Portal Vein Embolization is Associated with Reduced Liver Failure and Mortality in High-Risk Resections for Perihilar Cholangiocarcinoma

Background: Preoperative portal vein embolization (PVE) is frequently used to improve future liver remnant volume (FLRV) and to reduce the risk of liver failure after major liver resection. Objective: This paper aimed to assess postoperative outcomes after PVE and resection for suspected perihilar cholangiocarcinoma (PHC) in an international, multicentric cohort. Methods: Patients undergoing resection for suspected PHC across 20 centers worldwide, from the year 2000, were included. Liver failure, biliary leakage, and hemorrhage were classified according to the respective International Study Group of Liver Surgery criteria. Using propensity scoring, two equal cohorts were generated using matching parameters, i.e. age, sex, American Society of Anesthesiologists classification, jaundice, type of biliary drainage, baseline FLRV, resection type, and portal vein resection. Results: A total of 1667 patients were treated for suspected PHC during the study period. In 298 patients who underwent preoperative PVE, the overall incidence of liver failure and 90-day mortality was 27% and 18%, respectively, as opposed to 14% and 12%, respectively, in patients without PVE (p < 0.001 and p = 0.005). After propensity score matching, 98 patients were enrolled in each cohort, resulting in similar baseline and operative characteristics. Liver failure was lower in the PVE group (8% vs. 36%, p < 0.001), as was biliary leakage (10% vs. 35%, p < 0.01), intra-abdominal abscesses (19% vs. 34%, p = 0.01), and 90-day mortality (7% vs. 18%, p = 0.03). Conclusion: PVE before major liver resection for PHC is associated with a lower incidence of liver failure, biliary leakage, abscess formation, and mortality. These results demonstrate the importance of PVE as an integral component in the surgical treatment of PHC

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

The Goddess does throw dice: Creativity and non-intentionality in contemporary Pagan ritual

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"To know, to will, to dare and to … speak up!" development, self-disclosure, and self-validation of belief in Dutch-speaking Pagans

Contains fulltext : 99427.pdf (publisher's version ) (Closed access)In this paper I will focus on the problem of the self-validation of belief as a typical mode of making sense of alleged encounters with the divine in a ritual context. Drawing on examples taken from semi-structured interviews with Dutch Pagans, I will touch upon motives of self-actualisation and aesthetic appraisal in the process of interpreting these ritual experiences in an idiosyncratic fashion. I will then discuss the problem of self-disclosure. Finally, I will proceed to tie self-validation in with two competing theories on the nature of ritual knowledge. The ‘variation-theory’ understands knowledge as emergent only from gradually changing rituals, while the ‘masterpiece-theory’ emphasises the need for repetitive exposure to a ritual, gradually incorporating its essence

The Goddess does play dice: Creativity and non-intentionality in contemporary Pagan ritual

Sometimes referred to as open-source religions, con-temporary Paganisms are under continuous construction. In this paper, I will discuss, from a psychological perspective, the relation between creativity and Pagan ritual practice through notions like novelty, improvisation and non-intentionality. By elaborating on the plumber/diviner dichotomy in the work of Ronald Grimes, these notions will be fleshed out as practical and experiential aspects of the roles of the participants. On a grander scale, the discussion of ritual creativity will be tied in with the contemporary Paganisms’reconstructionism, egalitarianism, eclecticism, and their notion of immanent divinity, making a case for the importance of the phenomenon of creativity in interdisciplinary ritual studies.FGW – Publications without University Leiden contrac

The Goddess does throw dice: Creativity and non-intentionality in contemporary Pagan ritual

Sometimes referred to as open-source religions, con-temporary Paganisms are under continuous construction. In this paper, I will discuss, from a psychological perspective, the relation between creativity and Pagan ritual practice through notions like novelty, improvisation and non-intentionality. By elaborating on the plumber/diviner dichotomy in the work of Ronald Grimes, these notions will be fleshed out as practical and experiential aspects of the roles of the participants. On a grander scale, the discussion of ritual creativity will be tied in with the contemporary Paganisms’reconstructionism, egalitarianism, eclecticism, and their notion of immanent divinity, making a case for the importance of the phenomenon of creativity in interdisciplinary ritual studies.</p

Intracellular product recycling in high succinic acid producing yeast at low pH

Background: The metabolic engineering of Saccharomyces cerevisiae for the production of succinic acid has progressed dramatically, and a series of high-producing hosts are available. At low cultivation pH and high titers, the product transport can become bidirectional, i.e. the acid is reentering the cell and is again exported or even catabolized. Here, a quantitative approach for the identification of product recycling fluxes is developed. Results: The metabolic flux distributions at two time-points of the fermentation process were analyzed. 13C labeled succinic acid was added to the extracellular space and intracellular enrichments were measured and subsequently used for the estimation of metabolic fluxes. The labeling was introduced by a labeling switch experiment, leading to an immediate labeling of about 85% of the acid while keeping the total acid concentration constant. Within 100 s significant labeling enrichment of the TCA cycle intermediates fumarate, iso-citrate and α-ketoglutarate was observed, while no labeling was detected for malate and citrate. These findings suggest that succinic acid is rapidly exchanged over the cellular membrane and enters the oxidative TCA cycle. Remarkably, in the oxidative direction malate 13C enrichment was not detected, indicating that there is no flux going through this metabolite pool. Using flux modeling and thermodynamic assumptions on compartmentation it was concluded that malate must be predominantly cytosolic while fumarate and iso-citrate were more dominant in the mitochondria. Conclusions: Adding labeled product without changing the extracellular environment allowed to quantify intracellular metabolic fluxes under high producing conditions and identify product degradation cycles. In the specific case of succinic acid production, compartmentation was found to play a major role, i.e. the presence of metabolic activity in two different cellular compartments lead to intracellular product degradation reducing the yield. We also observed that the flux from glucose to succinic acid branches at two points in metabolism: (1) At the level of pyruvate, and (2) at cytosolic malate which was not expected.OLD BT/Cell Systems Engineerin

Pathway engineering strategies for improved product yield in yeast-based industrial ethanol production

Product yield on carbohydrate feedstocks is a key performance indicator for industrial ethanol production with the yeast Saccharomyces cerevisiae. This paper reviews pathway engineering strategies for improving ethanol yield on glucose and/or sucrose in anaerobic cultures of this yeast by altering the ratio of ethanol production, yeast growth and glycerol formation. Particular attention is paid to strategies aimed at altering energy coupling of alcoholic fermentation and to strategies for altering redox-cofactor coupling in carbon and nitrogen metabolism that aim to reduce or eliminate the role of glycerol formation in anaerobic redox metabolism. In addition to providing an overview of scientific advances we discuss context dependency, theoretical impact and potential for industrial application of different proposed and developed strategies.BT/Industrial MicrobiologyBT/Biotechnolog