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Sample records for bladder detrusor muscle

  1. Beta adrenoreceptors in the rabbit bladder detrusor muscle

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    Anderson, G.F.; Marks, B.H.

    1984-01-01

    This study examines the beta adrenergic receptors of the rabbit detrusor smooth muscle, employing [ 125 I]iodocyanopindolol (ICYP) as a ligand for the binding of beta adrenergic receptors. Saturation binding experiments on the isolated membrane fraction yielded a KD for ICYP of 14.7 pM and a maximum binding of 147.6 fmol/mg of protein. Displacement of labeled ICYP by a series of beta adrenergic agents yielded the following KD values for the combined high and low affinity binding sites: I-propranolol, 0.76 nM; ICI 118,551, 1.7 nM; zinterol, 38.0 nM; metoprolol, 3.5 microM; and practolol, 61.4 microM. When these displacement experimental results were compared to KD values from other reported binding studies with ICYP for beta adrenoreceptors, both the order of potency and the KD values indicated primarily beta-2 adrenergic receptor subtypes. Computer program Scatfit analysis of the displacement curves indicated a single slope and affinity constant for all five beta adrenergic agents. Hofstee plots for zinterol, ICI 118,551 and metoprolol, however, were not linear and indicated that minor populations of beta-1 adrenoreceptors were also present as both high and low affinity binding sites could be defined. It is concluded that the primary receptor population is beta-2 and that this tissue is heterogenous with a small population of beta-1 adrenoreceptors representing approximately 13 to 23% of the total beta adrenoreceptor population

  2. Beta adrenoreceptors in the rabbit bladder detrusor muscle

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, G.F.; Marks, B.H.

    1984-02-01

    This study examines the beta adrenergic receptors of the rabbit detrusor smooth muscle, employing (/sup 125/I)iodocyanopindolol (ICYP) as a ligand for the binding of beta adrenergic receptors. Saturation binding experiments on the isolated membrane fraction yielded a KD for ICYP of 14.7 pM and a maximum binding of 147.6 fmol/mg of protein. Displacement of labeled ICYP by a series of beta adrenergic agents yielded the following KD values for the combined high and low affinity binding sites: I-propranolol, 0.76 nM; ICI 118,551, 1.7 nM; zinterol, 38.0 nM; metoprolol, 3.5 microM; and practolol, 61.4 microM. When these displacement experimental results were compared to KD values from other reported binding studies with ICYP for beta adrenoreceptors, both the order of potency and the KD values indicated primarily beta-2 adrenergic receptor subtypes. Computer program Scatfit analysis of the displacement curves indicated a single slope and affinity constant for all five beta adrenergic agents. Hofstee plots for zinterol, ICI 118,551 and metoprolol, however, were not linear and indicated that minor populations of beta-1 adrenoreceptors were also present as both high and low affinity binding sites could be defined. It is concluded that the primary receptor population is beta-2 and that this tissue is heterogenous with a small population of beta-1 adrenoreceptors representing approximately 13 to 23% of the total beta adrenoreceptor population.

  3. Testosterone Modifies Alterations to Detrusor Muscle after Partial Bladder Outlet Obstruction in Juvenile Mice

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    Andrew S. Flum

    2017-06-01

    Full Text Available Lower urinary tract symptoms secondary to posterior urethral valves (PUV arise in boys during adolescence. The reasons for this have previously been attributed to increased urine output as boys experience increased growth. Additionally, there are few choices for clinicians to effectively treat these complications. We formed the new hypothesis that increased androgen levels at this time of childhood development could play a role at the cellular level in obstructed bladders. To test this hypothesis, we investigated the role of testosterone on bladder detrusor muscle following injury from partial bladder outlet obstruction (PO in mice. A PO model was surgically created in juvenile male mice. A group of mice were castrated by bilateral orchiectomy at time of obstruction (CPO. Testosterone cypionate was administered to a group of castrated, obstructed mice (CPOT. Bladder function was assessed by voiding stain on paper (VSOP. Bladders were analyzed at 7 and 28 days by weight and histology. Detrusor collagen to smooth muscle ratio (Col/SM was calculated using Masson’s trichrome stain. All obstructed groups had lower max voided volumes (MVV than sham mice at 1 day. Hormonally intact mice (PO continued to have lower MVV at 7 and 28 days while CPO mice improved to sham levels at both time points. In accordance, PO mice had higher bladder-to-body weight ratios than CPO and sham mice demonstrating greater bladder hypertrophy. Histologically, Col/SM was lower in sham and CPO mice. When testosterone was restored in CPOT mice, MVV remained low at 7 and 28 days compared to CPO and bladder-to-body weight ratios were also greater than CPO. Histologic changes were also seen in CPOT mice with higher Col/SM than sham and CPO mice. In conclusion, our findings support a role for testosterone in the fibrotic changes that occur after obstruction in male mice. This suggests that while other changes may occur in adolescent boys that cause complication in boys

  4. Characterization of muscarinic and P2X receptors in the urothelium and detrusor muscle of the rat bladder

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    Masaki Ogoda

    2016-05-01

    Full Text Available Muscarinic and purinergic (P2X receptors play critical roles in bladder urothelium under physiological and pathological conditions. Aim of present study was to characterize these receptors in rat bladder urothelium and detrusor muscle using selective radioligands of [N-methyl-3H]scopolamine methyl chloride ([3H]NMS and αβ-methylene ATP [2,8-3H]tetrasodium salt ([3H]αβ-MeATP. Similar binding parameters for each radioligand were observed in urothelium and detrusor muscle. Pretreatment with N-(2-chloroethyl-4-piperidinyl diphenylacetate (4-DAMP mustard mustard revealed co-existence of M2 and M3 receptors, with the number of M2 receptors being larger in the urothelium and detrusor muscle. Intravesical administration of imidafenacin and Dpr-P-4 (N → O (active metabolite of propiverine displayed significant binding of muscarinic receptors in the urothelium and detrusor muscle. The treatment with cyclophosphamide (CYP or resiniferatoxin (RTX resulted in a significant decrease in maximal number of binding sites (Bmax for [3H]NMS and/or [3H]αβ-MeATP in the urothelium and detrusor muscle. These results demonstrated that 1 pharmacological characteristics of muscarinic and P2X receptors in rat bladder urothelium were similar to those in the detrusor muscle, 2 that densities of these receptors were significantly altered by pretreatments with CYP and RTX, and 3 that these receptors may be pharmacologically affected by imidafenacin and Dpr-P-4 (N → O which are excreted in the urine.

  5. Urinary Bladder Detrusor Dysfunction Symptoms in Lyme Disease

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    Basant K. Puri

    2013-09-01

    Full Text Available Purpose Symptoms of urinary bladder detrusor dysfunction have been rarely reported in Lyme disease. The aim was to carry out the first systematic study to compare the prevalence of such symptoms in a group of Lyme disease patients and a group of matched controls. Methods A questionnaire relating to detrusor function was administered to 17 serologically positive Lyme disease patients and to 18 control subjects. Results The two groups were matched in respect of age, sex, body mass, and mean arterial blood pressure. None of the 35 subjects was taking medication which might affect urinary function and none had undergone a previous operative procedure on the lower urinary tract. Six of the Lyme patients (35% and none of the controls (0% had symptoms of detrusor dysfunction (P<0.01. Conclusions This first systematic controlled study confirms that Lyme disease is associated with urinary bladder detrusor dysfunction. Further evaluation of detrusor function is warranted in this disease.

  6. The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa

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    Dyer David W

    2006-01-01

    Full Text Available Abstract Background An organ such as the bladder consists of complex, interacting set of tissues and cells. Inflammation has been implicated in every major disease of the bladder, including cancer, interstitial cystitis, and infection. However, scanty is the information about individual detrusor and urothelium transcriptomes in response to inflammation. Here, we used suppression subtractive hybridizations (SSH to determine bladder tissue- and disease-specific genes and transcriptional regulatory elements (TREs. Unique TREs and genes were assembled into putative networks. Results It was found that the control bladder mucosa presented regulatory elements driving genes such as myosin light chain phosphatase and calponin 1 that influence the smooth muscle phenotype. In the control detrusor network the Pax-3 TRE was significantly over-represented. During development, the Pax-3 transcription factor (TF maintains progenitor cells in an undifferentiated state whereas, during inflammation, Pax-3 was suppressed and genes involved in neuronal development (synapsin I were up-regulated. Therefore, during inflammation, an increased maturation of neural progenitor cells in the muscle may underlie detrusor instability. NF-κB was specifically over-represented in the inflamed mucosa regulatory network. When the inflamed detrusor was compared to control, two major pathways were found, one encoding synapsin I, a neuron-specific phosphoprotein, and the other an important apoptotic protein, siva. In response to LPS-induced inflammation, the liver X receptor was over-represented in both mucosa and detrusor regulatory networks confirming a role for this nuclear receptor in LPS-induced gene expression. Conclusion A new approach for understanding bladder muscle-urothelium interaction was developed by assembling SSH, real time PCR, and TRE analysis results into regulatory networks. Interestingly, some of the TREs and their downstream transcripts originally involved in

  7. The cholinergic and purinergic components of detrusor contractility in a whole rabbit bladder model.

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    Chancellor, M B; Kaplan, S A; Blaivas, J G

    1992-09-01

    Whole rabbit bladders were suspended in a bath chamber and stimulated with ATP, bethanechol, electrical field stimulation, and bethanechol + ATP. Detrusor pressure and fluid expelled by the bladder were recorded, synchronized, and digitized. Detrusor work and power were calculated with a computer program. Maximum work was 61.4 +/- 28.7, 83.3 +/- 17.0, 85.0 +/- 15.0, 90.8 +/- 13.1 cm. H2O, ml. for ATP, bethanechol, electrical and bethanechol + ATP, respectively. Maximum power generated by ATP was 4.8 +/- 3.0 cm. H2O, ml./sec and was approximately 66% of that generated by bethanechol, and 50% of that generated by electrical stimulation, and bethanechol + ATP. ATP cannot empty the bladder with moderate outlet resistance while bethanechol and electrical stimulation can. Our results suggest that ATP is able to generate detrusor power and achieve work in bladder emptying. However, ATP generated power and work is considerably less than that of electrical stimulation or bethanechol alone. ATP mediated contraction is not inhibited by atropine or tetrodotoxin but is inhibited by P2 purinoceptor desensitization, suggesting a functional role of purine receptors on detrusor smooth muscle. Since ATP generated pressure is more rapid than with bethanechol alone, we support the hypothesis that ATP may be important in the initiation of micturition.

  8. Bladder contractility is modulated by Kv7 channels in pig detrusor

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    Svalø, Julie; Bille, Michala; Parameswaran Theepakaran, Neeraja

    2013-01-01

    Kv7 channels are involved in smooth muscle relaxation, and accordingly we believe that they constitute potential targets for the treatment of overactive bladder syndrome. We have therefore used myography to examine the function of Kv7 channels in detrusor, i.e. pig bladder, with a view...... relaxation, suggesting that Kv7.2 and/or Kv7.4 channels constitute the subtypes that are relevant to bladder contractility. The effects of retigabine and ML213 were attenuated by pre-incubation with 10µM XE991 (Kv7.1-7.5 channel blocker) (P...

  9. Detrusor Arreflexia as an End Stage of Neurogenic Bladder in HAM/TSP?

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    Matheus Tannus

    2011-01-01

    Full Text Available The HTLV-1 virus is a known agent involved in the development of HAM/TSP. Past studies have typically observed patients with autonomic dysfunction consisting of detrusor overactivity and detrusor-sphincter dyssynergia, with the occasional observation of underactive detrusor or detrusor arreflexia. However, studies have not yet evaluated the progression of neurogenic bladder over time. In this paper, we describe a HAM/TSP patient with the initial development of overactive detrusor, and subsequent development of detrusor arreflexia. Given a paucity of studies characterizing the effects of HTLV-1 on the autonomic nervous system, particularly aspects controlling continence, this patient's clinical course may represent one type of end point for patients with HAM/TSP and neurogenic bladder. Further cohort or case-series studies, with particular emphasis on the progression of neurogenic bladder, are needed to evaluate the significance of this described case in relation to typical disease progression patterns.

  10. Deletion of Dicer in smooth muscle affects voiding pattern and reduces detrusor contractility and neuroeffector transmission.

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    Mardjaneh Karbalaei Sadegh

    Full Text Available MicroRNAs have emerged as important regulators of smooth muscle phenotype and may play important roles in pathogenesis of various smooth muscle related disease states. The aim of this study was to investigate the role of miRNAs for urinary bladder function. We used an inducible and smooth muscle specific Dicer knockout (KO mouse which resulted in significantly reduced levels of miRNAs, including miR-145, miR-143, miR-22, miR125b-5p and miR-27a, from detrusor preparations without mucosa. Deletion of Dicer resulted in a disturbed micturition pattern in vivo and reduced depolarization-induced pressure development in the isolated detrusor. Furthermore, electrical field stimulation revealed a decreased cholinergic but maintained purinergic component of neurogenic activation in Dicer KO bladder strips. The ultrastructure of detrusor smooth muscle cells was well maintained, and the density of nerve terminals was similar. Western blotting demonstrated reduced contents of calponin and desmin. Smooth muscle α-actin, SM22α and myocardin were unchanged. Activation of strips with exogenous agonists showed that depolarization-induced contraction was preferentially reduced; ATP- and calyculin A-induced contractions were unchanged. Quantitative real time PCR and western blotting demonstrated reduced expression of Cav1.2 (Cacna1c. It is concluded that smooth muscle miRNAs play an important role for detrusor contractility and voiding pattern of unrestrained mice. This is mediated in part via effects on expression of smooth muscle differentiation markers and L-type Ca(2+ channels in the detrusor.

  11. Cultured smooth muscle cells of the human vesical sphincter are more sensitive to histamine than are detrusor smooth muscle cells.

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    Neuhaus, Jochen; Oberbach, Andreas; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

    2006-05-01

    To compare histamine receptor expression in cultured smooth muscle cells from the human detrusor and internal sphincter using receptor-specific agonists. Smooth muscle cells from the bladder dome and internal sphincter were cultured from 5 male patients undergoing cystectomy for bladder cancer therapy. Calcium transients in cells stimulated with carbachol, histamine, histamine receptor 1 (H1R)-specific heptanecarboxamide (HTMT), dimaprit (H2R), and R-(alpha)-methylhistamine (H3R) were measured by calcium imaging. Histamine receptor proteins were detected by Western blot analysis and immunocytochemistry. H1R, H2R, and H3R expression was found in tissue and cultured cells. Carbachol stimulated equal numbers of detrusor and sphincter cells (60% and 51%, respectively). Histamine stimulated significantly more cells than carbachol in detrusor (100%) and sphincter (99.34%) cells. Calcium responses to carbachol in detrusor and sphincter cells were comparable and did not differ from those to histamine in detrusor cells. However, histamine and specific agonists stimulated more sphincter cells than did carbachol (P <0.001), and the calcium increase was greater in sphincter cells than in detrusor cells. Single cell analysis revealed comparable H2R responses in detrusor and sphincter cells, but H1R and H3R-mediated calcium reactions were significantly greater in sphincter cells. Histamine very effectively induces calcium release in smooth muscle cells. In sphincter cells, histamine is even more effective than carbachol regarding the number of reacting cells and the intracellular calcium increase. Some of the variability in the outcome of antihistaminic interstitial cystitis therapies might be caused by the ineffectiveness of the chosen antihistaminic or unintentional weakening of sphincteric function.

  12. Effect of a Carbohydrate-Rich Diet on Rat Detrusor Smooth Muscle Contractility: An Experimental Study

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    Mustafa Suat Bolat

    2017-01-01

    Full Text Available Objectives. We aimed to investigate the effect of a carbohydrate-rich diet on detrusor contractility in rats. Materials and Methods. Sprague-Dawley rats were randomized into two groups. The control group received regular food and water. The study group received carbohydrate-rich diet for six weeks. The rats’ detrusor muscle was isolated for pharmacological and histopathological examinations. Results. In the control and study groups, mean body weights were 431.5 ± 27.6 g and 528.0 ± 36.2 g, respectively (p < 0.001. Electrical stimulation of the detrusor strips of the control group resulted in gradual contraction. A decreased contractile response was shown in the study group. Acetylcholine in 10-7-10-3 molar concentration produced a decreased contractile response in the study group, compared to the control group (p < 0.01. The study group showed marked subepithelial and intermuscular fibrosis in the bladder. Conclusion. Carbohydrate-rich diet causes marked subepithelial and extracellular fibrosis and changes in contractility in the detrusor within a six-week period. Changes have higher costs in therapeutic choices and correction of these changes remains difficult. Putting an end to carbohydrate-rich diet would seem to be more cost-effective than dealing with the effects of consuming it in high proportions which should be the national policy worldwide.

  13. Muscarinic receptor subtypes in porcine detrusor: comparison with humans and regulation by bladder augmentation

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    Goepel, M.; Gronewald, A.; Krege, S.; Michel, M. C.

    1998-01-01

    The properties of muscarinic acetylcholine receptors of porcine and human bladder detrusor were compared in radioligand binding studies using [3H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the radioligand and the density of muscarinic receptors was similar in male and

  14. Is Detrusor Contraction during Rapid Bladder Filling Caused by Cold or Warm Water? A Randomized, Controlled, Double-Blind Trial.

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    Kozomara, Marko; Mehnert, Ulrich; Seifert, Burkhardt; Kessler, Thomas M

    2018-01-01

    We investigated whether detrusor contraction during rapid bladder filling is provoked by cold or warm water. Patients with neurogenic lower urinary tract dysfunction were included in this randomized, controlled, double-blind trial. At the end of a standard urodynamic investigation patients underwent 2 bladder fillings using a 4C ice water test or a 36C warm water test saline solution at a filling speed of 100 ml per minute. The order was randomly selected, and patients and investigators were blinded to the order. The primary outcome measure was detrusor overactivity, maximum detrusor pressure and maximum bladder filling volume during the ice and warm water tests. Nine women and 31 men were the subject of data analysis. Neurogenic lower urinary tract dysfunction was caused by spinal cord injury in 33 patients and by another neurological disorder in 7. Irrespective of test order detrusor overactivity occurred significantly more often during the ice water test than during the warm water test (30 of 40 patients or 75% vs 25 of 40 or 63%, p = 0.02). When comparing the ice water test to the warm water test, maximum detrusor pressure was significantly higher and maximum bladder filling volume was significantly lower during the ice water test (each p warm water first) had no effect on the parameters. Our findings imply that the more frequent detrusor overactivity, higher maximum detrusor pressure and lower bladder filling volume during the ice water test compared to the warm water test were caused by cold water. This underlies the theory of a C-fiber mediated bladder cooling reflex in humans. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. Blebbistain, a myosin II inhibitor, as a novel strategy to regulate detrusor contractility in a rat model of partial bladder outlet obstruction.

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    Xinhua Zhang

    Full Text Available Partial bladder outlet obstruction (PBOO, a common urologic pathology mostly caused by benign prostatic hyperplasia, can coexist in 40-45% of patients with overactive bladder (OAB and is associated with detrusor overactivity (DO. PBOO that induces DO results in alteration in bladder myosin II type and isoform composition. Blebbistatin (BLEB is a myosin II inhibitor we recently demonstrated potently relaxed normal detrusor smooth muscle (SM and reports suggest varied BLEB efficacy for different SM myosin (SMM isoforms and/or SMM vs nonmuscle myosin (NMM. We hypothesize BLEB inhibition of myosin II as a novel contraction protein targeted strategy to regulate DO. Using a surgically-induced male rat PBOO model, organ bath contractility, competitive and Real-Time-RT-PCR were performed. It was found that obstructed-bladder weight significantly increased 2.74-fold while in vitro contractility of detrusor to various stimuli was impaired ∼50% along with decreased shortening velocity. Obstruction also altered detrusor spontaneous activities with significantly increased amplitude but depressed frequency. PBOO switched bladder from a phasic-type to a more tonic-type SM. Expression of 5' myosin heavy chain (MHC alternatively spliced isoform SM-A (associated with tonic-type SM increased 3-fold while 3' MHC SM1 and essential light chain isoform MLC(17b also exhibited increased relative expression. Total SMMHC expression was decreased by 25% while the expression of NMM IIB (SMemb was greatly increased by 4.5-fold. BLEB was found to completely relax detrusor strips from both sham-operated and PBOO rats pre-contracted with KCl, carbachol or electrical field stimulation although sensitivity was slightly decreased (20% only at lower doses for PBOO. Thus we provide the first thorough characterization of the response of rat bladder myosin to PBOO and demonstrate complete BLEB-induced PBOO bladder SM relaxation. Furthermore, the present study provides valuable

  16. Role of Nicotinic Acetylcholine Receptor α3 and α7 Subunits in Detrusor Overactivity Induced by Partial Bladder Outlet Obstruction in Rats

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    Hyo Sin Kim

    2015-03-01

    Full Text Available Purpose: To investigate the role of α3 and α7 nicotinic acetylcholine receptor subunits (nAChRs in the bladder, using a rat model with detrusor overactivity induced by partial bladder outlet obstruction (BOO. Methods: Forty Sprague-Dawley rats were used: 10 were sham-operated (control group and 30 were observed for 3 weeks after partial BOO. BOO-induced rats were further divided into 3 groups: Two groups of 10 rats each received intravesicular infusions with hexamethonium (HM group; n=10 or methyllycaconitine (MLC group; n=10, which are antagonists for α3 and α7 nAChRs, respectively. The remaining BOO-induced rats received only saline infusion (BOO group; n=10. Based on the contraction interval measurements using cystometrogram, the contraction pressure and nonvoiding bladder contractions were compared between the control and the three BOO-induced groups. Immunofluorescent staining and Western blotting were used to analyze α3 and α7 nAChRs levels. Results: The contraction interval of the MLC group was higher than that of the BOO group (P<0.05. Nonvoiding bladder contraction almost disappeared in the HM and MLC groups. Contraction pressure increased in the BOO group (P<0.05 compared with the control group and decreased in the HM and MLC groups compared with the BOO group (P<0.05. Immunofluorescence staining showed that the α3 nAChR signals increased in the urothelium, and the α7 nAChR signals increased in the urothelium and detrusor muscle of the BOO group compared with the control group. Western blot analysis showed that both α3 and α7 nAChR levels increased in the BOO group (P<0.05. Conclusions: Alpha3 and α7 nAChRs are associated with detrusor overactivity induced by BOO. Furthermore, nAChR antagonists could help in clinically improving detrusor overactivity.

  17. Enhancement of S1P-induced contractile response in detrusor smooth muscle of rats having cystitis.

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    Anjum, Irfan; Denizalti, Merve; Kandilci, Hilmi Burak; Durlu-Kandilci, Nezahat Tugba; Sahin-Erdemli, Inci

    2017-11-05

    Interstitial cystitis is a chronic disease characterized by lower abdominal pain and some nonspecific symptoms including an increase in urinary frequency and urgency. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that controls smooth muscle tone via G-protein coupled receptors (S1P 1-3 receptors). S1P production is known to take place both in physiological states and some pathological situations, such as in overactive bladder syndrome. The intracellular mechanism of S1P-induced contractile response was investigated in β-escin permeabilized detrusor smooth muscle of rats having cyclophosphamide-induced cystitis. The bladder was isolated from rats and detrusor smooth muscle strips were permeabilized with β-escin. S1P (50µM)-induced contraction and calcium sensitization response were significantly increased in cystitis. S1P-induced augmented contractile response was inhibited by S1P 2 receptor antagonist JTE-013 and S1P 3 receptor antagonist suramin. S1P 2 receptor protein expressions were increased in cystitis, where no change was observed in S1P 3 expressions between control and cystitis groups. S1P-induced contraction was reduced by Rho kinase (ROCK) inhibitor Y-27632 and protein kinase C (PKC) inhibitor GF-109203X in both control and cystitis group. S1P-induced increased calcium sensitization response was decreased by ROCK inhibitor and PKC inhibitor in cystitis. Our findings provide the first evidence that interstitial cystitis triggers S1P-induced increase in intracellular calcium in permeabilized detrusor smooth muscle of female rats. Both S1P 2 and S1P 3 receptors are involved in S1P mediated enhanced contractile response. The augmentation in S1P-induced contraction in interstitial cystitis involves both PKC and ROCK pathways of calcium sensitization. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Chronic treatment with fluoxetine and sertraline prevents forced swimming test-induced hypercontractility of rat detrusor muscle.

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    Bilge, Sirri; Bozkurt, Ayhan; Bas, Duygu B; Aksoz, Elif; Savli, Evren; Ilkaya, Fatih; Kesim, Yuksel

    2008-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors represent important targets for the development of new treatments for detrusor overactivity and urinary incontinence. The present study was undertaken to investigate the effects of the forced swimming test (FST) on the contractile response of isolated rat detrusor muscle and to examine the effects of in vivo treatments of fluoxetine and sertraline on altered detrusor muscle contractility. Fluoxetine (20 mg/kg ip) and sertraline (10 mg/kg ip) were administered once a day for 14 days. Rats were exposed to the FST on the 15th day. After the test, detrusor muscles were removed and placed in organ baths, and the contraction responses induced by carbachol, potassium chloride (KCl) and electrical field stimulation (EFS) were recorded. The contractile responses of detrusor muscle strips to carbachol and electrical field stimulation were found to be increased at all carbachol doses and frequencies, respectively. FST also increased the contractile responses to KCl, which is used to test the differences in postreceptor-mediated contractions. The hypercontractile responses of detrusor strips to carbachol, EFS and KCl were abolished by treatment with both fluoxetine and sertraline. These treatments also decreased the immobility duration in the FST consistent with an antidepressant-like effect in this test. The results of this study provide the first evidence that FST increases contractility of the rat detrusor muscle, and this hypercontractility was abolished by chronic treatments of fluoxetine and sertraline at antidepressant doses by decreasing the postreceptor-mediated events.

  19. Selective detrusor activation by electrical sacral nerve root stimulation in spinal cord injury

    NARCIS (Netherlands)

    Rijkhoff, N. J.; Wijkstra, H.; van Kerrebroeck, P. E.; Debruyne, F. M.

