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Biblio - Bibliographie IAL
Bibliographie IAL

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Recherche bibliographique scientifique

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Accueil > Références bibliographiques

biblio

2013

  • Luc, G, Collet, D, Reich, S, Stanislas, S & Sa-Cunha, A 2013, « Primary monophasic synovial sarcoma of the pancreas », J Visc Surg, vol. 150, no. 2, p. 159-61.
    Résumé : We report a case of synovial sarcoma of the pancreas in a 44-year-old male who presented with multiple episodes of retroperitoneal hemorrhage; the diagnosis was confirmed by histology. The patient underwent distal pancreatectomy without complication, and the hospital stay was nine days. No adjuvant treatment was administered. The patient is alive at 1 year.

  • Malfuson, J-V, Boutin, L, Clay, D, Thépenier, C, Desterke, C, Torossian, F, Guerton, B, Anginot, A, de Revel, T, Lataillade, J-J & Le Bousse-Kerdilès, M-C 2013, « SP/drug efflux functionality of hematopoietic progenitors is controlled by mesenchymal niche through VLA-4/CD44 axis », Leukemia.
    Résumé : Hematopoiesis is orchestrated by interactions between hematopoietic stem/progenitor cells (HSPCs) and stromal cells within bone marrow (BM) niches. Side population (SP) functionality is a major characteristic of HSPCs related to quiescence and resistance to drugs and environmental stresses. At steady state, SP cells are mainly present in the BM and are mostly absent from the circulation except in stress conditions, raising the hypothesis of the versatility of the SP functionality. However, the mechanism of SP phenotype regulation is unclear. Here we show for the first time that the SP functionality can be induced in lin(-) cells from unmobilized peripheral blood after nesting on mesenchymal stromal cells (MSCs). This MSC-induced SP fraction contains HSPCs as demonstrated by their (i) CD34(+) cell percentage, (ii) quiescent status, (iii) in vitro proliferative and clonogenic potential, (iv) engraftment in NSG (NOD SCID gamma chain) mice and (v) stemness gene expression profile. We demonstrate that SP phenotype acquisition/reactivation by circulating lin(-) cells is dependent on interactions with MSCs through VLA-4/α4β1-integrin and CD44. A similar integrin-dependent mechanism of SP phenotype acquisition in acute myeloid leukemia circulating blasts suggests an extrinsic regulation of ATP-binding cassette-transporter activity that could be of importance for a better understanding of adhesion-mediated chemoresistance mechanisms.Leukemia advance online publication, 1 October 2013; doi:10.1038/leu.2013.256.
  • Marcotte, E, Afaneh, C, Pomp, A & Cherqui, D 2013, « Image of the month-quiz. Cystadenoma of the cystic duct », JAMA Surg, vol. 148, no. 4, p. 395-6.
    Résumé : Marcotte, Eric; Afaneh, Cheguevara; Pomp, Alfons; Cherqui, Daniel; United States; JAMA Surg. 2013 Apr;148(4):395-6. doi: 10.1001/jamasurg.2013.317a.


  • Martel, C, Allouche, M, Esposti, DD, Fanelli, E, Boursier, C, Henry, C, Chopineau, J, Calamita, G, Kroemer, G, Lemoine, A & Brenner, C 2013, « Glycogen synthase kinase 3-mediated voltage-dependent anion channel phosphorylation controls outer mitochondrial membrane permeability during lipid accumulation », Hepatology, vol. 57, no. 1, p. 93-102, viewed sans date, .
    Résumé : Nonalcoholic steatosis is a liver pathology characterized by fat accumulation and severe metabolic alterations involving early mitochondrial impairment and late hepatocyte cell death. However, mitochondrial dysfunction mechanisms remain elusive. Using four models of nonalcoholic steatosis, i.e., livers from patients with fatty liver disease, ob/ob mice, mice fed a high-fat diet, and in vitro models of lipotoxicity, we show that outer mitochondrial membrane permeability is altered and identified a posttranslational modification of voltage-dependent anion channel (VDAC), a membrane channel and NADH oxidase, as a cause of early mitochondrial dysfunction. Thus, in nonalcoholic steatosis VDAC exhibits reduced threonine phosphorylation, which increases the influx of water and calcium into mitochondria, sensitizes the organelle to matrix swelling, depolarization, and cytochrome c release without inducing cell death. This also amplifies VDAC enzymatic and channel activities regulation by calcium and modifies its interaction with proteic partners. Moreover, lipid accumulation triggers a rapid lack of VDAC phosphorylation by glycogen synthase kinase 3 (GSK3). Pharmacological and genetic manipulations proved GSK3 to be responsible for VDAC phosphorylation in normal cells. Notably, VDAC phosphorylation level correlated with steatosis severity in patients. CONCLUSION: VDAC acts as an early sensor of lipid toxicity and its GSK3-mediated phosphorylation status controls outer mitochondrial membrane permeabilization in hepatosteatosis.
    Mots-clés : Animals Calcium/metabolism Cells, Cultured Fatty Liver/*metabolism Female Glycogen Synthase Kinase 3/*metabolism Hepatocytes/metabolism Humans Lipid Metabolism Male Mice Mice, Inbred C57BL Mitochondrial Membranes/*metabolism Phosphorylation Voltage-Dependent Anion Channels/*metabolism bcl-X Protein/*metabolism.

  • Melkus, M, Bennaceur-Griscelli, A, Valogne, Y, Flamant, S, Chomel, J-C, Sorel, N, Bonnet, M-L, Deininger, MW, Mitjavila-Garcia, M-T & Turhan, AG 2013, « Biological effects of T315I-mutated BCR-ABL in an embryonic stem cell-derived hematopoiesis model », Exp Hematol, vol. 41, no. 4, p. 335-45.e3, viewed sans date, .
    Résumé : The occurrence of T315I mutation during the course of targeted therapies of chronic myeloid leukemia is a major concern because it confers resistance to all currently approved tyrosine kinase inhibitors. The exact phenotype of the hematopoietic stem cell and the hierarchical level of the occurrence of this mutation in leukemic hematopoiesis has not been determined. To study the effects of T315I-mutated breakpoint cluster region-abelson (BCR-ABL) in a primitive hematopoietic stem cell, we have used the murine embryonic stem cell (mESC)-derived hematopoiesis model. Native and T315I-mutated BCR-ABL were introduced retrovirally in mESC-derived embryonic bodies followed by induction of hematopoiesis. In several experiments, T315I-mutated and nonmutated BCR-ABL-transduced embryonic bodies rapidly generated hematopoietic cells on OP-9 feeders, with evidence of hematopoietic stem cell markers. After injection into NOD/SCID mice, these cells induced myeloid and lymphoid leukemias, whereas transplantation of control (nontransduced) hematopoietic cells failed to produce any hematopoietic reconstitution in vivo. Moreover, the expression of native and T315I-mutated BCR-ABL conferred to mESC-derived hematopoietic cells a self-renewal capacity demonstrated by the generation of leukemias after secondary transplantations. Secondary leukemias were more aggressive with evidence of extramedullary tumors. The expression of stem cell regulator Musashi-2 was found to be increased in bone marrow of leukemic mice. These data show that T315I-mutated BCR-ABL is functional at the stem cell level, conferring to mESC-derived leukemic cells a long-term hematopoietic repopulation ability. This model could be of interest to test the efficiency of drugs at the stem cell level in leukemias with T315I mutation.
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  • Mokhtari, C, Marchadier, E, Haim-Boukobza, S, Jeblaoui, A, Tesse, S, Savary, J & Roque-Afonso, AM 2013, « Comparison of real-time RT-PCR assays for hepatitis E virus RNA detection », J Clin Virol, viewed sans date, .
    Résumé : BACKGROUND: Hepatitis E virus (HEV) is an increasing cause of acute viral hepatitis in developed countries. Serological testing alone may fail to diagnose acute infection, especially in immunocompromised patients, which justifies the use of molecular assays for diagnosis. Few studies have compared accuracy of HEV RNA detection assays. OBJECTIVES: The performances of five real-time PCR procedures for HEV RNA detection were compared. STUDY DESIGN: First, RNA quantification of hepatitis E diluted standards of 3a and 3b genotypes were performed. Secondly, forty-seven clinical samples of patients with known acute HEV infection were tested using five hepatitis E RNA detection methods of assigned letters A, B, C, D and E. RESULTS: Standards of HEV 3a genotype were detected in 100% of replicates with 2500UI/ml of sensitivity by using A, B and C assays. Standards of HEV 3b genotype were more accurately detected with a sensitivity of 25UI/ml in 100% of replicates using C assay and were detected in 100% of replicates with 2500UI/ml of sensitivity by using A, B and E assays. Overall, B assay detected all of 250UI/ml dilution and occasionally the 25UI/ml dilution on both subtypes. The detection rates of clinical samples were 100%, 100% 97%, 97% and 83% for the respective A, B, C, D and E assay. Assays A and B were well correlated, independently of the subtype. However, discrepancies were observed when these techniques were compared to C, D and E assays according to the different subtypes. CONCLUSION: A and B assays appear reliable for HEV RNA detection. These assays target the ORF2/3 overlapping region, described as more conserved than ORF2.
  • Montaruli, E, Rosa, FM, Martelli, H, Guerin, F, Paul, A, Guettier, C & Dufour, C 2013, « Mediastinal extramedullary hematopoiesis mimicking a neuroblastic tumor in a patient with beta-thalassemia », Pediatr Blood Cancer, vol. 60, no. 4, p. 711-2.
    Résumé : Montaruli, Ernesto; Rosa, Francesca Marchetti; Martelli, Helene; Guerin, Florent; Paul, Anu; Guettier, Catherine; Dufour, Christelle; Case Reports; Letter; United States; Pediatr Blood Cancer. 2013 Apr;60(4):711-2. doi: 10.1002/pbc.24455. Epub 2013 Jan 9.
    Mots-clés : Adolescent Diagnosis, Differential Ganglioneuroma/complications/ diagnosis Hematopoiesis, Extramedullary Humans Male Mediastinal Neoplasms/complications/ diagnosis Splenectomy beta-Thalassemia/ complications/surgery.
  • Moreau, R, Jalan, R, Gines, P, Pavesi, M, Angeli, P, Cordoba, J, Durand, F, Gustot, T, Saliba, F, Domenicali, M, Gerbes, A, Wendon, J, Alessandria, C, Laleman, W, Zeuzem, S, Trebicka, J, Bernardi, M & Arroyo, V 2013, « Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis », Gastroenterology, vol. 144, no. 7, p. 1426-37, 1437 e1-9.
    Résumé : BACKGROUND & AIMS: Patients with cirrhosis hospitalized for an acute decompensation (AD) and organ failure are at risk for imminent death and considered to have acute-on-chronic liver failure (ACLF). However, there are no established diagnostic criteria for ACLF, so little is known about its development and progression. We aimed to identify diagnostic criteria of ACLF and describe the development of this syndrome in European patients with AD. METHODS: We collected data from 1343 hospitalized patients with cirrhosis and AD from February to September 2011 at 29 liver units in 8 European countries. We used the organ failure and mortality data to define ACLF grades, assess mortality, and identify differences between ACLF and AD. We established diagnostic criteria for ACLF based on analyses of patients with organ failure (defined by the chronic liver failure-sequential organ failure assessment [CLIF-SOFA] score) and high 28-day mortality rate (>15%). RESULTS: Of the patients assessed, 303 had ACLF when the study began, 112 developed ACLF, and 928 did not have ACLF. The 28-day mortality rate among patients who had ACLF when the study began was 33.9%, among those who developed ACLF was 29.7%, and among those who did not have ACLF was 1.9%. Patients with ACLF were younger and more frequently alcoholic, had more associated bacterial infections, and had higher numbers of leukocytes and higher plasma levels of C-reactive protein than patients without ACLF (P < .001). Higher CLIF-SOFA scores and leukocyte counts were independent predictors of mortality in patients with ACLF. In patients without a prior history of AD, ACLF was unexpectedly characterized by higher numbers of organ failures, leukocyte count, and mortality compared with ACLF in patients with a prior history of AD. CONCLUSIONS: We analyzed data from patients with cirrhosis and AD to establish diagnostic criteria for ACLF and showed that it is distinct from AD, based not only on the presence of organ failure(s) and high mortality rate but also on age, precipitating events, and systemic inflammation. ACLF mortality is associated with loss of organ function and high leukocyte counts. ACLF is especially severe in patients with no prior history of AD.
    Mots-clés : Acute/complications/ diagnosis/mortality Male Middle Aged Prognosis Prospective Studies Severity of Illness Index Syndrome, Adult Aged Cohort Studies Disease Progression End Stage Liver Disease/complications/ diagnosis/mortality Female Humans Liver Cirrhosis/ complications/mortality Liver Failure.

