Role of Leptin and Adiponectin in Endometrial Cancer.

Endometrial cancer is the most common malignancy of the female genital tract. Obesity is a strong risk factor for endometrial cancer. Adipose tissue is an active endocrine organ that synthesizes biologically active cytokine peptides, called adipokines. Adiponectin and leptin are the main cytokines of adipose tissue, which may influence the development of metabolic diseases and carcinogenesis. In this scenario, we describe the role of leptin and adiponectin in the development of endometrial cancer. A better understanding of the signalling pathway of these cytokines in endometrial cancerogenesis will provide an opportunity for effective target therapy and may be usable in fertility-sparing treatment. In the future, clinical trials focusing on adipokines, molecular biology, and genetics of the tumour will be needed.

Global Changes of 5-mC/5h-mC Ratio and Methylation of Adiponectin and Leptin Gene in Placenta Depending on Mode of Delivery.

It was suggested that the epigenetic alterations of the placenta are associated with obesity, as well as the delivery mode. This study aimed to assess the effect of maternal outcome and delivery procedure on global placental DNA methylation status, as well as selected 5'-Cytosine-phosphate-Guanine-3' (CpG) sites in ADIPOQ and LEP genes. Global DNA methylation profile in the placenta was assessed using the 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) ratio evaluated with the ELISA, followed by target gene methylation patterns at selected gene regions which were determined using methylation-specific qPCR in 70 placentas from healthy, pregnant women with single pregnancy. We found no statistically significant differences in 5-mC/5-hmC ratio between intrapartum cesarean sections (CS) and vaginal deliveries (p = 0.214), as well as between elective cesarean sections and vaginal deliveries (p = 0.221). In intrapartum cesarean sections, the ADIPOQ demethylation index was significantly higher (the average: 1.75) compared to elective cesarean section (the average: 1.23, p = 0.010) and vaginal deliveries (the average: 1.23, p = 0.011). The LEP demethylation index did not significantly differ among elective CS, intrapartum CS, and vaginal delivery groups. The demethylation index of ADIPOQ correlated negatively with LEP in the placenta in the vaginal delivery group (r = -0.456, p = 0.017), but not with the global methylation. The methylation of a singular locus might be different depending on the mode of delivery and uterine contractions. Further studies should be conducted with locus-specific analysis of the whole genome to detect the methylation index of specific genes involved in metabolism.

Is PREHAB in Pelvic Floor Surgery Needed? A Topical Review.

Pelvic organ prolapse and urinary incontinence affect approximately 6-11% and 6-40% of women, respectively. These pathologies could result from a weakness of pelvic floor muscles (PFM) caused by previous deliveries, aging or surgery. It seems reasonable that improving PFM efficacy should positively impact both pelvic floor therapy and surgical outcomes. Nonetheless, the existing data are inconclusive and do not clearly support the positive impact of preoperative pelvic floor muscle training on the improvement of surgical results. The restoration of deteriorated PFM function still constitutes a challenge. Thus, further well-designed prospective studies are warranted to answer the question of whether preoperative PFM training could optimize surgical outcomes and if therapeutic actions should focus on building muscle strength or rather on enhancing muscle performance.

Genitourinary syndrome of menopause - is the problem solved? State of the art 2018.

Vulvovaginal atrophy accompanied by lower urinary tract dysfunction related to low levels of estrogen and androgens is labeled as genitourinary syndrome of menopause (GSM). Although this condition affects most postmenopausal women worldwide, it seems to be underdiagnosed and undertreated. Women should be properly advised to choose an adequate treatment modality to improve their quality of life, sexual relationships and social activity. The aim of this article to is increase knowledge of GSM. The current treatment options, both hormonal and non-hormonal, are reviewed. Topical estrogen therapy still remains the gold standard, but the demand for individually tailored therapy is growing. New treatment modalities are continuously included in clinical practice. They should consider the whole personality of a woman as well as cultural and social factors. Further studies on GSM and on the effectiveness of various treatment options are necessary to achieve this purpose.

Alternative Oral Agents in Prophylaxis and Therapy of Uterine Fibroids-An Up-to-Date Review.

