ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma.

The standard surgical treatment of endometrial carcinoma, consisting of total hysterectomy with bilateral salpingo-oophorectomy, drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) provide comprehensive information on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment.A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE), and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment (patient selection, tumor clinicopathological characteristics, treatment, special issues) in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts from across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified by a systematic search, was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives.

Anastrozole and levonorgrestrel-releasing intrauterine device in the treatment of endometriosis: a randomized clinical trial.

BACKGROUND: To study the effectiveness of an aromatase inhibitor (Anastrozole) associated with levonorgestrel-releasing intrauterine device (LNG-IUD, Mirena®) in the treatment of endometriosis. METHODS: Prospective, randomized clinical trial. SETTING: University Hospital (single center). Elegibility criteria: Endometriomas > 3 × 4 cm, CA-125 > 35 U/mL and endometriosis symptoms. PATIENTS: Thirty-one women randomized to anastrozole + Mirena® + Conservative Surgery(CS) (n = 8), anastrozole + Mirena® + transvaginal ultrasound-guided puncture-aspiration (TUGPA) (n = 7), Mirena® + CS (n = 9), or Mirena® + TUGPA (n = 7). INTERVENTIONS: Anastrozole 1 mg/day and/or only Mirena® for 6 months; CS (ovarian and fertility-sparing) or TUGPA of endometriomas one month after starting medical treatment. MAIN OUTCOME MEASURES: Visual analogic scale for symptoms, CA-125 levels, ultrasound findings of endometriomas and recurrences. RESULTS: A significant improvement in symptoms during the treatment (difference of 43%, 95% CI 29.9-56.2) occurred, which was maintained at 1 and 2 years. It was more significant in patients including anastrozole in their treatment (51%, 95% CI 33.3-68.7). For CA-125, the most significant decrease was observed in patients not taking anastrozole (73.8%, 95% CI 64.2-83.4 vs. 53.8%, 95% CI 25.7-81.6 under Mirena® + anastrozole). After CS for endometriosis, a reduction of ultrasound findings of endometriomas and long-term recurrence occurred, with or without anastrozole. At 4.2 ± 1.7 years (95% CI 3.57-4.85), 88% of the patients who underwent CS were asymptomatic, without medication or reoperation, compared to only 21% if TUGPA was performed, with or without anastrozole (p = 0.019). CONCLUSIONS: Dosing anastrozole for 6 months, starting one month before CS of endometriosis, reduces significantly the painful symptoms and delays recurrence, but has no other significant advantages over the single insertion of LNG-IUD (Mirena®) during the same time. Anastrozole and/or only Mirena® associated with TUGPA are not effective. TRIAL REGISTRATION: Eudra CT System of the European Medicines Agency (London, 29-Sept-2008) Nº EudraCT: 2008-005744-17 (07/11/2008). Date of enrolment of first patient: 15/01/2009.

Long-term outcomes of transvaginal ultrasound-guided aspiration versus traditional conservative surgery as treatment for endometriomas: A retrospective study of cohorts.

AIM: To evaluate if the long-term results (on fertility, need of hysterectomy and persistence of endometriosis) after a minimally invasive intervention (transvaginal ultrasound-guided puncture-aspiration [TUGPA]) for endometriomas are significantly different from performing the traditional conservative surgery (CS) by laparoscopy or laparotomy. METHODS: We performed a retrospective study of cohorts on patients undergoing surgery for ovarian endometriomas between January 1998 and April 2015. Cohort 1 consisted of 75 women whose first intervention for endometriomas had been TUGPA. For the cohort 2, we selected a randomized paired case in which the first operation for endometriomas had been CS by laparoscopic or laparotomy (another set of 75 patients). RESULTS: There were significantly more recurrences and the time to recurrence and repetition of operations were also significantly shorter in patients with TUGPA. However, there were no significant differences in overall pregnancy/delivery outcomes, in hysterectomy performances, or in endometriosis persistence at the last follow-up visit. There were no significant differences related to the symptoms or to analytical presurgical values but the application of multivariate analysis with binary logistic regression to each dependent variable adjusted for age, symptoms, and presurgical analyses showed a significant risk of recurrence and reoperation of TUGPA versus CS. CONCLUSIONS: Those patients with endometriomas who underwent TUGPA (with or without associated medications) had a significant increase in recurrence and the need for reoperation. However, in the long-term there were no significant differences in the results of pregnancy/childbirth, need for hysterectomy, or in the clinical or doubtful persistence of endometriosis.