    1997-01-01

    Electrical sacral nerve root stimulation can be used in spinal cord injury patients to induce urinary bladder contraction. However, existing stimulation methods activate simultaneously both the detrusor muscle and the urethral sphincter. Urine evacuation is therefore only possible using poststimulus

  20. Assessment of noninvasive predictors of bladder detrusor underactivity in BPH/LUTs patients.

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    Luo, Fei; Sun, Hong-Hong; Su, Yan-Hui; Zhang, Zhi-Hua; Wang, Ya-Shen; Zhao, Zhen; Li, Jian

    2017-05-01

    To retrospectively assess the diagnostic predictive value of clinical characteristics to improve the diagnostic accuracy of bladder detrusor underactivity (DU) among benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) patients who cannot undergo urodynamic examinations. A total of 704 BPH/LUTS patients at Tianjin Medical Union Center from January 2013 through June 2016 were enrolled in the study. All cases were stratified by maximum detrusor pressure (Pdet.max) into two groups (DU and control). Patient and clinical variables were analyzed in both groups. One hundred twelve and 592 cases were classified into the DU and control group, respectively. PV (OR 0.976, 95% CI 0.961-0.991, P = 0.002) and PVR (OR 1.004, 95% CI 1.001-1.007, P = 0.004) were independent predictors of DU. In addition, Pdet.max was positively correlated with HTN (≥10 years) (r = 0.373, P = 0.001), smoking (r = 0.108, P = 0.039), IPSS (20-23) (r = 0.257, P = 0.013), PV (r = 0.305, P 76 years) (r = -0.265, P = 0.015), BMI (21-23) (r = -0.382, P = 0.001), DM (0-20 years) (r = 0.365, P = 0.009) and PVR (50-400 mL) (r = 0.423, P = 0.001). The AUCs for BMI, PV, tPSA, PSAD, Q max , and PVR were 0.762, 0.739, 0.727, 0.681, 0.749, and 0.716, respectively. Combined ROC analysis showed the AUC for PV + PVR was 0.774 with sensitivity of 77.78% and specificity of 73.68%. Clinical factors were effective for predicting DU and could help improve the diagnostic accuracy for BPH/LUTS patients who cannot undergo urodynamic examinations.

  1. Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics.

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    Kuo, Hann-Chorng

    2011-09-01

    The purpose of this study was to evaluate the efficacy and safety of onabotulinumtoxinA injections at bladder base/trigone and compare with injections at bladder body or bladder body/trigone for the treatment of idiopathic detrusor overactivity (IDO) refractory to antimuscarinics. A single blind, randomized, paralleled, actively controlled trial was performed in patients with urodynamically proven IDO who failed antimuscarinic therapy. Patients were randomly assigned to receive intravesical injections of 100 U of onabotulinumtoxinA into three different bladder sites. All treatments were evaluated by voiding diary variables, urgency severity score, urodynamic studies, and patient perception of bladder condition. Long-term success rates over 12 months were also determined. Among the patients, 37 were randomized to injections in the bladder body, 35 into the bladder body/trigone, and 33 into the bladder base/trigone. Successful results were reported in 76 (72%) patients at 3 months: 26 (70%) in the bladder body group, 26 (74%) in the bladder body/trigone group, and 24 (73%) in the bladder base/trigone group. There were no significant differences in success rates, changes in urgency and urgency incontinence episodes, urodynamic variables, or long-term success rates among the three subgroups. The incidence of adverse events was similar among three groups. No vesicoureteral reflux was noted in all patients with or without involving trigone injection. Intravesical onabotulinumtoxinA injection is an effective treatment for IDO regardless of the bladder injection site. Bladder base/trigone injection is as safe and effective as bladder body injections with or without trigone involvement. Copyright © 2011 Wiley-Liss, Inc.

  2. Cerebral control of bladder storage in patients with detrusor overactivity: An activation study using SPECT with NEUROSTAT

    International Nuclear Information System (INIS)

    Yafu, Y.; Li, X.; Li, Y.

    2007-01-01

    Full text: The aim of this study was to identify the brain areas which control the bladder storage in the patients with detrusor overactivity (DO) and those without DO by 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) SPECT with Neurological Statistical Image Analysis Software (NEUROSTAT). Methods: SPECT scans were performed on fifteen healthy volunteers (Group I) and twenty-five patients with some storage symptoms of lower urinary tract, among whom nineteen patients were with DO (Group II) and six patients were with normal detrusor function (Group III). All the subjects were male and right-handed. Each subject was scanned twice without movement in a supine position. 444MBq and 555MBq 99mTc- HMPAO were separately injected intravenously under the following two conditions: resting state with empty bladder and urine withholding state with full bladder. The final image during urine withholding was obtained by subtracting the first scan data from the second. NEUROSTAT was adopted to analyze the difference in rCBF between groups in resting state and to analyze the change in rCBF between urine withholding and resting states in each group. The results were displayed on Z-score images at a significance threshold of P < 0.05 with correction for multiple comparisons. Results: No region reached significant threshold in comparison of Group II and Group III in resting state, although Group II and III , as compared with Group I, showed decreases in tracer activity in superior temporal gyrus, medial frontal gyrus, inferior frontal gyrus, anterior cingulate and cingulate gyrus. There were significant increases in tracer activity in bilateral inferior frontal gyri and the right middle temporal gyrus in urine withholding state as compared with resting state in Group III. Among the regions, the right inferior frontal gyrus was distinctly prominent at both Z-score and the extent. In Group II, the regions that were activated significantly in Group III did not reach significant

  3. Bladder instillation of Escherichia coli lipopolysaccharide alters the muscle contractions in rat urinary bladder via a protein kinase C-related pathway

    International Nuclear Information System (INIS)

    Weng, T.I.; Chen, W.J.; Liu, S.H.

    2005-01-01

    Uropathogenic Escherichia coli is a common cause of urinary tract infection. We determined the effects of intravesical instillation of E. coli lipopolysaccharide (LPS, endotoxin) on muscle contractions, protein kinase C (PKC) translocation, and inducible nitric oxide synthase (iNOS) expression in rat urinary bladder. The contractions of the isolated rat detrusor muscle evoked by electrical field stimulations were measured short-term (1 h) or long-term (24 h) after intravesical instillation of LPS. One hour after LPS intravesical instillation, bladder PKC-α translocation from cytosolic fraction to membrane fraction and endothelial (e)NOS protein was elevated, and detrusor muscle contractions were significantly increased. PKC inhibitors chelerythrine and Ro32-0432 inhibited this LPS-enhanced contractile response. Application of PKC activator β-phorbol-12,13-dibutyrate enhanced the muscle contractions. Three hours after intravesical instillation of LPS, iNOS mRNA was detected in the bladder. Immunoblotting study also demonstrated that the induction of iNOS proteins is detected in bladder in which LPS was instilled. 24 h after intravesical instillation of LPS, PKC-α translocation was impaired in the bladder; LPS did not affect PKC-δ translocation. Muscle contractions were also decreased 24 h after LPS intravesical instillation. Aminoguanidine, a selective iNOS inhibitor, blocked the decrease in PKC-α translocation and detrusor contractions induced by LPS. These results indicate that there are different mechanisms involved in the alteration of urinary bladder contractions after short-term and long-term treatment of LPS; an iNOS-regulated PKC signaling may participate in causing the inhibition of muscle contractions in urinary bladder induced by long-term LPS treatment

  4. The novel β3-adrenoceptor agonist mirabegron reduces carbachol-induced contractile activity in detrusor tissue from patients with bladder outflow obstruction with or without detrusor overactivity

    DEFF Research Database (Denmark)

    Svalø, Julie; Nordling, Jørgen; Bouchelouche, Kirsten

    2013-01-01

    preparations from patients with bladder outflow obstruction (BOO) with and without detrusor overactivity (DO), and from patients with normal bladder function. We compared the effects to those of isoprenaline, a non-selective β-adrenoceptor agonist. Detrusor specimens were obtained from patients with benign...... carbachol-induced tone in tissues from all groups. Isoprenaline decreased tension with higher potency than mirabegron in normal, BOO and BOO+DO detrusor strips with pIC(50) values of 7.49 ± 0.16 vs. 6.23 ± 0.26 (P=0.0002), 6.89 ± 0.34 vs. 6.04 ± 0.31 (P=0.01), and 6.57 ± 0.20 vs. 5.41 ± 0.08 (P...), respectively. The maximal relaxant effect of isoprenaline and mirabegron in the normal, BOO and BOO+DO detrusor was 37.7 ± 14.4% and 36.1 ± 23.3%, 14.4 ± 12.2% vs. 33.4 ± 21.0% and 18.3 ± 10.0% vs. 28.3 ± 12.2% (n=4, P>0.05), respectively. Mirabegron and isoprenaline reduced carbachol-induced tone in both...

  5. NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels

    Science.gov (United States)

    Parajuli, Shankar P; Hristov, Kiril L; Soder, Rupal P; Kellett, Whitney F; Petkov, Georgi V

    2013-01-01

    Background and Purpose Overactive bladder (OAB) is often associated with abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a selective and potent opener of the small or intermediate conductance Ca2+-activated K+ (SK or IK, respectively) channels, to evaluate how SK/IK channel activation modulates DSM function. Experimental Approach We employed single-cell RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM cells and isometric tension recordings of isolated DSM strips to explore how the pharmacological activation of SK/IK channels with NS309 modulates DSM function. Key Results We detected SK3 but not SK1, SK2 or IK channels expression at both mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells. NS309 (10 μM) significantly increased the whole cell SK currents and hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner. The inhibitory effect of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM-34, indicating no functional role of the IK channels in rat DSM. NS309 also significantly inhibited the pharmacologically and electrical field stimulation-induced DSM contractions. Conclusions and Implications Our data reveal that SK3 channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3 channels with NS309 decreases rat DSM cell excitability and contractility, suggesting that SK3 channels might be potential therapeutic targets to control OAB associated with detrusor overactivity. PMID:23145946

  6. [Distribution and significance of α1-adrenoceptor subtypes in patients with chronic prostatitis in prostate, bladder detrusor and posterior urethral tissue].

    Science.gov (United States)

    Yang, Yu; Xie, Hui; Zheng, Jian-jian; Chen, Bi-cheng; He, Qiu-xiang; Shen, Ji-hong

    2010-12-14

    To study the distribution of alpha1-adrenoceptor (α1-AR) subtype in prostate, posterior urethra and bladder detrusor of patients with chronic prostatitis (CP). The prostate specimens were collected at autopsy from 30 organ donors (aged 20-35 years old) dying of non-prostatic diseases. The pathological specimens of prostate peripheral zone were examined. The method of real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) was employed for quantification of α1a-AR and α1b-AR subtype expression in prostate transition zone and its surrounding zone, posterior urethra and bladder detrusor tissue. Among all donors, there were 24 cases with pathological inflammation in prostatic peripheral zone and 6 with pathological non-inflammation. The mRNA expression of α1-AR subtypes in bladder detrusor and posterior urethra was significantly higher in the inflammation group than in the control group (Pposterior urethra was significantly lower in the inflammation group than in the control group (Pposterior urethra may explain various urodynamic changes in CP and lead to the occurrence and development of CP in prostate, posterior urethra and bladder detrusor.

  7. Female urinary incontinence at orgasm: a possible marker of a more severe form of detrusor overactivity. Can ultrasound measurement of bladder wall thickness explain it?

    Science.gov (United States)

    Serati, Maurizio; Salvatore, Stefano; Cattoni, Elena; Siesto, Gabriele; Soligo, Marco; Braga, Andrea; Sorice, Paola; Cromi, Antonella; Ghezzi, Fabio; Cardozo, Linda; Bolis, Pierfrancesco

    2011-06-01

    Coital incontinence (CI) during orgasm is a form of urinary incontinence possibly because of detrusor overactivity (DO), as the underlying pathophysiological condition. Women with this symptom usually show a pharmacological lower cure rate than those with DO alone. The ultrasound measurement of the bladder wall thickness (BWT) allows an indirect evaluation of detrusor muscle thickness, giving a potential index of detrusor activity. We wanted to understand if CI at orgasm could be a marker of severity of DO by comparing BWT in women with both DO and CI at orgasm vs. women with DO alone. In addition we aimed to confirm if CI during orgasm is related to antimuscarinics treatment failure. This is a prospective cohort study performed in two tertiary urogynecological referral departments, recruiting consecutive patients seeking treatment for symptomatic DO. All patients were thoroughly assessed including physical examination, urodynamic evaluation, and BWT measurement according to the International Continence Society/International Urogynecological Association and ICI recommendations. Solifenacine 5 mg once daily was then prescribed and follow-up was scheduled to evaluate treatment. Multiple logistic regression (MLR) was performed to identify risk factors for treatment failure. Between September 2007 and March 2010, 31 (22.6%) and 106 (77.4%) women with DO with and without CI at orgasm were enrolled. Women complaining of CI at orgasm had significantly higher BWT than the control group (5.8 ± 0.6 mm vs. 5.2 ± 1.2 mm [P=0.007]). In patients with CI at orgasm, the nonresponder rate to antimuscarinics was significantly higher than controls (P=0.01). After MLR, CI at orgasm was the only independent predictor decreasing antimuscarinics efficacy (odds ratio [OR] 3.16 [95% CI 1.22-8.18], P=0.02). Women with DO and CI at orgasm showed a significantly higher BWT values and worse cure rates than women with DO alone. CI at orgasm could be a marker of a more severe form of DO.

  8. TGF-beta1 inhibits Cx43 expression and formation of functional syncytia in cultured smooth muscle cells from human detrusor.

    Science.gov (United States)

    Neuhaus, Jochen; Heinrich, Marco; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

    2009-02-01

    Human detrusor smooth muscle cells (hBSMCs) are coupled by connexin 43 (Cx43)-positive gap junctions to form functional syncytia. Gap junctional communication likely is necessary for synchronised detrusor contractions and is supposed to be altered in voiding disturbances. Other authors have shown that the pleiotropic cytokine TGF-beta1 upregulates Cx43 expression in human aortic smooth muscle cells. In this study, we examined the TGF-beta1 effects on Cx43 expression in cultured hBSMCs. hBSMC cultures, established from patients undergoing cystectomy, were treated with recombinant human TGF-beta1. Cx43 expression was then examined by Western blotting, real-time PCR, and immunocytochemistry. Dye-injection experiments were used to study the size of functional syncytia. Dye-coupling experiments revealed stable formation of functional syncytia in passaged cell cultures (P1-P4). Stimulation with TGF-beta1 led to significant reduction of Cx43 immunoreactivity and coupling. Cx43 protein expression was significantly downregulated and Cx43 mRNA was only 30% of the control level. Interestingly, low phosphorylation species of Cx43 were particularly affected. Our experiments demonstrated a significant down regulation of connexin 43 by TGF-beta1 in cultured hBSMCs. These findings support the view that TGF-beta1 is involved in the pathophysiology of urinary bladder dysfunction.

  9. Non-muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Malmström, Per-Uno; Agrawal, Sachin; Bläckberg, Mats

    2017-01-01

    The management of non-muscle-invasive bladder cancer (NMIBC) has evolved from the first reports on bladder endoscopy and transurethral resection to the introduction of adjuvant intravesical treatment. However, disease recurrence and progression remain an ongoing risk, placing a heavy burden...

  10. Novel role for the transient potential receptor melastatin 4 channel in guinea pig detrusor smooth muscle physiology

    Science.gov (United States)

    Smith, Amy C.; Hristov, Kiril L.; Cheng, Qiuping; Xin, Wenkuan; Parajuli, Shankar P.; Earley, Scott; Malysz, John

    2013-01-01

    Members of the transient receptor potential (TRP) channel superfamily, including the Ca2+-activated monovalent cation-selective TRP melastatin 4 (TRPM4) channel, have been recently identified in the urinary bladder. However, their expression and function at the level of detrusor smooth muscle (DSM) remain largely unexplored. In this study, for the first time we investigated the role of TRPM4 channels in guinea pig DSM excitation-contraction coupling using a multidisciplinary approach encompassing protein detection, electrophysiology, live-cell Ca2+ imaging, DSM contractility, and 9-phenanthrol, a recently characterized selective inhibitor of the TRPM4 channel. Western blot and immunocytochemistry experiments demonstrated the expression of the TRPM4 channel in whole DSM tissue and freshly isolated DSM cells with specific localization on the plasma membrane. Perforated whole cell patch-clamp recordings and real-time Ca2+ imaging experiments with fura 2-AM, both using freshly isolated DSM cells, revealed that 9-phenanthrol (30 μM) significantly reduced the cation current and decreased intracellular Ca2+ levels. 9-Phenanthrol (0.1–30 μM) significantly inhibited spontaneous, 0.1 μM carbachol-induced, 20 mM KCl-induced, and nerve-evoked contractions in guinea pig DSM-isolated strips with IC50 values of 1–7 μM and 70–80% maximum inhibition. 9-Phenanthrol also reduced nerve-evoked contraction amplitude induced by continuous repetitive electrical field stimulation of 10-Hz frequency and shifted the frequency-response curve (0.5–50 Hz) relative to the control. Collectively, our data demonstrate the novel finding that TRPM4 channels are expressed in guinea pig DSM and reveal their critical role in the regulation of guinea pig DSM excitation-contraction coupling. PMID:23302778

  11. Histamine receptors in human detrusor smooth muscle cells: physiological properties and immunohistochemical representation of subtypes.

    Science.gov (United States)

    Neuhaus, Jochen; Weimann, Annett; Stolzenburg, Jens-Uwe; Dawood, Waled; Schwalenberg, Thilo; Dorschner, Wolfgang

    2006-06-01

    The potent inflammatory mediator histamine is released from activated mast cells in interstitial cystitis (IC). Here, we report on the histamine receptor subtypes involved in the intracellular calcium response of cultured smooth muscle cells (cSMC). Fura-2 was used to monitor the calcium response in cSMC, cultured from human detrusor biopsies. The distribution of histamine receptor subtypes was addressed by immunocytochemistry in situ and in vitro. Histamine stimulated a maximum of 92% of the cells (n=335), being more effective than carbachol (70%, n=920). HTMT (H1R-agonist), dimaprit (H2R) and MTH (H3R) lead to significant lower numbers of reacting cells (60, 48 and 54%). Histamine receptor immunoreactivity (H1R, H2R, H3R, H4R) was found in situ and in vitro. Histamine-induced calcium increase is mediated by distinct histamine receptors. Thus, pre-therapeutic evaluation of histamine receptor expression in IC patients may help to optimize therapy by using a patient-specific cocktail of subtype-specific histamine receptor antagonists.

  12. Analysis of intravesical recurrence after bladder-preserving therapy for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Onozawa, Mizuki; Miyanaga, Naoto; Hinotsu, Shiro

    2012-01-01

    The aim of the present study was to analyze the pattern of recurrences after bladder-preserving therapy for muscle-invasive bladder cancer. The subjects were 77 patients with T2-3N0M0 bladder cancer whose bladder was preserved by intra-arterial chemotherapy and radiation. The patterns of the first recurrences were retrospectively analyzed. With a median follow-up of 38.5 months, 17 patients (22.1%) experienced intravesical recurrence without metastasis, 14 (82.4%) of which were cases of non-muscle-invasive bladder cancer recurrence and 3 (17.6%) of which were muscle-invasive bladder cancer recurrences. Muscle-invasive bladder cancer recurred at the same site as the initial tumor site in all three cases, whereas non-muscle-invasive bladder cancer recurred at different sites in 64% of the patients in that group. The peak hazard of the non-muscle-invasive bladder cancer recurrence was observed at around a year after treatment. Recurrent non-muscle-invasive bladder cancer was of a significantly lower histological grade with lower Ki-67-labeling indices than the initial muscle-invasive bladder cancer. Twelve (85.7%) of 14 patients with non-muscle-invasive bladder cancer recurrence achieved disease-free status. The multivariate analysis revealed that multiplicity, grade and tumor size were significantly correlated with the recurrence (P=0.0001, 0.0442 and 0.0412, respectively). Most of the recurrences after bladder-preserving therapy were cases of non-muscle-invasive bladder cancer. The recurrence pattern and characteristics of the tumors did not differ from those of primary non-muscle-invasive bladder cancer. Patients with high-risk factors would be candidates for prophylactic intravesical therapy for non-muscle-invasive bladder cancer recurrence. (author)

  13. The telocytes/myofibroblasts 3-D network forms a stretch receptor in the human bladder mucosa. Is this structure involved in the detrusor overactive diseases?

    Science.gov (United States)

    Vannucchi, Maria-Giuliana; Traini, Chiara

    2018-04-11

    Several connective tissue cells are present in the human bladder wall; among them, the myofibroblasts (MyF) and the so-called interstitial cells (IC) are a matter of investigation either by basic researchers or clinicians. The interest derives from the possibility that these two cell types could regulate the organ function forming a special sensory system in the bladder mucosa. Whereas attention for the myofibroblasts was mainly focused on understanding their role, the so-called IC are debatable starting from their nomenclature. Indeed, the IC should correspond to the previously called fibroblasts-like cells/interstitial Cajal-like cells (ICLC)/interstitial cells of Cajal (ICC) or PDGFRα positive cells, or CD34 positive cells. Recently a proper name was proposed to give them an identity, i.e. telocyte (TC). To date, this nomenclature is a better term than IC that is quite vague and can be used for all the cells that reside in the connective tissue. Noteworthy, in the bladder mucosa, TC and MyF form a hetero-cellular 3-D network. The detrusor overactivity/overactive bladder (DO/OAB) are pathological conditions characterized by hypersensitivity to filling. It has been hypothesized that erroneous afferent inputs generated in the mucosa affect the efferent pathways and, consequently, the detrusor response. Presently, we review the literature regarding the presence and the potential role of TC and MyF in control conditions and in DO/OAB. On the possibility that the 3D-network made up by these two cell types might play a major role in the genesis of anomalous afferent stimuli will be given attention. Copyright © 2018 Elsevier GmbH. All rights reserved.

  14. A systematic review of the diagnosis and treatment of patients with neurogenic hyperactivity of the detrusor muscle.

    Science.gov (United States)

    Borau, A; Adot, J M; Allué, M; Arlandis, S; Castro, D; Esteban, M; Salinas, J

    Neurogenic detrusor hyperactivity (NDH) is a urodynamic observation characterised by involuntary detrusor contractions during the filling phase that are caused by an underlying neurological disease. The common and severe complications that can result from NDH warrant the preparation of healthcare protocols for the proper management of patients with NDH. The aim of this study is to standardise the criteria for the decision-making process in the management of patients with diagnosed or suspected NDH, providing personalised medical care. We performed a systematic noncomprehensive literature review on the aspects of the diagnosis and treatment of NDH. Based on the review, recommendations were issued by nominal consensus of a group of urology specialists. In general, the diagnosis of NDH is arrived at by a proper review of the medical history, physical examination and voiding diary before performing any diagnostic study. The main treatment objectives are to protect the upper urinary tract, restore function of the lower tract and improve these patients' continence and quality of life. The treatment consists of several steps aimed at obtaining proper bladder storage that allows for sufficiently spaced voidings. The follow-up should be personalised based on each patient's needs. The identification and management of NDH is important for positively redirecting the function of the lower urinary tract, in terms of filling and voiding, thereby improving the patients' quality of life. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  15. Radiologic signs of detrusor instability in children

    International Nuclear Information System (INIS)

    Hidalgo Teran, D.G.; Podesta, M.; Mendel, R.

    2004-01-01

    Purpose: To revalue radiologic signs of detrusor instability in children. Material and Methods: Retrospective analysis of videourodynamic studies performed in 85 children consulting for urinary incontinence and/or infection. Patients were free from neuropathic diseases, alterations of the urinary tract, previous surgery or anticholinergic treatment. Images of the bladder coinciding to the peaks of unstable detrusor contractions in patients with unstable bladders, and those at the end of filling in stable bladders were analyzed. Results: Bladder outlets were open in 38 patients and close in 47. Detrusor instability was found in 97 % of those with an open bladder outlet and in 36 % when close. Bladder outlets were open in all cases with contractions stronger than 60 cm.water. All 'spinning-top' urethras were associated to contractions stronger than 70 cm.water. Most false negatives (close bladder outlet in unstable bladders) corresponded to contractions lower than 30 cm.water. Different shapes of the bladder were found irrespective of detrusor instability. Conclusions: 1) An open bladder outlet observed during bladder filling is a reliable sign of significant detrusor instability in children without neuropathy; 2) It is highly specific of instability; 3) Most false negatives coincide with low amplitude contractions; 4) 'Spinning-top' images indicate strong contractions. (author)

  16. Low amplitude rhythmic contraction frequency in human detrusor strips correlates with phasic intravesical pressure waves.

    Science.gov (United States)

    Colhoun, Andrew F; Speich, John E; Cooley, Lauren F; Bell, Eugene D; Barbee, R Wayne; Guruli, Georgi; Ratz, Paul H; Klausner, Adam P

    2017-08-01

    Low amplitude rhythmic contractions (LARC) occur in detrusor smooth muscle and may play a role in storage disorders such as overactive bladder and detrusor overactivity. The purpose of this study was to determine whether LARC frequencies identified in vitro from strips of human urinary bladder tissue correlate with in vivo LARC frequencies, visualized as phasic intravesical pressure (p ves ) waves during urodynamics (UD). After IRB approval, fresh strips of human urinary bladder were obtained from patients. LARC was recorded with tissue strips at low tension (rhythmic frequency similar to the in vitro LARC frequency quantified in human urinary bladder tissue strips. Further refinements of this technique may help identify subsets of individuals with LARC-mediated storage disorders.

  17. The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Tomonori Yamanishi

    2015-06-01

    Full Text Available The aim of this study was to compare the effect of antimuscarinic antagonists on carbachol-induced contraction of normal human bladder and detrusor overactivity associated with benign prostatic hyperplasia (DO/BPH. Samples of human bladder muscle were obtained from patients undergoing total cystectomy for bladder cancer (normal bladder, and those undergoing retropubic prostatectomy for BPH. All of the patients with DO/BPH had detrusor overactivity according to urodynamic studies. Detrusor muscle strips were mounted in 10-ml organ baths containing Krebs solution, and concentration–response curves for carbachol were obtained in the presence of antimuscarinic antagonists (4-DAMP, methoctramine, pirenzepine, tolterodine, solifenacin, trospium, propiverine, oxybutynin, and imidafenacin or vehicle. All antagonists competitively antagonized concentration–response curves to carbachol with high affinities in normal bladder. The rank order of mean pA2 values was as follows: trospium (10.1 > 4-DAMP (9.87, imidafenacin (9.3 > solifenacin (8.8 > tolterodine (8.6 > oxybutynin (8.3 > propiverine (7.7 > pirenzepine (7.4 > methoctramine (6.6. The effects of these antimuscarinic antagonists did not change when tested with DO/BPH bladder, suggesting that each antimuscarinic antagonist has a similar effect in this condition. Schild plots showed a slope corresponding to unity, except for propiverine with DO/BPH detrusor. In conclusion, M3-receptors mainly mediate contractions in human bladder strips with normal state and DO/BPH.

