Chronic Bladder Outlet Obstruction Research Articles

MRI-based radiomic features of the urinary bladder wall identify patients with moderate-to-severe international prostate symptom score

BackgroundThe International Prostate Symptom Score (IPSS) is a patient-reported measurement to assess the lower urinary tract symptoms of bladder outlet obstruction. Bladder outlet obstruction induces molecular and morphological alterations in the urothelium, suburothelium, detrusor smooth muscle cells, detrusor extracellular matrix, and nerves. We sought to analyze MRI-based radiomics features of the urinary bladder wall and their association with IPSS.MethodIn this retrospective study, 87 patients who had pelvic MRI scans were identified. A biomarker discovery approach based on the optimal biomarker (OBM) method was used to extract features of the bladder wall from MR images, including morphological, intensity-based, and texture-based features, along with clinical variables. Mathematical models were created using subsets of features and evaluated based on their ability to discriminate between low and moderate-to-severe IPSS (less than 8 vs. equal to or greater than 8).ResultsOf the 7,666 features per patient, four highest-ranking optimal features were derived (all texture-based features), which provided a classification accuracy of 0.80 with a sensitivity, specificity, and area under the receiver operating characteristic curve of 0.81, 0.81, and 0.87, respectively.ConclusionA highly independent set of urinary bladder wall features derived from MRI scans were able to discriminate between patients with low vs. moderate-to-severe IPSS with accuracy of 80%. Such differences in MRI-based properties of the bladder wall in patients with varying IPSS’s might reflect differences in underlying molecular and morphological alterations that occur in the setting of chronic bladder outlet obstruction.

Decreased Angiopoietin Expression in Underactive Bladder Induced by Long-term Bladder Outlet Obstruction.

Ischemia of the bladder can occur if neovascular formation cannot keep pace with hypoxia induced by chronic bladder outlet obstruction (BOO). The aim of this study was to examine changes in angiogenesis growth factor expression generated by chronic BOO in a rat model of underactive bladder. Twenty female Sprague-Dawley rats aged 6 weeks were assigned to 4 groups (5 rats per group). Group 1 was the control. Group 2 underwent sham surgery. The rats in groups 3 and 4 underwent BOO and were followed up for 1 week and 8 weeks. Cystometry was carried out together with bladder tissue analysis at 1 week and 8 weeks postoperatively. Real-time polymerase chain reaction (PCR) assays were conducted to determine the expression level of angiogenesis-related growth factors. A hypoxia signaling pathway PCR array was additionally carried out. The group that underwent BOO for 8 weeks showed abnormal bladder function, with a diminished intercontraction interval, decreased maximal voiding pressure, and higher volume of residual urine (P<0.05). Hypoxia-inducible factor-1 alpha expression was elevated in this group. The expression levels of vascular endothelial growth factor (VEGF) and VEGF receptor messenger RNA (mRNA) in the BOO group were comparable to those in the control group. However, angiotensin/tie receptor mRNA expression levels increased at 1 week after BOO, but decreased at 8 weeks after BOO. In animals that underwent BOO, fewer blood vessels exhibited positive immunofluorescent staining for von Willebrand factor. Alterations were also seen in the hypoxia signaling pathway PCR array. In a rat model of underactive bladder caused by surgical BOO, reduced angiopoietin expression was demonstrated. This observation might underlie visceral ischemia and fibrosis associated with the procedure. The findings of this study might offer an improved understanding of the disease processes underlying BOO and facilitate selection of the appropriate time to repair the organ in this condition.

Bladder-Induced Compression of the External Iliac Veins: Recognition and Implications for Treatment.

The effect of changes in bladder volume on the caliber of adjacent veins is underappreciated but essential to recognize to avoid complications such as unnecessary stenting or clot migration causing pulmonary embolism. Here the authors illustrate the importance of this finding in 3 cases using venographic and endovascular sonographic imaging: the first in which BPH-induced chronic bladder outlet obstruction resulted in DVT formation, the second in which the cause was unrecognized and unnecessary stenting performed, and the third in which inappropriate treatment was avoided by decompressing the bladder.

