Assistance Publique des Hopitaux de Marseille APHM

Saint-Pierre-du-Chemin, France

Assistance Publique des Hopitaux de Marseille APHM

Saint-Pierre-du-Chemin, France
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Carcopino X.,Assistance Publique des Hopitaux de Marseille APHM | Carcopino X.,Aix - Marseille University | Mancini J.,Aix - Marseille University | Charpin C.,Aix - Marseille University | And 9 more authors.
Archives of Gynecology and Obstetrics | Year: 2013

Purpose: To assess the value of direct colposcopic vision (DCV) for optimizing large loop excision of the transformation zone (LLETZ) for the treatment of cervical intraepithelial neoplasia (CIN). Methods: Data from 648 patients who underwent excisional procedures for CIN and were included in two previously published cohort studies were retrospectively reviewed. Women who had a LLETZ were included for analysis (n = 436). Margin status, surgical specimen dimensions and volume were analysed according to the use of colposcopy during procedure. Results: Compared to LLETZ guided by previous colposcopy report only, and to LLETZ performed immediately after colposcopy, DCV allowed for a significantly higher rate of clear margins: 33 (52.4 %), 104 (68.0 %) and 142 (84.5 %), respectively (p < 0.001). It also allowed for a significantly higher probability of achieving both negative margins and depth of specimen <10 mm: 10 (15.9 %) cases, 47 (30.7 %) cases and 125 (74.4 %) cases, respectively (p < 0.001). In multivariate analysis, when compared with the use of previous colposcopy report or with colposcopy immediately before the LLETZ, DCV allowed for a significantly higher probability of negative margins (AOR: 4.61; 95 % CI: 2.37-8.99 and AOR: 2.55; 95 % CI: 1.47-4.41), combined negative margins and depth <75th percentile (AOR: 3.67; 95 % CI: 1.97-6.86 and AOR: 3.05; 95 % CI: 1.91-4.87) and combined negative margins and volume <75th percentile (AOR: 12.96; 95 % CI: 5.99-28.05 and AOR: 6.16; 95 % CI: 3.75-10.14), respectively. Conclusions: When used with the LLETZ procedure, DCV allows for optimal outcomes in terms of negative resection margins, and minimized depth and volume of the excised specimen; and should therefore be recommended. © 2013 Springer-Verlag Berlin Heidelberg.


Grisot C.,Assistance Publique des Hopitaux de Marseille APHM | Mancini J.,Aix - Marseille University | Giusiano S.,Aix - Marseille University | Houvenaeghel G.,Aix - Marseille University | And 6 more authors.
Archives of Gynecology and Obstetrics | Year: 2012

Purpose To evaluate the value of colposcopy during excisional treatment of cervical intraepithelial neoplasia (CIN). Methods Data from 469 women who underwent excisional treatment for CIN in three different hospitals between January 2005 and December 2009 were reviewed. Margins status and surgical specimen dimensions were analyzed according to the use of colposcopy during procedure. Results The rate of negative margins was not significantly different between women who had excision performed without colposcopic examination, with colposcopy immediately before excision and with direct colposcopic vision (DCV): 74 (62.2%), 186 (72.9%) and 25 (67.6%), respectively (p = 0.107). DCV allowed for significantly higher probability to achieve both negative margins and depth of specimen of less than 10 mm: 22 (18.5%) versus 70 (27.5%) versus 14 (37.8%), respectively (p = 0.039). In multivariate analysis, compared to women who had excision without any use of colposcopy, DCV allowed for significant and independent reduction in both depth (ß: -2.46; 95%CI: -4.45 to -0.47; p = 0.015) and diameter (ß: -4.80; 95%CI: -7.14 to -2.47; p < 0.001) of the surgical specimen. Compared to the use of colposcopy immediately before excision, DCV allowed for a significant and independent reduction in diameter of the surgical specimen (ß: -6.57; 95%CI: -8.78 to -4.35; p < 0.001) without significantly changing its depth (ß: -1.10; 95%CI: -3.01 to -0.80; p = 0.255). Conclusions Use of colposcopy, and particularly of DCV during excisional procedures for CIN, allows for smaller surgical specimen without jeopardizing the margins status. © Springer-Verlag 2011.


