP values for the lowest-dose procedure (biliary drainage) were approximately 3-fold and 13-fold lower, respectively, than those for the highest-dose examination (transjugular intrahepatic portosystemic shunt, TIPS). Median E/DAP conversion factors from 0.12 (abdominal percutaneous transluminal angioplasty) to 0.25 (Nephrostomy) mSvGy(-1) cm(-2) were obtained and good correlations between E and DAP were found for all procedures, with R(2) coefficients ranging from 0.80 (abdominal angiography) to 0.99 (biliary stent insertion, Nephrostomy and TIPS). The DAP values obtained in this study showed general consistency with the values provided in the literature and median E values ranged from 4.0 mSv (biliary drainage) to 49.6 mSv (TIPS)., Conclusions: Values of E/DAP conversion factors were derived for each procedure from a comprehensive analysis of projection and dosimetric data: they could provide a good evaluation for the stochastic effects. These results can be obtained by means of a close cooperation between different interventional professionals involved in patient care and dose optimization.

In liver transplantation (LT), biliary strictures (BSs) are among the most common complications. The aim of this study was to evaluate the efficacy of percutaneous treatments in the management of post-LT BSs. Between 1999 and 2007, 48 patients underwent percutaneous treatments for posttransplant BSs. We divided the population into 2 groups according to the cause [ischemic (n = 14) or nonischemic (n = 34)] and into further subgroups according to the site [anastomotic (n = 34) or nonanastomotic (n = 14)]. All patients were treated with bilioplasty; in 9 patients who were refractory to bilioplasty, metallic stents were implanted. A technical success rate of 90% was achieved without differences between the ischemic and nonischemic groups or between the anastomotic and nonanastomotic subgroups (P = 0.10). The major complication rate was 4%. The overall 1- and 3-year primary patency rates were 94% and 45%, respectively, and better results were found for patients with nonischemic stenoses versus patients with ischemic stenoses (P = 0.032). The overall secondary patency rates were 94% and 83% at 1 and 3 years, respectively, and there were no statistical differences between the ischemic and nonischemic groups or between the anastomotic and nonanastomotic groups. In the stent subgroup, the overall primary 1- and 2-year patency rates were 100% and 71%, respectively, and the secondary patency rates were 100% and 100%, respectively. In conclusion, a percutaneous approach is highly effective for the treatment of post-LT BSs, and the best results are obtained for patients with simple, nonischemic BSs (technical success rate = 94%, 3-year primary patency rate = 81%, 3-year secondary patency rate = 75%). For patients with ischemic BSs, closer follow-up and retreatment are more frequently needed to achieve secondary patency rates comparable to (or even better than) those for patients with nonischemic stenoses., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Transcatheter embolization is the mainstay of the therapy of splenic artery aneurysms (SAAs) in patients with portal hypertension. It is indicated when the SAA diameter reaches 20 mm. Although endovascular techniques are effective and safe for the treatment of medium-sized SAAs, little is known about their applicability to large-sized SAAs. Herein, we report a case of giant SAA, which was treated with transcatheter coil embolization. The case was not considered suitable for surgery because of the presence of severe portal hypertension. The procedure was complicated by bacterial infection of the coils within the aneurismatic sac, leading to the development of hepatic failure. A liver transplant was then successfully performed despite the presence of a nonresponsive infection.

Background: Large regenerative nodules (LRNs) are hyperplastic benign nodules most commonly associated with Budd-Chiari syndrome (BCS), caused by outflow obstruction of the hepatic veins or vena cava. To our knowledge, no cases of LRNs arising in BCS after transjugular intrahepatic portosystemic shunt (TIPS) positioning and detected by Gd-EOB-DTPA MRI have been reported in the literature., Methods: A 58-year-old woman with BCS, on the liver transplantation (LT) list, underwent a follow-up enhanced MRI. Two years earlier, a TIPS had been placed. In 2008, recurrent hepaticoencephalopathy resistant to medical treatment fulfilled the LT criteria for BCS treated with TIPS and the patient was therefore added to the LT list. CT performed before TIPS had not detected any hepatic lesions. CT performed six months after TIPS showed its complete patency but documented two indeterminate hypervascular liver lesions., Results: MRI performed with Gd-EOB-DTPA revealed additional hypervascular lesions with uptake and retention of the medium in the hepatobiliary phase, thus reflecting a benign behavior of hepatocellular composition. These MRI features were related to LRNs as confirmed by histopathologic analysis., Conclusions: Gd-EOB-DTPA-enhanced MRI is potentially superior to standard imaging using gadolinium chelates or spiral CT, especially for the differential diagnosis of hypervascular lesions. Gd-EOB-DTPA MRI may become the imaging method of choice for evaluating LT list patients with BCS after TIPS placement.

