Retroperitoneoscopy-Assisted Cryoablation of Renal Tumors Using Multiple 1.5 mm Ultrathin Cryoprobes: A Preliminary Report

Abstract Objectives: Laparoscopic cryoablation has recently been proposed as a minimally invasive nephron-sparing treatment for selected patients. We report on our experience with a retroperitoneoscopic technique using multiple ultrathin cryoprobes. Methods: Seven patients underwent retroperitoneoscopic renal cryoablation for solid renal masses. Mean tumor size on the CT scan was 2.6 (1.5-3.5) cm. A double freeze-thaw cycle of renal cryoablation was performed under realtime ultrasound monitoring using a total of six 1.5-mm cryoprobes simultaneously. Results: Cryoablation was technically successful in all patients without any need for conversion. Mean duration of surgery was 161 (130-195) minutes and mean blood loss was 107 (50-250) ml. Perioperative biopsy of the tumor confirmed renal cell carcinoma in four patients and angiomyolipoma in two patients; it was inconclusive in one case. Mean follow-up for 13.6 (4-22) months showed no evidence of residual tumor or recurrence. Conclusions: Retroperitoneoscopy-assisted cryosurgical ablation using multiple ultrathin 1.5-mm cryoprobes is a minimally invasive treatment that is suitable to treat small renal tumors.

Treatment Algorithm for Metastatic Renal Cell Carcinoma – Recommendations Based on Evidence and Clinical Practice

Until a few years ago, the treatment options for metastatic renal cell cancer (mRCC) were very limited. The growing understanding of the molecular pathomechanisms underlying RCC allowed the development of new treatment approaches. Meanwhile, several approved target-oriented substances from different drug classes are available for mRCC. The mechanism of action of vascular endothelial growth factor (VEGF) and VEGF receptor or mTOR inhibition is well documented by phase III trials and reflected in the current guidelines. However, no predictive biomarkers have been identified in mRCC so far to demonstrate a benefit by a specific compound in an individual patient. Meanwhile, the sequential use of ‘targeted therapies' in mRCC has been established as standard treatment. The optimal sequence of available agents is still unclear. A German RCC expert panel discussed and developed an algorithm for the choices of first- and second-line treatment in mRCC based on established clinical criteria

Potential for CO2 sequestration in saline formations in the western offshore Netherlands: A preliminary study—Expanding carbon capture and storage beyond depleted fields

Against the background of anthropogenic climate change and the need to mitigate CO2 emissions, the Netherlands is planning for industrial-scale carbon capture and storage in depleted gas fields, where a total practical storage capacity of approximately 1600 Mt is estimated to be available. At present, neither government nor industry have initiated plans for carbon capture and storage in saline formations, and to investigate other storage candidates, we initiated a study of the geological potential for sequestering CO2 in saline formations in a part of the western Dutch offshore. We identified possible target formations in the Upper Jurassic and Lower Cretaceous fluvial to shoreface sandstones and lower Paleogene shallow-marine sandstones in the West Netherlands Basin and Broad Fourteens Basin, located close to the industrial areas near Amsterdam. Three-dimensional seismic data show that the most promising trapping geometries exist in synclinal structures involving the Lower Cretaceous Vlieland Sandstone Formation, which formed during Late Cretaceous inversion folding. Several scenarios suggest large pore volume space to be available in the subsurface below a depth of 800 m. We envisage that CO2 would be injected in the deeper parts of the target formation, from which it would migrate under buoyant flow until it reaches the seal and remains stratigraphically trapped. The main risk identified so far relates to the seal integrity of basal Paleogene deposits, against which the storage formation is truncated in places. This academic research project (Deep Offshore Carbon Storage) will continue following the publication of this paper. The next phase will address studies on the seal integrity, reservoir efficiency, and economic feasibility

Merkel Cell Polyomavirus DNA Replication Induces Senescence in Human Dermal Fibroblasts in a Kap1/Trim28-Dependent Manner

We here describe Kap1 as a restriction factor in MCPyV infection. We report a novel, indirect mechanism by which Kap1 affects MCPyV replication. In contrast with from other DNA viruses, Kap1 does not associate with the viral genome in MCPyV infection and has no impact on viral gene expression. In MCPyV-infected nHDF cells, Kap1 phosphorylation (pKap1 S824) accumulates because of genomic stress mainly induced by viral DNA replication. In contrast, ectopic expression of LT or LT MCPyV mutants, previously shown to be important for induction of genotoxic stress, does not result in a similar extent of pKap1 accumulation. We show that cells actively replicating MCPyV accumulate pKap1 (in a manner dependent on the presence of ATM) and display a senescence phenotype reflected by G2 arrest. These results are supported by transcriptome analyses showing that LT antigen, in a manner dependent on the presence of Kap1, induces expression of secreted factors, which is known as the senescence-associated secretory phenotype (SASP).Merkel cell polyomavirus (MCPyV) is the only polyomavirus known to be associated with tumorigenesis in humans. Similarly to other polyomaviruses, MCPyV expresses a large tumor antigen (LT-Ag) that, together with a small tumor antigen (sT-Ag), contributes to cellular transformation and that is of critical importance for the initiation of the viral DNA replication. Understanding the cellular protein network regulated by MCPyV early proteins will significantly contribute to our understanding of the natural MCPyV life cycle as well as of the mechanisms by which the virus contributes to cellular transformation. We here describe KRAB-associated protein 1 (Kap1), a chromatin remodeling factor involved in cotranscriptional regulation, as a novel protein interaction partner of MCPyV T antigens sT and LT. Kap1 knockout results in a significant increase in the level of viral DNA replication that is highly suggestive of Kap1 being an important host restriction factor during MCPyV infection. Differently from other DNA viruses, MCPyV gene expression is unaffected in the absence of Kap1 and Kap1 does not associate with the viral genome. Instead, we show that in primary normal human dermal fibroblast (nHDF) cells, MCPyV DNA replication, but not T antigen expression alone, induces ataxia telangiectasia mutated (ATM) kinase-dependent Kap1 S824 phosphorylation, a mechanism that typically facilitates repair of double-strand breaks in heterochromatin by arresting the cells in G2. We show that MCPyV-induced inhibition of cell proliferation is mainly conferred by residues within the origin binding domain and thereby by viral DNA replication. Our data suggest that phosphorylation of Kap1 and subsequent Kap1-dependent G2 arrest/senescence represent host defense mechanisms against MCPyV replication in nHDF cells

Quantifying the Elemental Distribution in Solar Cells from X-Ray Fluorescence Measurements with Multiple Detector Modules

Within the analysis of solar cells with multi-modalX-ray microscopy, X-ray fluorescence (XRF) measurements havebecome a reliable source for evaluating elemental distributions.While XRF measurements can unveil the elemental distributionat unparalleled sensitivity and spatial resolution, the quantitativeanalysis is challenged by effects such as self-absorption and furthercomplicated by the inclusion of multiple detector modules.Here, we showcase the exemplary analysis of XRF spectraobtained from a Cu(In,Ga)Se2 solar cell utilizing four detectormodules. After cataloging typical features found in XRF spectra,we demonstrate the inclusion of detector modules with individualabsorption correction. This results in quantitative stoichiometricratios of the critical absorber elements Cu, In, and Ga that arein good agreement with the nominal ratios.These results are particularly relevant in view of futuremeasurements at diffraction-limited synchrotron beamlines: inorder to profit from the boost of nano-focused photon flux, XRFmeasurements will require multiple detector modules, for whichwe demonstrate an approach of quantitative analysis