  • Nault, JC, Mallet, M, Pilati, C, Calderaro, J, Bioulac-Sage, P, Laurent, C, Laurent, A, Cherqui, D, Balabaud, C & Rossi, JZ 2013, « High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions », Nat Commun, vol. 4, p. 2218, viewed sans date, .
    Résumé : Somatic mutations activating telomerase reverse-trancriptase promoter were recently identified in several tumour types. Here we identify frequent similar mutations in human hepatocellular carcinomas (59%), cirrhotic preneoplastic macronodules (25%) and hepatocellular adenomas with malignant transformation in hepatocellular carcinomas (44%). In hepatocellular tumours, telomerase reverse-transcripase- and CTNNB1-activating mutations are significantly associated. Moreover, preliminary data suggest that telomerase reverse-trancriptase promoter mutations can increase the expression of telomerase transcript. In conclusion, telomerase reverse-trancriptase promoter mutation is the earliest recurrent genetic event identified in cirrhotic preneoplastic lesions so far and is also the most frequent genetic alteration in hepatocellular carcinomas, arising from both the cirrhotic or non-cirrhotic liver.
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  • Nkontchou, G, Tran Van Nhieu, J, Ziol, M, Tengher, I, Mahmoudi, A, Roulot, D, Bourcier, V, Ganne Carrie, N, Grando-Lemaire, V, Trinchet, JC, Cherqui, D & Beaugrand, M 2013, « Peripheral intrahepatic cholangiocarcinoma occurring in patients without cirrhosis or chronic bile duct diseases: epidemiology and histopathology of distant nontumoral liver in 57 White patients », Eur J Gastroenterol Hepatol, vol. 25, no. 1, p. 94-8.
    Résumé : BACKGROUND/AIM: Peripheral intrahepatic cholangiocarcinoma (ICC) occurring mainly in the absence of cirrhosis represents an increasing subgroup of primary liver tumors in Western countries. Histopathologic changes in the non-neoplastic liver in this context are not well characterized. PATIENTS AND METHODS: We assessed the clinical characteristics and histopathologic changes in the distant nontumoral liver of 57 consecutive White patients (34 men, mean age 59 years) referred to one medical and one surgical liver institution over a 16-year period who developed a peripheral ICC in the absence of cirrhosis or bile duct disease. RESULTS: High alcohol consumption was observed in 11 patients (20%), 38 patients (66%) had a BMI of 25 kg/m or more, 22 patients (40%) had diabetes, two patients had hepatitis B virus infection, two others had hepatitis C virus infection, three patients had genetic hemochromatosis, and two patients had cutaneous porphyria tarda. The distant nontumoral liver was normal in 10 patients (18%). The two main histopathologic changes observed were macrovesicular steatosis (>10% of hepatocytes) in 38 patients (66%), including 11 patients (19%) with steatohepatitis, and moderate or intense hepatocyte iron overload in 22 patients (38%). CONCLUSION: This study shows a high prevalence of macrovesicular steatosis associated or not with steatohepatitis and iron overload in patients who develop peripheral ICC in the absence of cirrhosis or bile duct disease.
    Mots-clés : Aged Biopsy Cholangiocarcinoma/ ethnology/ pathology European Continental Ancestry Group Fatty Liver/ethnology/pathology Fatty Liver, Alcoholic/ethnology/pathology Female France/epidemiology Humans Iron Overload/ethnology/pathology Liver/ pathology Liver Neoplasms/ ethnology/ pathology Male Middle Aged Prevalence Retrospective Studies Risk Factors Time Factors.


  • Obeid, M, Franetich, J-F, Lorthiois, A, Gego, A, Grüner, AC, Tefit, M, Boucheix, C, Snounou, G & Mazier, D 2013, « Skin-draining lymph node priming is sufficient to induce sterile immunity against pre-erythrocytic malaria », EMBO Mol Med, vol. 5, no. 2, p. 250-63, viewed sans date, .
    Résumé : The Plasmodium-infected hepatocyte has been considered necessary to prime the immune responses leading to sterile protection after vaccination with attenuated sporozoites. However, it has recently been demonstrated that priming also occurs in the skin. We wished to establish if sterile protection could be obtained in the absence of priming by infected hepatocytes. To this end, we developed a subcutaneous (s.c.) immunization protocol where few, possibly none, of the immunizing irradiated Plasmodium yoelii sporozoites infect hepatocytes, and also used CD81-deficient mice non-permissive to productive hepatocyte infections. We then compared and contrasted the patterns of priming with those obtained by intradermal immunization, where priming occurs in the liver. Using sterile immunity as a primary read-out, we exploited an inhibitor of T-cell migration, transgenic mice with conditional depletion of dendritic cells and adoptive transfers of draining lymph node-derived T cells, to provide evidence that responses leading to sterile immunity can be primed in the skin-draining lymph nodes with little, if any, contribution from the infected hepatocyte.
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  • Ortiz-Tudela, E, Mteyrek, A, Ballesta, A, Innominato, PF & Lévi, F 2013, « Cancer chronotherapeutics: experimental, theoretical, and clinical aspects », Handb Exp Pharmacol, no. 217, p. 261–88.
    Résumé : The circadian timing system controls cell cycle, apoptosis, drug bioactivation, and transport and detoxification mechanisms in healthy tissues. As a consequence, the tolerability of cancer chemotherapy varies up to several folds as a function of circadian timing of drug administration in experimental models. Best antitumor efficacy of single-agent or combination chemotherapy usually corresponds to the delivery of anticancer drugs near their respective times of best tolerability. Mathematical models reveal that such coincidence between chronotolerance and chronoefficacy is best explained by differences in the circadian and cell cycle dynamics of host and cancer cells, especially with regard circadian entrainment and cell cycle variability. In the clinic, a large improvement in tolerability was shown in international randomized trials where cancer patients received the same sinusoidal chronotherapy schedule over 24h as compared to constant-rate infusion or wrongly timed chronotherapy. However, sex, genetic background, and lifestyle were found to influence optimal chronotherapy scheduling. These findings support systems biology approaches to cancer chronotherapeutics. They involve the systematic experimental mapping and modeling of chronopharmacology pathways in synchronized cell cultures and their adjustment to mouse models of both sexes and distinct genetic background, as recently shown for irinotecan. Model-based personalized circadian drug delivery aims at jointly improving tolerability and efficacy of anticancer drugs based on the circadian timing system of individual patients, using dedicated circadian biomarker and drug delivery technologies.