The organic anion transporter peptides (OATP) 1B1 and 1B3 are hepatocytic-specific transporters determinant for the uptake of the contrast media Gd-EOB-DTPA during magnetic resonance, but variably lost in hepatocellular carcinoma (HCC). Here, we studied a series of HCCs from livers that underwent liver transplantation (OLT) and correlated the expression of OATP 1B1/1B3 with HCC morphological features and the expression of the biliary-type keratins K7 and K19, the latter previously correlated with a worse prognosis after OLT. Seventy-five HCCs from 69 OLT patients were evaluated by histology and immunohistochemistry with monoclonal antibodies against OATP 1B1/1B3, K7, and K19. Histopathological and immunohistochemical features were therefore compared to recipient follow-up data. Thirty-four (45%) HCCs were completely OATP-, and 18 (24%) showed positivity for K7 and/or K19. We observed a significant inverse correlation between OATP and K7/19 expression (P < 0.001): all OATP+ cases were K7/19-, while all K7+ and/or K19+ cases were OATP-. Sixteen cases were negative for all antibodies. No correlation was found between histopathological features and immunohistochemistry. Twenty-five recipients experienced HCC recurrence, and ten died from neoplastic recurrence. Neither OATP nor keratin expressions were correlated with HCC recurrence, while OATP negativity significantly correlated with HCC-related death after recurrence (P = 0.036). In conclusion, HCCs show a progressive loss in OATP immunoreactivity that correlates with the gain of a biliary phenotype. Although further studies are required to define these findings better, our results support the idea that OATP could be used together with K7/19 to identify a phenotypical "spectrum" in HCC progression.

Objective: To prospectively assess the additional value of the hepatobiliary (HB) phase of Gd-EOB-DTPA-MRI in identifying and characterising small (≤ 2 cm) hepatocellular carcinomas (HCCs) undetermined in dynamic phases alone because of their atypical features, according to the AASLD criteria., Methods: 127 cirrhotic patients were evaluated with Gd-EOB-DTPA-MRI in two sets: unenhanced and dynamic phases; unenhanced, dynamic and HB phases. Sixty-two out of 215 nodules (29%) were atypical in 42 patients (33%)., Results: 62 atypical nodules were reported at histology: high-grade dysplastic nodules (HGDN)/early HCC (n = 20), low-grade DN (LGDN) (n = 21), regenerative nodules (n = 17) and nodular regenerative hyperplasia (n = 4). The sensitivity, specificity, accuracy, positive and negative predictive value (PPV, NPV) were increased by the addition of the HB phase: 88.4-99.4%, 88-95%, 88-98.5%, 97-99%, and 65-97.5%, respectively. Twenty atypical nodules were malignant (32%), 19 of which were characterised only during the HB phase., Conclusions: The HB phase is 11% more sensitive in the classification of HGDN/early HCC than dynamic MRI, with an added value of 32.5% in the NPV. The high incidence (33%) of atypical nodules and their frequent malignancy (32%) suggest the widespread employment of Gd-EOB-DTPA-MRI in the follow-up of small nodules (≤ 2 cm) in cirrhosis.

We report the synthesis and evaluation of aminoalkylguanidine analogues and derivatives in C57BL/KsJ db/db diabetic mice, following identification by random screening of 1a and 1b as potential antihyperglycemics and/or modulators of food intake. These compounds are related to galegine, a gamma,gamma-dimethylallylguanidine. Between the newly identified compounds, 1h N-(cyclopropylmethyl)- N'-(4-(aminomethyl)cyclohexylmethyl)guanidine showed the most balanced activity as antihyperglycemic and food intake-reducing agent.