Clinical pilot study to evaluate the neovaginal PACIENA prosthesis® for vaginoplasty without skin grafts in women with vaginal agenesis.

BACKGROUND: To evaluate the feasibility and clinical outcomes of vaginoplasties using a neovaginal polylactic acid prosthesis made with 3-dimensional (3D) printing technology as an intraneovaginal mould. METHODS: This was an interventionist, prospective, and multicentre clinical pilot investigation of a sanitary product (PACIENA prosthesis®) aiming to recruit and operate on 8 patients over 6 months with a follow-up period of 6 months. Only six patients with Rokitansky syndrome and one patient with Morris syndrome (7 patients in total) were operated on in two university hospitals: "La Fe", Valencia (H1) and "Arrixaca", Murcia (H2). INTERVENTIONS: Extensive surgical dissection of a defined space between the urethra and bladder in the front and of the rectum in the back as well as insertion of the PACIENA prosthesis® covered with Interceed® were performed. After 12 days, the prosthesis was changed to the silicone-covered version for daily application. RESULTS: In the 6 patients with Rokitansky syndrome (86%), the primary endpoint (satisfactory vaginal outcome in terms of appearance, function, and sensation without relevant additional morbidity) was achieved, although only 2 patients (28%) were sexually active at the end of 6 months of follow-up. The patient with Morris syndrome withdrew from the study after 1 month. Patients without bacterial colonization showed positive Schiller tests at 1 month, and subsequent biopsies showed adequate keratinization and epidermization. Epithelization and iodopositivity were delayed in the patients who developed inflammatory granulomas. CONCLUSIONS: Good anatomical and functional results can be achieved with the PACIENA prosthesis® for vaginoplasties without skin grafts. However, adequate patient selection and education, good surgical techniques and haemostasis, postoperative support, and prevention of bacterial colonization are important. TRIAL REGISTRATION: This clinical study was approved by the Ethical Clinical Investigation Committee of San Juan University Hospital on September 27, 2016, to be conducted in the participating centres; it was authorized by the Spanish Agency of Medicines and Health Products (AEMPS) on April 24, 2017 (exp. no. 585/16/EC), to be carried out in that hospitals.

Epithelial ovarian cancers and endometriosis.

AIMS: To determine the prevalence of endometriosis in epithelial ovarian cancers (EOC) and the association among their histological subtypes and with endometrial carcinoma. METHODS: An observational cohort study performed in 192 patients operated on for EOC, 30 women with atypical endometriosis and 17 with p53 positive endometriosis. Data on associated endometriosis and endometrial carcinomas, histological subtypes, tumor stage, clinical and pathological characteristics and survival were analyzed. RESULTS: Twenty cases of EOC (10.4%) had also endometriosis (12.7 in borderline and 9.3% in invasive cases), being a synchronous finding in most cases. Endometriosis associated with serous or mucinous EOC was observed in 2.2 and 2.7% of cases, respectively. However, this association was observed in 50 of endometrioid and 23% of clear cell EOC. Age, parity and tumor stage were lower in endometriosis-associated EOC patients; and all associated cases were type I (Kurman and Shih's classification) and showed better results in survival rate. Endometrial carcinoma was more frequently associated with endometrioid EOC (25%). CONCLUSIONS: There is a significant association between endometriosis, including atypical forms, and endometrioid and clear cell carcinomas, but not with other EOC histotypes. The presence of endometriosis in EOC suggests a better prognosis and an intermediate stage within the progression endometriosis-carcinoma.

Reproductive outcome in uterine malformations with or without an associated unilateral renal agenesis.

