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Sainte-Foy-lès-Lyon, France

Castera L.,Center Hospitalier University Chu Of Bordeaux | Sebastiani G.,Venetian Institute of Molecular Medicine | Le Bail B.,Service danatomo pathologie | de Ledinghen V.,Center Hospitalier University Chu Of Bordeaux | And 2 more authors.
Journal of Hepatology

Background & Aims: Non-invasive assessment of liver fibrosis is a challenging area. Several methods have been proposed in patients with chronic hepatitis C (CHC) but their performance may be improved when they are combined as suggested by recently proposed algorithms using either transient elastography (TE) and Fibrotest (FT) (Castera) or AST-to-Platelet Ratio Index (APRI) and FT (SAFE biopsy). The aim of this prospective study was to compare the performance of these two algorithms for diagnosing significant fibrosis and cirrhosis in 302 CHC patients. Methods: All patients underwent TE, FT and APRI the same day as liver biopsy, taken as reference standard. Results: Significant fibrosis (Metavir F ≥ 2) was present in 76% of patients and cirrhosis (F4) in 25%. TE failure was observed in eight cases (2.6%). For significant fibrosis, Castera algorithm saved 23% more liver biopsies (71.9% vs. 48.3%, respectively; p < 0.0001) than SAFE biopsy but its accuracy was significantly lower (87.7% vs. 97.0%, respectively; p < 0.0001). Regarding cirrhosis, accuracy of Castera algorithm was significantly higher than that of SAFE biopsy (95.7% vs. 88.7%, respectively; p < 0.0001). The number of saved liver biopsies did not differ between the two algorithms (78.8% vs. 74.8%; p = NS). Conclusions: Both algorithms are effective for non-invasive staging of liver fibrosis in chronic hepatitis C. Although the number of liver biopsies avoided does not differ between algorithms for diagnosing cirrhosis, it is significantly higher with Castera algorithm than SAFE biopsy for significant fibrosis. © 2009 European Association for the Study of the Liver. Source

Guibal A.,Service dImagerie Abdominale | Boularan C.,Service dImagerie Abdominale | Bruce M.,Service dImagerie Abdominale | Bruce M.,SuperSonic Imagine | And 7 more authors.
European Radiology

Objectives: To determine the elasticity characteristics of focal liver lesions (FLLs) by shearwave elastography (SWE). Methods: We used SWE in 108 patients with 161 FLLs and in the adjacent liver for quantitative and qualitative FLLs stiffness assessment. The Mann-Whitney test was used to assess the difference between the groups of lesions where a P value less than 0.05 was considered significant. Results: SWE acquisitions failed in 22 nodules (14 %) in 13 patients. For the 139 lesions successfully evaluated, SWE values were (in kPa), for the 3 focal fatty sparings (FFS) 6.6 ± 0.3, for the 10 adenomas 9.4 ± 4.3, for the 22 haemangiomas 13.8 ± -5.5, for the 16 focal nodular hyperplasias (FNHs) 33 ± -14.7, for the 2 scars 53.7 ± 4.7, for the 26 HCCs 14.86 ± 10, for the 53 metastasis 28.8 ± 16, and for the 7 cholangiocarcinomas 56.9 ± 25.6. FNHs had significant differences in stiffness compared with adenomas (P = 0.0002). Fifty percent of the FNHs had a radial pattern of elevated elasticity. A significant difference was also found between HCCs and cholangiocarcinomas elasticity (P = 0.0004). Conclusions: SWE could be useful in differentiating FNHs and adenomas, or HCCs and cholangiocarcinomas by ultrasound. Key Points: • Elastography is becoming quite widely used as an adjunct to conventional ultrasound • Shearwave elastography (SWE) could help differentiate adenomas from fibrous nodular hyperplasia • SWE could also be helpful in distinguishing between hepatocellular carcinomas and cholangiocarcinomas • SWE could improve the identify hepatocellular carcinomas in cirrhotic livers © 2012 European Society of Radiology. Source

Duarte S.,University of Coimbra | Momier D.,University of Nice Sophia Antipolis | Baque P.,University of Nice Sophia Antipolis | Casanova V.,University of Nice Sophia Antipolis | And 8 more authors.
Stem Cells

