Intravascular Ultrasound in the Creation of Transhepatic Portosystemic Shunts Reduces Needle Passes, Radiation Dose, and Procedure Time: A Retrospective Study of a Single-Institution Experience.

PURPOSE: To assess whether intravascular ultrasound (US) guidance impacts number of needle passes, contrast usage, radiation dose, and procedure time during creation of transjugular intrahepatic portosystemic shunts (TIPS). MATERIALS AND METHODS: Intravascular US-guided creation of TIPS in 40 patients was retrospectively compared with conventional TIPS in 49 patients between February 2010 and November 2015 at a single tertiary care institution. Patient sex and age, etiology of liver disease (hepatitis C virus, alcohol abuse, nonalcoholic steatohepatitis), severity of liver disease (mean Model for End-Stage Liver Disease score), and indications for TIPS (variceal bleeding, refractory ascites, refractory hydrothorax) in conventional and intravascular US-guided cases were recorded. RESULTS: The two groups were well matched by sex, age, etiology of liver disease, Child-Pugh class, Model for End-Stage Liver Disease scores, and indication for TIPS (P range = .19-.94). Fewer intrahepatic needle passes were required in intravascular US-guided TIPS creation compared with conventional TIPS (2 passes vs 6 passes, P < .01). Less iodinated contrast material was used in intravascular US cases (57 mL vs 140 mL, P < .01). Radiation exposure, as measured by cumulative dose, dose area product, and fluoroscopy time, was reduced with intravascular US (174 mGy vs 981 mGy, P < .01; 3,793 µGy * m(2) vs 21,414 µGy * m(2), P < .01; 19 min vs 34 min, P < .01). Procedure time was shortened with intravascular US (86 min vs 125 min, P < .01). CONCLUSIONS: Intravascular US guidance resulted in fewer intrahepatic needle passes, decreased contrast medium usage, decreased radiation dosage, and shortened procedure time in TIPS creation.

Complete pathologic response to pretransplant locoregional therapy for hepatocellular carcinoma defines cancer cure after liver transplantation: analysis of 501 consecutively treated patients.

OBJECTIVES: To evaluate the rate, effect, and predictive factors of a complete pathologic response (cPR) in patients with hepatocellular carcinoma (HCC) undergoing locoregional therapy (LRT) before liver transplantation (LT). BACKGROUND: Eligible patients with HCC receive equal model for end-stage liver disease prioritization, despite variable risks of tumor progression, waitlist dropout, and posttransplant recurrence. Pretransplant LRT mitigates these risks by inducing tumor necrosis. METHODS: Comparisons were made among HCC recipients with cPR (n = 126) and without cPR (n = 375) receiving pre-LT LRT (1994-2013). Multivariable predictors of cPR were identified. RESULTS: Of 501 patients, 272, 148, and 81 received 1, 2, and 3 or more LRT treatments. The overall, recurrence-free, and disease-specific survival at 1-, 3-, and 5 years was 86%, 71%, 63%; 84%, 67%, 60%; and 97%, 90%, 87%. Compared with recipients without cPR, cPR patients had significantly lower laboratory model for end-stage liver disease scores, pretransplant alpha fetoprotein, and cumulative tumor diameters; were more likely to have 1 lesion, tumors within Milan/University of California, San Francisco (UCSF) criteria, LRT that included ablation, and a favorable tumor response to LRT; and had superior 1-, 3-, and 5-year recurrence-free survival (92%, 79%, and 73% vs 81%, 63%, and 56%; P = 0.006) and disease-specific survival (100%, 100%, and 99% vs 96%, 89%, and 86%; P < 0.001) with only 1 cancer-specific death and fewer recurrences (2.4% vs 15.2%; P < 0.001). Multivariate predictors of cPR included a favorable post-LRT radiologic/alpha fetoprotein tumor response, longer time interval from LRT to LT, and lower model for end-stage liver disease score and maximum tumor diameter (C-statistic 0.75). CONCLUSIONS: Achieving cPR in patients with HCC receiving LRT strongly predicts tumor-free survival. Factors predicting cPR are identified, allowing for differential prioritization of HCC recipients based on their variable risks of post-LT recurrence. Improving LRT strategies to maximize cPR would enhance posttransplant cancer outcomes.

Feasibility of Intraprocedural Transluminal Hepatic and Femoral Artery Blood Pressure Measurements as an Alternative Embolization Safety Endpoint When Antireflux Devices Are Used During Lobar Chemoembolization.

OBJECTIVE: The purpose of this study was to describe the technique for evaluating hepatic arterial blood pressure changes during lobar chemoembolization using antireflux devices. Intraprocedural femoral and hepatic arterial blood pressures were measured and chemoembolization terminated when significant reduction in the difference occurred. Liver toxicity was evaluated. Eleven patients underwent 24 lobar chemoembolization procedures. Early termination of delivery occurred in 11 of 24 (46%) procedures in which the mean relative reduction in systemic-hepatic arterial pressure differential was 48%. The mean liver toxicity score was 1.2. This compares to delivery of the entire dose in 13 of 24 (54%) procedures in which the mean relative reduction in systemic-hepatic arterial pressure differential was 12% with a mean liver toxicity score of 1.2. CONCLUSION: When antireflux devices are used, intraprocedural assessment of hepatic artery blood pressure changes may be a useful embolization safety endpoint.