OBJECTIVE: To analyze reproductive performance in women with genital malformations and to determine whether pregnancy outcomes are influenced by the asrenal agenesis (URA). STUDY DESIGN: This was a retrospective study of 174 patients with genitourinary malformations, with available images for reevaluation and classification and a history ofpregnancies. The main outcome measure was the reproductive performance depending on the type of uterine malformation and urinary tract anomalies. RESULTS: The lowest percentage of women who had only live births occurred in women with bicornuate unicollis uterus (28%). Considering only uterine anomalies that might be associated with URA, those cases had significantly better perinatal outcomes (72% had only living children) than those with no renal agenesis (40%). Of the total number of pregnancies (n=355), patients with URA were associated with term deliveries and living children, whereas women with uterine malformation without URA were more associated with abortions, premature births, and breech presentation. CONCLUSION: Uterine malformations are associated with a high rate of abortions, preterm births, breech presentation, and reproductive losses, but reproductive performance is significantly better for a given type of uterine malformation if it is associated with URA; that is, if the Müllerian anomaly is the consequence of mesonephric or Wolffian anomaly. Different embryological origin for the uterine malformations (mesonephric versus isolated Müllerian anomalies), the absence of 1 renal artery, and previous extrauterine surgery could be related.

Applicability and Suitability of the Embryological-Clinical Classification of Female Genital Malformations: A Systematic Review.

Complex urogenital malformations are clinically highly relevant; thus, they must be appropriately diagnosed and classified before initiating treatment. Background/Objectives: This study aimed to evaluate the applicability and suitability of the embryological-clinical classification of female genital malformations. Methods: A systematic review of cases of genital malformations reported in the literature from 2000 to 2020 was conducted. Case reports and series with the following combinations: "female genital tract" AND (malformation OR anomaly OR müllerian anomaly OR uterine anomaly OR cervical anomaly OR vaginal anomaly OR cloacal anomaly OR urogenital sinus); and "female genital tract" AND (renal agenesis OR ectopic ureter) were searched. A total of 3124 articles were identified, of which 824 cases of genital malformation were extracted. The characteristics of each malformation were included in a database for further analyses. Results: Using the embryological-clinical classification, 89.9% of the published cases and 86.5% of the 52 cases defined as unclassifiable by their authors have been classified in this review. In 73 cases (72.2%), the classification of the malformation using the AFS system was incomplete because although the type of uterine anomaly of the AFS classification matched that of the embryological-clinical classification, characteristics of the urinary system or the vagina were overlooked when using the AFS system. Following a dispersion matrix, we have been able to show that the embryological-clinical classification system is able to classify and subclassify the genitourinary malformations more accurately. Conclusions: The applicability of the embryological-clinical classification has been confirmed after classifying most of the cases of genital malformation previously published. This system also provides a more complete and accurate classification than other classifying systems exclusively based on Müllerian duct development or uterovaginal parameters, demonstrating its suitability.

A New Advanced and Validated Method for the Determination of Potentially Toxic Metals and Trace and Ultra-Trace Elements in Peritoneal Fluid to Assess the Health Risks of Women with Gynecological Pathologies.

Toxic metals found in the environment have been linked to female infertility and gynecological illnesses. Reliable analytical methods, such as inductively coupled plasma tandem mass spectrometry (ICP-MS/MS), are necessary to determine the elemental composition of biological samples. Currently, the multielemental profile of peritoneal fluid (PF) samples has not yet been established. Due to the complexity of the PF matrix, an ICP-MS/MS-based method has been optimized to mitigate matrix effects and spectral interferences. A dilution factor of 1:4 was the best option to mitigate matrix effects while keeping sensitivity at an appropriate level. A collision gas (He) was useful to lower the extent of spectral interferences for 56Fe, 52Cr, 63Cu, and 68Zn. An intermediate validation test was performed to evaluate accuracy, achieving recoveries ranging from 90 to 110%. The method was validated in terms of intermediate precision, reproducibility, and trueness, with an expanded uncertainty lower than 15%. Afterward, it was applied to perform the multielemental analysis of 20 PF samples. The concentrations for major analytes were up to 151 µg L-1. Meanwhile,209Bi, 111Cd, 52Cr, 55Mn, 95Mo, 60Ni, 208Pb, 118Sn, and 51V were present at concentrations included within the 1-10 µg L-1 range, while 59Co and 139La were found at concentrations below 1 µg L-1.

Elevated Lead, Nickel, and Bismuth Levels in the Peritoneal Fluid of a Peritoneal Endometriosis Patient without Toxic Habits or Occupational Exposure following a Vegetarian Diet.