  • Oughlis, S, Lessim, S, Changotade, S, Poirier, F, Bollotte, F, Peltzer, J, Felgueiras, H, Migonney, V, Lataillade, JJ & Lutomski, D 2013, « The osteogenic differentiation improvement of human mesenchymal stem cells on titanium grafted with polyNaSS bioactive polymer », J Biomed Mater Res A, vol. 101, no. 2, p. 582-9, viewed sans date, .
    Résumé : Osseointegration of metallic implants used in orthopedic surgery requires that osteoprogenitor cells attach and adhere to the surface, then proliferate, differentiate into osteoblasts, and finally produce mineralized matrix. Because the ability of progenitor cells to attach to a scaffold surface during early stages is important in the development of new tissue structures, we developed in our laboratory, a strategy involving grafting of implants with a polymer of sodium styrene sulfonate (polyNaSS) used as a scaffold which enables human mesenchymal stem cells (hMSCs) interactions. In the present study, we investigated the cellular response of hMSCs to polyNaSS surfaces of titanium (Ti). In particular, cell proliferation, cell viability, cell differentiation, and cell spreading were evaluated. Results showed that cell proliferation and cell viability did not differ with any statistical significance between modified and unmodified Ti surfaces. Interestingly, culture of MSCs on polyNaSS surfaces resulted in a significant increase of cell spreading and cell differentiation compared with the other tested surfaces. These results suggest that titanium surface grafted with polyNaSS is a suitable scaffold for bone tissue engineering.
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  • Pean, N, Doignon, I, Garcin, I, Besnard, A, Julien, B, Liu, B, Branchereau, S, Spraul, A, Guettier, C, Humbert, L, Schoonjans, K, Rainteau, D & Tordjmann, T 2013, « The receptor TGR5 protects the liver from bile acid overload during liver regeneration in mice », Hepatology.
    Résumé : Background and aims. Many regulatory pathways are involved in liver regeneration after partial hepatectomy (PH), to initiate growth, protect liver cells and sustain functions of the remnant liver. Bile acids (BA), whose levels rise in the blood early after PH, stimulate both hepatocyte proliferation and protection, in part through their binding to the nuclear Farnesoid X Receptor (FXR). However, the impact of the BA receptor TGR5 (G Protein-Coupled BA Receptor 1, GPBAR1) after PH remains to be studied. Methods. Liver histology, hepatocyte proliferation, BA concentrations (plasma, bile, liver, urine, feces), bile flow and composition, and cytokine production were studied in wild type (WT) and TGR5-KO mice, before and after PH. Results. BA composition (plasma, bile, liver, urine, feces) was more hydrophobic in TGR5-KO than in WT mice. After PH, severe hepatocyte necrosis, prolonged cholestasis, exacerbated inflammatory response and delayed regeneration were observed in TGR5-KO mice. While hepatocyte adaptive response to post-PH BA overload was similar in WT and TGR5-KO mice, kidney and biliary adaptive responses were strongly impaired in TGR5-KO mice. Cholestyramine treatment as well as Kupffer cell depletion, significantly improved the post-PH TGR5-KO mice phenotype. After bile duct ligation or upon cholic acid-enriched diet, TGR5-KO mice exhibited more severe liver injury than WT, and impaired BA elimination in urines. Conclusion. TGR5 is crucial for liver protection against BA overload after PH, primarily through the control of bile hydrophobicity and cytokine secretion. In the absence of TGR5, intrahepatic stasis of abnormally hydrophobic bile and excessive inflammation, in association with impaired bile flow adaptation and deficient urinary BA efflux, lead to BA overload-induced liver injury and delayed regeneration. (HEPATOLOGY 2013.).


  • Potel, J, Rassam, P, Montpellier, C, Kaestner, L, Werkmeister, E, Tews, BA, Couturier, C, Popescu, C-I, Baumert, TF, Rubinstein, E, Dubuisson, J, Milhiet, P-E & Cocquerel, L 2013, « EWI-2wint promotes CD81 clustering that abrogates Hepatitis C Virus entry », Cell Microbiol, vol. 15, no. 7, p. 1234-52, viewed sans date, .
    Résumé : CD81 is a major receptor for Hepatitis C Virus (HCV). It belongs to the tetraspanin family whose members form dynamic clusters with numerous partner proteins and with one another, forming tetraspanin-enriched areas in the plasma membrane. In our study, we combined single-molecule microscopy and biochemistry experiments to investigate the clustering and membrane behaviour of CD81 in the context of cells expressing EWI-2wint, a natural inhibitor of HCV entry. Interestingly, we found that EWI-2wint reduces the global diffusion of CD81 molecules due to a decrease of the diffusion rate of mobile CD81molecules and an increase in the proportion of confined molecules. Indeed, we demonstrated that EWI-2wint promotes CD81 clustering and confinement in CD81-enriched areas. In addition, we showed that EWI-2wint influences the colocalization of CD81 with Claudin-1 - a co-receptor required for HCV entry. Together, our results indicate that a change in membrane partitioning of CD81 occurs in the presence of EWI-2wint. This study gives new insights on the mechanism by which HCV enters into its target cells, namely by exploiting the dynamic properties of CD81.
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  • Ramasamy, R, Reifsnyder, JE, Husseini, J, Eid, PA, Bryson, C & Schlegel, PN 2013, « Localization of sperm during microdissection testicular sperm extraction in men with nonobstructive azoospermia », J Urol, vol. 189, no. 2, p. 643-6, viewed sans date, .
    Résumé : PURPOSE: We determined the location where sperm were identified during microdissection testicular sperm extraction and characterized the subset of patients for whom complete bilateral exploration was most beneficial. MATERIALS AND METHODS: A total of 900 men underwent a first attempt at microdissection testicular sperm extraction. Sperm extraction began with an initial wide incision in the larger testis. If no sperm were identified, the deeper tissue was extensively microdissected. A similar technique was used on the contralateral testis if no sperm were found on the initial side. RESULTS: In 474 men (52.6%) sperm were identified at the first microdissection testicular sperm extraction. Of these men 308 (65%) had sperm identified through the initial wide incision alone. In men with lower preoperative follicle-stimulating hormone, larger testicular volume, a varicocele history and hypospermatogenesis on preoperative or intraoperative diagnostic biopsy there was a greater chance of finding sperm in the initial wide incision alone (p <0.05). Only 40 of the 506 men (8%) who underwent bilateral testicular microdissection had sperm found on the contralateral side when no sperm were identified on the initial side. In men with Klinefelter syndrome and small testes the chance of sperm retrieval was higher on the contralateral side after negative unilateral microdissection (p <0.05). CONCLUSIONS: More than a third of the men with nonobstructive azoospermia required complete microdissection of the testes to identify sperm. Sperm were found on the contralateral side in up to 8% of the men in whom no sperm were identified in the initial testis.
    Mots-clés : *Azoospermia, *Microdissection, *Sperm, Adult, Humans, Male, Retrieval, Retrospective, Studies, Testis.

  • Richard, R, Thomassin, I, Chapellier, M, Scemama, A, de Cremoux, P, Varna, M, Giacchetti, S, Espié, M, de Kerviler, E & de Bazelaire, C 2013, « Diffusion-weighted MRI in pretreatment prediction of response to neoadjuvant chemotherapy in patients with breast cancer », Eur Radiol, vol. 23, no. 9, p. 2420-31, viewed sans date, .
    Résumé : PURPOSE: To evaluate the accuracy of the apparent diffusion coefficient (ADC) provided by diffusion-weighted imaging (DWI) in predicting the response to neoadjuvant chemotherapy (NACT) at baseline in patients according to their breast tumour phenotypes. MATERIALS & METHODS: This retrospective study was approved by our institutional review board. One hundred eighteen consecutive women with locally advanced breast cancer who had undergone NACT followed by breast surgery were included. DWI was performed at 1.5 T less than 2 weeks before NACT. We studied the correlation between pretreatment ADC and response in pathology after surgery according to immunohistochemical features and intrinsic subtypes (luminal A, luminal B, HER2-enriched, and triple-negative tumours). RESULTS: After surgery, the pathologist recognized 24 complete responders (CRps) and 94 non-complete responders (NCRps). No difference was identified between the pretreatment ADCs of the CRp and NCRp patients. There were differences in pretreatment ADCs among the luminal A (1.001 ± 0.143 × 10(-3) mm(2)/s), luminal B (0.983 ± 0.150 × 10(-3) mm(2)/s), HER2-enriched (1.132 ± 0.216 × 10(-3) mm(2)/s), and triple-negative (1.168 ± 0.245 × 10(-3) mm(2)/s; P = 0.0003) tumour subtypes. In triple-negative tumours, the pretreatment ADC was higher in NCRp (1.060 ± 0.143 × 10(-3) mm(2)/s) than in CRp patients (1.227 ± 0.271 × 10(-3) mm(2)/s; P = 0.047). CONCLUSION: Pretreatment ADC can predict the response of breast cancer to NACT if tumour subtypes are considered. Key Points • Apparent diffusion coefficient helps clinicians to assess patients with breast cancer. • Pretreatment ADC is related to tumour grade and hormone receptor status. • Pretreatment ADC is lower in luminal A and B than in triple-negative tumours. • Pretreatment ADC is higher in complete than in non-complete responders to neoadjuvant chemotherapy.
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  • Risco-Castillo, V, Son, O, Franetich, J-F, Rubinstein, E, Mazier, D & Silvie, O 2013, « [Plasmodium sporozoite entry pathways during malaria liver infection] », Biologie Aujourd'hui, vol. 207, no. 4, p. 219-229.
    Résumé : Plasmodium parasites, the causative agents of malaria, are transmitted by female Anopheles mosquitoes, which inject sporozoites into the skin of the host. The motile sporozoites enter the blood stream and, upon reaching the liver, transform into liver stages inside hepatocytes. The parasites enter host cells actively, using their actomyosin motor machinery to propel themselves through a specialized structure called junction. Penetration inside an invagination of the host cell plasma membrane results in the formation of the parasitophorous vacuole, which is essential for parasite further development. The mechanisms of sporozoite entry into host cells remain poorly understood at the molecular level. We reported for the first time a host factor required for infection of hepatocytes by Plasmodium sporozoites, the tetraspanin CD81, which also serves as a receptor for the hepatitis C virus. CD81 is involved at an early step of the infection, however no evidence for a direct interaction between CD81 and the parasite could be found. Although sporozoites can use several independent pathways to enter hepatocytes, depending on the parasite species and the host cell type, we showed that P. falciparum, the deadliest human malaria parasite, depends on CD81 to infect hepatocytes. We identified structural determinants in the CD81 large extracellular domain, and demonstrated that CD81 function is regulated by its molecular environment in specialized tetraspanin-enriched membrane microdomains. Based on these data we propose that CD81 acts indirectly during malaria infection, by interacting with other essential but still unidentified factor(s), possibly a receptor for the sporozoites, within specific microdomains of the hepatocyte plasma membrane.