  18. Selective bladder preservation with curative intent for muscle-invasive bladder cancer. A contemporary review

    International Nuclear Information System (INIS)

    Koga, Fumitaka; Kihara, Kazunori

    2012-01-01

    Radical cystectomy plus urinary diversion, the reference standard treatment for muscle-invasive bladder cancer, associates with high complication rates and compromises quality of life as a result of long-term effects on urinary, gastrointestinal and sexual function, and changes in body image. As a society ages, the number of elderly patients unfit for radical cystectomy as a result of comorbidity will increase, and thus the demand for bladder-sparing approaches for muscle-invasive bladder cancer will also inevitably increase. Trimodality bladder-sparing approaches consisting of transurethral resection, chemotherapy and radiotherapy (Σ55-65 Gy) yield overall survival rates comparable with those of radical cystectomy series (50-70% at 5 years), while preserving the native bladder in 40-60% of muscle-invasive bladder cancer patients, contributing to an improvement in quality of life for such patients. Limitations of the trimodality therapy include muscle-invasive bladder cancer recurrence in the preserved bladder, which most often arises in the original muscle-invasive bladder cancer site; potential lack of curative intervention for regional lymph nodes; and increased morbidity in the event of salvage radical cystectomy for remaining or recurrent disease as a result of high-dose pelvic irradiation. Consolidative partial cystectomy with pelvic lymph node dissection followed by induction chemoradiotherapy at lower dose (exempli gratia (e.g.) 40 Gy) is a rational strategy for overcoming such limitations by strengthening locoregional control and reducing radiation dosage. Molecular profiling of the tumor and functional imaging might play important roles in optimal patient selection for bladder preservation. Refinement of radiation techniques, intensified concurrent or adjuvant chemotherapy, and novel sensitizers, including molecular targeting agent, are also expected to improve outcomes and consequently provide more muscle-invasive bladder cancer patients with favorable

  19. Restoration of bladder function in spastic neuropathic bladder using sacral deafferentation and different techniques of neurostimulation.

    Science.gov (United States)

    Schumacher, S; Bross, S; Scheepe, J R; Alken, P; Jünemann, K P

    1999-01-01

    Conventional sacral anterior root stimulation (SARS) results in simultaneous activation of both the detrusor muscle and the external urethral sphincter. We evaluated the possibilities of different neurostimulation techniques to overcome stimulation induced detrusor-sphincter-dyssynergia and to achieve a physiological voiding. The literature was reviewed on different techniques of sacral anterior root stimulation of the bladder and the significance of posterior rhizotomy in patients with supraconal spinal cord injury suffering from the loss of voluntary bladder control, detrusor hyperreflexia and sphincter spasm. The achievement of selective detrusor activation would improve current sacral neurostimulation of the bladder, including the principle of "poststimulus voiding". This is possible with the application of selective neurostimulation in techniques of anodal block, high frequency block, depolarizing prepulses and cold block. Nowadays, sacral deafferentation is a standard therapy in combination with neurostimulation of the bladder because in conclusion advantages of complete rhizotomy predominate. The combination of sacral anterior root stimulation and sacral deafferentation is a successful procedure for restoration of bladder function in patients with supraconal spinal cord injury. Anodal block technique and cryotechnique are excellent methods for selective bladder activation to avoid detrusor-sphincter-dyssynergia and thus improve stimulation induced voiding.

  20. Smooth muscle fatigue due to repeated urinary bladder neurostimulation: an in vivo study.

    Science.gov (United States)

    Bross, S; Schumacher, S; Scheepe, J R; Seif, C; Jünemann, K P; Alken, P

    1999-01-01

    The presented study investigates the influence of different pause lengths between two consecutive stimulations of the S3 roots on intravesical pressure during bladder neurostimulation. In eight male foxhounds (aged 7-18 months), laminectomy and placement of a modified Brindley electrode were performed. In four series with different pause lengths between two consecutive stimulations (1, 3, 5, and 15 min), the maximum intravesical pressure was measured during stimulation. The changes in intravesical pressure were registered in these four series, each series with six stimulations. A 15-min interval elapsed before the commencement of each series. In the series with a pause length of 15 min, the consecutive stimulations did not result in significant changes in maximum intravesical pressure. In the 5-min series, a significant decrease in intravesical pressure was not observed after the third stimulation. In the 3-min series, a significant decrease was seen at almost every stimulation (average decrease of 3.8% per stimulation) and in the 1-min series, a significant decrease was also observed at almost every stimulation (average decrease of 5.9% per stimulation). The results of repeated bladder neurostimulation demonstrate that the maximum intravesical pressure is dependent on the pause length between two consecutive stimulations. The detrusor muscle showed reversible and short-lived signs of fatigue. This implies the importance of a minimum 5-min interval between two subsequent stimulations. A pause length <5 min leads to a falsification of the results and thus to lower validity of the investigation.

  1. Functional and Molecular Evidence for Kv7 Channel Subtypes in Human Detrusor from Patients with and without Bladder Outflow Obstruction

    DEFF Research Database (Denmark)

    Svalø, Julie; Sheykhzade, Majid; Nordling, Jørgen

    2015-01-01

    The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expressi...... between Kv7 channels and β-adrenoceptors in the human urinary bladder. The performed gene expression analysis combined with the organ bath studies imply that compounds that activate Kv7 channels could be useful for treatment of overactive bladder syndrome.......The aim of the study was to investigate whether Kv7 channels and their ancillary β-subunits, KCNE, are functionally expressed in the human urinary bladder. Kv7 channels were examined at the molecular level and by functional studies using RT-qPCR and myography, respectively. We found mRNA expression...... (activator of Kv7.1 channels, 10 μM) and ML213 (activator of Kv7.2, Kv7.4, Kv7.4/7.5 and Kv7.5 channels, 10 μM), reduced the tone of 1 μM carbachol pre-constricted bladder strips. XE991 (blocker of Kv7.1-7.5 channels, 10 μM) had opposing effects as it increased contractions achieved with 20 mM KPSS...

  2. Evaluation of flurbiprofen in detrusor instability.

    OpenAIRE

    Cardozo, L D; Stanton, S L; Robinson, H; Hole, D

    1980-01-01

    Thirty women with detrusor instability (27 cases idiopathic, and three secondary to multiple sclerosis) completed a double-blind, cross-over trial of the prostaglandin synthetase inhibitor flurbiprofen and a placebo, results being evaluated by questionnaire and cystometry. Frequency, urgency, and urge incontinence were all significantly reduced with flurbiprofen (P less than 0.001, P less than 0.025, and P less than 0.025 respectively), as was the detrusor-pressure rise during bladder filling...

  3. Bladder cancer: overview and disease management. Part 1: non-muscle-invasive bladder cancer.

    Science.gov (United States)

    Anderson, Beverley

    2018-05-10

    Part 1 of this two-part article provides an overview of bladder cancer and discusses its management. Since publication of a previous article entitled 'Understanding the role of smoking in the aetiology of bladder cancer' ( Anderson, 2009 ), the author has received many requests for an update. This article provides an overview of bladder cancer and its current management practices, underlining the continued role of smoking as the predominant risk factor in the disease's development. The management of bladder cancer is governed by specific guidelines. Management of non-muscle-invasive cancers, including surgical intervention with transurethral resection, and intravesical therapy using chemotherapy and immunotherapy agents, is discussed. Cystectomy (removal of the bladder), is sometimes necessary. Treatments are effective in reducing tumour recurrence, but the effects of the risks and side-effects on the individual's quality of life can be significant. The prevalence of bladder cancer, and the nature of its management make this cancer one of the most expensive for the NHS to treat. The effectiveness of health promotional strategies in increasing peoples' awareness of their risk of developing the disease, and in enabling them to change long-term health behaviours is discussed. The role of the multidisciplinary team is explored, along with that of the uro-oncology cancer nurse specialist. Part 2 will consider the management of muscle-invasive and metastatic bladder cancer.

  4. Importance of contraction history on muscle force of porcine urinary bladder smooth muscle.

    Science.gov (United States)

    Menzel, Robin; Böl, Markus; Siebert, Tobias

    2017-02-01

    The purpose of this study was to provide a comprehensive dataset of porcine urinary bladder smooth muscle properties. Particularly, the history dependence of force production, namely force depression (FD) following shortening and force enhancement (FE) following stretch, was analysed. During active micturition, the circumference of the urinary bladder changes enormously. Thus, FD might be an important phenomenon during smooth muscle contraction. Electrically stimulated, intact urinary bladder strips from pigs (n = 10) were suspended in an aerated-filled organ bath, and different isometric, isotonic, and isokinetic contraction protocols were performed to determine the force-length and the force-velocity relation. FD and FE were assessed in concentric and eccentric contractions with different ramp lengths and ramp velocities. Bladder smooth muscles exhibit considerable amounts of FD and FE. The amount of FD increased significantly with ramp length, while FE did not change. However, FE and FD were independent of ramp velocity. The results imply that smooth muscle bladder strips exhibit similar muscle properties and history-dependent behaviour compared to striated muscles. The provided dataset of muscle properties is important for bladder modelling as well as for the analyses and interpretation of dynamic bladder filling and voiding.

  5. Results of radiotherapy on ureteric obstruction in muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Honnens De Lichtenberg, Mette; Miskowiak, J; Rolff, H

    1995-01-01

    To evaluate the effect of radiotherapy on ureteric obstruction due to muscle-invasive bladder cancer.......To evaluate the effect of radiotherapy on ureteric obstruction due to muscle-invasive bladder cancer....

  6. Do β3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?

    Science.gov (United States)

    Afeli, Serge A. Y.; Hristov, Kiril L.

    2012-01-01

    In many species, β3-adrenergic receptors (β3-ARs) have been reported to play a primary role in pharmacologically induced detrusor smooth muscle (DSM) relaxation. However, their role in guinea pig DSM remains controversial. The aim of this study was to investigate whether β3-ARs are expressed in guinea pig DSM and to evaluate how BRL37344 and L-755,507, two selective β3-AR agonists, modulate guinea pig DSM excitability and contractility. We used a combined experimental approach including RT-PCR, patch-clamp electrophysiology, and isometric DSM tension recordings. β3-AR mRNA message was detected in freshly isolated guinea pig DSM single cells. BRL37344 but not L-755,507 caused a slight decrease in DSM spontaneous phasic contraction amplitude and frequency in a concentration-dependent manner. In the presence of atropine (1 μM), only the spontaneous phasic contractions frequency was inhibited by BRL37344 at higher concentrations. Both BRL37344 and L-755,507 significantly decreased DSM carbachol-induced phasic and tonic contractions in a concentration-dependent manner. However, only BRL37344 inhibitory effect was partially antagonized by SR59230A (10 μM), a β3-AR antagonist. In the presence of atropine, BRL37344 and L-755,507 had no inhibitory effect on electrical field stimulation-induced contractions. Patch-clamp experiments showed that BRL37344 (100 μM) did not affect the DSM cell resting membrane potential and K+ conductance. Although β3-ARs are expressed at the mRNA level, they play a minor to no role in guinea pig DSM spontaneous contractility without affecting cell excitability. However, BRL37344 and L-755,507 have pronounced inhibitory effects on guinea pig DSM carbachol-induced contractions. The study outlines important DSM β3-ARs species differences. PMID:21993887

  7. Effects of electroacupuncture at BL33 on detrusor smooth muscle activity in a rat model of urinary retention.

    Science.gov (United States)

    Liu, Xiaoxu; Liu, Kun; Zhi, Mujun; Mo, Qian; Gao, Xinyan; Liu, Zhishun

    2017-12-01

    Detrusor smooth muscle (DSM) underactivity may lead to urinary retention (UR). Electroacupuncture (EA) at BL33 may be effective in improving DSM contractions. This study aimed to investigate: (1) the effect of EA at BL33; and (2) the effect of different manipulation methods at BL33 on the modulation of DSM contractions in UR rats. 30 male Sprague-Dawley rats were anaesthetised with urethane and modelled by urethral outlet obstruction. First, 2 Hz EA at BL33, SP6 and LI4 wasrandomly applied to the UR rats for 5 min to observe the immediate effects (n=10); second, manual acupuncture (MA) (n=10) and 100 Hz EA (n=10) were applied with the same programme. DSM electromyography (EMG) and cystometrogram data were evaluated. (1) 2 Hz EA at BL33 and SP6 significantly increased DSM discharging frequency (0.80±0.10 Hz, P0.05). Compared with SP6, EA at BL33 had greater positive effects on DSM discharging frequency, duration of discharging, and duration of voiding (all P<0.05). (2) No statistically significant differences were shown between MA, 2 Hz EA and 100 Hz EA interventions when stimulating at BL33, SP6 or LI4. EA at BL33 improved DSM contractions to a greater degree than EA at SP6 or LI4. There were no differences in effect when stimulating using 2 Hz EA, 100 Hz EA and MA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Contemporary management of muscle-invasive bladder cancer

    Science.gov (United States)

    Dall’Era, Marc A; Cheng, Liang; Pan, Chong-Xian

    2012-01-01

    The current standard treatment for muscle-invasive nonmetastatic bladder cancer is neoadjuvant platinum-based chemotherapy followed by radical cystectomy. However, neoadjuvant chemotherapy is not widely accepted even with level 1 evidence. Adjuvant chemotherapy should be discussed if patients have not received neoadjuvant chemotherapy before surgery and have high-risk pathologic features. Although not considered standard of care, bladder-sparing therapy can be considered for highly selected patients and for those medically unfit for surgery. Even though there are no level 1 data, the treatment outcomes for highly select patients given bladder-sparing therapy appear promising, with many patients retaining a functional bladder. Personalized chemotherapy is currently being actively pursued to target the underlying molecular changes and tailor to individual needs. PMID:22845409

  9. Pelvic floor muscle training for overactive bladder symptoms – A prospective study

    Directory of Open Access Journals (Sweden)

    Fátima Fitz

    Full Text Available Summary Introduction: Pelvic floor muscle training (PFMT involves the contraction of the puborectal, anal sphincter and external urethral muscles, inhibiting the detrusor contraction, what justify its use in the treatment of overactive bladder (OAB symptoms. Objective: To verify the effects of isolated PFMT on the symptoms of OAB. Method: Prospective clinical trial with 27 women with mixed urinary incontinence (MUI, with predominance of OAB symptoms and loss ≥ 2 g in the pad test. It was evaluated: pelvic floor muscles (PFMs function (digital palpation and manometry; urinary symptoms (nocturia, frequency and urinary loss; degree of discomfort of OAB symptoms; and quality of life (Incontinence Quality-of-Life Questionnaire [I-QoL]. The PFMT program consisted of 24 outpatient sessions (2x/week + home PFMT. The Mann-Whitney and Wilcoxon tests (with a significance level of 5% were used to analyse the data. Results: There was a significant improvement of the urinary symptoms to the pad test (5.8±9.7, p<0.001, urinary loss (0.7±1.1, p=0.005 and nocturia (0.8±0.9, p=0.011. Reduction in the degree of discomfort of urinary symptoms was observed according to OAB-V8 questionnaire (10.0±7.7, p=0.001. There were also significant results in PFMs function: Oxford (3.6±0.9, p=0.001, endurance (5.2±1.8, p<0.001, fast (8.9±1.5, p<0.001 and manometry (26.6±15.8, p=0.003. In addition, quality of life had a significant improvement in the three domains evaluated by I-QoL. Conclusion: The PFMT without any additional guidelines improves the symptomatology, the function of PFMs and the quality of life of women with OAB symptoms.

  10. Concomitant boost radiotherapy for muscle invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pos, Floris J; Tienhoven, Geertjan van; Hulshof, Maarten C.C.M.; Koedooder, Kees; Gonzalez Gonzalez, Dionisio

    2003-07-01

    Purpose: To evaluate the feasibility and efficacy of a concomitant partial bladder boost schedule in radiotherapy for invasive bladder cancer, coupling a limited boost volume with shortening of the overall treatment time. Methods and materials: Between 1994 and 1999, 50 patients with a T2-T4 N0M0 transitional cell carcinoma of the bladder received radiotherapy delivered in a short overall treatment time with a concomitant boost technique. With this technique a dose of 40 Gy in 2-Gy fractions was administered to the small pelvis with a concomitant boost limited to the bladder tumor area plus margin of 15 Gy in fractions of 0.75 Gy. The total tumor dose was 55 Gy in 20 fractions in 4 weeks. Toxicity was scored according to EORTC/RTOG toxicity criteria. Results: The feasibility of the treatment was good. Severe acute toxicity {>=}G3 was observed in seven patients (14%). Severe late toxicity {>=}G3 was observed in six patients (13%). Thirty-seven patients (74%) showed a complete and five (10 %) a partial remission after treatment. The actuarial 3-year freedom of local progression was 55%. Conclusion: In external radiotherapy for muscle invasive bladder cancer a concomitant boost technique coupling a partial bladder boost with shortening of the overall treatment time provides a high probability of local control with acceptable toxicity.

  11. Concomitant boost radiotherapy for muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Pos, Floris J.; Tienhoven, Geertjan van; Hulshof, Maarten C.C.M.; Koedooder, Kees; Gonzalez Gonzalez, Dionisio

    2003-01-01

    Purpose: To evaluate the feasibility and efficacy of a concomitant partial bladder boost schedule in radiotherapy for invasive bladder cancer, coupling a limited boost volume with shortening of the overall treatment time. Methods and materials: Between 1994 and 1999, 50 patients with a T2-T4 N0M0 transitional cell carcinoma of the bladder received radiotherapy delivered in a short overall treatment time with a concomitant boost technique. With this technique a dose of 40 Gy in 2-Gy fractions was administered to the small pelvis with a concomitant boost limited to the bladder tumor area plus margin of 15 Gy in fractions of 0.75 Gy. The total tumor dose was 55 Gy in 20 fractions in 4 weeks. Toxicity was scored according to EORTC/RTOG toxicity criteria. Results: The feasibility of the treatment was good. Severe acute toxicity ≥G3 was observed in seven patients (14%). Severe late toxicity ≥G3 was observed in six patients (13%). Thirty-seven patients (74%) showed a complete and five (10 %) a partial remission after treatment. The actuarial 3-year freedom of local progression was 55%. Conclusion: In external radiotherapy for muscle invasive bladder cancer a concomitant boost technique coupling a partial bladder boost with shortening of the overall treatment time provides a high probability of local control with acceptable toxicity

  12. Expression and function of K(V)2-containing channels in human urinary bladder smooth muscle.

    Science.gov (United States)

    Hristov, Kiril L; Chen, Muyan; Afeli, Serge A Y; Cheng, Qiuping; Rovner, Eric S; Petkov, Georgi V

    2012-06-01

    The functional role of the voltage-gated K(+) (K(V)) channels in human detrusor smooth muscle (DSM) is largely unexplored. Here, we provide molecular, electrophysiological, and functional evidence for the expression of K(V)2.1, K(V)2.2, and the electrically silent K(V)9.3 subunits in human DSM. Stromatoxin-1 (ScTx1), a selective inhibitor of K(V)2.1, K(V)2.2, and K(V)4.2 homotetrameric channels and of K(V)2.1/9.3 heterotetrameric channels, was used to examine the role of these channels in human DSM function. Human DSM tissues were obtained during open bladder surgeries from patients without a history of overactive bladder. Freshly isolated human DSM cells were studied using RT-PCR, immunocytochemistry, live-cell Ca(2+) imaging, and the perforated whole cell patch-clamp technique. Isometric DSM tension recordings of human DSM isolated strips were conducted using tissue baths. RT-PCR experiments showed mRNA expression of K(V)2.1, K(V)2.2, and K(V)9.3 (but not K(V)4.2) channel subunits in human isolated DSM cells. K(V)2.1 and K(V)2.2 protein expression was confirmed by Western blot analysis and immunocytochemistry. Perforated whole cell patch-clamp experiments revealed that ScTx1 (100 nM) inhibited the amplitude of the voltage step-induced K(V) current in freshly isolated human DSM cells. ScTx1 (100 nM) significantly increased the intracellular Ca(2+) level in DSM cells. In human DSM isolated strips, ScTx1 (100 nM) increased the spontaneous phasic contraction amplitude and muscle force, and enhanced the amplitude of the electrical field stimulation-induced contractions within the range of 3.5-30 Hz stimulation frequencies. These findings reveal that ScTx1-sensitive K(V)2-containing channels are key regulators of human DSM excitability and contractility and may represent new targets for pharmacological or genetic intervention for bladder dysfunction.

  13. The effect of intravesical oxybutynin on the ice water test and on electrical perception thresholds in patients with neurogenic detrusor overactivity.

    Science.gov (United States)

    Van Meel, Tom David; De Wachter, Stefan; Wyndaele, Jean Jacques

    2010-03-01

    The C-fiber-mediated bladder-cooling reflex and the determination of the current perception thresholds (CPTs) permit to investigate afferent LUT pathways. They have both been proposed to detect and differentiate neurologic bladder dysfunction. This study evaluates, prospectively, the effect of oxybutynin, an antimuscarinic with direct antispasmodic effect on smooth muscle, on repeated ice water test (IWT) and CPTs in patients with a known incomplete neurogenic bladder. Patients with a known incomplete lesion of the bladder innervation, detrusor overactivity during cystometric bladder filling and a continuous positive response to repeated IWT were included. After the initial tests, 30 mg intravesical oxybutynin (1 mg/ml) was instilled and left in the bladder for 15 min. Afterwards CPTs and IWT were re-assessed. After the drug application, the bladder-cooling reflex could not be initiated, even after three instillations, in 16/17 patients. The bladder CPT increased from 29.7 +/- 11.3 to 39.1 +/- 15.7 mA after oxybutynin (P = 0.001). No difference was found in CPT of the left forearm (P = 0.208). Intravesical oxybutynin blocks the bladder-cooling reflex and increases but does not block CPT sensation in the bladder in most patients with incomplete neurogenic lesion and detrusor overactivity. These results help explain the clinical effect of intravesical oxybutynin in neurogenic patients. They also indicate that a pharmacological local influence on C-fiber-related activity can give different clinical effects. (c) 2009 Wiley-Liss, Inc.

  14. Chemoradiotherapy as a bladder-preservation approach for muscle-invasive bladder cancer. Current status and perspectives

    International Nuclear Information System (INIS)

    Sumiyoshi, Yoshiteru

    2004-01-01

    Radical cystectomy has been considered the (gold standard for the treatment of muscle-invasive bladder r cancer. However, because of disappointing results with radical surgery in terms of survival and decreased quality of life (QOL), bladder-preservation treatment has been introduced as an alternative to radical cystectomy. The primary purpose of the bladder-preservation approach has been to maximize overall cure rates, with the secondary purpose being to preserve the patient's bladder. The modalities used to ensure successful bladder preservation include radical transurethral resection (TUR), concurrent cisplatin (CDDP)-based chemotherapy, and radiotherapy. In patients who achieve a complete response (CR) after trimodality therapy, 5-year survival rates of more than 50%, the same as those of radical cystectomy, can be achieved and 70% of this group will retain an intact functional bladder. In this article, bladder-preservation studies using chemoradiotherapy are reviewed. (author)

  15. Health-related quality of life after bladder preservation therapy for muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Hashine, Katsuyoshi; Miura, Noriyoshi; Numata, Kousaku; Shirato, Akitomi; Sumiyoshi, Yoshiteru; Kataoka, Masaaki

    2008-01-01

    The objective of this study was to assess health-related quality of life (QOL) of bladder cancer patients following bladder preservation therapy (BPT). Eighty patients with muscle-invasive bladder cancer had been treated between January 1992 and July 2005 at our institutions with BPT consisting of transurethral resection, intra-arterial chemotherapy and radiotherapy. Among them, 48 were alive and free from recurrence at the time of survey and were asked to participate. A total of 168 patients who had been treated for superficial bladder cancer in the same period were used as a control group. Three questionnaires, namely the International Prostate Symptom Score (IPSS), the SF-36, and the Expanded Prostate Cancer Index Composite (EPIC) were used. Thirty-three patients in the BPT group (68.8%) and 128 patients in the control group (76.2%) answered the QOL survey. There was no significant difference in age, gender and other clinical factors among these two groups. No significant difference was found between the groups according to IPSS. The QOL score of BPT was lower than that of the control group in the SF-36, but there was no significant difference without body pain (P=0.047). There was a tendency toward a diminished physical functioning (P=0.053) and role-physical (P=0.064) in BPT. The EPIC scores for urinary function, especially storage and voiding symptoms, and bowel function were significantly lower in the BPT group. At multivariable analysis, body pain and bowel function were associated with the type of treatment. Although some of the QOL outcome parameters after BPT were found to be lower than the control group, these differences were not significant. Overall, patients retaining their bladder had an acceptable health related QOL. (author)

  16. β-adrenoceptor agonist effects in experimental models of bladder dysfunction

    NARCIS (Netherlands)

    Michel, Martin C.; Ochodnicky, Peter; Homma, Yukio; Igawa, Yasuhiko

    2011-01-01

    β-adrenoceptor stimulation can enhance the storage function of the urinary bladder by acting on detrusor smooth muscle tone, mediator release from the urothelium and/or afferent nerve activity. In humans this may occur predominantly if not exclusively via the β₃-subtype. The effects of

  17. Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the rat bladder contractility.

    Science.gov (United States)

    Yuan, Yuan; Tan, Yin-Feng; Xu, Peng; Li, Hailong; Li, Yong-Hui; Chen, Wen-Ya; Zhang, Jun-Qing; Chen, Feng; Huang, Guo-Jun

    2014-01-01

    Alpinia oxyphylla (Zingiberaceae), an herbaceous perennial plant, its capsular fruit is commonly used in traditional Chinese medicine for the treatment of different urinary incontinence symptoms including frequency, urgency and nocturia. These symptoms are similar to the overactive bladder syndrome. In our lab, we found that the 95% ethanol extract of the capsular fruits exhibited significant anti-muscarinic activity. Some constituents in capsular fruits including flavonoids (e.g., izalpinin and tectochrysin), diarylheptanoids (e.g., yakuchinone A and yakuchinone B) and sesquiterpenes (e.g., nootkatone), are regarded as representative chemicals with putative pharmacological activities. This study aimed to evaluate the in vitro antagonistic actions of izalpinin on carbachol-induced contraction of the rat detrusor muscle. In vitro inhibition of rat detrusor contractile response to carbachol was used to study the functional activity of izalpinin. The isolated detrusor strips of rats were mounted in organ baths containing oxygenated Krebs' solution. The cumulative consecutive concentration-response curves to carbachol-evoked contractions in strips of rat bladder were obtained. Carbachol induced concentration-dependent contractions of isolated rat bladder detrusor strips. The vehicle DMSO had no impact on the contraction response. The contraction effects were concentration-dependently antagonized by izalpinin, with a mean EC50 value of 0.35 µM. The corresponding cumulative agonist concentration-response curves shifted right-ward. Izalpinin exhibits inhibitory role of muscarinic receptor-related detrusor contractile activity, and it may be a promising lead compound to treat overactive bladder.

  18. Neurogenic Bladder

    Directory of Open Access Journals (Sweden)

    Peter T. Dorsher

    2012-01-01

    Full Text Available Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented.

