Ewa Rechberger

SN003, a CRF1 receptor antagonist, attenuates depressive-like behavior and detrusor overactivity symptoms induced by 13-cis-retinoic acid in rats.

&NA; Overactive bladder (OAB) often co‐exists with depression in women. The corticotropin‐releasing factor (CRF) system participates in the pathophysiology of both disorders. Therefore, we tested the effects of acute treatment with a reversible CRF receptor type‐1 (CRF1) antagonist, SN003 (1 mg/kg, i.v.), representatives of first (solifenacin, 0.03 mg/kg, i.v.) and second (mirabegron, 1 mg/kg, i.v.) line treatments for OAB as well as an antidepressant imipramine (30 mg/kg, i.p.) on changes in depressive‐like behavior and detrusor overactivity (DO) symptoms induced by a 6‐week administration of 13‐cis‐retinoic acid (13‐cis‐RA, 1 mg/kg/day, i.p.) in female Wistar rats, using in vivo cystometric investigations, forced swim test (FST) and spontaneous locomotor activity test. Following cystometric and behavioral studies, tissue was harvested and CRF level was assessed in the hypothalamus, amygdala and plasma. 13‐cis‐RA‐induced depressive‐like behavior and DO symptoms were associated with increased CRF levels in the hypothalamus, amygdala and plasma. Solifenacin and mirabegron attenuated DO symptoms induced by 13‐cis‐RA, did not display antidepressant‐like activity and did not influence CRF levels in brain tissues or plasma. Imipramine and SN003 displayed antidepressant‐like activity and lowered increased levels of CRF in brain tissues and plasma. Imipramine attenuated changes in some of the cystometric parameters, which are associated with OAB dry (without urge incontinence), whereas SN003 attenuated changes in almost all cystometric parameters that were induced by 13‐cis‐RA. CRF1 antagonist may be beneficial in case of OAB wet (with urge incontinence) or dry co‐existing with depression. The possible mechanism may be related to the effects on central/peripheral CRF system.

Antimicrobial Resistance Patterns in Women with Positive Urine Culture: Does Menopausal Status Make a Significant Difference?

Aim. Urinary tract infection (UTI) is considered one of the most common bacterial infections in women. The aim of this study was to investigate the types of uropathogens present, as well as the degree of antimicrobial drug resistance seen among premenopausal (n = 2748) and postmenopausal (n = 1705) women with uncomplicated UTI. Methods. Urinary samples (n = 4453) collected from women with UTI were analyzed in terms of uropathogens present. These were considered as positive if bacterial growth was ≥105 colony forming units (CFUs)/mL. Susceptibility and resistance testing for commonly used antibiotics was subsequently assessed. Results. The most common uropathogens cultured from urine samples were Escherichia coli (65.5%), followed by Enterococcus faecalis (12.2%), Klebsiella pneumoniae (4.7%), and Proteus mirabilis (4.2%). The resistance to ampicillin exceeded 40%, independently of menopausal status. Of note, resistance to ciprofloxacin exceeded 25% among postmenopausal patients. Moreover, resistance of all uropathogens to commonly used antimicrobials was significantly higher in postmenopausal women. Conclusion. Due to the high resistance rate, ampicillin, ciprofloxacin, and the trimethoprim/sulfamethoxazole combination should be avoided in treating postmenopausal women affected by UTI without being indicated by initial urine culture report. Finally, cephalexin and cefuroxime are promising alternatives as initial treatment in postmenopausal women.

Are there any differences in quality of life and sexual functions after various types of hysterectomy - does prophylactic salpingectomy matter?

Objectives: To assess if general quality of life and sexuality following hysterectomy performed due to benign conditions depends on the surgical approach. The SF 36v2 and FSFI were analyzed postoperatively among women after: supracervical laparoscopic hysterectomy (SLH), total abdominal hysterectomy (TAH), supracervical abdominal hysterectomy (SAH) and vaginal hysterectomy (VH). Material and methods: Study group consisted of 392 women who underwent SLH, TAH, SAH or VH for benign indications between 2010 and 2013. Additionally we analyzed patients: I-with bilateral salpingectomy and IIwithout salpingectomy. Sexuality and general quality of life status were assessed 12 months after operation using two questionnaires: the FSFI and the SF 36v2. Results: Postoperative SF 36v2 scores were significantly higher only in SLH group (p≤0,05). Furthermore postoperative FSFI scores were significantly higher in SLH when compared to SAH, TAH and VH groups (p≤0,05) and also significantly higher in SAH group than in VH group (p≤0,05). Additional prophylactic salpingectomy did not affect the woman’s quality of life and sexuality. Conclusions: Quality of life and sexual functions after SLH are better than after TAH, SAH and VH. Salpingectomy does not exert any significant influence, either on the general quality of life or sexuality in patients after different types of hysterectomy.

Power morcellation for women undergoing laparoscopic supracervical hysterectomy — safety of procedure and clinical experience from 426 cases

OBJECTIVES Minimally invasive gynaecological surgeries are performed for several malignant and nonmalignant indications. The aim of our study was to evaluate the rate of unexpected malignancies among women who underwent laparoscopical supracervical hysterectomy (LASH) with power morcellation. MATERIAL AND METHODS The retrospective analysis included clinical data of 426 consecutive female patients who underwent LASH with power morcellation due to presumed benign disorders (78.4% - symptomatic uterine fibromas, 12.7% - abnormal uterine bleeding, 8.9% - suspicion of uterine adenomyosis) between January 2011 and December 2015. Pre-malignant or malignant preoperative abnormalities in the cervix and the uterine corpus were contraindications for LASH. RESULTS The unexpected malignancies were found in four patients from study group: one ovarian cancer located on the inner part of simple ovarian cyst and 3 endometrial carcinomas (0.9%) were documented. All these patients underwent abdominal reoperations and no histological abnormalities were detected in the extirpated cervix and adnexa. CONCLUSIONS The incidence of unintended endometrial carcinoma in morcellated uterus after LASH was relatively small. However, careful pre-operative counseling should be undertaken in order to exclude the possibility of any malignant disease in uteri among women scheduled to power morcellation.

