Polyphenols Influence the Development of Endometrial Cancer by Modulating the Gut Microbiota.

Dysbiosis of the microbiota in the gastrointestinal tract can induce the development of gynaecological tumours, particularly in postmenopausal women, by causing DNA damage and alterations in metabolite metabolism. Dysbiosis also complicates cancer treatment by influencing the body's immune response and disrupting the sensitivity to chemotherapy drugs. Therefore, it is crucial to maintain homeostasis in the gut microbiota through the effective use of food components that affect its structure. Recent studies have shown that polyphenols, which are likely to be the most important secondary metabolites produced by plants, exhibit prebiotic properties. They affect the structure of the gut microbiota and the synthesis of metabolites. In this review, we summarise the current state of knowledge, focusing on the impact of polyphenols on the development of gynaecological tumours, particularly endometrial cancer, and emphasising that polyphenol consumption leads to beneficial modifications in the structure of the gut microbiota.

Effects of topical dehydroepiandrosterone therapy in women after pelvic organ prolapse surgery.

OBJECTIVE: Pelvic organ prolapse (POP) occurs predominantly in postmenopausal women. Restoration of the proper estrogenization of vaginal mucosa is important in preoperative and postoperative treatment, increasing the effectiveness of this approach. The objective of this study was the development of intravaginal vaginal suppositories containing DHEA and comparison of the clinical effects of vaginal topical therapy with DHEA, estradiol, or antibiotic after POP surgery. METHOD: Nine types of vaginal suppositories containing 6.5 mg DHEA in different bases were prepared to find optimal formulation for the vaginal conditions. Ninety women referred for POP surgery were randomly assigned to one of three groups receiving topical treatment in the postoperative period (estradiol, DHEA, or antibiotic). On admission to hospital and during follow-up vaginal pH, vaginal maturation index and vaginal symptoms were assessed. RESULTS: Vaginal suppositories with the base made from polyethylene glycol 1,000 without surfactants characterized the highest percentage of the released DHEA. In women treated with topical estradiol or DHEA a significant decrease in the number of parabasal cells, increase in superficial and intermediate cells in the vaginal smears, decrease in vaginal pH, and reduction of vaginal symptoms were observed. CONCLUSIONS: The use of topical therapy with DHEA or the use of topical therapy with estradiol in the postoperative period were both shown to improve maturation index, vaginal pH, and vaginal symptoms. The benefits of topical therapy with DHEA after pelvic organ prolapse repair brings similar results as estradiol, without potential systemic exposure to increased concentrations of sex steroids above levels observed in postmenopausal women.

International Natural Procreative Technology Evaluation and Surveillance of Treatment for Subfertility (iNEST): enrollment and methods.

