Gemma Mancebo

Treatment of endometrial hyperplasia without atypia in peri- and postmenopausal women with a levonorgestrel intrauterine device.

Objective: To assess the effectiveness of the Mirena levonorgestrel-releasing intrauterine system (LNG-IUS) in peri- and postmenopausal women with endometrial hyperplasia without atypia. Design: All consecutive women with histologically documented endometrial hyperplasia without atypia recruited during a 1-year period participated in an open, prospective, single-center study. They were followed for at least 2 years after levonorgestrel-releasing intrauterine system insertion. The pattern of uterine bleeding was evaluated on a 4-point qualitative scale (1 = amenorrhea, 2 = scarce, 3 = normal, 4 = abundant). Results: The study population consisted of 15 women with a mean (SD) age of 49 (2.7) years. Compared with baseline, bleeding decreased quantitatively from a mean score of 3 at baseline (normal bleeding) to 2 (scarce) at 3and 6 months, and 1 (amenorrhea) at 24 months. Endometrial biopsies performed at 12 months revealed atrophicendometrium in 14 women (93.3%) and secretory endometrium in 1 (6.7%) (P < 0.001). At 24 months, endometrial atrophy was documented in 100% of women. Conclusions: The levonorgestrel-releasing intrauterine system seems to be an effective and safe alternative in the treatment of peri- and postmenopausal women with (simple) endometrial hyperplasia without atypia.

L1CAM expression in endometrial carcinomas: an ENITEC collaboration study

Background:Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas.Methods:The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated.Results:In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs.Conclusions:The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied.

Human papillomavirus detection in urine samples: an alternative screening method.

Objectives. To investigate the usefulness of human papillomavirus detection in the urine of women with poor gynecologic attention. Materials and Methods. Fifty urine and 50 cervical samples from 50 women were analyzed. Polymerase chain reaction was performed on these 100 samples using consensus primers and a low-density microarray-based method for human papillomavirus typing. Results. The concordance of the results between both sample groups was 80%. In the urine samples, the sensitivity of polymerase chain reaction for high-grade squamous intraepithelial lesion was 100%, the specificity was 80%, the positive predictive value was 91%, and the negative predictive value was 100%. Conclusions. Human papillomavirus detection in urine samples may be used as an alternative screening method for women with poor gynecologic attention.

Feasibility of a new two-step procedure for office hysteroscopic resection of submucous myomas: results of a pilot study

OBJECTIVE To assess the feasibility of a new two-step technique for office hysteroscopic resection of submucous myomas. STUDY DESIGN Between January 2010 and December 2011, all consecutive patients of reproductive age with symptomatic lesions sonographically diagnosed as single mainly intracavitary (G1 or G2) myoma ≤4.0 cm were eligible to participate in a prospective study. They underwent a two-step hysteroscopic procedure, which included preparation of partially intramural myomas with incision of the endometrial mucosa and the pseudocapsule covering the myoma in the first step, and excision of the myoma by means of diode laser four weeks later. All procedures were performed on an outpatient basis and without anesthesia. RESULTS A total of 43 women (mean age 36.7 years) were included. The two-step myomectomy technique was successfully performed in 34 (79.1%) patients. All myomas ≤18 mm were successfully enucleated as compared with 85% of 19-30 mm, and 0% of ≥30 mm (P<0.001). Also, myomas located in the anterior/posterior walls and those located in the fundus/lateral walls were enucleated in 87.9% and 50% of cases, respectively (P=0.020). Success of surgery was not influenced by the initial type of myoma. CONCLUSION The new two-step hysteroscopic myomectomy carried out as an outpatient procedure and without anesthesia is feasible for the excision of symptomatic submucous fibroids.