Cancer stem cells (CSCs) represent a minor population of self-renewing cancer cells that fuel tumor growth. As CSCs are generally spared by conventional treatments, this population is likely to be responsible for relapses that are observed in most cancers. In this work, we analyzed the preventive efficiency of a CSC-based vaccine on the development of liver metastasis from colon cancer in a syngeneic rat model. We isolated a CSC-enriched population from the rat PROb colon carcinoma cell line on the basis of the expression of the aldehyde dehydrogenase-1 (ALDH1) marker. Comparative analysis of vaccines containing lysates of PROb or ALDHhigh cells by mass spectrometry identifies four proteins specifically expressed in the CSC subpopulation. The expression of two of them (heat shock protein 27- kDa and aldose reductase) is already known to be associated with treatment resistance and poor prognosis in colon cancer. Preventive intraperitoneal administration of vaccines was then performed before the intrahepatic injection of PROb cancer cells. While no significant difference in tumor occurrence was observed between control and PROb-vaccinated groups, 50% of the CSC-based vaccinated animals became resistant to tumor development. In addition, CSC-based vaccination induced a 99.5% reduction in tumor volume compared to the control group. To our knowledge, this study constitutes the first work analyzing the potential of a CSC-based vaccination to prevent liver metastasis development. Our data demonstrate that a CSCbased vaccine reduces efficiently both tumor volume and occurrence in a rat colon carcinoma syngeneic model. © AlphaMed Press. Source

Dalat F.,Center Hospitalier Lyon Sud | Barnoud R.,Service danatomo pathologie | Fessy M.-H.,Center Hospitalier Lyon Sud | Fessy M.-H.,University of Lyon | And 2 more authors.
Orthopaedics and Traumatology: Surgery and Research

Introduction: Medium-term results for total ankle replacement (TAR) are in general satisfactory, but there is a high redo rate for periprosthetic osteolysis associated with the AES implant. Hypothesis: Comparing radioclinical findings and histologic analysis of implant revision procedure specimens can account for the elevated rate of osteolysis associated with the AES TAR implant. Material and method: In a prospective series of 84 AES TAR implants (2003-2008), 25 underwent revision for osteolysis (including three undergoing revision twice) at a mean 59.8. months. Eight patients had hydroxyapatite (HA) coated models and the others had titanium-hydroxyapatite (Ti-HA) coatings. Radiographs were systematically analyzed on Besse's protocol and evolution was monitored on AOFAS scores. The 94 specimens taken for histologic analysis during revision were re-examined, focusing specifically on foreign bodies. Results: Macroscopically, no metallosis or polyethylene wear was found at revision. AOFAS global and pain scores fell respectively from 89.7/100 at 1. year postoperatively to 72.9 before revision and from 32.5/40 to 20.6/40, although global scores were unchanged in 25% of patients. Radiologically, all patients showed tibial and talar osteolytic lesions, 45% showed cortical lysis and in 25% the implant had collapsed into the cysts. All specimens showed macrophagic granulomatous inflammatory reactions in contact with a foreign body; the cysts showed necrotic remodeling. Some of the foreign bodies could be identified on optical histologic examination with polyethylene in 95% of the specimens and metal in 60% (100% of HA-coated models and 33.3% of Ti-HA-coated models). Unidentifiable material was associated: a brownish pigment in Ti-HA-coated models (33.3%) and flakey bodies in 44.4% of the HA-coated models and 18.2% of the Ti-HA-coated models. Discussion: The phenomenon of periprosthetic osteolysis is still poorly understood, although implant wear debris seems to be implicated. All the patients with HA-coated implants with modular tibial stem had metal particles in the tissue around the implant, although their exact nature could not be determined. The double-layer Ti-HA coating may induce delamination by fretting while the biological bone anchorage is forming.Level of evidence: Prospective cohort study-Level IV. © 2013 Elsevier Masson SAS. Source

Pell G.,Service de Nephrologie Transplantation Renale | Shweke N.,Service de Nephrologie Transplantation Renale | Van Huyen J.-P.D.,Service danatomo pathologie | Tricot L.,Service de Nephrologie Transplantation Renale | And 4 more authors.
American Journal of Kidney Diseases

Intravenous injection of angiogenesis-inhibitor drugs is used widely to treat cancers. Associated renal complications primarily involve proteinuria and hypertension, and thrombotic microangiopathies also have been described. Intravitreal antivascular endothelial growth factor (VEGF) therapy currently is used by ophthalmologists to treat neovascularization in age-related macular degeneration. However, there is some evidence that intravitreal anti-VEGF injections may result in systemic absorption, with the potential for injury in organs that are reliant on VEGF, such as the kidney. We report the first case to our knowledge of a patient who developed an acute decrease in kidney function, nonimmune microangiopathic hemolytic anemia with schistocytes, and thrombocytopenia after 4 intravitreal injections of ranibizumab. Light microscopy of a kidney biopsy specimen showed segmental duplications of glomerular basement membranes with endothelial swelling and several recanalized arteriolar thrombi. Because of the increasing use of intravitreal anti-VEGF agents, ophthalmologists and nephrologists should be aware of the associated risk of kidney disease. Early detection is crucial so that intravitreal injections can be stopped before severe kidney disease occurs. © 2011 National Kidney Foundation, Inc. Source

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