Simeprevir and Sofosbuvir (SMV-SOF) for 12 Weeks for the Treatment of Chronic Hepatitis C Genotype 1 Infection: A Real World (Transplant) Hepatology Practice Experience.

OBJECTIVES: The combination of simeprevir (SMV) and sofosbuvir (SOF) was found to be well-tolerated with high sustained virologic response (SVR) rates in patients with genotype 1 chronic hepatitis C in clinical trials. Previous experience with hepatitis C virus (HCV) therapy has shown that patient tolerability and treatment efficacy described in controlled clinical trials did not necessarily mirror the "real world" experience. The goal of this study was to define SVR rates in a "real world" analysis and to explore predictors of treatment response with SMV and SOF. METHODS: This is a retrospective study examining the "real world" treatment of 170 patients with chronic HCV genotype 1 using the combination of SMV and SOF with or without ribavirin (RBV) for a fixed 12-week duration irrespective of prior interferon therapy, transplant status or fibrosis stage. Differences between SVR cohorts were analyzed by both intention-to-treat (ITT) and per protocol. RESULTS: The vast majority of patients were genotype 1a, 77% were cirrhotic in the non-LT group, and 35% of the entire cohort was African-American. Combination treatment with SMV and SOF in genotype 1 chronic HCV patients achieved an overall SVR rate at 12 weeks after completion of therapy (SVR12) of 78% by ITT and 86% by per protocol (84% in non-liver transplant (LT) patients and 89% in post-LT recipients). The presence of hepatocellular carcinoma was found to be a significant negative predictor of SVR12, whereas an undetectable week eight VL was a significant positive predictor of SVR in the entire cohort. CONCLUSIONS: Our data confirm excellent SVR outcomes with favorable safety and tolerability profiles in patients who carry many traditional high-risk features for non-response, including post-LT recipients and patients with advanced liver disease.

Percutaneous Management of Benign Biliary Strictures with Large-Bore Catheters: Comparison between Patients with and without Orthotopic Liver Transplantation.

PURPOSE: To prospectively evaluate stricture resolution and patency rates of benign biliary strictures treated with percutaneous large-bore catheter "stenting" in patients with and without previous orthotopic liver transplantation (OLT) and to compare treatment outcomes between these two groups. MATERIALS AND METHODS: Forty-six consecutive patients (25 with OLT) underwent percutaneous catheter placement in extrahepatic and single-site biliary stricture for 6-8 months, with progressive catheter upsizing to 18-20 F. Primary patency rate was defined as the proportion of patients without recurrent bile duct stricture during the follow-up period after successful stricture resolution. Secondary patency rate was defined as the proportion of patients with a patent bile duct at the end of follow-up after stricture resolution, including patients with stricture recurrence and successful repeat percutaneous biliary catheter treatment. RESULTS: Eleven patients terminated the protocol early, 6 as a result of treatment-related reasons in the orthotopic liver transplantation (OLT) group. Sixty-four percent of the OLT group and 86.4% of control patients successfully completed the protocol, with resolved biliary strictures (P = .1) after a median treatment time of 7 months for both groups (P = .96). During mean follow-up times of 20.3 months ± 11.8 (standard deviation) and 13.1 months ± 11.73 for OLT and non-OLT patients (P = .08), respectively, the primary/secondary patency rates were comparable between groups, at 81.25%/87.5% for OLT patients and 89.5%/100% for non-OLT patients (P = .64/P = .2). The mean time to recurrent stricture was 11.2 months ± 11.88. CONCLUSIONS: Percutaneous large-bore catheter treatment of benign, single-site biliary strictures showed a promising rate of stricture resolution, with comparable high primary and secondary patency rates in patients with and without previous OLT.

Open-label prospective study of the safety and efficacy of glass-based yttrium 90 radioembolization for infiltrative hepatocellular carcinoma with portal vein thrombosis.

