Association between 3D membranous urethral parameters and urinary continence recovery after RARP.

OBJECTIVES: To evaluate whether the urinary continence (UC) recovery after robotic-assisted radical prostatectomy (RARP) relates to the membranous urethral length (MUL) and the membranous urethral complex volume (MUV). MATERIALS AND METHODS: 120 patients who underwent RARP were enrolled according to the different times of UC recovery and examined using prostate magnetic resonance imaging (MRI) before surgery. The membranous urethral (MU) parameters were measured using the three-Dimensional (3D) model reconstructed by holographic technology, such as total MUV (tMUV), exposed MUV (eMUV), full MUL (fMUL) and exposed MUL (eMUL). Statistical software SPSS 26.0 was used to analyze the data and compare the MU parameters and baseline data in different groups. RESULTS: Patients with larger tMUV (p = 0.038), eMUV (p = 0.003), longer fMUL (p = 0.025), eMUL (p = 0.044) had better UC after removal of the catheter, and eMUV (OR = 1.002, 95%CI = 1.001-1.004, p = 0.004) was a predictor; the patients with younger age (p = 0.021), lower VPSS score (p = 0.004) and larger eMUV (p = 0.012) and longer eMUL (p = 0.049) had better UC recovery one month after RARP while eMUV (OR = 1.002, 95% CI = 1.000-1.003, p = 0.008) and VPSS score (OR = 0.886, 95% CI = 0.806-0.973, p = 0.011) were independent risk factors; The patients with younger age (p = 0.018), larger tMUV (p = 0.029), eMUV (p = 0.016) had better UC recovery three months after RARP. eMUV (OR = 1.002, 95% CI = 1.000-1.004, p = 0.042) and age (OR = 0.904, 95% CI = 0.818-0.998, p = 0.046) were independent risk factors. CONCLUSION: This clinical study shows that patients with larger MUV and longer MUL can return to UC earlier after surgery. Among that, eMUV is a better predictor.

Preoperative predictive model of early urinary continence recovery after laparoscopic radical prostatectomy.

PURPOSE: To develop and validate a predictive model include magnetic resonance imaging (MRI) parameters preoperatively which can assess the risk of incontinence after laparoscopic radical prostatectomy (LRP) accurately. METHODS: We retrospectively reviewed and included 170 patients with prostate cancer who underwent LRP between July 2015 and June 2018 in our institution. All 170 patients were randomly resampled and divided into training set (n = 124) and verification set (n = 46) according to the ratio of 7:3. The Nomogram prediction model of the risk of incontinence after LRP was established through the training set and verified by the verification set. Baseline patient characteristics were obtained, including age, body mass index, and prostate volume. Perioperative characteristics such as pre-biopsy prostate specific antigen, biopsy Gleason score, clinical staging, and NVB sparing status were also collected. MRI parameters preoperatively including membranous urethral length (MUL), prostate apex depth ratio (PADR), and intravesical prostatic protrusion length (IPPL) were obtained. The C index and visual inspection of calibration curve were used to evaluate the discrimination and calibration of the model. RESULTS: According to the urinary incontinence (UI) at 3 months postoperatively, the patients were divided into 104 cases (61.2%) in the group with no incontinence and 66 patients (38.8%) in the group with incontinence. Multivariate logistic regression analysis of training set showed that cT3a (OR = 0.427, 95% CI 0.142-1.281, P = 0.1288), MUL (OR = 0.237, 95% CI 0.102-0.551, P < 0.01), PADR (OR = 0.276, 95% CI 0.116-0.655, P < 0.01), and IPPL (OR = 0.073, 95% CI 0.030-0.179, P < 0.01) were independent predictors of urinary incontinence at 3 months postoperatively. The model showed good discrimination with an area under the receiver operating characteristic (ROC) curve of 0.880, with the sensitivity and specificity 0.800 and 0.816, respectively, and good calibration (Hosmer-Lemeshow test result of 5.57, P = 0.695). Decision curve analysis demonstrated that the model was clinically useful. CONCLUSION: This study developed and validated a preoperative model in the form of a nomogram to predict the risk of UI after LRP at 3 months. MUL, PADR, and IPPL were significant independent predictive factors of the postoperative early urinary continence.