  • Roche, B & Samuel, D 2013, « Treatment of Patients with HBV-related Decompensated Cirrhosis and Liver Transplanted Patients », Clin Liver Dis, vol. 17, no. 3, p. 451-73, viewed sans date, .
    Résumé : Antiviral therapy using newer nucleos(t)ide analogs with lower resistance rates could suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or decompensated cirrhosis, delay or obviate liver transplantation in some patients, and reduce the risk of HBV recurrence. Some form of HBV prophylaxis needs to be continued indefinitely posttransplant. However, in patients with a low-risk of HBV recurrence it is possible to discontinue hepatitis B immunoglobulins and maintain long-term nucleos(t)ide analog therapy. Currently, treatment of posttransplantation hepatitis B is a less important clinical problem than it was historically because effective antiviral therapies exist to rescue patients who failed initial prophylaxis.
  • Roux, M, Baranes, L, Decaens, T, Cherqui, D, Nhieu, JT, Pigneur, F, Djabbari, M, Levy, M, Laurent, A, Rahmouni, A & Luciani, A 2013, « Recurring multicystic inflammatory pseudotumor of the liver: a case report », Clin Res Hepatol Gastroenterol, vol. 37, no. 2, p. e51-7.
    Résumé : Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion for which imaging diagnosis remains a challenge. We report the case of a 39-year-old Algerian woman, who presented epigastric pains combined with fever and jaundice. Ultrasound, CT scan and MRI showed the presence of a 10 cm-long multi-septated cystic mass of the left lobe, with peripheral enhancement. A left-hepatectomy was performed and histopathology revealed an IPT of the liver. During the 4 following years, the patient had three other recurrences of liver IPT at various locations distinct from the original, revealed by the same clinical symptoms. During these relapses, the lesions did regress thanks to a medical treatment. This observation underlines the difficulty of the diagnosis and treatment of liver IPT.
  • Salceda, J, Tayar, C, Laurent, A, Alain, L, Cherqui, D & Azoulay, D 2013, « [Inflammatory pseudotumor of the liver: a case of recurrence after resection] », Acta Gastroenterol Latinoam, vol. 43, no. 1, p. 48-52.
    Résumé : Inflammatory pseudo-tumor of the liver is a rare benign condition. Usually presented as a large liver mass, may cause obstruction or infiltration of the main vessels or biliary tree. The clinical presentation is mostly an inflammatory syndrome with acute abdominal pain. We present a 39-year-old female patient with abdominal pain, fever and jaundice. Images showed a 15-cm liver lesion in the left lobe of the liver. Malignancy could not be discarded and the patient underwent left hepatectomy. The histologic examination reported an inflammatory pseudo-tumor of the liver. The patient recurred after one year with the same symptoms and a 10-cm new lesion occupying segment I. Considered as a recurrence, medical treatment was decided tumor size decreased 50% after the first month and completely disappeared during the follow up. Two years later, the patient was readmitted with a new episode and a new 8-cm liver lesion in segment VII. She was treated again with anti-inflammatory medication and imaging control. Although inflammatory pseudo-tumor of the liver is a benign condition, it can have a recurrent behaviour. The differentiation with other malignant tumors sometimes is impossible by clinical and imaging presentation.
    Mots-clés : Adult Female Granuloma, Plasma Cell/ diagnosis/surgery Hepatectomy Humans Liver Diseases/ diagnosis Magnetic Resonance Imaging Recurrence Tomography, X-Ray Computed.
  • Saliba, F, Camus, C, Durand, F, Mathurin, P, Delafosse, B, Barange, K, Perrigault, PF, Belnard, M, Letierce, A, Ichai, P & Samuel, D 2013, « Albumin Dialysis with MARS® in Patients with Fulminant and Subfulminant Hepatic Failure: A Randomized Controlled Trial », Annals of Internal Medicine, vol. In Press.
  • Saliba, F, De Simone, P, Nevens, F, De Carlis, L, Metselaar, HJ, Beckebaum, S, Jonas, S, Sudan, D, Fischer, L, Duvoux, C, Chavin, KD, Koneru, B, Huang, MA, Chapman, WC, Foltys, D, Dong, G, Lopez, PM, Fung, J & Junge, G 2013, « Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study », Am J Transplant, vol. 13, no. 7, p. 1734-45.
    Résumé : In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m(2) (97.5% CI 1.9, 11.4 mL/min/1.73 m(2) , p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m(2) in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m(2) in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant.

  • Saliba, F, Ichai, P, Levesque, E & Samuel, D 2013, « Cirrhotic patients in the ICU: prognostic markers and outcome », Curr Opin Crit Care, vol. 19, no. 2, p. 154-60.
    Résumé : PURPOSE OF REVIEW: Give an update on the importance of prognostic scores at admission to the ICU for defining short-term outcome in critically ill cirrhotic patients. Highlight the correlation between the development of sepsis and/or organ failure and outcome. RECENT FINDINGS: ICU mortality rate of cirrhotic patients admitted to the ICU ranges from 34 to 69%. Few improvements in the management of these patients occurred during the last decade. Definitive treatment relies mainly on the availability of transplant organs. ICU scores (mainly Sequential Organ Failure Assessment score) when performed at admission or within 2-4 days from admission are superior to liver specific scores (Model for End-Stage Liver Disease and Child-Pugh scores) to determine outcome. Cirrhotic patients with three or more organ failures have higher mortality then general ICU patients in the same condition. An attempt to define an entity called 'acute on chronic liver failure' that characterizes better those patients with worse outcomes according to the numbers of organ failures is currently undergoing. SUMMARY: Early referral of cirrhotic patients to ICU before the development of multiple extrahepatic organ failure is essential to improve outcome. Current scores should be used only for clinical trials and not to determine the potential futility or costs of an ICU admission.

  • Saliba, F & Samuel, D 2013, « Acute liver failure: Current trends », J Hepatol, vol. 59, no. 1, p. 6-8.
    Résumé : Saliba, Faouzi; Samuel, Didier; Editorial; Netherlands; J Hepatol. 2013 Jul;59(1):6-8. doi: 10.1016/j.jhep.2013.04.001. Epub 2013 Apr 6.