BACKGROUND: The safety and efficacy of yttrium 90 ((90) Y) therapy for unresectable infiltrative hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) requires further evaluation. METHODS: A prospective, single-center safety and feasibility study recruited patients with unresectable (Barcelona Clinic Liver Cancer stage C) infiltrative HCC with PVT. Safety was assessed according to Common Terminology Criteria for Adverse Events version 4.0. Overall survival (OS) and time to progression (TTP) were measured from the first (90) Y therapy. Survival analysis was performed with Kaplan-Meier estimation. Prognostic factors were tested with a log-rank test and Cox proportional regression analysis. RESULTS: Overall, 45 patients were recruited, and 30 patients who met the study's inclusion criteria underwent glass-based (90) Y therapy. Four patients (13%) had transient hepatobiliary toxicity (grade ≥ 2). Ten patients (33%) had related emergency department visits, with 5 patients (17%) requiring short-term hospitalization. No radiation pneumonitis, gastrointestinal ulceration, or procedure-related mortality occurred. The median OS was 13 months (95% confidence interval, 4.4-22 months) with a TTP of 9 months (95% confidence interval, 6.2-13.1 months). Absence of ascites, an international normalized ratio < 1.2, an Eastern Cooperative Oncology Group (ECOG) performance status of 0, Child-Pugh class A, a macroaggregated albumin lung shunt fraction (LSF) < 10%, and no hepatobiliary toxicity were significant predictors of prolonged OS according to a univariate analysis (P < .05). A multivariate analysis found an ECOG performance status of 0, Child-Pugh class A, an LSF < 10%, and lack of transient hepatobiliary toxicity (grade ≥ 2) to be independent predictors of prolonged OS (P < .05). An ECOG performance status of 0, Child-Pugh class A, and an LSF < 10% were also predictors of prolonged TTP according to the multivariate analysis (P < .05). CONCLUSIONS: In patients with unresectable infiltrative HCC and PVT, (90) Y therapy appears to be a safe and viable therapy.

Age-related increases in basal ganglia glutamate are associated with TNF, reduced motivation and decreased psychomotor speed during IFN-alpha treatment: Preliminary findings.

Inflammation-induced alterations in central nervous system (CNS) metabolism have focused on glutamate. At excessive concentrations, glutamate is toxic to glia and neurons, and inflammatory cytokines have been shown to influence glutamate turnover by blocking glutamate reuptake and increasing glutamate release. Increased glutamate has also been found in depression, a disorder associated with increased inflammation. Data by our group have shown increased glutamate as measured by magnetic resonance spectroscopy (MRS) in basal ganglia and dorsal anterior cingulate cortex of patients administered the inflammatory cytokine interferon (IFN)-alpha. Given data that increasing age is associated with an exaggerated CNS inflammatory response, we examined whether older age (>55years) would be associated with a greater IFN-alpha-induced increase in CNS glutamate. Using a longitudinal design, 31 patients with hepatitis C virus (HCV) underwent MRS, blood sampling for inflammatory markers, and behavioral assessments before (Visit 1) and after 4weeks (Visit 2) of either IFN-alpha (n=17) or no treatment (n=14). Older patients treated with IFN-alpha exhibited a significantly greater increase in glutamate from Visit 1 to Visit 2 as reflected by the glutamate/creatine ratio (Glu/Cr) in left basal ganglia compared to older controls and younger IFN-alpha-treated and untreated subjects. In addition, increased Glu/Cr in older but not younger IFN-alpha-treated and untreated patients was associated with increased tumor necrosis factor, reduced motivation as measured by the Multidimensional Fatigue Inventory and increased choice movement time on the Cambridge Neuropsychological Test Automated Battery. Taken together, these preliminary data support the notion that older age may interact with inflammation to exaggerate the effects of inflammatory stimuli on CNS glutamate and behavior.

Preservation of quality of life with doxorubicin drug-eluting bead transarterial chemoembolization for unresectable hepatocellular carcinoma: Longitudinal prospective study.

