[Notice of expert for modality and prescriptions limits of local estrogenotherapy for urinairy inconfinence in women]. / Avis d'experts sur les modalités et limites de prescription des estrogènes locaux dans l'incontinence urinaire chez la femme.

OBJECTIVE: To develop a consensus of experts on the use of local estrogens in female urinary incontinence. MATERIAL AND METHOD: Following a formalized consensus method (DELPHI), a questionnaire was produced and sent to a first round and then to a second round of experts. The questionnaire consisted of proposals for recommendations for the use of local estrogens in the context of female urinary incontinence. The Survey Monkey® survey software allowed the questionnaire to be distributed and the answers obtained to be analyzed. RESULTS: Eight experts responded to the first round questionnaire. Seven formulations were deleted, 3 amended and 4 added to the first round questionnaire following expert advice. Twenty-six experts replied to the second round questionnaire, 24 of which were complete. Ten of the 21 proposals were approved at more than 80%, including five with strong agreement regarding the recognized benefit of local estrogens in urinary incontinence due to overactive bladder, the absence of data from the literature to demonstrate over-risk of hormone-dependent cancer under local estrogens and the need for follow-up of patients under this treatment. Six proposals were not the subject of a consensus and concerned the prescription modalities (maximum duration, effective minimum dose, prescription before surgery for incontinence). CONCLUSION: Although local estrogens did not have regulatory approval in urinary incontinence, more than 80% of these experts recognized their benefit in the management of urinary incontinence in women with vulvo-vaginal atrophy, particularly in the case of urinary urge incontinence. LEVEL OF PROOF: 4.

In vivo confocal laser endomicroscopy during laparoscopy for gynecological surgery: A promising tool.

INTRODUCTION: To investigate the technical feasibility of optical biopsy (probe-based confocal laser endomicroscopy [pCLE]) during laparoscopy and by the vaginal route in the exploration of pelvic gynecological cancers. METHODS: Prospective study including 31 patients undergoing laparoscopic hysterectomy (benign or malignant indication). Confocal microlaparoscopy (analysis of tubes, ovaries, and depending on the type de cancer, pelvic adenopathies) and optical biopsy of the endometrium were first carried out by the vaginal route under general anesthesia. The surgical procedure was then carried out. RESULTS: Thirty-one consecutive patients were included (16 for benign hysterectomy, 12 for endometrial cancer and 3 for ovarian carcinoma). pCLE offered dynamic pictures that were correlated with the histopathological images. DISCUSSION AND CONCLUSION: pCLE provides high resolution imaging of cancerous and benign tissues in real-time similar to histopathological results. Both feasibility and safety were confirmed.

[Lucy's cancer(s): A prehistorical origin?] / Le(s) cancer(s) de Lucy : une origine préhistorique ?

OBJECTIVES: The recent discovery of the earliest hominin cancer, a 1.7-million-year-old osteosarcoma from South Africa has raised the question of the origin of cancer and its determinants. We aimed to determine whether malignant and benign tumors exist in the past societies. METHODS: A review of literature using Medline database and Google about benign and malignant tumors in prehistory and antiquity. Only cases with morphological and paraclinical analysis were included. The following keywords were used: cancer; paleopathology; malignant neoplasia; benign tumor; leiomyoma; myoma; breast cancer; mummies; soft tissue tumor; Antiquity. RESULTS: Thirty-five articles were found in wich there were 34 malignant tumors, 10 benign tumors and 11 gynecological benign tumors. CONCLUSIONS: The fact that there were some malignant tumors, even few tumors and probably underdiagnosed, in the past may be evidence that cancer is not only a disease of the modern world. Cancer may be indeed a moving target: we have likely predisposing genes to cancer inherited from our ancestors. The malignant disease could therefore appear because of our modern lifestyle (carcinogens and risk factors related to the modern industrial society).