STUDY QUESTION: What is the feasibility of a prospective protocol to follow subfertile couples being treated with natural procreative technology for up to 3 years at multiple clinical sites? SUMMARY ANSWER: Overall, clinical sites had missing data for about one-third of participants, the proportion of participants responding to follow-up questionnaires during time periods when participant compensation was available (about two-thirds) was double that of time periods when participant compensation was not available (about one-third) and follow-up information was most complete for pregnancies and births (obtained from both clinics and participants). WHAT IS KNOWN ALREADY: Several retrospective single-clinic studies from Canada, Ireland and the USA, with subfertile couples receiving restorative reproductive medicine, mostly natural procreative technology, have reported adjusted cumulative live birth rates ranging from 29% to 66%, for treatment for up to 2 years, with a mean women's age of about 35 years. STUDY DESIGN SIZE DURATION: The international Natural Procreative Technology Evaluation and Surveillance of Treatment for Subfertility (iNEST) was designed as a multicenter, prospective cohort study, to enroll subfertile couples seeking treatment for live birth, assess baseline characteristics and follow them up for up to 3 years to report diagnoses, treatments and outcomes of pregnancy and live birth. In addition to obtaining data from medical record abstraction, we sent follow-up questionnaires to participants (both women and men) to obtain information about treatments and pregnancy outcomes, including whether they obtained treatment elsewhere. The study was conducted from 2006 to 2016, with a total of 10 clinics participating for at least some of the study period across four countries (Canada, Poland, UK and USA). PARTICIPANTS/MATERIALS SETTING METHODS: The 834 participants were subfertile couples with the woman's age 18 years or more, not pregnant and seeking a live birth, with at least one clinic visit. Couples with known absolute infertility were excluded (i.e. bilateral tubal blockage, azoospermia). Most women were trained to use a standardized protocol for daily vulvar observation, description and recording of cervical mucus and vaginal bleeding (the Creighton Model FertilityCare System). Couples received medical and sometimes surgical evaluation and treatments aimed to restore and optimize female and male reproductive function, to facilitate in vivo conception. MAIN RESULTS AND THE ROLE OF CHANCE: The mean age of women starting treatment was 34.0 years; among those with additional demographic data, 382/478 (80%) had 16 or more years of education, and 199/659 (30%) had a prior live birth. Across 10 clinical sites in four countries (mostly private clinical practices) with family physicians or obstetrician-gynecologists, data about clinic visits were submitted for 60% of participants, and diagnostic data for 77%. For data obtained directly from the couple, 59% of couples had at least one follow-up questionnaire, and the proportion of women and men responding to fill out the follow-up questionnaires was 69% and 67%, respectively, when participant financial compensation was available, compared to 38% and 33% when compensation was not available. Among all couples, 57% had at least one pregnancy and 44% at least one live birth during the follow-up time period, based on data obtained from clinic and/or participant questionnaires. All sites reported on female pelvic surgical procedures, and among all participants, 22% of females underwent a pelvic diagnostic and/or therapeutic procedure, predominantly laparoscopy and hysterosalpingography. Among the 643 (77%) of participants with diagnostic information, ovulation-related disorders were diagnosed in 87%, endometriosis in 31%, nutritional disorders in 47% and abnormalities of semen analysis in 24%. The mean number of diagnoses per couple was 4.7. LIMITATIONS REASONS FOR CAUTION: The level of missing data was higher than anticipated, which limits both generalizability and the ability to study different components of treatment and prognosis. Loss to follow-up may also be differential and introduce bias for outcomes. Most of the participating clinicians were not surgeons, which limits the opportunity to study the impact of surgical interventions. Participants were geographically dispersed but relatively homogeneous with regard to socioeconomic status, which may limit the generalizability of current and future findings. WIDER IMPLICATIONS OF THE FINDINGS: Multicenter studies are key to understanding the outcomes of subfertility treatments beyond IVF or IUI in broader populations, and the association of different prognostic factors with outcomes. We anticipate that the iNEST study will provide insight for clinical and treatment factors associated with outcomes of pregnancy and live birth, with appropriate attention to potential biases (including adjustment for potential confounders, multiple imputation for missing data, sensitivity analysis and inverse probability weighting for potential differential loss to follow-up, and assessments for clinical site heterogeneity). Future studies will need to either have: adequate funding to compensate clinics and participants for robust data collection, including targeted randomized trials; or a scaled-down, registry-based approach with targeted data points, similar to the multiple national and regional ART registries. STUDY FUNDING/COMPETING INTERESTS: Funding for the study came from the International Institute for Restorative Reproductive Medicine, the University of Utah, Department of Family and Preventive Medicine, Health Studies Fund, the Primary Children's Medical Foundation, the Mary Cross Tippmann Foundation, the Atlas Foundation, the St. Augustine Foundation and the Women's Reproductive Health Foundation. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: The iNEST study is registered at clinicaltrials.gov, NCT01363596.

Antioxidative, Anti-Inflammatory, Anti-Obesogenic, and Antidiabetic Properties of Tea Polyphenols-The Positive Impact of Regular Tea Consumption as an Element of Prophylaxis and Pharmacotherapy Support in Endometrial Cancer.

