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.

A prospective cohort trial evaluating sexual function after urethral diverticulectomy.

OBJECTIVE: Dyspareunia is a main symptom of urethral diverticulum in the female population, reported up to 60% of patients. Pain may cease after diverticulectomy as published in previous retrospective studies. To date scarce or no data exists on the postoperative outcome in terms of sexual function. The present study wants to quantify sexual function and evaluate lower urinary tract symptoms in sexually active patients after resection of urethral diverticulum. STUDY DESIGN: In this prospective cohort trial at a tertiary referral center, we evaluated 40 female patients who presented with symptomatic urethral diverticulum and were sexually active. All of them underwent a standardized surgical procedure with inverted U-shape colpotomy between 2008 and 2018. The patients completed the Female Sexual Function Index (FSFI), which is determined by the mean score of the different domains, and underwent urodynamic assessment both at baseline examination before surgery and 12 months postoperatively. For statistical analysis, we conducted a paired Wilcoxon rank sum test analyzing the non-normally distributed non-parametric variables of the female sexual function index. RESULTS: In two patients a malignancy was found in postoperative histology and received a different therapeutical approach. They have been excluded from statistical analysis. Sexual function improved in all domains (n = 38): total score (Z = -5.4, P < 0.000), satisfaction (Z = -5.3, P < 0.000), pain (Z = -5.4, P < 0.000), arousal (Z = -2.6, P = 0.010), lubrication (Z = -2.4, P = 0.020), desire (Z = -2.6, P = 0.009) and orgasm (Z = -2.2, P = 0.029). Maximum urethral closure pressure deteriorated from 39 to 36 cmH2O (P = 0.0008) and residual urine increased from 10 ml to 20 ml after surgery (P = 0.0019). No statistical significance is found for bladder capacity and free urinary flow. CONCLUSIONS: All domains of the female sexual function index improved. Patients' bothersome symptoms, mainly pain may cease and sexual satisfaction increases, which is reassuring concerning patients' preoperative consent. We should be aware that occasionally an unexpected malignancy may be detected and it is mandatory to examine all excised tissue histologically. Lower urinary tract function remains clinically unchanged, although maximum urethral closure pressure deteriorated and postvoid residual increased though not being clinically significant.

Geometry, Structure and Surface Quality of a Maraging Steel Milling Cutter Printed by Direct Metal Laser Melting.

This article considers the use of additive manufacturing to produce cutting tools for various machining operations, especially turning, milling, and drilling. The right geometry and material of the tool as well as coatings applied on cutting edges are crucial as they improve the life and performance of the tool. The study described here focused on a four-flute end mill made of maraging steel 1.2709 using a Concept Laser M2 Cusing Direct Metal Laser Melting (DMLM) machine. Before the printed tool was first used, it was examined to determine its dimensional and geometric accuracy, surface roughness, and surface structure. The measurement data showed that the tool required machining, e.g., grinding, to improve its geometry because the total runout of the shank and the cutting edge radius were too high, amounting to 120 µm and 217 µm, respectively. The cutting edges were sharpened to obtain a fully functional cutting tool ready to perform milling operations. The study aimed to check the dimensional and geometric accuracy of the 3D printed milling cutter and determine the optimal machining allowance for its finishing.

Analyzing the Effects of the Kinematic System on the Quality of Holes Drilled in 42CrMo4 + QT Steel.

This article discusses the relationship between the kinematic system used in drilling and the quality of through-holes. The drilling was done on a CTX Alpha 500 universal turning center using a TiAlN-coated 6.0 mm drill bit with internal cooling, mounted in a driven tool holder. The holes were cut in cylindrical 42CrMo4 + QT steel samples measuring 30 mm in diameter and 30 mm in length. Three types of hole-drilling kinematic systems were considered. The first consisted of a fixed workpiece and a tool performing rotary (primary) and linear motions. In the second system, the workpiece rotated (primary motion) while the tool moved linearly. In the third system, the workpiece and the tool rotated in opposite directions; the tool also moved linearly. The analysis was carried out for four output parameters characterizing the hole quality (i.e., cylindricity, straightness, roundness, and diameter errors). The experiment was designed using the Taguchi approach (orthogonal array). ANOVA multi-factor statistical analysis was used to determine the influence of the input parameters (cutting speed, feed per revolution and type of kinematic system) on the geometrical and dimensional errors of the hole. From the analysis, it is evident that the kinematic system had a significant effect on the hole roundness error.