[Current surgical practice of prophylactic and opportunistic salpingectomy in France]. / État des lieux de la salpingectomie prophylatique en France.

OBJECTIVES: Since the recent evidence of a tubal origin of most ovarian cancers, opportunistic salpingectomy could be discussed as a prophylactic strategy in the general population and with hereditary predisposition. We aimed to survey French gynecological surgeons about their current surgical practice of prophylactic salpingectomy. METHODS: An anonymous online survey was sent to French obstetrician-gynaecologists and gynecological surgeons. There were 13 questions about their current clinical practice and techniques of salpingectomy during a benign hysterectomy or as a tubal sterilization method, salpingectomy versus salpingo-oophorectomy in the population with genetic risk, salpingectomy in relationship with endometriosis and questions including histopathological considerations. RESULTS: Among the 569 respondents, opportunistic salpingectomy was always performed between 42.48% and 43.44% during laparoscopic, laparoscopic-assisted vaginal or laparotomic hysterectomy and only 12.26% in case of vaginal route. In the genetic population, salpingo-oophorectomy was mainly performed. Tubal sterilization was often practiced by the hysteroscopic route. More than 90% of respondents didn't perform salpingectomy in case of endometriosis. There was not any specific tubal histopathological protocol in 71.54% of cases. CONCLUSIONS: Salpingectomy may be a preventing strategy in the low- and high-risk population. The survey's responses show that salpingectomy seems to be a current practice during benign hysterectomy for more than 40% doctors. However, there is not any change with no more salpingectomy in the population with genetic risk, or in case of endometriosis or tubal sterilization.

[Is endometriosis a precancerous lesion? Perspectives and clinical implications]. / L'endométriose est-elle une lésion pré-cancéreuse ? Perspectives et implications cliniques.

Epidemiological studies have shown a relationship between endometriosis and clear cell/endometrioid ovarian cancers (named "Endometriosis Associated Ovarian Cancer" or EAOC). The recent discovery of signaling pathways (especially the SWI/SNF and PI3K/AKT/mTOR pathways) that linked endometriosis and EAOC could lead to the development of specific biomarkers as ARID1A to screen benign to premalignant endometriosis and to new targeted treatment. Moreover, the better understanding of the pathogenesis of the epithelial ovarian cancer arising from the Fallopian tube could allow new early prevention strategies that will be described in this review.

[Feasibility of opportunistic salpingectomy at the time of vaginal hysterectomy for benign pathology and evaluation of occult tubal lesions prevalence: Preliminary study]. / Faisabilité de la salpingectomie prophylactique lors d'une hystérectomie d'indication bénigne par voie vaginale et évaluation de la prévalence des lésions tubaires occultes : étude préliminaire.

AIM: To assess the feasibility of prophylactic salpingectomy during vaginal hysterectomy for benign pathology and the prevalence of occult tubal lesions. MATERIALS AND METHODS: In this prospective study from 09/01/2013 to 11/01/2014, patients who underwent vaginal hysterectomy with salpingectomy or salpingo-oophorectomy were included. The prevalence of bilateral salpingectomy with or without ovariectomy and the prevalence of histopathological and immunohistochemical (p53 expression) abnormalities were evaluated. RESULTS: Bilateral salpingectomy was performed in 51/69 patients (73.9%). An elevated BMI was statistically associated with a failure of the salpingectomy (29.4 vs 25.8; P=0.01). There was only one case of postoperative hemorrhage in the salpingectomy group. On the 51fallopian tubes, there were 4 (12.9%) immunohistochemical abnormalities "p53 signature". CONCLUSION: The recent tubal origin of most ovarian cancer cases raised the question of the prophylactic salpingectomy in the population with genetic risk as well as in the general population. Bilateral salpingectomy may be performed during vaginal hysterectomy. However caution is needed because we do not know what is the exact evolution of the p53 signatures.

A randomized controlled trial comparing anatomical and functional outcome between vaginal colposuspension and transvaginal mesh.