Endometrial cancer (EC) is second only to cervical carcinoma among the most commonly diagnosed malignant tumours of the female reproductive system. The available literature provides evidence for the involvement of 32 genes in the hereditary incidence of EC. The physiological markers of EC and coexisting diet-dependent maladies include antioxidative system disorders but also progressing inflammation; hence, the main forms of prophylaxis and pharmacotherapy ought to include a diet rich in substances aiding the organism's response to this type of disorder, with a particular focus on ones suitable for lifelong consumption. Tea polyphenols satisfy those requirements due to their proven antioxidative, anti-inflammatory, anti-obesogenic, and antidiabetic properties. Practitioners ought to consider promoting tea consumption among individuals genetically predisposed for EC, particularly given its low cost, accessibility, confirmed health benefits, and above all, suitability for long-term consumption regardless of the patient's age. The aim of this paper is to analyse the potential usability of tea as an element of prophylaxis and pharmacotherapy support in EC patients. The analysis is based on information available from worldwide literature published in the last 15 years.

Fertility-Sparing Methods in Adolescents Affected by Endometrial Cancer: A Comprehensive Review.

Although in developed countries endometrial cancer (EC) is the most common gynecological malignancy, its occurrence in adolescents is exceedingly rare. The increasing rate of obesity in children and adolescents is held responsible for the increasing prevalence of EC in younger cohorts of patients. The diagnosis of this malignancy can have devastating consequences for future fertility because standard treatment protocols for EC include hysterectomy. Here, we present the first detailed review of the world literature on EC in subjects aged 21 years or younger (n = 19). The mean age at diagnosis was 16.7 ± 0.6 years. One patient (5.3%) had a Type II (high-risk) disease. No communication retrieved from the search reported on patient death; however, two (10.5%) patients were lost to follow-up. There was also a high proportion (five subjects, or 26.3%) of cases with genetic background (Cowden syndrome and Turner syndrome), therefore genetic screening or a direct genetic study should be considered in very young patients with EC. The current fertility-sparing options, limited to Type I (low-risk) disease, are presented and discussed. Such information, obtained from studies on older women, translates well to adolescent girls and very young women. Careful anatomopathological monitoring at follow-up is essential for the safety of a conservative approach. Improved survival in very young EC patients makes the preservation of fertility a central survivorship issue, therefore both patients and caregivers should undergo counseling regarding available options. Moreover, our study suggests that genetic syndromes other than Lynch syndrome may be associated with EC more frequently than previously thought.

Surgical Technique for Endometrioma in 10 Steps.

OBJECTIVE: Laparoscopic cystectomy for endometrioma has the advantages of a minimally invasive approach. The standardization and description of the technique are the main objectives of this video. We described the surgery in 10 steps, which could help to make this procedure easier and safer. DESIGN: Step-by-step video demonstration of the technique. SETTING: A French university tertiary care hospital. INTERVENTION: Two standardized laparoscopic cystectomy were recorded to realize the video. The local institutional review board ruled that approval was not required because the video describes a technique and does not report a clinical case. This video presents a systematic approach to cystectomy for endometrioma clearly divided into 10 steps: (1) preoperative evaluation [1]; (2) diagnosis and exploration [2]; (3) adhesiolysis, mobilization of the ovary; (4) cyst rupture, exposition of the entry site; (5) identification of the cleavage plan; (6) endometrioma easy dissection; (7) endometrioma difficult dissection; (8) hemostasis, reconstruction of the ovary [3]; (9) exploration of the ovarian fossa; and (10) washing, extraction of the cyst [3,4]. CONCLUSION: Standardization of laparoscopic cystectomy for endometrioma could make this procedure easier and safer to perform. The 10 steps presented help to perform each part of the surgery in a logical sequence, making the procedure easier to realize. Moreover, the standardization of the surgical techniques may reduce the learning curve.

Laparoscopic Ovarian Dermoid Cystectomy in 10 Steps.