Uterine fibroids (UFs) are the most common tumors of the female genital tract. The effect of UFs on the quality of life and the overall cost of treatment are significant issues worldwide. Tumor size and location are the two specific factors which influence the occurrence of symptoms, the need for, and method of, treatment (some tumors require surgery while some can be treated with selected drugs). Primary prevention and treatment of early UF disease are worthy goals that might have a great impact on health care systems. Several treatments and prophylactic methods can be used in this endeavor. This publication presents current data about lesser-known substances which may have a beneficial effect on the treatment or prophylaxis of UFs and can be administered orally, serving as an alternative to (or complement of) surgery or selective progesterone receptor modulators (SPRMs). Early prevention and treatment of UFs in women from high-risk groups should be our priority. Innovative forms of UF management are under intensive investigation and may be promising options in the near future. Many of them evaluated vitamin D, paricalcitol, epigallocatechin gallate (EGCG), elagolix, aromatase inhibitors (AIs), and cabergoline and deemed them to be safe and effective. The next step in such projects should be properly constructed randomized control trials (RCTs), carried out by successive phases.

Role of Transforming Growth Factor ß in Uterine Fibroid Biology.

Uterine fibroids (UFs) are benign tumors of the female genital tract made of the smooth muscle of the uterus. UF growth depends mostly on the influence of the steroid hormones and selected growth factors. Transforming growth factor ß (TGF-ßs) is a polypeptide that consists of three isoforms: TGF-ß1, TGF-ß2, and TGF-ß3. At present, TGF-ß is considered to be one of the key factors in the pathophysiology of UFs. It plays a major role in cellular migration within the tumor, stimulates tumor growth, and enhances tumor metabolism. As a consequence of various dependencies, the synthesis and release of TGF-ß in a UF tumor is increased, which results in excessive extracellular matrix production and storage. High concentrations or overexpression of TGF-ß mediators may be responsible for clinically symptomatic UFs. The aim of this review was to check the available evidence for the influence of the TGF-ß family on UF biology. We conducted their search in PubMed of the National Library of Medicine with the use of the following selected keywords: "uterine fibroid", "leiomyoma", and "transforming growth factor ß". After reviewing the titles and abstracts, more than 115 full articles were evaluated. We focused on the TGF-ß-related molecular aspects and their influence on the most common symptoms that are associated with UFs. Also, we described how the available data might implicate the current medical management of UFs.

Case report of ovarian torsion mimicking ovarian cancer as an uncommon late complication of laparoscopic supracervical hysterectomy.

Laparoscopic supracervical hysterectomy (LSH) is an example of a partial hysterectomy, performed due to benign gynaecological complaints. Better endoscopic instruments and operational techniques have led to a great reduction in the number of abdominal hysterectomies. It is believed that LSH is a safe and minimally invasive hysterectomy technique. The Cochrane Database meta-analysis proves the benefits of minimally invasive surgery compared with abdominal gynaecological surgery, including decreased pain, surgical-site infections and hospital stay, quicker return to activity, and fewer postoperative adhesions. According to recent publications, the overall complication rate of all hysterectomy methods is about 1-4.5%. Adnexal torsion is a correlated complication. About 3-5% of patients undergoing emergency surgery due to pelvic pain are diagnosed with this condition. It may be the cause of acute abdomen and correlated symptoms such as vomiting, nausea, or severe pain. To the best of our knowledge a case of asymptomatic, delayed ovarian torsion mimicking ovarian tumour has not been reported so far. In the presented case, torsion successfully imitated neoplastic process as both ROMA score and IOTA 'simple rules' indicated a malignancy with high degree of probability. This case demonstrates that, if ovarian tumour is detected in the postoperative period, a torsion of ovarian pedicle should be taken into consideration as it may mimic malignant neoplasm.

Vaginal foreign body mimicking cervical cancer in postmenopausal woman - case study.