Acute myeloid leukemia (AML) remains the most common form of leukemia and the most common cause of leukemia death. Although conventional chemotherapy can cure between 25 and 45% of AML patients, the majority of patients die after relapse or of complications associated with treatment. Thus, more specific and less toxic treatments for AML patients are needed, especially for elderly patients. An indispensable prerequisite to investigate tailored approaches for AML is the recent progress in the understanding the molecular features that distinguish leukemia progenitors from normal hematopoietic counterparts and the identification of a variety of dysregulated molecular pathways. This in turn would allow the identification of tumor-specific characteristics that provide a rational basis for the development of more tailored, and hence potentially more effective and less toxic, therapeutic approaches. In this review, we describe some of the signaling pathways that are aberrantly regulated in AML, with a specific focus on their pathogenetic and therapeutic significance, and we examine some recent therapies directed against these targets, used in clinical trial for relapsed patients or unfit for conventional chemotherapy.

T(4;14) chromosomal abnormality is one of the most adverse prognostic factors predicting for poor outcome in multiple myeloma (MM) patients. It has been recently suggested that bone disease, as evaluated by spinal magnetic resonance imaging (MRI), is relatively infrequent in these patients. In the present study, we aimed at further testing this hypothesis by analyzing the extent of whole bone involvement in patients showing t(4;14) chromosomal translocation as compared with negative patients. For this purpose, 53 consecutive newly diagnosed MM patients (35M, 18F, median age = 55 yr) underwent evaluation of total skeletal X-ray, whole spine MRI, and at the same time, quantification of markers of bone resorption (urinary N-terminal telopeptide, pyridinoline, deoxypyridinoline, serum crosslaps), and bone formation (bone alkaline phosphatase and osteocalcin) was performed. The presence of IgH/MMSET fusion gene as a surrogate marker for t(4;14), was detected in 11 patients (20.7%), whose clinical characteristics were similar to those observed in t(4;14) negative patients. The type of marrow involvement at spinal MRI (diffuse vs. focal vs. negative) was the same in both groups of patients, even though overt vertebral fractures were more frequently found in t(4;14) positive cases (82% vs. 43%, P = 0.05); in line with this finding, skeletal lesions were more common in t(4;14) positive patients (mean skeletal score = 8.54 +/- 1.36 SE, as compared with 3.42 +/- 0.57 SE in t(4;14) negative cases, P = 0.000). These data were confirmed by the evaluation of serum crosslaps, that were significantly increased in patients with t(4;14) abnormality as compared with negative individuals (10,400 pmol/L +/- 2160 SE vs. 5640 pmol/L +/- 859 SE P = 0.02) Our results indicate that, at variance to what has been previously reported, bone resorption is more prominent in t(4;14) positive patients.

Purpose: Chronic myeloid leukemia is a clonal myeloproliferative disorder characterized by the presence of the fusion gene BCR/ABL. We had previously demonstrated an increased proapoptotic effect of imatinib (STI571) in combination with amifostine (AMI) in K562 cell line. In this study, we used genomic scale gene expression profiling to monitor changes at transcriptional level in K562 cells during the treatment with AMI + STI571., Materials and Methods: cRNA from Control and treated K562 cells were mixed in equal amounts and incubated with a microarray slide for hybridization. RNA from six independent paired experiments was subjected to transcriptional profiling. With the aim to automate the process of biological theme determination, selected genes were further analyzed by EASE. Validation of the expression was carried out by quantitative real-time PCR and western blotting., Results: As expected, a small percentage of genes accounts for the effects of the combined drug treatment. We identified 61 sequences corresponding to known genes; 17 of the 61 genes were up regulated, such as RHO6, PPP2R5E, PPM1E and BTF that appear to reflect favorable events for apoptosis induction. Between down regulated genes, API5, TUBB2 and TLK1 are also of considerable interest., Conclusion: We identified a transcriptional repressor of survival genes, known as BTF, which triggers a proapoptotic signal, potentially helpful to overcome the resistance to STI571. This finding could be particularly useful to design novel therapeutic strategies for leukemia patients. This study demonstrates the importance of in vitro testing of a novel drug combination most likely to predict its potential usefulness for in vivo application.

Klatskin-type cholangiocarcinoma is a rare tumor, bearing a very poor prognosis: at diagnosis, most patients can only undergo palliation. Evaluation of outcome, mean survival and quality of life was performed in patients with unresectable hilar cholangiocarcinoma treated with multimodality approach in comparison with surgical palliation, biliary stenting or brachytherapy alone. Twenty-six patients with hilar cholangiocarcinoma were studied: 16 patients were enrolled in the multimodality protocol (bilateral biliary drainage; Iridium-192 brachytherapy; plastic endoprosthesis or metallic stent positioning and external radiotherapy plus systemic chemotherapy), 5 patients underwent surgical palliation and 5 percutaneous decompression alone. Nine patients completed the protocol and 7 were treated with brachytherapy followed by biliary stenting alone. The multimodality approach obtained mean survival (10 months) similar to that for surgery and higher than that of the brachytherapy and metallic stenting groups (6 and 2.75 months, respectively). The average hospital stay (15 days) was lower than that of the surgical group (20 days). A multimodality approach is a suitable alternative to palliative surgery of unresectable hilar cholangiocarcinoma.