[The role of estriol in the treatment of atrophy of the mucous membrane of the lower genitourinary tract in postmenopausal women].

Studies of recent decades show a steady increase in the average life expectancy of a person, and women in particular. The World Health Organization predicts a four-fold increase in the number of women over 70 by 2030, and many of them over the age of 45 may face menopausal problems. Menopause is a physiological state in a woman's life, during which, against the background of age-related changes, there is a gradual decrease and shutdown of ovarian function and the cessation of estrogen production. Genitourinary syndrome occurs in every third woman in this period. Estriol is the main estrogen that specifically addresses problems associated with estrogen deficiency: dyspareunia, dryness and itching in the vagina and lower genitourinary tract, urinary incontinence, moderate urinary incontinence, and recurrent vulvovaginitis and cystitis. Vulvovaginal dystrophy in women of the older age group is a multidisciplinary problem at the intersection of gynecology, urology and dermatology, which can and should be solved to prevent more severe gynecological and urological pathologies.

Prevalence of urinary incontinence among women with diabetes in the Lolland-Falster Health Study, Denmark.

AIMS: To investigate the prevalence of urinary incontinence (UI) and UI subtypes (stress, urgency, and mixed UI) in women with or without diabetes mellitus; and to investigate the association between diabetes and UI (any and subtypes). METHODS: A cross-sectional study based on the Lolland-Falster, Denmark population-based health study. From 2016 to 2020, clinical measurement, questionnaires, and blood tests were collected. A total of 8563 women aged 18 or older were enrolled. Data analysis included 7906 women. UI was defined as any involuntary leakage of urine during the previous 4 weeks. Multiple logistic regression was used to adjust for confounders: age, body mass index, parity, physical activity, previous gestational diabetes, education, and smoking. RESULTS: UI prevalence was 50.3% in women with diabetes and 39.3% in women without diabetes. The unadjusted and adjusted odds ratio (OR) for UI in women with diabetes was OR 1.56 (95% confidence interval [CI], 1.27-1.92) and 1.11 (95% CI, 0.88-1.38), respectively. Mixed UI was associated with diabetes after controlling for confounders. A subgroup analysis found women using multiple antidiabetic medications had increased odds of UI, 2.75 (95% CI, 1.38-5.48), after controlling for confounders. CONCLUSION: The prevalence of UI in women with diabetes was higher than in women without diabetes. The odds of UI was 56% higher in women with diabetes compared with women without diabetes but the effect was attenuated when controlling for confounders and statistically significance was not achieved. For a subgroup using multiple antidiabetic medications, the risk of UI was higher than in women without diabetes.

Alterations in detrusor contractility in rat model of bladder cancer.

Urinary incontinence of idiopathic nature is a common complication of bladder cancer, yet, the mechanisms underlying changes in bladder contractility associated with cancer are not known. Here by using tensiometry on detrusor smooth muscle (DSM) strips from normal rats and rats with bladder cancer induced by known urothelial carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), we show that bladder cancer is associated with considerable changes in DSM contractility. These changes include: (1) decrease in the amplitude and frequency of spontaneous contractions, consistent with the decline of luminal pressures during filling, and detrusor underactivity; (2) diminution of parasympathetic DSM stimulation mainly at the expense of m-cholinergic excitatory transmission, suggestive of difficulty in bladder emptying and weakening of urine stream; (3) strengthening of TRPV1-dependent afferent limb of micturition reflex and TRPV1-mediated local contractility, promoting urge incontinence; (4) attenuation of stretch-dependent, TRPV4-mediated spontaneous contractility leading to overflow incontinence. These changes are consistent with the symptomatic of bladder dysfunction in bladder cancer patients. Considering that BBN-induced urothelial lesions in rodents largely resemble human urothelial lesions at least in their morphology, our studies establish for the first time underlying reasons for bladder dysfunction in bladder cancer.

Reducing Neuron Apoptosis in the Pontine Micturition Center by Nerve Root Transfer for Restoration of Micturition Function after Spinal Cord Injury.