White Matter Integrity in Men With Benign Prostatic Hyperplasia and Bladder Outlet Obstruction and Its Contribution to Lower Urinary Tract Symptoms.

PurposeLower urinary tract symptoms (LUTS) associated with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) can negatively impact quality of life. We evaluated the structural connectivity of the brain in men with BPH with chronic BOO using diffusion tensor imaging (DTI).MethodsAmbulatory male patients aged ≥45 years with BPH and BOO were recruited. LUTS was defined as an International Prostate Symptom Score (IPSS) ≥12 and a maximum urinary flow rate ≤15 mL/sec. Upon recruitment, uroflowmetry and validated questionnaires regarding bladder status were collected. DTI images from each subject were aligned with the ICBM-DTI-81 atlas, defining 50 white matter tracts (WMTs). The mean values of DTI parameters—fractional anisotropy and mean diffusivity—for each WMT were extracted. These measures were then utilized to compute Pearson correlation coefficients with clinical parameters. Objective clinical parameters included uroflowmetry parameters, postvoid residual (PVR) volume, and bladder capacity. Subjective clinical parameters were assessed using validated questionnaires: the IPSS, Incontinence Symptom Index, and Sexual Health Inventory for Men.ResultsThe correlation analysis revealed 15 WMTs that showed statistically significant associations (P<0.05) with objective and subjective clinical parameters. Eight tracts were associated with uroflowmetry parameters: maximum flow rate (Qmax), mean flow rate (Qmean), and PVR. Among these tracts, the middle cerebellar peduncles and left medial lemniscus were associated with Qmax; the genu of the corpus callosum, left superior corona radiata, corticospinal tract, right medial lemniscus, posterior corona radiata with Qmean; and the left posterior corona radiata with PVR. Seven tracts also demonstrated significant associations with the IPSS.ConclusionsOur results suggest correlations between the preserved white matter integrity of specific WMTs and the severity of LUTS based on objective and subjective clinical parameters, leading us to believe that a distinct pathology of the central nervous system might exist.

PD11-05 PRELIMINARY RESULTS OF BASELINE CORTICAL NEURAL ACTIVITY IN MEN WITH BENIGN PROSTATIC HYPERPLASIA AND BLADDER OUTLET OBSTRUCTION

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (PD11)1 Sep 2021PD11-05 PRELIMINARY RESULTS OF BASELINE CORTICAL NEURAL ACTIVITY IN MEN WITH BENIGN PROSTATIC HYPERPLASIA AND BLADDER OUTLET OBSTRUCTION Ricardo Gonzalez, Logan Hubbard, Khue Tran, Natalia Hernandez, Christof Karmonik, Shi Zhaoyue, and Rose Khavari Ricardo GonzalezRicardo Gonzalez More articles by this author , Logan HubbardLogan Hubbard More articles by this author , Khue TranKhue Tran More articles by this author , Natalia HernandezNatalia Hernandez More articles by this author , Christof KarmonikChristof Karmonik More articles by this author , Shi ZhaoyueShi Zhaoyue More articles by this author , and Rose KhavariRose Khavari More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001986.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) affects the entire micturition cycle including filling/storage phases, creating bothersome lower urinary tract symptoms (LUTS). Chronic bladder outlet obstruction (BOO) remodels the entire lower urinary tract including the detrusor, connective tissue and local neural network; yet the extent to which it alters the central nervous system (CNS) in BPH is unknown. This study explores brain activation patterns on fMRI in men with BPH and BOO. METHODS: Men age ≥45 who failed conservative BPH therapy planning to undergo BOO procedures were recruited. Eligible men underwent concurrent fMRI-urodynamics (UDS) examination, their bladder was filled until a strong desire to void was signaled. Subjects were asked to hold for 30 seconds, before receiving permission to void while concurrent UDS was performed. After voiding/attempt to void, the bladder was drained and the cycle was repeated up to four times. fMRI images were obtained via a T1W 3 Tesla MRI. Significant activated voxels (p <0.05) were identified at strong urge to void and voiding initiation/attempt to void. RESULTS: Seven men with baseline demographics are represented in table 1. At strong urge to void, there was activation in the right inferior frontal gyrus (IFG) (p <0.05), fig 1a. Deactivation was seen bilaterally in thalamus, middle frontal gyrus, insula and parahippocampal gyrus, and in left middle/superior temporal gyrus (p <0.05). At voiding initiation activation was seen in the left angular gyrus/superior temporal gyrus, and the IFG, fig 1b. Only four of seven patients were able to void supine during fMRI scan. CONCLUSIONS: This is the first study evaluating cortical activity in men with BPH and BOO. At full urge there was significant activation of the IFG, consistent with data from Harvie et al showing its significance during the voiding phase. However, there were important deactivations including bilateral thalamus, insula, and IFG during initiation and voiding attempts previously shown to be important regions in normal micturition in healthy adults. Further studies should evaluate whether deactivation in these regions reflect the inability to void of multiple subjects and/or represent neuroplastic changes of supraspinal micturition control in response to chronic BOO in men with BPH. Source of Funding: This study is supported by Pilot project funding through University of Pittsburgh O’Brien Cooperative Research Center program U54DK112079. Dr. Khavari is partially supported by K23DK118209, by National Institute of Heath, NIDDK and by Houston Methodist Clinician Scientist Award © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e199-e199 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ricardo Gonzalez More articles by this author Logan Hubbard More articles by this author Khue Tran More articles by this author Natalia Hernandez More articles by this author Christof Karmonik More articles by this author Shi Zhaoyue More articles by this author Rose Khavari More articles by this author Expand All Advertisement Loading ...

