Natural history of surgically treated high-risk prostate cancer

BACKGROUND No data exist on the patterns of biochemical recurrence (BCR) and their effect on survival in patients with high-risk prostate cancer (PCa) treated with surgery. The aim of our investigation was to evaluate the natural history of PCa in patients treated with radical prostatectomy (RP) alone. MATERIALS AND METHODS Overall, 2,065 patients with high-risk PCa treated with RP at 7 tertiary referral centers between 1991 and 2011 were identified. First, we calculated the probability of experiencing BCR after surgery. Particularly, we relied on conditional survival estimates for BCR after RP. Competing-risks regression analyses were then used to evaluate the effect of time to BCR on the risk of cancer-specific mortality (CSM). RESULTS Median follow-up was 70 months. Overall, the 5-year BCR-free survival rate was 55.2%. Given the BCR-free survivorship at 1, 2, 3, 4, and 5 years, the BCR-free survival rates improved by+7.6%,+4.1%,+4.8%,+3.2%, and+3.7%, respectively. Overall, the 10-year CSM rate was 14.8%. When patients were stratified according to time to BCR, patients experiencing BCR within 36 months from surgery had higher 10-year CSM rates compared with those experiencing late BCR (19.1% vs. 4.4%; P<0.001). At multivariate analyses, time to BCR represented an independent predictor of CSM (P<0.001). CONCLUSIONS Increasing time from surgery is associated with a reduction of the risk of subsequent BCR. Additionally, time to BCR represents a predictor of CSM in these patients. These results might help provide clinicians with better follow-up strategies and more aggressive treatments for early BCR.

Pretreatment Tables Predicting Pathologic Stage of Locally Advanced Prostate Cancer

BACKGROUND Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. OBJECTIVE To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. INTERVENTION Retropubic RP and pelvic lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. RESULTS AND LIMITATIONS In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. CONCLUSIONS These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. PATIENT SUMMARY Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment.

Stratification of high-risk prostate cancer into prognostic categories: a European multi-institutional study

BACKGROUND High-risk prostate cancer (PCa) is an extremely heterogeneous disease. A clear definition of prognostic subgroups is mandatory. OBJECTIVE To develop a pretreatment prognostic model for PCa-specific survival (PCSS) in high-risk PCa based on combinations of unfavorable risk factors. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective multicenter cohort study including 1360 consecutive patients with high-risk PCa treated at eight European high-volume centers. INTERVENTION Retropubic radical prostatectomy with pelvic lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Two Cox multivariable regression models were constructed to predict PCSS as a function of dichotomization of clinical stage (< cT3 vs cT3-4), Gleason score (GS) (2-7 vs 8-10), and prostate-specific antigen (PSA; ≤ 20 ng/ml vs > 20 ng/ml). The first "extended" model includes all seven possible combinations; the second "simplified" model includes three subgroups: a good prognosis subgroup (one single high-risk factor); an intermediate prognosis subgroup (PSA >20 ng/ml and stage cT3-4); and a poor prognosis subgroup (GS 8-10 in combination with at least one other high-risk factor). The predictive accuracy of the models was summarized and compared. Survival estimates and clinical and pathologic outcomes were compared between the three subgroups. RESULTS AND LIMITATIONS The simplified model yielded an R(2) of 33% with a 5-yr area under the curve (AUC) of 0.70 with no significant loss of predictive accuracy compared with the extended model (R(2): 34%; AUC: 0.71). The 5- and 10-yr PCSS rates were 98.7% and 95.4%, 96.5% and 88.3%, 88.8% and 79.7%, for the good, intermediate, and poor prognosis subgroups, respectively (p = 0.0003). Overall survival, clinical progression-free survival, and histopathologic outcomes significantly worsened in a stepwise fashion from the good to the poor prognosis subgroups. Limitations of the study are the retrospective design and the long study period. CONCLUSIONS This study presents an intuitive and easy-to-use stratification of high-risk PCa into three prognostic subgroups. The model is useful for counseling and decision making in the pretreatment setting.