BACKGROUND AND AIM: The study aims to determine the effects of doxorubicin drug-eluting bead transarterial chemoembolization (DEB-TACE) therapies on health-related quality of life (HRQOL) in patients with unresectable hepatocellular carcinoma (HCC). METHODS: This is a single-center, prospective study assessing HRQOL of consecutive patients with unresectable HCC who underwent DEB-TACE. Longitudinal assessment of HRQOL scores via Short-Form-36 (SF-36) was performed. Baseline HRQOL scores were evaluated for significant change (P < 0.05) pre-therapy, post-therapy, and at 6- and 12-month follow-up. Analysis of overall survival (OS) from HCC diagnosis and OS from first DEB-TACE was performed. Paired t-tests were used to compare HRQOL domain scores. RESULTS: One hundred eighteen patients (83 male; median age 60 years) were enrolled. Patients had lower baseline scores within all eight HRQOL domains of the SF-36 compared with US age-adjusted healthy norms. No significant changes in all eight domains were observed post-therapy and at 6- or 12-month follow-up compared with baseline (P > 0.05). No significant differences in all eight domains were observed between patients receiving ≥ 4 versus ≤ 3 DEB-TACE (P > 0.05). Both groups were similar for age at HCC diagnosis, gender, ethnicity, HCC etiology, Child-Pugh class and Eastern Cooperative Oncology Group Performance Status (P > 0.05). Patients receiving staged DEB-TACE demonstrated significantly greater median OS from HCC diagnosis (≥ 4 vs ≤ 3 DEB-TACE procedures, 31.9 vs 23.7 months, P = 0.04) and from first DEB-TACE (≥ 4 vs ≤ 3 DEB-TACE, 29.1 vs 20.2 months, P = 0.03). CONCLUSION: DEB-TACE therapy for HCC demonstrated long-term preservation of HRQOL. In addition, staged DEB-TACE with four or more therapies does not significantly impact long-term HRQOL compared with patients who received three or fewer therapies.

Performance Comparison of a Pretied Suture Knot With Three Conventional Arthroscopic Knots.

PURPOSE: To compare the knot characteristics of a pretied suture knot with 3 of the most commonly used arthroscopic knots tied with various high-strength sutures. METHODS: Three commonly used arthroscopic knots (surgeon's knot, Seoul Medical Center, and Duncan loop) tied with no. 2 high-strength sutures were compared with a pretied knot secured with either 1, 2, or 3 reversed half hitches (RHAPS). An orthopaedic sports medicine surgeon and fellow tied a total of 120 knots. All knot combinations were tested for strength, knot bulk, cyclic loop elongation, ultimate loop elongation, and ultimate strength. RESULTS: All pretied configurations had statistically significant improved strength (P = .048, P ≤ .001, and P < .001) versus all other knot groups with mean ± standard deviation loads of 206.3 ± 37.5, 285.6 ± 68.6, and 357.6 ± 61.1 N, respectively. The pretied knot with 1, 2, or 3 RHAPs has significantly smaller volume than the arthroscopic knots in all suture materials. All pretied knot configurations demonstrated no significant difference in cyclic loop elongation compared with standard arthroscopic knots; however, they had a statistically significant lower ultimate loop elongation (P = .001 for each pretied knot configuration). CONCLUSIONS: Compared with other commonly tied arthroscopic knots using no. 2 high-strength suture, the pretied knot with doubled no. 1 high-tensile-strength suture tied with 1, 2, or 3 RHAPs results in a statistically significantly improved strength. The pretied knot has an equivalent cyclic loop elongation and lower ultimate loop elongation with all RHAP configurations. The pretied knot with 2 or 3 RHAPs has a significantly higher ultimate strength than all combinations of arthroscopic knots excluding one. The pretied knot with 1, 2, or 3 RHAPs has significantly less knot volume than all other knots tested and offers a more reproducible knot. CLINICAL RELEVANCE: The pre-tied knot offers equivalent or improved strength while having a smaller knot volume.

A review of dry (CO2) reforming of methane over noble metal catalysts.

Dry (CO2) reforming of methane (DRM) is a well-studied reaction that is of both scientific and industrial importance. This reaction produces syngas that can be used to produce a wide range of products, such as higher alkanes and oxygenates by means of Fischer-Tropsch synthesis. DRM is inevitably accompanied by deactivation due to carbon deposition. DRM is also a highly endothermic reaction and requires operating temperatures of 800-1000 °C to attain high equilibrium conversion of CH4 and CO2 to H2 and CO and to minimize the thermodynamic driving force for carbon deposition. The most widely used catalysts for DRM are based on Ni. However, many of these catalysts undergo severe deactivation due to carbon deposition. Noble metals have also been studied and are typically found to be much more resistant to carbon deposition than Ni catalysts, but are generally uneconomical. Noble metals can also be used to promote the Ni catalysts in order to increase their resistance to deactivation. In order to design catalysts that minimize deactivation, it is necessary to understand the elementary steps involved in the activation and conversion of CH4 and CO2. This review will cover DRM literature for catalysts based on Rh, Ru, Pt, and Pd metals. This includes the effect of these noble metals on the kinetics, mechanism and deactivation of these catalysts.