Revascularized Pyelo-Uretero-Cystoplasty in Patients with Chronic Bladder Outlet Obstruction Due to Ectopic Ureterocele: A Safe Surgical Technique with Superior Continence Outcomes

Purpose To present the outcomes of revascularized pyeloureterocystoplasty with ureterocele unroofing in end stage bladder patients with duplex system and ureterocele. Methods Thirteen patients with obstruction of intrauterine outlet from an ectopic obstructive ureterocele were included. Fourteen units of duplex systems underwent upper pole partial nephrectomy in conjunction with augmentation revascularized pyeloureterocystoplaty and ureterocele unroofing. The anterior and lateral walls of the ureterocele were excised before cystoplasty, and the resultant edges of the posterior wall were sutured to the bladder epithelium. Anastomosis of the upper pole vein and artery to the inferior iliac artery and the common iliac vein was performed. Detubularization of the whole ureter was performed with exception of the intramural ureteric part that kept tubularized for ‘jet/turbulent’ occurrence. Five patients (control group) underwent pyeloureterocystoplasty without revascularization. Patients underwent several evaluations in long-term follow-up. Results Patients were all dry by day and night in our long-term follow-up. Urinary incontinence improved in patients with no need for re-augmentation technique. Vesicoureteral reflux subsided in all patients postoperatively except one, who was asymptomatic. After five years, median bladder capacity rose from 128.5 ml to 395 ml and bladder compliance showed significant improvement from 15 ml/cm H2O to 29 ml/cm H2O, in experimental group and remained stable for 24–36 months. Median bladder capacity did not rise significantly in control group. Conclusion Pyeloureterocystoplasty is an efficient choice in this type of patients, which may prevent the recurrence of hypocompliant bladders and prevent ischemia and subsequent fibrosis.

New mouse model of underactive bladder developed by placement of a metal ring around the bladder neck.

