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.

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.

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.

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.

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.

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.

Significance of TGFBR3 allelic loss in the deregulation of TGFß signaling in primary human endometrial carcinomas.

Downregulation of betaglycan (ß-glycan) [transforming growth factor ß receptor type III (TGFßR3)], which belongs to co-receptors of the TGFß pathway, occurs in a broad spectrum of primary human malignancies. However, in the case of endometrial cancer (EC), the mechanisms responsible for genetic alterations are still unknown. Therefore, we investigated allelic imbalance at the TGFBR3 locus (1p33­p32) in the context of ß-glycan mRNA and protein expression, as a possible genetic event determining ß-glycan deregulation in EC patients. Study of ß-glycan allelic imbalance in 48 primary human ECs was performed with the use of three different microsatellite markers, spanned within or in direct proximity to the TGFBR3 locus. Real­time PCR and western blotting were used for ß-glycan mRNA and protein quantification methods, respectively. Altogether, 25 of 39 (64%) informative cases and 25 of 48 (52%) of all specimens showed allelic imbalance in at least one microsatellite marker, concomitantly with decrease at both the ß-glycan transcript and protein levels. Interestingly, 54% (15/28), 36% (8/22) and 35% (7/20) of informative ECs displayed allelic loss in D1S188, D1S435 and D1S1588 microsatellite markers, respectively. It is worth pointing out that 5 out of 39 (13%) informative cases showed loss of heterozygosity (LOH) at two microsatellite markers. Microsatellite instability (MSI) was found in two markers, but to a very strictly limited extent. None of the clinicoprognostic features was found to be of significance. Our results suggest that LOH in the TGFBR3 locus may be one of the mechanisms responsible for loss of ß-glycan expression. No correlation of LOH at the TGFBR3 locus with clinicopathological parameters suggests that allelic imbalance may be an early genetic event during neoplastic transformation of human endometrium.