We present a case report of a 73-year-old, postmenopausal woman with detailed history of breast cancer and oncology treatment including tamoxifen therapy. She presented at the clinic of gynecology and obstetrics with recurrent inflammation of the urinary and genital tract and suspicion of a cervical mass. She also presented occasional abdominal complaints and malodorous vaginal discharge. These symptoms were observed in the patient for several years. Before hospitalization she received many kinds of empirical, antimicrobial treatment such as chlorquinaldol, metronidazole, nifuratel, and nystatin. She did not receive further guidance from doctors about the causes of ailments and further diagnostic and treatment capabilities. In our clinic a detailed diagnostic process including ultrasound transvaginal examination and a minisurgical procedure revealed the presence of a vaginal foreign body (which turned out to be a plastic, shampoo bottle cap) surrounded by a mass of inflamed tissue mimicking a cervical tumor. All symptoms and complaints subsided after surgical removal of the foreign body and antibacterial therapy with metronidazole and cefuroxime. Our study draws attention to the need of thorough gynecological care including prophylaxis, especially in the case of complaints of an intimate nature. Even trivial, frequently occurring disorders can be dangerous and require proper and responsible doctor's supervision and management through the healing process.

Andropause - state of the art 2015 and review of selected aspects.

The term 'male menopause' was first used in 1944 to describe various complaints of ageing men which at least partially mirrored the climacteric symptoms in women. Continuous research resulted in the evolution of opinions about the nature of these complaints, from the clinical syndrome, diagnosed with the use of disease-targeted questionnaires, to a well-defined clinical and biochemical syndrome. The pathophysiological causes - gonad ageing (with a compensatory rise in luteinizing hormone), age-related increase in serum sex hormone-binding globulin (SHBG) levels, the role of visceral adipose tissue as a place for aromatization of androgen to estrogen, and lower sensitivity of testosterone receptors - have been described. However, no consensus was reached as far as the definition, incidence, treatment, and especially testosterone therapy, are concerned. Our review presents the current standpoints, indicating the predictive role of late-onset hypogonadism (LOH) in evaluating male health as well as the current literature reports on the risks and benefits of using testosterone therapy.

Cervical microbiota dysbiosis associated with high-risk Human Papillomavirus infection.

High-risk Human Papillomavirus (HR-HPV) genotypes, specifically HPV16 and HPV18, pose a significant risk for the development of cervical intraepithelial neoplasia and cervical cancer. In the multifaceted cervical microenvironment, consisting of immune cells and diverse microbiota, Lactobacillus emerges as a pivotal factor, wielding significant influence in both stabilizing and disrupting the microbiome of the reproductive tract. To analyze the distinction between the cervical microbiota and Lactobacillus-dominant/non-dominant status of HR-HPV and non-infected healthy women, sixty-nine cervical swab samples were analyzed, included 44 with HR-HPV infection and healthy controls. All samples were recruited from Human Papillomavirus-based cervical cancer screening program and subjected to 16s rRNA sequencing analysis. Alpha and beta diversity analyses reveal no significant differences in the cervical microbiota of HR-HPV-infected women, including 16 and 18 HPV genotypes, and those with squamous intraepithelial lesion (SIL), compared to a control group. In this study we identified significantly lower abundance of Lactobacillus mucosae in women with HR-HPV infection compared to the control group. Furthermore, changes in bacterial diversity were noted in Lactobacillus non-dominant (LND) samples compared to Lactobacillus-dominant (LD) in both HR-HPV-infected and control groups. LND samples in HR-HPV-infected women exhibited a cervical dysbiotic state, characterized by Lactobacillus deficiency. In turn, the LD HR-HPV group showed an overrepresentation of Lactobacillus helveticus. In summary, our study highlighted the distinctive roles of L. mucosae and L. helveticus in HR-HPV infections, signaling a need for further research to demonstrate potential clinical implications of cervical microbiota dysbiosis.

Sacral Neuromodulation in Pregnant Women-A Case Report and Literature Review.

Millions of women around the world suffer from an overactive bladder and urinary retention. A significant number of them are of reproductive age. For 25 years, SNM has been an effective therapy for treatment-resistant hyperactive bladder and idiopathic urinary retention. The paper presents a case of a 35-year-old pregnant woman with an overactive bladder resistant to pharmacological treatment, who responded positively to sacral neuromodulation. The patient decided against deactivating the neuromodulator and, after an uneventful course of pregnancy, she gave birth by a caesarean section to a healthy female infant. The use of SNM in pregnant patients remains a constant clinical challenge. The current literature was reviewed, but published studies do not provide a clear answer. Further studies with a long follow-up period are necessary to determine more accurately the effects of SNM therapy on the fetus and the course of pregnancy. Currently, it is recommended to deactivate SNM during pregnancy. However, it seems that an individual approach to the patient with information on the risks and benefits of continuing or discontinuing therapy should be the current procedure.