  19. Muscle invasive bladder cancer: examining survivor burden and unmet needs.

    Science.gov (United States)

    Mohamed, Nihal E; Chaoprang Herrera, Phapichaya; Hudson, Shawna; Revenson, Tracey A; Lee, Cheryl T; Quale, Diane Z; Zarcadoolas, Christina; Hall, Simon J; Diefenbach, Michael A

    2014-01-01

    Although improvements in perioperative care have decreased surgical morbidity after radical cystectomy for muscle invasive bladder cancer, treatment side effects still have a negative impact on patient quality of life. We examined unmet patient needs along the illness trajectory. A total of 30 patients (26.7% women) treated with cystectomy and urinary diversion for muscle invasive bladder cancer participated in the study. Patients were recruited from the Department of Urology at Mount Sinai and through advertisements on the Bladder Cancer Advocacy Network (BCAN) website between December 2011 and September 2012. Data were collected at individual interviews, which were audiotaped and transcribed. Transcribed data were quantitatively analyzed to explore key unmet needs. At diagnosis unmet informational needs were predominant, consisting of insufficient discussion of certain topics, including urinary diversion options and their side effects, self-care, the recovery process and medical insurance. Unmet psychological needs related to depression, and worries about changes in body image and sexual function were reported. Postoperative unmet needs revolved around medical needs (eg pain and bowel dysfunction) and instrumental needs (eg need of support for stomal appliances, catheters and incontinence). During survivorship (ie 6 to 72 months postoperatively) unmet needs centered around psychological support (ie depression, poor body image and sexual dysfunction) and instrumental support (eg difficulty adjusting to changes in daily living). Meeting patient needs is imperative to ensure adequate patient involvement in health care and enhance postoperative quality of life. An effective support provision plan should follow changes in patient needs. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. Interleukin-4 and 13 induce the expression and release of monocyte chemoattractant protein 1, interleukin-6 and stem cell factor from human detrusor smooth muscle cells: synergy with interleukin-1beta and tumor necrosis factor-alpha

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Andresen, Lars; Alvarez, Susana

    2006-01-01

    Interstitial cystitis is characterized by an increased number of activated MCs in the detrusor muscle. However, to our knowledge the factors that influence the anatomical relationship between MCs and HDSMCs are unknown. MCP-1, IL-6 and SCF have a critical role in the regulation of MC development,......, signaling and function. We investigated whether HDSMCs are capable of expressing and releasing MCP-1, IL-6 and SCF in response to IL-4, IL-13, IL-1beta and tumor necrosis factor-alpha.......Interstitial cystitis is characterized by an increased number of activated MCs in the detrusor muscle. However, to our knowledge the factors that influence the anatomical relationship between MCs and HDSMCs are unknown. MCP-1, IL-6 and SCF have a critical role in the regulation of MC development...

  1. Prognosis of muscle-invasive bladder cancer: difference between primary and progressive tumours and implications for therapy.

    NARCIS (Netherlands)

    Schrier, B.P.; Hollander, M.P.; Rhijn, B.W. van; Kiemeney, L.A.L.M.; Witjes, J.A.

    2004-01-01

    OBJECTIVE: To evaluate the difference in prognosis between progressive and primary muscle-invasive bladder cancer. MATERIALS AND METHODS: From 1986 to 2000, 74 patients with progressive muscle-invasive bladder cancer were identified. Eighty-nine patients with primary muscle-invasive bladder cancer

  2. [Structure and function of suburothelial myofibroblasts in the human urinary bladder under normal and pathological conditions].

    Science.gov (United States)

    Neuhaus, J; Heinrich, M; Schlichting, N; Oberbach, A; Fitzl, G; Schwalenberg, T; Horn, L-C; Stolzenburg, J-U

    2007-09-01

    Myofibroblasts play a pivotal role in numerous pathological alterations. Clarification of the structure and function and of the cellular plasticity of this cell type in the bladder may lead to new insights into the pathogenesis of lower urinary tract disorders. Bladder biopsies from patients with bladder carcinoma and interstitial cystitis were used to analyse the morphology and receptor expression using confocal immunofluorescence and electron microscopy. Cytokine effects and coupling behavior were tested in cultured myofibroblasts and detrusor smooth muscle cells. Myofibroblasts are in close contact with the suburothelial capillary network. They express Cx43 and form functional syncytia. The expression of muscarinic and purinergic receptors is highly variable. Dye coupling experiments showed differences to detrusor myocytes. Upregulation of smooth muscle cell alpha-actin and/or transdifferentiation into smooth muscle cells may contribute to the etiology of urge incontinence. A multi-step model is presented as a working hypothesis.

  3. [Pelvic floor muscles training, electrical stimulation, bladder training and lifestyle interventions to manage lower urinary tract dysfunction in multiple sclerosis: a systematic review].

    Science.gov (United States)

    Gaspard, L; Tombal, B; Castille, Y; Opsomer, R-J; Detrembleur, C

    2014-03-01

    To assess the effectiveness of conservative therapeutic approaches in a multiple sclerosis population. Review was performed in PubMed, PEDro, Scopus and Cochrane Library using combinations of the following keywords: multiple sclerosis; bladder dysfunction; overactive bladder; detrusor hyperreflexia; urge incontinence; urgency; stress incontinence; pelvic floor muscle; biofeedback; PTNS; tibial nerve; bladder training; physical therapy; physiotherapy; conservative treatment and behavioral therapy. Six randomized articles including 289 patients were selected. Four papers exhibited strong scores for the methodological quality assessment. The parameters always significantly improved concerned: number of incontinence episodes (decreased from 64% to 86% after treatment versus before treatment), quality of life (P≤0.001), severity of irritative symptoms (decreased by more than 50% after treatment versus before treatment), and nocturia (P=0.035 to Ptreatment of urinary disorders in multiple sclerosis populations with mild disability. However, the analyses are based on six studies within only four showed good methodological quality. No strong conclusions regarding treatment approaches can be drawn from this review. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Urodynamic and molecular characteristics of detrusor underactivity in a rat cryoinjury model and effects of low energy shock wave therapy.

    Science.gov (United States)

    Chuang, Yao-Chi; Tyagi, Pradeep; Wang, Hung-Jen; Huang, Chao-Cheng; Lin, Chih-Chieh; Chancellor, Michael B

    2018-02-01

    Low energy shock wave (LESW) has been shown to facilitate tissue regeneration and reduce inflammation. We investigated the effects of LESW in an underactive (DU) model induced by cryoinjury of rat detrusor. Forty-six female Sprague-Dawley rats were divided into sham, cryoinjury with or without LESW (0.12 mJ/mm 2 ; 200 pulses). Under halothane anesthesia, a low midline incision was made and a cryoinjury of detrusor was induced by placing an aluminum rod (chilled with dry ice) for 30 s on the serosal side of the bladder filled with 1 mL sterile saline bilaterally. Awake cystometrogram (CMG), molecular and histopathology studies were performed on Day 8 or 15 after cryoinjury. Significant urodynamic, histological, and molecular changes induced by cryoinjury of rat detrusor were detected on Day 8 and decrease in the contraction amplitude (54.3%), a significant increase in wet bladder weight (64.1%), edematous changes, muscle thinning and downregulation of α-SMA, IL-6, and upregulation of COX-2. LESW reversed the cryoinjury induced histological and COX-2 expression to cause a 49.0% increase in the contraction amplitude (P < 0.05). LESW induced cell proliferation was revealed by increased CD31 and Ki67 immunostaining. The effect of cryoinjury on urodynamic and histological changes was maintained till Day 15. The cryoinjury of rat detrusor models myogenic DU, which is partially reversed by LESW. LESW may afford a simple, non-invasive modality to facilitate tissue regeneration and improve voiding function in myogenic detrusor underactivity. © 2017 Wiley Periodicals, Inc.

  5. Detrusor after-contraction: a new insight

    Directory of Open Access Journals (Sweden)

    Françoise A. Valentini

    2015-06-01

    Full Text Available ABSTRACTAims:Detrusor after-contractions (DAC are non-common in adults. Both definition (nothing in ICS reports and significance (artefact, link with detrusor overactivity (DO or bladder outlet obstruction (BOO remain discussed. Our purpose was to carry out an analysis of the urodynamic parameters during voidings with DAC and, using the VBN model, to simulate pathophysiological conditions able to explain both voiding phase and DAC.Materials and Methods:From large urodynamic database of patients referred for evaluation of lower urinary tract dysfunction, DAC were observed in 60 patients (5.7%. Criteria for DAC were post-void residual 10cmH2O. VBN model was used for analysis of both pressure and flow curves, and simulations of pathophysiological conditions.Results:Onset of DAC (ODAC occurred when Q=7.3±5.7mL/s and bladder volume=17.9±15.4mL. Urgency-frequency syndrome and urodynamic diagnosis of DO were the more frequent scenarios associated with DAC. ODAC was associated to an inversion of the slope of detrusor pressure curve without any perturbation in flow curve. Among tested pathophysiological hypothesis (great, abnormal, detrusor force, sphincter contraction, none allowed restoring all recorded curves (flow rate, voiding pressure and DAC.Conclusion:No urodynamic characteristic of the first part of voiding is an index of occurrence of DAC. ODAC is a significant phenomenon linked with the bladder collapse. DAC is not associated with BOO but more probably with DO and appears as the result of local conditions in an almost empty bladder (concentration of stresses around a transducer; thus DAC seems of weak clinical significance.

  6. Preoperative radiation therapy for muscle-invading bladder carcinoma

    International Nuclear Information System (INIS)

    Cox, J.A.; Greven, K.M.; Anscher, M.S.; Morgan, T.M.; Scott, J.

    1991-01-01

    This paper reports on low-dose and high-dose radiation therapy (RT) followed by cystectomy for bladder carcinoma that was evaluated for survival, failure patterns, and complications as these outcomes have been incompletely documented in the past. One hundred five patients with clinical stages T2-T4 (muscle-invading) transitional cell carcinoma of the bladder who completed preoperative RT followed by total cystectomy were evaluated. Eighty-five patients received 20-27 Gy in 4-7 fractions (group A). Twenty patients received 40-50 Gy in 20-28 fractions (group B). Actuarial 5-year survival was 45% and 29% (P = .06) for groups A and B, respectively; 6% of group A was stage T4 compared with 30% of group B. Five-year actuarial survival for patients with stages T2-T3 in groups A and B was 46% and 42%, respectively, while that for T4 was 33% and 0% in groups A and B, respectively. Multivariate analysis revealed that stage, grade, and presence of hydronephrosis independently affected survival. Five-year actuarial local control rates for T2, T3, and T4 were 93%, 93%, and 22%, respectively, with no significant difference between RT groups. Rates of distant metastasis and complications versus preoperative regime and stage were similar

  7. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

    Science.gov (United States)

    Robertson, A Gordon; Kim, Jaegil; Al-Ahmadie, Hikmat; Bellmunt, Joaquim; Guo, Guangwu; Cherniack, Andrew D; Hinoue, Toshinori; Laird, Peter W; Hoadley, Katherine A; Akbani, Rehan; Castro, Mauro A A; Gibb, Ewan A; Kanchi, Rupa S; Gordenin, Dmitry A; Shukla, Sachet A; Sanchez-Vega, Francisco; Hansel, Donna E; Czerniak, Bogdan A; Reuter, Victor E; Su, Xiaoping; de Sa Carvalho, Benilton; Chagas, Vinicius S; Mungall, Karen L; Sadeghi, Sara; Pedamallu, Chandra Sekhar; Lu, Yiling; Klimczak, Leszek J; Zhang, Jiexin; Choo, Caleb; Ojesina, Akinyemi I; Bullman, Susan; Leraas, Kristen M; Lichtenberg, Tara M; Wu, Catherine J; Schultz, Nicholaus; Getz, Gad; Meyerson, Matthew; Mills, Gordon B; McConkey, David J; Weinstein, John N; Kwiatkowski, David J; Lerner, Seth P

    2017-10-19

    We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Results of chemoradiotherapyfor muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Yu. V. Gumenetskaya

    2013-01-01

    Full Text Available This study presents the results of chemoradiotherapy (CRT in 108 patients with muscle-invasive bladder cancer in whom surgery was contraindicated. The efficacies and toxicities of three variants of CRT were evaluated. Group 1 (neoadjuvant chemotherapy: 2–3 cycles of cisplatin-containing combination chemotherapy followed by a continuous course of external beam radiation therapy (EBRT. Group 2: concurrent CRT – cisplatin i.v., 70–100 mg/m 2 during the first and last weeks of continuous-course EBRT. Group 3: sequential neoadjuvant chemotherapy, 2–3 cycles and concurrent CRT. The comparative analysis of long-term outcomes following CRT indicated an improvement in survival rates in group 3 in which the 5-and 10-year cancer-specific survival rates were 42,3 ± 8,8 % and 31,3 ± 9,4 %, respectively, compared with 28,6 ± 9,7 % and 28,6 ± 9,7 % in group 1, and 29,5 ± 8,5 % and 14,8 ± 7,4 % in group 2, respectively (р=0,093. Acute toxicity (GU Grade 1 or 2 arose more often from concurrent radiation and chemotherapy: in 40,0 % and 40,5 % of cases in groups 2 and 3, respectively, whereas in group 1 it occurred in 25,9 % of cases (р<0,2. Late radiation toxicity (GU Grade 2 occurred more often in the concurrent CRT groups: 11,4 % and 11,9 % versus 3,2 % in the neoadjuvant chemotherapy group; Grade 3 was noted in 5,7 % and 2,4 % of patients in groups 2 and 3, respectively. The results indicated that chemoradiotherapy including neoadjuvant and concomitant chemotherapy improved the outcomes in patients with muscle-invasive bladder cancer in whom surgery was contraindicated. There was an acceptable rate of clinically significant complications.

  9. Quality of life in patients with muscle invasive and non-muscle invasive bladder cancer.

    Science.gov (United States)

    Singer, S; Ziegler, C; Schwalenberg, T; Hinz, A; Götze, H; Schulte, T

    2013-05-01

    Compared to the literature on other malignancies, data on quality of life (QoL) in bladder cancer are sparse. This study sought answers to the following questions: In what QoL domains do patients with bladder cancer differ from the general population? Do patients with radical cystectomy differ in QoL compared to those who received conservative treatment? Do patients with neobladder generally have better QoL compared to patients with other diversion methods? At the beginning of inpatient rehabilitation, N = 823 patients with bladder cancer were assessed. Data of a representative community sample (N = 2037) were used for comparison. The questionnaire EORTC QLQ-C30 was used to measure QoL. Multivariate linear regression models were computed to investigate differences between groups. Patients with both non-muscle invasive and muscle invasive bladder cancer reported significantly more problems and worse functioning than the general population. Radiotherapy is associated with clinically relevant more pain, dyspnoea, constipation, appetite loss and decreased social functioning while chemotherapy is associated more with dyspnoea. Cystectomy patients reported more fatigue, appetite loss and decreased role functioning. Male patients ≥70 years with conduit experienced more sleep and emotional problems. These effects of urinary diversion were not observed in women and younger patients. Patients with bladder cancer experience various QoL concerns at the beginning of inpatient rehabilitation. These problems can partly be explained by the type of treatment the patients receive. Type of urinary diversion is relevant for QoL in subgroups of patients.

  10. Luminal DMSO: Effects on Detrusor and Urothelial/Lamina Propria Function

    Directory of Open Access Journals (Sweden)

    Katrina J. Smith

    2014-01-01

    Full Text Available DMSO is used as a treatment for interstitial cystitis and this study examined the effects of luminal DMSO treatment on bladder function and histology. Porcine bladder was incubated without (controls or with DMSO (50% applied to the luminal surface and the release of ATP, acetylcholine, and LDH assessed during incubation and in tissues strips after DMSO incubation. Luminally applied DMSO caused ATP, Ach, and LDH release from the urothelial surface during treatment, with loss of urothelial layers also evident histologically. In strips of urothelium/lamina propria from DMSO pretreated bladders the release of both ATP and Ach was depressed, while contractile responses to carbachol were enhanced. Detrusor muscle contractile responses to carbachol were not affected by DMSO pretreatment, but neurogenic responses to electrical field stimulation were enhanced. The presence of an intact urothelium/lamina propria inhibited detrusor contraction to carbachol by 53% and this inhibition was significantly reduced in DMSO pretreated tissues. Detection of LDH in the treatment medium suggests that DMSO permeabilised urothelial membranes causing leakage of cytosolic contents including ATP and Ach rather than enhancing release of these mediators. The increase in contractile response and high levels of ATP are consistent with initial flare up in IC/PBS symptoms after DMSO treatment.

  11. Relation between flexor spasms, uninhibited detrusor contractions and anal sphincter activity

    DEFF Research Database (Denmark)

    Pedersen, E; Petersen, T; Schrøder, H D

    1986-01-01

    The time relation between flexor spasms, detrusor contractions and anal sphincter activity was recorded in a consecutive series of 111 patients with hyperreflexic bladder and flexor spasms. In 76 of the patients flexor spasms were preceded by detrusor contractions. The opposite pattern, namely de...

  12. Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer

    NARCIS (Netherlands)

    Witjes, J.A.; Lebret, T.; Comperat, E.M.; Cowan, N.C.; Santis, M. de; Bruins, H.M.; Hernandez, V.; Espinos, E.L.; Dunn, J.; Rouanne, M.; Neuzillet, Y.; Veskimae, E.; Heijden, A.G. van der; Gakis, G.; Ribal, M.J.

    2017-01-01

    CONTEXT: Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis,

  13. Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Coen, John J., E-mail: jcoen@harthosp.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Paly, Jonathan J.; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kaufman, Donald S. [Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Heney, Niall M. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2013-06-01

    Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.

  14. Renal deterioration after spinal cord injury is associated with length of detrusor contractions during cystometry

    DEFF Research Database (Denmark)

    Elmelund, Marlene; Klarskov, Niels; Bagi, Per

    2017-01-01

    AIMS: To investigate which urodynamic parameters are associated with renal deterioration over a median of 41 years follow-up after traumatic spinal cord injury. METHODS: Medical records of patients with a traumatic spinal cord injury sustained 1944-1975 were reviewed from time of injury until 2012....... Patients who attended regular renography and/or renal clearance examinations and had minimum one cystometry and pressure-flow study were included. Renal deterioration was diagnosed as split renal function ≤30% in one kidney or relative glomerular filtration rate ≤51% of expected according to age and gender....... Detrusor function, presence of detrusor sphincter dyssynergia, maximum detrusor pressure, post-void residual volume, and cystometric bladder capacity were obtained. In patients with detrusor overactivity, a detrusor overactivity/cystometry ratio was calculated using duration of detrusor contraction...

  15. An Investigation into the Nature of Non-Voiding Contractions Resulting from Detrusor Hyperreflexia in Neurogenic Bladders Following Spinal Cord Injury

    Science.gov (United States)

    2015-06-01

    occasioned by numerous, rhythmic high pressure non-voiding contractions (NVC) during normal bladder filling. These NVC are responsible for incontinence...month experiment period) 2c. Final data analysis (data analysis will be ongoing throughout, this will represent the finalization of data period, 0.25...Sub-Tasks 2a and 2b. As of 9/2/14, we have completed much of the data analysis (Sub-Task 2c; see below for results). Analysis of abdominal

  16. Neuromodulation of detrusor hyper-reflexia by functional magnetic stimulation of the sacral roots.

    Science.gov (United States)

    Sheriff, M K; Shah, P J; Fowler, C; Mundy, A R; Craggs, M D

    1996-07-01

    To investigate the acute effects of functional magnetic stimulation (FMS) on detrusor hyper-reflexia using a multi-pulse magnetic stimulator. Seven male patients with established and intractable detrusor hyper-reflexia following spinal cord injury were studied. No patient was on medication and none had had previous surgery for detrusor hyper-reflexia. After optimization of magnetic stimulation of S2-S4 sacral anterior roots by recording toe flexor electromyograms, unstable detrusor activity was provoked during cystometry by rapid infusion of fluid into the bladder. The provocation test produced consistent and predictable detrusor hyper-reflexia. On some provocations, supramaximal FMS at 20 pulses/s for 5 s was applied at detrusor pressures which were > 15 cmH2O. Following FMS there was an obvious acute suppression of detrusor hyper-reflexia. There was a profound reduction in detrusor contraction, as assessed by the area under the curves of detrusor pressure with time. Functional magnetic stimulation applied over the sacrum can profoundly suppress detrusor hyper-reflexia in man. It may provide a non-invasive method of assessing patients for implantable electrical neuromodulation devices and as a therapeutic option in its own right.

  17. Detrusor wall thickness compared to other non-invasivemethods in ...

    African Journals Online (AJOL)

    Introduction: The current study aims to compare the diagnostic accuracy of detrusor wall thickness to othernoninvasive, tools, using pressure flow studies as a reference, in the assessment of bladder outlet, obstructionamong men presenting with lower urinary tract symptoms. Patients and Methods: Men aged 50 or older ...

  18. Bladder Preservation for Localized Muscle-Invasive Bladder Cancer: The Survival Impact of Local Utilization Rates of Definitive Radiotherapy

    International Nuclear Information System (INIS)

    Kozak, Kevin R.; Hamidi, Maryam; Manning, Matthew; Moody, John S.

    2012-01-01

    Purpose: This study examines the management and outcomes of muscle-invasive bladder cancer in the United States. Methods and Materials: Patients with muscle-invasive bladder cancer diagnosed between 1988 and 2006 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified according to three mutually exclusive treatment categories based on the primary initial treatment: no local management, radiotherapy, or surgery. Overall survival was assessed with Kaplan-Meier analysis and Cox models based on multiple factors including treatment utilization patterns. Results: The study population consisted of 26,851 patients. Age, sex, race, tumor grade, histology, and geographic location were associated with differences in treatment (all p < 0.01). Patients receiving definitive radiotherapy tended to be older and have less differentiated tumors than patients undergoing surgery (RT, median age 78 years old and 90.6% grade 3/4 tumors; surgery, median age 71 years old and 77.1% grade 3/4 tumors). No large shifts in treatment were seen over time, with most patients managed with surgical resection (86.3% for overall study population). Significant survival differences were observed according to initial treatment: median survival, 14 months with no definitive local treatment; 17 months with radiotherapy; and 43 months for surgery. On multivariate analysis, differences in local utilization rates of definitive radiotherapy did not demonstrate a significant effect on overall survival (hazard ratio, 1.002; 95% confidence interval, 0.999–1.005). Conclusions: Multiple factors influence the initial treatment strategy for muscle-invasive bladder cancer, but definitive radiotherapy continues to be used infrequently. Although patients who undergo surgery fare better, a multivariable model that accounted for patient and tumor characteristics found no survival detriment to the utilization of definitive radiotherapy. These results support continued

  19. The force recovery following repeated quick releases applied to pig urinary bladder smooth muscle

    NARCIS (Netherlands)

    R. van Mastrigt (Ron)

    1991-01-01

    textabstractA method for measuring several quick-releases during one contraction of a pig urinary bladder smooth muscle preparation was developed. The force recovery following quick release in this muscle type was studied by fitting a multiexponential model to 926 responses measured during the first

  20. Pathologic bladder microenvironment attenuates smooth muscle differentiation of skin derived precursor cells: implications for tissue regeneration.

    Directory of Open Access Journals (Sweden)

    Cornelia Tolg

    Full Text Available Smooth muscle cell containing organs (bladder, heart, blood vessels are damaged by a variety of pathological conditions necessitating surgery or organ replacement. Currently, regeneration of contractile tissues is hampered by lack of functional smooth muscle cells. Multipotent skin derived progenitor cells (SKPs can easily be isolated from adult skin and can be differentiated in vitro into contractile smooth muscle cells by exposure to FBS. Here we demonstrate an inhibitory effect of a pathologic contractile organ microenvironment on smooth muscle cell differentiation of SKPs. In vivo, urinary bladder strain induces microenvironmental changes leading to de-differentiation of fully differentiated bladder smooth muscle cells. Co-culture of SKPs with organoids isolated from ex vivo stretched bladders or exposure of SKPs to diffusible factors released by stretched bladders (e.g. bFGF suppresses expression of smooth muscle markers (alpha SMactin, calponin, myocardin, myosin heavy chain as demonstrated by qPCR and immunofluorescent staining. Rapamycin, an inhibitor of mTOR signalling, previously observed to prevent bladder strain induced de-differentiation of fully differentiated smooth muscle cells in vitro, inhibits FBS-induced smooth muscle cell differentiation of undifferentiated SKPs. These results suggest that intended precursor cell differentiation may be paradoxically suppressed by the disease context for which regeneration may be required. Organ-specific microenvironment contexts, particularly prevailing disease, may play a significant role in modulating or attenuating an intended stem cell phenotypic fate, possibly explaining the variable and inefficient differentiation of stem cell constructs in in vivo settings. These observations must be considered in drafting any regeneration strategies.

  1. Bladder preservation in non-metastatic muscle-invasive bladder cancer (MIBC): a single-institution experience.

    Science.gov (United States)

    Gerardi, Marianna A; Jereczek-Fossa, Barbara A; Zerini, Dario; Surgo, Alessia; Dicuonzo, Samantha; Spoto, Ruggero; Fodor, Cristiana; Verri, Elena; Rocca, Maria Cossu; Nolè, Franco; Muto, Matteo; Ferro, Matteo; Musi, Gennaro; Bottero, Danilo; Matei, Deliu V; De Cobelli, Ottavio; Orecchia, Roberto

    2016-01-01

    The aim of this study is to access the feasibility, toxicity profile, and tumour outcome of an organ preservation curative approach in non-metastatic muscle-invasive bladder cancer. A retrospective analysis was conducted on patients affected by M0 bladder cancer, who refused cystectomy and were treated with a curative approach. The standard bladder preservation scheme included maximal transurethral resection of bladder tumour (TURBT) and combination of radiotherapy and platin-based chemotherapy, followed by endoscopic evaluation, urine cytology, and instrumental evaluation. Thirteen patients fulfilled the inclusion criteria. TNM stage was cT2cN0M0 and cT2cNxM0, in 12 and one patients, respectively. All patients had transitional cell cancer. Twelve patients completed the whole therapeutic programme (a bimodal treatment without chemotherapy for one patient). Median follow-up is 36 months. None of the patients developed severe urinary or intestinal acute toxicity. In 10 patients with a follow-up > 6 months, no cases of severe late toxicity were observed. Response evaluated in 12 patients included complete response and stable disease in 11 patients (92%), and one patient (8%), respectively. At the time of data analysis (March 2016), 10 patients (77%) are alive with no evidence of disease, two patients (15%) died for other reasons, and one patient has suspicious persistent local disease. The trimodality approach, including maximal TURBT, radiotherapy, and chemotherapy for muscle-invasive bladder cancer, is well-tolerated and might be considered a valid and feasible option in fit patients who refuse radical cystectomy.

  2. Clinical results of a concomitant boost radiotherapy technique for muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Piet, A H.M.; Hulshof, M C.C.M.; Pieters, B R; Koning, C C.E. [Dept. of Radiation Oncology, Academic Medical Center, Univ. of Amsterdam (Netherlands); Pos, F J [Dept. of Radiation Oncology, The Netherlands Cancer Inst., Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Reijke, T.M. de [Dept. of Urology, Academic Medical Center, Univ. of Amsterdam (Netherlands)

    2008-06-15

    Purpose: to update the results of external radiotherapy with a focal concomitant boost technique on local control and bladder function in patients with muscle-invasive bladder cancer. Patients and methods: the authors retrospectively evaluated 92 elderly or disabled patients with localized T2-4 N0-1 M0 transitional cell carcinoma of the bladder and a median age of 79 years, not suitable for radical surgery and treated between 1994 and 2005. Treatment consisted of a dose of 40 Gy/2 Gy to the small pelvis with a daily concomitant boost of 0.75 Gy to the tumor. Total dose was 55 Gy in 4 weeks. Results: complete remission rate after evaluation by means of cystoscopy at 3 months was 78%. 3-year local control rate amounted to 56%, and 3-year overall survival to 36%. The posttreatment bladder capacity was comparable with the pretreatment capacity and was {>=} 200 ml in 81% of the cases. Mean bladder capacity did not deteriorate at longer follow-up. Conclusion: the local control rate after external beam radiotherapy in elderly patients with a focal concomitant boost for localized muscle-invasive bladder cancer was 56% at 3 years. Functional bladder outcome was good. (orig.)

