The use of neoadjuvant lobar radioembolization prior to major hepatic resection for malignancy results in a low rate of post hepatectomy liver failure

BackgroundNeoadjuvant yttrium-90 transarterial radioembolization (TARE) is increasingly being used as a strategy to facilitate resection of otherwise unresectable tumors due to its ability to generate both tumor response and remnant liver hypertrophy. Perioperative outcomes after the use of neoadjuvant lobar TARE remain underinvestigated.MethodsA single center retrospective review of patients who underwent lobar TARE prior to major hepatectomy for primary or metastatic liver cancer between 2007 and 2018 was conducted. Baseline demographics, radioembolization parameters, pre- and post-radioembolization volumetrics, intra-operative surgical data, adverse events, and post-operative outcomes were analyzed.ResultsTwenty-six patients underwent major hepatectomy after neoadjuvant lobar TARE. The mean age was 58.3 years (17–88 years). 62% of patients (n=16) had primary liver malignancies while the remainder had metastatic disease. Liver resection included right hepatectomy or trisegmentectomy, left or extended left hepatectomy, and sectorectomy/segmentectomy in 77% (n=20), 8% (n=2), and 15% (n=4) of patients, respectively. The mean length of stay was 8.3 days (range, 3–33 days) and there were no grade IV morbidities or 90-day mortalities. The incidence of post hepatectomy liver failure (PHLF) was 3.8% (n=1). The median time to progression after resection was 4.5 months (range, 3.3–10 months). Twenty-three percent (n=6) of patients had no recurrence. The median survival was 28.9 months (range, 16.9–46.8 months) from major hepatectomy and 37.6 months (range, 25.2–53.1 months) from TARE.ConclusionsMajor hepatectomy after neoadjuvant lobar radioembolization is safe with a low incidence of PHLF.     

The Importance of Venous Return in Starling‐Like Control of Rotary Ventricular Assist Devices

Rotary ventricular assist devices (VADs) are less sensitive to preload than the healthy heart, resulting in inadequate flow regulation in response to changes in patient cardiac demand. Starling‐like physiological controllers (SLCs) have been developed to automatically regulate VAD flow based on ventricular preload. An SLC consists of a cardiac response curve (CRC) which imposes a nonlinear relationship between VAD flow and ventricular preload, and a venous return line (VRL) which determines the return path of the controller. This study investigates the importance of a physiological VRL in SLC of dual rotary blood pumps for biventricular support. Two experiments were conducted on a physical mock circulation loop (MCL); the first compared an SLC with an angled physiological VRL (SLC‐P) against an SLC with a vertical VRL (SLC‐V). The second experiment quantified the benefit of a dynamic VRL, represented by a series of specific VRLs, which could adapt to different circulatory states including changes in pulmonary (PVR) and systemic (SVR) vascular resistance versus a fixed physiological VRL which was calculated at rest. In both sets of experiments, the transient controller responses were evaluated through reductions in preload caused by the removal of fluid from the MCL. The SLC‐P produced no overshoot or oscillations following step changes in preload, whereas SLC‐V produced 0.4 L/min (12.5%) overshoot for both left and right VADs. Additionally, the SLC‐V had increased settling time and reduced controller stability as evidenced by transient controller oscillations. The transient results comparing the specific and standard VRLs demonstrated that specific VRL rise times were improved by between 1.2 and 4.7 s ( = 3.05 s), while specific VRL settling times were improved by between 2.8 and 16.1 seconds ( = 8.38 s) over the standard VRL. This suggests only a minor improvement in controller response time from a dynamic VRL compared to the fixed VRL. These results indicate that the use of a fixed physiologically representative VRL is adequate over a wide variety of physiological conditions.     

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

The Presence of Portal Vein Thrombosis Alters the Classic Enhancement Associated with Diagnosis of Hepatocellular Carcinoma

Digestive Diseases and Sciences - To determine whether the presence of portal vein thrombosis (PVT) where venous flow within the liver may be altered may delay the diagnosis of HCC and be...     

Emerging from their burrow: Hedgehog pathway inhibitors for cancer

Introduction: Cancer treatment is moving away from conventional cytotoxic drugs and towards agents that target specific proteins and mechanisms important to cancer development or survival. The Hedgehog Pathway (HhP) is a signal transduction pathway and its constitutive activation is tumorigenic in basal cell carcinoma (BCC). The HhP enables phenotypic flexibility, and channels tumor-stroma interactions. As a result, it is over-expressed in numerous cancers as well as in the tumor microenvironment and may represent a promising therapeutic target.

Areas covered: In this article, we review the rationale for targeting HhP and its role as an oncogenic driver, in tumor epithelial-to-mesenchymal transition (EMT), and in the tumor microenvironment and describe the results of preclinical and clinical studies involving HhP inhibitors.

Expert opinion: HhP activation plays an important role in both the tumor microenvironment and tumor EMT which can lead to treatment resistance for a number of different malignancies. In addition to standard use in BCC, several HhP inhibitors are in preclinical, early, and mid-stage clinical development for other solid and hematologic malignancies.     

Isolation and characterization of fifteen microsatellite loci for the giant clam Tridacna maxima

Conservation Genetics Resources - Fifteen polymorphic microsatellite markers were developed for Tridacna maxima in order to assess self-recruitment and larval dispersal within and among MPAs in New...     

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

Revisiting the Hydrogen Storage Behavior of the Na-O-H System

Solid-state reactions between sodium hydride and sodium hydroxide are unusual among hydride-hydroxide systems since hydrogen can be stored reversibly. In order to understand the relationship between hydrogen uptake/release properties and phase/structure evolution, the dehydrogenation and hydrogenation behavior of the Na-O-H system has been investigated in detail both ex- and in-situ. Simultaneous thermogravimetric-differential thermal analysis coupled to mass spectrometry (TG-DTA-MS) experiments of NaH-NaOH composites reveal two principal features: Firstly, an H₂ desorption event occurring between 240 and 380 °C and secondly an additional endothermic process at around 170 °C with no associated weight change. In-situ high-resolution synchrotron powder X-ray diffraction showed that NaOH appears to form a solid solution with NaH yielding a new cubic complex hydride phase below 200 °C. The Na-H-OH phase persists up to the maximum temperature of the in-situ diffraction experiment shortly before dehydrogenation occurs. The present work suggests that not only is the inter-phase synergic interaction of protic hydrogen (in NaOH) and hydridic hydrogen (in NaH) important in the dehydrogenation mechanism, but that also an intra-phase H^δ+… H^δ– interaction may be a crucial step in the desorption process.