INTRODUCTION AND HYPOTHESIS: Our aim was to compare anatomical and functional outcome between vaginal colposuspension and transvaginal mesh. METHODS: This was a prospective randomized controlled trial in a teaching hospital. Sixty-eight women with stage ≥3 anterior vaginal wall prolapse according to the Pelvic Organ Prolapse Quantification (POP-Q) system were assessed, randomized, and analyzed. Patients were randomized to anterior colporrhaphy with vaginal colposuspension (n = 35) or transvaginal mesh (n = 33). Primary outcome was objective cure rate of the anterior vaginal wall, defined as POP-Q ≤1 at 2 years. Secondary outcomes were functional results, quality-of-life (QoL) scores, mesh-related morbidity, and onset of urinary incontinence. RESULTS: The anatomical result for point Ba was significantly better at 2 years in the mesh group (-2.8 cm) than in the colposuspension group (-2.4 cm) (p = 0.02). Concerning POP-Q stages, the anatomical success rate at 2 years was 84.4 % for colposuspension and 100 % for mesh (p = 0.05). There were 5 anatomic recurrences (15.6 %) in the colposuspension group. The erosion rate was 6 % (n = 2). No significant difference was noted regarding minor complications. Analysis of QoL questionnaires showed overall improvement in both groups, with no significant difference between them. CONCLUSIONS: The vaginal colposuspension technique of anterior vaginal wall prolapse repair gave good anatomical and functional results at 2 years. Transobturator vaginal mesh gave better 2-year anatomical results than vaginal colposuspension, with overall improvement in QoL in both groups.

Small molecule sensitization to TRAIL is mediated via nuclear localization, phosphorylation and inhibition of chaperone activity of Hsp27.

The small chaperone protein Hsp27 confers resistance to apoptosis, and therefore is an attractive anticancer drug target. We report here a novel mechanism underlying the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitizing activity of the small molecule LY303511, an inactive analog of the phosphoinositide 3-kinase inhibitor inhibitor LY294002, in HeLa cells that are refractory to TRAIL-induced apoptosis. On the basis of the fact that LY303511 is derived from LY294002, itself derived from quercetin, and earlier findings indicating that quercetin and LY294002 affected Hsp27 expression, we investigated whether LY303511 sensitized cancer cells to TRAIL via a conserved inhibitory effect on Hsp27. We provide evidence that upon treatment with LY303511, Hsp27 is progressively sequestered in the nucleus, thus reducing its protective effect in the cytosol during the apoptotic process. LY303511-induced nuclear translocation of Hsp27 is linked to its sustained phosphorylation via activation of p38 kinase and MAPKAP kinase 2 and the inhibition of PP2A. Furthermore, Hsp27 phosphorylation leads to the subsequent dissociation of its large oligomers and a decrease in its chaperone activity, thereby further compromising the death inhibitory activity of Hsp27. Furthermore, genetic manipulation of Hsp27 expression significantly affected the TRAIL sensitizing activity of LY303511, which corroborated the Hsp27 targeting activity of LY303511. Taken together, these data indicate a novel mechanism of small molecule sensitization to TRAIL through targeting of Hsp27 functions, rather than its overall expression, leading to decreased cellular protection, which could have therapeutic implications for overcoming chemotherapy resistance in tumor cells.

[High-level HCG in non-gravidic situations: About two cases]. / Élévation de l'HCG en dehors d'un contexte gravidique : à propos de deux cas.

Ovarian dysgerminoma is the most common germinal tumor in women; however, a lot of different symptoms can lead to its diagnosis. In the two cases reported here, misdiagnosis of ectopic pregnancy was first done because of inappropriate secretion of HCG by the tumor. These two cases point out the particularity of dysgerminoma with its various secretion capacity. Conversely, facing a raised level of HCG in non-gravidic situation, physicians have to consider different gynaecological and extragynaecological hypothesis.