  3. Clinical results of a concomitant boost radiotherapy technique for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Piet, A.H.M.; Hulshof, M.C.C.M.; Pieters, B.R.; Koning, C.C.E.; Pos, F.J.; Reijke, T.M. de

    2008-01-01

    Purpose: to update the results of external radiotherapy with a focal concomitant boost technique on local control and bladder function in patients with muscle-invasive bladder cancer. Patients and methods: the authors retrospectively evaluated 92 elderly or disabled patients with localized T2-4 N0-1 M0 transitional cell carcinoma of the bladder and a median age of 79 years, not suitable for radical surgery and treated between 1994 and 2005. Treatment consisted of a dose of 40 Gy/2 Gy to the small pelvis with a daily concomitant boost of 0.75 Gy to the tumor. Total dose was 55 Gy in 4 weeks. Results: complete remission rate after evaluation by means of cystoscopy at 3 months was 78%. 3-year local control rate amounted to 56%, and 3-year overall survival to 36%. The posttreatment bladder capacity was comparable with the pretreatment capacity and was ≥ 200 ml in 81% of the cases. Mean bladder capacity did not deteriorate at longer follow-up. Conclusion: the local control rate after external beam radiotherapy in elderly patients with a focal concomitant boost for localized muscle-invasive bladder cancer was 56% at 3 years. Functional bladder outcome was good. (orig.)

  4. Reducing recurrence in non-muscle-invasive bladder cancer using photodynamic diagnosis and immediate post-transurethral resection of the bladder chemoprophylaxis

    DEFF Research Database (Denmark)

    Risager, Malene Bøg; Nielsen, Tommy Kjærgaard; Zieger, Karsten Egbert Arnold

    2015-01-01

    Abstract Objective. The aim of this study was to evaluate the effect of fluorescence cystoscopy and immediate post-transurethral resection of the bladder (TURB) chemoprophylaxis on the risk of recurrence of non-muscle-invasive bladder cancer (NMIBC) under routine clinical conditions. Materials...

  5. Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group

    NARCIS (Netherlands)

    Kamat, A.M.; Sylvester, R.J.; Bohle, A.; Palou, J.; Lamm, D.L.; Brausi, M.; Soloway, M.; Persad, R.; Buckley, R.; Colombel, M.; Witjes, J.A.

    2016-01-01

    PURPOSE: To provide recommendations on appropriate clinical trial designs in non-muscle-invasive bladder cancer (NMIBC) based on current literature and expert consensus of the International Bladder Cancer Group. METHODS: We reviewed published trials, guidelines, meta-analyses, and reviews and

  6. Botulinum Toxin in Neurogenic Detrusor Overactivity

    Directory of Open Access Journals (Sweden)

    Carlos Arturo Levi D'Ancona

    2012-09-01

    Full Text Available Purpose To evaluate the effects of botulinum toxin on urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity. Methods Thirty four adult patients with spinal cord injury and detrusor overactivity were selected. The patients received 300 units of botulinum toxin type A. The endpoints evaluated with the episodes of urinary incontinence and measured the maximum cystometric capacity, maximum amplitude of detrusor pressure and bladder compliance at the beginning and end of the study (24 weeks and evaluated the quality of life by applying the Qualiveen questionnaire. Results A significant decrease in the episodes of urinary incontinence was observed. All urodynamic parameters presented a significant improvement. The same was observed in the quality of life index and the specific impact of urinary problems scores from the Qualiveen questionnaire. Six patients did not complete the study, two due to incomplete follow-up, and four violated protocol and were excluded from the analyses. No systemic adverse events of botulinum toxin type A were reported. Conclusions A botulinum toxin type A showed a significantly improved response in urodynamics parameters and specific and general quality of life.

  7. Results of radiotherapy for ureteric obstruction in muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Holm, M.; Miskowiak, J.; Rolff, H.

    1996-01-01

    Retrospective evaluation of the records of 574 patients with muscle-invasive bladder cancer revealed 90 patients (16%) with ureteric obstruction; the obstruction was bilateral in 24%. The effect of radiotherapy was assessed in 55 patients with 68 obstructed kidneys. Six patients with eight obstructed kidneys required percutaneous nephrostomy or ureteric catheters in addition to radiotherapy. Drainage improved in only 20% of kidneys and the diverting catheter could be withdrawn permanently in only one (17%) of the diverted patients. The median survival was 11 months. Irradiation was followed by significant complications in 37 patients (67%). This raises doubts about the assumed beneficial effect of irradiation on ureteric obstruction due to muscle invasive bladder cancer. The short median survival of 11 months confirms that ureteric obstruction is a poor prognostic factor in muscle invasive bladder cancer. (au) 10 refs

  8. Risk prediction scores for recurrence and progression of non-muscle invasive bladder cancer : An international validation in primary tumours

    NARCIS (Netherlands)

    M.M. Vedder (Moniek); M. Márquez (Mirari); E.W. de Bekker-Grob (Esther); M.L. Calle (Malu); L. Dyrskjot (Lars); M. Kogevinas (Manolis); U. Segersten (Ulrika); P.-U. Malmström (Per-Uno); F. Algaba (Ferran); W. Beukers (Willemien); T.F. Orntoft (Torben); E.C. Zwarthoff (Ellen); F.X. Real (Francisco); N. Malats (Núria); E.W. Steyerberg (Ewout)

    2014-01-01

    textabstractObjective: We aimed to determine the validity of two risk scores for patients with non-muscle invasive bladder cancer in different European settings, in patients with primary tumours. Methods: We included 1,892 patients with primary stage Ta or T1 non-muscle invasive bladder cancer who

  9. Neurogenic bladder in Hunter's syndrome.

    Science.gov (United States)

    Koyama, K; Moda, Y; Sone, A; Tanaka, H; Hino, Y

    1994-01-01

    We encountered a rare patient with Hunter's syndrome who exhibited urinary retention as a result of a neurogenic bladder, uninhibited detrusor contractions, and detrusor-sphincter dyssynergia. Neurological findings were consistent with cervical myelopathy and cervical MR imaging showed very narrow segments at the cord level C2-4. We speculate that this Hunter's syndrome patient has cervical myelopathy and that this neurological dysfunction causes the neurogenic bladder. PMID:8014981

  10. Hospitalization for transurethral bladder resection reduces quality of life in Danish patients with non-muscle-invasive bladder tumour

    DEFF Research Database (Denmark)

    Mogensen, Karin; Christensen, Karl B.; Vrang, Marie-Louise

    2016-01-01

    Objective: The aim of the study was to evaluate the impact of transurethral resection of bladder tumour (TURBT) on patients’ quality of life (QoL) and to validate a tool to quantify problems associated with TURBT in a Danish population. Materials and methods: A prospective study was carried out...... using a combination of questionnaires and interviews. The study included 165 consecutive patients undergoing a TURBT owing to non-muscle-invasive bladder cancer (NMIBC) from 1 May 2011 to 30 April 2012. Seven patients were selected for interviews. The Danish translation of the QLQ-NMIBC24 Quality...... of Life Questionnaire for NMIBC, from the European Organisation for Research and Treatment of Cancer (EORTC), was used. The interviews were semi-structured. The reliability of the subscales quantifying QoL as defined by the EORTC was tested by computing Cronbach’s coefficient alpha and confirmatory factor...

  11. Bladder cancer: utility of MRI in detection of occult muscle-invasive disease

    International Nuclear Information System (INIS)

    Rosenkrantz, Andrew B.; Mussi, Thais C.; Melamed, Jonathan; Taneja, Samir S.; Huang, William C.

    2012-01-01

    Background. The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose. To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods. This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results. Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion. MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better

  12. Bladder cancer: utility of MRI in detection of occult muscle-invasive disease

    Energy Technology Data Exchange (ETDEWEB)

    Rosenkrantz, Andrew B. [Dept. of Radiology, NYU Langone Medical Center, New York (United States)], E-mail: Andrew.rosenkrantz@nyumc.org; Mussi, Thais C. [Dept. of Radiology, NYU Langone Medical Center, New York (United States); Hospital Israelita Albert Einstein, Sao Paulo (Brazil); Melamed, Jonathan [Dept. of Pathology, NYU Langone Medical Center, New York (United States); Taneja, Samir S.; Huang, William C. [Dept. of Urology, Div. of Urologic Oncology, NYU Langone Medical Center, New York (United States)

    2012-07-15

    Background. The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose. To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods. This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results. Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion. MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better

  13. Status of Her2 over expression in muscle invasive urothelial bladder carcinoma: Report of 21 cases

    Directory of Open Access Journals (Sweden)

    Nesrine Mejri

    2014-01-01

    Four patients died from disease, one of them had Her2 3+ score. Conclusion: Her2 overexpression can be observed in muscle invasive urothelial bladder carcinoma in an important number of patients. Evaluation criteria must be standardized, especially with heterogeneous cases. Metastases tests can also readdress the expression of Her2, which gives the patient a supplementary therapeutic tool.

  14. Should patients with muscle-invasive bladder cancer undergo more-extensive pelvic lymph node dissection?

    DEFF Research Database (Denmark)

    Steven, Kenneth Eric

    2008-01-01

    This Practice Point commentary discusses the paper by Dhar and colleagues, which compared outcomes between two cohorts of patients with muscle-invasive bladder cancer who received either 'limited' pelvic lymph node dissection (LND) or 'extended' pelvic LND at clinics in the US or Switzerland...

  15. Treatment of Muscle-Invasive and Metastatic Bladder Cancer: Update of the EAU Guidelines.

    NARCIS (Netherlands)

    Stenzl, A.; Cowan, N.C.; Santis, M. de; Kuczyk, M.A.; Merseburger, A.S.; Ribal, M.J.; Sherif, A.; Witjes, J.A.

    2012-01-01

    CONTEXT: New data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines for MiM-BC with a specific focus on treatment. EVIDENCE

  16. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. | Office of Cancer Genomics

    Science.gov (United States)

    We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival.

  17. BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG

    NARCIS (Netherlands)

    Kamat, A.M.; Colombel, M.; Sundi, D.; Lamm, D.; Boehle, A.; Brausi, M.; Buckley, R.; Persad, R.; Palou, J.; Soloway, M.; Witjes, J.A.

    2017-01-01

    Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Most patients initially respond, but recurrence is frequent and progression to invasive cancer is a concern. No established

  18. The length dependence of the series elasticity of pig bladder smooth muscle

    NARCIS (Netherlands)

    R. van Mastrigt (Ron)

    1988-01-01

    textabstractStrips of urinary bladder smooth muscle were subjected to a series of quick release measurements. Each measurement consisted of several releases and resets to the original length, made during one contraction. The complete length-force characteristic of series elasticity was quantified by

  19. Medical management of overactive bladder

    Directory of Open Access Journals (Sweden)

    Sarvpreet S Ubee

    2010-01-01

    Full Text Available Overactive bladder (OAB, as defined by the International Continence Society, is characterized by a symptom complex including urinary urgency with or without urge incontinence, usually associated with frequency and nocturia. OAB syndrome has an incidence reported from six European countries ranging between 12-17%, while in the United States; a study conducted by the National Overactive Bladder Evaluation program found the incidence at 17%. In Asia, the prevalence of OAB is reported at 53.1%. In about 75%, OAB symptoms are due to idiopathic detrusor activity; neurological disease, bladder outflow obstruction (BOO intrinsic bladder pathology and other chronic pelvic floor disorders are implicated in the others. OAB can be diagnosed easily and managed effectively with both non-pharmacological and pharmacological therapies. The first-line treatments are lifestyle interventions, bladder training, pelvic floor muscle exercises and anticholinergic drugs. Antimuscarinics are the drug class of choice for OAB symptoms; with proven efficacy, and adverse event profiles that differ somewhat.

  20. p63 expression defines a lethal subset of muscle-invasive bladder cancers.

    Directory of Open Access Journals (Sweden)

    Woonyoung Choi

    Full Text Available p63 is a member of the p53 family that has been implicated in maintenance of epithelial stem cell compartments. Previous studies demonstrated that p63 is downregulated in muscle-invasive bladder cancers, but the relationship between p63 expression and survival is not clear.We used real-time PCR to characterize p63 expression and several genes implicated in epithelial-to-mesenchymal transition (EMT in human bladder cancer cell lines (n = 15 and primary tumors (n = 101. We correlated tumor marker expression with stage, disease-specific (DSS, and overall survival (OS. Expression of E-cadherin and p63 correlated directly with one another and inversely with expression of the mesenchymal markers Zeb-1, Zeb-2, and vimentin. Non-muscle-invasive (Ta and T1 bladder cancers uniformly expressed high levels of E-cadherin and p63 and low levels of the mesenchymal markers. Interestingly, a subset of muscle-invasive (T2-T4 tumors maintained high levels of E-cadherin and p63 expression. As expected, there was a strongly significant correlation between EMT marker expression and muscle invasion (p<0.0001. However, OS was shorter in patients with muscle-invasive tumors that retained p63 (p = 0.007.Our data confirm that molecular markers of EMT are elevated in muscle-invasive bladder cancers, but interestingly, retention of the "epithelial" marker p63 in muscle-invasive tumors is associated with a worse outcome.

  1. Molecular Landscape of Non-Muscle Invasive Bladder Cancer.

    Science.gov (United States)

    Meeks, Joshua J; Lerner, Seth P

    2017-11-13

    In this issue of Cancer Cell, Hurst et al. report an integrated analysis of non-invasive (stage Ta) bladder cancer. Two genomic subtypes are distinguished by chromosome 9q loss, resulting in increased AKT/PI3K/mTOR signaling. Tumors from female patients have a higher frequency of KDM6A mutations. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Factors influencing treatment results of definitive radiotherapy following transurethral surgery for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Abe, Tatsuyuki; Kanehira Chihiro

    1999-01-01

    To determine the prognostic factors influencing the outcome of bladder cancer patients treated with definitive radiotherapy following transurethral tumor resection (TURBT). From March 1977 through August 1991, 83 patients with muscle-invasive bladder cancer were treated with TURBT (as thoroughly as possible) and definitive radiotherapy (median total dose: 64 Gy, median fractional dose: 2 Gy). Cystectomy was performed when possible for the residual or recurrent invasive cancer following radiotherapy. The median follow-up period was 76 months. The overall survival (OS) and bladder-preserving survival (BPS) rates at 5 years were 38% and 28%, respectively. Univariate analysis indicated that depth of invasion (T2 vs T3), tumor diameter (<3 cm vs. ≥3 cm), and visible (R1) or not visible (R0) residual tumor after TURBT influenced both OS and BPS. In multivariate analysis, absence of visible residual tumor after TURBT was the only significant prognostic factor related to OS (p<0.001) and BPS (p=0.002). Five-year OS and BPS were 54% and 43% in T2-3R0 and 14% and 7% in T2-3R1, respectively. Absence of visible residual tumor after TURBT was significantly associated with better overall survival and bladder-preserving survival for muscle-invasive bladder cancer patients treated with definitive radiotherapy following TURBT. (author)

  3. Phasic or terminal detrusor overactivity in women: age, urodynamic findings and sphincter behavior relationships

    Directory of Open Access Journals (Sweden)

    Françoise A. Valentini

    2011-12-01

    Full Text Available OBJECTIVES: To search for relationships between phasic (P and terminal (T DO with age, urodynamic findings and sphincter behavior during involuntary detrusor contraction in woman. MATERIALS AND METHODS: Urodynamic studies (triple lumen catheter 7F, seated position of 164 successive women referred for LUTS with diagnosis of DO were reviewed. Patients were stratified in 4 sub-groups: pre- (18-44y, peri- (45-54 y, post-menopause (55-74 y and oldest old (≥ 75 y. The urethral sensor was positioned at the level of the maximum urethral closure pressure for sphincter behavior analysis. A variation of at least 5 cmH2O in pressure (detrusor or urethra was chosen to assert DO or sphincter response. Sphincter response was classified as relaxation (re before or during DO, or steady (st. RESULTS: Occurrence of P and TDO was similar: 77 P and 87 T. The PDO group was significantly younger (p = 0.0003. TDO was more frequent in patients with a history of neurological disease. The percentage of PDO remained almost constant in age groups, while that of TDO increased with age from 6.7% to 23.2% (p = 0.0013. Uninhibited contraction occurred at a smaller bladder volume in the P group: 149 ± 95 vs. 221 ± 113 mL (p < 0.0001. Steady sphincter predominated in the TDO subgroup: 45.9% vs. 32.1% and increased significantly in each DO sub-group of ³ 75y. CONCLUSION: Steady sphincter during both P and TDO, and occurrence of TDO appear as specific of aging. The last result could be related to structural changes in the detrusor muscle with aging.

  4. Comparative study of the organisation and phenotypes of bladder interstitial cells in human, mouse and rat.

    Science.gov (United States)

    Gevaert, Thomas; Neuhaus, Jochen; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Der Aa, Frank Van; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Pintelon, Isabel; De Ridder, Dirk

    2017-12-01

    With most research on interstitial cells (IC) in the bladder being conducted on animal models, it remains unclear whether all structural and functional data on IC from animal models can be translated to the human context. This prompted us to compare the structural and immunohistochemical properties of IC in bladders from mouse, rat and human. Tissue samples were obtained from the bladder dome and subsequently processed for immunohistochemistry and electron microscopy. The ultrastructural properties of IC were compared by means of electron microscopy and IC were additionally characterized with single/double immunohistochemistry/immunofluorescence. Our results reveal a similar organization of the IC network in the upper lamina propria (ULP), the deep lamina propria (DLP) and the detrusor muscle in human, rat and mouse bladders. Furthermore, despite several similarities in IC phenotypes, we also found several obvious inter-species differences in IC, especially in the ULP. Most remarkably in this respect, ULP IC in human bladder predominantly displayed a myoid phenotype with abundant presence of contractile micro-filaments, while those in rat and mouse bladders showed a fibroblast phenotype. In conclusion, the organization of ULP IC, DLP IC and detrusor IC is comparable in human, rat and mouse bladders, although several obvious inter-species differences in IC phenotypes were found. The present data show that translating research data on IC in laboratory animals to the human setting should be carried out with caution.

  5. Reconstitution of experimental neurogenic bladder dysfunction using skeletal muscle-derived multipotent stem cells.

    Science.gov (United States)

    Nitta, Masahiro; Tamaki, Tetsuro; Tono, Kayoko; Okada, Yoshinori; Masuda, Maki; Akatsuka, Akira; Hoshi, Akio; Usui, Yukio; Terachi, Toshiro

    2010-05-15

    BACKGROUND.: Postoperative neurogenic bladder dysfunction is a major complication of radical hysterectomy for cervical cancer and is mainly caused by unavoidable damage to the bladder branch of the pelvic plexus (BBPP) associated with colateral blood vessels. Thus, we attempted to reconstitute disrupted BBPP and blood vessels using skeletal muscle-derived multipotent stem cells that show synchronized reconstitution capacity of vascular, muscular, and peripheral nervous systems. METHODS.: Under pentobarbital anesthesia, intravesical pressure by electrical stimulation of BBPP was measured as bladder function. The distal portion of BBPP with blood vessels was then cut unilaterally (experimental neurogenic bladder model). Measurements were performed before, immediately after, and at 4 weeks after transplantation as functional recovery. Stem cells were obtained from the right soleus and gastrocnemius muscles after enzymatic digestion and cell sorting as CD34/45 (Sk-34) and CD34/45 (Sk-DN). Suspended cells were autografted around the damaged region, whereas medium alone and CD45 cells were transplanted as control groups. To determine the morphological contribution of the transplanted cells, stem cells obtained from green fluorescent protein transgenic mouse muscles were transplanted into a nude rat model and were examined by immunohistochemistry and immunoelectron microscopy. RESULTS.: At 4 weeks after surgery, the transplantation group showed significantly higher functional recovery ( approximately 80%) than the two controls ( approximately 28% and 24%). The transplanted cells showed an incorporation into the damaged peripheral nerves and blood vessels after differentiation into Schwann cells, perineurial cells, vascular smooth muscle cells, pericytes, and fibroblasts around the bladder. CONCLUSION.: Transplantation of multipotent Sk-34 and Sk-DN cells is potentially useful for the reconstitution of damaged BBPP.

  6. Monitoring Detrusor Oxygenation and Hemodynamics Noninvasively during Dysfunctional Voiding

    Science.gov (United States)

    Macnab, Andrew J.; Stothers, Lynn S.; Shadgan, Babak

    2012-01-01

    The current literature indicates that lower urinary tract symptoms (LUTSs) related to benign prostatic hyperplasia (BPH) have a heterogeneous pathophysiology. Pressure flow studies (UDSs) remain the gold standard evaluation methodology for such patients. However, as the function of the detrusor muscle depends on its vasculature and perfusion, the underlying causes of LUTS likely include abnormalities of detrusor oxygenation and hemodynamics, and available treatment options include agents thought to act on the detrusor smooth muscle and/or vasculature. Hence, near infrared spectroscopy (NIRS), an established optical methodology for monitoring changes in tissue oxygenation and hemodynamics, has relevance as a means of expanding knowledge related to the pathophysiology of BPH and potential treatment options. This methodological report describes how to conduct simultaneous NIRS monitoring of detrusor oxygenation and hemodynamics during UDS, outlines the clinical implications and practical applications of NIRS, explains the principles of physiologic interpretation of NIRS voiding data, and proposes an exploratory hypothesis that the pathophysiological causes underlying LUTS include detrusor dysfunction due to an abnormal hemodynamic response or the onset of oxygen debt during voiding. PMID:23019422

  7. Monitoring Detrusor Oxygenation and Hemodynamics Noninvasively during Dysfunctional Voiding

    Directory of Open Access Journals (Sweden)

    Andrew J. Macnab

    2012-01-01

    Full Text Available The current literature indicates that lower urinary tract symptoms (LUTSs related to benign prostatic hyperplasia (BPH have a heterogeneous pathophysiology. Pressure flow studies (UDSs remain the gold standard evaluation methodology for such patients. However, as the function of the detrusor muscle depends on its vasculature and perfusion, the underlying causes of LUTS likely include abnormalities of detrusor oxygenation and hemodynamics, and available treatment options include agents thought to act on the detrusor smooth muscle and/or vasculature. Hence, near infrared spectroscopy (NIRS, an established optical methodology for monitoring changes in tissue oxygenation and hemodynamics, has relevance as a means of expanding knowledge related to the pathophysiology of BPH and potential treatment options. This methodological report describes how to conduct simultaneous NIRS monitoring of detrusor oxygenation and hemodynamics during UDS, outlines the clinical implications and practical applications of NIRS, explains the principles of physiologic interpretation of NIRS voiding data, and proposes an exploratory hypothesis that the pathophysiological causes underlying LUTS include detrusor dysfunction due to an abnormal hemodynamic response or the onset of oxygen debt during voiding.

  8. The effect of smoking and timing of smoking cessation on clinical outcome in non-muscle-invasive bladder cancer

    NARCIS (Netherlands)

    Grotenhuis, A.J.; Ebben, C.W.; Aben, K.K.H.; Witjes, J.A.; Vrieling, A.; Vermeulen, H.H.; Kiemeney, B.

    2015-01-01

    OBJECTIVES: Cigarette smoking is the most important risk factor for urinary bladder cancer. The prognostic effect of cigarette smoking on disease recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC), however, is still unclear. We evaluated the effect of smoking

  9. Can we predict detrusor overactivity in women with lower urinary tract symptoms? The King's Detrusor Overactivity Score (KiDOS)

    OpenAIRE

    Giarenis, Ilias; Musonda, Patrick; Mastoroudes, Heleni; Robinson, Dudley; Cardozo, Linda

    2016-01-01

    Objective Traditionally, urodynamic studies (UDS) have been used to assess lower urinary tract symptoms (LUTS), but their routine use is now discouraged. While urodynamic stress incontinence is strongly associated with the symptom of stress urinary incontinence (SUI) and a positive cough test, there is a weak relationship between symptoms of overactive bladder and detrusor overactivity (DO). The aim of our study was to develop a model to predict DO in women with LUTS. Study Design This prospe...

  10. Effect of bladder wall thickness on miniature pneumatic artificial muscle performance.

    Science.gov (United States)

    Pillsbury, Thomas E; Kothera, Curt S; Wereley, Norman M

    2015-09-28

    Pneumatic artificial muscles (PAMs) are actuators known for their high power to weight ratio, natural compliance and light weight. Due to these advantages, PAMs have been used for orthotic devices and robotic limbs. Small scale PAMs have the same advantages, as well as requiring greatly reduced volumes with potential application to prostheses and small scale robotics. The bladder of a PAM affects common actuator performance metrics, specifically: blocked force, free contraction, hysteresis, and dead-band pressure. This paper investigates the effect that bladder thickness has on static actuation performance of small scale PAMs. Miniature PAMs were fabricated with a range of bladder thicknesses to quantify the change in common actuator performance metrics specifically: blocked force, free contraction, and dead-band pressure. These PAMs were then experimentally characterized in quasi-static conditions, where results showed that increasing bladder wall thickness decreases blocked force and free contraction, while dead-band pressure increases. A nonlinear model was then applied to determine the structure of the stress-strain relationship that enables accurate modeling and the minimum number of terms. Two nonlinear models are compared and the identified parameters are analyzed to study the effect of the bladder thickness on the model.

  11. Review of underactive bladder

    Directory of Open Access Journals (Sweden)

    Yi-Huei Chang

    2018-03-01

    Full Text Available In clinical practice, many patients cannot empty their bladders within an acceptable duration. Common complaints include weak urinary stream and incomplete emptying, which may affect quality of life. Bladder emptying requires sufficient detrusor contractile power, velocity, and durability. The urodynamic term for inadequate detrusor contraction is detrusor underactivity (DU. Although this definition was provided by the ICS, it may not be clinically practical. Analogous to the relationship between overactive bladder (OAB and detrusor overactivity (DO, the symptom complex caused by DU is termed underactive bladder (UAB. Many conditions lead to UAB, such as advanced age, neurogenic bladder and BOO, but the definite pathophysiology directly leading to UAB is still being widely studied without a widely-accepted consensus. The preferred mainstream treatment for increased residual urine volume caused by UAB is intermittent catheterization, while pharmacotherapy is still disappointing after decades of development. There are no studies on surgical treatment for UAB with an acceptable level of evidence. We reviewed the recent literature on UAB and DU to provide a comprehensive discussion of the related presentation, etiology, diagnosis and management.