Sich erlaufen. Pilgern als Identitätsstärkung

Against the background of an unexpected upswing in pilgrimages, this article states the thesis that pilgrimage enables a strengthening of one’s identity. In addition, the problem of a fragmented and indefinite identity is sketched, with reference to Zygmunt Bauman. In contrast stands a model of identity (connected with Albrecht Grçzinger) in which one contributes to a tradition in which one already is situated. In its main part, the article investigates the various factors of pilgrimage that contribute to this process of gaining one’s identity. Thus, a route frequented as much as theWay of St. James forms an already patterned space that offers the pilgrim traditioned roles to adopt. Walking, as a characteristic element of pilgrimage, is interpreted as physically generating and distinctively opening the space in which pilgrims understand themselves in the world. It also can be shown how walking as a form of physical being that leads from an instrumental relationship to one’s body to an immediate being in living one’s life, conveys certainty about one’s self and the world, activates one’s potential to overcome challenges, and provides self-empowerment. The author makes a strong case for a definition of pilgrimage oriented to an understanding of the hardship of crossing a foreign land, which is an image of a goal-oriented understanding of existence. The resulting poles of self-assurance and self-estrangement in pilgrimage are, in connection with Wilhelm Gräb, interpreted as an expression of a truly known but at the same time distanced self-understanding. Pilgrimage is therefore a form of physical self-interpretation in which people learn to view and be aware of their self-familiarity. Finally, against the background of this representation, criteria are elaborated for organizing a pilgrimage journey that is conducive to identity.

Grenzen des Machbaren. Was Pilgerwege erfolgreich macht

Auch in Deutschland versuchen immer mehr Touristiker vom Pilgerboom zu profitieren. Die neuen Wege werden oft nur wenig genutzt. Wer versteht, was Pilgern ausmacht, kann auch erfolgreich agieren. Auf Basis eines empirischen Forschungsprojektes entfaltet der Beitrag das Spezifikum des Pilgerns als einen bestimmten Erfahrungsmodus: Pilger erfahren sich selbst eingebunden in den Zusammenhang des Seins, einen sie tragenden Grund. Es geht um ein Unverfügbares, dem sie sich überlassen, weil es Gewissheit stiftet. Dies setzt dem touristischen Inszenieren enge Grenzen. Werden diese beachtet, entstehen nachhaltige und erfahrungswirksame Pilgerwege. Schlagworte: Pilgern, Erfahrung, Körper, Natur

Heimat Fremde

Urlauber suchen die Ungebundenheit der Fremde. Aber entfliehen sie wirklich einem normierten, durchrationalisierten, von Rollenfestlegungen, Notwendigkeiten und Bekanntem geprägten „modernen“ Alltag, wie es das gängige kulturwissenschaftliche Erklärungsmuster des Urlaubs im Anschluss v.a.an Enzensberger, Cohen und Turner behauptet? Im Urlaub wird nach dieser Auffassung eine Gegenwelt auf Zeit gesucht, in der spielerisch Rollentausch und Identitätsverflüssigung möglich wird. Dieses Essay kontrastiert diese Auffassung des Urlaubs mit der Situationsdiagnose der Postmoderne von Zygmunt Bauman: In der Postmoderne ist bereits der Alltag durch spielerischen Wechsel verschiedener Rollen und die Vermeidung von Identitätsfestlegung geprägt. Im Folgenden werden überraschende Konsequenzen aus Baumans Diagnose für eine veränderte Funktion des Urlaubs aufgezeigt: Wenn der Lifestyleswitch den Alltag selbst zum Unterwegssein in der Fremde werden lässt, dann bleibt das nicht ohne Folgen für den Urlaub, so die zentrale These: Der Urlaub bleibt ein Kontrast zum Alltag, aber nun gerade indem er dem im Alltag nicht realisierbaren Wunsch nach Beheimatung folgt. Solche regressive touristische Heimatsuche geschieht durch Romantisierung, Erleben von Natur und Geselligkeit, Bestätigung von Vorwissen und neuerdings besonders in der Wellness durch reflexive leibliche Selbstbezüglichkeit und Spiritualität. Bewegt sich der Alltag in der unvertrauten Fremde, reist der Urlauber in die vertraute Heimat. Ausgehend von dieser These wird das Modell einer durch das Reisen geschulten alltagstauglichen fragmentarischen Identität entwickelt: Es wird gezeigt, dass Urlaub zugleich Verwandlung wie Vergewisserung bewirken kann, wenn im Ausprobieren fremder Kulturmuster spielerische Leichtigkeit mit Authentizität und Sinnverstehen verbunden werden.

