Gautier Chene

Early Telomere Shortening and Genomic Instability in Tubo-Ovarian Preneoplastic Lesions

Purpose: Genetic instability plays an important role in ovarian carcinogenesis. We investigated the level of telomere shortening and genomic instability in early and preinvasive stages of ovarian cancer, serous tubal intraepithelial carcinoma (STIC), and tubo-ovarian dysplasia (TOD). Experimental Design: Fifty-one TOD from prophylactic salpingo-oophorectomies with BRCA1 or 2 mutation, 12 STICs, 53 tubo-ovarian high-grade serous carcinoma, and 36 noncancerous controls were laser capture microdissected from formalin-fixed, paraffin-embedded sections, analyzed by comparative genomic hybridization (array CGH) and for telomere length (using quantitative real-time PCR based on the Cawthons method). TOD and STICs were defined by morphologic scores and immunohistochemical expressions of p53, Ki67, and γH2AX. Results: TOD showed marked telomere shortening compared with noncancerous controls (P < 10−7). STICs had even shorter telomeres than TOD (P = 0.0008). Ovarian carcinoma had shorter telomeres than controls but longer than STICs and dysplasia. In TOD, telomeres were significantly shorter in those with BRCA1 mutation than in those with BRCA2 mutation (P = 0.005). In addition, γH2AX expression in TOD and STIC groups with short telomeres was significantly increased (P < 10−7). In dysplastic epithelium, we found subtle genomic alterations, in contrast to more important genomic imbalances in STICs. The total number of genetic alterations was the highest in ovarian cancers. Conclusions: These findings suggest that genetic instability occurs in early stages of ovarian tumorigenesis. STICs and noninvasive dysplasia are likely an important step in early serous ovarian neoplasia. Clin Cancer Res; 19(11); 2873–82. ©2013 AACR.

Facteurs de risque d’exposition de prothèse dans les cures de prolapsus génital par voie vaginale

OBJECTIVES We analysed the risk factors of vaginal surgery of pelvic organ prolapse with non resobable prothesis. PATIENTS AND METHODS This is a continuous, retrospective study of the 208 patients who had surgery between 2003 and 2007. Depending on the localisation of the prolapse, they had a prothesis under the bladder and/or a posterior tape through the sacrospinous ligament. An hysterectomy and a levator myorraphy were done if necessary. RESULTS After a 3 years follow-up, we found 16.8% mesh exposure (23% were treated by a conservative way). The highest rate of incidence was at 4 and 10 months. The independent risk factors of exposure were the kind of prothesis, age under 60 and concomitant hysterectomy. Women treated by vaginal estrogens and those operated by the most experienced surgeon had less exposure. We had 5% of complications during the surgery. DISCUSSION AND CONCLUSION Hysterectomy, kind of prothesis and inverted T colpotomy of Crossen are well known risk factors. Age, stage of prolapse, size of prothesis and surgeon experience are discussed. Vaginal surgery of pelvic organ prolapse with non resobable prothesis must be used only when prolapse stage is higher than 3, hysterectomy has to be avoid and vaginal estrogens must be prescribed.

Early Preinvasive Lesions in Ovarian Cancer

Faced with the catastrophic prognosis for ovarian cancer due to the fact that it is most often diagnosed late at the peritoneal carcinomatosis stage, screening and early detection could probably reduce the mortality rate. A better understanding of the molecular characteristics of the different ovarian cancer subtypes and their specific molecular signatures is indispensable prior to development of new screening strategies. We discuss here the early natural history of ovarian cancer and its origins.

Is There a Relationship between Ovarian Epithelial Dysplasia and Infertility

Aim. Ovarian epithelial dysplasia was initially described in material from prophylactic oophorectomies performed in patients at genetic risk of ovarian cancer. Similar histopathological abnormalities have been revealed after ovulation stimulation. Since infertility is also a risk factor for ovarian neoplasia, the aim of this study was to study the relationship between infertility and ovarian dysplasia. Methods. We blindly reviewed 127 histopathological slides of adnexectomies or ovarian cystectomies according to three groups—an exposed group to ovulation induction (n = 30), an infertile group without stimulation (n = 35), and a spontaneously fertile control group (n = 62)—in order to design an eleven histopathological criteria scoring system. Results. The ovarian dysplasia score was significantly higher in exposed group whereas dysplasia score was low in infertile and control groups (resp., 8.21 in exposed group, 3.69 for infertile patients, and 3.62 for the controls). In the subgroup with refractory infertility there was a trend towards a more severe dysplasia score (8.53 in ovulation induction group and 5.1 in infertile group). Conclusion. These results raise questions as to the responsibility of drugs used to induce ovulation and/or infertility itself in the genesis of ovarian epithelial dysplasia.

Échelle d’évaluation de la dysplasie épithéliale de l’ovaire

INTRODUCTION Precancerous ovarian epithelial dysplasia was first described after prophylactic oophorectomy (OP) for genetic risk (BRCA mutation) or because of a strong family history of ovarian and/or breast cancer. The objective of this study was to describe histopathological features of ovarian dysplasia and to propose a dysplasia scoring sheme with a cut-off. PATIENTS AND METHOD One hundred and twenty-five bilateral oophorectomies (genetic predisposition: n=35 and control group: n=90) were reviewed by two pathologists blinded to clinical data. Eleven epithelial cytological and architectural features were studied and an ovarian dysplasia score was defined to compare the degree of ovarian epithelial abnormalities between the two groups. RESULTS Mean ovarian dysplasia score was significantly higher in prophylactic oophorectomy group than in control group (9.0 versus 3.5, P<0.001). Dysplasia was more severe in OP with BRCA mutation than in OP without (11.6 in BRCA 1; 7.6 in BCRA 2; 7.1 in family history). The cut off for dysplasia was 8 with a sensitivity of 60% and a specificity of 93.3%. CONCLUSION The increased dysplasia score in OP and the gradation in dysplastic severity in OP with proven BRCA mutations may suggest that ovarian dysplasia could be a pre-malignant non invasive histopathological lesion. The 11 cytological and architectural features in the dysplasia scoring sheme could be a useful tool to study ovarian dysplasia.