  • Saliba, F, Delvart, V, Ichaï, P, Kassis, N, Botterel, F, Mihaila, L, Azoulay, D, Adam, R, Castaing, D, Bretagne, S & Samuel, D 2013, « Fungal infections after liver transplantation: outcomes and risk factors revisited in the MELD era », Clin Transplant, vol. 27, no. 4, p. E454-61, viewed sans date, .
    Résumé : Antifungal prophylaxis is recommended in high-risk patients, but risk criteria remain unclear and the predictive value of Model of End-Stage Liver Disease (MELD) score is unknown. In a retrospective, single-center analysis of 667 liver transplants, potential risk factors for fungal infection were assessed, including MELD score. Antifungal prophylaxis was administered in 198 patients (29.4%). During follow-up (mean 43.6 ± 29.6 months), 263 patients (39.4%) developed ≥1 episode of fungal infection, and 187 (28.0%) patients developed a probable or proven invasive fungal infection requiring systemic antifungal treatment. Patients receiving antifungal prophylaxis had a lower incidence of fungal infection (29.8% vs. 43.5% without prophylaxis, p < 0.001) and invasive fungal infection (17.7% vs. 32.4%, p < 0.001). One-yr patient survival was 91%, 85% and 69%, respectively, in patients with no fungal infection, fungal colonization and treated invasive fungal infection (p < 0.001); graft survival was 88%, 85% and 66% (p < 0.001). Multivariate analysis indicated that MELD score of 20-30 or ≥30 was associated with a 2.0-fold or 4.3-fold increase in relative risk of fungal infection, respectively, and a 2.1-fold or 3.1-fold increase in relative risk of invasive fungal infection. In conclusion, liver transplant patients with a MELD score ≥20, and particularly patients with a score ≥30, are candidates for antifungal prophylaxis.
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  • Saliba, F, Delvart, V, Ichaï, P, Kassis, N, Botterel, F, Mihaila, L, Azoulay, D, Adam, R, Castaing, D, Bretagne, S & Samuel, D 2013, « Outcomes associated with amphotericin B lipid complex (ABLC) prophylaxis in high-risk liver transplant patients », Med Mycol, vol. 51, no. 2, p. 155-63, viewed sans date, .
    Résumé : Antifungal prophylaxis with liposomal amphotericin B in high-risk liver transplant recipients is recommended, but experience with amphotericin B lipid complex (ABLC, Abelcet(®)) in this setting is limited. Data from 615 liver transplants performed during 1999-2005 were analyzed retrospectively. High-risk patients (n = 146) received a mean cumulative ABLC dose of 955 ± 609 mg (mean duration of 23.3 ± 11.9 days). Low-risk patients (n = 469) received no prophylaxis. During a mean follow-up of 43.8 ± 29.2 months, fungal infections occurred in 32.2% of ABLC patients versus 43.5% of non-prophylaxis patients (P = 0.015). The overall rate of invasive fungal infection was 12.3% in the ABLC group versus 15.6% in the non-prophylaxis patients (P = 0.34). Any Candida infection (ABLC 29.5%, non-prophylaxis 41.2%, P = 0.011), probable or proven invasive Candida infection requiring systemic antifungal treatment (ABLC 18.5%, non-prophylaxis 32.4%, P = 0.001) and invasive abdominal candidiasis during the first 3 months (ABLC 4.1%, non-prophylaxis 9.2%, P = 0.049) were significantly less frequent in the ABLC group. There was no significant difference between groups in the incidence of Aspergillus infections. The ABLC group showed no evidence of nephrotoxicity. In conclusion, the marked and significant differences in infection rates and requirement for systemic treatment in this large population suggest that targeted use of low-dose ABLC therapy to high-risk patients is a valid prophylactic strategy following liver transplantation.
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  • Samuel, D & Duclos-Vallee, JC 2013, « Liver transplantation in the human immunodeficiency virus-hepatitis C virus coinfected patient: time to sum up », Hepatology, vol. 57, no. 1, p. 409-11.
    Résumé : Samuel, Didier; Duclos-Vallee, Jean-Charles; Comment; United States; Hepatology. 2013 Jan;57(1):409-11. doi: 10.1002/hep.26123.
  • Santambrogio, R, Kluger, MD, Costa, M, Belli, A, Barabino, M, Laurent, A, Opocher, E, Azoulay, D & Cherqui, D 2013, « Hepatic resection for hepatocellular carcinoma in patients with Child-Pugh's A cirrhosis: is clinical evidence of portal hypertension a contraindication? », HPB (Oxford), vol. 15, no. 1, p. 78-84.
    Résumé : BACKGROUND: According to international guidelines [European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD)], portal hypertension (PHTN) is considered a contraindication for liver resection for hepatocellular carcinoma (HCC), and patients should be referred for other treatments. However, this statement remains controversial. The aim of this study was to elucidate surgical outcomes of minor hepatectomies in patients with PHTN (defined by the presence of esophageal varices or a platelet count of <100,000 in association with splenomegaly) and well-compensated liver disease. METHODS: Between 1997 and 2012, a total of 223 cirrhotic patients [stage A according to the Barcelona Clinic Liver Cancer (BCLC) classification] were eligible for this analysis and were divided into two groups according to the presence (n = 63) or absence (n = 160) of PHTN. The demographic data were comparable in the two patient groups. RESULTS: Operative mortality was not different (only one patient died in the PHTN group). However, patients with PHTN had higher liver-related morbidity (29% versus 14%; P = 0.009), without differences in hospital stay (8.8 versus 9.8 days, respectively). The PHTN group showed a worse survival rate only if biochemical signs of liver decompensation existed. Multivariate analysis identified albumin levels as an independent predictive factor for survival. CONCLUSIONS: PHTN should not be considered an absolute contraindication to a hepatectomy in cirrhotic patients. Patients with PHTN have short- and long-term results similar to patients with normal portal pressure. A limited hepatic resection for early-stage tumours is an option for Child-Pugh class A5 patients with PHTN.
    Mots-clés : Aged Carcinoma, Hepatocellular/etiology/mortality/pathology/ surgery Female Hepatectomy/ contraindications/mortality Humans Hypertension.
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  • Santambrogio, R, Salceda, J, Costa, M, Kluger, MD, Barabino, M, Laurent, A, Opocher, E, Azoulay, D & Cherqui, D 2013, « External validation of a simplified BCLC staging system for early hepatocellular carcinoma », Eur J Surg Oncol, vol. 39, no. 8, p. 850-7.
    Résumé : BACKGROUND AND AIMS: The aim was to externally validate the capability of a simplified Barcelona Clinic Liver Cancer (s-BCLC) staging system in allocating patients to hepatic resection (HR) and the effect on survival: S-BCLC was defined by only 2 groups: AA included BCLC A1 + A2 classes with alpha-fetoprotein (AFP) </= 20 ng/ml and AB included A1 + A2 with AFP > 20 ng/ml plus A3 + A4 subgroups. METHODS: This study compared a training group (TG) with hepatocellular carcinoma (HCC) submitted to hepatic resection (HR) in Milan with another group of patients, the validation group (VG) in Creteil. All patients underwent ultrasound-guided anatomical resection (<3 segments). RESULTS: Overall survival got worse from A1 to A4 (p = 0.0271) in TG (n = 132), as well as in VG (n = 100) (p = 0.0044) with a more important overlapping of each curves. According s-BCLC classification, the survival curves of TG (p = 0.0001) and VG (p = 0.0250) showed a definitive separation in two different staging groups. The s-BCLC provided the best predictive accuracy and it also presented the highest separability index and C-statistics in both TG and VG. On the other hand, in the evaluation of discriminatory ability for death, measured by ROC curve areas, the s-BCLC system gave better results than the others. CONCLUSION: This experience stressed the high value of BCLC system in staging of HCC, but the s-BCLC system seems to be more useful for therapeutic decision making.
  • Sebagh, M, Castillo-Rama, M, Azoulay, D, Coilly, A, Delvart, D, Allard, MA, Dos Santos, A, Johanet, C, Roque-Afonso, AM, Saliba, F, Duclos-Vallee, JC, Samuel, D & Demetris, A-J 2013, « Histological findings predictive of a diagnosis of de novo auto-immune hepatitis after liver transplantation in adults », Transplantation, vol. In Press.
    Résumé : Backgrounds: Autoimmune hepatitis (AIH) after liver transplantation has been defined histologically as a “hepatitic” pattern of injury, characterized by lymphoplasmacytic inflammation with necro-inflammatory activity (NIA), comparable to findings seen in native livers. This definition, however, is difficult to apply in practice because specific histological criteria are not clearly delineated. This study aimed to determine which histological features correlated best with clinical and serological features of dAIH. Methods: Index liver biopsies from patients with autoimmune-like hepatitis transplanted for non-AIH in two centers (N=35 and N=20) were reviewed. Histological features were correlated with the clinical diagnosis of AIH based on a retrospective review of clinical and serological data, including therapeutic response. Results: A clinical diagnosis of AIH was retrospectively assigned to 24/35 (68%) and 18/20 (90%) patients, respectively (p=0.10). In multivariate analysis, centrilobular NIA and centrilobular plasma cell ratio of 30-50% were independently discriminating for a clinical diagnosis of AIH (p= 0.04 and 0.05, respectively). The best level of predictability (99.6%) was mathematically achieved when severe centrilobular NIA and centrilobular plasma cell ratio of 30-50% were both present. Conclusion: A histological pattern of centrilobular injury including increased NIA and increased plasma cell infiltration correlates with measurements of autoimmunity in liver recipients. It could be used to segregate cases for further study and introduced into the AIH scoring systems when applied in the context of liver transplantation.
  • Shindoh, J, Andreou, A, Aloia, TA, Zimmitti, G, Lauwers, GY, Laurent, A, Nagorney, DM, Belghiti, J, Cherqui, D, Poon, RT, Kokudo, N & Vauthey, JN 2013, « Microvascular invasion does not predict long-term survival in hepatocellular carcinoma up to 2 cm: reappraisal of the staging system for solitary tumors », Ann Surg Oncol, vol. 20, no. 4, p. 1223-9.
    Résumé : BACKGROUND: Excellent long-term outcomes have been reported recently for patients with small (</=2 cm) hepatocellular carcinoma (HCC). However, the significance of microvascular invasion (MVI) in small HCC remains unclear. The purpose of this study was to determine the impact of MVI in small HCC up to 2 cm. METHODS: In 1,109 patients with solitary HCC from six major international hepatobiliary centers, the impact of MVI on long-term survival in patients with small HCC (</=2 cm) and patients with tumors larger than 2 cm was analyzed. RESULTS: In patients with small HCC, long-term survival was not affected by MVI (p = 0.8), whereas in patients with larger HCC, significantly worse survival was observed in patients with MVI (p < 0.0001). In multivariate analysis, MVI (hazard ratio [HR] 1.59; 95 % confidence interval (CI) 1.27-1.99; p < 0.001), elevated alpha-fetoprotein (HR 1.41; 95 % CI 1.11-1.8; p = 0.005), and higher histologic grade (HR 1.29; 95 % CI 1.01-1.64; p = 0.04) were significant predictors of worse survival in patients with HCC larger than 2 cm but were not correlated with long-term survival in small HCC. When the cohort was divided into three groups-HCC </=2, >2 cm without MVI, and HCC >2 cm with MVI-significant between-group survival difference was observed (p < 0.0001). CONCLUSIONS: Small HCC is associated with an excellent prognosis that is not affected by the presence of MVI. The discriminatory power of the 7th edition of the AJCC classification for solitary HCC could be further improved by subdividing tumors according to size (</=2 vs. >2 cm).
  • Shukla, R, Upton, KR, Munoz-Lopez, M, Gerhardt, DJ, Fisher, ME, Nguyen, T, Brennan, PM, Baillie, JK, Collino, A, Ghisletti, S, Sinha, S, Iannelli, F, Radaelli, E, Dos Santos, A, Rapoud, D, Guettier, C, Samuel, D, Natoli, G, Carninci, P, Ciccarelli, FD, Garcia-Perez, JL, Faivre, J & Faulkner, GJ 2013, « Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma », Cell, vol. 153, no. 1, p. 101-11.
    Résumé : LINE-1 (L1) retrotransposons are mobile genetic elements comprising 17% of the human genome. New L1 insertions can profoundly alter gene function and cause disease, though their significance in cancer remains unclear. Here, we applied enhanced retrotransposon capture sequencing (RC-seq) to 19 hepatocellular carcinoma (HCC) genomes and elucidated two archetypal L1-mediated mechanisms enabling tumorigenesis. In the first example, 4/19 (21.1%) donors presented germline retrotransposition events in the tumor suppressor mutated in colorectal cancers (MCC). MCC expression was ablated in each case, enabling oncogenic beta-catenin/Wnt signaling. In the second example, suppression of tumorigenicity 18 (ST18) was activated by a tumor-specific L1 insertion. Experimental assays confirmed that the L1 interrupted a negative feedback loop by blocking ST18 repression of its enhancer. ST18 was also frequently amplified in HCC nodules from Mdr2(-/-) mice, supporting its assignment as a candidate liver oncogene. These proof-of-principle results substantiate L1-mediated retrotransposition as an important etiological factor in HCC.
    Mots-clés : Adult Aged Animals Carcinoma, Hepatocellular/ genetics Cell Line, Insertional P-Glycoproteins/genetics Repressor Proteins/genetics Tumor Suppressor Proteins/genetics, Neoplastic DNA Mutational Analysis Female Genes, Tumor Cell Transformation, Tumor Suppressor Humans Liver Neoplasms/ genetics Long Interspersed Nucleotide Elements Male Mice Middle Aged Mutagenesis.

