[Melanosis of the bladder-a rare diagnosis]. / Melanose der Harnblase ­ eine Rarität.

Melanosis of the urinary bladder is an extremely rare benign condition in which melanin deposits occur in the urothelial and stromal cells. We report such a case in which melanosis of the urinary bladder was detected in a 55-year-old woman with known multiple sclerosis during an extended workup due to urinary urgency complaints. The findings were confirmed by biopsy.

Autoimmunity to urothelial antigen causes bladder inflammation, pelvic pain, and voiding dysfunction: a novel animal model for Hunner-type interstitial cystitis.

Recent evidence revealed that Hunner-type interstitial cystitis (HIC) is a robust inflammatory disease potentially associated with enhanced immune responses and histologically characterized by epithelial denudation and lymphoplasmacytic infiltration with frequent clonal expansion of infiltrating B cells. To date, few animal models that reproduce the histological and clinical correlates of HIC have yet been established. In the present study, we aimed to develop a novel animal model for HIC via autoimmunity to the bladder urothelium using the transgenic mouse model (URO-OVA) that expresses the membrane form of the model antigen ovalbumin (OVA) as a self-antigen on the bladder urothelium. OVA-specific lymphocytes (splenocytes) were generated by immunization of C57BL/6 mice with OVA protein and injected intravenously into URO-OVA mice. The splenocytes from OVA-immunized C57BL/6 mice showed increased interferon (IFN)-γ production in response to OVA stimulation in vitro. URO-OVA mice adoptively transferred with OVA-primed splenocytes developed cystitis exhibiting histological chronic inflammatory changes such as remarkable mononuclear cell infiltration predominantly composed of T and B lymphocytes, increased vascularity, and mucosal hyperemia in the bladder at days 7-28 with a peak at day 21 tested. No systemic inflammation was found in cystitis-induced URO-OVA mice, nor was any inflammation found in wild-type C57BL/6 mice adoptively transferred with OVA-primed splenocytes. Along with bladder inflammation, URO-OVA mice demonstrated significantly increased pelvic nociceptive responses, voiding dysfunction, and upregulated mRNA expression levels for IFN-γ, tumor necrosis factor-α (TNF-α), and substance P precursor in the bladder. This model reproduces the histological and clinical features of human HIC, providing a novel model for HIC research.

Disfunción miccional en el adulto. Un artículo docente / Voiding dysfunction in the adult. A teaching article

Voiding dysfunction is defined as an abnormally slow and/or incomplete micturition, and can be divided in bladder outlet obstruction (BOO) and detrusor underactivity (or hypocontractility). BOO is characterized by reduced urine flow rate and increased detrusor pressure, and can be of anatomical or functional origin. Detrusor underactivity encompasses a reduced urine flow rate associated to low pressure and/or poorly sustained detrusor contraction, and its etiology is multifactorial. Lower urinary tract symptoms are classified as storage, voiding and post micturition symptoms, may be objectively quantified with specific questionnaires, and don't correlate properly with voiding dysfunction. Patients' evaluation requires a directed physical examination of the abdomen, pelvis and genitals focused to detect anatomical and neurological abnormalities. Voiding dysfunction can be demonstrated non-invasively using uroflowmetry and pelvic ultrasound. Uroflowmetry allows determining urinary flow characteristics and their most important parameters are voided volume, maximum flow rate and shape of the curve. Pelvic ultrasound permits to estimate prostatic size and post void residual, suspect detrusor hypertrophy (due to BOO) and detect bladder stones. Invasive test must be reserved for special cases of confirmed voiding dysfunction: cystoscopy when there is concomitant hematuria, urethrocystography to study urethral stenosis and urodynamics to differentiate BOO from detrusor underactivity. (AU)

Anterior bladder wall thickness, post-void urine residue, and bladder emptying efficiency as indicators of bladder dysfunction in Nigerian men with benign prostatic hyperplasia.