Catalytic aromatization of methane.

Recent developments in natural gas production technology have led to lower prices for methane and renewed interest in converting methane to higher value products. Processes such as those based on syngas from methane reforming are being investigated. Another option is methane aromatization, which produces benzene and hydrogen: 6CH4(g) → C6H6(g) + 9H2(g) ΔG°(r) = +433 kJ mol(-1) ΔH°(r) = +531 kJ mol(-1). Thermodynamic calculations for this reaction show that benzene formation is insignificant below ∼600 °C, and that the formation of solid carbon [C(s)] is thermodynamically favored at temperatures above ∼300 °C. Benzene formation is insignificant at all temperatures up to 1000 °C when C(s) is included in the calculation of equilibrium composition. Interestingly, the thermodynamic limitation on benzene formation can be minimized by the addition of alkanes/alkenes to the methane feed. By far the most widely studied catalysts for this reaction are Mo/HZSM-5 and Mo/MCM-22. Benzene selectivities are generally between 60 and 80% at methane conversions of ∼10%, corresponding to net benzene yields of less than 10%. Major byproducts include lower molecular weight hydrocarbons and higher molecular weight substituted aromatics. However, carbon formation is inevitable, but the experimental findings show this can be kinetically limited by the use of H2 or oxidants in the feed, including CO2 or steam. A number of reactor configurations involving regeneration of the carbon-containing catalyst have been developed with the goal of minimizing the cost of regeneration of the catalyst once deactivated by carbon deposition. In this tutorial review we discuss the thermodynamics of this process, the catalysts used and the potential reactor configurations that can be applied.

Survival, efficacy, and safety of small versus large doxorubicin drug-eluting beads TACE chemoembolization in patients with unresectable HCC.

OBJECTIVE: The purpose of this study was to investigate the overall survival, efficacy, and safety of small (100-300 µm) versus large (300-500 and 500-700 µm) doxorubicin drug-eluting beads transarterial chemoembolization (DEB TACE) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Ninety-four consecutive patients with unresectable HCC who underwent 269 DEB TACE procedures in 48 months were studied. DEB TACE procedures were performed using different DEB sizes: 100-300 µm (Group A, 59 patients) and with mixed 300-500 and 500-700 µm DEB (Group B, 35 patients). Survival rates were compared between the groups. RESULTS: The overall median survival in groups A and B were 15.1 and 11.1 months, respectively (p=0.005). Both groups were similar in demographics, tumor burden, and differential staging (p>0.5). Substratification of overall survival according to Child-Pugh class and Okuda, Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer (BCLC) staging were significantly higher in group A than in group B (p<0.05). Common terminology criteria for adverse events (CTCAE) grade III adverse events and 30-day mortality were significantly lower in group A than in group B (6.8% vs 20%; p=0.04, and 0% vs 14.3%; p=0.001, respectively). The particle size, Child-Pugh class, and serum α-fetoprotein level were significant prognostic indicators of survival on multivariate analysis. CONCLUSION: TACE with 100-300 µm sized DEB is associated with significantly higher survival rate and lower complications than TACE with 300-500 and 500-700 µm sized DEB.

Design and synthesis of copper-cobalt catalysts for the selective conversion of synthesis gas to ethanol and higher alcohols.

Combining quantum-mechanical simulations and synthesis tools allows the design of highly efficient CuCo/MoO(x) catalysts for the selective conversion of synthesis gas (CO+H2) into ethanol and higher alcohols, which are of eminent interest for the production of platform chemicals from non-petroleum feedstocks. Density functional theory calculations coupled to microkinetic models identify mixed Cu-Co alloy sites, at Co-enriched surfaces, as ideal for the selective production of long-chain alcohols. Accordingly, a versatile synthesis route is developed based on metal nanoparticle exsolution from a molybdate precursor compound whose crystalline structure isomorphically accommodates Cu(2+) and Co(2+) cations in a wide range of compositions. As revealed by energy-dispersive X-ray nanospectroscopy and temperature-resolved X-ray diffraction, superior mixing of Cu and Co species promotes formation of CuCo alloy nanocrystals after activation, leading to two orders of magnitude higher yield to high alcohols than a benchmark CuCoCr catalyst. Substantiating simulations, the yield to high alcohols is maximized in parallel to the CuCo alloy contribution, for Co-rich surface compositions, for which Cu phase segregation is prevented.