Potentially toxic elements (PTEs), found as environmental contaminants, have been related to endometriosis disease. In this context, the peritoneal fluid (PF) matrix has been poorly studied despite its importance. PF is the environment in which endometriotic lesions reside and communicate with surrounding tissues including tissues and nerve cells. In this work, our investigation group reports the special case of a peritoneal endometriosis patient presenting elevated lead, nickel, and bismuth levels in PF. This patient reported following a vegetarian diet and no toxic habits or occupational exposure. In conclusion, the elevated levels of PTEs found may result from a vegetarian diet or an unidentified environmental exposure source. This report provides new insights regarding the possible etiology of endometriosis disease and potential biomarkers for its diagnosis in early stages, although additional research is needed.

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma.

STUDY QUESTION: How should fertility-sparing treatment of patients with endometrial carcinoma be performed? SUMMARY ANSWER: Forty-eight recommendations were formulated on fertility-sparing treatment of patients with endometrial carcinoma. WHAT IS KNOWN ALREADY: The standard surgical treatment of endometrial carcinoma consisting of total hysterectomy with bilateral salpingo-oophorectomy drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) provide comprehensive guidelines on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment. STUDY DESIGN SIZE DURATION: A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. PARTICIPANTS/MATERIALS SETTING METHODS: ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practising clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgement was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives. MAIN RESULTS AND THE ROLE OF CHANCE: The multidisciplinary development group formulated 48 recommendations in four sections; patient selection, tumour clinicopathological characteristics, treatment and special issues. LIMITATIONS REASONS FOR CAUTION: Of the 48 recommendations, none could be based on level I evidence and only 16 could be based on level II evidence, implicating that 66% of the recommendations are supported only by observational data, professional experience and consensus of the development group. WIDER IMPLICATIONS OF THE FINDINGS: These recommendations provide guidance to professionals caring for women with endometrial carcinoma, including but not limited to professionals in the field of gynaecological oncology, onco-fertility, reproductive surgery, endoscopy, conservative surgery and histopathology, and will help towards a holistic and multidisciplinary approach for this challenging clinical scenario. STUDY FUNDING/COMPETING INTERESTS: All costs relating to the development process were covered from ESGO, ESHRE and ESGE funds. There was no external funding of the development process or manuscript production. G.S. has reported grants from MSD Italia S.r.l., advisory boards for Storz, Bayer, Astrazeneca, Metronic, TESARO Bio Italy S.r.l and Johnson & Johnson, and honoraria for lectures from Clovis Oncology Italy S.r.l. M.G. has reported advisory boards for Gedeon Richter and Merck. The other authors have reported no conflicts of interest. DISCLAIMER: This document represents the views of ESHRE, ESGO and ESGE which are the result of consensus between the relevant stakeholders and where relevant based on the scientific evidence available at the time of preparation. The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type.

Impact of Heavy Metals on Human Male Fertility-An Overview.

Heavy metals are endocrine disruptors which interfere with processes mediated by endogenous hormones of the organism, negatively affecting endocrine functions. Some studies have correlated heavy metal exposure with male infertility. However, the number of studies conducted on humans are limited. Therefore, the aim of this study is to summarize the current knowledge on how heavy metals influence human male fertility. Hence, three distinct databases were consulted-PubMed, Scopus and Web of Science-using single keywords and combinations of them. The total number of identified articles was 636. Nevertheless, by using the inclusion and exclusion criteria, 144 articles were finally included in this work. Results display that the development of adequate instruments for heavy metal assessment may play an important function in human male fertility diagnosis and treatment. Furthermore, clinical trials could be useful to confirm the role of heavy metals in human male fertility diagnosis. Overall, further research is required to fully understand the molecular and cellular basis of the influence of environmental and occupational exposure to heavy metals on human male infertility and reproductive outcomes.

Blind hemibladder, ectopic ureterocele, or Gartner's duct cyst in a woman with Müllerian malformation and supposed unilateral renal agenesis: a case report.