BACKGROUND: Benign Prostatic Hypertrophy [BPH] is associated with voiding dysfunctions. Urodynamic study is the gold standard for diagnosis of voiding dysfunctions but is invasive. Bladder wall thickness (BWT), post-void urine residue (PVR), and bladder emptying efficiency (BEE) are noninvasive predictors of voiding dysfunction. OBJECTIVE: To study the relationship among BWT, PVR, and BEE in BPH. SUBJECTS AND METHODS: A hospital-based cross-sectional prospective study of new BPH patients at Nnamdi Azikiwe University Teaching Hospital, Nnewi. The participants had abdominal ultrasonography measurement of anterior BWT (at bladder volume ≥200 mls), prostate volume (PV), and PVR using Prosound SSD3500 (Aloka Co Ltd, Tokyo, Japan) with an abdominal probe frequency of 3.5 MHz. Then the BEE was calculated. The anterior BWT was divided into two groups: <5 mm and ≥5 mm. The data were analyzed using SPSS version 20. Pearson's correlation was used to assess correlation and the differences between the means of the two groups of BWT were compared by Mann-Whitney test. A P- Value <0.05 was considered significant. RESULTS: Seventy seven men with a mean age of 66.66 ± 10.74 years were included in the study. Sixty one percent had symptoms lasting >12 months. The average anterior BWT, PBV, PVR, BEE, PV, and PSA were 4.55 ± 1.02 mm, 260.98 ± 57.44 mls, 58.36 ± 52.94 mls, 77.98 ± 17.37%, 66.31 ± 46.38 mls, and 8.04 ± 5.97 ng/ml, respectively. There was a significant positive correlation between BWT and duration of symptoms (P = 0.044) and a significant negative correlation between BWT and BEE (P = 0.005). An insignificant positive correlation was found between BWT and PVR (P = 0.255). Fifty four (70.1%) had BWT <5 mm and 29.9% had BWT ≥5 mm. The mean IPSS (P = 0.000), PV (P = 0.032) and PVR (P = 0.020) were significantly higher in the ≥5 mm group. The ≥5 mm group also had a significantly lower BEE (P = 0.002). CONCLUSION: Voiding dysfunction was more severe in patients with BWT of 5 mm or more. There was a positive, but insignificant, correlation between anterior BWT and PVR and a significant negative correlation between BWT and BEE.

Moderately HRT vs. CRT for localized prostate cancer using image-guided VMAT with SIB: evaluation of acute and late toxicities.

PURPOSE: This retrospective study aims at investigating the effects of moderately hypofractionated radiation therapy (HRT) on acute and late toxicities as well as on early biochemical control and therapeutic efficiency compared to conventional radiation therapy (CRT) in prostate cancer. PATIENTS AND METHODS: We analyzed 55 HRT patients irradiated with the total dose of 60 Gy in 20 fractions delivered over 4 weeks. These patients were compared to a control group of 55 patients who received CRT with a total of <78 Gy in 37-39 fractions delivered over circa 8 weeks. External beam radiation therapy (EBRT) was conducted using daily image-guided (cone beam CT) volumetric modulated arc therapy (VMAT) and a simultaneously integrated boost (SIB) for both groups to protect the rectum. Acute toxicities were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v5, whereas chronic toxicities were assessed in accordance with LENT-SOMA. Patient traits were compared by implementing t­tests and Wilcoxon-Whitney tests for continuous variables, whereas discrete characteristics were evaluated by applying two-tailed Fisher's exact tests. In addition, we calculated average treatment effects (ATE). Thereby, propensity score matching (PSM) based on nearest-neighbor matching considering age, comorbidities, and risk stratification as covariates was applied. The statistical analysis was conducted using Stata 14.2 (StataCorp LLC, TX, USA). RESULTS: As confirmed by the descriptive tests, the ATE revealed that the intensity and occurrence of urinary frequency (p = 0.034) and proctitis (p = 0.027) significantly decreased for the HRT group, whereas all other acute toxicities did not differ significantly between the HRT and CRT groups. For late toxicities, neither statistical tests nor ATE estimation showed significant differences. Also, no significant difference was found regarding the decrease in prostate specific antigen (PSA) after a median follow-up of 13 months (range 2-28 months), which indicates biochemical freedom from progression. CONCLUSION: HRT offers several medical and economic advantages and should therefore be considered as a useful alternative to CRT.