N’oubliez pas les trompes ! Étude morphologique et immunohistochimique des trompes à risque génétique (mutation BRCA)

OBJECTIVES The objective of this study was to describe morphologic and immunohistochemical features of precursor tubal lesions in prophylactically removed Fallopian tubes. PATIENTS AND METHODS Hundred and forty-seven bilateral salpingectomies (genetic predisposition or group A: n=57; and control group or group B: n=90) were reviewed by two pathologists blinded to clinical data. Seven epithelial cytological and architectural features were studied to compare the degree of tubal epithelial abnormalities between the two groups. Immunohistochemical expression patterns of Ki67 and p53 were also evaluated. RESULTS Serous tubal intraepithelial lesions (STIL) have been identified in group A with stronger expression for Ki67 and p53 (especially in BRCA 1 group) than in group B. DISCUSSION AND CONCLUSION The current results show the importance of salpingo-oophrectomy in BRCA mutation carriers and the complete histopathological sampling of the Fallopian tubes.

[Are there anatomical and clinical correlations between minimal and deep endometriosis? First results of Auvergne's Registry of Endometriosis].

OBJECTIVE With a prospective study, to evaluate the existence of two distinct clinical diseases in the endometriosis syndrome, by comparing pain symptoms and quality of life from patients with minimal endometriosis (AFS-R<5) and data from patients with severe disease (deep infiltrating nodules and/or ovarian endometrioma). PATIENTS AND METHODS Patients with minimal disease (group A with AFS-R<5) and severe endometriosis (group B) are selected from the Auvergne Endometriosis Registry which started in January 2004. They have never been treated before for endometriosis. A surgical laparoscopic and a pathological diagnosis are required for the subjects to be included. Pelvic pain is assessed using a standardized questionnaire, and a visual analogue scale, quality of life using SF-36. The two groups are compared for the incidence and the severity of pelvic pain and for the impairment of their quality of life. RESULTS Forty-seven patients have a minimal disease, whereas 111 have a severe endometriosis. Demographic characteristics are similar in both groups. Quality of life (SF-36) and pelvic pains included chronic pelvic pain, dyspareunia, dysuria, and defecation disorders are as common and severe in both groups. However, dysmenorrhea is more affected in group B than in group A (p=0.03). DISCUSSION AND CONCLUSION We find no relationship between severity of symptoms, quality of life, and the extent of endometriotic lesions at surgery. There would be no differences between minimal and severe disease. It could be explained by different painful mechanisms between minimal and severe endometriosis.

Female urinary incontinence and intravaginal electrical stimulation: an observational prospective study☆

OBJECTIVE To assess the efficacy of intravaginal electrical stimulation in the management of female urinary incontinence. STUDY DESIGN 359 Women with urinary incontinence (207 with stress incontinence [group A], 33 with urge incontinence [group B] and 119 with mixed urinary incontinence [group C]) were included in this multicenter prospective observational study. Patients were managed by home intravaginal electrical stimulation of the pelvic floor for 20-30 min per day, 5 days a week, for a period of 10 weeks. Identical clinical assessments were performed before and after pelvic floor rehabilitation, comprising a voiding diary and validated symptom and quality of life scores. RESULTS Objective assessment demonstrated an overall cure rate of 63.5% (228/359): 65.7% (136/207) for group A, 57.6% (19/33) for group B, and 61.3% (73/119) for group C. The overall significant improvement rate was 15.6% (56/359): 14.6% (30/207) for group A, 24.2% (8/33) for group B and 15.1% (18/119) for group C. All domains of quality of life were significantly improved after pelvic floor muscle training (p<0.0001) with a patient satisfaction rate of 83.6%. Treatment was well tolerated with 1.4% (5/359) of patients describing pain at the highest stimulation intensities. No significant difference was observed between the various types of electrodes used (p<0.0001). CONCLUSION The quantitative and qualitative efficacy in terms of social and psychological consequences and quality of life of home pelvic floor muscle training stimulators probably make this treatment modality one of the first-line treatments for female stress urinary incontinence.

La cancérogenèse ovarienne : théories actuelles et passées

Ovarian carcinogenesis and the early stages of malignant transformation are limited because of the lack of a candidate precursor. There have been several proposed hypotheses: first, ovary and the ovarian surface epithelium and more recently observations have increasingly focused attention of the Fallopian tube. Moreover, molecular genetic analysis has designed two main pathways of tumorogenesis. In this review, we discuss the different and perhaps complementary hypotheses about ovarian carcinogenesis.

Three-dimensional sonographic diagnosis of abdominal wall endometriosis: a useful tool?

OBJECTIVE To report the usefulness of three-dimensional (3D) ultrasonography for the assessment of parietal endometriosis. DESIGN Case report. SETTING Academic research hospital. PATIENT(S) A 35-year-old woman with a noncyclic, painful abdominal nodule near a caesarean delivery scar. INTERVENTION(S) 3D ultrasonography and wide surgical resection with healthy margins. MAIN OUTCOME MEASURE(S) 3D ultrasonographic assessment of the endometriotic nodule. RESULT(S) We found that 3D ultrasonography offered a more specific description of parietal endometriosis with irregular and spiculated margins and depth infiltration as well as provided preoperative evaluation of volume measurements. CONCLUSION(S) Three-dimensional ultrasonography is a useful, noninvasive tool in extrapelvic endometriosis.