Hpv Determination in the Control After Leep Due to Cin Ii-iii: Prospective Study and Predictive Model

To evaluate the usefulness of the endocervical cytology immediately after loop electrosurgical excision procedure (LEEP) and viral human papilloma virus (HPV) determination as predictive factors of persistence/recurrence (P/R) of squamous intraepithelial lesion (SIL) in the remaining cervix of patients treated with LEEP due to cervical intraepithelial neoplasia (CIN) II or III. We retrospectively selected 105 samples from 100 patients with histologic diagnosis of CIN II-III with cytology immediately after LEEP with a first control post-LEEP between 2 and 6 months after treatment that included HPV determination, a minimal follow-up period of 12 months and maximum of 24 months, and at least 2 colpocytologic controls post-LEEP. In 71 of the 105 patients (67.6%), the determination was negative, finding the presence of HPV in 34 patients (32.4 %). Almost two-thirds of the patients had negative endocervical cytology and absence of HPV. During the follow-up, 20 P/R were detected, 16 (15.2%) of them being high-grade squamous intraepithelial lesions (7 CIN II and 9 CIN III). The combination of endocervical cytology and HPV determination in the remaining cervix seems to be a good strategy to predict the risk of SIL after conization. The probability of P/R can be estimated based on the results of these 2 variables. The negativity of HPV determination together with a negative endocervical cytology guarantees enough security and a favorable evolution.

Nidogen 1 and Nuclear Protein 1: novel targets of ETV5 transcription factor involved in endometrial cancer invasion

Endometrial cancer is the most frequent malignancy of the female genital tract in western countries. Our group has previously characterized the upregulation of the transcription factor ETV5 in endometrial cancer with a specific and significant increase in those tumor stages associated with myometrial invasion. We have shown that ETV5 overexpression in Hec1A endometrial cancer cells induces epithelial to mesenchymal transition resulting in the acquisition of migratory and invasive capabilities. In the present work, we have identified Nidogen 1 (NID1) and Nuclear Protein 1 (NUPR1) as direct transcriptional targets of ETV5 in endometrial cancer cells. Inhibition of NID1 and NUPR1 in ETV5 overexpressing cells reduced cell migration and invasion in vitro and reduced tumor growth and dissemination in an orthotopic endometrial cancer model. Importantly, we confirmed a significant increase of NUPR1 and NID1 protein expression in the invasion front of the tumor compared to their paired superficial zone, concomitant to ETV5 overexpression. Altogether, we conclude that NID1 and NUPR1 are novel targets of ETV5 and are actively cooperating with ETV5 at the invasion front of the tumor in the acquisition of an invasive phenotype to jointly drive endometrial cancer invasion.

Human papillomavirus detection and p16INK4a expression in cervical lesions: a comparative study

p16(INK4a) expression in dysplastic cervical lesions is related to high-risk human papillomavirus (HR-HPV) infection. The immunohistochemical expression of this protein in these lesions allows an increase in diagnostic reproducibility in biopsies and the introduction of prognostic factors in low-grade lesions. Here, we studied the immunohistochemical expression of p16 in 86 dysplastic cervical lesions, 54 cervical intraepithelial neoplasms-grade 1 (CIN-I), 23 CIN-II, and 9 CIN-III. In addition, we performed HPV detection and genotyping. We detected HR-HPV in 19/54 CIN-I, 21/23 CIN-II and 9/9 CIN-III cases. p16(INK4a) immunoreactivity was observed in 7/19 CIN-I HR-HPV-positive, 17/21 CIN-II HR-HPV-positive and all CIN-III cases. Immunoreactivity for p16(INK4a) was found in 7/54 CIN-I and in 17/23 CIN-II cases. In the follow-up, we detected 3 p16-positive high-grade squamous epithelial lesions (CIN-II and CIN-III) in the CIN-I/p16-negative group and 5 p16-positive high-grade squamous epithelial lesions cases in the CIN-II/p16-negative group. We conclude that p16 negativity in CIN-I and CIN-II biopsies does not always imply regression of the lesion and that the diagnosis of CIN-II should not be based solely on p16 results.