Cystic dilation of a ventriculus terminalis. Case report and review of the literature.

The ventriculus terminalis (VT) is a small ependyma-lined cavity within the conus medullaris that is in direct continuity with the central canal of the spinal cord. Cystic dilatation of the ventriculus terminalis on its own is an extremely rare pathological event in adults whose pathogenesis is uncertain. VT has been described in children as a normal developmental phenomenon. These lesions are often diagnosed incidentally during imaging and are in most cases asymptomatic, especially in children. Symptomatic dilatation of VT in adults is a rare condition with 61cases being reported to date. Symptomatic dilatation of VT in children has not been reported till now. We present a 5 year-old-boy with a sphincteric and walking disorder. The patient was assessed by clinical, electrophysiological and urodynamic investigations as well as magnetic resonance imaging (MRI) of the lumbar-sacral segment with and without gadolinium enhancement. Lumbar-sacral MRI demonstrated the presence of a cystic lesion containing cerebrospinal fluid (CSF), which did not enhance after gadolinium, compatible with the diagnosis of the ventriculus terminalis dilation.The patient underwent laminectomy and the cyst wall was fenestrated with a midline myelotomy. In 6-month of follow-up, urinary problems and gait disturbance improved.

Endocrine disruptor bisphenol A is implicated in urinary voiding dysfunction in male mice.

Estrogens, acting synergistically with androgens, are known from animal experiments to be important in lower urinary tract symptoms (LUTS) and benign prostate enlargement. Human exposure to environmental estrogens occurs throughout the life span, but the urologic health risks in men are largely unknown. Bisphenol A (BPA) is an endocrine disruptor implicated in male urogenital malformations. Given the role of estrogens in male LUTS, we studied the effects of BPA administered in combination with testosterone (T) on the urinary voiding behavior of adult male mice. Adult male mice underwent subcutaneous implantation with slow-release pellets of 25 mg BPA or 2.5 mg estradiol-17ß (E2), plus 25 mg T, and were compared with untreated (UNT) mice that underwent sham surgery. We studied urinary voiding behavior noninvasively for 1 mo before treatment and for 4 mo after treatment. After euthanasia, we evaluated bladder volume and mass. Mice treated with T+BPA had increased bladder volume ( P < 0.05) and mass ( P < 0.01) compared with UNT mice. After 4 mo of treatment with T+BPA, three of five mice developed voiding dysfunction in the form of droplet voiding or an intermediate pattern of voiding different from both UNT and T+E2-treated mice. Treatment of male mice with BPA or estradiol induces voiding dysfunction that manifests at later time points, implicating the endocrine disruptor, BPA, as a contributor to male LUTS.

Interstitial cystitis: elements of diagnosis and place of histopathological examination. About 16 cases.

BACKGROUND: Interstitial cystitis (IC) is a rare disease, of difficult diagnosis. The diagnostic utility of histopathological examination of bladder biopsy remains controversial. AIM: We conducted a retrospective study to assess the frequency of interstitial cystitis, to analyze its clinical presentation and the data from the paraclinical examinations. We discuss the steps and criteria of diagnosis, as well as the place of histopathological examination for diagnosis. METHODS: Sixteen patients diagnosed with IC were followed in the Urology Department of the Sahloul University Hospital between 1996 and 2013. The diagnosis was suggested by clinical history and confirmed on the basis of clinical symptoms and results of the paraclinical explorations: urodynamic assessment, cystoscopy and bladder biopsy. RESULTS: Six men (37.5%) and ten women (62.5%), with an average age of 56 years complained of pelvic pain and urination disorders for two years on average before the diagnosis. The urodynamic study found decreased bladder compliance in 13 cases and bladder instability in nine cases. Cystoscopy demonstrated inflammatory mucosa in 13 patients (81%). Histologically, the classic ulcerative form accounted for 50% of the cases. The number of mast cells was high in both the mucosa and the muscular in 12 cases, both in the classical and non-ulcerative forms. CONCLUSION: The IC remains a diagnosis of exclusion. The first line of diagnosis is patient selection based on symptoms and an exclusion of diseases with similar presentation. Vesical biopsy is useful for confirmation and classification of the disease.