To develop a new mouse model of underactive bladder (UAB) caused by chronic bladder outlet obstruction (BOO). BOO was created in 6-week-old male C57BL/6 mice using surgery to loosely place a silver jump ring around the bladder neck of each mouse. Micturition behavior (assessed with a metabolic cage) and cystometry were used to evaluate bladder function at 8 and 16 weeks after BOO. Following completion of the functional studies, the bladders of the mice were excised, weighed, and subjected to histological analysis. Micturition behavior analysis showed that mice subjected to BOO for 16 weeks had a lower frequency of micturition (7.3 ± 1.1 vs 12.5 ± 3.0 times/d, P < .05) and volume per void (106.0 ± 0.1 vs 133.9 ± 3.2 μL, P < .05) than mice subjected to BOO for 8 weeks. Cystometry revealed that mice subjected to BOO for 16 weeks had lower baseline pressure (8.4 ± 0.6 vs 14.0 ± 0.7 cmH2 O, P < .01) and micturition pressure (13.9 ± 1.1 vs 42.8 ± 1.7 cmH2 O, P < .05) than mice subjected to BOO for 8 weeks. BOO caused progressive increases in bladder mass and collagen deposition over time. We successfully established a novel mouse model of UAB using surgery to place a silver jump ring loosely on the bladder neck. BOO initially induced bladder overactivity but subsequently resulted in UAB due to deterioration of detrusor smooth muscle contractility and progressive deposition of collagen in the bladder wall.

A possible mechanism underlying mood disorders associated with LUTS: Chronic bladder outlet obstruction causes NLRP3‐dependent inflammation in the hippocampus and depressive behavior in rats

Reports link urinary dysfunction and mood disorders, such as depression, but a causative mechanism has never been postulated. Contemporary discoveries demonstrate a local inflammatory response in peripheral organs can trigger inflammation in the brain, particularly the hippocampus, mediated through the NLRP3 inflammasome. Critically, central inflammation causes depressive behavior. Since bladder outlet obstruction (BOO) evokes a local inflammatory response in the bladder, we hypothesize it will induce NLRP3-dependent inflammation in the hippocampus and depressive behavior. There were four groups of rats: control, sham, BOO, or BOO + glyburide (an NLRP3 inhibitor). BOO was created by urethral ligation over a 1 mm catheter. Sham was tied loosely. Glyburide was provided by slow-release pellet (subcutaneous 50 mg, 21 day, replaced as needed). Rats were analyzed 12 weeks post-op for: hippocampal inflammation, microglial density, neurogenesis, and depression symptoms (open field and sucrose preference). BOO elicited hippocampal inflammation, accompanied by an increase in activated microglia (22%) and a decrease in neurogenesis (35%), which was blocked by glyburide. In addition, BOO rats displayed anxiety (57% decrease in exploratory behavior in the open field assay) and anhedonia (21% decrease in sucrose preference), two symptoms of depression. Like inflammation, these symptoms were diminished by glyburide to levels not statistically significantly different from controls. BOO, a bladder-localized event, stimulates NLRP3-dependent inflammation in the rat hippocampus after 12 weeks and this inflammation causes depressive behavior. This is the first mechanistic explanation of the link between BOO and depression and provides evidence for a distinct bladder-brain axis.

Prostate Tuberculosis

Prostate tuberculosis (PTB) is an extremely rare complication of pulmonary tuberculosis (TB) that is alien to many urologists due to unaccustomed prostate involvement, thus posing a high tendency of confusion with prostate cancer. A 55-year-old Nigerian male presented with lower urinary tract symptoms with micturition difficulty, characterized by dysuria and weak urine stream that did not improve with straining, urge incontinence, and feeling of incomplete bladder emptying, some months after the completion of anti-Koch chemotherapy. The assessment of chronic bladder outlet obstruction secondary to benign prostatic hyperplasia was done, following a digital rectal examination which showed malignant features. The finding prompted requests for serum prostate-specific antigen (PSA) level and prostate biopsy. PSA level was 22.6 ng/ml, whereas histopathological examination showed Langhans-type giant cells suggestive of PTB. There is a high chance of missing out PTB in the diagnosis. Hence, a high index of suspicion is crucial in all TB-burden countries to make a differential diagnosis of PTB from classical prostate cancer.

Bladder decompensation and reduction in nerve density in a rat model of chronic bladder outlet obstruction are attenuated with the NLRP3 inhibitor glyburide.

