Adequate debridement and drainage of the mediastinum using open thoracotomy or video-assisted thoracoscopic surgery for Boerhaave’s syndrome

Background Boerhaave's syndrome has a high mortality rate (14-40%). Surgical treatment varies from a minimal approach consisting of adequate debridement with drainage of the mediastinum and pleural cavity to esophageal resection. This study compared the results between a previously preferred open minimal approach and a video-assisted thoracoscopic surgery (VATS) procedure currently considered the method of choice. Methods In this study, 12 consecutive patients treated with a historical nonresectional drainage approach (1985-2001) were compared with 12 consecutive patients treated prospectively after the introduction of VATS during the period 2002-2009. Baseline characteristics were equally distributed between the two groups. Results In the prospective group, 2 of the 12 patients had the VATS procedure converted to an open thoracotomy, and 2 additional patients were treated by open surgery. In the prospective group, 8 patients experienced postoperative complications compared with all 12 patients in the historical control group. Four patients (17%), two in each group, underwent reoperation. Six patients, three in each group, were readmitted to the hospital. The overall in-hospital mortality was 8% (1 patient in each group), which compares favorably with other reports (7-27%) based on drainage alone. Conclusions Adequate surgical debridement with drainage of the mediastinum and pleural cavity resulted in a low mortality rate. The results for VATS in this relatively small series were comparable with those for an open thoracotomy

Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment

Cancer cells show a broad spectrum of bioenergetic states, with some cells using aerobic glycolysis while others rely on oxidative phosphorylation as their main source of energy. In addition, there is mounting evidence that metabolic coupling occurs in aggressive tumors, between epithelial cancer cells and the stromal compartment, and between well-oxygenated and hypoxic compartments. We recently showed that oxidative stress in the tumor stroma, due to aerobic glycolysis and mitochondrial dysfunction, is important for cancer cell mutagenesis and tumor progression. More specifically , increased autophagy/mitophagy in the tumor stroma drives a form of parasitic epithelial-stromal metabolic coupling. These findings explain why it is effective to treat tumors with either inducers or inhibitors of autophagy, as both would disrupt this energetic coupling. We also discuss evidence that glutamine addiction in cancer cells produces ammonia via oxidative mitochondrial metabolism. Ammonia production in cancer cells, in turn, could then help maintain autophagy in the tumor stromal compartment. In this vicious cycle, the initial glutamine provided to cancer cells would be produced by autophagy in the tumor stroma. Thus, we believe that parasitic epithelial-stromal metabolic coupling has important implications for cancer diagnosis and therapy, for example, in designing novel metabolic imaging techniques and establishing new targeted therapies. In direct support of this notion, we identified a loss of stromal caveolin-1 as a marker of oxidative stress, hypoxia, and autophagy in the tumor microenvironment, explaining its powerful predictive value. Loss of stromal caveolin-1 in breast cancers is associated with early tumor recurrence, metastasis, and drug resistance, leading to poor clinical outcome

Can metabolic plasticity be a cause for cancer? Warburg–Waddington legacy revisited

Fermentation of glucose to lactate in the presence of sufficient oxygen, known as aerobic glycolysis or Warburg effect, is a universal phenotype of cancer cells. Understanding its origin and role in cellular immortalization and transformation has attracted considerable attention in the recent past. Intriguingly, while we now know that Warburg effect is essential for tumor growth and development, it is thought to arise because of genetic and/or epigenetic changes. In contrast to the above, we propose that Warburg effect can also arise due to normal biochemical fluctuations, independent of genetic and epigenetic changes. Cells that have acquired Warburg effect proliferate rapidly to give rise to a population of heterogeneous progenitors of cancer cells. Such cells also generate more lactate and alter the fitness landscape. This dynamic fitness landscape facilitates evolution of cancer cells from its progenitors, in a fashion analogous to Darwinian evolution. Thus, sporadic cancer can also occur first by the acquisition of Warburg effect, then followed by mutation and selection. The idea proposed here circumvents the inherent difficulties associated with the current understanding of tumorigenesis, and is also consistent with many experimental and epidemiological observations. We discuss this model in the context of epigenetics as originally enunciated by Waddington