  • Soares, F, Tattoli, I, Wortzman, ME, Arnoult, D, Philpott, DJ & Girardin, SE 2013, « NLRX1 does not inhibit MAVS-dependent antiviral signalling », Innate Immun, vol. 19, no. 4, p. 438-48, viewed sans date, .
    Résumé : NLRX1 is a member of the Nod-like receptor family of intracellular sensors of microbial- and danger-associated molecular patterns. NLRX1 has a N-terminal mitochondrial addressing sequence that localizes the protein to the mitochondrial matrix. Recently, conflicting reports have been presented with regard to the putative implication of NLRX1 as a negative regulator of MAVS-dependent cytosolic antiviral responses. Here, we generated a new NLRX1 knockout mouse strain and observed that bone marrow-derived macrophages and murine embryonic fibroblasts from NLRX1-deficient mice displayed normal antiviral and inflammatory responses following Sendai virus infection. Importantly, wild type and NLRX1-deficient mice exhibited unaltered antiviral and inflammatory gene expression following intranasal challenge with influenza A virus or i.p. injection of Poly (I:C). Together, our results demonstrate that NLRX1 does not participate in the negative regulation of MAVS-dependent antiviral responses.


  • Soubrane, O, Goumard, C, Laurent, A, Tranchart, H, Truant, S, Gayet, B, Salloum, C, Luc, G, Dokmak, S, Piardi, T, Cherqui, D, Dagher, I, Boleslawski, E, Vibert, E, Sa Cunha, A, Belghiti, J, Pessaux, P, Boelle, PY & Scatton, O 2013, « Laparoscopic resection of hepatocellular carcinoma: a French survey in 351 patients », HPB (Oxford), viewed sans date, .
    Résumé : OBJECTIVES: Current clinical studies report the results of laparoscopic resection of hepatocellular carcinoma (HCC) obtained in small cohorts of patients. Because France was involved in the very early development of laparoscopic surgery, the present study was conducted in order to report the results of a large, multicentre experience. METHODS: A total of 351 patients underwent laparoscopic liver resection for HCC during the period from 1998 to 2010 in nine French tertiary centres. Patient characteristics, postoperative mortality and morbidity, and longterm survival were retrospectively reviewed. RESULTS: Overall, 85% of the study patients had underlying liver disease. Types of resection included wedge resection (41%), left lateral sectionectomy (27%), segmentectomy (24%), and major hepatectomy (11%). Median operative time was 180 min. Conversion to laparotomy occurred in 13% of surgeries and intraoperative blood transfusion was necessary in 5% of patients. The overall morbidity rate was 22%. The 30-day postoperative mortality rate was 2%. Negative resection (R0) margins were achieved in 92% of patients. Rates of overall and progression-free survival at 1, 3 and 5 years were 90.3%, 70.1% and 65.9%, and 85.2%, 55.9% and 40.4%, respectively. CONCLUSIONS: This multicentre, large-cohort study confirms that laparoscopic liver resection for HCC is a safe and efficient approach to treatment and can be proposed as a first-line treatment in patients with resectable HCC.