Nitrogen-doped fullerene as a potential catalyst for hydrogen fuel cells.

We examine the possibility of nitrogen-doped C60 fullerene (N-C60) as a cathode catalyst for hydrogen fuel cells. We use first-principles spin-polarized density functional theory calculations to simulate the electrocatalytic reactions on N-C60. The first-principles results show that an O2 molecule can be adsorbed and partially reduced on the N-C complex sites (Pauling sites) of N-C60 without any activation barrier. Through a direct pathway, the partially reduced O2 can further react with H(+) and additional electrons and complete the water formation reaction (WFR) with no activation energy barrier. In the indirect pathway, reduced O2 reacts with H(+) and additional electrons to form H2O molecules through a transition state (TS) with a small activation barrier (0.22-0.37 eV). From an intermediate state to a TS, H(+) can obtain a kinetic energy of ∼0.95-3.68 eV, due to the Coulomb electric interaction, and easily overcome the activation energy barrier during the WFR. The full catalytic reaction cycles can be completed energetically, and N-C60 fullerene recovers to its original structure for the next catalytic reaction cycle. N-C60 fullerene is a potential cathode catalyst for hydrogen fuel cells.

Millifluidics for time-resolved mapping of the growth of gold nanostructures.

Innovative in situ characterization tools are essential for understanding the reaction mechanisms leading to the growth of nanoscale materials. Though techniques, such as in situ transmission X-ray microscopy, fast single-particle spectroscopy, small-angle X-ray scattering, etc., are currently being developed, these tools are complex, not easily accessible, and do not necessarily provide the temporal resolution required to follow the formation of nanomaterials in real time. Here, we demonstrate for the first time the utility of a simple millifluidic chip for an in situ real time analysis of morphology and dimension-controlled growth of gold nano- and microstructures with a time resolution of 5 ms. The structures formed were characterized using synchrotron radiation-based in situ X-ray absorption spectroscopy, 3-D X-ray tomography, and high-resolution electron microscopy. These gold nanostructures were found to be catalytically active for conversion of 4-nitrophenol into 4-aminophenol, providing an example of the potential opportunities for time-resolved analysis of catalytic reactions. While the investigations reported here are focused on gold nanostructures, the technique can be applied to analyze the time-resolved growth of other types of nanostructured metals and metal oxides. With the ability to probe at least a 10-fold higher concentrations, in comparison with traditional microfluidics, the tool has potential to revolutionize a broad range of fields from catalysis, molecular analysis, biodefense, and molecular biology.

Randomized trial of emtricitabine/tenofovir disoproxil fumarate after hepatitis B immunoglobulin withdrawal after liver transplantation.

Long-term prophylaxis with hepatitis B immunoglobulin (HBIG) for the prevention of hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) in patients with chronic HBV infection is inconvenient and costly. This randomized, prospective phase 2 study compared emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) after HBIG withdrawal to FTC/TDF plus HBIG for the prevention of HBV recurrence after OLT. Forty patients with a median time since liver transplantation of 3.4 years (interquartile range = 1.9-5.6 years) received 24 weeks of open-label FTC/TDF plus HBIG before randomization. Patients who maintained confirmed viral suppression were randomized to continue FTC/TDF plus HBIG (n = 19) or receive FTC/TDF alone (n = 18) for an additional 72 weeks. No patient experienced HBV recurrence through 72 weeks of the study while he or she was receiving the randomized treatment. Both treatment arms were safe and well tolerated; no serious or severe drug-related adverse events were observed. Renal function was consistent with that observed in a posttransplant population. The withdrawal of HBIG after 6 months' treatment with FTC/TDF should be considered in liver transplant recipients to prevent chronic HBV recurrence.

Ligand-stabilized and atomically precise gold nanocluster catalysis: a case study for correlating fundamental electronic properties with catalysis.