  12. Role of PKC and CaV1.2 in detrusor overactivity in a model of obesity associated with insulin resistance in mice.

    Directory of Open Access Journals (Sweden)

    Luiz O Leiria

    Full Text Available Obesity/metabolic syndrome are common risk factors for overactive bladder. This study aimed to investigate the functional and molecular changes of detrusor smooth muscle (DSM in high-fat insulin resistant obese mice, focusing on the role of protein kinase C (PKC and Ca(v1.2 in causing bladder dysfunction. Male C57BL/6 mice were fed with high-fat diet for 10 weeks. In vitro functional responses and cystometry, as well as PKC and Ca(v1.2 expression in bladder were evaluated. Obese mice exhibited higher body weight, epididymal fat mass, fasting glucose and insulin resistance. Carbachol (0.001-100 µM, α,β-methylene ATP (1-10 µM, KCl (1-300 mM, extracellular Ca(2+ (0.01-100 mM and phorbol-12,13-dibutyrate (PDBu; 0.001-3 µM all produced greater DSM contractions in obese mice, which were fully reversed by the Ca(v1.2 blocker amlodipine. Cystometry evidenced augmented frequency, non-void contractions and post-void pressure in obese mice that were also prevented by amlodipine. Metformin treatment improved the insulin sensitivity, and normalized the in vitro bladder hypercontractility and cystometric dysfunction in obese mice. The PKC inhibitor GF109203X (1 µM also reduced the carbachol induced contractions. PKC protein expression was markedly higher in bladder tissues from obese mice, which was normalized by metformin treatment. The Ca(v1.2 channel protein expression was not modified in any experimental group. Our findings show that Ca(v1.2 blockade and improvement of insulin sensitization restores the enhanced PKC protein expression in bladder tissues and normalizes the overactive detrusor. It is likely that insulin resistance importantly contributes for the pathophysiology of this urological disorder in obese mice.

  13. A contribution to improved radiotherapy for muscle invading urinary bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Muren, Ludvig PAul

    2002-07-01

    Cystectomy has traditionally been regarded the treatment of choice for muscle invading urinary bladder cancer in most countries. Radiotherapy has been offered patients considered unfit for cystectomy. Since the contraindications of surgery are frequent among bladder cancer patients, a substantial amount of patients with muscle invading bladder cancer (typically 50%) are still managed primarily with radiation. Recently, a tri-modality, organsparing treatment (trans-urethral resection and radio-chemotherapy) has been proposed for bladder cancer, like in the management of a range of other common malignancies. This approach may provide as high control rates as cystectomy yet maintain a higher quality of life for selected patient groups. In both the radical radiotherapy and the combined modality approach, high radiation doses are needed to improve local disease control. Radiation dose escalation requires improved conformation of dose distributions. This PhD programme aimed to develop improved conformal radiotherapy procedures in the management of patients with muscle invading urinary bladder cancer. In the initial phase of this work, computer-controlled movement of the linear accelerator collimator jaws during beam delivery was applied to shape so-called partially wedged beams (PWBs), that were designed specifically to tailor the dose distribution in bladder irradiation closer to the defined bladder target. The dosimetric verification and treatment planning implementation of this beam delivery concept were addressed, and we documented that these dynamic beams were delivered as accurately as standard beams. Particular attention was given to the BMS-96 diode array system, as it was adapted to dynamic beam dosimetry. Next, the potential clinical impact of these beams was analysed. In a retrospectively study of a set of urinary bladder treatment plans, the PWBs were seen to improve the dose homogeneity inside the bladder target as well as to reduce normal tissue (small

  14. A contribution to improved radiotherapy for muscle invading urinary bladder cancer

    International Nuclear Information System (INIS)

    Muren, Ludvig PAul

    2002-01-01

    Cystectomy has traditionally been regarded the treatment of choice for muscle invading urinary bladder cancer in most countries. Radiotherapy has been offered patients considered unfit for cystectomy. Since the contraindications of surgery are frequent among bladder cancer patients, a substantial amount of patients with muscle invading bladder cancer (typically 50%) are still managed primarily with radiation. Recently, a tri-modality, organsparing treatment (trans-urethral resection and radio-chemotherapy) has been proposed for bladder cancer, like in the management of a range of other common malignancies. This approach may provide as high control rates as cystectomy yet maintain a higher quality of life for selected patient groups. In both the radical radiotherapy and the combined modality approach, high radiation doses are needed to improve local disease control. Radiation dose escalation requires improved conformation of dose distributions. This PhD programme aimed to develop improved conformal radiotherapy procedures in the management of patients with muscle invading urinary bladder cancer. In the initial phase of this work, computer-controlled movement of the linear accelerator collimator jaws during beam delivery was applied to shape so-called partially wedged beams (PWBs), that were designed specifically to tailor the dose distribution in bladder irradiation closer to the defined bladder target. The dosimetric verification and treatment planning implementation of this beam delivery concept were addressed, and we documented that these dynamic beams were delivered as accurately as standard beams. Particular attention was given to the BMS-96 diode array system, as it was adapted to dynamic beam dosimetry. Next, the potential clinical impact of these beams was analysed. In a retrospectively study of a set of urinary bladder treatment plans, the PWBs were seen to improve the dose homogeneity inside the bladder target as well as to reduce normal tissue (small

  15. [New insights in the differential diagnosis of bladder pain syndrome].

    Science.gov (United States)

    Schwalenberg, T; Neuhaus, J; Horn, L-C; Alexander, H; Zimmermann, G; Ho Thi, P; Mallock, T; Stolzenburg, J-U

    2010-03-01

    The diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is challenging, since pathogenetic mechanisms and the definition of clinical relevant parameters are still under lively discussion. The criteria recently proposed by the European Society for the Study of Interstitial Cystitis (ESSIC) define a collective of patients based on the cardinal symptom of bladder pain which is heterogeneous, and therefore cannot receive standardised consistent therapy. Thus an extended diagnosis based on molecular markers seems to be indicated to render individual pharmacotherapy possible, and to contribute to elucidation of BPS/IC pathogenesis. For this purpose we feel the vital need for taking a bladder biopsy. The diagnosis of BPS/IC should rely on 3 "columns": (1) clinical diagnostics; (2) histopathology; (3) molecular diagnostics/protein expression. Since a significant contribution of the 3 functional units of the bladder to the pathophysiology is most evident, the examinations should ideally include urothelium, lamina propria, and detrusor musculature. Generation of receptor profiles of the detrusor muscle represents a first attempt to define a diagnostic tool for the individualisation of BPS/IC pharmacotherapy. Other factors, e.g., beta-hCG expression in the urothelium, need further evaluation. Extended BPS/IC diagnostics could be realistically integrated into routine patient care within a clinic/laboratory network. Georg Thieme Verlag Stuttgart New York.

  16. Radiation therapy outcomes in muscle invasive urinary bladder cancer: A single institution experience.

    Science.gov (United States)

    Tiwana, M S; Ni, L H; Saini, S; Verma, S K; Doddamani, D; Jain, N; Biswas, M; Gupta, Meenu; Gupta, Madhur; Saini, M; Chauhan, N

    2016-01-01

    To audit the survival outcomes and loco-regional control in muscle invasive urinary bladder cancer patients treated with external beam radiation therapy (RT). From November 2008 through December 2011, 50 consecutively diagnosed muscle invasive urinary bladder carcinoma (T2-4a N0-2, M0) patients were included in this retrospective study. All these patients received external beam RT to a median dose of 60 Gy (range 30-66 Gy), and were not suitable for radical surgery due to patients' preference or medical comorbidities. A stepwise procedure using proportional hazard regression was used to identify prognostic factors with respect to survival. Completion trans-urethral resection of bladder tumor was done in 38 (76%) patients of the cohort and 47 (94%) had transitional cell carcinoma on histopathology. Clinical stage T2 was diagnosed in 40 (80%) patients. The median follow-up for the entire cohort was 14 ± 8.9 months (range 1-36 months). In conclusion, 24 patients (48%) were free of disease, 5 patients (10%) had residual disease, and 13 patients (26%) had died of disease. Two-year and 3 year overall survival of intact bladder for the entire cohort was 58% and 43.6%, respectively. Cox regression modeling strongly suggested clinical stage (P = 0.01) and RT dose (P = 0.001) as being predictors for overall survival. RT shows reliable outcomes and excellent compliance in this advanced disease. Prescribing a higher RT dose could potentially correlate to better intact bladder control rates while maintaining good quality of life in selected patients.

  17. Cost-effective treatment of low-risk carcinoma not invading bladder muscle.

    Science.gov (United States)

    Green, David A; Rink, Michael; Cha, Eugene K; Xylinas, Evanguelos; Chughtai, Bilal; Scherr, Douglas S; Shariat, Shahrokh F; Lee, Richard K

    2013-03-01

    Study Type - Therapy (cost effectiveness analysis) Level of Evidence 2a What's known on the subject? and What does the study add? Bladder cancer is one of the costliest malignancies to treat throughout the life of a patient. The most cost-effective management for low-risk non-muscle-invasive bladder cancer is not known. The current study shows that employing cystoscopic office fulguration for low-risk appearing bladder cancer recurrences can materially impact the cost-effectiveness of therapy. In a follow-up protocol where office fulguration is routinely employed for low-risk bladder cancers, peri-operative intravesical chemotherapy may not provide any additional cost-effectiveness benefit. To examine the cost-effectiveness of fulguration vs transurethral resection of bladder tumour (TURBT) with and without perioperative intravesical chemotherapy (PIC) for managing low-risk carcinoma not invading bladder muscle (NMIBC). Low-risk NMIBC carries a low progression rate, lending support to the use of office-based fulguration for small recurrences rather than traditional TURBT. A Markov state transition model was created to simulate treatment of NMIBC with vs without PIC, with recurrence treated by formal TURBT vs treatment with fulguration. Costing data were obtained from the Medicare Resource Based Relative Value Scale. Data regarding the success of PIC were obtained from the peer-reviewed literature, as were corresponding utilities for bladder cancer-related procedures. Sensitivity analyses were performed. At 5-year follow-up, a strategy of fulguration without PIC was the most cost-effective (mean cost-effectiveness = US $654.8/quality-adjusted life year), despite a lower recurrence rate with PIC. Both fulguration strategies dominated each TURBT strategy. Sensitivity analysis showed that fulguration without PIC dominated all other strategies when the recurrence rate after PIC was increased to ≥14.2% per year. Similarly, the cost-effectiveness of TURBT becomes more

  18. Prognostic value of sex-hormone receptor expression in non-muscle-invasive bladder cancer.

    Science.gov (United States)

    Nam, Jong Kil; Park, Sung Woo; Lee, Sang Don; Chung, Moon Kee

    2014-09-01

    We investigated sex-hormone receptor expression as predicting factor of recurrence and progression in patients with non-muscle invasive bladder cancer. We retrospectively evaluated tumor specimens from patients treated for transitional cell carcinoma of the bladder at our institution between January 2006 and January 2011. Performing immunohistochemistry using a monoclonal androgen receptor antibody and monoclonal estrogen receptor-beta antibody on paraffin-embedded tissue sections, we assessed the relationship of immunohistochemistry results and prognostic factors such as recurrence and progression. A total of 169 patients with bladder cancer were evaluated in this study. Sixty-threepatients had expressed androgen receptors and 52 patients had estrogen receptor beta. On univariable analysis, androgen receptor expression was significant lower in recurrence rates (p=0.001), and estrogen receptor beta expression was significant higher in progression rates (p=0.004). On multivariable analysis, significant association was found between androgen receptor expression and lower recurrence rates (hazard ratio=0.500; 95% confidence interval, 0.294 to 0.852; p=0.011), but estrogen receptor beta expression was not significantly associated with progression rates. We concluded that the possibility of recurrence was low when the androgen receptor was expressed in the bladder cancer specimen and it could be the predicting factor of the stage, number of tumors, carcinoma in situ lesion and recurrence.

  19. Long-term results of radiation combined with cisplatin in localized muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Hara, Takahiro; Nishijima, Jun; Miyachika, Yoshihiro; Yamamoto, Yoshiaki; Nagao, Kazuhiro; Sakano, Shigeru; Matsuyama, Hideyasu; Naito, Katsusuke

    2011-01-01

    Although radical cystectomy is the standard treatment for localized muscle invasive-bladder cancer, bladder preservation therapies have been tried for selective patients in several institutes. However, the indication of bladder preservation therapy remains controversial. To select patients who are good candidates for bladder preservation therapy, we evaluated our long-term experience with radiation therapy (conformal radiotherapy (CRT)) combined with cisplatin. Between 1994 and 2009, 90 patients with bladder cancer (clinical stage T2-4N0M0) with no evidence of upper urinary tract cancer were treated with CRT. The response was evaluated by transurethral resection (TUR) of the tumor, urine cytology and CT scan. Thirty-seven cases (41.1%) achieved pathological complete response (CR) which was defined as no microscopic residual tumor in the bladder. After TUR, 74 cases (82.2%) achieved local control of the cancer that was considered as clinical CR. Among 16 patients for whom clinical CR was not achieved, 8 cases were treated with immediate radical cystectomy. We evaluated the long-term results of CRT in 82 cases with bladder preservation. The median follow-up was 36.6 months (range, 4.1-155.1). The five-year overall survival rate and the 5-year progression-free survival rate were 73.0% and 59.2%, respectively. Clinical T stage and type of tumor (primary or recurrent) were prognostic factors for overall survival (p=0.003 and p=0.017). Likewise, clinical T stage and type of tumor were prognostic factors for progression-free survival (p=0.022 and p=0.033). In addition, primary cT2 cases had a significantly better prognosis than those with other T stage and recurrence in overall survival and progression-free survival (p=0.007 and p=0.018). Based on these data, we concluded that primary cT2 tumors were good candidates for radiation combined with cisplatin for bladder preservation therapy. (author)

  20. Prognostic value of cell cycle regulatory proteins in muscle-infiltrating bladder cancer.

    Science.gov (United States)

    Galmozzi, Fabia; Rubagotti, Alessandra; Romagnoli, Andrea; Carmignani, Giorgio; Perdelli, Luisa; Gatteschi, Beatrice; Boccardo, Francesco

    2006-12-01

    The aims of this study were to investigate the expression levels of proteins involved in cell cycle regulation in specimens of bladder cancer and to correlate them with the clinicopathological characteristics, proliferative activity and survival. Eighty-two specimens obtained from patients affected by muscle-invasive bladder cancer were evaluated immunohistochemically for p53, p21 and cyclin D1 expression, as well as for the tumour proliferation index, Ki-67. The statistical analysis included Kaplan-Meier curves with log-rank test and Cox proportional hazards models. In univariate analyses, low Ki-67 proliferation index (P = 0.045) and negative p21 immunoreactivity (P = 0.04) were associated to patient's overall survival (OS), but in multivariate models p21 did not reach statistical significance. When the combinations of the variables were assessed in two separate multivariate models that included tumour stage, grading, lymph node status, vascular invasion and perineural invasion, the combined variables p21/Ki-67 or p21/cyclin D1 expression were independent predictors for OS; in particular, patients with positive p21/high Ki-67 (P = 0.015) or positive p21/negative cyclin D1 (P = 0.04) showed the worst survival outcome. Important alterations in the cell cycle regulatory pathways occur in muscle-invasive bladder cancer and the combined use of cell cycle regulators appears to provide significant prognostic information that could be used to select the patients most suitable for multimodal therapeutic approaches.

  1. Idiopathic detrusor sphincter dyssynergia in neurologically normal patients with voiding abnormalities

    DEFF Research Database (Denmark)

    Jørgensen, T M; Djurhuus, J C; Schrøder, H D

    1982-01-01

    Symptomatology and clinical manifestations of detrusor sphincter dyssynergia are described in 23 patients without neurological disease. Their cardinal symptoms were recurrent cystitis, enuresis, frequent voiding, back pain during voiding and anal discomfort. The major objective finding was vesico......Symptomatology and clinical manifestations of detrusor sphincter dyssynergia are described in 23 patients without neurological disease. Their cardinal symptoms were recurrent cystitis, enuresis, frequent voiding, back pain during voiding and anal discomfort. The major objective finding...... was vesicoureteral reflux in 11 cases with kidney scarring in 10. Bladder trabeculation was found in 13 patients, bladder hyperreflexia in 8, and significant residual urine in 16 patients. The etiology of detrusor sphincter dyssynergia in non-neurological patients is discussed. By means of exclusion it is most...

  2. Characterization of dynamic physiology of the bladder by optical coherence tomography

    Science.gov (United States)

    Yuan, Zhijia; Keng, Kerri; Pan, Rubin; Ren, Hugang; Du, Congwu; Kim, Jason; Pan, Yingtian

    2012-03-01

    Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide important information that can be used to diagnose the physiological and functional characteristics of biological tissues. Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements. Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.

  3. Fluorescence cystoscopy in patients with non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    I. G. Rusakov

    2015-01-01

    Full Text Available The main challenge of treating non-muscle invasive bladder cancer is multifocal tumors. Current methods of diagnosis are failed to detect all superficial flat tumor lesions in bladder mucosa. The use of fluorescence imaging with 5-aminolevulinic acid (5-ALA allows to improve the sensibility of routine cystoscopy, but low specificity decreases its diagnostic accuracy. The method of fluorescence imaging combined with local fluorescence spectroscopy developed in P.A. Herzen MCRI has been shown to increase the specificity from 71% to 84%. Thus, local fluorescence spectroscopy in visible fluorescence of 5-ALA-induced protoporphyrin allows to perform guided biopsy and decrease the rate of diagnostic mistakes. 

  4. Botulinum toxin for the management of bladder dysfunction.

    Science.gov (United States)

    Schurch, Brigitte

    2006-01-01

    This review highlights a recent innovation in the medical treatment of detrusor overactivity (DO). Anticholinergics are usually the gold standard to treat bladder overactivity. Adverse effects and lack of efficacy are the two main causes for considering alternative treatments. Until recently, invasive surgery (mainly bladder augmentation) was the only available treatment option for patients with intractable DO. This article considers botulinum toxin type A (BTX-A) injection as an alternative treatment to surgery in patients with DO who do not respond to anticholinergic therapy. To identify papers for inclusion in this review, we searched PubMed with the keywords 'botulinum toxin', 'overactive bladder', 'urinary incontinence' and 'neurogenic bladder' for the years 2000-5. Review articles were not included. Abstracts were cited only if they contained important new information. Experimental animal studies and articles or book chapters related to the use of botulinum toxin for other indications (such as achalasia and cervical dystonia) were analysed with regard to the mechanisms of action of botulinum toxin. From this review, it appears that BTX-A injection into the detrusor muscle is a very effective method for treating urinary incontinence secondary to neurogenic detrusor overactivity (NDO), as well as urinary incontinence due to idiopathic overactive bladder (IDO). In both conditions, the duration of effect seems to be at least 6 months. Overall success rates seem to be similar in both patient populations. For NDO, only one evidence-based medicine level 1 study is available, whereas for IDO, only evidence-based medicine level 3 or 4 studies have been published. Particularly in this latter indication, injection technique and outcome parameters vary from study to study and need to be standardised. Without randomised controlled studies aimed at comparing different techniques and dosages, it remains difficult to decide what technique is optimal for treating patients

  5. Post-transcriptional regulation of MRE11 expression in muscle-invasive bladder tumours.

    Science.gov (United States)

    Martin, Rebecca M; Kerr, Martin; Teo, Mark T W; Jevons, Sarah J; Koritzinsky, Marianne; Wouters, Bradly G; Bhattarai, Selina; Kiltie, Anne E

    2014-02-28

    Predictive assays are needed to help optimise treatment in muscle-invasive bladder cancer, where patients can be treated by either cystectomy or radical radiotherapy. Our finding that low tumour MRE11 expression is predictive of poor response to radiotherapy but not cystectomy was recently independently validated. Here we investigated further the mechanism underlying low MRE11 expression seen in poorly-responding patients. MRE11 RNA and protein levels were measured in 88 bladder tumour patient samples, by real-time PCR and immunohistochemistry respectively, and a panel of eight bladder cancer cell lines was screened for MRE11, RAD50 and NBS1 mRNA and protein expression. There was no correlation between bladder tumour MRE11 protein and RNA scores (Spearman's rho 0.064, p=0.65), suggesting MRE11 is controlled post-transcriptionally, a pattern confirmed in eight bladder cancer cell lines. In contrast, NBS1 and RAD50 mRNA and protein levels were correlated (p=0.01 and p=0.03, respectively), suggesting primary regulation at the level of transcription. MRE11 protein levels were correlated with NBS1 and RAD50 mRNA and protein levels, implicating MRN complex formation as an important determinant of MRE11 expression, driven by RAD50 and NBS1 expression. Our findings of the post-transcriptional nature of the control of MRE11 imply that any predictive assays used in patients need to be performed at the protein level rather than the mRNA level.

  6. Gene expression signatures predict outcome in non-muscle invasive bladder carcinoma - a multi-center validation study

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, Karsten; Real, Francisco X.

    2007-01-01

    and carcinoma in situ (CIS) and for predicting disease recurrence and progression. EXPERIMENTAL DESIGN: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic....... CONCLUSION: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non-muscle-invasive bladder cancer. This information may be useful to better guide patient treatment....

  7. Effectiveness of pelvic floor muscle training on symptoms and uroflowmetry parameters in female patients with overactive bladder

    OpenAIRE

    KULAKSIZOĞLU, HALUK; AKAND, MURAT; ÇAKMAKÇI, EVRİM; GÜL, MURAT; SEÇKİN, BEDREDDİN

    2015-01-01

    Background/aim: To evaluate the effects of pelvic floor muscle training (PFMT) on symptoms of overactive bladder (OAB) as well as uroflowmetry parameters and functional bladder capacity. Materials and methods: Fifty-nine female patients with OAB symptoms were included. Patients were assessed by SEAPI-QMM, uroflowmetry, and abdominal ultrasound. A specially designed PFMT program using a Pilates ball was generated for patients. The training period was 1-h sessions twice a week for 6 weeks and ...

  8. A combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Okuno, Yumiko; Zaitsu, Masayoshi; Mikami, Koji; Takeuchi, Takumi; Matsuda, Izuru; Arahira, Satoko

    2017-01-01

    The gold standard for the treatment of muscle-invasive bladder cancer Without metastasis is radical cystectomy. However, there increase patients very elderly and with serious complications. They are not good candidates for invasive surgical operation. Intraarterial infusion of 70 mg/m"2 of cisplatin and 30 mg/m"2 of pirarubicin into bilateral bladder arteries was conducted for 5 patients diagnosed with muscle invasive bladder cancers without distant metastasis. Right and left distribution of anti-cancer drugs was determined based on the location of bladder tumor(s). External beam radiation therapy was commenced immediately following intraarterial infusion. The patients were followed up with clinical and radiographic investigations and bladderbiopsy was performed as needed. Patients were all males who are smoking or with smoking history ranging from 73 to 85 years of age (median 82). The duration between transurethral resection of bladder tumors (TUR-Bt) and intraarterial infusion of anti-cancer drugs was 47.4 days (range 26-68), the median follow-up period after intraarterial infusion was 21.5 months (range 87-547) without death. Total radiation dose was 59.2 ±3.0 Gy. Complete remission was accomplished in all cases. One patient showed intravesical recurrence of non muscle-invasive tumors 45.8 months following intraarterial infusion and underwent TUR-Bt. Two cases underwent bladder biopsies showing no tumors. All patients but one case with bladder recurrence were free of tumor recurrence with radiographic investigation. For adverse events, acute renal failure was in one case and leukocytopenia was in all 5 cases, Grade 2 for one and Grade 3 for 4 cases. Follow-up periods are not long enough, but early results of a combination therapy of selective intraarterial anti-cancer drug infusion and radiation therapy for muscle-invasive bladder cancer were good. (author)

  9. Collagen content in the bladder of men with LUTS undergoing open prostatectomy: A pilot study.

    Science.gov (United States)

    Averbeck, Marcio A; De Lima, Nelson G; Motta, Gabriela A; Beltrao, Lauro F; Abboud Filho, Nury J; Rigotti, Clarice P; Dos Santos, William N; Dos Santos, Steven K J; Da Silva, Luis F B; Rhoden, Ernani L

    2018-03-01

    To evaluate the collagen content in the bladder wall of men undergoing open prostate surgery. From July 2014 to August 2016, men aged ≥ 50 years, presenting LUTS and undergoing open prostate surgery due to benign prostatic enlargement (BPE) or prostate cancer were prospectively enrolled. Preoperative assessment included validated questionnaires (IPSS and OAB-V8), lower urinary tract ultrasound, and urodynamics. Bladder biopsies were obtained during open prostatectomy for determination of collagen content (sirius red-picric acid stain; polarized light analysis). Collagen to smooth muscle ratio (C/M) in the detrusor was measured and its relationship with preoperative parameters was investigated. The level of significance was P non-diabetic patients (17.71 ± 6.82% vs 12.46 ± 5.2%, respectively; P = 0.024). Reduced bladder compliance was also marker for higher collagen content (P = 0.042). Bladder outlet obstruction (BOO) was not a predictor of increased collagen deposition in the bladder wall (P = 0.75). Patients with PVR ≥ 200 mL showed a higher collagen to smooth muscle ratio in the bladder wall (P = 0.036). DM2 and urodynamic parameters, such as increased PVR and reduced bladder compliance, were associated with higher collagen content in the bladder wall of men with LUTS. © 2017 Wiley Periodicals, Inc.

  10. Muscle invasive bladder cancer treated by transurethral resection, followed by external beam radiation and interstitial iridium-192

    International Nuclear Information System (INIS)

    Wijnmaalen, Arendjan; Helle, Peter A.; Koper, Peter C.M.; Jansen, Peter P.; Hanssens, Patrick E.J.; Boeken Kruger, Cornelis G.G.; Putten, Wim L.J. van

    1996-01-01

    Purpose: In our center interstitial radiation has played an important role in the treatment of bladder cancer patients for over 40 years. Radium needles, that were initially used, were replaced by caesium needles in 1983, whereas the afterloading iridium wire technique was adopted in 1989. Patients with solitary tumors (T1, T2 and T3) with a surface diameter of < 5 cm are considered for interstitial radiation. In this study we report on the results of the afterloading iridium wire technique in patients with muscle invasive bladder cancer. Materials and Methods: From May 1989 to September 1993 interstitial radiation using iridium wires was part of the treatment in 46 patients with muscle invasive bladder cancer (37 T2, 9 T3). The mean age was 67 years. After transurethral resection of all visible tumor (if possible), in most cases 40 Gy (20 x 2.0 Gy, midplane dose) external beam radiation was delivered to the true pelvis, followed by 30 Gy interstitial radiation using iridium-192 wires covering the tumor area in the bladder. Results: After a median follow-up of 26 months, bladder relapses occurred in 7 patients. In 5 of them the tumor relapsed in the initial area, in 1 patient elsewhere in the bladder and in 1 patient tumor recurred in and outside the initial site. Recurrence was superficial (T1) in 4 patients. A relapse in the urethra was found once. Metastases developed in 13 patients, in 8 without bladder relapse. During the observation period 17 patients died, 13 due to bladder cancer. The actuarial bladder relapse-free survival at 4 years was 74% and 82% for T2 and T3 tumors, respectively. The actuarial distant metastases-free survival was 65% for both categories. No serious toxicity was recorded. Conclusion: In a selected group of patients with muscle invasive bladder cancer transurethral resection in combination with external beam and interstitial radiation provides an excellent opportunity to preserve the bladder with a high chance of success. Development of

  11. Molecular Expression and Pharmacological Evidence for a Functional Role of Kv7 Channel Subtypes in Guinea Pig Urinary Bladder Smooth Muscle

    Science.gov (United States)

    Afeli, Serge A. Y.; Malysz, John; Petkov, Georgi V.