STUDY OBJECTIVE: Laparoscopic cystectomy for ovarian teratomas has the advantages of a minimally invasive approach [1]. The standardization and description of the technique are the main objectives of this video (Video 1). We described the surgery in 10 steps [2], which could help make this procedure easier and safer. DESIGN: A step-by-step video demonstration of the technique. SETTING: A French university tertiary care hospital. PATIENTS: Patients with ovarian teratomas with indication for laparoscopic cystectomy [3]. The local institutional review board ruled that approval was not required for this video article because the video describes a technique and does not report a clinical case. INTERVENTIONS: Standardized laparoscopic cystectomies were recorded to realize the video. MEASUREMENTS AND MAIN RESULTS: This video presents a systematic approach to cystectomy for teratoma clearly divided into 10 steps: (1) planning of the surgery, (2) ergonomy and materials, (3) exploration and cytology, (4) prevention of peritoneal spillage [4], (5) mobilization of the ovary, (6) incision of the ovary, (7) dissection, (8) hemostasis, (9) exteriorization of the cyst, and (10) washing and exploration. CONCLUSION: Standardization of laparoscopic cystectomy for ovarian teratoma could make this procedure easier and safer to perform. The 10 steps presented help to perform each part of the surgery in a logical sequence, making the procedure ergonomic and easier to adopt and learn. Moreover, the standardization of the surgical techniques could reduce the learning curve.

Ovarian endometrioma - a possible finding in adolescent girls and young women: a mini-review.

Young girls before menarche or menstruating adolescent women may experience long-term drug-resistant chronic pelvic pain, as well as other symptoms associated with pelvic mass. In such cases, it is of great importance to consider ovarian endometrioma in the differential diagnosis. In general, endometrioma is recognized as an ovarian cyst. However, in most cases, the pathology represents pseudocyst with a partial or complete endometrial-like lining with extraovarian adhesions and endometriotic implants which are likely to occur at the sites of ovarian adhesions and at the ceiling of the ovarian fossa. Ovarian endometriomas occur in 17-44% patients with endometriosis and account for 35% of all benign ovarian cysts. The time span from the onset of menarche to the time of endometrioma formation, which requires surgical intervention, has been evaluated to be a minimum of 4 years. The pathogenesis of early-life endometrioma may be different from other types of endometriosis. Diagnosis is often delayed, especially in adolescents, who tend to wait too long before seeking professional help. The three specific aims of treatment in adolescents with endometriosis and endometriomas are control of symptoms, prevention of further progression of the disease as well as preservation of fertility. Increasing evidence demonstrates association between ovarian endometriosis and ovarian cancer. In the present mini-review, we draw the particular attention of clinicians to such a possibility, even if relatively infrequently reported.

Laparoscopic Myomectomy in 10 Steps.

STUDY OBJECTIVE: Laparoscopic myomectomy has the advantages of a minimally invasive approach for the surgical treatment of myomas. The standardization and description of the technique are the main objectives of this video. We described laparoscopic myomectomy in 10 steps, which could help make this procedure easier and safer [1]. SETTING: A French university tertiary care hospital. PATIENTS: Patients with indication for laparoscopic myomectomy. The local institutional review board ruled that approval was not required for this video article because the video describes a technique and does not report a clinical case. INTERVENTION: Standardized laparoscopic myomectomies were recorded to realize the video. MEASUREMENTS AND MAIN RESULTS: This video presents a systematic approach to myomectomy clearly divided into 10 steps: (1) prepare your surgery, make selection and prehabilitation of patient [2], provide a good cartography of the myoma(s), and plan the surgery [3,4]; (2) ergonomy and material; (3) preventive hemostasis: triple occlusion; (4) hysterotomy; (5) enucleation by fast dissection and traction; (6) bipolar hemostasis; (7) check for missing myomas; (8) suture; (9) extraction/morcellation; and (10) prevent adhesions [5]. CONCLUSION: Standardization of laparoscopic myomectomy could make this procedure easier and safer to perform. The 10 steps presented help to perform each part of surgery in logical sequence making the procedure ergonomic and easier to adopt and learn. Standardization of laparoscopic techniques could help to reduce the learning curve.

Serum paraoxonase 1 activity and protein N-homocysteinylation in primary human endometrial cancer.