Genital anomalies associated with unilateral renal agenesis are generally due to agenesis or hypoplasia of the entire urogenital ridge or distal mesonephric aberrations. However, renal adysplasia could also occur in association with anomalies of the ventral urogenital sinus. The patient presented didelphys uterus in the superior uterine segment, a septate cervix, and a simple vagina. After transvaginal puncture and injection of a contrast agent into the bulge observed in the right vaginal wall, a filled sac or cavity was detected, possibly a hemibladder. This structure continued upward with a possible dilated tortuous ureter that filled retrogradely. Magnetic resonance imaging also showed the presence of the right blind paravaginal sac. Right hemitrigone and ureteral orifice were absent in the cystourethroscopy. No right kidney was found, despite the use of multiple imaging techniques. Blind hemibladder, ectopic ureterocele, and Gartner's duct cyst seem to be a possible diagnosis associated to Müllerian malformations and supposed unilateral renal agenesis. Therefore, Müllerian anomalies without combined mesonephric alteration could be associated with conditions of the ventral urogenital sinus, including blind hemibladder or ectopic ureterocele with secondary renal dysplasia.

Unilateral renal agenesis and female genital tract pathologies.

OBJECTIVES: To analyze the gynecological pathologies and extragenital anomalies associated with unilateral renal agenesis (URA) and the possible origin of these congenital anomalies. DESIGN: Retrospective case-control study. SETTING: University Hospital. POPULATION: This study included 276 women with genitourinary malformations who had undergone hysterosalpingography (and/or laparoscopy) and pyelography with images available for review. METHODS: There were 60 cases of women diagnosed with genital malformations and congenital URA and 216 control cases of women with genital tract malformations and both kidneys present. All cases were categorized according to an embryological-clinical classification and the type of Müllerian malformation (American Society for Reproductive Medicine (ASRM) classification) and then compared by type for the presence of gynecological and extragenital pathologies. MAIN OUTCOME MEASURES: Genital malformations, endometriosis, leiomyomas and skeletal anomalies. RESULTS: URA was generally associated with either agenesis of all of the derivatives of the urogenital ridge on the same side of the body, which were usually found on the left, or distal mesonephric anomalies such as a double uterus with a blind hemivagina or unilateral cervico-vaginal atresia, which were most frequently on the right. The uterine malformations that were most commonly seen in women with renal agenesis were bicornis-bicollis, didelphys and unicornuate uteri. Women with bicornuate or didelphys uteri and renal agenesis had more gynecological pathologies, such as endometriosis, than those with both kidneys present. CONCLUSIONS: URA and major uterine malformations are frequently related, and individuals with bicornuate or didelphys uteri have endometriosis more often than those without renal agenesis. Those malformations that seem to be caused by the absence or anomaly of a mesonephric duct lead to renal agenesis, ipsilateral vaginal anomalies (blind or atretic hemivagina) and failure of the induction function of the Wolffian ducts on the Müllerian ducts, causing uterine malformations.

Treatment of endometriosis with transvaginal ultrasound-guided drainage and recombinant interleukin-2 left in the cysts: a third clinical trial.

BACKGROUND: To analyze the therapeutic results of recombinant interleukin-2 (rIL-2) left in the cysts after transvaginal ultrasound (US)-guided drainage of endometriomas as an alternative to surgery. METHODS: Prospective and randomized clinical trial. A total of 25 consecutive patients were included. Two transvaginal US-guided punctures were performed, and 3 million IU of rIL-2 were left in the aspirated cysts once (group I) or both (group II) times according to randomization. MAIN OUTCOME MEASURES: Clinical results, prevented surgeries, and recurrences. RESULTS: Results were moderate or good in only 16% of subjects at 3 months and in 33% of subjects at 6 months after treatment in group I; these numbers were 66 and 33%, respectively, in group II. Differences were not statistically significant. However, the evolution of symptoms, endometriomas, and CA-125 revealed the low efficacy of rIL-2 left intracyst as well as a poor control of the clinical manifestations. After 1 year, 20% (group I) and 73% (group II) of patients had to be operated; after 2 years, these numbers were 55 and 82%, respectively. CONCLUSIONS: Treatment of endometriomas with transvaginal US-guided drainage and rIL-2 left in the cysts, without using endometrial suppressive therapy with GnRH analogues as done in previous studies, has low efficacy. Recurrences are even more frequent after the use of two rIL-2 doses.

Disorders of Sex Development: Classification, Review, and Impact on Fertility.