Vaginal Aging-What We Know and What We Do Not Know.

The aging of the organism is a complex and multifactorial process. It can be viewed in the context of the whole organism, but also of individual tissues and organs. The problem of vaginal aging and the related genitourinary syndrome of menopause significantly reduces the quality of women's lives. The aging process of the vagina includes estrogen deficiencies, changes in the microbiome, and changes at the genetic level associated with DNA methylation. During the menopause, the number of Lactobacillus colonies decreases, and the number of pathological bacteria colonies increases. The decrease in estrogen levels results in a decrease in vaginal epithelial permeability, perfusion, and elastin levels, resulting in vaginal dryness and atrophy. Changes at the molecular level are the least clear. It can also be assumed that, similarly to the tissues studied so far, there are changes in cytosine methylation and TET (ten-eleven translocation) expression. The interrelationships between DNA methylation, hormonal changes, and the vaginal microbiome have not yet been fully elucidated.

Fowler's Syndrome-The Cause of Urinary Retention in Young Women, Often Forgotten, but Significant and Challenging to Treat.

Urinary retention in young women is a relatively rare clinical problem and is often underdiagnosed. In particular, functional causes of urinary retention pose a diagnostic challenge. One of them is Fowler's syndrome, which is associated with impaired urethral relaxation. Fowler's syndrome is characterized by a large bladder capacity, reduced sensation, increased maximal urethral closure pressure, and detrusor underactivity. Several hypotheses have arisen to explain the cause of urethral relaxation disorders: hormonal changes characteristic of Polycystic Ovary Syndrome (PCOS), causing abnormal stabilization of the muscle membrane, primary failure of relaxation of the striated muscle of the urethra sphincter, and increased urethral afferent activity, inhibiting the bladder afferent signals from reaching the brain by potentiating a spinal mechanism of urinary continence. Currently, sacral neuromodulation is the only intervention that can restore an atypical voiding pattern in women with Fowler's syndrome. The therapeutic effectiveness exceeds 70%, although the revision rate is relatively high, exceeding 50%. Well-designed, long-term prospective studies comparing sacral neuromodulation (SNM) with other therapies such as pelvic floor muscle physiotherapy are warranted to offer the best patient-tailored treatment.

Cervicovaginal Microbiome after Cervical Intraepithelial Neoplasia Treatment. A Protocol for Systematic Review and Meta-Analysis.

(1) Background: The microbiome consists of microorganisms from various kingdoms with numerous physical and chemical properties Lactobacillus species constitute the highest percentage of healthy cervical and vaginal microbiota. Dysbiosis may cause adverse outcomes, e.g., bacterial vaginosis, pelvic inflammatory disease and pregnancy complications. The cervicovaginal microbiome might contribute to the development of a persistent HPV infection-the main risk factor of cervical cancer-and influence progression to malignancy The aim is to perform a systematic review of current literature and a meta-analysis regarding microbiome changes after cervical intraepithelial neoplasia treatment. (2) Methods: We will search PubMed, Scopus, Google Scholar and Embase Database and trace citations in the reference sections. Randomized and non-randomized controlled studies, case-control and cohort studies published between January 2000 and May 2021 will be included in the study protocol. The following keywords will be used: 'microbiome', 'vaginal microbiome', 'cervical microbiome', 'cervical neoplasia treatment', 'conization', 'electroconization', and 'electrosurgical treatment'. Statistical analyses will be performed using RevMan 5.4. (3) Results: The results will be published as a peer-reviewed article. (4) Conclusions: The study will show which forms of intraepithelial neoplasia treatment change the cervicovaginal microbiome. Finding the best form of treatment by studying the cervicovaginal microbiome after various forms of treatment is essential. Patients would benefit not only from the treatment of the initial disease but also the management of dysbiosis, which might underlie other pathologies.