Paraoxonase 1 plays an important role in protection from oxidative stress and also decomposes homocysteine thiolactone, the toxic metabolite of homocysteine. A limited number of reports evaluated the role of paraoxonase 1 in women affected by female genital tract neoplasms, including endometrial cancer. This study aimed to analyze the paraoxonase activity in the group of endometrial cancer patients (n = 48) who underwent primary surgery and to compare the data available with a well-matched control group (n = 30). Due to the role of paraoxonase 1 in the metabolism of homocysteine (Hcy) thiolactone, the amount of Hcy-thiolactone as well as total serum Hcy concentrations was also measured. Serum paraoxonase 1 activity toward synthetic substrates, paraoxon and phenyl acetate, in the study group was significantly lower compared to the control one. The mean paraoxonase 1 activity toward homocysteine thiolactone tended to be lower in the endometrial cancer group but this difference was not significant. There was no relationship between endometrial cancer and Q192R polymorphism of PON1 assessed by the dual substrate method. No differences in paraoxonase 1 activity between endometrial cancer subgroups according to clinico-pathological features were detected. Total serum homocysteine and protein-bound homocysteine thiolactone did not differ between control and cancer groups. In conclusion, reduced paraoxonase 1 activity suggests diminished important antioxidant mechanisms during the development of primary endometrial cancers in humans. PON1 Q192R polymorphism is not associated with the risk of endometrial cancer. Despite lower paraoxonase 1 activity, homocysteine concentration, and protein N-homocysteinylation in endometrial cancers do not differ from matched controls.

Fas-Related Apoptosis of Peritoneal Fluid Macrophages in Endometriosis Patients: Understanding the Disease.

Recent studies of the peritoneal cavity environment in endometriosis demonstrate quantitative and qualitative changes in the cells responsible for cell-mediated immunity. Such changes may have led to disturbances in the surveillance, recognition, and destruction of misplaced endometrial cells and might have, in fact, brought about the disease. The aim of the study was to assess CD95 (Fas) expression on (activated) peritoneal fluid (PF) macrophages, as well as to ascertain soluble Fas (sFas) concentration in the PF of endometriosis patients, as compared to the nonendometriotic group. The concentration of leukocytes in the PF, the percentage of cells expressing CD45+/CD14+, and the percentage of PF macrophages expressing the HLA-DR antigen were significantly higher in patients with stages I and II endometriosis. The percentage of Fas- (CD95+-) expressing macrophages was significantly higher in all stages of the disease, in comparison with controls. Moreover, the concentration of sFas in the PF of patients with moderate and severe endometriosis was significantly higher, as compared to the reference group. The high number of immune cells in PF in early stage endometriosis and their increased susceptibility to apoptosis confirm the role of the impaired peritoneal environment and immune defects in the development and progression of the disease.

Should we be more aware of endometrial cancer in adolescents?

Although endometrial cancer is generally diagnosed in women after menopause, it may incidentally develop in young women or even in adolescents. Diagnostic tools should be applied in young teenage girls complaining of abnormal genital bleeding, particularly those with hereditary cancer syndromes (such as Cowden or Lynch syndromes). Adolescents affected by polycystic ovary syndrome and obesity may also be at increased risk for the development of atypical endometrial hyperplasia and endometrial cancer, and should be carefully managed when the distressing symptoms occur. In the present article, we briefly summarize the principal clinical correlates associated with endometrial cancer in adolescents.

Nonabsorbable urethral bulking agent - clinical effectiveness and late complications rates in the treatment of recurrent stress urinary incontinence after 2 years of follow-up.

OBJECTIVE: Those patients who failed to achieve continence after a procedure aimed to correct it, require a special attitude and precise management due to the sophisticated anatomical and functional field of interest. The purpose of the present study was to assess long-term clinical efficacy and evaluate the frequency and severity of any complications related to recurrent stress urinary incontinence treatment with a non-absorbable bulking agent periurethral injections. STUDY DESIGN: Between February 2012-September 2013, 66 patients with recurrent stress urinary incontinence were treated with Urolastic in the tertiary referral gynecologic department. The efficacy of the procedure was assessed objectively at each follow-up visit, scheduled at two, six weeks and 3, 6, 12 and 24 months after primary procedure. Material was injected under local anesthesia according to the manufacturer's instructions, at 10, 2, 4 and 8 o'clock positions with 0.5-1.25ccm per spot. Statistical analyses were performed with Statistica package version 8.0 (StatSoft Inc., Tulsa, OK, USA). A p value <0.05 was considered statistically significant. RESULTS: Objective success rate at 24 months was found in 32.7% of patients, including 22.4% patients who were completely dry. The efficacy of Urolastic, when considering the intention to treat, is 24.2% and 16.7%, respectively. In 4.5% patients an oval shaped material was found inside the bladder. Overall, complications were observed in 17 (25.8%) patients. CONCLUSIONS: Although only 30% of patients will benefit from Urolastic injection on the long-term basis it seems to be a safe procedure in the treatment of recurrent stress urinary incontinence.