Bladder outlet obstruction (BOO) leads to progressive voiding dysfunction. Acutely, obstruction triggers inflammation that drives bladder dysfunction. Over time, inflammation leads to decreased bladder nerve density and increased fibrosis, responsible for eventual decompensation and irreversibility. We have previously shown that BOO triggers inflammation, reduced bladder nerve density and increased fibrosis via activation of the NLRP3 inflammasome in an acutely obstructed (12-day) rat model. However, as BOO progresses, the bladder may become decompensated with an increase in postvoid residual volume and decreased voiding efficiency. Currently, we have examined rat bladder function and nerve densities after chronic BOO to determine whether NLRP3 plays a role in the decompensation at this stage. Four groups were examined: control, sham-operated, BOO, or BOO+gly (glyburide; an NLRP3 inhibitor). After 42 days, bladder weight, inflammation (Evans blue), urodynamics, and nerve density were measured. BOO greatly enhanced bladder weights and inflammation, while inflammation was prevented by glyburide. Voiding pressures were increased, and flow rates decreased in BOO and BOO+gly groups, demonstrating physical obstruction. No difference in frequency or voided volume was detected. However, postvoid residual volumes were greatly increased in BOO rats while BOO+gly rats were not different than controls. Moreover, there was a dramatic decrease in voiding efficiency in the chronic BOO rats, which was prevented with glyburide treatment. Finally, a reduction in nerve density was apparent with BOO and attenuated with glyburide. Together the results suggest a critical role for NLRP3 in mediating bladder decompensation and nerve density during chronic BOO.

MP09-16 PHARMACOLOGICAL INHIBITION OF THE NLRP3 INFLAMMASOME PREVENTS BLADDER DECOMPENSATION IN A RAT MODEL OF CHRONIC BLADDER OUTLET OBSTRUCTION

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2018MP09-16 PHARMACOLOGICAL INHIBITION OF THE NLRP3 INFLAMMASOME PREVENTS BLADDER DECOMPENSATION IN A RAT MODEL OF CHRONIC BLADDER OUTLET OBSTRUCTION Francis Hughes, Stephanie Sexton, Patrick Leidig, Huixia Jin, and J. Purves Francis HughesFrancis Hughes More articles by this author , Stephanie SextonStephanie Sexton More articles by this author , Patrick LeidigPatrick Leidig More articles by this author , Huixia JinHuixia Jin More articles by this author , and J. PurvesJ. Purves More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.342AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder outlet obstruction (BOO), most often the result of benign prostatic hyperplasia, may lead to progressive voiding dysfunction. BOO can create an overactive bladder (OAB) phenotype defined by increased frequency of voiding and decreased voiding volume (VV)). We have previously shown in the rat that acute BOO (12 days) activates the NLRP3 inflammasome which mediates inflammation and the OAB phenotype. Initially, the bladder can compensate for the obstruction by generating higher voiding pressures. However, over time the bladder decompensates which results in an increase in post-void residual volume (PVR) and decreased voiding efficiency. In this study we have examined the role of NLRP3 on rat bladder function after chronic BOO (42 days) and investigated the utility of an NLRP3 inhibitor in preventing decompensation. METHODS 4 groups were examined: 1) control, 2) sham-operated, 3) BOO and 4) BOO + gly (glyburide; an NLRP3 inhibitor). BOO was created by inserting a 1 mm transurethral catheter, tying a suture around the urethra, and removing the catheter. Gly was provided via 50 mg, 21 day release pellet (s.c.) that was replaced after 21 days. Suprapubic tubes were implanted on Day 35 and urodynamics performed on Day 42. PVR was assessed immediately after the final micturition by drawing back on the catheter with a syringe. The rat was immediately sacrificed and any additional post void liquid remaining in the bladder removed by needle puncture and added to the total PVR volume. RESULTS Voiding pressures were increased and flow rates decreased in BOO and BOO + gly groups, demonstrating physical obstruction of the urethra. No difference in frequency or VV were detected among groups. However, PVRs were greatly increased in BOO rats while BOO + gly rats were not different than controls (Figure 1). Moreover, also shown in Figure 1, there was a dramatic decrease in voiding efficiency in the chronically obstructed rats which was completely prevented by glyburide treatment. CONCLUSIONS The results suggest a critical role for NLRP3 in the progression to bladder decompensation during chronic BOO and that treatment with an NLRP3 inhibitor preserves voiding efficiency. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e112-e113 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Francis Hughes More articles by this author Stephanie Sexton More articles by this author Patrick Leidig More articles by this author Huixia Jin More articles by this author J. Purves More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Was Ugo Foscolo (1778–1827) affected by alpha-1 antitrypsin deficiency?