Quantification of anandamide and 2-arachidonoylglycerol plasma levels to examine potential influences of tetrahydrocannabinol application on the endocannabinoid system in humans

The effects of tetrahydrocannabinol (THC) and endogenous cannabinoids (endocannabinoids, ECs) are both mediated by activation of the cannabinoid receptors CB1 and CB2. Exogenous activation of these receptors by THC could therefore alter EC levels. We tested this hypothesis in healthy volunteers (n = 25) who received a large intravenous dose of THC (0.10 mg/kg). Effects on the EC system were quantified by serial measurements of plasma ECs after THC administration. Eleven blood samples were drawn during the first 5 h after THC administration and two more samples after 24 and 48 h. THC, its metabolites THC-OH (biologically active) and THC-COOH (non-active), and the ECs anandamide and 2-arachidonoylglycerol (2-AG) were quantified by liquid chromatography-mass spectrometry. EC-plasma levels showed a biphasic response after THC injection reaching maximal values at 30 min. Anandamide increased slightly from 0.58 ± 0.21 ng/ml at baseline to 0.64 ± 0.24 ng/ml (p < 0.05) and 2-AG from 7.60 ± 4.30 ng/ml to 9.50 ± 5.90 ng/ml (p < 0.05). After reaching maximal concentrations, EC plasma levels decreased markedly to a nadir of 300 min after THC administration (to 0.32 ± 0.15 ng/ml for anandamide and to 5.50 ± 3.01 ng/ml for 2-AG, p < 0.05). EC plasma concentrations returned to near baseline levels until 48 h after the experiment. THC (0.76 ± 0.16 ng/ml) and THC-OH (0.36 ± 0.17 ng/ml) were still measurable at 24 h and remained detectible until 48 h after THC administration. Although the underlying mechanism is not clear, high doses of intravenous THC appear to influence endogenous cannabinoid concentrations and presumably EC-signalling.

Intransitive competition is widespread in plant communities and maintains their species richness

Intransitive competition networks, those in which there is no single best competitor, may ensure species coexistence. However, their frequency and importance in maintaining diversity in real-world ecosystems remain unclear. We used two large data sets from drylands and agricultural grasslands to assess: (1) the generality of intransitive competition, (2) intransitivity–richness relationships and (3) effects of two major drivers of biodiversity loss (aridity and land-use intensification) on intransitivity and species richness. Intransitive competition occurred in > 65% of sites and was associated with higher species richness. Intransitivity increased with aridity, partly buffering its negative effects on diversity, but was decreased by intensive land use, enhancing its negative effects on diversity. These contrasting responses likely arise because intransitivity is promoted by temporal heterogeneity, which is enhanced by aridity but may decline with land-use intensity. We show that intransitivity is widespread in nature and increases diversity, but it can be lost with environmental homogenisation.

Drivers of nitrogen leaching from organic layers in Central European beech forests