Influence of Relative Displacement on Surface Roughness in Longitudinal Turning of X37CrMoV5-1 Steel.

The shaping process of surface texture is complicated and depends on many factors and phenomena accompanying them. This article presents the author's test stand for the measurement of relative displacements in a tool-workpiece system during longitudinal turning. The aim of this study was to determine the influence of edge radius on the relative displacement between the tool and workpiece. The cutting process was carried out with inserts with different edge radii for X37CrMoV5-1 steel. As a result of the research, vibration charts of the tool-workpiece system were obtained. In the range of feed 0.03-0.18 mm/rev, the values of the standard deviation of relative displacements in the x-axis were obtained in the range of 0.36-0.78 µm for the insert with an edge radius of rn = 48.8 µm. As a result of the work, it was determined that for the feed value of 0.12 mm/rev for all inserts, the relative displacements are the smallest. As the final effect, the formula for forecasting the Ra roughness parameter was presented.

Predictive value of classification systems and single fistula-related factors in surgical management of vesicovaginal fistula.

AIMS: The aim of this study was to find the most clinically useful vesicovaginal fistula (VVF) classification system or single fistula-related factor, which would be helpful in determining the most proper management leading to successful treatment. METHODS: Between 2018 and 2020, 30 patients were diagnosed with VVF and underwent the Latzko procedure. Nineteen patients, after previously failed surgery, were injected with platelet-rich-plasma (PRP) before a final attempt to close VVF. Patients with primary VVF were included into the surgery only group and patients with secondary VVF were included into PRP and surgery group. Each patient was classified according to 13 different classification systems. RESULTS: Statistical evaluation revealed some significant differences between the patients who required PRP injection and repeated surgery, compared with patients who were successfully treated at first surgery but only with Lawson, Waaldijk, Arrowsmith, and Tafesse classifications. Patients who succeded with the fistula closure after the first surgical procedure had significantly higher body mass index (BMI) when compared with patients who required PRP injection prior surgical procedure (30.9 vs. 25.7, respectively; p < .05). CONCLUSIONS: None of the classification systems allows to precisely predict VVF surgery outcome. There are several factors such as previous surgery, lack of urethral involvement, lack of circumferential defect which might suggest that PRP injection would help to preserve watertightness of the closure. The most important finding is that overweight is the most positive predicting demographic feature of surgical success. Thus we may conclude that Martius flap technique should be taken into consideration in patients with low BMI.

Blebbistatin reveals beneficial effects on the cystometric parameters in an animal model of detrusor overactivity.

The aims of the study were to determine the effectiveness of blebbistatin (BLEB) on detrusor overactivity (DO) in an animal model induced by retinyl acetate (RA) and, because of potential urothelial permeability, to evaluate the degenerative impact of BLEB on the urothelium. Three days after RA instillation into the urinary bladder, BLEB was administered into the bladder and immediately after cystometric assessment was performed. Furthermore, Evans Blue extravasation into bladder tissue and urothelium thickness were measured. Sixty female Wistar rats were used and randomly assigned to one of four groups (n = 15 in each group): (1) control, (2) RA, (3) BLEB, and (4) RA + BLEB. RA administration induced changes in cystometric parameters reflecting DO, as previously reported. Treatment with BLEB did not significantly alter cystometric parameters in rats which did not receive RA. Administration of BLEB to rats pretreated with RA reversed changes in cystometric parameters induced by RA in basal pressure, threshold pressure, detrusor overactivity index, amplitude of nonvoiding contractions, frequency of nonvoiding contractions, voided volume, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions. There were no significant differences in Evans Blue extravasation into bladder tissue or urothelium thickness between the groups. The current research provides new data on the possible utility of blebbistatin in the pharmacotherapy of DO, which is an important feature of overactive bladder (OAB). Further studies in human patients with DO/OAB are warranted to confirm these preclinical results.

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.

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.

Prevalence of common comorbidities among urogynaecological patients.