Niccolò Ugo Foscolo (1778–1827), known as Ugo, is one of the masters of the Italian poetry. A writer and a revolutionary, he embraced the ideals of the French Revolution and took part in the stormy political discussions, which the fall of the Republic of Venice had provoked. Despite his poor health, Foscolo lived an adventurous life serving as a volunteer in the Guardia Nazionale and in the Napoleonic army. Following Napoleon’s fall (1814), he went into voluntary exile in early 1815. He reached London in Sept. 1816 and lived in poverty at Turnham Green (Chiswick) until his premature death.Foscolo’s medical history has been poorly investigated and the cause of his death remains unclear. In an attempt to shed light on his clinical history, we analyzed his Correspondence (Epistolario), a series of more than 3000 letters written between 1794 and 1827. From the age of 26 (1808), Foscolo had frequent episodes of cough and dyspnea that progressively worsened. Four acute respiratory exacerbations occurred in 1812. Between September 1812 and April 1813, he had breathlessness as that of asthma.Frail and ailing, he developed a chronic liver disease in 1826. In August 1827, weakness, dyspepsia and drowsiness further increased and dropsy became manifest. He went into coma on September 7, 1827 and died aged 49 three days later.Based on a brief history of urethritis and urinary obstructions (1811–1812), previous scholars have suggested that Foscolo had urethral stenosis that caused a chronic bladder outlet obstruction and led to consequent renal failure. This hypothesis, however, does not mention the respiratory symptomatology present since 1804, which is a pivotal feature of Foscolo’s illness.We surmise that Foscolo suffered from alpha-1 anti trypsin (AAT) deficiency, a rare genetic disease, which caused his premature death and support our interpretation with documental evidence.

Did Ugo Foscolo suffer from chronic renal insufficiency?

Ugo Foscolo, was an Italian poet whose works rank among the masterpieces of Italian literature. Talented and well educated in philosophy, classics, and Italian literature, Foscolo gave literary expression to his ideological aspirations and to the numerous amorous experiences in odes, sonnets, plays, poems and an epistolary novel. Concurrent with his rich literary output, Foscolo’s correspondence represents a unique perspective from which to monitor his literary and political views and investigate aspects of his everyday life. Among other interesting information, one can find elements of Foscolo’s medical history which is generally unknown. Based on his testimonies we suggest that he suffered of longstanding bladder outlet obstruction presumably due to urethral stricture. In the present article we investigate the possibility that chronic bladder outlet obstruction and the consequent renal insufficiency was attributed to the death of Ugo Foscolo.

Ischemia, Hypoxia and Oxidative Stress in Bladder Outlet Obstruction and Bladder Overdistention Injury.

Ischemia and the accompanied hypoxia significantly impair the function of the urinary bladder, which is further damaged by ischemia/reperfusion (I/R) injury following the re-establishment of the blood supply. Current evidences have confirmed that blood flow of the bladder is decreased by bladder outlet obstruction (BOO) and acute overdistention and that functional impairment of the urinary bladder following chronic BOO and acute overdistention might partly come from tissue ischemia and ischemia/reperfusion injury. Antioxidants, free radical scavengers or substances inhibiting I/R injury may reduce bladder damages caused by BOO or overdistention.

Is There a Relationship Between Bladder Outlet Obstruction due to Benign Prostatic Hyperplasia and Pulmonary Thromboembolism?

Benign prostatic hyperplasia with chronic bladder outlet obstruction has been associated with deep venous thrombosis (DVT) and fatal pulmonary thromboembolism (PTE). To evaluate this further, 60 autopsy cases of men with PTE were compared with 60 age-matched controls. The criteria for outlet obstruction were macroscopic prostatic enlargement with bladder trabeculation and benign prostatic hyperplasia on microscopy. Ten of the 60 men (16.7%) with fatal PTE had evidence of bladder outlet obstruction (age 57-78 years; mean 71.4 years). Of the 60 controls, 12 had evidence of bladder outlet obstruction (20%) (age 67-86 years; mean 75.5 years). No significant relationship could be demonstrated between bladder outlet obstruction and fatal PTE cases (p = 0.8). Given reports of this association, however, it is possible that bladder distension with venous compression may act as a risk modifier in certain individuals in association with other significant comorbidities, but this risk appears low.