Videourodynamic Studies of Women with Voiding Dysfunction.

This retrospective study is aimed to present videourodynamic findings of women with symptoms of voiding dysfunction in a medical center. Of 1914 women, the diagnoses included bladder outlet obstruction (BOO, n = 810, 42.3%), bladder dysfunction (n = 1,048, 54.8%) and normal tracings (n = 56, 2.9%). Anatomic BOO (n = 49) included cystocele (n = 19) and urethral stricture (n = 30). Common functional BOOs included dysfunctional voiding (n = 325, 17.0%) and poor relaxation of the external sphincter (n = 336, 17.6%). Common bladder dysfunction subtypes included detrusor underactivity (n = 337, 17.6%), detrusor hyperactivity with impaired contractility (n = 231, 12.1%), and bladder oversensitivity (n = 325, 17.0%). Receiver operating characteristic (ROC) analysis were performed, and the following optimum cutoff values were determined: (1) voiding detrusor pressure at a maximum flow rate (Pdet.Qmax) = 30 cmH2O for differentiating BOO from bladder dysfunction and normal tracings, with an ROC area of 0.78; (2) the Abrams-Griffiths number = 30 for differentiating anatomic from functional BOO, with an ROC area of 0.66; (3) post-void residual = 200 mL for differentiating bladder neck dysfunction from the other BOOs, with an ROC area of 0.69; (4) Pdet.Qmax = 30 cmH2O for differentiating dysfunctional voiding from poor relaxation of the external sphincter with an ROC area of 0.93. The above findings can be used as initial guide for management of female BOO.

Predictive Factors for Prolonged Urination Disorder After Permanent 125I Brachytherapy for Localized Prostate Cancer.

BACKGROUND: We assessed the change in LUTS after prostate brachytherapy to reveal factors for prolonged urination disorder. MATERIALS AND METHODS: Four hundred and four patients received prostate brachytherapy at our institution and were followed-up for at least 2 years. We evaluated the correlation of mean IPSS changes and clinical factors. Using multivariate analysis, we also evaluated clinical factors with potential to delay IPSS resolution. RESULTS: In cases with prostate volume more than 30 cm3, radiation dose to 90% of prostate volume (D90) more than 160 Gy, and radiation dose to 30% of the urethral volume (UD30) more than 240 Gy, mean IPSS levels were significantly higher, even 30 months after treatment. On multivariate analysis, baseline IPSS more than 8 points and D90 more than 160 Gy were significant predictors for delayed IPSS resolution. CONCLUSION: Our data suggest that higher baseline IPSS and higher D90 were predictors for prolonged urination disorder.

Obesity-initiated metabolic syndrome promotes urinary voiding dysfunction in a mouse model.