Acute aortic dissection continues to be one of the most catastrophic cardiovascular events. While there is a general consensus on immediate surgical repair when the ascending aorta is involved, the optimal treatment strategy for type B aortic dissection (B-AD) remains controversial. Recently, endovascular treatment with percutaneous stent-graft implantation, originally used for aortic aneurysm exclusion, has acquired an important role in the treatment of B-AD. Imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and angiography have a fundamental role in the search for the anatomic details necessary to tailor the stent graft and in evaluating the most suitable anatomy for stent graft. Transesophageal echocardiography is fundamental during the procedure to monitor the correct release of the stent graft and evaluate the result of the procedure expressed by immediate thrombosis out of the stent-graft. Again, imaging techniques, more notably CT, have a fundamental role in the postoperative followup after stent-graft placement. The risk of endoleaks may compromise the result of endovascular repair and increase the risk of aortic rupture. Several reports and a few trials attesting to technical feasibility and safety of stent-graft implantation procedures for B-AD have been reported so far. Also, a randomised trial comparing type B aortic stent-graft placement with medical therapy is currently underway. According to the investigators, new therapeutic indications are likely to emerge also in uncomplicated B-AD.

Diseases of the thoracic aorta can present with a broad clinical spectrum of symptoms and signs. Their prevalence appears to be increasing in western populations, most likely corresponding to aging and heightened clinical awareness but also influenced by the progress of high-resolution, noninvasive imaging modalities. Among them, MRI provides an excellent visualization of vascular structures and is well suited for evaluation of thoracic aorta disease. Currently, in many centers, noninvasive imaging modalities are the first choice in the cardiovascular system evaluation and diagnosis, reserving conventional angiography for use only before therapeutic intervention. Understanding the principle MRA techniques is essential for acquiring consistent diagnostic images. Basic technical considerations, which include fast spin-echo, fast gradient-echo, and MRA techniques with phase contrast and contrast-enhanced methods, are discussed and applied in the evaluation of acquired thoracic aorta diseases.

Aortic malformations may be associated with other congenital heart abnormalities or may present independently, as incidental findings in asymptomatic patients. For more than 30 years, conventional imaging techniques for detection and assessment of congenital anomalies of the aorta have been chest X-ray, echocardiography and angiography. In recent times, considerable interest in congenital aortic diseases has been shown, due to technical progresses of noninvasive imaging modalities. Among them, magnetic resonance imaging (MRI) almost certainly offers the greatest advantages, especially in young patients in which a radiation exposure must be avoided as much as possible. MRI provides an excellent visualization of vascular structures with a wide field of view, well suited for evaluation of the thoracic aorta malformations. With the implementation of magnetic resonance angiography (MRA) it is also possible to depict any relationship with supra-aortic or mediastinal vessels. Phase contrast technique allows identification of the hemodynamic significance of the aortic alteration. Some technical considerations, which include fast spin-echo, gradient-echo and, especially, MRA techniques with phase-contrast and contrast enhanced methods, are discussed and applied in the evaluation of congenital thoracic aorta diseases.

Forty-one patients with ventricular septal rupture after myocardial infarction were operated over about a 4-year period. The "early" group included 17 patients operated upon within the first 24 hours and 13 of them died. A total of 29 patients were operated within the first week and 21 died. The other 12 were operated after the first week since the diagnosis was made and 11 (92%) survived. The most relevant risk factors were: cardiogenic shock, hypertension and diabetes. The initial management was based on digitalis, diuretics, inotropes (dopamine, dobutamine) and the intra-aortic balloon pump. There was no significant difference in mortality between those patients with associated procedures and those without them, except in those cases of coronary grafts with infartectomy, whose mortality was higher. Early surgical repair of ventricular septal rupture implies a very high mortality (72%), which is even worse when the operation is performed within the first 24 hours (76%).