OBJECTIVE: The rate of neuronal apoptosis increases after spinal cord injury (SCI). Anastomosing the normal nerve roots above the SCI level to the injured sacral nerve roots can enhance the functional recovery of neurons. Therefore, we evaluated the effect of sacral nerve root transfer after SCI on pontine neuronal survival. METHODS: Sprague-Dawley rats were randomly divided into three groups: Group A, reconstruction of afferent and efferent nerve pathways of the bladder after SCI; Group B, SCI only; and Group C, control group. We examined pontine neuronal morphology using hematoxylin and eosin (H&E) staining after SCI and nerve transfer. Bcl-2 and Bax protein expression changes in the pontine micturition center were quantified by immunohistochemistry. The number of apoptotic neurons was determined by TUNEL staining. We examined pontine neuronal apoptosis by transmission electron microscopy (TEM) at different time points. RESULTS: H&E staining demonstrated that the number of neurons had increased in Group A, but more cells in Group B displayed nuclear pyknosis, with the disappearance of the nucleus. Compared with Group B, Group A had significantly higher Bcl-2 expression, significantly lower Bax expression, and a significantly higher Bcl-2/Bax ratio. The number of apoptotic neurons and neuron bodies in Group A was significantly lower than that in Group B, as indicated by TUNEL staining and TEM. CONCLUSIONS: These findings demonstrate that lumbosacral nerve transfer can reduce neuronal apoptosis in the pontine micturition center and enhance functional recovery of neurons. This result further suggests that lumbosacral nerve transfer can be used as a new approach for reconstructing bladder function after spinal cord injury.

Human T-lymphotropic virus type 1 (HTLV-1) and cellular immune response in HTLV-1-associated myelopathy/tropical spastic paraparesis.

Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is an inflammatory disease of the spinal cord and clinically characterized by progressive spastic paraparesis, urinary incontinence, and mild sensory disturbance. The interaction between the host immune response and HTLV-1-infected cells regulates the development of HAM/TSP. HTLV-1 preferentially infects CD4+ T cells and is maintained by proliferation of the infected T cells. HTLV-1-infected cells rarely express viral antigens in vivo; however, they easily express the antigens after short-term culture. Therefore, such virus-expressing cells may lead to activation and expansion of antigen-specific T cell responses. Infected T cells with HTLV-1 and HTLV-1-specific CD8+ cytotoxic T lymphocytes invade the central nervous system and produce various proinflammatory cytokines and chemokines, leading to neuronal damage and degeneration. Therefore, cellular immune responses to HTLV-1 have been considered to play important roles in disease development of HAM/TSP. Recent studies have clarified the viral strategy for persistence in the host through genetic and epigenetic changes by HTLV-1 and host immune responses including T cell function and differentiation. Newly developed animal models could provide the opportunity to uncover the precise pathogenesis and development of clinically effective treatment. Several molecular target drugs are undergoing clinical trials with promising efficacy. In this review, we summarize recent advances in the immunopathogenesis of HAM/TSP and discuss the perspectives of the research on this disease.

Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder.

AIM: To characterize purinergic signaling in overactive bladder (OAB). METHODS: Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n = 12) and Western blot analysis (n = 28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid-stream urine sample. Bioluminescent assays were used to quantify adenosine triphosphate (ATP; n = 66) and adenosine diphosphate (ADP; n = 60) concentrations, which were normalized to creatinine (Cr) concentration. All participants completed a questionnaire (International Consultation on Incontinence Questionnaire - Overactive Bladder) to score urinary symptoms of OAB. RESULTS: P2Y6 immunoreactivity, more prominent in the urothelium (colocalized with the uroepithelial marker pan-cytokeratin), was more greatly expressed in OAB compared to age- and sex-matched controls (benign prostatic hyperplasia) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (P = .009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (P = .010 and P = .042, respectively). CONCLUSIONS: The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signaling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.

Visualization of peri-prostatic neurovascular fibers before and after radical prostatectomy by means of diffusion tensor imaging (DTI) with clinical correlations: preliminary report.