Blanc J.,Assistance Publique des Hopitaux de Marseille APHM | Le Du R.,Assistance Publique des Hopitaux de Marseille APHM | Le Du R.,Aix - Marseille University | Le Du R.,French Institute of Health and Medical Research | And 6 more authors.
American Journal of Obstetrics and Gynecology | Year: 2013

Objective: We sought to evaluate the efficacy of maternal posturing during labor on the prevention of persistent occiput posterior (OP) position. Study Design: We conducted a randomized trial including 220 patients in labor with a single fetus in documented OP position. Main outcome was the proportion of anterior rotation from OP position. Results: The rates of anterior rotation were, respectively, 78.2% and 76.4% in the intervention group and the control group without significant difference (P =.748). Rates of instrumental and cesarean section deliveries were not significantly different between intervention and control groups (18.2% vs 19.1%, P =.89, and 19.1% vs 17.3%, P =.73, respectively). In intervention and control groups, persistent OP position rates were significantly higher among women who had cesarean section (71.4% and 89.5%, respectively) and an instrumental delivery (25% and 33.3%, respectively) than among women who achieved spontaneous vaginal birth (5.8% and 2.8%, respectively). In multivariable analysis, body mass index and parity were found to have significant and independent impact on the probability of fetal head rotation. Conclusion: Our study failed to demonstrate any maternal or neonatal benefit to a policy of maternal posturing for the management of OP position during labor. © 2013 Mosby, Inc.


PubMed | Assistance Publique des Hopitaux de Marseille APHM, Sanofi S.A., University of Lorraine, University of Franche Comte and 3 more.
Type: Journal Article | Journal: Sexual health | Year: 2016

Background The objective was to evaluate the effect of a HPV vaccination program on the incidence proportion of a proxy, genital warts (GW), in women in France.The number of primary GW cases was prospectively recorded over two 4-month periods before (T0: Dec 2008 to March 2009) and after (T1: Dec 2011 to March 2012) a HPV vaccination program. A total of 160 gynaecologists participated in T0 and 189 in T1. Primary genital herpes (HSV) infection was used as a control.During T0, 39190 15- to 26 year-old women were seen, of whom 176 were diagnosed with GW (incidence proportion: 0.45%) and 155 with primary HSV infection (incidence proportion: 0.39%). During T1, 45628 females were seen [229 with GW (incidence proportion: 0.50%) and 202 with HSV (incidence proportion: 0.44%)]. In the 15-20 years age category, the incidence proportion of primary GW decreased from 0.41% to 0.30% (P=0.128) between T0 and T1, and the proportion of women newly diagnosed with primary genital herpes diseases slightly increased from 0.34% to 0.38% (P=0.620). In the 15-18 years age group, this decrease became significant (0.34% to 0.18%; P=0.048).A trend for a non-significant decreased incidence proportion of GW was observed in young women below 20 years who are more frequently vaccinated. This may be the result of HPV vaccination and suggests that a substantial increase in vaccine coverage could lead to a more pronounced decreased incidence proportion of GW in the future.


Jacquin E.,University of Franche Comte | Baraquin A.,Besancon University Hospital Center | Ramanah R.,Besancon University Hospital Center | Carcopino X.,Assistance Publique des Hopitaux de Marseille APHM | And 12 more authors.
Journal of Clinical Microbiology | Year: 2013

High-risk (HR) human papillomavirus (HPV)-associated carcinogenesis is driven mainly by the overexpression of E7 and E6 oncoproteins following viral DNA integration and the concomitant loss of the E2 open reading frame (ORF). However, the integration of HR-HPV DNA is not systematically observed in cervical cancers. The E2 protein acts as a transcription factor that governs viral oncogene expression. The methylation of CpGs in the E2-binding sites (E2BSs) in the viral long control region abrogates E2 binding, thus impairing the E2-mediated regulation of E7/E6 transcription. Here, high-resolution melting (HRM)-PCR was developed to quantitatively analyze the methylation statuses of E2BS1, E2BS2, and the specificity protein 1 (Sp1)-binding site in 119 HPV16-positive cervical smears. This is a rapid assay that is suitable for the analysis of cervical samples. The proportion of cancer samples with methylated E2BS1, E2BS2, and Sp1-binding site CpGs was 47%, whereas the vast majority of samples diagnosed as being within normal limits, low-grade squamous intraepithelial lesions (LSIL), or high-grade squamous intraepithelial lesions (HSIL) harbored unmethylated CpGs. Methylation levels varied widely, since some cancer samples harbored up to 60% of methylated HPV16 genomes. A pyrosequencing approach was used as a confirmation test and highlighted that quantitative measurement of methylation can be achieved by HRM-PCR. Its prognostic value deserves to be investigated alone or in association with other biomarkers. The reliability of this single-tubeassay offers great opportunities for the investigation of HPV16 methylation in other HPV-related cancers, such as head and neck cancers, which are a major public health burden. Copyright © 2013, American Society for Microbiology.