A Systematic Review and Meta-Analysis of Wound Complications after a Caesarean Section in Obese Women.

(1) Background: Caesarean sections in obese patients are associated with an increased risk of surgical wound complications, including hematomas, seromas, abscesses, dehiscence, and surgical site infections. The aim of the present study is to perform a meta-analysis and systematic review of the current literature focusing on the strategies available to decrease wound complications in this population. (2) Methods: We reviewed the data available from the PubMed and the Science Direct databases concerning wound complications after caesarean sections in obese women. The following key words were used: "caesarean section", "cesarean section", "wound complication", "wound morbidity", and "wound infection". A total of 540 papers were retrieved, 40 of which were selected for the final systematic review and whereas 21 articles provided data for meta-analysis. (3) Results: The conducted meta-analyses revealed that the use of prophylactic drainage does not increase the risk of wound complications in obese women after a caesarean sections (pooled OR = 1.32; 95% CI 0.64-2.70, p = 0.45) and that vertical skin incisions increase wound complications (pooled OR = 2.48; 95% CI 1.85-3.32, p < 0.01) in obese women, including extremely obese women. (4) Conclusions: Subcutaneous drainage does not reduce the risk of a wound complications, wound infections, and fever in obese women after caesarean sections. Negative prophylactic pressure wound therapy (NPWT) may reduce the risk of surgical site infections. The evidence of using a prophylactic dose of an antibiotic before the caesarean section is still lacking.

Effect of Excessive Body Weight and Emotional Disorders on the Course of Pregnancy and Well-Being of a Newborn before and during COVID-19 Pandemic.

This study aimed to evaluate whether excessive body weight and the COVID-19 pandemic affect depression, and subsequently whether depression, excessive body weight, and the COVID-19 pandemic affect the course of pregnancy, as well as the well-being of a newborn. The research material included data retrieved from the medical records of 280 pregnant women who were provided with care by medical facilities in Lublin (100 women with normal weight, 100 overweight women, 50 with Class I and 30 with Class II obesity). They completed a Beck depression inventory (BDI) in pregnancy twice, in order to assess the risk of occurrence of postpartum depression. Pre-pregnancy BMI positively correlated with the severity of depression, both at 10-13 weeks of pregnancy (p < 0.001), and at 32 weeks of pregnancy (p < 0.001). The higher the pre-pregnancy BMI, on average the higher the severity of depression. The severity of depression was significantly higher during the pandemic than before it in women with normal body weight before pregnancy (p < 0.001), as well as in those overweight (p < 0.001) and with Class II obesity (p = 0.015). Excessive body weight before pregnancy leads to depressive disorders during pregnancy, increases the risk of preterm delivery, and exerts a negative effect on the state of a newborn. Depressive symptoms among pregnant, overweight and obese women intensified during the COVID-19 pandemic.

Pelvic venous insufficiency - an often-forgotten cause of chronic pelvic pain.

Chronic pelvic pain is a common health problem that afflicts 39% of women at some time in their life. It is a common challenge for gynecologists, internists, surgeons, gastroenterologists, and pain management physicians. Pelvic venous insufficiency (PVI) accounts for 16-31% of cases of chronic pain but it seems to be often overlooked in differential diagnosis. The aim of this article was to summarize current data concerning PVI. The embolization of insufficient ovarian veins remains the gold standard of therapy but the optimal procedure is yet to be determined. Well-designed randomized trials are required to establish the best treatment modalities.

Intraoperative and early postoperative complications in women with stress urinary incontinence treated with suburethral slings: a randomised trial.

