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

Cathepsin K deficiency in mice induces structural and metabolic changes in the central nervous system that are associated with learning and memory deficits

<p>Abstract</p> <p>Background</p> <p>Cathepsin K is a cysteine peptidase known for its importance in osteoclast-mediated bone resorption. Inhibitors of cathepsin K are in clinical trials for treatment of osteoporosis. However, side effects of first generation inhibitors included altered levels of related cathepsins in peripheral organs and in the central nervous system (CNS). Cathepsin K has been recently detected in brain parenchyma and it has been linked to neurobehavioral disorders such as schizophrenia. Thus, the study of the functions that cathepsin K fulfils in the brain becomes highly relevant.</p> <p>Results</p> <p>Cathepsin K messenger RNA was detectable in all brain regions of wild type (WT) mice. At the protein level, cathepsin K was detected by immunofluorescence microscopy in vesicles of neuronal and non-neuronal cells throughout the mouse brain. The hippocampus of WT mice exhibited the highest levels of cathepsin K activity in fluorogenic assays, while the cortex, striatum, and cerebellum revealed significantly lower enzymatic activities. At the molecular level, the proteolytic network of cysteine cathepsins was disrupted in the brain of cathepsin K-deficient (<it>Ctsk</it>^-/-) animals. Specifically, cathepsin B and L protein and activity levels were altered, whereas cathepsin D remained largely unaffected. Cystatin C, an endogenous inhibitor of cysteine cathepsins, was elevated in the striatum and hippocampus, pointing to regional differences in the tissue response to <it>Ctsk </it>ablation. Decreased levels of astrocytic glial fibrillary acidic protein, fewer and less ramified profiles of astrocyte processes, differentially altered levels of oligodendrocytic cyclic nucleotide phosphodiesterase, as well as alterations in the patterning of neuronal cell layers were observed in the hippocampus of <it>Ctsk</it>^-/-mice. A number of molecular and cellular changes were detected in other brain regions, including the cortex, striatum/mesencephalon, and cerebellum. Moreover, an overall induction of the dopaminergic system was found in <it>Ctsk</it>^-/-animals which exhibited reduced anxiety levels as well as short- and long-term memory impairments in behavioral assessments.</p> <p>Conclusion</p> <p>We conclude that deletion of the <it>Ctsk </it>gene can lead to deregulation of related proteases, resulting in a wide range of molecular and cellular changes in the CNS with severe consequences for tissue homeostasis. We propose that cathepsin K activity has an important impact on the development and maintenance of the CNS in mice.</p

Real-time investigation of dynamic protein crystallization in living cells

X-ray crystallography requires sufficiently large crystals to obtain structural insights at atomic resolution, routinely obtained in vitro by time-consuming screening. Recently, successful data collection was reported from protein microcrystals grown within living cells using highly brilliant free-electron laser and third-generation synchrotron radiation. Here, we analyzed in vivo crystal growth of firefly luciferase and Green Fluorescent Protein-tagged reovirus μNS by live-cell imaging, showing that dimensions of living cells did not limit crystal size. The crystallization process is highly dynamic and occurs in different cellular compartments. In vivo protein crystallization offers exciting new possibilities for proteins that do not form crystals in vitroL.R., M.K., D.R., and C.B. thank the German Federal Ministry for Education and Research (BMBF) for funding (Grant Nos. 01KX0806 and 01KX0807). L.R., M.D., and C.B. acknowledge support from the BMBF in the context of the Röntgen-Angström-Cluster (Grant No. 05K12GU3). J.M.-C. and A.B.-N. acknowledge support from the Spanish Ministerio Economía y Competitividad (MINECO, Grant No. BFU2013-43513-R). I.V.M., R.D., and L.R. are grateful for support from the DFG Cluster of Excellence “Inflammation at Interfaces” (EXC 306)S

Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker

BACKGROUND: To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies. METHODS: The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up. RESULTS: Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%) and 3+ (41%). Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001) and median overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor. CONCLUSION: Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention

Aufbau enantiomerenreiner #beta#-Hydroxyl-#gamma#-Lactone durch Homoaldol-Reaktion Synthese von 2,6-Didesoxyhexonsaeuren und Dihydroxyethylen-Dipeptidisosteren

SIGLEAvailable from TIB Hannover: DW 5788 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Differenzierte chirurgische Therapie von rectovaginalen Fisteln

Objective: Rectovaginal fistulae (RVF) are a serious and debilitating problem for patients and a challenge for the treating surgeons. We present our experiences in the surgical treatment of these patients. Methods: Study population consisted of 22 consecutive patients (range 26-70 years) with RVF treated in our department between 2003 and 2009. 13 RVF were observed after colorectal or gynaecological surgery, 3 occurred after radiotherapy, 2 due to tumour infiltration, 4 because of local inflammation (3x diverticultis, 1x ulcus simplex recti). The RVF was classified in all patients before treatment as either 'low' or 'high'. Results: Local procedures (transvaginal excision, preanal repair) as initial treatment were performed in 9 patients with low fistula. In 13 cases with high fistula an abdominal approach was performed to close the fistula. A recurrence was observed in 8/22 cases (36%), which were treated by a gracilis flap (n=2), a bulbospongiosus composite (n=1), a second abdominal approach (n=4), and a re-local excision (n=1). Ultimatively, in 19 cases the defect healed but in 3 patients the RVF persisted. Conclusions: Most important predictor of healing/failure is etiology followed by localization and recurrence of the RVF. Local (preanal, transvaginal) procedures are suitable for low RVF, whereas abdominal surgery is necessary in high RVF. In recurrent RVF, muscle flaps are promising procedures.Hintergrund: Rektovaginale Fisteln (RVF) stellen für betroffene Patientinnen ein schwerwiegendes psychosoziales Problem dar und bedeuten für den Chirurgen eine komplexe therapeutische Herausforderung. Wir berichten über unsere Erfahrung in der chirurgischen Therapie dieser Patientinnen.Methoden: Wir berichten über 22 Patientinnen (26-70 Jahre) mit RVF, die zwischen 2003 und 2009 in unserer Klinik behandelt wurden. 13 RVF wurden nach colorektaler oder gynäkologischer Operation festgestellt. 3 als postaktinische Folgeschäden, 2 durch Karzinominfiltrationen und 4 durch entzündliche Veränderung aufgetreten (3x Divertikulitis, 1x ulcus simplex recti). Die RVF wurden in tiefe und hohe Fistel unterteilt.Ergebnisse: Initiale Therapie zum Fistelverschluss war bei 9 Pat. durch lokale Exzision/preanal repair, bei 13 Pat. durch einen transabdominellen Zugang. Eine Rezidivfistel war in 8/22 (36%) Fällen nachweisbar. Dann wurde definitiver Fistelverschluss erreicht: 1x lokale Exzision, 4x transabdominell, 2x Gracilis-Plastik, 1x M. bulbospongiosus composite. In 19 Fällen kam es zur Ausheilung des Defektes, bei drei Patientinnen besteht eine Persistenz der RVF.Schlussfolgerungen: Die Ätiologie einer RVF hat den größten Einfluss auf die Heilungsrate gefolgt von der Lokalisation und dem Rezidiv. Bei tief liegenden Fisteln empfehlen wir zunächst ein lokales Vorgehen wie beispielsweise preanal repair und Fistelexzision. Transabdominelles Vorgehen bietet sich bei hoch liegenden Fisteln an. Bei RVF-Rezidiven ist an die Interposition eines Muskelschwenklappens (z.B. Gracilis-Plastik) zu denken