Yttrium-90 resin microsphere radioembolization using an antireflux catheter: an alternative to traditional coil embolization for nontarget protection.

PURPOSE: Serious complications can result from nontarget embolization during yttrium-90 (Y-90) transarterial radioembolization. Hepatoenteric artery coil embolization has been traditionally performed to prevent nontarget radioembolization. The U.S. Food and Drug Administration-approved Surefire Infusion System (SIS) catheter, designed to prevent reflux, is an alternative to coils. The hypothesis that quantifiable SIS procedural parameters are comparable to coil embolization was tested. METHODS: Fourteen patients aged 36-79 years with colorectal, neuroendocrine, hepatocellular, and other predominantly bilobar hepatic tumors who underwent resin microsphere Y-90 radioembolization using only the SIS catheter (n = 7) versus only detachable coils (n = 7) for nontarget protection were reviewed retrospectively. Procedure time, fluoroscopy time, contrast dose, radiation dose, and cost were evaluated. RESULTS: Multivariate analysis identified significant cohort differences in the procedural parameters evaluated (F(10, 3) = 10.39, p = 0.04). Between-group comparisons of the pretreatment planning procedure in the SIS catheter group compared to the coil embolization group demonstrated a significant reduction in procedure time (102.6 vs. 192.1 min, respectively, p = 0.0004), fluoroscopy time (14.3 vs. 49.7 min, respectively, p = 0.0016), and contrast material dose (mean dose of 174.3 vs. 265.0 mL, respectively, p = 0.0098). Procedural parameters were not significantly different between the two groups during subsequent dose delivery procedures. Overall cost of combined first-time radioembolization procedures was significantly less in the SIS group ($4252) compared to retrievable coil embolization ($11,123; p = 0.001). CONCLUSION: The SIS catheter results in a reduction in procedure time, fluoroscopy time, and contrast material dose and may be an attractive cost-effective alternative to detachable coil embolization for prevention of nontarget radioembolization.

Nickel hypersensitivity in patients with inferior vena cava filters: case report and literature and MAUDE database review.

Placement of a prophylactic retrievable inferior vena cava (IVC) filter was requested in a 73-year-old woman with nickel hypersensitivity resulting in a clinical dilemma. Given that all retrievable filters contain nickel, the published literature and the Manufacturer and User Facility Device Experience (MAUDE) database were reviewed; no documented case of IVC filter placement in a patient with nickel hypersensitivity or reported hypersensitivity reaction in a patient after IVC filter placement could be identified. This article presents the uneventful course of the case described and a review of the literature and recommendations on use of nickel-containing devices in patients with nickel hypersensitivity.

Amphetamine-associated contextual learning is accompanied by structural and functional plasticity in the basolateral amygdala.

Drug seeking and the vulnerability to relapse occur when individuals are exposed to an environment with sensory cues in which drug taking has occurred. Memory formation is thought to require plasticity in synaptic circuits, and so we examined whether the memory for a drug-paired environment correlates with changes in the synaptic circuits of the basolateral amygdala (BLA), in which emotional learning is a recognized phenomenon. We used amphetamine (AMPH) as the unconditioned stimulus in the conditioned place preference (CPP) paradigm. Rats were conditioned with 1.0 mg/kg AMPH and tested, drug free, 72 h after the last conditioning session. Controls included a saline-conditioned group and a home cage AMPH injection group, whose exposure to the CPP apparatus was delayed by 4 h, long enough to clear the AMPH from the brain. We counted excitatory synapses in the BLA using the electron microscope and the physical disector design (stereology). Rats that expressed AMPH CPP had an increase in excitatory synapses compared with controls. Excitatory synaptic activity was measured using in vivo intracellular recordings from the BLA in anesthetized rats. We found that AMPH CPP, but not drug alone, increased measures of synaptic drive, including the frequency of synaptic events, and the paired-pulse ratio of synaptic inputs to BLA pyramidal neurons. The in vivo findings suggest that the increase in BLA neuronal excitatory drive reflects the change in excitatory synapse number. Thus, context-drug associations are accompanied by structural and functional plasticity in the BLA, findings that have important implications for drug-seeking behavior.

Increased synapses in the medial prefrontal cortex are associated with repeated amphetamine administration.