To evaluate if diffusion tensor imaging (DTI) is able to detect morphological changes of peri-prostatic neurovascular fibers (PNF) before and after robot-assisted radical prostatectomy (RARP) and if these changes are related to urinary incontinence (UI) and erectile dysfunction (ED). From October 2014 and August 2017, 26 patients with biopsy-proven prostate cancer underwent prostatic multiparametric magnetic resonance imaging (mp-MRI) including DTI sequencing before, and 6 months after, RARP. Images were analyzed by placing six regions of interest (ROI), respectively, at base, mid gland, and apex, one for each side, to obtain tractographic reconstruction of the PNF. Patients were asked to complete International Consultation Incontinence Questionnaire-Short Form (ICIQ-SF) and International Index of Erectile Function (IIEF-5) questionnaires before RARP and 6 months post-operatively. Fractional anisotropy (FA), number (N), and length (L) of PNF before and after RARP were compared by means of Student's t test; Spearman's test was used to evaluate correlation between DTI parameters and questionnaires' scores. We observed a significant difference in N values before and after RARP (p < 0.001) and a negative correlation between IIEF-5 score and post-operative FA values at both the right (rho = - 0.42; p = 0.0456) and left (rho = - 0.66; p = 0.0006) base of the prostate. DTI with tractography of PNF is able to detect quantitative changes in N, L, and FA values in PNF after RARP. In particular, we observed an inverse correlation between FA of PNF and ED at 6 months after RARP. Further investigations are needed to confirm this trend.

Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence Are Damaged by In Vitro Exposure to its Dyslipidemic Serum, Predicting Inadequate Repair Capacity In Vivo.

Female stress urinary incontinence (FSUI) is prevalent in women with type 2 diabetes/obesity (T2D/O), and treatment is not optimal. Autograph stem cell therapy surprisingly has poor efficacy. In the male rat model of T2D/O, it was demonstrated that epigenetic changes, triggered by long-term exposure to the dyslipidemic milieu, led to abnormal global transcriptional signatures (GTS) of genes and microRNAs (miR), and impaired the repair capacity of muscle-derived stem cells (MDSC). This was mimicked in vitro by treatment of MDSC with dyslipidemic serum or lipid factors. The current study aimed to predict whether these changes also occur in stem cells from female 12 weeks old T2D/O rats, a model of FSUI. MDSCs from T2D/O (ZF4-SC) and normal female rats (ZL4-SC) were treated in vitro with either dyslipidemic serum (ZFS) from late T2D/O 24 weeks old female Zucker fatty (ZF) rats, or normal serum (ZLS) from 24 weeks old female Zucker lean (ZL) rats, for 4 days and subjected to assays for fat deposition, apoptosis, scratch closing, myostatin, interleukin-6, and miR-GTS. The dyslipidemic ZFS affected both female stem cells more severely than in the male MDSC, with some gender-specific differences in miR-GTS. The changes in miR-GTS and myostatin/interleukin-6 balance may predict in vivo noxious effects of the T2D/O milieu that might impair autograft stem cell (SC) therapy for FSUI, but this requires future studies.

Morphologic changes after bladder neck intussusception in laparoscopic radical prostatectomy contribute to early postoperative continence.

PURPOSE: To explore the mechanism and efficacy of the modified bladder neck intussusception in laparoscopic radical prostatectomy (LSRP) on postoperative early continence. METHODS: We prospectively collected clinical information of prostate cancer patients who underwent LSRP with modified bladder neck intussusception (n = 10) and non-intussusception (n = 10). At postoperative 1 month, the prostate-specific antigen (PSA), pad test, real-time magnetic resonance imaging (rt-MRI), and flow rate were performed. At postoperative 3 months, the PSA, pad test, international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), incontinence questionnaire short form (ICI-Q-SF), and quality of life (Qol) were recorded. RESULTS: The intussusception and non-intussusception patients had similar baseline characteristics. At postoperative 3 months, intussusception patients had lower OABSS than non-intussusception patients (P = 0.038). The non-intussusception patients suffered from more severe incontinence (P = 0.026). The continence rate of intussusception patients was significantly higher (90% vs. 20%, P = 0.005). And intussusception patients had significantly lower Qol scores (P = 0.038). According to the morphologic analysis by rt-MRI, there were 7/10 non-intussusception patients and 2/10 intussusception patients having funnel-shaped bladder necks at Valsalva movement. The intussusception patients had larger angle between anterior and posterior wall at bladder neck (P = 0.029) and longer length of functional posterior urethra (P = 0.029). During micturition, the intussusception bladder neck was found to move less dynamically on X-axis and Y-axis, but the difference did not reach significance. CONCLUSIONS: The modified technique of bladder neck intussusception in laparoscopic radical prostatectomy prolongs the length of functional posterior urethra and is effective to improve postoperative early continence.

