43 research outputs found
Leiomyosarcoma of the inferior vena cava: Radical surgery and vascular reconstruction
<p>Abstract</p> <p>Background</p> <p>Vascular leiomyosarcoma are rare tumors typically originating from the inferior vena cava (IVC). Due to nonspecific clinical signs most tumors are diagnosed at advanced stages. Complete surgical resection remains the only potential curative therapeutic option. Surgical strategy is particularly influenced by the level of the IVC affected. Due to the topographic relation to the renal veins level-II involvement of the IVC raises special surgical challenges with respect to the maintenance of venous outflow.</p> <p>Case presentation</p> <p>We herein report two cases of leiomyosarcoma of the IVC with successful en bloc resection and individualized caval reconstruction. One patient presented with a large intramural and intraluminal mass and received a complete circumferential resection. Reconstruction was performed by graft replacement of the caval segment affected. The other patient displayed a predominantly extraluminal tumor growth and underwent semicircumferential resection of the IVC including the confluence of the left renal vein. In this case vascular reconstruction was performed by cavoplasty and reinsertion of the left renal vein into the proximal portion of the IVC. Resection margins of both patients were tumor free and no clinical signs of venous insufficiency of the lower extremity occurred.</p> <p>Conclusion</p> <p>This paper presents two cases of successfully managed leiomyosarcomas of the vena cava and exemplifies two different options for vascular reconstruction in level II sarcomas and includes a thorough review of the literature.</p
The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis
Although necrosis and necroinflammation are central features of many liver diseases, the role of programmed necrosis in the context of inflammation-dependent hepatocellular death remains to be fully determined. Here, we have demonstrated that the pseudokinase mixed lineage kinase domain-like protein (MLKL), which plays a key role in the execution of receptor interacting protein (RIP) lcinase-dependent necroptosis, is upregulated and activated in human autoimmune hepatitis and in a murine model of inflammation-dependent hepatitis. Using genetic and pharmacologic approaches, we determined that hepatocellular necrosis in experimental hepatitis is driven by an MLKL-dependent pathway that occurs independently of RIPK3. Moreover, we have provided evidence that the cytotoxic activity of the proinflammatory cytokine IFN-gamma in hepatic inflammation is strongly connected to induction of MLKL expression via activation of the transcription factor STAT1. In summary, our results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases
Preanalytical variables and performance of diagnostic RNA-based gene expression analysis in breast cancer
Prognostic multigene expression assays have become widely available to provide additional information to standard clinical parameters and to support clinicians in treatment decisions. In this study, we analyzed the impact of variations in tissue handling on the diagnostic EndoPredict test results. EndoPredict is a quantitative reverse transcription PCR assay conducted on RNA from formalin-fixed, paraffin-embedded (FFPE) tissue that predicts the likelihood of distant recurrence in patients with ER-positive/HER2-negative breast cancer. In this study, we performed a total of 138 EndoPredict assays to study the effects of preanalytical variables such as time to fixation, fixation time, tumor cell content, and section storage time on the EndoPredict test results. A time to fixation of up to 12 h and fixation of up to 5 days did not affect the results of the gene expression test. Paired samples of FFPE sections with tumor cell content ranging from 15 to 95 % and tumor-enriched samples showed a correlation coefficient of 0.97. Test results of tissue sections that have been stored for 12 months at +4 or +20 °C showed a correlation of 0.99 when compared to results of nonstored sections. In conclusion, preanalytical tissue handling is not a critical factor for diagnostic gene expression analysis with the EndoPredict assay. The test can therefore be easily integrated into the standard workflow of molecular pathology
Quantitative phase microscopy for evaluation of intestinal inflammation and wound healing utilizing label-free biophysical markers
Inflammatory bowel diseases (IBD) are
inflammatory disorders of the gastrointestinal tract
characterized by a chronic relapsing disease course. As
uncontrolled intestinal inflammation can result in severe
disease complications, recent treatment targets of IBD
evolved toward seeking the absence of mucosal and
histological inflammation. However, this approach
requires adequate histological evaluation of IBD disease
activity. The diagnostic challenge of histological
examination of intestinal inflammation is documented by
the multitude of proposed histological scoring systems.
In this context, we review quantitative phase imaging
(QPI) techniques such as digital holographic microscopy
(DHM) for characterizing intestinal inflammation. DHM
determines optical path-length delays in a stain-free
manner, thereby providing the tissue refractive index as
a biophysical marker that directly correlates to tissue
density. Recently, DHM has been successfully applied in
cell biology, cancer cell research and infectious-induced
cellular alterations. We summarized the capabilities of
DHM and related QPI techniques to assess the severity
of intestinal inflammation in experimental colitis as well
as in colonic samples from human IBD patients.
Moreover, we illustrate major advantages of DHM
facilitated multimodal evaluation of epithelial wound
healing processes as assessed by physical parameters
like cell volume, density, thickness and dry mass in
vitro. Furthermore, potential limitations of DHM and
future utilities of QPI are discussed. In conclusion, DHM
represents a promising, easy-to-use quantitative tool to
provide accurate and objective assessment of intestinal
inflammation and may pave the way towards automated
label-free digital pathology and related in vitro cell
culture analysis in future
Prognostic Value of PAX-FKHR Fusion Status in Alveolar Rhabdomyosarcoma: A Report From the Cooperative Soft Tissue Sarcoma Study Group (CWS)
Background. Alveolar Rhabdomyosarcomas (RMA) are characterized by chromosomal translocations, fusing the PAX3 or PAX7 gene with FKHR in about 85%. Previous studies have suggested that the fusion type is associated with prognosis. In order to investigate the predictive value of the PAX-FKHR fusion status on disease outcome of patients with RMA treated in the CWS trials we performed a retrospective analysis. Procedure. Between 1986 and 2004, out of 446 patients with RMA treated in four consecutive CWS trials, tumor samples from 126 patients were available for RT-PCR analysis. Survival depending on fusion status in context with known clinical risk-factors was analyzed. Results. Out of 126 samples, 121 had adequate quality for PAX-FKHR fusion status analysis. PAX-FKHR fusions were detected in 101 samples: 60% PAX3-FKHR and 24% PAX7-FKHR fusions, 17% were fusion-negative. There was no significant difference in survival between patients with PAX3-FKHR versus PAX7-FKHR positive tumors. The fusion transcript negative cohort showed a more favorable outcome than the fusion transcript positive cohort among patients with metastatic disease. From the established clinical risk-factors none was associated with a significantly higher risk of failure or death in a multivariate analysis. Conclusions. PAX-FKHR fusion type was not a significant predictor for survival in our analysis. Moreextensive molecular analyses are needed to identify features with prognostic relevance and useful therapeutic impact. Pediatr Blood Cancer 2011; 57: 406-414. (C) 2011 Wiley-Liss, Inc