Mesenchymal Stem Cell Recruitment and Improved Bladder Function After Bladder Outlet Obstruction: Preliminary Data

Mesenchymal stem cells have various therapeutic benefits in various organ injury models. Bladder outlet obstruction causes smooth muscle hypertrophy and fibrosis, leading to lowered compliance, increased storage pressures and renal injury. Decreased blood flow and hypoxia may contribute to obstruction related bladder decompensation. We used a mouse model to determine whether mesenchymal stem cell recruitment occurred after bladder outlet obstruction and whether this was associated with changes in bladder hypoxia, histology and function. We also identified potential chemokines involved in mesenchymal stem cell recruitment. A total of 20 female mice underwent bladder outlet obstruction. Three days later 2 million green fluorescent protein labeled mesenchymal stem cells were intravenously administered. After 4 weeks urodynamic and histological evaluation was performed. Quantitative reverse transcriptase-polymerase chain reaction was done to determine relative expression of the chemokines CCL2, CCL20, CCL25, CXCL9 and CXCL16. We simultaneously studied mice with bladder outlet obstruction only without mesenchymal stem cell injection and a control group. In 10 of 15 surviving mesenchymal stem cell injected mice mesenchymal stem cells were identified in the detrusor, and decreased hypoxia, hypertrophy and fibrosis was seen. Nine of 10 mice with mesenchymal stem cell engraftment had improved compliance compared to those without engraftment (mean±SD 9.6±5.1 vs 3.9±2.6 μl/cm H2O, p=0.012). Polymerase chain reaction revealed a 2-fold increase in CCL2 expression but there were no significant changes in other chemokine levels. Mesenchymal stem cell recruitment to the bladder after bladder outlet obstruction appears to be associated with increased blood flow and decreased tissue hypoxia, which may contribute to improvement in histopathological and functional parameters. Mesenchymal stem cell recruitment may be related to CCL2 over expression. Additional studies in larger samples are needed but these initial results suggest a potential role for mesenchymal stem cell based therapy for bladder outlet obstruction related bladder injury.

The effect of alpha-blocker treatment on bladder hypoxia inducible factor-1 alpha regulation during lower urinary tract obstruction

To determine whether alpha1-blocker treatment, in chronic bladder outlet obstruction (BOO), influences bladder tissue ischemia. This prospective study included 60 patients with BOO, of which 40 were under alpha1-blocker medication and 20 without treatment. Patients underwent transurethral resection of the prostate (TURP) or suprapubic prostatectomy (SPP). Ten patients with non-muscle invasive bladder cancer underwent transurethral resection of the bladder tumor and served as the control group. Tissue specimens were immunohistochemically stained for hypoxia inducible factor-1alpha (HIF-1alpha). Bladder tissue from obstructed subjects showed high immunoreactivity to HIF-1alpha. The specimens from the control group, showed no or weak, mainly cytoplasmic immunoreactivity to HIF-1alpha. Patients under alpha -blocker treatment did not differ in the number of HIF-1alpha positive cells compared to subjects with no treatment (median number 86.8 [20-150] and 88.6 [0-175], respectively) (p > 0.05). The lowest bladder pressure at which HIF-1alpha was up regulated, was detected at detrusor pressure Qmax (PdetQmax) = 60 cm H2O. Treatment with alpha-blockers in obstructed patients considered as non-responders, does not result in HIF-1alpha down regulation, thus bladder continues to be under chronic stress.