Blebbistatin, a Myosin II Inhibitor, Exerts Antidepressant-Like Activity and Suppresses Detrusor Overactivity in an Animal Model of Depression Coexisting with Overactive Bladder

Overactive bladder (OAB) coexists with depression in women. Here, we assessed the effects of a 1-week treatment with blebbistatin, a myosin II inhibitor, on changes in behavior and detrusor overactivity (DO) symptoms induced by a 6-week administration of 13-cis-retinoic acid (13-cis-RA), with the aid of the forced swim test (FST), spontaneous locomotor activity test, and in vivo cystometric investigations in female Wistar rats. 13-cis-RA-induced depressive-like behavior and DO symptoms were associated with increased corticotropin-releasing factor (CRF) level in the plasma, prefrontal cortex (PFC), hippocampus (Hp), Barrington’s nucleus (BN), and urinary bladder. Moreover, 13-cis-RA decreased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in plasma, PFC, Hp, and BN, while it increased BDNF and NGF levels in urinary bladder. Blebbistatin exerted antidepressant-like effect and attenuated changes in the cystometric parameters as well as the central and peripheral levels of CRF, BDNF, and NGF that were induced by 13-cis-RA, while it did not affect urine production, mean, systolic or diastolic blood pressure, or heart rate. The results point to blebbistatin as a potential treatment option for OAB coexisting with depression.

Inhibition of Rho kinase by GSK 269962 reverses both corticosterone-induced detrusor overactivity and depression-like behaviour in rats

ABSTRACT Literature data give clear evidence that upregulated RhoA/Rho‐kinase signalling is one of the factors that may lead to the development of detrusor overactivity and various disorders of the central nervous system. Therefore, the main objective of our study was to investigate whether administration of a Rho‐kinase inhibitor – GSK 269962 could reverse corticosterone‐induced depressive‐like behaviour and changes in cystometric parameters associated with detrusor overactivity, as well as undo the alterations of several biomarkers related to both disorders (i.e., pro‐inflammatory/anti‐inflammatory cytokines and neurotrophins) in serum, urinary bladder, and different brain structures. The experiments were carried out on female Wistar rats. Surgical procedures, cystometric investigations, biochemical analyses, and behavioural studies (measurement of the locomotor activity and the forced swim test) were performed according to the published literature. As expected, administration of corticosterone at a daily dose of 20mg/kg for 14 days increased the immobility time of animals in the forced swim test, induced changes in the cystometric parameters specific to bladder overactivity, reduced levels of neurotrophins, and elevated concentrations of the pro‐inflammatory cytokines. Inhibition of Rho‐kinase by 7‐day treatment with GSK 269962 (10mg/kg/day) reversed the symptoms of both detrusor overactivity and depression as well as normalized levels of the tested biomarkes. Our findings encourage the idea of Rho‐kinase inhibitors as a potential future treatment option for overactive bladder accompanied by depression.

Urinary incontinence after hysterectomy- does type of surgery matter?

Objectives The aim of the study was to assess the effect of different types of hysterectomy on the development of postoperative urinary incontinence (UI). Materials and Methods The study group consisted of 392 women who underwent supracervical laparoscopic hysterectomy (SLH), total abdominal hysterectomy (TAH), supervical abdominal hysterectomy (SH), or vaginal hysterectomy (VH) for benign indications 2010 and 2013. The patients reported no UI-related complaints before surgery. UI status was assessed 12 months postoperatively using the cough test and the 24-hour pad test. Results UI developed within 12 months after surgery in 149 (38%) out of 392 women. No statistically significant correlation between the type of treatment and UI incidence was detected. The percentage of patients affected by UI did not differ between the study groups. Conclusions Hysterectomy constitutes a risk factor for the development of urinary incontinence but the occurrence of postoperative UI does not depend on the type of surgery.

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.

[Ovarian cancer during pregnancy--presentation of three cases and current diagnostic and treatment algorithms].

INTRODUCTION Malignant tumors are rarely diagnosed during pregnancy and their incidence ranges from 2.4% to 5.7%. Ovarian cancer is ranked fifth among all cancer types and second among all genital cancers diagnosed during pregnancy The course of the disease is asymptomatic in most cases and the initial diagnose is typically made during a routine ultrasound examination. Management of ovarian cancer during pregnancy presents a considerable challenge due to the absence of clear standards of treatment. OBJECTIVES We present three clinical cases of patients suffering from ovarian cancer diagnosed during pregnancy a review of the literature, as well as possible therapeutic options. RESULTS Three different clinical scenarios in patients with ovarian cancer diagnosed during pregnancy have been presented. In addition, we reviewed current diagnostic and therapeutic algorithms for patients with ovarian cancer and co-existing pregnancy. CONCLUSIONS Approximately 5% of ovarian tumors diagnosed in pregnancy are malignant. There are no treatment standards for ovarian cancer diagnosed during pregnancy. Surgical treatment and the subsequent chemotherapy in the 2nd trimester of pregnancy appear to be safe for both, the mother and the child. However, the potential risks and benefits associated with the treatment have to be thoroughly analyzed on a case-by-case basis, to establish optimal diagnostic and treatment algorithms.