Gastric Varices Bleed at Lower Portosystemic Pressure Gradients than Esophageal Varices.

PURPOSE: To quantify and compare portosystemic pressure gradients (PSGs) between bleeding esophageal varices (EV) and gastric varices (GV). MATERIALS AND METHODS: In a single-center, retrospective study, 149 patients with variceal bleeding (90 men, 59 women, mean age 52 y) with EV (n = 69; 46%) or GV (n = 80; 54%) were selected from 320 consecutive patients who underwent successful transjugular intrahepatic portosystemic shunt (TIPS) creation from 1998 to 2016. GV were subcategorized using the Sarin classification as gastroesophageal varices (GEV) (n = 57) or isolated gastric varices (IGV) (n = 23). PSG before TIPS was measured from the main portal vein to the right atrium. PSGs were compared across EV, GEV, and IGV groups using 1-way analysis of variance. RESULTS: Overall mean baseline PSG was 21 mm Hg ± 6. PSG was significantly higher in patients with EV versus GV (23 mm Hg vs 19 mm Hg; P < .001). Mean PSG was highest among EV (23 mm Hg) with lower PSGs identified for GEV (20 mm Hg) and IGV (16 mm Hg); this difference was statistically significant (P < .001). Among 95 acute bleeding cases, a similar pattern was evident (EV 23 mm Hg vs GEV mm Hg 20 vs IGV 17 mm Hg; P < .001). At baseline PSG < 12 mm Hg, 13% (3/23) of IGV bled versus 9% (5/57) of GEV and 3% (2/69) of EVs (P = .169). Mean final PSG after TIPS was 8 mm Hg (IGV 6 mm Hg vs EV and GEV 8 mm Hg; P = .005). CONCLUSIONS: GV bleed at lower PSGs than EV. EV, GEV, and IGV bleeding is associated with successively lower PSGs. These findings highlight distinct physiology, anatomy, and behavior of GV compared with EV.

Feasibility of robotic neuroendovascular surgery.

BACKGROUND: Several recent reports of CorPath GRX vascular robot (Cordinus Vascular Robotics, Natick, MA) use intracranially suggest feasibility of neuroendovascular application. Further use and development is likely. During this progression it is important to understand endovascular robot feasibility principles established in cardiac and peripheral vascular literature which enabled extension intracranially. Identification and discussion of robotic proof of concept principals from sister disciplines may help guide safe and accountable neuroendovascular application. OBJECTIVE: Summarize endovascular robotic feasibility principals established in cardiac and peripheral vascular literature relevant to neuroendovascular application. METHODS: Searches of PubMed, Scopus and Google Scholar were conducted under PRISMA guidelines1 using MeSH search terms. Abstracts were uploaded to Covidence citation review (Covidence, Melbourne, AUS) using RIS format. Pertinent articles underwent full text review and findings are presented in narrative and tabular format. RESULTS: Search terms generated 1642 articles; 177, 265 and 1200 results for PubMed, Scopus and Google Scholar respectively. With duplicates removed, title review identified 176 abstracts. 55 articles were included, 45 from primary review and 10 identified during literature review. As it pertained to endovascular robotic feasibility proof of concept 12 cardiac, 3 peripheral vascular and 5 neuroendovascular studies were identified. CONCLUSIONS: Cardiac and peripheral vascular literature established endovascular robot feasibility and efficacy with equivalent to superior outcomes after short learning curves while reducing radiation exposure >95% for the primary operator. Limitations of cost, lack of haptic integration and coaxial system control continue, but as it stands neuroendovascular robotic implementation is worth continued investigation.

Conventional versus drug-eluting embolic transarterial chemoembolization with doxorubicin: comparative drug delivery, pharmacokinetics, and treatment response in a rabbit VX2 tumor model.