  • Tahiri Joutei Hassani, R, Adam, R, El Sanharawi, M, Nordmann, J-P & Baudouin, C 2013, « [Sclerotomies analysis using Spectral Domain OCT in sutureless vitrectomies complicated by endophthalmitis] », J Fr Ophtalmol, vol. 36, no. 2, p. 138-45, viewed sans date, .
    Résumé : INTRODUCTION: Transconjunctival sutureless vitrectomy is a recent advance in vitreoretinal surgery. Some authors have reported an increased risk of postoperative hypotony and endophthalmitis and recommend the creation of oblique incisions, intended to be self-sealing, so as to reduce these risks. However, there is still a debate about the best architecture for transconjunctival sutureless incisions. MATERIALS AND METHODS: We report two cases of acute endophthalmitis occurring after 23 and 25 gauge transconjunctival sutureless vitrectomy. We analyzed the scleral incisions using the anterior segment module of the Spectralis(®) OCT. To our knowledge, this is the first direct description of the appearance of sclerotomies associated with endophthalmitis. RESULTS: The anterior segment module of Spectralis(®) OCT permitted a high-resolution evaluation of the architecture of the scleral incisions. We found straight, gaping incisions with misaligned edges and vitreous incarceration. DISCUSSION: By way of these two case reports and a review of the literature, we discuss the contribution of anterior segment OCT in the analysis of scleral incision architecture in sutureless vitrectomy. Our findings are consistent with those reported in the literature. The presence of a direct incision, wound gap or edge misalignment are associated with an increased risk of early leakage and postoperative hypotony. CONCLUSIONS: The anterior segment module of the Spectralis(®) OCT is a valuable tool for non-invasive, painless and high-resolution documentation of sutureless vitrectomy incisions. It allows for causal analysis and better understanding of the conditions associated with endophthalmitis after sutureless vitrectomy.
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  • Tahiri Joutei Hassani, R, El Sanharawi, M, Adam, R, Monin, C, Dupont-Monod, S & Baudouin, C 2013, « Influence of sutureless 23-gauge sclerotomy architecture on postoperative intraocular pressure decrease: results of a multivariate analysis », Graefes Arch Clin Exp Ophthalmol, vol. 251, no. 5, p. 1285-92, viewed sans date, .
    Résumé : PURPOSE: To evaluate the factors affecting the postoperative intraocular pressure (IOP) decrease in 23-gauge (23-G) sutureless vitrectomy, including incision architecture evaluated by anterior segment spectral-domain optical coherence tomography (SD-OCT). METHODS: A prospective cohort study of 43 patients who underwent primary transconjunctival 23-G pars plana vitrectomy. All sclerotomy wounds were imaged 1 day after surgery using the anterior segment module of SD-OCT (OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany). 23-G sclerotomy architecture, preoperative and postoperative medical data were also prospectively collected. RESULTS: Multivariate logistic regression analysis, with backward elimination, found that surgery duration (adjusted OR = 9.17, p = 0.020) and loss of wound apposition (adjusted OR = 15.12, p = 0.022) were risk factors for significant postoperative IOP decrease (≥3 mmHg) 1 day after surgery; while age, gender, myopia, and gas tamponade were not risk or protective factors for postoperative IOP decrease. CONCLUSIONS: In 23-G pars plana vitrectomy, the early postoperative decrease in IOP is mainly influenced by surgery duration and the self-sealing nature of the sclerotomy. The IOP decrease was not influenced by the presence or the absence of gas tamponade.
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  • Tahiri Joutei Hassani, R, El Sanharawi, M, Adam, R, Monin, C, Dupont-Monod, S & Baudouin, C 2013, « Comparison of 23-gauge sutureless sclerotomy architecture and clinical outcomes in macular and non-macular surgery using spectral-domain optical coherence tomography », Acta Ophthalmol, vol. 91, no. 3, p. e203-10, viewed sans date, .
    Résumé : PURPOSE: To compare the 23-gauge (23-G) sutureless vitrectomy incision architecture in macular and non-macular surgery, using anterior segment spectral-domain optical coherence tomography (SD-OCT), and to evaluated its influence on clinical outcomes. METHODS: A prospective, observational case series of 43 patients who underwent primary transconjunctival 23-G pars plana vitrectomy (PPV) for macular and non-macular diseases. All sclerotomy wounds were imaged 1 day after surgery using the anterior segment module of SD-OCT (OCT Spectralis; Heidelberg Engineering, Heidelberg, Germany). Sclerotomy architecture, including good wound apposition, presence of gaping and misalignment of the roof and floor of the incisions were evaluated. Preoperative, intraoperative and postoperative medical record data were also prospectively collected. Results: Incision gaping and misalignment of the roof and floor occurred more frequently in the superotemporal and superonasal quadrants than in the inferotemporal quadrant (p < 0.05) and was more frequent in the non-macular group than in the macular group (p < 0.05). The incidence of incision gaping increased significantly as the incision angle increased. In the macular group, the mean postoperative intraocular pressure (IOP) did not change from the preoperative value, whereas in the non-macular group, the mean IOP decreased significantly from 15.09 ± 2.58 mmHg preoperatively to 12.18 ± 3.25 mmHg on the first postoperative day (p < 0.005). The mean IOP did not differ significantly between the two groups of surgery at 1 week, and at 1 month postoperatively. Conclusions: In 23-G PPV, non-macular surgery is associated with a significant postoperative IOP decrease in comparison with macular surgery, which could be explained by the most remodelled wound architecture.
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  • Thevenot, T, Degand, T, Grelat, N, Elkrief, L, Christol, C, Moreau, R, Henrion, J, Cadranel, JF, Sheppard, F, Bureau, C, di Martino, V & Pauwels, A 2013, « A French national survey on the use of antibiotic prophylaxis in cirrhotic patients », Liver Int, vol. 33, no. 3, p. 389-97, viewed sans date, .
    Résumé : BACKGROUND: Guidelines recommend antibiotic prophylaxis (AP) in well-selected groups of cirrhotic patients, but the impact of these recommendations has not been assessed in France. AIM: To evaluate AP prescription tendencies for gastrointestinal bleeding, and primary and secondary prophylaxis of spontaneous bacterial peritonitis (SBP). METHODS: Practitioners (n = 1,159) working in general hospitals (GH) or in university hospitals (UH) received a self-administered questionnaire. RESULTS: Three hundred and eighty-nine (33.6%; GH 35% and UH 30.4%) practitioners responded. AP was prescribed by 97.7%, 72.3% and 94.8% of practitioners, without significant differences between UH and GH, respectively, for gastrointestinal bleeding (quinolones 48.2%, third-generation cephalosporins 27.7% and amoxicillin-clavulanic acid 22.2%), primary (quinolones 97.2%) and secondary prophylaxis of SBP (quinolones 99%). For gastrointestinal bleeding, ofloxacin (47.6%) and norfloxacin (37.4%) were the main quinolones prescribed, and ceftriaxone (77%) was the main third-generation cephalosporin prescribed. The principal reasons for prescribing AP were a decrease in bacterial infection (88.9% for gastrointestinal bleeding, 91.3% for primary and 94.3% for secondary prophylaxis of SBP), a recommendation by a consensus conference (83%, 38% and 74.4% respectively) and an improvement in survival (72.8%, 41.3% and 57.7% respectively). Only 31.7% of practitioners (39.6% for UH vs. 28.6% for GH; P = 0.038) believed that AP may reduce the risk of bleeding recurrence. Reported side effects (28%) of AP mainly concerned the risk of quinolone resistance (62% of cases). CONCLUSION: Antibiotic prophylaxis is well-recognized by French practitioners, but its routine use depends on the expertise of practitioners. Quinolones remain the main antibiotic class prescribed irrespective of the type of prophylaxis.
  • Thibault, V, Gaudy-Graffin, C, Colson, P, Gozlan, J, Schnepf, N, Trimoulet, P, Pallier, C, Saune, K, Branger, M, Coste, M & Thoraval, FR 2013, « Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study », Virol J, vol. 10, p. 87.
    Résumé : BACKGROUND: Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. METHODS: A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. RESULTS: Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. CONCLUSIONS: Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management and to promote vaccination in HIV-infected patients.
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  • Thomas, F, Fisher, D, Fort, P, Marie, J-P, Daoust, S, Roche, B, Grunau, C, Cosseau, C, Mitta, G, Baghdiguian, S, Rousset, F, Lassus, P, Assenat, E, Grégoire, D, Missé, D, Lorz, A, Billy, F, Vainchenker, W, Delhommeau, F, Koscielny, S, Itzykson, R, Tang, R, Fava, F, Ballesta, A, Lepoutre, T, Krasinska, L, Dulic, V, Raynaud, P, Blache, P, Quittau-Prevostel, C, Vignal, E, Trauchessec, H, Perthame, B, Clairambault, J, Volpert, V, Solary, E, Hibner, U & Hochberg, ME 2013, « Applying ecological and evolutionary theory to cancer: a long and winding road », Evol Appl, vol. 6, no. 1, p. 1-10, viewed sans date, .
    Résumé : Since the mid 1970s, cancer has been described as a process of Darwinian evolution, with somatic cellular selection and evolution being the fundamental processes leading to malignancy and its many manifestations (neoangiogenesis, evasion of the immune system, metastasis, and resistance to therapies). Historically, little attention has been placed on applications of evolutionary biology to understanding and controlling neoplastic progression and to prevent therapeutic failures. This is now beginning to change, and there is a growing international interest in the interface between cancer and evolutionary biology. The objective of this introduction is first to describe the basic ideas and concepts linking evolutionary biology to cancer. We then present four major fronts where the evolutionary perspective is most developed, namely laboratory and clinical models, mathematical models, databases, and techniques and assays. Finally, we discuss several of the most promising challenges and future prospects in this interdisciplinary research direction in the war against cancer.
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  • Trouillas, M, Prat, M, Doucet, C, Ernou, I, Laplace-Builhé, C, Blancard, PS, Holy, X & Lataillade, J-J 2013, « A new platelet cryoprecipitate glue promoting bone formation after ectopic mesenchymal stromal cell-loaded biomaterial implantation in nude mice », Stem Cell Res Ther, vol. 4, no. 1, p. 1, viewed sans date, .
    Résumé : ABSTRACT: INTRODUCTION: This study investigated the promising effect of a new Platelet Glue obtained from Cryoprecipitation of Apheresis Platelet products (PGCAP) used in combination with Mesenchymal Stromal Cells (MSC) loaded on ceramic biomaterials to provide novel strategies enhancing bone repair. METHODS: PGCAP growth factor content was analyzed by ELISA and compared to other platelet and plasma-derived products. MSC loaded on biomaterials (65% hydroxyapatite/35% beta-TCP or 100% beta-TCP) were embedded in PGCAP and grown in presence or not of osteogenic induction medium for 21 days. Biomaterials were then implanted subcutaneously in immunodeficient mice for 28 days. Effect of PGCAP on MSC was evaluated in vitro by proliferation and osteoblastic gene expression analysis and in vivo by histology and immunohistochemistry. RESULTS: We showed that PGCAP, compared to other platelet-derived products, allowed concentrating large amount of growth factors and cytokines which promoted MSC and osteoprogenitor proliferation. Next, we found that PGCAP improves the proliferation of MSC and osteogenic-induced MSC. Furthermore, we demonstrated that PGCAP up-regulates the mRNA expression of osteogenic markers (Collagen type I, Osteonectin, Osteopontin and Runx2). In vivo, type I collagen expressed in ectopic bone-like tissue was highly enhanced in biomaterials embedded in PGCAP in the absence of osteogenic pre-induction. Better results were obtained with 65% hydroxyapatite/35% beta-TCP biomaterials as compared to 100% beta-TCP. CONCLUSIONS: We have demonstrated that PGCAP is able to enhance in vitro MSC proliferation, osteoblastic differentiation and in vivo bone formation in the absence of osteogenic pre-induction. This clinically adaptable platelet glue could be of interest for improving bone repair.
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  • Turrini, O, Paye, F, Bachellier, P, Sauvanet, A, Sa Cunha, A, Le Treut, YP, Adham, M, Mabrut, JY, Chiche, L & Delpero, JR 2013, « Pancreatectomy for adenocarcinoma in elderly patients: postoperative outcomes and long term results: a study of the French Surgical Association », Eur J Surg Oncol, vol. 39, no. 2, p. 171-8.
    Résumé : AIM: To determine the benefit of surgery for resectable pancreatic adenocarcinomas (PAs) in elderly patients. METHODS: From 2004 to 2009, 932 patients with resectable PAs underwent pancreatectomies without neoadjuvant treatment in 37 institutions. The patients were divided into three groups according to age: <70 years (control group; n = 580); 70-79 years (70s group, n = 288), and >/= 80 years (80s group; n = 64). Preoperative, intraoperative, postoperative, and histological data were recorded to assess the postoperative course and survival. RESULTS: Preoperative or intraoperative characteristics, and the histological findings were comparable in the three groups. Postoperative mortality and morbidity rates did not differ in the three groups. Adjuvant therapies were more frequently used in younger patients than in elderly patients (p < 0.01). The overall 1-year, 3-year, and 5-year survival rates of control group/70's group/80's group were 82.2%/75.7%/75.7%, 49.9%/41.8%/31%, and 38.7%/33.2%/0%, respectively (p = 0.16). The median survival of the control, 70s, and 80s groups was 24 months, 35.3 months, and 30 months, respectively. Four independent prognostic indicators were identified by multivariate analysis: venous invasion (hazard ratio (HR) = 2.12), arterial invasion (HR = 2.96), positive lymph nodes (HR = 2.25), and adjuvant treatment (HR = 0.65). CONCLUSIONS: Fit elderly patients with resectable PAs should not be excluded from surgical resection of PA solely because of their real age. Moreover, elderly patients seem to obtain similar advantages from pancreatectomies than younger patients.
    Mots-clés : 80 and over Biliary Tract Chemotherapy, Adenocarcinoma/complications/mortality/ pathology/ surgery Aged Aged, Adjuvant Comorbidity Disease-Free Survival Female Humans Kaplan-Meier Estimate Lymphatic Metastasis Male Neoplasm Invasiveness Pancreatectomy/methods Pancreatic Neoplasms/complications/mortality/ pathology/ surgery Patient Selection Prognosis Radiotherapy, Adjuvant Retrospective Studies Risk Factors Stents Time Factors Treatment Outcome.
  • Vallet, S, Larrat, S, Laperche, S, Le Guillou-Guillemette, H, Legrand-Abravanel, F, Bouchardeau, F, Pivert, A, Henquell, C, Mirand, A, Andre-Garnier, E, Giordanengo, V, Lagathu, G, Thibault, V, Scholtes, C, Schvoerer, E, Gaudy-Graffin, C, Maylin, S, Trimoulet, P, Brochot, E, Hantz, S, Gozlan, J, Roque-Afonso, AM, Soussan, P, Plantier, JC, Charpentier, C, Chevaliez, S, Colson, P, Mackiewicz, V, Aguilera, L, Rosec, S, Gouriou, S, Magnat, N, Lunel-Fabiani, F, Izopet, J, Morand, P, Payan, C & Pawlotsky, JM 2013, « Multicenter quality control of hepatitis C virus protease inhibitor resistance genotyping », J Clin Microbiol, vol. 51, no. 5, p. 1428-33.
    Résumé : Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents.
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  • Vallot, C, Huret, C, Lesecque, Y, Resch, A, Oudrhiri, N, Bennaceur-Griscelli, A, Duret, L & Rougeulle, C 2013, « XACT, a long noncoding transcript coating the active X chromosome in human pluripotent cells », Nat Genet, vol. 45, no. 3, p. 239-41, viewed sans date, .
    Résumé : X-chromosome inactivation (XCI) in mammals relies on XIST, a long noncoding transcript that coats and silences the X chromosome in cis. Here we report the discovery of a long noncoding RNA, XACT, that is expressed from and coats the active X chromosome specifically in human pluripotent cells. In the absence of XIST, XACT is expressed from both X chromosomes in humans but not in mice, suggesting a unique role for XACT in the control of human XCI initiation.
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  • Vibert, E, Pittau, G, Gelli, M, Sa Cunha, A, Jamot, L, Faivre, J, Castro Benitez, C, Castaing, D & Adam, R 2013, « Actual incidence and long-term consequences of post-hepatectomy liver failure after hepatectomy for colorectal liver metastases », Surgery, vol. In Press.
    Résumé : Introduction: Post-hepatectomy liver failure (PHLF) is a severe complication following hepatectomy for colorectal liver metastases. This study evaluated its actual incidence and its effects on short and long-term overall survival (OS) in a specialized centre. Materials and Methods: Between 2006 and 2008, 193 patients who underwent 232 hepatectomies (147 minor and 85 major) for CLM were studied prospectively. Hepatectomy was performed if the remnant liver volume was >0.5% of body weight. Uni- and multivariate analyses on OS after all hepatectomies (n=232) or major resection only (n=85) were then performed on pre-, intra- and postoperative (including pathological) data in order to determine the consequences of PHLF by comparison with those of other intra- and post-operative events. Results: The 3-month postoperative mortality rate was 0.8%. PHLF was observed in six patients (7%) after major hepatectomy and in one (0.6%) after minor hepatectomy. With a 25-month follow-up, the 2-year OS rate was 84%. Preoperatively, pulmonary metastasis was the only determinant of OS. Intra- and postoperatively, four factors were determinant of OS: PHLF (RR=3.84, p=0.04), mental confusion (RR=3.11, p=0.006), fluid collection (RR=2.9, p=0.01) and transfusion (RR=2.27, p=0.009). After major hepatectomy, only PHLF (RR=4.14, p=0.01) and confusion (RR=3.6, p=0.02) were identified. Conclusion: With improvements in postoperative management, PHLF was found to be less responsible for 3-month mortality but remains an event that exerts a major impact on 2-year survival.
    Mots-clés : Colorectal, failure, Hepatectomy, Liver, metastasis, Post-operative.