Baron C.,Marseille University Hospital Center | Henry M.,Marseille University Hospital Center | Tamalet C.,Marseille University Hospital Center | Villeret J.,Assistance Publique des Hopitaux de Marseille APHM | And 2 more authors.
Journal of Medical Virology | Year: 2015

Better understanding of the correlation between high-risk HPV DNA testing, viral load quantitation, and E6/E7 mRNA detection is required. The aim of this study was to assess the relationship between these markers and the severity of cervical lesions. One-hundred and fifty one directed cervical specimens were analysed (normal, cervical intraepithelial neoplasia, and cancer). HPV types 16, 18, 31, 33, and 45 DNA detection and quantititation and E6/E7 mRNA detection were performed. DNA was detected in 87 (57.6%) samples and increased from 0% (normal) to 93.9% (cancer). E6/E7 mRNA was detected in 65 (43%) samples and increased with the severity of the lesions from 0% (normal) to 78.8% (26/33) (cancers) (P<0.001). HPV DNA and E6/E7 mRNA detection were compared in the 141 samples harbouring HPV16, 18, 31, 33, or 45 infection: 45.4% (64/141) of specimens were DNA-/mRNA-, 46% (65/141) were DNA+/mRNA+ and 8.5% (12/141) were DNA+/mRNA-. The proportion of DNA+/mRNA+ specimens increased with the severity of the lesions (P<0.001). All normal cervix specimens were DNA-/mRNA-. Among grade 2 cervical intraepithelial neoplasia, prevalence of DNA was higher than that of mRNA: 41.6% (5/12) versus 25% (3/12), whereas it was 79.3% (46/58) versus 62% (36/58) among grade 3 cervical intraepithelial neoplasia. Full concordance was observed in cancers as all the 26 DNA+ specimens were mRNA+. Median overall HPV load was higher in DNA+/mRNA+ than in DNA+/mRNA- specimens (1.41×106 vs. 9.1×102 copies per million cells, P<0.001). Both E6/E7 mRNA detection and concordant DNA+/mRNA+ detection increases with the severity of the lesions and with the HPV DNA load. © 2015 Wiley Periodicals, Inc..


Tosello B.,Aix - Marseille University | Blanc J.,Assistance Publique des Hopitaux de Marseille APHM | Haumonte J.-B.,Assistance Publique des Hopitaux de Marseille APHM | D'Ercole C.,Aix - Marseille University | Gire C.,Assistance Publique des Hopitaux de Marseille APHM
Journal of Perinatal Medicine | Year: 2014

Objective: To evaluate short and medium term outcomes of children born of monochorionic pregnancies complicated by twin-twin transfusion syndrome treated by fetoscopic laser surgery. Methods: This was a retrospective observational study performed between May 2007 and 2012. Neonatal data was from 45 patients under 5 years of age. The prospective observational study was of the neurologic outcome of these children using the Ages and Stages Questionnaire (ASQ), 2 nd edition, French version, at up to 5 years of age. Results: Neurologic assessment at discharge from maternity unit was normal for 41 infants (93.2%). Logistic regression suggested that the risk of neurosensory sequelae was significantly related to the status of donor [odds ratio=4.62 (1.18; 18.0)] and significantly preterm birth <32 weeks of gestation [odds ratio=5.50 (1.38; 21.9)]. Eleven questionnaires were considered abnormal (31.1%). Two children presented a severe neurologic abnormality (5.7%). There was no significant correlation between any area of the questionnaire and status at birth (donor or recipient). Conclusions: The data from our cohort, particularly as regards neurologic outcome, were satisfactory and concordant with previously published results. The use of the ASQ as a screening tool for neurologic outcome in children is original, which allowed in our cohort to highlight early neurological disorders. © 2014 by Walter de Gruyter Berlin Boston 2014.


PubMed | Aix - Marseille University and Assistance Publique des Hopitaux de Marseille APHM
Type: Journal Article | Journal: Archives of gynecology and obstetrics | Year: 2016

