Telomeres and Genomic Instability from Precancerous Lesions to Advanced Cancer – Understanding Through Ovarian Cancer

Genetic instability plays an important role in ovarian carcinogenesis. Genetic instability is one of the characteristics shared by most human cancers and seems to exist (at various levels) at all stages of the disease, from precancerous lesions to advanced cancer. It is possible that this instability is one of the first trigger events, which would facilitate the subsequent establishment of all the other cancer hallmarks. Telomere shortening appears to take place in most human preinvasive epithelial lesions: short telomeres are found in up to 88% of early precancerous conditions of the bladder, cervix, colon, esophagus, or prostate. However, little is known about ovarian carcinogenesis and telomere shortening. Recent evidence has shown that the fallopian tube may be the origin of ovarian cancer. A new tubal carcinogenic sequence has been described with precancerous lesions that could metastasize to the ovary and result in invasive ovarian cancer. In this review, we will describe the degree of telomere shortening and genomic instability (estimated by the expression of DNA damage response proteins, such as H2AX, Chk2, ATM, 53BP1, p53, and TRF2, and by array comparative genomic hybridization) in early preinvasive stages of ovarian cancer (serous tubal intraepithelial carcinoma (STIC)), ovarian high-grade serous carcinoma, and benign controls. Given that STICs have the shortest telomeres, they could be in a telomere crisis phase preceding genomic stabilization due to telomerase activation (see appended diagram). Concordant results were obtained in immunohistochemical and molecular studies. The expression of all DNA damage proteins increased from benign fallopian tubes to STICs suggesting an early activation of the DNA damage response (DDR) pathways in STICs and indicating that genomic instability may occur early in the precancerous lesions of high-grade serous ovarian cancer (HGSC). In this chapter, we propose to review current knowledge about the function of human telomeres and telomerase and their relevance in genomic instability in cancer and to focus on specific results for ovarian cancer

Risk Factors of Inadequate Colposcopy After Large Loop Excision of the Transformation Zone: A Prospective Cohort Study

International audienceObjective: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) inadequate colposcopy. Materials and Methods: From December 2013 to July 2014, a total of 157 patients who had a LLETZ performed for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. All procedures were performed using semicircular loops. The use of colposcopy made during each procedure was systematically documented. Dimensions and volume of LLETZ specimens were measured at the time of procedure, before formaldehyde fixation. All participants were invited for a follow-up colposcopy 3 to 6 months after LLETZ. Primary end point was the diagnosis of post-LLETZ inadequate colposcopy, defined by a not fully visible cervical squamocolumnar junction and/or cervical stenosis. Results: Colposcopies were performed in a mean (SD) delay of 136 (88) days and were inadequate in 22 (14%) cases. Factors found to significantly increase the probability of post-LLETZ inadequate colposcopy were a history of previous excisional cervical therapy [adjusted odds ratio (aOR) = 4.29, 95% CI = 1.12-16.37, p = .033] and the thickness of the specimen (aOR = 3.12, 95% CI = 1.02-9.60, p = .047). The use of colpos-copy for the guidance of LLETZ was statistically associated with a decrease in the risk of post-LLETZ inadequate colposcopy (aOR = 0.19, 95% CI = 0.04-0.80, p = .024) as the achievement of negative endocervical margins (aOR = 0.26, 95% CI = 0.08-0.86, p = .027). Conclusions: Although the risk of post-LLETZ inadequate colpos-copy is increased in patients with history of excisional therapy and with the thickness of the excised specimen, it could be reduced with the use of colposcopic guidance and the achievement of negative endocervical margins. L arge loop excision of the transformation zone (LLETZ) is a routine procedure worldwide, because it is the first-line treatment of high-grade intraepithelial lesion (HSIL) of the cervix. Quality criteria for optimal LLETZ include the completeness of excision with the achievement of negative margins, while producing the minimal excised volume and depth of excision to minimize subsequent obstetrical and neonatal morbidity. 1,2 Obtaining negative margins is important, because incomplete excision exposes women to a significant risk of posttreatment residual and/or recurrent disease, particularly when the lesion involves the endo-cervical canal. 3,4 However, this risk remains higher to the general female population, even when negative margins are achieved. Women who had had a LLETZ remain therefore exposed to a 3-to 4-fold increased risk of developing subsequent cervical cancer at least for 20 years. 5-8 Thus, prolonged and careful post-LLETZ follow-up is mandatory, whatsoever the margins status. For the last decade, the value of human papillomavirus testing has been demonstrated in this indication. Although a negative human papillomavirus test has now been admitted as the best test of cure for patients, colposcopy remains needed when this test is found to be positive. 9-12 Although being the key examination in this indication, the accuracy of colposcopy performed after previous excisional therapy of HSIL is however questionable because the healing process might result in changes in the appearance of the transformation zone (TZ). However, the main limitation of post-LLETZ colposcopic examination is the possibility of inadequate colposcopy due to the inability to visualize the entire TZ. Known risk factors for inadequate colposcopy include age, severity of lesion, and estrogen status of the patient. 13 However, inadequate colposcopy is also one of the main adverse effects of excisional therapies of the cervix, including LLETZ. 13 However, data on the precise risk factors for inadequate colposcopy after LLETZ are limited because most studies have focused on the sole risk of cervical stenosis without considering the position and visibility of the squamocolumnar junction. 14-17 This point is however crucial because it is clinically essential to identify how post-LLETZ inadequate colposcopy could be avoided, thus preserving the possibility for the follow-up of these women

ASSOCIATION RADIO-CHIRURGICALE DANS LE TRAITEMENT DU CANCER DU COL UTERIN DE PLUS DE 4 CM (A PROPOS D'UNE SERIE DE 95 PATIENTES OPEREES DANS LE SERVICE DE GYNECOLOGIE DE L'HOPITAL EDOUARD HERRIOT (PROFESSEUR DARGENT))