  • Vibert, E, Azoulay, D, Cunha, AS, Adam, R, Samuel, D & Castaing, D 2013, « Portal stenting for hepatocellular carcinoma extending into the portal vein in cirrhotic patients », J Surg Oncol, vol. 107, no. 7, p. 696-701, viewed sans date, .
    Résumé : BACKGROUND AND AIMS: Macroscopic portal vein invasion complicating hepatocellular carcinoma in the setting of cirrhosis is associated with a very low survival. To prevent the malignant progression from a portal branch to the main portal trunk, we have placed noncovered metallic stents extending from the portal trunk to the contralateral tumor free portal pedicle. METHODS: Fifty-Four patients (age: 60 ± 11 years) were treated. Thirty-four (60%) patients were Child A and 20 (40%) were Child B-C. Tumoral thrombosis involved 1st or 2nd order branches in 41 (82%) patients and partially the main trunk in 13 (24%). Open surgical insertion (via ileal vein) as an alternative to a percutaneous approach was used in 14 (24%) patients. RESULTS: Early mortality (<30 days) was 7%. Following stent insertion, a transarterial chemoembolization was performed in 26 (48%) patients. After stenting, overall survival at 6, 12, and 24 months were 47%, 44%, and 36%, respectively. Bilirubin > 30 µmol/L and open surgical insertion were predictive of short-term mortality. In the good group, overall survival at 6, 12, and 24 months were 69%, 61%, and 46%, respectively. CONCLUSIONS: The transhepatic deployment of metallic stent seems to improve survival of patients with hepatocellular carcinoma complicated by portal vein tumoral thrombosis and could allow subsequent treatments.
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  • Vija, L, Meduri, G, Comperat, E, Vasiliu, V, Izard, V, Ferlicot, S, Boukari, K, Camparo, P, Viengchareun, S, Constancis, E, Dumitrache, C, Lombes, M & Young, J 2013, « Expression and characterization of androgen receptor coregulators, SRC-2 and HBO1, during human testis ontogenesis and in androgen signaling deficient patients », Mol Cell Endocrinol, vol. 375, no. 1-2, p. 140-8, viewed sans date, .
    Résumé : Androgen receptor (AR) is essential for testicular physiology and spermatogenesis. SRC-2 and HBO1 are two AR coregulators yet their expression and roles in human testis are unknown. For the first time, we studied by immunohistochemistry and RT-PCR, the expression and distribution of these two coregulators during human testicular ontogenesis, in patients with altered AR signaling (Androgen insensitivity syndrome, AIS) and evaluated the functional impact of SRC-2 and HBO1 on AR signaling in a Sertoli cell context. SRC-2 was present in Sertoli cells at all developmental stages. HBO1 was barely or focally detected in the fetal testis yet its expression, in Sertoli and germ cells, drastically increased postnatally from early infancy to adulthood. In transient co-transfection studies we showed that SRC-2 induced, while HBO1 inhibited AR-mediated transactivation of reporter constructs in murine Sertoli SMAT1 cells. HBO1, but not SRC-2, expression was reduced in testes of patients with AIS compared to normal testes.

  • Wicherts, DA, de Haas, RJ, Salloum, C, Andreani, P, Pascal, G, Sotirov, D, Adam, R, Castaing, D & Azoulay, D 2013, « Repeat hepatectomy for recurrent colorectal metastases », Br J Surg, vol. 100, no. 6, p. 808-18, viewed sans date, .
    Résumé : BACKGROUND: The oncological benefit of repeat hepatectomy for patients with recurrent colorectal metastases is not yet proven. This study assessed the value of repeat hepatectomy for these patients within current multidisciplinary treatment. METHODS: Consecutive patients treated by repeat hepatectomy for colorectal metastases between January 1990 and January 2010 were included. Patients undergoing two-stage hepatectomy were excluded. Postoperative outcome was analysed and compared with that of patients who had only a single hepatectomy. RESULTS: A total of 1036 patients underwent 1454 hepatectomies for colorectal metastases. Of these, 288 patients had 362 repeat hepatectomies for recurrent metastases. Some 225 patients (78·1 per cent) had two hepatectomies, 52 (18·1 per cent) had three hepatectomies, and 11 patients (3·8 per cent) had a fourth hepatectomy. Postoperative morbidity following repeat hepatectomy was similar to that after initial liver resection (27·1 per cent after first, 34·4 per cent after second and 33·3 per cent after third hepatectomy) (P = 0·069). The postoperative mortality rate was 3·1 per cent after repeat hepatectomy versus 1·6 per cent after first hepatectomy. Three- and 5-year overall survival rates following first hepatectomy in patients who underwent repeat hepatectomy were 76 and 54 per cent respectively, compared with 58 and 45 per cent in patients who had only one hepatectomy (P = 0·003). In multivariable analysis, repeat hepatectomy performed between 2000 and 2010 was the sole independent factor associated with longer overall survival. CONCLUSION: Repeat hepatectomy for recurrent colorectal metastases offers long-term survival in selected patients.
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  • Wyplosz, B, Burdet, C, Francois, H, Durrbach, A, Duclos-Vallee, JC, Mamzer-Bruneel, MF, Poujol, P, Launay, O, Samuel, D, Vittecoq, D & Consigny, PH 2013, « Persistence of Yellow Fever Vaccine-Induced Antibodies After Solid Organ Transplantation », Am J Transplant.
    Résumé : Immunization using live attenuated vaccines represents a contra-indication after solid organ transplantation (SOT): consequently, transplant candidates planning to travel in countries where yellow fever is endemic should be vaccinated prior to transplantation. The persistence of yellow fever vaccine-induced antibodies after transplantation has not been studied yet. We measured yellow-fever neutralizing antibodies in 53 SOT recipients vaccinated prior to transplantation (including 29 kidney recipients and 18 liver recipients). All but one (98%) had protective titers of antibodies after a median duration of 3 years (min.: 0.8, max.: 21) after transplantation. The median antibody level was 40 U/L (interquartile range: 40-80). For the 46 patients with a known or estimated date of vaccination, yellow-fever antibodies were still detectable after a median time of 13 years (range: 2-32 years) post-immunization. Our data suggest there is long-term persistence of antibodies to yellow fever in SOT recipients who have been vaccinated prior to transplantation.

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