Psychostimulant drug experience leads not only to long-lasting changes in behavior but also modifications in the activity and morphology of pyramidal neurons in the medial prefrontal cortex (mPFC). The objective of this study was to establish whether repeated treatment of rats with amphetamine (AMPH) is accompanied by changes in the pattern or types of synapses in the mPFC and, specifically, onto neurons that project to the lateral hypothalamus, where our earlier work has shown increased markers of neuronal activity after repeated AMPH treatment (Morshedi and Meredith [2008] Psychopharmacology (Berl) 197:179-189). Rats were treated with a behaviorally sensitizing regimen of AMPH, following which synapses in the infralimbic and prelimbic cortices of the mPFC, were analyzed with unbiased stereology (physical disector and electron microscopy). All synapses were counted and their targets were identified by standard methodological criteria. Repeated AMPH administration was associated with a significant increase in the number of asymmetric axospinous synapses, no change in axodendritic or axosomatic contacts, and no change in the total number of synapses on corticolateral hypothalamic pyramidal neurons compared to vehicle-treated rats. Therefore, behavioral sensitization as a result of repeated exposure to AMPH is accompanied by the increased formation of spine, but not dendritic, synapses onto pyramidal neurons in the mPFC.

Repeated amphetamine administration induces Fos in prefrontal cortical neurons that project to the lateral hypothalamus but not the nucleus accumbens or basolateral amygdala.

RATIONALE: The development of sensitization to amphetamine (AMPH) is dependent on increases in excitatory outflow from the medial prefrontal cortex (mPFC) to subcortical centers. These projections are clearly important for the progressive enhancement of the behavioral response during drug administration that persists through withdrawal. OBJECTIVES: The objective of this study was to identify the mPFC subcortical pathway(s) activated by a sensitizing regimen of AMPH. MATERIALS AND METHODS: Using retrograde labeling techniques, Fos activation was evaluated in the predominant projection pathways of the mPFC of sensitized rats after a challenge injection of AMPH. RESULTS: There was a significant increase in Fos-immunoreactive cells in the mPFC, nucleus accumbens (NAc), basolateral amygdala (BLA), and lateral hypothalamus (LH) of rats treated repeatedly with AMPH when compared to vehicle-treated controls. The mPFC pyramidal neurons that project to the LH but not the NAc or BLA show a significant induction of Fos after repeated AMPH treatment. In addition, we found a dramatic increase in Fos-activated orexin neurons. CONCLUSIONS: The LH, a region implicated in natural and drug reward processes, may play a role in the development and persistence of sensitization to repeated AMPH through its connections with the mPFC and possibly through its orexin neurons.

The global transcriptional response of Bacillus subtilis to peroxide stress is coordinated by three transcription factors.

Bacillus subtilis exhibits a complex adaptive response to low levels of peroxides. We used global transcriptional profiling to monitor the magnitude and kinetics of changes in the mRNA population after exposure to either hydrogen peroxide (H(2)O(2)) or tert-butyl peroxide (t-buOOH). The peroxide stimulons could be largely accounted for by three regulons controlled by the PerR, sigma(B), and OhrR transcription factors. Three members of the PerR regulon (katA, mrgA, and zosA) were strongly induced by H(2)O(2) and weakly induced by t-buOOH. The remaining members of the PerR regulon were only modestly up-regulated by peroxide treatment. Overall, the magnitude of peroxide induction of PerR regulon genes corresponded well with the extent of derepression in a perR mutant strain. The sigma(B) regulon was activated by 58 micro M H(2)O(2) but not by 8 micro M H(2)O(2) and was strongly activated by either t-buOOH or, in a control experiment, tert-butyl alcohol. Apart from the sigma(B) regulon there was a single gene, ohrA, that was strongly and rapidly induced by t-buOOH exposure. This gene, controlled by the peroxide-sensing repressor OhrR, was not induced by any of the other conditions tested.

Defining the Bacillus subtilis sigma(W) regulon: a comparative analysis of promoter consensus search, run-off transcription/macroarray analysis (ROMA), and transcriptional profiling approaches.

The Bacillus subtilis extracytoplasmic function (ECF) sigma factor sigma(W) controls a large regulon that is strongly induced by alkali shock. To define the physiological role of sigma(W) we have sought to identify the complete set of genes under sigma(W) control. Previously, we described a promoter consensus search procedure to identify sigma(W) controlled genes. Herein, we introduce a novel method to identify additional target promoters: run-off transcription followed by macroarray analysis (ROMA). We compare the resulting list of targets with those identified in conventional transcriptional profiling studies and using the consensus search approach. While transcriptional profiling identifies genes that are strongly dependent on sigma(W) for in vivo expression, some sigma(W)-dependent promoters are not detected due to the masking effects of other promoter elements, overlapping recognition with other ECF sigma factors, or both. Taken together, the consensus search, ROMA, and transcriptional profiling approaches establish a minimum of 30 promoter sites (controlling approximately 60 genes) as direct targets for activation by sigma(W). Significantly, no single approach identifies more than approximately 80% of the regulon so defined. We therefore suggest that a combination of two or more complementary approaches be employed in studies seeking to achieve maximal coverage when defining bacterial regulons. Our results indicate that sigma(W) controls genes that protect the cell against agents that impair cell wall biosynthesis but fail to reveal any connection to operons likely to function in adaptation to alkaline growth conditions. This is consistent with the observation that a sigW mutant is unaffected in its ability to survive alkali shock. We conclude that in B. subtilis sudden imposition of alkali stress activates the sigma(W) stress response, perhaps by impairing the ability of the cell wall biosynthetic machinery to function.