A Simple Approach for COnsumption and RElease (CORE) Analysis of Metabolic Activity in Single Mammalian Embryos

Non-invasive assay of the consumption and release of metabolites by individual human embryos could allow selection at the cleavage stage of development and facilitate Single Embryo Transfer in clinical IVF but will require simple, high throughput, sensitive methods applicable to small volume samples. A rapid, simple, non-invasive method has therefore been devised using a standard fluorescence plate reader, and used to measure the consumption of pyruvate and glucose, and release of lactate by single bovine embryos at all stages of preimplantation development in culture; amino acid profiles have been determined using HPLC. Early embryos with an ‘intermediate’ level (6.14±0.27 pmol/embryo/h) of pyruvate uptake were associated with the highest rate (68.3%) of blastocyst development indicating that a mid “optimum” range of pyruvate consumption correlates with high viability in this bovine model

Pop-Up-Bibliotheken. Eine Machbarkeitsstudie

Pop-Up-Stores dienen diversen Unternehmen, von großen Konzernen bis hin zum kleinen Start-Up-Projekt, als einzigartige Möglichkeit, neuartige Produkte für potenzielle Kunden sichtbar zu machen, deren Attraktivität zu testen und unkonventionelles Marketing zu betreiben. Auch in Deutschland sind die Läden auf Zeit mittlerweile ein etabliertes Konzept. Insbesondere in Großstädten sind sie prägende Elemente von Einkaufszentren, Fußgängerzonen, etc., die durch ihr kurzzeitiges Erscheinen und ihre einzigartigen Angebote auch eine Antwort auf die dynamische Entwicklung von Innenstädten und das Innovationsbedürfnis von Konsumenten darstellen. Durch die begrenzte Verfügbarkeit, die damit zumindest suggerierte Exklusivität und den besonderen Eventcharakter erzeugen Pop-Up-Stores ein hohes Maß an Aufmerksamkeit, Mundpropaganda sowie Attraktivität und sind dabei für die durchführenden Unternehmen annähernd risikolos. Ob und wie dieses Konzept auch für Bibliotheken geeignet ist, welche Vorteile Bibliotheken aus einem derartigen Projekt gegebenenfalls ziehen können und was bei der Umsetzung einer Pop-Up-Bibliothek zu beachten ist, ist Inhalt der vorliegenden Machbarkeitsstudie. Im Rahmen der ersten Recherchen wurde bereits ersichtlich, dass die Bandbreite von Pop-Up-Konzepten an sich sehr groß ist. Darüber hinaus zeigte sich auch, dass Bibliotheken auf unterschiedlichste Weise dazu in der Lage sind, diese Konzepte wiederum an die eigenen Bedürfnisse bzw. Gegebenheiten anzupassen: Vom Testen neuer Raum- oder Veranstaltungsangebote bis zum Schaffen temporärer Bibliotheksstandorte in bisher wenig bis nicht erschlossenen Stadtteilen, und nicht zuletzt als imagewirksame Öffentlichkeitsarbeit – die Möglichkeiten der Ausrichtung einer Pop-Up-Bibliothek sind so divers, wie die Bibliotheksarbeit an sich

The oncogenic potential of Epstein-Barr virus nuclear antigen 1 in transgenic mice

The human herpes virus, Epstein-Barr virus (EBV) is highly prevalent among all communities. Although largely asymptomatic prior to puberty it is the etiologic agent of the lymphoproliferative disorder, infectious mononucleosis. The virus is also tightly associated with two major forms of human B-cell malignancy: endemic Burkitt’s lymphoma (BL) and the lymphomas to which immunosupressed individuals are prone (for review see Epstein and Achong, 1986)