We present results from our investigations into correlating the styrene-oxidation catalysis of atomically precise mixed-ligand biicosahedral-structure [Au25(PPh3)10(SC12H25)5Cl2](2+) (Au25-bi) and thiol-stabilized icosahedral core-shell-structure [Au25(SCH2CH2Ph)18](-) (Au25-i) clusters with their electronic and atomic structure by using a combination of synchrotron radiation-based X-ray absorption fine-structure spectroscopy (XAFS) and ultraviolet photoemission spectroscopy (UPS). Compared to bulk Au, XAFS revealed low Au-Au coordination, Au-Au bond contraction and higher d-band vacancies in both the ligand-stabilized Au clusters. The ligands were found not only to act as colloidal stabilizers, but also as d-band electron acceptor for Au atoms. Au25-bi clusters have a higher first-shell Au coordination number than Au25-i, whereas Au25-bi and Au25-i clusters have the same number of Au atoms. The UPS revealed a trend of narrower d-band width, with apparent d-band spin-orbit splitting and higher binding energy of d-band center position for Au25-bi and Au25-i. We propose that the differences in their d-band unoccupied state population are likely to be responsible for differences in their catalytic activity and selectivity. The findings reported herein help to understand the catalysis of atomically precise ligand-stabilized metal clusters by correlating their atomic or electronic properties with catalytic activity.

Liver MRI and histological correlates in chronic liver disease on multiphase gadolinium-enhanced 3D gradient echo imaging.

PURPOSE: To evaluate intrinsic hepatic enhancement patterns on multiphase, gadolinium-enhanced, fat-suppressed, 3D T1-weighted, gradient echo magnetic resonance imaging (MRI) as a quantitative correlate for severity of pathological changes in chronic liver disease (CLD). MATERIALS AND METHODS: This study was HIPAA-compliant and Institutional Review Board-approved. In all, 75 patients were studied by contrast-enhanced multiphase abdominal MRI. CLD patients had liver histology correlation derived from right lobe liver biopsies. Contrast-enhanced arterial- and delayed-phase 3D gradient recalled echo (GRE) liver MRI were scored using feature categorization templates to quantify enhancement patterns by three independent readers. Liver histopathology was staged/graded for fibrosis/inflammation using the Scheuer system. Statistical testing for MRI histology correlates used a Pearson's product moment correlation and a Wilcoxon-Mann-Whitney two-sample rank-sum test. Reader agreement was analyzed by a modified Fleiss' kappa test. RESULTS: MRI histology correlation was high for delayed-phase MRI versus fibrosis stage (95% confidence interval [CI] 0.941 < r < 0.976, P = 5 × 10(-7)), but lower for all other comparisons (delayed-phase vs. inflammation and arterial-phase vs. inflammation or fibrosis all showed a CI no greater than 0.64). Paired testing between delayed-phase MRI score and histology fibrosis staging incremental levels was significant (from P < 10(-2) to P < 10(-5)). CONCLUSION: A standard gadolinium-enhanced liver MRI may provide a correlate measure of hepatic fibrosis over a spectrum of severity.

Synthesis, characterization, and testing of supported Au catalysts prepared from atomically-tailored Au38(SC12H25)24 clusters.

Nearly monodispersed Au(38)(SC(12)H(25))(24) clusters (1.7 ± 0.2 nm) were synthesized using a modified Brust process while utilizing a "thiol etching" approach for the ligand exchange. HRTEM, MALDI, FTIR, and XAS analysis confirmed the formation of the 38-atom clusters in solution. This solution was used to impregnate a microporous TiO(2) support to give 0.7% Au(38)/TiO(2) catalyst. Subsequent drying in air and treatment with H(2)/He at 400 °C removed most of the sulfur ligands, and also increased the Au cluster size to 3.9 ± 0.96 nm. XPS and EXAFS analysis of this supported catalyst showed trace levels of residual sulfides, apparently located at the Au-TiO(2) interface. CO oxidation tests on these supported clusters show an activation energy and range of TOFs comparable to those reported by others. These results suggest that supported Au clusters of controllable size can be prepared with this thiol-ligated solution-based method, providing a new approach to the synthesis of these catalysts.

Hepatocellular carcinoma lesion characterization: single-institution clinical performance review of multiphase gadolinium-enhanced MR imaging--comparison to prior same-center results after MR systems improvements.