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Development of an Innovative Surgical Navigation System for Sacrospinous Fixation in Pelvic Surgery

STUDY OBJECTIVE: To validate the use of an innovative navigation method for sacrospinous fixation in surgery-like conditions as a new teaching tool and surgical method. DESIGN: Two-month experimental prospective pilot study between July and August 2021. SETTING: Biomechanics laboratory academic research. PATIENTS: A total of 29 participants took part in the study: 9 gynecological surgeons and 20 participants with no medical background. INTERVENTIONS: All participants used the 2 mocks-up. MEASUREMENTS AND MAIN RESULTS: The experiment was composed of 2 training phases dedicated to improving the hand-eye coordination and suture skills on a training mock-up and of a suturing phase on a pelvic mock-up designed to recreate the surgery-like conditions of a sacrospinous fixation. The surgeons provided qualitative feedback on the bio-accuracy of the mock-ups and evaluated the ease of use of the navigation software. Nonsurgeons were included to assess the progression of the suture performance between 2 experiments performed 1 week apart (session 1 and 2). The main objective for participants was to reach a virtual target and to stitch sacrospinous ligaments. For session 1, an overall comfort score of 7.2 of 10 was attributed to the tool; 14 (42%) surgeon suture attempts and 63 (65%) nonsurgeon suture attempts were accurate (i.e., below the 5-mm threshold). Twenty-two (67%) surgeon suture attempts and 28 (34%) nonsurgeon suture attempts were fast (i.e., in the first 2 quantiles of the duration dataset). An improvement in the nonsurgeon performance was observed between the 2 sessions in terms of duration (session 1: 46 ± 20 s; session 2: 37 ± 18 s; p=.047) and distance (session 1: 3.8 ± 1.3 mm; session 2: 3.2 ± 1.4 mm; p=10-5) for the last suturing exercise. CONCLUSION: This new motion capture-based navigation method for sacrospinous fixation tested under surgery-like conditions seemed to be accurate and effective. The next step will be to design a pelvis model more adapted to the constraints of a sacrospinous fixation and to validate the benefits of this method compared with current techniques

Ovarian torsion in a twin pregnancy at 32 weeks and 6 days: A case-report

BACKGROUND: Ovarian torsion during pregnancy is a rare event and occurs mostly during the first trimester. This is the first case describing the diagnosis and management of an ovarian torsion at 33 weeks in a twin pregnancy with a normal term delivery. CASE SUMMARY: The patient presented with irregular uterine contraction due to an acute abdominal pain in the right iliac fossa. A cyst was discovered during the ultrasound scan on the right ovary and a torsion was highly suspected. A small laparotomy facing the ovarian mass after an ultrasound guidance was chosen. The patient finally delivered at 37 weeks. CONCLUSION: The clinic holds a preponderant place in the diagnosis of ovarian torsion. Our surgical approach by laparotomy under ultrasound guidance was less risky than by laparoscopy

Biomécanique et physiologie des cystocèles, simulations de la chirurgie prothétique des cystocèles.

National audienc

Simultaneous bilateral tubal ectopic pregnancy after intracytoplasmic sperm injection and embryo transfer, in a patient with Stage 3 endometriosis

Introduction: The incidence of extrauterine pregnancy increases to 2â12% following in vitro fertilizationâembryo transfer. Several pathogenic theories have been suggested, including abnormal hormonal secretion or exogenous hormones administered in assisted reproductive technology (ART). Case report: A 32-year-old nulliparous woman with primary infertility and Stage 3 endometriosis was treated by ART with intracytoplasmic sperm injection and embryo transfer. The patient showed simultaneous bilateral extrauterine pregnancy, managed by laparoscopic salpingectomy. Discussion: The various possible pathophysiological mechanisms are described, with a review of the literature on simultaneous bilateral extrauterine pregnancy following ART. In pregnancies following ART, ectopic pregnancy should always be screened for by serum β-human chorionic gonadotropin monitoring and transvaginal ultrasound until the implantation site can be confirmed as the incidence is higher than in spontaneous pregnancy. Even if serum β-human chorionic gonadotropin concentration increases normally, possible bilateral ectopic pregnancy should always be investigated if no intrauterine gestational sac can be seen. Keywords: bilateral ectopic pregnancy, embryo transfer, endometriosis, in vitro fertilization, intracytoplasmic sperm injectio

Modélisation des différentes techniques chirurgicales.

National audienc

Mobility and stress analysis of different surgical simulations during a sacral colpopexy, using a finite element model of the pelvic system

International audienc

Glue mesh fixation in laparoscopic sacrocolpopexy: results at 3years' follow-up

INTRODUCTION AND HYPOTHESIS: We assessed 3-year anatomic and functional results using synthetic glue to fix mesh in laparoscopic sacrocolpopexy.METHODS: Prospective multicenter cohort study in three academic urogynecology departments. Seventy consecutive patients with stage ? 3 POP-Q (Pelvic Organ Prolapse Quantification) anterior and/or apical prolapse underwent laparoscopic sacrocolpopexy using synthetic surgical glue to fix anterior and posterior meshes to the vagina. Patients were followed up at 1, 2 and 3years. Primary outcome was anterior and apical anatomic success (POP-Q stage ? 1) at 3years. Secondary outcomes comprised functional results (international quality of life and sexuality scales), mesh-related morbidity and urinary incontinence at 3years.RESULTS: Mean age was 56.7?±?1.2years. Mean follow-up was 43months. Anterior compartment anatomic success rate was 87% at 2years (Ba, -2.4cm; p