Nerve sprouting and neurogenic inflammation characterize the neurogenic detrusor overactive bladder of patients no longer responsive to drug therapies.

Urothelium and Lamina Propria (LP) are considered an integrate sensory system which is able to control the detrusor activity. Complete supra-sacral spinal cord lesions cause Neurogenic Detrusor Overactivity (NDO) whose main symptoms are urgency and incontinence. NDO therapy at first consists in anti-muscarinic drugs; secondly, in intra-vesical injection of botulinum toxin. However, with time, all the patients become insensitive to the drugs and decide for cystoplastic surgery. With the aim to get deeper in both NDO and drug's efficacy lack pathogenesis, we investigated the innervation, muscular and connective changes in NDO bladders after surgery by using morphological and quantitative methodologies. Bladder innervation showed a significant global loss associated with an increase in the nerve endings located in the upper LP where a neurogenic inflammation was also present. Smooth muscle cells (SMC) anomalies and fibrosis were found in the detrusor. The increased innervation in the ULP is suggestive for a sprouting and could condition NDO evolution and drug efficacy length. Denervation might cause the SMC anomalies responsible for the detrusor altered contractile activity and intra-cellular traffic and favour the appearance of fibrosis. Inflammation might accelerate these damages. From the clinical point of view, an early anti-inflammatory treatment could positively influence the disease fate.

Detrusorrhaphy during Robot-Assisted Radical Prostatectomy: Early Recovery of Urinary Continence and Surgical Technique.

Robot-assisted radical prostatectomy (RARP) has largely replaced open radical prostatectomy as the standard surgical treatment for prostate cancer. However, postoperative urinary incontinence still persists and has a significant impact on quality of life. We report the superior results of the detrusorrhaphy technique during RARP that helps achieve early continence. Our prospective study involved 95 consecutive patients who underwent RARP between March 2015 and May 2017; fifty patients underwent RARP using the new detrusorrhaphy technique (group 1) and 45 underwent standard RARP (group 2). The postoperative oncological and functional outcomes were compared between the two groups. The postoperative continence was assessed at 0 day, 1 week, 4 weeks, 8-12 weeks, and 6 months after catheter removal. Continence was defined as the use of no pad over a 24 h period. Mean operative time in groups 1 and 2 were 250 and 220 min, respectively. Intraoperative complications were not encountered in any patient. The continence rates after catheter removal in groups 1 and 2 were 68% and 0% at 0 day, 78% and 17.8% at 1 week, 86% and 64.4% at 4 weeks, 92% and 73.3% at 8-12 weeks, and 100% and 91.1% at 6 months, respectively. In the multivariate analysis, the nerve sparing technique, D'Amico risk groups, and prostate volume were involved in the early recovery of urinary continence. The detrusorrhaphy technique is simple, safe, and feasible, which helped achieve earlier continence. It showed significantly better outcomes than those achieved with the standard RARP technique in terms of urinary incontinence. Nevertheless, our findings need to be validated in further studies.

Disseminated cysticercosis in an immunocompetent individual.

Cysticercosis is a major public health problem, particularly in developing countries. It is caused by the larvae of the cestode Taenia solium (pork tapeworm). It usually presents as a solitary lesion in the muscle or brain (neurocysticercosis). Disseminated cysticercosis is an uncommon manifestation, especially in an immunocompetent individual. We hereby report the case of a 31-year-old male who presented with new-onset generalized tonic-clonic seizures and who also had multiple soft-tissue swellings all over his body. Imaging studies revealed multiple cysticerci in the brain parenchyma, extraocular muscles, and muscles of all the four limbs, which was subsequently established by histopathology also. The patient was started on anticonvulsants, steroids, and albendazole following which he made a complete recovery.