    2013-01-01

    Voltage-gated Kv7 (KCNQ) channels are emerging as essential regulators of smooth muscle excitability and contractility. However, their physiological role in detrusor smooth muscle (DSM) remains to be elucidated. Here, we explored the molecular expression and function of Kv7 channel subtypes in guinea pig DSM by RT-PCR, qRT-PCR, immunohistochemistry, electrophysiology, and isometric tension recordings. In whole DSM tissue, mRNAs for all Kv7 channel subtypes were detected in a rank order: Kv7.1~Kv7.2Kv7.3~Kv7.5Kv7.4. In contrast, freshly-isolated DSM cells showed mRNA expression of: Kv7.1~Kv7.2Kv7.5Kv7.3~Kv7.4. Immunohistochemical confocal microscopy analyses of DSM, conducted by using co-labeling of Kv7 channel subtype-specific antibodies and α-smooth muscle actin, detected protein expression for all Kv7 channel subtypes, except for the Kv7.4, in DSM cells. L-364373 (R-L3), a Kv7.1 channel activator, and retigabine, a Kv7.2-7.5 channel activator, inhibited spontaneous phasic contractions and the 10-Hz electrical field stimulation (EFS)-induced contractions of DSM isolated strips. Linopiridine and XE991, two pan-Kv7 (effective at Kv7.1-Kv7.5 subtypes) channel inhibitors, had opposite effects increasing DSM spontaneous phasic and 10 Hz EFS-induced contractions. EFS-induced DSM contractions generated by a wide range of stimulation frequencies were decreased by L-364373 (10 µM) or retigabine (10 µM), and increased by XE991 (10 µM). Retigabine (10 µM) induced hyperpolarization and inhibited spontaneous action potentials in freshly-isolated DSM cells. In summary, Kv7 channel subtypes are expressed at mRNA and protein levels in guinea pig DSM cells. Their pharmacological modulation can control DSM contractility and excitability; therefore, Kv7 channel subtypes provide potential novel therapeutic targets for urinary bladder dysfunction. PMID:24073284

  12. Detrusor Acontractility after Acute Spinal Cord Injury-Myth or Reality?

    Science.gov (United States)

    Bywater, Mirjam; Tornic, Jure; Mehnert, Ulrich; Kessler, Thomas M

    2018-01-17

    We assessed urodynamic parameters within the first 40 days after spinal cord injury to investigate whether the detrusor is acontractile during the acute phase of spinal cord injury. We performed a prospective cohort study in 54 patients with neurogenic lower urinary tract dysfunction due to acute spinal cord injury who underwent urodynamic investigation within the first 40 days after injury at a single university spinal cord injury center. Urodynamic investigation revealed an acontractile detrusor in only 20 of the 54 patients (37%) but unfavorable urodynamic parameters in 34 (63%). We found detrusor overactivity in 32 patients, detrusor-sphincter dyssynergia in 25, maximum storage detrusor pressure greater than 40 cm H 2 O in 17, vesicoureteral reflux in 3 and low bladder compliance (less than 20 ml/cm H 2 O) in 1. More than 1 unfavorable urodynamic parameter per patient was possible. In contrast to the common notion of an acontractile detrusor during acute spinal cord injury, almost two-thirds of our patients showed unfavorable urodynamic parameters within the first 40 days after spinal cord injury. Considering that early treatment of neurogenic lower urinary tract dysfunction in patients with acute spinal cord injury might improve the long-term urological outcome, urodynamic investigation should be performed timely to optimize patient tailored therapy. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  13. Neurogenic detrusor overactivity is associated with decreased expression and function of the large conductance voltage- and Ca(2+-activated K(+ channels.

    Directory of Open Access Journals (Sweden)

    Kiril L Hristov

    Full Text Available Patients suffering from a variety of neurological diseases such as spinal cord injury, Parkinson's disease, and multiple sclerosis often develop neurogenic detrusor overactivity (NDO, which currently lacks a universally effective therapy. Here, we tested the hypothesis that NDO is associated with changes in detrusor smooth muscle (DSM large conductance Ca(2+-activated K(+ (BK channel expression and function. DSM tissue samples from 33 patients were obtained during open bladder surgeries. NDO patients were clinically characterized preoperatively with pressure-flow urodynamics demonstrating detrusor overactivity, in the setting of a clinically relevant neurological condition. Control patients did not have overactive bladder and did not have a clinically relevant neurological disease. We conducted quantitative polymerase chain reactions (qPCR, perforated patch-clamp electrophysiology on freshly-isolated DSM cells, and functional studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO patients showed decreased BK channel mRNA expression in comparison to controls. Patch-clamp experiments demonstrated reduced whole cell and transient BK currents (TBKCs in freshly-isolated DSM cells from NDO patients. Functional studies on DSM contractility showed that spontaneous phasic contractions had a decreased sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips isolated from NDO patients. These results reveal the novel finding that NDO is associated with decreased DSM BK channel expression and function leading to increased DSM excitability and contractility. BK channel openers or BK channel gene transfer could be an alternative strategy to control NDO. Future clinical trials are needed to evaluate the value of BK channel opening drugs or gene therapies for NDO treatment and to identify any possible adverse effects.

  14. Treatment results of radiation therapy for muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Langsenlehner, Tanja; Doeller, Carmen; Stranzl-Lawatsch, Heidi; Kapp, Karin S. [Univ. Clinic of Therapeutic Radiology and Oncology, Medical Univ. of Graz (Austria); Quehenberger, Franz [Inst. for Medical Informatics, Statistics and Documentation, Medical Univ. of Graz (Austria); Langsenlehner, Uwe [Internal Outpatient Dept., Steiermaerkische GKK, Graz (Austria); Pummer, Karl [Dept. of Urology, Medical Univ. of Graz (Austria)

    2010-04-15

    Purpose: To assess local control and survival rates in patients with muscle-invasive bladder cancer treated with external-beam radiotherapy and to investigate prognostic factors. Patients and methods: Between 1997 and 2007, 75 patients (male, n = 58; female, n = 17, median age, 74.2 years) with localized transitional cell carcinoma of the bladder (T2, n = 34; T3, n = 32; T4, n = 9) not suitable for radical surgery due to advanced age, comorbidity or inoperability underwent external-beam radiotherapy without simultaneous chemotherapy at the University Clinic of Therapeutic Radiology and Oncology, Medical University of Graz, Austria. A conformal four-field technique was used in all patients to treat the tumor and regional lymph nodes with single daily fractions of 1.8-2 Gy to a total dose of 50-50.4 Gy, followed by a cone-down to encompass the empty bladder which was boosted to 70-70.4 Gy. All patients had undergone transurethral tumor resection prior to radiotherapy which was macroscopically incomplete in 62 patients. Results: Complete response was achieved in 65% of patients. Actuarial 3-year local control and metastases-free survival rates were 52.5% and 63.7%, 3-year local recurrence-free survival rate in complete responders was 71%. In univariate analysis, hydronephrosis, lymph vessel invasion, and macroscopic residual tumor were significantly predictive of disease progression. Hydronephrosis and lymph vessel invasion were also associated with a higher risk of local recurrence. The actuarial 3-year progression-free and overall survival rates were 40.1% and 56.9%, respectively. Conclusion: Radiotherapy is an effective treatment option in terms of local control and survival even in elderly patients with locally advanced bladder cancer not suitable for cystectomy. (orig.)

  15. Chemoradiotherapy for muscle invading bladder carcinoma. final report of a single institutional organ-sparing program

    International Nuclear Information System (INIS)

    Arias, Fernando; Dominguez, Miguel A.; Martinez, Enrique; Illarramendi, Jose J.; Miquelez, Santiago; Pascual, Ignacio; Marcos, Marta

    2000-01-01

    Purpose: Chemoradiotherapy is becoming an alternative to radical cystectomy among patients with muscle invading bladder cancer. We began a prospective study in 1988 to determine the possibilities of conservative treatment and aiming to improve the results obtained by cystectomy alone in invasive bladder cancer. A combination of methotrexate, vinblastine, adriamycin, and cisplatin (M-VAC), followed by radiotherapy and concomitant cisplatin was used. Methods: Fifty patients with good performance status and with stages T2 to T4 operable untreated invasive bladder cancer were entered in the study. Treatment protocol was as follows: (i) cytoreductive transurethral resection; (ii) two cycles of M-VAC chemotherapy; (iii) radiotherapy, 45 Gy on pelvic volume and, at the same time, 20 mg/m 2 cisplatin on days 1 to 5. Cystoscopic evaluation: if there was a complete response, radiotherapy was completed up to 65 Gy; if there was not a complete response, a cystectomy was performed. Median follow-up of the series was 73 months (18-180 m). Results: Tumor response was as follows: 34 complete responses (68%), 9 partial responses (18%), and 7 nonresponses (14%) were observed. The 5-year overall survival and local control were 48% and 47%, respectively. For the complete responder patient, 5-year survival and local control were 65% and 70%, respectively. Severe toxicity was uncommon. The most frequent were leucopenia and cystitis. No treatment-related deaths occurred with either treatment protocol. Conclusions: Conservative combination treatment may be an acceptable alternative to immediate cystectomy in selected patients with bladder cancer, although a randomized clinical trial would be required to produce definitive results

  16. Managing Patients with Non-Muscle Invasive Bladder Cancer: Old Disease, New Ideas

    Directory of Open Access Journals (Sweden)

    Per-Uno Malmström

    2016-04-01

    Full Text Available Prof Per-Uno Malmström opened this symposium on non-muscle invasive bladder cancer (NMIBC by describing the medical and economic burden caused by the increasing incidence of bladder cancer and the lack of new therapeutic options available to address the challenges of the management of NMIBC. Prof Marko Babjuk followed with a presentation that demonstrated that risk stratification using European Organisation for Research and Treatment of Cancer (EORTC and Spanish Urological Club for Oncological Treatment (CUETO risk scores remains a useful tool for determining the best individual treatment options for patients. The next presentation, given by Dr Carsten Ohlmann, described the use of mitomycin C (MMC for low and intermediate-risk patients as per the European Association of Urology (EAU guidelines. However, despite a favourable safety profile, single case reports of severe adverse events following treatment with MMC should not be dismissed. MMC should therefore be given with care, with an emphasis on performing high quality transurethral resection of the bladder (TURB. Prof Bernard Malavaud then presented details of newer diagnostic methods, such as photodynamic diagnosis (PDD and narrow band imaging (NBI, which offer better optical tumour recognition for the surgeon than the old standard of white light cystoscopy. The uptake of PDD and NBI in the future will facilitate an increase in the quality of TURB. Finally, Prof Ashish Kamat explained that recurrence of bladder cancer after bacillus Calmette–Guérin (BCG treatment (‘BCG failure’ needs to be more clearly defined and stratified. He stated that optimal recognition of timing with relation to BCG immunotherapy is critical to determine the next steps. For example, in the past, patients with late recurrence who may have benefitted from challenge with BCG may have been overlooked.

  17. Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Li, Yingrui; Xu, Xun; Song, Luting

    2012-01-01

    sequencing of 66 individual tumor cells from a muscle-invasive bladder transitional cell carcinoma (TCC). Analyses of the somatic mutant allele frequency spectrum and clonal structure revealed that the tumor cells were derived from a single ancestral cell, but that subsequent evolution occurred, leading...... to two distinct tumor cell subpopulations. By analyzing recurrently mutant genes in an additional cohort of 99 TCC tumors, we identified genes that might play roles in the maintenance of the ancestral clone and in the muscle-invasive capability of subclones of this bladder cancer, respectively...

  18. Effect of diabetes on the ion pumps of the bladder.

    Science.gov (United States)

    Mustafa, Seham

    2013-01-01

    To establish whether the activities of Na+/K+-adenosine triphosphatase (ATPase) and Ca2+-ATPases ion pumps in bladder smooth muscle are altered as a consequence of diabetes and, if so, how this might contribute to bladder cystopathy. Urinary bladder dysfunction is a common occurrence in patients with diabetes. Pressure generation requires calcium and cytosolic ATP. Activities of these pumps are responsible for calcium homeostasis. Rat urinary detrusor muscle strips were suspended in organ baths containing Krebs solution for isometric tension recording. Tissue responses to the Na+/K+-ATPase pump inhibitor, ouabain, the plasma membrane Ca2+ ATPase inhibitor, vanadate, and the sarcoplasmic reticulum Ca2+ ATPase inhibitor, cyclopiazonic acid (CPA), were examined from normal and streptozocin-induced diabetic rats for 2, 4, and 12 weeks. Ouabain, vanadate, and CPA caused concentration-dependent contractions of bladder strips from diabetic and normal rats. The degree of contraction of diabetic bladder muscle was lower than that of controls. This reduction was a function of duration of diabetes. For ouabain, the reduction peaked at 2 weeks, with partial restoration to normal after diabetes induction. For vanadate and CPA, the reduction increased with the duration of diabetes. The ion pumps are important modulators of bladder smooth muscle tone, and in a rat model of streptozotocin-induced diabetes, the activity of these pumps is impaired. Although this is only a single model of diabetes, these findings suggest that a defect in these pumps may be an important component of the development of diabetic bladder cystopathy. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Muscarinic Acetylcholine Receptor M3 Mutation Causes Urinary Bladder Disease and a Prune-Belly-like Syndrome.

    Science.gov (United States)

    Weber, Stefanie; Thiele, Holger; Mir, Sevgi; Toliat, Mohammad Reza; Sozeri, Betül; Reutter, Heiko; Draaken, Markus; Ludwig, Michael; Altmüller, Janine; Frommolt, Peter; Stuart, Helen M; Ranjzad, Parisa; Hanley, Neil A; Jennings, Rachel; Newman, William G; Wilcox, Duncan T; Thiel, Uwe; Schlingmann, Karl Peter; Beetz, Rolf; Hoyer, Peter F; Konrad, Martin; Schaefer, Franz; Nürnberg, Peter; Woolf, Adrian S

    2011-11-11

    Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. We here describe a muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation in familial congenital bladder malformation associated with a prune-belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the M3 muscarinic acetylcholine receptor, which we show is present in developing renal epithelia and bladder muscle. These observations may imply that M3 has a role beyond its known contribution to detrusor contractions. This Mendelian disease caused by a muscarinic acetylcholine receptor mutation strikingly phenocopies Chrm3 null mutant mice. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  20. Muscle invasive bladder cancer treated by transurethral resection, followed by external beam radiation and interstitial iridium-192

    International Nuclear Information System (INIS)

    Wijnmaalen, Arendjan; Helle, Peter A.; Koper, Peter C.M.; Jansen, Peter P.; Hanssen, Patrick E.; Kruger, Cornelis G.G. Boeken; Putten, Wim L.J. van

    1997-01-01

    Purpose: To evaluate the results of transurethral resection (TUR), external beam radiotherapy (EBRT), and interstitial radiation (IRT) with iridium-192, using the afterloading technique in patients with muscle invasive bladder cancer. Methods and Materials: From May 1989 until September 1995, 66 patients with primary, solitary muscle invasive bladder cancer were treated with TUR, EBRT, and IRT, aiming at bladder preservation. According to the protocol, in three patients low-dose EBRT was applied, whereas 63 patients received high-dose EBRT. Immediately prior to IRT, 42 patients underwent a lymphnode dissection, and in 16 cases a partial cystectomy was performed. For IRT, two to five catheters were used and IRT was started within 24 h after surgery. The majority of patients received 30 Gy of IRT, with a mean dose rate of .58 Gy/h. In three patients, additional EBRT was applied following IRT. Follow-up consisted of regular cystoscopies, mostly done during joint clinics of urologist and radiation oncologist, with urine cytology routinely performed. The median follow-up period was 26 months. The Kaplan-Meier method was used for the determination of survival rates. Results: In seven patients, a bladder relapse developed. The probability of remaining bladder relapse free at 5 years was 88%. The bladder was preserved in 98% of the surviving patients. Metastases developed in 16 patients, and the probability of remaining metastasis free at 5 years was 66%. The cumulative 5-year overall and bladder and distant relapse free survival were 48% and 69%, respectively. Acute toxicity was not serious in the majority of cases; surgical correction of a persisting vesicocutaneous fistula was necessary in two patients, whereas a wound toilet had to be performed in another patient. Serious late toxicity (bladder, RTOG Grade 3) was experienced by only one patient. Conclusions: Interstitial radiation preceded by TUR and EBRT, in a selected group of patients with muscle invasive bladder

  1. Contrast-enhanced computed tomography of the primary tumor in muscle invasive carcinoma of the urinary bladder

    International Nuclear Information System (INIS)

    Sager, E.M.

    1991-01-01

    Patients with muscle invasive carcinoma of the urinary bladder were examined with contrast-enhanced CT of the primary tumor. A specially designed technique was developed to increase the diagnostic potential of CT. The most important points about the technique were controlled filling of the bladder, the use of thin slices, series of scans before and after intravenous injection of contrast medium, and long scanning times in the precontrast series. The absorbed dose to the patient resulting from the new technique was found to be within the range of the dose from urography or barium enema. This dose was considered to be acceptable given the diagnostic gain of the procedure. Features of irradiated bladder tumors were analysed to find which parameter correlated with persistent malignancy. High contrast enhancement of a tumor relative to the bladder wall was found to be the best indicator of a malignant tumour after irradiation. 127 refs

  2. Myogenic conversion of bladder fibroblasts by construction and ...

    African Journals Online (AJOL)

    use

    2011-12-21

    Dec 21, 2011 ... Gene therapy of detrusor underactivity, by autologous cells transplantation, is limited by the ... vivo is an alternative strategy of bladder repair, because it ... tissues. Extraction of total RNA was performed by following the.

  3. Bladder pressure sensors in an animal model

    NARCIS (Netherlands)

    Koldewijn, E. L.; van Kerrebroeck, P. E.; Schaafsma, E.; Wijkstra, H.; Debruyne, F. M.; Brindley, G. S.

    1994-01-01

    Urinary incontinence due to detrusor hyperreflexia might be inhibited on demand if changes in bladder pressure could be detected by sensors and transferred into pudendal nerve electrostimulation. The aim of this study is to investigate how the bladder wall reacts on different sensor implants.

  4. Muscle invasive bladder cancer treated by transurethral resection, followed by external beam radiation and interstitial iridium-192

    NARCIS (Netherlands)

    A. Wijnmaalen (Arendjan); P.A. Helle (Peter); P.C.M. Koper (Peter); P.P. Jansen (Peter); P. Hanssens (Patrick); C.G.G. Boeken Kruger (Cornelis); W.L.J. van Putten (Wim)

    1997-01-01

    textabstractPurpose: To evaluate the results of transurethral resection (TUR), external beam radiotherapy (EBRT), and interstitial radiation (IRT) with iridium-192, using the afterloading technique in patients with muscle invasive bladder cancer. Methods and Materials: From May 1989 until September

  5. Chromosomal imbalance in the progression of high-risk non-muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Zieger, Karsten; Wiuf, Carsten; Jensen, Klaus Møller-Ernst; Ørntoft, Torben Falck; Dyrskjøt, Lars

    2009-01-01

    Non-muscle invasive bladder neoplasms with invasion of the lamina propria (stage T1) or high grade of dysplasia are at 'high risk' of progression to life-threatening cancer. However, the individual course is difficult to predict. Chromosomal instability (CI) is associated with high tumor stage and grade, and possibly with the risk of progression. To investigate the relationship between CI and subsequent disease progression, we performed a case-control-study of 125 patients with 'high-risk' non-muscle invasive bladder neoplasms, 67 with later disease progression, and 58 with no progression. Selection criteria were conservative (non-radical) resections and full prospective clinical follow-up (> 5 years). We investigated primary lesions in 59, and recurrent lesions in 66 cases. We used Affymetrix GeneChip ® Mapping 10 K and 50 K SNP microarrays to evaluate genome wide chromosomal imbalance (loss-of-heterozygosity and DNA copy number changes) in 48 representative tumors. DNA copy number changes of 15 key instability regions were further investigated using QPCR in 101 tumors (including 25 tumors also analysed on 50 K SNP microarrays). Chromosomal instability did not predict any higher risk of subsequent progression. Stage T1 and high-grade tumors had generally more unstable genomes than tumors of lower stage and grade (mostly non-primary tumors following a 'high-risk' tumor). However, about 25% of the 'high-risk' tumors had very few alterations. This was independent of subsequent progression. Recurrent lesions represent underlying field disease. A separate analysis of these lesions did neither reflect any difference in the risk of progression. Of specific chromosomal alterations, a possible association between loss of chromosome 8p11 and the risk of progression was found. However, the predictive value was limited by the heterogeneity of the changes. Chromosomal instability (CI) was associated with 'high risk' tumors

  6. Muscle invasive bladder cancer in Upper Egypt: the shift in risk factors and tumor characteristics

    International Nuclear Information System (INIS)

    Zarzour, Ali H; Selim, Mohie; Abd-Elsayed, Alaa A; Hameed, Diaa A; AbdelAziz, Mohammad A

    2008-01-01

    In Egypt, where bilharziasis is endemic, bladder cancer is the commonest cancer in males and the 2 nd in females; squamous cell carcinoma (SCC) is the commonest type found, with a peculiar mode of presentation. The aim of this study is to identify and rank the risk factors of muscle invasive bladder cancer (MIBC) in Upper Egypt and describe its specific criteria of presentation and histopathology. This is an analytical, hospital based, case controlled study conducted in south Egypt cancer institute through comparing MIBC cases (n = 130) with age, sex and residence matched controls (n = 260) for the presence of risk factors of MIBC. Data was collected by personal interview using a well designed questionnaire. Patients' records were reviewed for histopathology and Radiologic findings. The risk factors of MIBC were positive family history [Adjusted odds ratio (AOR) = 7.7], exposure to pesticides [AOR = 6.2], bladder stones [AOR = 5], consanguinity [AOR = 3.9], recurrent cystitis [AOR = 3.1], bilharziasis [odds ratio (OR) = 5.8] and smoking [OR = 5.3]. SCC represented 67.6% of cases with burning micturition being the presenting symptom in 73.8%. MIBC in Upper Egypt is usually of the SCC type (although its percentage is decreasing), occurs at a younger age and presents with burning micturition rather than hematuria. Unlike the common belief, positive family history, parents' consanguinity, exposure to pesticides and chronic cystitis seem to play now more important roles than bilharziasis and smoking in the development of this disease in this area

  7. Promising results with image guided intensity modulated radiotherapy for muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Whalley, D.; Caine, H.; McCloud, P.; Guo, L.; Kneebone, A.; Eade, T.

    2015-01-01

    To describe the feasibility of image guided intensity modulated radiotherapy (IG-IMRT) using daily soft tissue matching in the treatment of bladder cancer. Twenty-eight patients with muscle-invasive carcinoma of the bladder were recruited to a protocol of definitive radiation using IMRT with accelerated hypofractionation with simultaneous integrated boost (SIB). Isotropic margins of .5 and 1 cm were used to generate the high risk and intermediate risk planning target volumes respectively. Cone beam CT (CBCT) was acquired daily and a soft tissue match was performed. Cystoscopy was scheduled 6 weeks post treatment. The median age was 83 years (range 58-92). Twenty patients had stage II or III disease, and eight were stage IV. Gross disease received 66 Gy in 30 fractions in 11 patients (ten with concurrent chemotherapy) or 55 Gy in 20 fractions for those of poorer performance status or with palliative intent. All patients completed radiation treatment as planned. Three patients ceased chemotherapy early due to toxicity. Six patients (21 %) had acute Grade ≥ 2 genitourinary (GU) toxicity and six (21 %) had acute Grade ≥ 2 gastrointestinal (GI) toxicity. Five patients (18 %) developed Grade ≥2 late GU toxicity and no ≥2 late GI toxicity was observed. Nineteen patients underwent cystoscopy following radiation, with complete response (CR) in 16 cases (86 %), including all patients treated with chemoradiotherapy. Eight patients relapsed, four of which were local relapses. Of the patients with local recurrence, one underwent salvage cystectomy. For patients treated with definitive intent, freedom from locoregional recurrence (FFLR) and overall survival (OS) was 90 %/100 % for chemoradiotherapy versus 86 %/69 % for radiotherapy alone. IG- IMRT using daily soft tissue matching is a feasible in the treatment of bladder cancer, enabling the delivery of accelerated synchronous integrated boost with good early local control outcomes and low toxicity

  8. Defining Priorities to Improve Patient Experience in Non-Muscle Invasive Bladder Cancer.

    Science.gov (United States)

    Garg, Tullika; Connors, Jill Nault; Ladd, Ilene G; Bogaczyk, Tyler L; Larson, Sharon L

    2018-01-20

    Although approximately 75% of bladder cancers are non-muscle invasive (NMIBC) at diagnosis, most research tends to focus on invasive disease (e.g., experiences related to radical cystectomy and urinary diversion). There is a lack of studies on quality of life, and especially qualitative research, in bladder cancer generally. As a result, relatively little is known about the experiences and needs of NMIBC patients. To understand patient experience, define care priorities, and identify targets for care improvement in NMIBC across the cancer continuum. Through focus groups, patients treated for NMIBC (stage influences on decision-making, and role of social support. Patients with NMIBC desired timely access to care and honest and caring provider communication. They described urinary function and emotional quality of life changes resulting from diagnosis and treatment. Avoiding cystectomy and being alive for family were the major decision influencers. In this qualitative study, we identified access to care, provider characteristics and communication, quality of life, values/influences on decision-making, and social support as priority areas to improve patient experience in NMIBC. Care redesign efforts should focus on improving access, enhancing provider communication, reducing side effects, and supporting caregiver roles.

  9. Detrusor instability in children with recurrent urinary tract infection and/or enuresis. I

    DEFF Research Database (Denmark)

    Qvist, N; Kristensen, E S; Nielsen, K K

    1986-01-01

    Forty-one children, aged 5-15 years, were referred because of recurrent urinary infections and/or enuresis. They were examined prospectively by means of cystometry. CO2 cystometry revealed detrusor instability in 18 children (44%), but if complete reproducibility were to be requested in repeated ...... tests, only 7 children (17%) would have presented instability. Detrusor instability was not significantly related to definite pathological changes in the urinary tract or to irritative bladder symptoms.......Forty-one children, aged 5-15 years, were referred because of recurrent urinary infections and/or enuresis. They were examined prospectively by means of cystometry. CO2 cystometry revealed detrusor instability in 18 children (44%), but if complete reproducibility were to be requested in repeated...

