Endoscopic and Percutaneous Preoperative Biliary Drainage in Patients with Suspected Hilar Cholangiocarcinoma

INTRODUCTION: Controversy exists over the preferred technique of preoperative biliary drainage (PBD) in patients with hilar cholangiocarcinoma (HCCA) requiring major liver resection. The current study compared outcomes of endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) in patients with resectable HCCA. METHODS: One hundred fifteen consecutive patients were explored for HCCA between 2001 and July 2008 and assigned by initial PBD procedure to either EBD or PTBD. RESULTS: Of these patients, 101 (88%) underwent PBD; 90 patients underwent EBD as primary procedure, and 11 PTBD. The technical success rate of initial drainage was 81% in the EBD versus 100% in the PTBD group (P = 0.20). Stent dislocation was similar in the EBD and PTBD groups (23% vs. 20%, P = 0.70). Infectious complications were significantly more common in the endoscopic group (48% vs. 9%, P < 0.05). Patients in the EBD group underwent more drainage procedures (2.8 vs. 1.4, P < 0.01) and had a significantly longer drainage period until laparotomy (mean 15 weeks vs. 11 weeks in the PTBD group; P < 0.05). In 30 patients, EBD was converted to PTBD due to failure of the endoscopic approach. CONCLUSIONS: Preoperative percutaneous drainage could outperform endoscopic stent placement in patients with resectable HCCA, showing fewer infectious complications, using less procedure

Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial)

BACKGROUND: Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life. METHODS/DESIGN: Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8). DISCUSSION: The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor

A mitochondrial mutator plasmid that causes senescence under dietary restricted conditions

BACKGROUND: Calorie or dietary restriction extends life span in a wide range of organisms including the filamentous fungus Podospora anserina. Under dietary restricted conditions, P. anserina isolates are several-fold longer lived. This is however not the case in isolates that carry one of the pAL2-1 homologous mitochondrial plasmids. RESULTS: We show that the pAL2-1 homologues act as 'insertional mutators' of the mitochondrial genome, which may explain their negative effect on life span extension. Sequencing revealed at least fourteen unique plasmid integration sites, of which twelve were located within the mitochondrial genome and two within copies of the plasmid itself. The plasmids were able to integrate in their entirety, via a non-homologous mode of recombination. Some of the integrated plasmid copies were truncated, which probably resulted from secondary, post-integrative, recombination processes. Integration sites were predominantly located within and surrounding the region containing the mitochondrial rDNA loci. CONCLUSION: We propose a model for the mechanism of integration, based on innate modes of mtDNA recombination, and discuss its possible link with the plasmid's negative effect on dietary restriction mediated life span extension

PPARβ activation inhibits melanoma cell proliferation involving repression of the Wilms’ tumour suppressor WT1

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that strongly influence molecular signalling in normal and cancer cells. Although increasing evidence suggests a role of PPARs in skin carcinogenesis, only expression of PPARγ has been investigated in human melanoma tissues. Activation of PPARα has been shown to inhibit the metastatic potential, whereas stimulation of PPARγ decreased melanoma cell proliferation. We show here that the third member of the PPAR family, PPARβ/δ is expressed in human melanoma samples. Specific pharmacological activation of PPARβ using GW0742 or GW501516 in low concentrations inhibits proliferation of human and murine melanoma cells. Inhibition of proliferation is accompanied by decreased expression of the Wilms’ tumour suppressor 1 (WT1), which is implicated in melanoma proliferation. We demonstrate that PPARβ directly represses WT1 as (1) PPARβ activation represses WT1 promoter activity; (2) in chromatin immunoprecipitation and electrophoretic mobility shift assays, we identified a binding element for PPARβ in the WT1 promoter; (3) deletion of this binding element abolishes repression by PPARβ and (4) the WT1 downstream molecules nestin and zyxin are down-regulated upon PPARβ activation. Our findings elucidate a novel mechanism of signalling by ligands of PPARβ, which leads to suppression of melanoma cell growth through direct repression of WT1

A Common Anterior Insula Representation of Disgust Observation, Experience and Imagination Shows Divergent Functional Connectivity Pathways

Similar brain regions are involved when we imagine, observe and execute an action. Is the same true for emotions? Here, the same subjects were scanned while they (a) experience, (b) view someone else experiencing and (c) imagine experiencing gustatory emotions (through script-driven imagery). Capitalizing on the fact that disgust is repeatedly inducible within the scanner environment, we scanned the same participants while they (a) view actors taste the content of a cup and look disgusted (b) tasted unpleasant bitter liquids to induce disgust, and (c) read and imagine scenarios involving disgust and their neutral counterparts. To reduce habituation, we inter-mixed trials of positive emotions in all three scanning experiments. We found voxels in the anterior Insula and adjacent frontal operculum to be involved in all three modalities of disgust, suggesting that simulation in the context of social perception and mental imagery of disgust share a common neural substrates. Using effective connectivity, this shared region however was found to be embedded in distinct functional circuits during the three modalities, suggesting why observing, imagining and experiencing an emotion feels so different

Chapitre 14: Phytopathogènes et stratégies de contrôle en aquaponie

peer reviewedAmong the diversity of plant diseases occurring in aquaponics, soil-borne pathogens, such as Fusarium spp., Phytophthora spp. and Pythium spp., are the most problematic due to their preference for humid/aquatic environment conditions. Phytophthora spp. and Pythium spp. which belong to the Oomycetes pseudo-fungi require special attention because of their mobile form of dispersion, the so-called zoospores that can move freely and actively in liquid water. In coupled aquaponics, curative methods are still limited because of the possible toxicity of pesticides and chemical agents for fish and beneficial bacteria (e.g. nitrifying bacteria of the biofilter). Furthermore, the development of biocontrol agents for aquaponic use is still at its beginning. Consequently, ways to control the initial infection and the progression of a disease are mainly based on preventive actions and water physical treatments. However, suppressive action (suppression) could happen in aquaponic environment considering recent papers and the suppressive activity already highlighted in hydroponics. In addition, aquaponic water contains organic matter that could promote establishment and growth of heterotrophic bacteria in the system or even improve plant growth and viability directly. With regards to organic hydroponics (i.e. use of organic fertilisation and organic plant media), these bacteria could act as antagonist agents or as plant defence elicitors to protect plants from diseases. In the future, research on the disease suppressive ability of the aquaponic biotope must be increased, as well as isolation, characterisation and formulation of microbial plant pathogen antagonists. Finally, a good knowledge in the rapid identification of pathogens, combined with control methods and diseases monitoring, as recommended in integrated plant pest management, is the key to an efficient control of plant diseases in aquaponics.Cos