In this review, the elements included in both sex determination and sex differentiation are briefly analyzed, exposing the pathophysiological and clinical classification of disorders or anomalies of sex development. Anomalies in sex determination without sex ambiguity include gonadal dysgenesis, polysomies, male XX, and Klinefelter syndrome (dysgenesis and polysomies with a female phenotype; and sex reversal and Klinefelter with a male phenotype). Other infertility situations could also be included here as minor degrees of dysgenesis. Anomalies in sex determination with sex ambiguity should (usually) include testicular dysgenesis and ovotesticular disorders. Among the anomalies in sex differentiation, we include: (1) males with androgen deficiency (MAD) that correspond to those individuals whose karyotype and gonads are male (XY and testes), but the phenotype can be female due to different hormonal abnormalities. (2) females with androgen excess (FAE); these patients have ovaries and a 46,XX karyotype, but present varying degrees of external genital virilization as a result of an enzyme abnormality that affects adrenal steroid biosynthesis and leads to congenital adrenal hyperplasia; less frequently, this can be caused by iatrogenia or tumors. (3) Kallman syndrome. All of these anomalies are reviewed and analyzed herein, as well as related fertility problems.

Could Training in an Anatomical Model Be Useful to Teach Different Neovagina Surgical Techniques? A Descriptive Study about Knowledge and Experience of Techniques for Neovagina Surgery.

Neovagina surgery in patients with vaginal agenesis is rare. No consensus exists regarding the best surgical technique. The aims of the current study were to show a new Thiel-embalmed cadaveric model to teach the surgical steps for different techniques of neovagina surgery and to evaluate opinions of this surgical teaching procedure. Four techniques-modified McIndoe, Vecchietti, Davydov, and vulvoperineal pediculated flaps-were recorded using an external camera and/or laparoscopic vision during their execution in a dissection room on "feminized" male cadavers. To determine the opinion of this teaching model, we designed an anonymous online survey that was available to participants via a computer application. After watching the video, more than 92% of participants agreed that feminized male cadavers were an excellent procedure for teaching these surgical techniques. Before watching this video, the most employed techniques were the McIndoe and Vecchietti procedures. After watching the video, modified McIndoe and vulvoperineal flaps were preferred by participants because they were considered to be easier to perform. It was considered that this model was useful for training neovagina techniques and, moreover, it should be recommended before techniques were performed on a real patient. Further investigation is needed to validate this model.

Endometriosis and ovarian cancer: Their association and relationship.

OBJECTIVES: To study endometriosis-associated borderline or malignant ovarian epithelial tumors by analyzing their differential clinical features, as well as the histological pattern, survival and immunohistochemical data compared with those without associated endometriosis. STUDY DESIGN: Setting: Hospital Marina Baixa and San Juan University Hospital, Alicante, Spain. This retrospective study included clinical and pathological data from 36 operated cases with endometriosis-associated ovarian epithelial tumors and 305 cases of ovarian epithelial tumors without endometriosis, including borderline and invasive tumors. We also studied hormonal receptors and p53 protein expression in 13 cases with endometriosis-associated endometrioid and clear cell tumors, and report two cases with histologically-confirmed previous endometriosis. RESULTS: Associated endometriosis was observed in 10.5% of patients with borderline or invasive ovarian epithelial tumor, 53% of those with endometrioid, and 22% with clear cell tumors. Patients with endometriosis-associated ovarian epithelial tumors were younger, had lower parity, were more frequently premenopausal, had a lower tumor stage or were borderline, and in general had better prognosis and longer survival, although they also more frequently had an associated endometrial carcinoma. Associated endometriosis and endometrioid tumors were generally estrogen-receptor positive, whereas they were negative in the clear cell tumor component. p53 protein positivity was generally observed in clear cell tumors and in associated endometriosis. Two reported cases with previous, known endometriosis were followed in their evolution to borderline endometrioid carcinoma and clear cell carcinoma, respectively. CONCLUSIONS: Our results and review of the literature suggest that the association of ovarian epithelial tumors and endometriosis is a factor for good prognosis for ovarian cancer and that this association might correspond in many cases to an intermediate stage in the development of endometriosis to endometrioid, clear cell, or other invasive carcinomas.

Genomic instability in rat: breakpoints induced by ionising radiation and interstitial telomeric-like sequences.