Excitatory and Inhibitory Influence of Pathways in the Pelvic Nerve on Bladder Activity in Rats with Bladder Outlet Obstruction

OBJECTIVES: This study was undertaken to investigate whether chronic bladder outlet obstruction (BOO) in female rats influences the tonic parasympathetic excitatory or inhibitory reflex control of bladder activity. METHODS: Bladder activity during isovolumetric cystometry (1.5-12 mL) was examined after transection of dorsal and ventral lumbosacral spinal roots (L4-S4) and administration of hexamethonium, a ganglionic blocking agent, in urethane anesthetized female rats with sympathectomy and BOO. RESULTS: Lumbosacral dorsal root transection abolished reflex bladder contractions, but did not influence intravesical baseline pressure. However, ventral root transection after dorsal root transection decreased baseline intravesical pressure (y: % change) at low bladder volumes (x) and increased pressure at high volumes. The calculated (y = 1.9x - 16.5) transition volume was 9 mL. Administration of hexamethonium (100 mg/kg, intraperitoneally) after dorsal and ventral root transection increased the amplitude and decreased the frequency of myogenic bladder contractions. CONCLUSION: The bladder is tonically excited or inhibited depending upon bladder volume by the interactions between a parasympathetic preganglionic pathway in the pelvic nerve and a peripheral reflex. However, in rats with BOO, the volume at which the response shifts from excitation to inhibition was very large, and tonic function of the parasympathetic preganglionic pathway was weak compared to previously reported results in rats without BOO. The persistence of reflex tonic excitatory control of bladder tone over a broad range of bladder volumes may be one of the reasons for overactivity of the bladder with outlet obstruction.

Radical soft tissue mobilization and reconstruction (Kelly procedure) for bladder exstrophy repair in males: initial experience with nine cases

to report the early experience with the Kelly procedure for the treatment of bladder exstrophy (BE) in males. Nine boys with BE were treated at our institute. One had an untouched BE, four had epispadias after neonatal bladder closure, and four were secondary phalloplasties. Data on surgical complications, continence status, presence of erections and parental satisfaction with penile appearance and length are reported. Mean patient age was 4.7 (1-8.9) years. No intra-operative complications occurred. Two secondary cases experienced formation of a bladder-neck fistula and glans ischemia, respectively. The latter led to glans loss. All the patients had some residual degree of hypospadias after surgery. After a median follow-up of 18.1 (10-22) months, one patient developed chronic bladder outlet obstruction. Overall, five patients are dry (including two on clear intermittent catheterization and one with a Minz II pouch). The other four are still younger than 3 years, all have spontaneous micturitions and dry interval between 30 and 120 min. Of the eight patients without phalloplasty complications, all had erections, and parents judged the penile length and appearance as being satisfactory in six cases. The Kelly procedure is feasible in a vast array of BE patients, but may be formidable, especially in secondary phalloplasties. It allows for complete reconfiguration and lightening of the penis, but exposes to potentially catastrophic complications, such as partial or complete penile loss. Longer follow-up is needed to assess the results in terms of continence.

Urodynamics and bladder muscarinic receptors in rats with cerebral infarction and bladder outlet obstruction

We characterized muscarinic receptor binding and urodynamic parameters in rats with cerebral infarction and chronic bladder outlet obstruction as models of detrusor overactivity. Bladder weight showed little significant difference between the cerebral-infarcted and sham rats, but the bladder weight was about three times greater in the bladder outlet-obstructed rats. Bladder capacity and voided volume were significantly lower (36.7 and 55.1%, respectively) in the cerebral-infarcted than in the sham rats. Involuntary contractions before micturition were seen in the bladder outlet-obstructed rats but not in sham rats. The bladder outlet-obstructed rats showed significant increases (2.65 and 2.57 times, respectively) in bladder capacity and voided volume, compared with those in sham rats. Bmax values for specific [N-methyl-3H]scopolamine ([3H]NMS) binding in the bladder were significantly (34%) increased in the cerebral-infarcted rats compared with sham rats, whereas Kd was unaffected by infarction. On the other hand, there was little significant change in Kd and Bmax for specific [3H]NMS binding in the bladder-obstructed rats compared with sham rats. In conclusion, the present study shows that cerebral infarction but not bladder outlet obstruction in rats causes up-regulation of bladder muscarinic receptors, and that such regulation of bladder muscarinic receptors may be at least partly associated with the symptoms of detrusor overactivity subsequent to cerebral infarction.