Résumé La cysticercose bovine est un problème majeur de santé publique, en particulier dans les pays en développement. Elle est causée par les larves du cestode Taenia solium (pork tapeworm). Il se présente généralement comme une lésion solitaire dans le muscle ou du cerveau (neurocysticercose). La cysticercose disséminée est une manifestation rare, en particulier dans un individu immunocompétent. Nous rapportons le cas d'un 31 ans qui présentaient une apparition nouvelle tonico-cloniques et qui avaient également plusieurs gonflements des tissus mous sur tout son corps. Les études d'imagerie ont révélé plusieurs cysticerques dans le parenchyme du cerveau, des muscles extraoculaires, et les muscles de l'ensemble des quatre membres, qui a été établi par l'histopathologie également. Le patient a commencé à prendre des anticonvulsivants, stéroïdes, et de l'albendazole à la suite de laquelle il s'est complètement rétabli.

Quality of life in men living with advanced and localised prostate cancer in the UK: a population-based study.

BACKGROUND: Little is known about the health-related quality of life (HRQOL) of men living with advanced prostate cancer. We report population-wide functional outcomes and HRQOL in men with all stages of prostate cancer and identify implications for health-care delivery. METHODS: For this population-based study, men in the UK living 18-42 months after diagnosis of prostate cancer were identified through cancer registration data. A postal survey was administered, which contained validated measures to assess functional outcomes (urinary incontinence, urinary irritation and obstruction, bowel, sexual, and vitality and hormonal function), measured with the Expanded Prostate Cancer Index Composite short form (EPIC-26), plus questions about use of interventions for sexual dysfunction) and generic HRQOL (assessed with the 5-level EuroQol five dimensions questionnaire [EQ-5D-5L] measuring mobility, self-care, usual activities, pain or discomfort, and anxiety or depression, plus a rating of self-assessed health). Log-linear and binary logistic regression models were used to compare functional outcomes and HRQOL across diagnostic stages and self-reported treatment groups. Each model included adjustment for age, socioeconomic deprivation, and number of other long-term conditions. FINDINGS: 35 823 (60·8%) of 58 930 men responded to the survey. Disease stage was known for 30 733 (85·8%) of 35 823 men; 19 599 (63·8%) had stage I or II, 7209 (23·4%) stage III, and 3925 (12·8%) stage IV disease. Mean adjusted EPIC-26 domain scores were high, indicating good function, except for sexual function, for which scores were much lower. Compared with men who did not receive androgen deprivation therapy, more men who received the therapy reported moderate to big problems with hot flushes (30·7% [95% CI 29·8-31·6] vs 5·4% [5·0-5·8]), low energy (29·4% [95% CI 28·6-30·3] vs 14·7% [14·2-15·3]), and weight gain (22·5%, 21·7-23·3) vs 6·9% [6·5-7·3]). Poor sexual function was common (81·0%; 95% CI 80·6-81·5), regardless of stage, and more than half of men (n=18 782 [55·8%]) were not offered any intervention to help with this condition. Overall, self-assessed health was similar in men with stage I-III disease, and although slightly reduced in those with stage IV cancer, 23·5% of men with metastatic disease reported no problems on any EQ-5D dimension. INTERPRETATION: Men diagnosed with advanced disease do not report substantially different HRQOL outcomes to those diagnosed with localised disease, although considerable problems with hormonal function and fatigue are reported in men treated with androgen deprivation therapy. Sexual dysfunction is common and most men are not offered helpful intervention or support. Service improvements around sexual rehabilitation and measures to reduce the effects of androgen deprivation therapy are required. FUNDING: The Movember Foundation, in partnership with Prostate Cancer UK.

Endoplasmic reticulum stress contributes to the pathogenesis of stress urinary incontinence in postmenopausal women.

OBJECTIVE: To investigate the relationship between endoplasmic reticulum stress (ERS) and the pathogenesis of stress urinary incontinence (SUI) in postmenopausal women. METHODS: Anterior vaginal wall tissue was collected from postmenopausal women with SUI and control subjects. Western blotting was performed for glucose-regulated protein (GRP78), inositol-requiring enzyme 1(IRE1), protein kinase-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), C/EBP-homologous protein (CHOP), and B-cell lymphoma 2 (Bcl-2). Additionally, mRNA expression levels of PERK, activating transcription factor 4 (ATF4), and CHOP were examined by real-time polymerase chain reaction. RESULTS: GRP78 protein and mRNA expression levels were significantly lower in women with SUI, compared with control subjects. PERK and p-PERK expression levels were higher in women with SUI than in control subjects. However, no differences in IRE1 or ATF6 expression levels were observed in either group. Notably, higher CHOP and lower Bcl-2 protein expression levels were detected in women with SUI, compared with control subjects. Furthermore, PERK, ATF4, and CHOP mRNA expression levels were significantly higher in women with SUI than in control subjects. CONCLUSIONS: Alterations of ERS markers in SUI suggest that ERS may be involved in the development of SUI in postmenopausal women.

