Bleeding complications after pancreatic surgery : Interventional radiology management

Surgical intervention in the pancreas region is complex and carries the risk of complications, also of vascular nature. Bleeding after pancreatic surgery is rare but characterized by high mortality. This review reports epidemiology, classification, diagnosis and treatment strategies of hemorrhage occurring after pancreatic surgery, focusing on the techniques, roles and outcomes of interventional radiology (IR) in this setting. We then describe the roles and techniques of IR in the treatment of other less common types of vascular complications after pancreatic surgery, such as portal vein (PV) stenosis, portal hypertension and bleeding of varices

Negative Echo in the Density Evolution of Ultracold Fermionic Gases

We predict a nonequilibrium critical phenomenon in the space-time density evolution of a fermionic gas above the temperature of transition into the superfluid phase. On the BCS side of the BEC-BCS crossover, the evolution of a localized density disturbance exhibits a negative echo at the point of the initial inhomogeneity. Approaching the BEC side, this effect competes with the slow spreading of the density of bosonic molecules. However, even here the echo dominates for large enough times. This effect may be used as an experimental tool to locate the position of the transition.Comment: 4 pages, 2 figure

Infection caused by Sporothrix schenckii: an autochthonous case in Bari, Southern Italy

An autochthonous case of lymphocutaneous sporotrichosis caused by Sporothrix schenckii is reported. The patient developed skin lesions localized along the lymphatics that appeared after he suffered an injury while collecting wicker canes in marshy water. The fungus was identified as Sporothrix schenckii by MALDI-TOF and sequencing. Phylogenetic analysis was also performed. Low MIC values were detected for all tested echinocandins and azoles except for fluconazole. The patient was treated with itraconazole without significant improvement. A regression of lesions was observed after 3 months of therapy with voriconazole. Few cases of sporotrichosis have been reported in Europe. However, several cases of sporotrichosis have been described in Italy. The incidence of sporotrichosis in Italy may be underestimated and microbiologists, and clinicians must be aware of this fungal infection

Assessment of the response of hepatocellular carcinoma to interventional radiology treatments

According to Barcelona Clinic Liver Cancer (BCLC) guidelines, interventional radiology procedures are valuable treatment options for many hepatocellular carcinomas (HCCs) that are not amenable to resection or transplantation. Accurate assessment of the efficacy of therapies at earlier stages enables completion of treatment, optimal follow-up and to prevent potentially unnecessary treatments, side effects and costly failure. The goal of this review is to summarize and describe the radiological strategies that have been proposed to predict survival and to stratify HCC responses after interventional radiology therapies. New techniques currently in development are also described

Simultaneous Combination of the CDK4/6 Inhibitor Palbociclib With Regorafenib Induces Enhanced Anti-tumor Effects in Hepatocarcinoma Cell Lines

Advanced hepatocarcinoma (HCC) is an aggressive malignancy with poor prognosis and limited treatment options. Alterations of the cyclin D-CDK4/6-Rb pathway occur frequently in HCC, providing the rationale for its targeting at least in a molecular subset of HCC. In a panel of HCC cell lines, we investigated whether the CDK4/6 inhibitor palbociclib might improve the efficacy of regorafenib, a powerful multi-kinase inhibitor approved as second-line treatment for advanced HCC after sorafenib failure and currently under clinical investigation as first-line therapy in combination with immunotherapy. In Rb-proficient cells, the simultaneous drug combination, but not the sequential schedules, inhibited cell proliferation, either in short or in long-term experiments, and induced cell death more strongly than individual treatments. Moreover, the combination significantly reduced spheroid cell growth and inhibited cell migration/invasion. The superior efficacy of palbociclib plus regorafenib emerged also under hypoxia and was associated with a significant down-regulation of CDK4/6-Rb-myc and mTORC1/p70S6K signaling. Moreover, regorafenib suppressed palbociclib-induced expression of cyclin D1 contributing to the cytotoxic effects of the combination. Besides these inhibitory effects on cell viability/proliferation, palbociclib and regorafenib reduced glucose uptake, although this effect was dependent on the cell model and on the oxygen availability (normoxia or hypoxia). Palbociclib and regorafenib combination impaired glucose uptake and utilization, down-regulating basal and hypoxia-induced expression of HIF-1α, HIF-2α, GLUT-1, and MCT4 proteins as well as the activity/expression of glycolytic enzymes (HK2, PFKP, aldolase A, PKM2). In addition, regorafenib alone reduced mitochondrial respiration. The combined treatment impaired glucose metabolism and respiration without enhancing the effects of the single agents. Our findings provide pre-clinical evidence for the effectiveness of palbociclib and regorafenib combination in HCC cell models

Dual inhibition of CDK4/6 and PI3K/AKT/mTOR signaling impairs energy metabolism in MPM cancer cells

Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated to asbestos exposure. One of the most frequent genetic alteration in MPM patients is CDKN2A/ARF loss, leading to aberrant activation of the Rb pathway. In MPM cells, we previously demonstrated the therapeutic efficacy of targeting this signaling with the CDK4/6 inhibitor palbociclib in combination with PI3K/mTOR inhibitors. Here, we investigated whether such combination may have an impact on cell energy metabolism. Methods: The study was performed in MPM cells of different histotypes; metabolic analyses were conducted by measuring GLUT-1 expression and glucose uptake/consumption, and by SeaHorse technologies. Results: MPM cell models differed for their ability to adapt to metabolic stress conditions, such as glucose starvation and hypoxia. Independently of these differences, combined treatments with palbociclib and PI3K/mTOR inhibitors inhibited cell proliferation more efficaciously than single agents. The drugs alone reduced glucose uptake/consumption as well as glycolysis, and their combination further enhanced these effects under both normoxic and hypoxic conditions. Moreover, the drug combinations significantly impaired mitochondrial respiration as compared with individual treatments. These metabolic effects were mediated by the concomitant inhibition of Rb/E2F/c-myc and PI3K/AKT/mTOR signaling. Conclusions: Dual blockade of glycolysis and respiration contributes to the anti-tumor efficacy of palbociclib-PI3K/mTOR inhibitors combination