To assess whether the use of direct colposcopic vision during excision therapy of cervical intraepithelial neoplasia (CIN) has an impact on the risk of treatment failure.Data from 285 patients who had had excision therapy with proven CIN at specimen histological analysis were reviewed. Primary endpoint was the occurrence of post-treatment failure defined by the histological diagnosis of CIN 2-3 during follow-up. Data were analysed according to the use of colposcopy at the time of initial therapy of CIN.The use of direct colposcopic vision (DCV) resulted in a significant reduction in the mean height (p = 0.008) and diameter (p < 0.001) of the excised specimen. Patients median follow-up was 28.4 (1.3) months. A total of 43 (15.2 %) patients were diagnosed with treatment failure. Compared to excisions performed without any use of colposcopy, DCV was not found to have any significant impact on the risk of treatment failure (HR: 0.58; 95 % CI 0.16-2.13, p = 0.412), neither when compared to excisions performed immediately after colposcopy (HR: 0.91; 95 % CI 0.47-1.79; p = 0.794). The only factors found to have a significant impact on the risk of treatment failure was the identification of clear margins (HR: 0.36; 95 %CI 0.19-0.69; p = 0.002) and the diameter of the surgical specimen (HR: 0.94; 95 %CI 0.89-0.99; p = 0.040).Although the use of DCV during excision therapy of CIN was associated with a significant reduction in the dimensions of the excised cervical specimen, it did not result in a significant change in the risk of treatment failure.


PubMed | Aix - Marseille University, Marseille University Hospital Center and Assistance Publique des Hopitaux de Marseille APHM
Type: Journal Article | Journal: Journal of medical virology | Year: 2015

Better understanding of the correlation between high-risk HPV DNA testing, viral load quantitation, and E6/E7 mRNA detection is required. The aim of this study was to assess the relationship between these markers and the severity of cervical lesions. One-hundred and fifty one directed cervical specimens were analysed (normal, cervical intraepithelial neoplasia, and cancer). HPV types 16, 18, 31, 33, and 45 DNA detection and quantititation and E6/E7 mRNA detection were performed. DNA was detected in 87 (57.6%) samples and increased from 0% (normal) to 93.9% (cancer). E6/E7 mRNA was detected in 65 (43%) samples and increased with the severity of the lesions from 0% (normal) to 78.8% (26/33) (cancers) (P<0.001). HPV DNA and E6/E7 mRNA detection were compared in the 141 samples harbouring HPV16, 18, 31, 33, or 45 infection: 45.4% (64/141) of specimens were DNA-/mRNA-, 46% (65/141) were DNA+/mRNA+ and 8.5% (12/141) were DNA+/mRNA-. The proportion of DNA+/mRNA+ specimens increased with the severity of the lesions (P<0.001). All normal cervix specimens were DNA-/mRNA-. Among grade 2 cervical intraepithelial neoplasia, prevalence of DNA was higher than that of mRNA: 41.6% (5/12) versus 25% (3/12), whereas it was 79.3% (46/58) versus 62% (36/58) among grade 3 cervical intraepithelial neoplasia. Full concordance was observed in cancers as all the 26 DNA+ specimens were mRNA+. Median overall HPV load was higher in DNA+/mRNA+ than in DNA+/mRNA- specimens (1.4110(6) vs. 9.110(2) copies per million cells, P<0.001). Both E6/E7 mRNA detection and concordant DNA+/mRNA+ detection increases with the severity of the lesions and with the HPV DNA load.


Beaufils N.,Assistance Publique des Hopitaux de Marseille APHM | Lassoued A.B.,Assistance Publique des Hopitaux de Marseille APHM | Essaydi A.,Assistance Publique des Hopitaux de Marseille APHM | Dales J.-P.,Assistance Publique des Hopitaux de Marseille APHM | And 5 more authors.
Leukemia Research | Year: 2012

Determination of T-cell clonality has an important additional value for diagnosis of T-cell lymphomas. Various molecular methods have been developed, including polymerase chain reaction (PCR) of T-cell receptor γ (TCRγ). The detection of PCR products usually relies commonly on either GeneScan (GS) analysis or heteroduplex (HD) analysis by polyacrylamide gel electrophoresis (PAGE). These techniques have their disadvantages, being relatively time-consuming and laborious or requiring expensive equipment. Here, we propose an alternative method that combines multiplex PCR and HD analysis by microcapillary electrophoresis (ME) on the Agilent 2100 Bioanalyzer. The sensitivity of the method was determined with clonal PEER T-cell line DNA dilution in polyclonal DNA and was evaluated as 1-5%. Fifty-three samples from patients with T-cell lymphoproliferative disorders were analyzed by HD analysis using ME and GS analyses. Comparison of the two techniques showed them to be highly concordant (93% similarity). The rate of clonality detection by GS analysis was higher than HD analysis by ME, but none of the discordant patients (n=5) has yet developed lymphoma. HD analysis by ME to reveal TCRγ gene rearrangements in clinical specimens was consistent with clinical data and the outcome of patients. Detection of T-cell clonality by HD analysis with ME is sensitive, practical, safe and represents a potential alternative to PAGE and GS analysis. © 2012 Elsevier Ltd.

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