OBJECTIVE: Accumulating evidences suggests that obesity and metabolic syndrome (MetS) contribute towards lower urinary tract symptoms (LUTS) through alterations in the phenotype of bladder and prostate gland. Clinical studies indicate a link between MetS and LUTS. Nevertheless, there is lack of suitable animal model(s) which could illustrate an association linking obesity to LUTS. We examined the lower urinary tract function in an obesity-initiated MetS mouse model. METHODS: Male C57BL/6N wild-type and obese B6.V-Lepob/J maintained on regular diet for 28 weeks were subjected to the assessment of body weight (BW), body length (BL), waist circumference (WC), body mass index (BMI), blood glucose (BG), plasma insulin (INS), plasma leptin (LEP), total cholesterol (CHO), free fatty acid (FFA), and measurement of urinary functions. Whole animal peritoneal and subcutaneous adipose tissue measurements as well as prostate and bladder volumes were analyzed by MRI followed by histological evaluation. These parameters were used to draw correlations between MetS and LUTS. RESULTS: Obesity parameters such as BW, WC, and BMI were significantly higher in B6.V-Lepob/J mice compared to C57BL/6N mice (P < 0.01). Higher levels of total CHO and FFA were noted in B6.V-Lepob/J mice than C57BL/6N mice (P < 0.05). These results were concurrent with frequency, lower average urine volume and other urinary voiding dysfunctions in B6.V-Lepob/J mice. MRI assessments demonstrate marked increase in body fat and prostate volume in these mice. Compared to C57BL/6N mice, histological analysis of the prostate from B6.V-Lepob/J mice showed increased proliferation, gland crowding, and infiltration of immune cells in the stroma; whereas the bladder urothelium was slightly thicker and appears more proliferative in these mice. The regression and correlation analysis indicate that peritoneal fat (R = 0.853; P < 0.02), CHO (R = 0.729; P < 0.001), BG (R = 0.712; P < 0.001) and prostate volume (R = 0.706; P < 0.023) strongly correlate with LUTS whereas BMI, WC, INS, and FFA moderately correlate with the prevalence of bladder dysfunction. CONCLUSION: Our results suggest that LUTS may be attributable in part to obesity and MetS. Validation of an in vivo model may lead to understand the underlying pathophysiological mechanisms of obesity-related LUTS in humans. Prostate 76:964-976, 2016. © 2016 Wiley Periodicals, Inc.

A review of antidepressant-induced urinary hesitancy: a focus on levomilnacipran ER including two case presentations(5633).

INTRODUCTION: Levomilnacipran ER was recently FDA approved as Fetzima® for the treatment of MDD. Urinary hesitancy can be an adverse event associated with levomilnacipran treatment. AREAS COVERED: This manuscript details the longitudinal course of levomilnacipran-induced urinary hesitancy in 2 cases that were in a pivotal clinical trial, examining possible predisposing factors and treatment issues. This manuscript also reviews the literature comparing urinary hesitancy associated with levomilnacipran versus other antidepressants. Antidepressants that are potent norepinephrine reuptake inhibitors like levomilnacipran, may have increased rates of associated urinary hesitancy. The latter can cause significant discomfort and a compromised quality of life. Occasionally, it can progress to urinary retention necessitating an emergency medical intervention. EXPERT OPINION: All patients being treated with antidepressants should be carefully monitored for this side effect. Discontinuation of treatment or reduction of the dose of antidepressant frequently relieves urinary hesitancy; alternatively, treatment with an alpha1A antagonist, e.g., tamsulosin may relieve antidepressant-induced urinary hesitancy within hours to days; such strategies allow for continued antidepressant treatment without urinary hesitancy recurring. Thus, with appropriate clinical care, the benefits using levomilnacipran outweigh its risks.

Stranded under the Prom: impacted gravid uterus presenting as acute urinary retention.

Acute urinary retention in pregnancy secondary to an impacted uterus is a rare occurrence. It can have non-specific presentations, leading to delay in diagnosis, hence potentially increasing maternal and fetal morbidity and mortality. A number of risk factors for the condition have been identified. We describe the case of a 31-year-old woman presenting with urinary retention at 18 weeks' gestation. Clinical examination revealed features consistent with a gravid uterus impacted in the pelvis. Management with urinary catheterisation followed by gentle manual disimpaction of the uterus was successful.

Micturition disorders.

Evaluation of dogs and cats with micturition disorders can be challenging. It is important to determine the duration, timing, and frequency of the disorder, as well as assessing for any additional medical problems, such as neurologic or orthopedic disease, that may be affecting micturition. Observation of the patient during voiding can be particularly helpful in determining the type of disorder. Treatment of micturition disorders is varied and outcome depends on an accurate diagnosis. Patient response is also highly variable, even with appropriate therapy, and owners' expectations must be set accordingly.

