Massive variceal bleeding secondary to splenic vein thrombosis successfully treated with splenic artery embolization: a case report

<p>Abstract</p> <p>Introduction</p> <p>Splenic vein thrombosis results in localized portal hypertension called sinistral portal hypertension, which may also lead to massive upper gastrointestinal bleeding. Symptomatic sinistral portal hypertension is usually best treated by splenectomy, but interventional radiological techniques are safe and effective alternatives in the management of a massive hemorrhage, particularly in cases that have a high surgical risk.</p> <p>Case presentation</p> <p>We describe a 23-year-old Greek man with acute massive gastric variceal bleeding caused by splenic vein thrombosis due to a missing von Leiden factor, which was successfully managed with splenic arterial embolization.</p> <p>Conclusions</p> <p>Interventional radiological techniques are attractive alternatives for patients with a high surgical risk or in cases when the immediate surgical excision of the spleen is technically difficult. Additionally, surgery is not always successful because of the presence of numerous portal collaterals and adhesion. Splenic artery embolization is now emerging as a safe and effective alternative to surgery in the management of massive hemorrhage from gastric varices due to splenic vein thrombosis, which often occurs in patients with hypercoagulability.</p

Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio

BACKGROUND: Treatment records and follow-up data on 40 patients with primary and metastatic liver malignancies who underwent a single whole-liver treatment with Y-90 resin microspheres (SIR-Spheres(® )Sirtex Medical, Lake Forest, IL) were retrospectively reviewed. The objective of the study was to evaluate the anatomic and physiologic determinants of radiation dose distribution, and the dose response of tumor and liver toxicity in patients with liver malignancies who underwent hepatic arterial Y-90 resin microsphere treatment. METHODS: Liver and tumor volume calculations were performed on pre-treatment CT scans. Fractional tumor and liver flow characteristics and lung shunt fractions were determined using hepatic arterial Tc-99m MAA imaging. Absorbed dose calculations were performed using the MIRD equations. Liver toxicity was assessed clinically and by liver function tests. Tumor response to therapy was assessed by CT and/or tumor markers. RESULTS: Of the 40 patients, 5 had hepatocellular cancer (HCC), and 35 had metastatic liver tumors (15 colorectal cancer, 10 neuroendocrine tumors, 4 breast cancer, 2 lung cancer, 1 ovarian cancer, 1 endometrial cancer, and 2 unknown primary adenocarcinoma). All patients were treated in a salvage setting with a 3 to 80 week follow-up (mean: 19 weeks). Tumor volumes ranged from 15.0 to 984.2 cc (mean: 294.9 cc) and tumor to normal liver uptake ratios ranged from 2.8 to 15.4 (mean: 5.4). Average administered activity was 1.2 GBq (0.4 to 2.4 GBq). Liver absorbed doses ranged from 0.7 to 99.5 Gy (mean: 17.2 Gy). Tumor absorbed doses ranged from 40.1 to 494.8 Gy (mean: 121.5 Gy). None of the patients had clinical venoocclusive disease or therapy-induced liver failure. Seven patients (17.5 %) had transient and 7 patients (17.5 %) had persistent LFT abnormalities. There were 27 (67.5%) responders (complete response, partial response, and stable disease). Tumor response correlated with higher tumor flow ratio as measured by Tc-99m MAA imaging. CONCLUSION: Doses up to 99.5 Gy to uninvolved liver are tolerated with no clinical venoocclusive disease or liver failure. The lowest tumor dose producing a detectable response is 40.1 Gy. The utilization of MAA-based imaging techniques to determine tumor and liver blood flow for clinical treatment planning and the calculation of administered activity may improve clinical outcomes

Design of RNAi Hairpins for Mutation-Specific Silencing of Ataxin-7 and Correction of a SCA7 Phenotype

Spinocerebellar ataxia type 7 is a polyglutamine disorder caused by an expanded CAG repeat mutation that results in neurodegeneration. Since no treatment exists for this chronic disease, novel therapies such post-transcriptional RNA interference-based gene silencing are under investigation, in particular those that might enable constitutive and tissue-specific silencing, such as expressed hairpins. Given that this method of silencing can be abolished by the presence of nucleotide mismatches against the target RNA, we sought to identify expressed RNA hairpins selective for silencing the mutant ataxin-7 transcript using a linked SNP. By targeting both short and full-length tagged ataxin-7 sequences, we show that mutation-specific selectivity can be obtained with single nucleotide mismatches to the wild-type RNA target incorporated 3′ to the centre of the active strand of short hairpin RNAs. The activity of the most effective short hairpin RNA incorporating the nucleotide mismatch at position 16 was further studied in a heterozygous ataxin-7 disease model, demonstrating significantly reduced levels of toxic mutant ataxin-7 protein with decreased mutant protein aggregation and retention of normal wild-type protein in a non-aggregated diffuse cellular distribution. Allele-specific mutant ataxin7 silencing was also obtained with the use of primary microRNA mimics, the most highly effective construct also harbouring the single nucleotide mismatch at position 16, corroborating our earlier findings. Our data provide understanding of RNA interference guide strand anatomy optimised for the allele-specific silencing of a polyglutamine mutation linked SNP and give a basis for the use of allele-specific RNA interference as a viable therapeutic approach for spinocerebellar ataxia 7

Quantitative determination of vitamin D metabolites in plasma using UHPLC-MS/MS

Vitamin D is an important determinant of bone health at all ages. The plasma concentrations of 25-hydroxy vitamin D (25-OH D) and other metabolites are used as biomarkers for vitamin sufficiency and function. To allow for the simultaneous determination of five vitamin D metabolites, 25-OH D3, 25-OH D2, 24,25-(OH)2 D3, 1,25-(OH)2 D3, and 1,25-(OH)2 D2, in low volumes of human plasma, an assay using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) was established. Plasma samples were spiked with isotope-labeled internal standards and pretreated using protein precipitation, solid-phase extraction (SPE) and a Diels–Alder derivatization step with 4-phenyl-1,2,4-triazoline-3,5-dione. The SPE recovery rates ranged from 55% to 85%, depending on the vitamin D metabolite; the total sample run time was <5 min. Mass spectrometry was conducted using positive ion electrospray ionization in the multiple reaction monitoring mode on a quadrupole–quadrupole-linear ion trap instrument after pre-column addition of methylamine to increase the ionization efficiency. The intra- and inter-day relative standard deviations were 1.6–4.1% and 3.7–6.8%, respectively. The limit of quantitation for these compounds was determined to be between 10 and 20 pg/mL. The 25-OH D results were compared with values obtained for reference materials (DEQAS). In addition, plasma samples were analyzed with two additional Diasorin antibody assays. All comparisons with conventional methods showed excellent correlations (r2 = 0.9738) for DEQAS samples, demonstrating the high degree of comparability of the new UHPLC-MS/MS technique to existing methods