The purpose of this study was to compare intra-tumoral drug delivery, pharmacokinetics, and treatment response after doxorubicin (DOX) conventional (c-) versus drug-eluting embolic (DEE-) transarterial chemoembolization (TACE) in a rabbit VX2 liver tumor model. Twenty-four rabbits with solitary liver tumors underwent c-TACE (n = 12) (1:2 water-in-oil emulsion, 0.6 mL volume, 2 mg DOX) or DEE-TACE (n = 12) (130,000 70-150 µm 2 mg DOX-loaded microspheres). Systemic, intra-tumoral, and liver DOX levels were measured using mass spectrometry up to 7-day post-procedure. Intra-tumoral DOX distribution was quantified using fluorescence imaging. Percent tumor necrosis was quantified by a pathologist blinded to treatment group. Lobar TACE was successfully performed in all cases. Peak concentration (CMAX, µg/mL) for plasma, tumor tissue, and liver were 0.666, 4.232, and 0.270 for c-TACE versus 0.103, 8.988, and 0.610 for DEE-TACE. Area under the concentration versus time curve (AUC, µg/mL ∗ min) for plasma, tumor tissue, and liver were 18.3, 27,078.8, and 1339.1 for c-TACE versus 16.4, 26,204.8, and 1969.6 for DEE-TACE. A single dose of intra-tumoral DOX maintained cytotoxic levels through 7-day post-procedure for both TACE varieties, with a half-life of 1.8 (c-TACE) and 0.8 (DEE-TACE) days. Tumor-to-normal liver DOX ratio was high (c-TACE, 20.2; DEE-TACE, 13.3). c-TACE achieved significantly higher DOX coverage of tumor vs. DEE-TACE (10.8% vs. 2.3%; P = 0.003). Percent tumor necrosis was similar (39% vs. 37%; P = 0.806). In conclusion, in a rabbit VX2 liver tumor model, both c-TACE and DEE-TACE achieved tumoricidal intra-tumoral DOX levels and high tumor-to-normal liver drug ratios, though c-TACE resulted in significantly greater tumor coverage.

Does doxorubicin survive thermal ablation? Results of an ex vivo bench top study.

PURPOSE: We aimed to test the hypothesis that doxorubicin (DOX) survives thermal ablative heating in an ex vivo model of combined transarterial chemoembolization (TACE) and thermal ablation. METHODS: Fresh porcine psoas major muscle (3 samples, 15×10×3 cm) was submerged in aqueous DOX solution (60 µg/mL, 0.1 M) for 24 hours to passively saturate tissue. DOX-infused tissue was then dried and treated with microwave ablation (MWA) using a 2.45 GHz antenna at 65 W for 2, 5, and 10 minutes. Ablations were repeated in triplicate (9 total). Tissue was then sampled at both ablated and unablated control sites, and DOX concentration was quantified via ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), with samples analyzed in triplicate. Tissue DOX levels in ablation and control groups were compared using one-way ANOVA. RESULTS: Homogeneous DOX uptake into porcine tissue was evident in all three samples. Mean DOX concentration in unablated tissue was 8.0±2.2 µg/mL. MWA was technically successful in all 9 procedures (100%), with tissue heating to 95-100°C. Mean tissue DOX concentration showed progressive reduction with increasing ablation time, measuring 6.7±1.3, 4.9±0.9, and 4.8±1.3 µg/mL in MWA-treated tissue after 2, 5, and 10 minutes, respectively. Differences in tissue DOX levels between unablated tissue and MWA groups were statistically significant (P < 0.001). CONCLUSION: Contrary to the initial hypothesis, tissue DOX concentration progressively decreased after MWA of longer ablation times. These results suggest that TACE followed by ablation may result in lower intratumoral DOX than would otherwise be anticipated for TACE alone.

Decision Making for Selection of Transarterial Locoregional Therapy of Metastatic Neuroendocrine Tumors.

Transarterial locoregional therapies (LRTs) are indispensable components of the modern interventional oncologic therapy of liver-dominant metastatic neuroendocrine tumors (NETs). The scope of available LRTs and their nuanced differences mandates a thorough understanding of their relative applicability and effectiveness in certain clinical circumstances to prescribe appropriate, patient-specific, image-guided therapy. This article aims to provide an overview of transarterial LRT options for liver-dominant metastatic NETs and therapy selection by reviewing procedure types, their advantages and disadvantages, and comparative efficacy in common case scenarios.

A Chemical Biology Study of Human Pluripotent Stem Cells Unveils HSPA8 as a Key Regulator of Pluripotency.

Chemical biology methods such as high-throughput screening (HTS) and affinity-based target identification can be used to probe biological systems on a biomacromolecule level, providing valuable insights into the molecular mechanisms of those systems. Here, by establishing a human embryonal carcinoma cell-based HTS platform, we screened 171,077 small molecules for regulators of pluripotency and identified a small molecule, Displurigen, that potently disrupts hESC pluripotency by targeting heat shock 70-kDa protein 8 (HSPA8), the constitutively expressed member of the 70-kDa heat shock protein family, as elucidated using affinity-based target identification techniques and confirmed by loss-of-function and gain-of-function assays. We demonstrated that HSPA8 maintains pluripotency by binding to the master pluripotency regulator OCT4 and facilitating its DNA-binding activity.