When and how should we treat cesarean scar defect - isthmocoele?

The reported number of cesarean sections in Poland is approximately 30% and is associated with increasing number of early and late complications. The myometrial discontinuity at the site of previous cesarean section is known in the literature as "isthmocoele", "niche", "pouch" or cesarean scar defect. In most cases presence of isthmocoele has no clinical significance, but in some patients it may cause abnormal uterine bleeding, dysmenorrhea, dyspareunia, pelvic pain or be associated with secondary infertility. This defect may be treated by laparoscopy, hysteroscopy or vaginal surgery.

Laparoscopic extraperitoneal lumboaortic lymphadenectomy in 10 steps - Let's make it easier!

OBJECTIVE: Laparoscopic extraperitoneal lymphadenectomy has both advantages of minimally invasive approach and retroperitoneal access. Although procedure is described for more than two decades there is a lack of diffusion of the technique. Standardization and simple description of the technique is main objective of this video. We described this procedure in 10 logical steps which could help to understand and perform this procedure. METHODS: This video presents systematic approach to extraperitoneal lumboaortic lymphadenectomy which was clearly divided in ten steps ordered in a counter-clockwise direction. RESULTS: CONCLUSIONS: Laparoscopic extraperitoneal access to lumboaortic lymph nodes is an effective method of lymphadenectomy which may bring benefits to a patient and physician. Presented ten steps help to perform each part of surgery in logical sequence making procedure ergonomic, easier to adopt and learn. Prior development of operative area in the extraperitoneal space followed by identification of anatomical landmarks is an important step which should precede lymph node dissection. Standardization of laparoscopic techniques could help to reduce learning curve.

Hysterectomy trends for benign indications over a 15-year period in an academic teaching center in Poland: a retrospective cohort study.

OBJECTIVES: The aim of the study was to evaluate changes in the operative trends for various types of hysterectomy due to benign indications, between 2001 and 2015, at the 2nd Department of Gynecology, Medical University of Lublin, as compared to the National Health Service (NHS) registry in Poland. MATERIAL AND METHODS: A retrospective cohort study was conducted. Data from the Internal Hospital Discharge Registry and Pathological Results Registry have been compared to the NHS database, which has been available nationwide since 2009. RESULTS: The study group included 5629 women who underwent hysterectomy due to benign indications. During the study period, the following number of procedures were performed: total abdominal hysterectomy - 344 (6.11%), total abdominal hysterectomy with bilateral salpingo-oophorectomy - 1760 (31.27%), total vaginal hysterectomy - 563 (10.00%), subtotal abdominal hysterectomy - 2536 (45.05%), and laparoscopically-assisted subtotal hysterectomy (LASH) - 426 (7.57%). The abdominal route, with the preference for subtotal abdominal hysterectomy, was the main approach to hysterectomy. Symptomatic fibroids were the most common indication for the procedure. Comparison of data collected over the last five years revealed a significant difference in the approach to hysterectomy in favor of subtotal abdominal hysterectomy (SAH) and LASH. CONCLUSIONS: Less invasive techniques of hysterectomy (LASH, SAH), which are the preferred choice at the 2nd Department of Gynecology (Lublin), are safe and effective options of treating benign conditions. We are of the opinion that these ap-proaches should be offered to patients instead of more radical techniques. Proper training of physicians may influence the decision-making process in favor of minimally invasive techniques.