PURPOSE: To measure diagnostic performance in the detection of hepatocellular carcinoma (HCC) by using the most recent technology and multiphase gadolinium-enhanced magnetic resonance (MR) imaging and to compare with earlier results at the same institution. MATERIALS AND METHODS: This retrospective study was institutional review board approved and HIPAA compliant. Informed consent was obtained. Between January 2008 and April 2010, 101 patients underwent liver transplantation and pretransplantation abdominal MR imaging within 90 days. Prospective image interpretations from the clinical record were reviewed for documentation of HCC, including size, number, and location. Liver explant histologic examination provided the reference standard for lesion analysis and was performed in axial gross slices in conjunction with the MR imaging report for direct comparison. Tumors were categorized according to size (≥ 2 cm or <2 cm), and MR imaging detection sensitivity, specificity, predictive values, and accuracy were calculated according to category. The Fisher exact test was used to compare results from this study against prior reported results. RESULTS: Thirty-five (34.7%) of 101 patients had HCC at explant analysis. Patient-based analysis of all lesions showed a sensitivity and specificity of 97.1% (34 of 35) and 100% (66 of 66), respectively. For lesions 2 cm or larger, MR imaging had a sensitivity and specificity of 100% (23 of 23) and 100% (78 of 78), respectively. For lesions smaller than 2 cm, MR imaging had a sensitivity and specificity of 82.6% (19 of 23) and 100% (78 of 78), respectively. Lesion-based sensitivity for all tumors was 91.4% (53 of 58) in the current study, compared with 77.8% in 2007 (P = .07). For lesions smaller than 2 cm, the sensitivity was 87.5% (28 of 32) in the current study, compared with 55.6% previously (P = .02). CONCLUSION: MR imaging remains a highly accurate diagnostic method for the preoperative evaluation of HCC, and detection of small (<2 cm) tumors has been significantly improved compared with that of earlier studies.

Transjugular intrahepatic portosystemic shunt for symptomatic refractory hepatic hydrothorax in patients with cirrhosis.

OBJECTIVES: We sought to study effectiveness, survival, and complications after transjugular intrahepatic portosystemic shunt (TIPS) in patients with cirrhosis and symptomatic refractory hepatic hydrothorax. METHODS: Consecutive patients who underwent TIPS between January 1992 and December 2008 for refractory hydrothorax were reviewed retrospectively. Clinical, laboratory, and procedural data were collected for all patients by retrospective chart review. Chi-square test was used to compare categorical variables and t-test to compare continuous variables. The Kaplan-Meier method was used for survival analysis. Survival curves were compared using the log-rank test. RESULTS: Seventy-three patients were included in the study, and their mean age at TIPS creation was 55.62 years (s.d. 11.65). The mean pre- and post-TIPS portosystemic gradients were 18.9 (s.d. 4.7) mm Hg and 5.7 (s.d. 2.4) mm Hg (P<0.001), respectively. The rates of favorable clinical response within 1 month and at 6 months after TIPS were 79% (58/73) and 75% (30/40), respectively. Median survival of the study group was 517 days (95% CI 11-626). The short-term survival rates at 30, 60, and 90 days were 81, 78, and 72%, respectively. The long-term survival rates at 1, 3, and 5 years were 48, 26, and 15%, respectively. Multivariate analysis by Cox proportional hazards method showed that pre-TIPS model for end-stage liver disease (MELD) score (P=0.039, HR 1.9 (95% CI 1.0-3.7)) and clinical response (P=0.003, HR 2.5 (95% CI 1.4-4.5)) were significantly and independently associated with overall survival. The 30-day mortality rate was 19%. Pre-TIPS creatinine levels (P=0.024, HR 3.42 (95% CI 1.2-9.9)) were significantly associated with 30-day mortality. CONCLUSIONS: TIPS can be successfully used to achieve symptomatic relief in patients with refractory hepatic hydrothorax. Better clinical response after TIPS and pre-TIPS MELD score less than 15 were associated with longer survival after TIPS.

The effectiveness of locoregional therapies versus supportive care in maintaining survival within the Milan criteria in patients with hepatocellular carcinoma.

PURPOSE: To compare survival after treatment with either locoregional therapy (LRT) or supportive care in patients with hepatocellular carcinoma (HCC) within the Milan criteria. MATERIALS AND METHODS: Patients with HCC who were classified within the Milan criteria (solitary HCC