INTRODUCTION: The midurethral sling has become the current standard for the treatment of female stress urinary incontinence. AIM: To assess intraoperative complications, early post-operative complications as well as the efficacy of tension-free vaginal tape: retropubic and trans-obturator tape procedures. MATERIAL AND METHODS: The analysis involved 91 tension-free vaginal tape (TVT) and 60 transobturator tape (TOT) procedures. Both groups were comparable in terms of patient characteristics, urodynamic results, and preoperative quality of life (QoL) assessment. The complications were registered, and the effectiveness of the procedures was assessed subjectively by the patients at 1-, 3-, 6- and 12-month follow-up. RESULTS: A significantly lower risk of intraoperative and early post-operative complications was noted in the case of TOT procedures (OR = 0.35%, 95% CI: 0.13-0.92). Moreover, regardless of the method used, patients with two or more vaginal deliveries in their history had a reduced risk of complications, as compared to nulliparas and uniparas (OR = 0.38%, 95% CI: 0.16-0.91). Previous gynaecological surgery and old age increase the risk of complications with borderline significance (OR = 2.5, 95% CI: 0.97-6.3; OR = 2.3, 95% CI: 0.95-5.5 respectively). The rates of cure, improvement and failure were similar in both groups, as was the significant positive change in post-operative life quality. CONCLUSIONS: TVT and TOT procedures are characterised by a high cure rate and improvement in the post-operative quality of life. However, it seems that the transobturator approach should be the preferred method of treatment of SUI due to the reduced risk of complications, shorter procedure time, and lower intraoperative blood loss.

Pediatrics Consequences of Caesarean Section-A Systematic Review and Meta-Analysis.

BACKGROUND: Cesarean section is a surgical procedure, which is the most frequently performed in gynecology and obstetrics. It is commonly believed that an operative delivery is a less painful and safer mode of delivery, which translates into an increasing number of the procedures performed without medical indications. The maternal sequelae of cesarean sections are well elucidated and widely discussed in the literature, while long-term neonatal consequences still remain the issue of research and scientific dispute. The aim of the present paper was to perform a systematic review of current literature regarding pediatrics consequences of cesarean section. METHODS: We reviewed available data from PubMed, Science Direct as well as Google Scholar bases concerning early and long-term neonatal sequelae of operative deliveries. The following key words were used: "cesarean section", "caesarean section", "neonatal outcomes", "respiratory disorders", "asthma", "obesity", "overweight", and "neurological disorders". A total of 1636 papers were retrieved out of which 27 were selected for the final systematic review whereas 16 articles provided data for meta-analysis. Statistical analyses were performed using RevMan 5.4. To determine the strength of association between the caesarean section and respiratory tract infections, asthma, diabetes type 1 as well as obesity the pooled odds ratios (OR) with the 95% confidence intervals (CI) were calculated. RESULTS: Conducted meta-analyses revealed that caesarean section is a risk factor for respiratory tract infections (pooled OR = 1.30 95%CI 1.06-1.60, p = 0.001), asthma (pooled OR = 1.23 95%CI 1.14-1.33, p < 0.00001) as well as obesity (pooled OR = 1.35 95%CI 1.29-1.41, p < 0.00001) in offspring. CONCLUSIONS: The results of the studies included indicated that children delivered by cesarean section more commonly developed respiratory tract infections, obesity and the manifestations of asthma than children delivered vaginally. The risk of developing diabetes mellitus type 1 or neurological disorders in offspring after caesarean section is still under discussion.

Successful pregnancy in women with inferior vena cava stenosis - case report and discussion.

OBJECTIVES: Inferior vena cava syndrome (IVCS) is a heterogenous group of symptoms resulting in obstruction of the main vein inflow . Common reasons are thrombotic changes and tumors. Incidence of inferior vena cava (IVC) anomalies is 0.3% in general population. Iatrogenic IVC lesions caused by catheter insertion play increasing role. Treatment varies depending on the condition. MATERIAL AND METHODS: 32-year old patient was diagnosed with IVC stenosis during infertility related preconception evaluation and informed about increased risk in planned pregnancy. Throughout the well progressing pregnancy patient received low molecular weight heparin. RESULTS: The diagnosis was confirmed intraoperatively during the planned cesarean section. Early postpartum period was normal and patient was discharged with antithrombotic prophylaxis. CONCLUSIONS: Isolated IVC stenosis in pregnancy has not been yet reported in medical literature. Even though IVC anomalies may be associated with other congenital changes, in this case the central venous line treatment in infancy seems to be the most likely cause. Malformations are often accidentally diagnosed because patients are usually asymptomatic. CT and MRI are recommended diagnostic tools. Conservative treatment is recommended for asymptomatic patients, as opposed to surgical treatment for symptomatic. However, due to condition's rarity, there is no evidence based approach management.