The Norwegian rat (Rattus norvegicus) is the most widely studied experimental species in biomedical research although little is known about its chromosomal structure. The characterisation of possible unstable regions of the karyotype of this species would contribute to the better understanding of its genomic architecture. The cytogenetic effects of ionising radiation have been widely used for the study of genomic instability, and the importance of interstitial telomeric-like sequences (ITSs) in instability of the genome has also been reported in previous studies in vertebrates. In order to describe the unstable chromosomal regions of R. norvegicus, the distribution of breakpoints induced by X-irradiation and ITSs in its karyotype were analysed in this work. For the X-irradiation analysis, 52 foetuses (from 14 irradiated rats) were studied, 4803 metaphases were analysed, and a total of 456 breakpoints induced by X-rays were detected, located in 114 chromosomal bands, with 25 of them significantly affected by X-irradiation (hot spots). For the analysis of ITSs, three foetuses (from three rats) were studied, 305 metaphases were analysed and 121 ITSs were detected, widely distributed in the karyotype of this species. Seventy-six percent of all hot spots analysed in this study were co-localised with ITSs.

The presentation and management of complex female genital malformations.

BACKGROUND: Common uterine anomalies are important owing to their impact on fertility, and complex mesonephric anomalies and certain Müllerian malformations are particularly important because they cause serious clinical symptoms and affect woman's quality of life, in addition to creating fertility problems. In these cases of complex female genital tract malformations, a correct diagnosis is essential to avoid inappropriate and/or unnecessary surgery. Therefore, acquiring and applying the appropriate embryological knowledge, management and therapy is a challenge for gynaecologists. Here, we considered complex malformations to be obstructive anomalies and/or those associated with cloacal and urogenital sinus anomalies, urinary and/or extragenital anomalies, or other clinical implications or symptoms creating a difficult differential diagnosis. METHODS: A diligent and comprehensive search of PubMed and Scopus was performed for all studies published from 1 January 2011 to 15 April 2015 (then updated up to September 2015) using the following search terms: 'management' in combination with either 'female genital malformations' or 'female genital tract anomalies' or 'Müllerian anomalies'. The MeSH terms 'renal agenesis', 'hydrocolpos', 'obstructed hemivagina' 'cervicovaginal agenesis or atresia', 'vaginal agenesis or atresia', 'Herlyn-Werner-Wunderlich syndrome', 'uterine duplication' and 'cloacal anomalies' were also used to compile a list of all publications containing these terms since 2011. The basic embryological considerations for understanding female genitourinary malformations were also revealed. Based on our experience and the updated literature review, we studied the definition and classification of the complex malformations, and we analysed the clinical presentation and different therapeutic strategies for each anomaly, including the embryological and clinical classification of female genitourinary malformations. RESULTS: From 755 search retrieved references, 230 articles were analysed and 120 studied in detail. They were added to those included in a previous systematic review. Here, we report the clinical presentation and management of: agenesis or hypoplasia of one urogenital ridge; unilateral renal agenesis and ipsilateral blind or obstructed hemivagina or unilateral cervicovaginal agenesis; cavitated and non-communicating uterine horns and Müllerian atresias or agenesis, including Rokitansky syndrome; anomalies of the cloaca and urogenital sinus, including congenital vagino-vesical fistulas and cloacal anomalies; malformative combinations and other complex malformations. The clinical symptoms and therapeutic strategies for each complex genitourinary malformation are discussed. In general, surgical techniques to correct genital malformations depend on the type of anomaly, its complexity, the patient's symptoms and the correct embryological interpretation of the anomaly. Most anomalies can typically be resolved vaginally or by hysteroscopy, but laparoscopy or laparotomy is often required as well. We also include additional discussion of the catalogue and classification systems for female genital malformations, the systematic association between renal agenesis and ipsilateral genital malformation, and accessory and cavitated uterine masses. CONCLUSIONS: Knowledge of the correct genitourinary embryology is essential for the understanding, study, diagnosis and subsequent treatment of genital malformations, especially complex ones and those that lead to gynaecological and reproductive problems, particularly in young patients. Some anomalies may require complex surgery involving multiple specialties, and patients should therefore be referred to centres that have experience in treating complex genital malformations.