OBJECTIVES: Due to prolonged life expectancy, regardless of the fact that elderly women are more likely to suffer from comorbidities, urogynaecologists worldwide should expect a growing demand for counseling and effective treatment for patients with pelvic floor defects. The aim of the study was to investigate the incidence of popular comorbidities among urogynaecological patients. MATERIAL AND METHODS: The retrospective analysis included clinical data of 4,065 consecutive female patients who under-went surgical treatment in the 2nd Department of Gynaecology at the Medical University of Lublin due to urogynaecological disorders between January 2005 and December 2014. Patients were divided into two groups (< 65 years and ≥ 65 years). The vast majority of patients affected by stress urinary incontinence were treated with mid-urethral slings. Most of patients affected by pelvic organ prolapse underwent reconstructive vaginal surgery with reinforcement using anterior and/or pos-terior meshes. Statistical analysis was performed using STATISTICA 10.0 PL (unpaired Student t-test, U Mann Whitney, χ2 test). RESULTS: In both study groups, overweight and obesity were the most common disorders affecting urogynaecological patients (72.6% overall). Furthermore, the elderly patients suffered more often from the most common comorbidities, such as hypertension (p < 0.01), coronary artery disease (p < 0.001) and diabetes mellitus (p < 0.005). CONCLUSIONS: Common comorbidities such as overweight and obesity, followed by hypertension and coronary heart diseases, are usual among urogynaecological patients. Changes in lifestyle leading to a decrease in obesity should be considered as an important line treatment when counselling urogynaecological patients.

[The influence of mesh pelvic floor reconstructive surgery on OAB symptoms]. / Wplyw operacji naprawczych zaburzen statyki narzadu rodnego na redukcje objawów zespolu pecherza nadreaktywnego.

OBJECTIVES: The working hypothesis was that pelvic organs prolapse can induce overactive bladder symptoms. Therefore, restoration of pelvic anatomy with accompanying proper urodynamic parameters (cystometric volume, micturition volume, uroflow) should resolve OAB (Overactive Bladder) symptoms. MATERIALS AND METHODS: Forty eight women, aged 51-77 years (mean 62.4±7.32), with stage II, III or IV prolapse (POP-Q scale) were included into the study. Patients with LUTS (Lower Urinary Tract Symtoms--inflammation, infection, pain) were excluded. Each patient underwent clinical evaluation and full urodynamic examination (cystometry and uroflowmetry MMS Libra +). Depending on the type of the anatomical defect on the POP-Q scale--anterior defect, posterior defect or both anterior and posterior--a repair using polypropylene monofilament mesh was performed (TVM anterior, TVM posterior or TVM Total). Patients were asked to complete King's Health questionnaire before and after the reconstructive surgery. Statistical analysis was performed using Kolmogorov-Smirnov and U Mann-Whitney tests. RESULTS: Overactive bladder symptoms were diagnosed in 27 patients. Detrusor overactivity was found in 10 patients. In 17 patients, out of 27 with OAB before surgery overactivity symptoms completely resolved after the surgery (63%). On the other hand, post-op de novo OAB symptoms appeared in 2 patients (4.1%). Half of the patients with OAB symptoms after surgery had detrusor overactivity before mesh repair while only 30% of patients without OAB symptoms after surgery had DO (Detrusor Overactivity) before the surgical procedure. Micturition volume in group of patients with OAB significantly increased after the surgery (293.78 ml vs. 364.15 ml; p=0.006). Maximal cystometric capacity in patients with overactive bladder also significantly increased after the surgery (318.78 ml vs. 407 ml; p=0.0001). Quality of life measured by King's questionnaire improved in the group of patients with resolution of OAB symptoms in such domains as: Incontinence Impact, Role Limitations and Sleep/emotions, p<0.05. CONCLUSIONS: Correction of pelvic organ prolapse stage II, III and IV in patients with OAB symptoms leads to an improvement in bladder conditions in half of the patients. Such treatment also resulted in symptom resolution of detrusor overactivity ascertained in urodynamic studies. Overactive bladder syndrome with DO was more resistant to surgical treatment as compared to OAB without DO. Quality of life improved in patients who did not present with OAB bladder symptoms after the mesh surgery. Restoration of proper anatomy might also cure or improve bladder symptoms in patients with OAB symptoms, coexisting with advanced pelvic organ prolapse.

Laparoscopic mesh procedures for the treatment of pelvic lorgan prolapse--review of the literature.

OBJECTIVES: The main aim of the article was to describe laparoscopic mesh procedures for the treatment of pelvic organ prolapse, as well as evaluate their role, outcomes and limitations. MATERIAL AND METHODS: In February 2014, online search of English-language literature in PubMed was performed. This paper presents the analysis of reports published over the last decade that included at least 50 patients with a minimum of 12 months of follow-up. RESULTS: Numerous laparoscopic techniques to restore proper anatomy in patients with pelvic organ prolapse have been described. Laparoscopy provides a number of important advantages, including enhanced visualization of the pelvic anatomy reduction of adhesion formation, lower morbidity and blood loss, decreased postoperative pain, smaller incision and quicker recovery Nonetheless, this access is technically more difficult than an open or vaginal surgery due to two-dimensional vision and decreased degrees of freedom. It requires high level of laparoscopic suturing skills and longer operative time, especially at the beginning of the learning curve. CONCLUSIONS: Laparoscopic sacrocolpopexy hysteropexy and lateral suspension are interesting and effective options for the treatment of pelvic organ prolapse, providing a number of important advantages characteristic for endoscopic techniques.