The role of ATP signalling in response to mechanical stimulation studied in T24 cells using new microphysiological tools.

The capacity to store urine and initiate voiding is a valued characteristic of the human urinary bladder. To maintain this feature, it is necessary that the bladder can sense when it is full and when it is time to void. The bladder has a specialized epithelium called urothelium that is believed to be important for its sensory function. It has been suggested that autocrine ATP signalling contributes to this sensory function of the urothelium. There is well-established evidence that ATP is released via vesicular exocytosis as well as by pannexin hemichannels upon mechanical stimulation. However, there are still many details that need elucidation and therefore there is a need for the development of new tools to further explore this fascinating field. In this work, we use new microphysiological systems to study mechanostimulation at a cellular level: a mechanostimulation microchip and a silicone-based cell stretcher. Using these tools, we show that ATP is released upon cell stretching and that extracellular ATP contributes to a major part of Ca2+ signalling induced by stretching in T24 cells. These results contribute to the increasing body of evidence for ATP signalling as an important component for the sensory function of urothelial cells. This encourages the development of drugs targeting P2 receptors to relieve suffering from overactive bladder disorder and incontinence.

Case of acute severe postpartum urinary incontinence: an extravesical subsphincteric prolapsed ureterocoele.

A 32-year-old woman presents to outpatients 10 days postpartum, with symptoms of an intermittent vaginal lump and urinary incontinence. Vaginal examination revealed no demonstrable prolapse or stress incontinence. A swelling in the bladder was noted during an antenatal scan suggesting a ureterocoele. She was referred for pelvic floor physiotherapy in the first instance. Forty-eight hours later, she represented to casualty with discomforting vaginal lump symptoms and continuous urinary incontinence. At this stage on vaginal inspection, there was an evident dusky lump emerging from the urethra with continuous incontinence. An extravesical subsphincteric prolapsed ureterocoele was evident, 5 cm beyond the external urethral meatus. The diagnosis was confirmed with an MRI scan which demonstrated the prolapsed obstructing ureterocoele causing significant left-sided hydroureteronephrosis. The ureterocoele was managed with a cystoscopy and transurethral incision of the ureterocoele under anaesthesia, which facilitated drainage and resolution. At 3-month postoperatively, the patient remains continent and satisfied.

Impact of dose intensified salvage radiation therapy on urinary continence recovery after radical prostatectomy: Results of the randomized trial SAKK 09/10.

INTRODUCTION: Adjuvant radiation therapy (aRT) after radical prostatectomy (RP) is associated with impaired urinary continence recovery as compared to surveillance. Less is known regarding the effect of salvage radiation therapy (sRT) dose intensification on continence outcomes. MATERIALS AND METHODS: Urinary continence recovery was investigated within a multicentre randomized trial in biochemically recurrent prostate cancer patients who received either 64 Gy (32 fractions) or 70 Gy (35 fractions) sRT. Incontinence was assessed using Common Toxicity Criteria for Adverse Events v4.0 at baseline, at the end of sRT and 3 months afterward. Quality of life (QoL) was assessed with the EORTC QoL questionnaires C30 and PR25 at baseline and 3 months after completion of sRT. A total of 344 patients were evaluable. RESULTS: At baseline 233 (68%) of patients were fully continent and 14% in both arms became incontinent three months after treatment. Of the remaining 111 (32%) patients being incontinent at baseline, continence recovery was achieved 3 months after sRT by 44% vs. 41% with 64 vs. 70 Gy, respectively (p = 0.8). This analysis is limited by its short follow-up. CONCLUSIONS: Dose intensification of sRT had no impact on early urinary continence recovery or prevalence of de novo incontinence.