Usefulness of p16(INK4a) staining for managing histological high-grade squamous intraepithelial cervical lesions.

p16INK4a (p16) tumor-suppressor protein is a biomarker of human papillomavirus (HPV) oncogenic activity that has revealed a high rate of positivity in histological high-gade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN2) lesions. However, there is a paucity of data regarding p16 status as a surrogate marker of HSIL/CIN2 evolution. The aim of this study was to evaluate the outcome of HSIL/CIN2 patients followed up without treatment for 12 months according to p16 immunohistochemical staining. Patients diagnosed with HSIL/CIN2 colposcopy-directed biopsy, were recruited prospectively between December 2011 and October 2013. p16 staining was performed in all HSIL/CIN2 diagnostic biopsies. Follow-up was conducted every 4 months by cytology, colposcopy and biopsy if suspicion of progression and once the 12 months of follow-up completed. Complete regression, partial regression, persistence, and progression rates of HSIL/CIN2 were defined as a final outcome. A total of 96 patients were included in the analysis. The rate of spontaneous regression was 64%, while 28% had persistent disease, and 8% progressed at 12 months of follow-up. p16 was positive in 81 (84%) initial HSIL/CIN2 biopsies. Regression was observed in all 15 p16 negative cases and in 46 of 81 (57%) p16 positive cases (P=0.001). In conclusion, patients with p16 negative HSIL/CIN2 biopsy had a high rate of regression during first 12 months of follow-up. Status of p16 staining could be considered for HSIL/CIN2 management.

Endometrial Preparation With Desogestrel Before Essure Hysteroscopic Sterilization: Preliminary Study

STUDY OBJECTIVE To assess the effect of desogestrel on endometrial preparation for transcervical sterilization using the Essure device. DESIGN Prospective nonrandomized clinical study (Canadian Task Force classification II-3). SETTING Acute-care university-affiliated hospital in Barcelona, Spain. PATIENTS Women undergoing sterilization using the Essure device between January 2010 and January 2011. INTERVENTIONS Participants were offered desogestrel, 75 μg/d, for 6 weeks before the procedure. Sixteen who accepted were included in the desogestrel group, and 18 who refused were allocated to the no-treatment group. Endometrial biopsy samples were also obtained. MEASUREMENTS AND MAIN RESULTS In women who received desogestrel, decidual transformation was observed in eight, glandular atrophy in three, and proliferative endometrium in five. In the no-treatment group, two women had menstruation, nine had proliferative endometrium, and seven had secretory endometrium. In the desogestrel group, the procedure was successful in all women. In the no-treatment group, the procedure was cancelled in two women because of menstruation and in four women with secretory endometrium in whom the tubal ostia were difficult to visualize because of endometrial thickness and bleeding. The median (interquartile range, 25th-75th percentile) duration of the procedure was shorter in the desogestrel group than in the no-treatment group (7 [6-7] minutes vs 8 [7-12] minutes; p = .002). CONCLUSION Desogestrel, 75 μg/d, could be an alternative to combined hormonal contraception before placement of Essure inserts, facilitating the procedure and serving as a contraceptive method during the following 12 weeks until occlusion of the tubes.

Incidence of human papillomavirus infection in male sexual partners of women diagnosed with CIN II-III

INTRODUCTION Human papillomavirus (HPV) infection is a very common sexually transmitted disease which has been strongly related to cervical cancer and cervical intraepithelial neoplasia (CIN), penile cancer and intraepithelial and infiltrating anal squamous cell carcinoma. OBJECTIVES To describe the HPV status of male sexual partners of women diagnosed with CIN II/III and to evaluate the practical usefulness of the HPV detection in urine as a reliable marker of genital high-risk HPV infection in men. METHODS Ninety-one heterosexual male partners (mean age 32.7) were included in the study. A panel of epidemiological data was recorded. Peniscopy was performed at the first visit and after 6 months. Urine samples and anal and penile scrapings were obtained and Hybrid Capture II test for high-risk HPV was performed. Physical examination disclosed clinically or peniscopic lesions in only 5.4% patients. HPV was isolated in 12.9% and 6.2% of penile and anal scrapings respectively whereas HPV detection was positive in 28% of urine samples. Overall, 41% of the evaluated patients presented at least one finding diagnostic of HPV infection. CONCLUSION HPV detection in male partners of women with CIN is a frequent event, and urine HPV detection by Hybrid Capture test is a sensitive method for its detection. The determination of HPV in urine samples seems to be a simple method to investigate the subrogated genital HPV infection in men.