[Clinical effectiveness of transobturator midurethral sling (T-sling) with additional 2-point tape fixation performed on an outpatient and inpatient basis]. / Ocena efektywnosci klinicznej operacji typu T-Sling z fiksacja tasmy wykonywanej w ramach procedury jednodniowej i standardowej.

INTRODUCTION: Nowadays, mid-urethral slings are considered the gold standard in surgical treatment of female stress urinary incontinence (SUI). Traditionally this technique has been followed by short inpatient hospitalization and convalescence. From the perspective of both, the patient and the physician, this technique has become increasingly popular due to very high clinical effectiveness and fast recovery ' OBJECTIVES: The aim of the study was to compare the efficacy and safety of transobturator monofilament sling (T-sling-Hernia Mesh, Italy) with additional 2-point tape fixation in the treatment of SUI in women operated on an inpatient and outpatient basis. MATERIAL AND METHODS: A total of 200 women with stress urinary incontinence were included into the study Clinical diagnosis was based on detailed medical history voiding diary gynecological examination, and positive cough test. Exclusion criteria were as follows: previous urogynecologic surgery detrusor overactivity on urodynamics and advanced urogenital prolapse (pelvic organ prolapse-quantification [POP-Q] scale grades--II, III, IV). In both groups the surgery was performed by two (TR; A W) surgeons. Using identical surgical technique, all patients had a monofilament tape inserted at the mid-urethra with 2 absorbable sutures parallel to the urethra in order to fix the tape and prevent its displacement during tape tensioning. Patients were discharged home after the first spontaneous voiding (outpatient group) or 2 days (inpatient group) postoperatively After 12 months, 192 patients (99 in outpatient and 93 in inpatient group) were available for assessment of clinical effectiveness of surgery Success was defined as lack of any leakage during cough stress test. The subjective cure rate was determined by Sandvik scale also after 12 months. Statistical analysis was performed with Statistica 7.1 pl and Mann-Whitney U and Chl tests were used. P-level of < or = 0.05 was considered as statistically significant. RESULTS: There were no differences in demographical data of patients from both groups. The only difference between the two groups concerned the body mass index (mean 26.6 +/- 3.9 vs. 28.67 +/- 3.99; p<0.001) and age (50.48 +/- 9.71 vs. 61.7 +/- 9.2; p<0.001) in the outpatient versus inpatient group, respectively There was no significant difference between the two groups in terms of the overall patients satisfaction and cure rate after the 12-month follow-up (chi2=4.039, p=0.133). CONCLUSIONS: Proper surgical technique but not length of hospitalization is the main factor determining the effectiveness of surgical treatment of SUI. Tape fixation is a simple surgical maneuver that ensures proper sling placement at mid-urethra and does not markedly increase procedure duration or cost of the treatment. Outpatient surgery for SUI using transobturator mid-urethral sling ensures the same cure and satisfaction rates as inpatient orocedure. allowing to reduce the cost of the treatment without compromising clinical effectiveness.

[Nerve growth factor as a biomarker in the diagnosis and treatment of overactive bladder (OAB)]. / Czynnik wzrostu nerwów (NGF) jako biomarker w diagnostyce i terapii peccherza nadreaktywnego (OAB).

Nerve growth factor is a complex regulator of neural plasticity along the micturition pathways. The aim of this review is to summarize the current evidence for a role of NGF in urinary bladder function both in experimental and clinical settings. There is bulk of strong evidence that experimental administration of NGF elicits the symptoms of increased sensation, urgency and bladder hyperreflexia which strongly resemble overactive bladder syndrome (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS). Therefore in human studies there are attempts to employ urinary NGF levels as a diagnostic marker in various forms of OAB and IC/PBS. It has been shown that urinary NGF levels are correlated with severity of OAB symptoms and in patients successfully treated with antimuscarinics agents or detrusor botulinum toxin injection, urinary NGF levels decrease significantly in association with reduction of urgency severity