Histopathology of excised midurethral sling mesh.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to compare the histological characteristics of pathological specimens of excised midurethral sling mesh and surrounding vaginal tissue in patients who presented preoperatively with pain and/or exposure of mesh to patients who underwent mesh excision for voiding dysfunction without pain and/or erosion. METHODS: This is a retrospective case-control study of women who underwent excision of midurethral sling mesh between 2008 and 2013. Three groups were identified: (1) voiding dysfunction without pain or exposure (control group), (2) pain and/or mesh exposure, and (3) voiding dysfunction with pain and/or mesh exposure. All original pathological specimens were rereviewed by one pathologist blinded to indication for excision and the previous pathology report. Degree of inflammation and fibrosis were recorded based on a 4-point scale along with the presence of giant cell reaction. RESULTS: A total of 130 subjects met inclusion criteria: 60 (46.2 %) with voiding dysfunction only, 21 (16.2 %) with pain/erosion, and 49 (37.7 %) with both pain/exposure and voiding dysfunction. The voiding dysfunction only group was found to have significantly higher levels of inflammation, median grade 2 (1-3), compared to the other two groups with a p value of 0.007. There were no statistical differences in fibrosis and giant cell reaction between the three groups. CONCLUSIONS: Midurethral sling mesh excised for voiding dysfunction demonstrates elevated levels of inflammation compared to mesh that is excised for pain and/or exposure. The vaginal tissue fibrosis and giant cell reaction are similar in patients who undergo mesh excision for voiding dysfunction and pain, and/or mesh exposure.

Pattern of voiding dysfunction after acute brainstem infarction.

BACKGROUND: The purpose of this study is to compare the patterns of voiding dysfunction according to the locations of brainstem lesions. METHODS: Between November 2008 and December 2011, a total of 30 patients participated in this study. All 30 subjects, consisting of 16 men and 14 women, aged between 41 and 82 years (mean age, 63.0±11.0 years) underwent a urodynamic study within 7 days after the onset of a stroke. RESULTS: Twenty-one (70%) patients had a pontine lesion and 9 (30%) had a medullary lesion. Fourteen of these patients (46.7%) had bladder storage disorder, 7 patients (23.3%) had bladder emptying disorder, and 9 patients (30%) had a normal report. Five of the patients who had a medullary lesion (55.6%) had bladder emptying disorder, whereas only 2 patients who had a pontine lesion (9.5%) had bladder emptying disorder. Thirteen patients who had a pontine lesion (61.9%) showed bladder storage disorder. DISCUSSION: The descending pathway from the midbrain tegmentum is inhibitory, and the pathway from the pontine tegmentum is stimulatory. Because of their location pontine lesions could disrupt the descending fibers of the midbrain tegmentum and medullary lesions could disrupt the descending fibers of the pontine tegmentum.

[Combined treatment of patients with erectile dysfunction and urination disorders].

The article presents the results of the study aimed to the evaluation the efficacy of combination therapy with alpha1-blocker (tamsulosin) and phosphodiesterase type 5 inhibitor (sildenafil) in patients with urination disorders and erectile dysfunction (ED). A pilot observational study involving 60 men aged from 50 and 80 years divided into 3 groups of 20 people was performed. Group 1 of patients received sildenafil 25 mg daily (dynamico), Group 2--tamsulosin 0.4 mg daily (Omnic-Ocas), and Group 3--tamsulosin 0.4 mg (Omnic-Ocas) and sildenafil 25 mg (dynamico) daily. The visits were carried out at the stage of screening, further--every 10 days (a total number--4 visits). Combination therapy of urination disorders and ED contributed to the significant improvement in uroflowmetry, the stopping of complaints according to the IPSS and IIEF-15 questionnaires, and improving the quality of life (according to the QoL questionnaire). Combination therapy significantly decreased obstructive and irritative symptoms, increased the maximum urine flow rate within the period of observation, as well as significantly decreased the residual urine volume, more pronounced when compared with monotherapy. Significant positive effect on erectile component and all components of the overall satisfaction in the sexual sphere were registered, that as a consequence led to the positive impact on the quality of life in patients treated with PDE5 inhibitor. Given the high prevalence of urinary disorders and erectile dysfunction, combined therapy with alpha1-blockers and PDE5 inhibitors in this case should be a promising area for drug therapy.