Background and Aims: The response of forest ecosystems to continuous nitrogen (N) deposition is still uncertain. We investigated imports and exports of dissolved N from mull-type organic layers to identify the controls of N leaching in Central European beech forests under continuous N deposition. Methods: Dissolved N fluxes with throughfall and through mull-type organic layers (litter leachate) were measured continuously in 12 beech forests on calcareous soil in two regions in Germany over three consecutive growing seasons. Results Mean growing season net (i.e. litter leachate – throughfall flux) fluxes of total dissolved N (TDN) from the organic layer were low (2.3 ± 5.6 kg ha −1 ) but varied widely from 12.9 kg ha −1 to –8.3 kg ha −1 . The small increase of dissolved N fluxes during the water passage through mull-type organic layers suggested that high turnover rates coincided with high microbial N assimilation and plant N uptake. Stand basal area had a positive feedback on N fluxes by providing litter for soil organic matter forma- tion. Plant diversity, especially herb diversity, reduced dissolved N fluxes. Soil fauna biomass increased NO3−-N fluxes with litter leachate by stimulating mineralization. Microbial biomass measures were not related to dissolved N fluxes. Conclusions Our results show that dissolved N exports from organic layers contain significant amounts of throughfall-derived N (mainly NO3−-N) that flushes through the organic layer but also highlight that N leaching from organic layers is driven by the complex interplay of plants, animals and microbes. Furthermore, diverse understories reduce N leaching from Central European beech forests.

Definitions and outcome measures for mucous membrane pemphigoid: recommendations of an international panel of experts

Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index.

Gottes Werk und Adams Beitrag; Formen der Interaktion zwischen Mensch und Gott im Mittelalter

Der Band eröffnet die neue Reihe des Mediävistenverbandes, in der interdisziplinäre Studien aus dem Bereich der Mittelalterforschung veröffentlicht werden. Er dokumentiert ausgewählte Beiträge des 14. Symposiums des Verbandes, das vom 27. bis 31. März 2011 in Jena stattfand. Im Zentrum stehen die mehr oder weniger expliziten Verhältnisbestimmungen des Menschen zu Gott, von denen die monotheistische mittelalterliche Welt in all ihren Bereichen geprägt ist, im Christentum ebenso wie in Islam und Judentum. Dabei geht es um die Wechselbeziehungen zwischen Gott und Mensch, Gottesbild und Menschenbild, Schöpfer und Kreatur sowie göttlicher und menschlicher Schöpfung beziehungsweise Schöpferkraft. Beiträge aus Literatur-, Musik- und Kunstwissenschaft reflektieren unterschiedliche Formen der Kommunikation zwischen Mensch und Gott, historische Hinführungen zur Geschichte von Konzepten und Vorstellungen sind ebenso vertreten wie klassische theologische oder philosophische Studien. So erscheinen die Formen und Inhalte der Interaktion zwischen Gott und Mensch im Mittealter in all ihrer Fülle.

Impact of above- and below-ground invertebrates on temporal and spatial stability of grassland of different diversity

1. Recent theoretical studies suggest that the stability of ecosystem processes is not governed by diversity per se, but by multitrophic interactions in complex communities. However, experimental evidence supporting this assumption is scarce.2. We investigated the impact of plant diversity and the presence of above- and below-ground invertebrates on the stability of plant community productivity in space and time, as well as the interrelationship between both stability measures in experimental grassland communities.3. We sampled above-ground plant biomass on subplots with manipulated above- and below-ground invertebrate densities of a grassland biodiversity experiment (Jena Experiment) 1, 4 and 6 years after the establishment of the treatments to investigate temporal stability. Moreover, we harvested spatial replicates at the last sampling date to explore spatial stability.4. The coefficient of variation of spatial and temporal replicates served as a proxy for ecosystem stability. Both spatial and temporal stability increased to a similar extent with plant diversity. Moreover, there was a positive correlation between spatial and temporal stability, and elevated plant density might be a crucial factor governing the stability of diverse plant communities.5. Above-ground insects generally increased temporal stability, whereas impacts of both earthworms and above-ground insects depended on plant species richness and the presence of grasses. These results suggest that inconsistent results of previous studies on the diversity–stability relationship have in part been due to neglecting higher trophic-level interactions governing ecosystem stability.6. Changes in plant species diversity in one trophic level are thus unlikely to mirror changes in multitrophic interrelationships. Our results suggest that both above- and below-ground invertebrates decouple the relationship between spatial and temporal stability of plant community productivity by differently affecting the homogenizing mechanisms of plants in diverse plant communities.7.Synthesis. Species extinctions and accompanying changes in multitrophic interactions are likely to result not only in alterations in the magnitude of ecosystem functions but also in its variability complicating the assessment and prediction of consequences of current biodiversity loss.