  10. Effects of acute urinary bladder overdistension on bladder response during sacral neurostimulation.

    Science.gov (United States)

    Bross, S; Schumacher, S; Scheepe, J R; Zendler, S; Braun, P M; Alken, P; Jünemann, K

    1999-10-01

    Urinary retention and micturition disorders after overdistension are clinically well-known complications of subvesical obstruction. We attempted to evaluate whether bladder overdistension influences bladder response and whether overdistension supports detrusor decompensation. Following lumbal laminectomy in 9 male foxhounds, the sacral anterior roots S2 and S3 were placed into a modified Brindley electrode for reproducible and controlled detrusor activation. The bladder was filled in stages of 50 ml from 0 to 700 ml, corresponding to an overdistension. At each volume, the bladder response during sacral anterior root stimulation was registered. After overdistension, the bladder was refilled stepwise from 0 to 300 ml and stimulated. In all dogs, the bladder response was influenced by the intravesical volume. The maximum pressure (mean 69.1 cm H(2)O) was observed at mean volume of 100 ml. During overdistension, a significant reduction in bladder response of more than 80% was seen. After overdistension, a significant reduction in intravesical pressure of 19.0% was observed. In 2 cases, reduction in bladder response was more than 50% after a single overdistension. We conclude that motoric bladder function is influenced during and after overdistension. A single bladder overdistension can support acute and long-lasting detrusor decompensation. In order to protect motoric bladder function, bladder overdistension must be prevented.

  11. Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats.

    Science.gov (United States)

    Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Gautam, Sudha Silwal; Nishizawa, Osamu

    2014-10-01

    This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats. Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats. Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity. © 2014 The Japanese Urological Association.

  12. The prognostic factors affecting survival in muscle invasive bladder cancer treated with radiotherapy

    International Nuclear Information System (INIS)

    Chung, Woong Ki; Oh, Bong Ryoul; Ahn, Sung Ja; Nah, Byung Sik; Kwon, Dong Deuk; Park, Kwang Sung; Ryu, Soo Bang; Park, Yang Il

    2002-01-01

    This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Twenty eight patient with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were performed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uniformed in 3. Radiation therapy was performed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was performed on the prognostic factors affecting the survival rate. The survival rate was 76%, 46%, 33%, 33% at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, T-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uni- and multivariate analysis. In univariate analysis, the T-stage (ρ 0.078) and radiation dose (ρ = 0.051) were marginally significant, and the treatment response (ρ = 0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival rate. The

  13. The prognostic factors affecting survival in muscle invasive bladder cancer treated with radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Woong Ki; Oh, Bong Ryoul; Ahn, Sung Ja; Nah, Byung Sik; Kwon, Dong Deuk; Park, Kwang Sung; Ryu, Soo Bang; Park, Yang Il [Chonnam National University Medical School, Chonnam National University Hospital, Kwangju (Korea, Republic of)

    2002-06-15

    This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Twenty eight patient with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were performed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uniformed in 3. Radiation therapy was performed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was performed on the prognostic factors affecting the survival rate. The survival rate was 76%, 46%, 33%, 33% at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, T-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uni- and multivariate analysis. In univariate analysis, the T-stage ({rho} 0.078) and radiation dose ({rho} = 0.051) were marginally significant, and the treatment response ({rho} = 0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival

  14. Layer-dependent role of collagen recruitment during loading of the rat bladder wall.

    Science.gov (United States)

    Cheng, Fangzhou; Birder, Lori A; Kullmann, F Aura; Hornsby, Jack; Watton, Paul N; Watkins, Simon; Thompson, Mark; Robertson, Anne M

    2018-04-01

    In this work, we re-evaluated long-standing conjectures as to the source of the exceptionally large compliance of the bladder wall. Whereas these conjectures were based on indirect measures of loading mechanisms, in this work we take advantage of advances in bioimaging to directly assess collagen fibers and wall architecture during biaxial loading. A custom biaxial mechanical testing system compatible with multiphoton microscopy was used to directly measure the layer-dependent collagen fiber recruitment in bladder tissue from 9 male Fischer rats (4 adult and 5 aged). As for other soft tissues, the bladder loading curve was exponential in shape and could be divided into toe, transition and high stress regimes. The relationship between collagen recruitment and loading curves was evaluated in the context of the inner (lamina propria) and outer (detrusor smooth muscle) layers. The large extensibility of the bladder was found to be possible due to folds in the wall (rugae) that provide a mechanism for low resistance flattening without any discernible recruitment of collagen fibers throughout the toe regime. For more extensible bladders, as the loading extended into the transition regime, a gradual coordinated recruitment of collagen fibers between the lamina propria layer and detrusor smooth muscle layer was found. A second important finding was that wall extensibility could be lost by premature recruitment of collagen in the outer wall that cut short the toe region. This change was correlated with age. This work provides, for the first time, a mechanistic understanding of the role of collagen recruitment in determining bladder extensibility and capacitance.

  15. Pathways Involving Beta-3 Adrenergic Receptors Modulate Cold Stress-Induced Detrusor Overactivity in Conscious Rats.

    Science.gov (United States)

    Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Nishizawa, Osamu

    2015-01-01

    To investigate pathways involving beta-3 adrenergic receptors (ARs) in detrusor overactivity induced by cold stress, we determined if the beta-3 AR agonist CL316243 could modulate the cold stress-induced detrusor overactivity in normal rats. Two days prior to cystometric investigations, the bladders of 10-week-old female Sprague-Dawley rats were cannulated. Cystometric measurements of the unanesthetized, unrestricted rats were taken to estimate baseline values at room temperature (RT, 27 ± 2 °C) for 20 min. They were then intravenously administered vehicle, 0.1, or 1.0 mg/kg CL316243 (n = 6 in each group). Five minutes after the treatments, they were gently and quickly transferred to the low temperature (LT, 4 ± 2 °C) room for 40 min where the cystometric measurements were again made. Afterward, the rats were returned to RT for final cystometric measurements. The cystometric effects of CL316243 were also measured at RT (n = 6 in each group). At RT, both low and high dose of CL316243 decreased basal and micturition pressure while the high dose (1.0 mg/kg) significantly increased voiding interval and bladder capacity. During LT exposure, the high dose of CL316243 partially reduced cold stress-induced detrusor overactivity characterized by increased basal pressure and urinary frequency. The high drug dose also significantly inhibited the decreases of both voiding interval and bladder capacity compared to the vehicle- and low dose (0.1 mg/kg)-treated rats. A high dose of the beta-3 agonist CL316243 could modulate cold stress-induced detrusor overactivity. Therefore, one of the mechanisms in cold stress-induced detrusor overactivity includes a pathway involving beta-3 ARs. © 2014 Wiley Publishing Asia Pty Ltd.

  16. INITIAL EXPERIENCE WITH ADJUVANT INTRAVESICAL THERMOCHEMOTHERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    K. A. Pavlenko

    2011-01-01

    Full Text Available Objective: to reveal the benefits of adjuvant intravesical thermochemotherapy (TCT and to evaluate its efficiency in the treatment of moderateand high-risk non-muscle invasive bladder cancer (BC.Subjects and methods. In the period 2009 to 2010, the Urology Clinic, Federal Medical Biophysical Center, treated 21 patients with nonmuscle invasive BC, by using a Thermotron RF-8 clinical hyperthermal system. Intravesical TCT with mitomycin C 40 mg for 60–80 min was performed at 42 ± 2 °С as one session weekly for 6 weeks. Control cystoscopy was carried out every 3 months.Results. Of the 21 patients, 19 were found to tolerate the procedure well. No complications were recorded in these patients during the sessions and throughout the course of intravesical TCT. A recurrence was histologically verified in 2 patients at 6-month follow-up. There was no evidence suggesting a recurrence in 12 (57.14 % patients at one-year follow-up. The follow-up of the other patients is now less than 12 months.Conclusion. The proposed method of hyperthermia may be used as an alternative to the existing one of intracavitary hyperthermia to treat high- and moderate-risk BC and in case of inefficiency of other adjuvant therapy options for non-muscle invasive BC.

  17. Summary and Recommendations from the National Cancer Institute's Clinical Trials Planning Meeting on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer

    NARCIS (Netherlands)

    Lerner, S.P.; Bajorin, D.F.; Dinney, C.P.; Efstathiou, J.A.; Groshen, S.; Hahn, N.M.; Hansel, D.; Kwiatkowski, D.; O'Donnell, M.; Rosenberg, J.; Svatek, R.; Abrams, J.S.; Al-Ahmadie, H.; Apolo, A.B.; Bellmunt, J.; Callahan, M.; Cha, E.K.; Drake, C.; Jarow, J.; Kamat, A.; Kim, W.; Knowles, M.; Mann, B.; Marchionni, L.; McConkey, D.; McShane, L.; Ramirez, N.; Sharabi, A.; Sharpe, A.H.; Solit, D.; Tangen, C.M.; Amiri, A.T.; Allen, E. Van; West, P.J.; Witjes, J.A.; Quale, D.Z.

    2016-01-01

    The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from

  18. An evaluation of morphological and functional multi-parametric MRI sequences in classifying non-muscle and muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Panebianco, Valeria; Barchetti, Giovanni; Grompone, Marcello Domenico; Del Monte, Maurizio; Carano, Davide; Catalano, Carlo; De Berardinis, Ettore; Leonardo, Constantino; Simone, Giuseppe; Gallucci, Michele; National Cancer Insitute, Rome; Catto, James

    2017-01-01

    Our goal is to determine the ability of multi-parametric magnetic resonance imaging (mpMRI) to differentiate muscle invasive bladder cancer (MIBC) from non-muscle invasive bladder cancer (NMIBC). Patients underwent mpMRI before tumour resection. Four MRI sets, i.e. T2-weighted (T2W) + perfusion-weighted imaging (PWI), T2W plus diffusion-weighted imaging (DWI), T2W + DWI + PWI, and T2W + DWI + PWI + dif-fusion tensor imaging (DTI) were interpreted qualitatively by two radiologists, blinded to histology results. PWI, DWI and DTI were also analysed quantitatively. Accuracy was determined using histopathology as the reference standard. A total of 82 tumours were analysed. Ninety-six percent of T1-labeled tumours by the T2W + DWI + PWI image set were confirmed to be NMIBC at histopathology. Overall accuracy of the complete mpMRI protocol was 94% in differentiating NMIBC from MIBC. PWI, DWI and DTI quantitative parameters were shown to be significantly different in cancerous versus non-cancerous areas within the bladder wall in T2-labelled lesions. MpMRI with DWI and DTI appears a reliable staging tool for bladder cancer. If our data are validated, then mpMRI could precede cystoscopic resection to allow a faster recognition of MIBC and accelerated treatment pathways. (orig.)

  19. An evaluation of morphological and functional multi-parametric MRI sequences in classifying non-muscle and muscle invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, Valeria; Barchetti, Giovanni; Grompone, Marcello Domenico; Del Monte, Maurizio; Carano, Davide; Catalano, Carlo [Sapienza Univ. Rome (Italy). Dept. of Radiological Sciences, Oncology and Pathology; De Berardinis, Ettore; Leonardo, Constantino [Sapienza Univ. Rome (Italy). Dept. of Gynaecological-Obstetric and Urological Sciences; Simone, Giuseppe; Gallucci, Michele [' ' Regina Elena' ' National Cancer Insitute, Rome (Italy). Dept. of Urology; Catto, James [Sheffield Univ. (United Kingdom). Aademic Urology Unit

    2017-09-15

    Our goal is to determine the ability of multi-parametric magnetic resonance imaging (mpMRI) to differentiate muscle invasive bladder cancer (MIBC) from non-muscle invasive bladder cancer (NMIBC). Patients underwent mpMRI before tumour resection. Four MRI sets, i.e. T2-weighted (T2W) + perfusion-weighted imaging (PWI), T2W plus diffusion-weighted imaging (DWI), T2W + DWI + PWI, and T2W + DWI + PWI + dif-fusion tensor imaging (DTI) were interpreted qualitatively by two radiologists, blinded to histology results. PWI, DWI and DTI were also analysed quantitatively. Accuracy was determined using histopathology as the reference standard. A total of 82 tumours were analysed. Ninety-six percent of T1-labeled tumours by the T2W + DWI + PWI image set were confirmed to be NMIBC at histopathology. Overall accuracy of the complete mpMRI protocol was 94% in differentiating NMIBC from MIBC. PWI, DWI and DTI quantitative parameters were shown to be significantly different in cancerous versus non-cancerous areas within the bladder wall in T2-labelled lesions. MpMRI with DWI and DTI appears a reliable staging tool for bladder cancer. If our data are validated, then mpMRI could precede cystoscopic resection to allow a faster recognition of MIBC and accelerated treatment pathways. (orig.)

  20. Efficacy of pelvic floor muscle training in women with overactive bladder syndrome: a systematic review.

    Science.gov (United States)

    Monteiro, Silvia; Riccetto, Cassio; Araújo, Angélica; Galo, Laryssa; Brito, Nathália; Botelho, Simone

    2018-04-11

    Our objective was to evaluate the effectiveness of pelvic floor muscle training (PFMT) in reducing overactive bladder (OAB) symptoms in women. Searches were performed at MEDLINE, PubMed, Physiotherapy Evidence Database (PEDro), Scielo, and Central Cochrane Library PubMed until January 2017. Controlled trials were researched by two independent reviewers. Eligible studies were restricted to random and controlled clinical trials that investigated the effectiveness of PFMT in decreasing OAB symptoms. Qualitative methodology was evaluated using the PEDro scale. Data was analyzed and interpreted qualitatively. The final search retrieved eight studies (n = 1161 women with urgency symptoms), which were published between 2002 and 2016. The methodological scores varied between 4 and 7 in the PEDro scale. PFMT, with the objective of controlling urgent micturition, demonstrated improvements in quality of life in women with OAB. Most data in this revision came from small- to moderate-sized trials, with different and inconsistent outcome measures, which could have impacted the end results. The literature regarding the effectiveness of PFMT in OAB remains heterogeneous and inconclusive.

  1. Guideline-based management of non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Justin R Gregg

    2015-01-01

    Full Text Available Introduction: Non-muscle invasive bladder cancer (NMIBC represents a broad spectrum of disease, the hallmarks of which include disease recurrence and progression. Clinicians have a number of surgical and therapeutic options at their disposal when treating this disease, and the underlying evidence continues to evolve. A number of professional organizations have invested in the development of clinical practice guidelines to guide patient management. Materials and Methods: We review and summarize four major guidelines, the American Urological Association, the European Association of Urology, the International Consultation on Urological Disease and the National Comprehensive Cancer Network. Results: Guideline panels differed in their composition, methodological approach and structure of recommendations. Despite this, many recommendations were similar between various panels, although differences are present in panel recommendations related to initial diagnosis and treatment, adjuvant therapy and disease surveillance. Conclusions: Guideline recommendations are similar at many decision points that clinicians face when managing NMIBC, although they are far from uniform. While future prospective, well-designed studies will hopefully clarify NMIBC management, urologists ultimately must rely on a combination of evidence-based recommendations, which they should seek to integrate with patients' values and preferences and the individual circumstances to provide the best possible patient care.

  2. Bladder cancer: the combination of chemotherapy and irradiation in the treatment of patients with muscle-invading tumors

    International Nuclear Information System (INIS)

    Shipley, William U.; Zietman, Anthony L.

    1995-01-01

    In the USA the recommended treatment for patients with muscle-invading transitional cell cancer of the bladder is usually radical cystectomy. Conservative surgery (transurethral resection and partial cystectomy), irradiation, and cis-platinum based systemic chemotherapy are, however, each effective for some patients. Although they provide the opportunity for bladder preservation, each modality, when used alone, is inferior to radical cystectomy in terms of local control and, perhaps, survival. Initial response and local control rates are improved when a multimodality approach is used. Up to 85% of patients selected for bladder sparing therapy on the basis of their initial response to chemo-radiation may keep their bladders. This figure could increase further when other powerful prognostic factors, such as the presence of hydronephrosis or carcinoma in situ, are taken into account in initial patient selection. Deferring the patient from immediate cystectomy does not appear to compromise survival. The most appropriate sequencing of radiation and chemotherapy is yet to be established. Concomitant cis-platinum and irradiation improves local control and bladder preservation when compared with irradiation alone but does not decrease the metastatic rate. It is hoped that the well recognized activity of cis-platinum based combination chemotherapy in advanced disease will translate into effective eradication of micrometastatic disease (known to be present in up to 40% of patients at diagnosis). This has yet to be clearly demonstrated in a randomized trial. The addition of combination chemotherapy to radiation does not increase bladder morbidity but carries a considerable systemic risk. Thus, despite promising phase II studies, until a survival benefit is proven in a randomized trial, neoadjuvant or adjuvant combination chemotherapy in conjunction with irradiation should continue to be regarded as experimental

  3. Adaptive radiotherapy in muscle invasive urinary bladder cancer - An effective method to reduce the irradiated bowel volume

    International Nuclear Information System (INIS)

    Tuomikoski, Laura; Collan, Juhani; Keyrilaeinen, Jani; Visapaeae, Harri; Saarilahti, Kauko; Tenhunen, Mikko

    2011-01-01

    Background and purpose: To evaluate the benefits of adaptive radiotherapy for bladder cancer in decreasing irradiation of small bowel. Material and methods: Five patients with muscle invasive bladder cancer received adaptive radiotherapy to a total dose of 55.8-65 Gy with daily cone-beam computed tomography scanning. The whole bladder was treated to 45-50.4 Gy, followed by a partial bladder boost. The plan of the day was chosen from 3 to 4 pre-planned treatment plans according to the visible extent of bladder wall in cone-beam computed tomography images. Dose volume histograms for intestinal cavity volumes were constructed and compared with corresponding histograms calculated for conventional non-adaptive radiotherapy with single treatment plan of 2 cm CTV-PTV margins. CTV dose coverage in adaptive treatment technique was compared with CTV dose coverage in conventional radiotherapy. Results: The average volume of intestinal cavity receiving ≥45 Gy was reduced from 335 ± 106 cm 3 to 180 ± 113 cm 3 (1SD). The maximum volume of intestinal cavity spared at 45 Gy on a single patient was 240 cm 3 , while the minimum volume was 65 cm 3 . The corresponding reduction in average intestinal cavity volume receiving ≥45 Gy calculated for the whole bladder treatment only was 66 ± 36 cm 3 . CTV dose coverage was improved on two out of five patients and decreased on three patients. Conclusions: Adaptive radiotherapy considerably reduces dose to the small bowel, while maintaining the dose coverage of CTV at similar level when compared to the conventional treatment technique.

  4. Enhancement of rat bladder contraction by artificial sweeteners via increased extracellular Ca2+ influx

    International Nuclear Information System (INIS)

    Dasgupta, Jaydip; Elliott, Ruth A.; Doshani, Angie; Tincello, Douglas G.

    2006-01-01

    Introduction: Consumption of carbonated soft drinks has been shown to be independently associated with the development of overactive bladder symptoms (OR 1.62, 95% CI 1.18, 2.22) [Dallosso, H.M., McGrother, C.W., Matthews, R.J., Donaldson, M.M.K., 2003. The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int. 92, 69-77]. We evaluated the effects of three artificial sweeteners, acesulfame K, aspartame and sodium saccharin, on the contractile response of isolated rat detrusor muscle strips. Methods: Strips of detrusor muscle were placed in an organ bath and stimulated with electrical field stimulation (EFS) in the absence and presence of atropine, and with α,β methylene ATP, potassium, calcium and carbachol. Results: Sweeteners 10 -7 M to 10 -2 M enhanced the contractile response to 10 Hz EFS compared to control (p -6 M, aspartame 10 -7 M and sodium saccharin 10 -7 M. Acesulfame K 10 -6 M increased the maximum contractile response to α,β methylene ATP by 35% (± 9.6%) (p -6 M increased the log EC 5 from -2.79 (± 0.037) to -3.03 (± 0.048, p -7 M from -2.74 (± 0.03) to 2.86 (± 0.031, p +2 channels

  5. Bladder cancer: The combination of chemotherapy and irradiation in the treatment of patients with muscle-invading tumors

    International Nuclear Information System (INIS)

    Shipley, William U.; Zietman, Anthony L.

    1996-01-01

    In the USA the recommended treatment for patients with muscle-invading transitional cell cancer of the bladder is usually radical cystectomy. Conservative surgery irradiation, and cisplatin-based systemic chemotherapy are, however, each effective for some patients. Although they provide the opportunity for bladder preservation, each modality, when used alone, is inferior to radical cystectomy in terms of local control and, perhaps, survival. Many recent publications have now documented the efficacy of combined modality treatment protocols employing all three of these modalities together. All employ a selective approach in which the patients only receive full-dose radiation if they have had a complete response to induction CMT. Overall survival data for T2-T3a patients are certainly as good as any reported cystectomy series of similarly clinically staged and similar aged patients. Radiation adds very significantly to the transurethral resection and systemic chemotherapy to maintain the bladder free of tumor. Substantially higher rates of pathologic confirmation of complete response are found following transurethral surgery and chemoradiation when compared with transurethral surgery and chemotherapy omitting the radiation. Overall survival is as good as cystectomy based approaches at 48-54% and over 80% of these long-term survivors keep their bladders. Following such therapies, 20-30% will subsequently develop superficial tumors. These patients may still be well treated by standard methods using transurethral resection and intravesical drugs. The concern of urologists that the conserved irradiated bladder functions poorly has also been answered by recent reports using modern radiation techniques. The instance of cystectomy for bladder shrinkage is repeatedly below 2%. Furthermore, sexual function is commonly preserved. The systemic morbidity of the chemotherapy is relatively high, but new approached using anti-emetics and GCSF now allow this to be reduced. In many

  6. Quality of Life in Long-term Survivors of Muscle-Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mak, Kimberley S. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts (United States); Smith, Angela B. [University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Eidelman, Alec; Clayman, Rebecca; Niemierko, Andrzej; Cheng, Jed-Sian [Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Matthews, Jonathan [University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Drumm, Michael R. [Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Nielsen, Matthew E. [University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Feldman, Adam S.; Lee, Richard J.; Zietman, Anthony L. [Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Chen, Ronald C. [University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Shipley, William U. [Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Milowsky, Matthew I. [University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Efstathiou, Jason A., E-mail: jefstathiou@partners.org [Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    2016-12-01

    Purpose: Health-related quality of life (QOL) has not been well-studied in survivors of muscle-invasive bladder cancer (MIBC). The present study compared long-term QOL in MIBC patients treated with radical cystectomy (RC) versus bladder-sparing trimodality therapy (TMT). Methods and Materials: This cross-sectional bi-institutional study identified 226 patients with nonmetastatic cT2-cT4 MIBC, diagnosed in 1990 to 2011, who were eligible for RC and were disease free for ≥2 years. Six validated QOL instruments were administered: EuroQOL EQ-5D, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire and EORTC MIBC module, Expanded Prostate Cancer Index Composite bowel scale, Cancer Treatment and Perception Scale, and Impact of Cancer, version 2. Multivariable analyses of the mean QOL scores were conducted using propensity score matching. Results: The response rate was 77% (n=173). The median follow-up period was 5.6 years. Of the 173 patients, 64 received TMT and 109, RC. The median interval from diagnosis to questionnaire completion was 9 years after TMT and 7 years after RC (P=.009). No significant differences were found in age, gender, comorbidities, tobacco history, performance status, or tumor stage. On multivariable analysis, patients who received TMT had better general QOL by 9.7 points of 100 compared with those who had received RC (P=.001) and higher physical, role, social, emotional, and cognitive functioning by 6.6 to 9.9 points (P≤.04). TMT was associated with better bowel function by 4.5 points (P=.02) and fewer bowel symptoms by 2.7 to 7.1 points (P≤.05). The urinary symptom scores were similar. TMT was associated with better sexual function by 8.7 to 32.1 points (P≤.02) and body image by 14.8 points (P<.001). The patients who underwent TMT reported greater informed decision-making scores by 13.6 points (P=.01) and less concern about the negative effect of cancer by 6.8 points (P=.006). The study

  7. Quality of Life in Long-term Survivors of Muscle-Invasive Bladder Cancer

    International Nuclear Information System (INIS)

    Mak, Kimberley S.; Smith, Angela B.; Eidelman, Alec; Clayman, Rebecca; Niemierko, Andrzej; Cheng, Jed-Sian; Matthews, Jonathan; Drumm, Michael R.; Nielsen, Matthew E.; Feldman, Adam S.; Lee, Richard J.; Zietman, Anthony L.; Chen, Ronald C.; Shipley, William U.; Milowsky, Matthew I.; Efstathiou, Jason A.

    2016-01-01

    Purpose: Health-related quality of life (QOL) has not been well-studied in survivors of muscle-invasive bladder cancer (MIBC). The present study compared long-term QOL in MIBC patients treated with radical cystectomy (RC) versus bladder-sparing trimodality therapy (TMT). Methods and Materials: This cross-sectional bi-institutional study identified 226 patients with nonmetastatic cT2-cT4 MIBC, diagnosed in 1990 to 2011, who were eligible for RC and were disease free for ≥2 years. Six validated QOL instruments were administered: EuroQOL EQ-5D, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire and EORTC MIBC module, Expanded Prostate Cancer Index Composite bowel scale, Cancer Treatment and Perception Scale, and Impact of Cancer, version 2. Multivariable analyses of the mean QOL scores were conducted using propensity score matching. Results: The response rate was 77% (n=173). The median follow-up period was 5.6 years. Of the 173 patients, 64 received TMT and 109, RC. The median interval from diagnosis to questionnaire completion was 9 years after TMT and 7 years after RC (P=.009). No significant differences were found in age, gender, comorbidities, tobacco history, performance status, or tumor stage. On multivariable analysis, patients who received TMT had better general QOL by 9.7 points of 100 compared with those who had received RC (P=.001) and higher physical, role, social, emotional, and cognitive functioning by 6.6 to 9.9 points (P≤.04). TMT was associated with better bowel function by 4.5 points (P=.02) and fewer bowel symptoms by 2.7 to 7.1 points (P≤.05). The urinary symptom scores were similar. TMT was associated with better sexual function by 8.7 to 32.1 points (P≤.02) and body image by 14.8 points (P<.001). The patients who underwent TMT reported greater informed decision-making scores by 13.6 points (P=.01) and less concern about the negative effect of cancer by 6.8 points (P=.006). The study

  8. Co-delivery of micronized urinary bladder matrix damps regenerative capacity of minced muscle grafts in the treatment of volumetric muscle loss injuries.

    Directory of Open Access Journals (Sweden)

    Stephen M Goldman

    Full Text Available Minced muscle grafts (MG promote de novo muscle fiber regeneration and neuromuscular strength recovery in small and large animal models of volumetric muscle loss. The most noteworthy limitation of this approach is its reliance on a finite supply of donor tissue. To address this shortcoming, this study sought to evaluate micronized acellular urinary bladder matrix (UBM as a scaffolding to promote in vivo expansion of this MG therapy in a rat model. Rats received volumetric muscle loss injuries to the tibialis anterior muscle of their left hind limb which were either left untreated or repaired with minced muscle graft at dosages of 50% and 100% of the defect mass, urinary bladder matrix in isolation, or a with an expansion product consisting of a combination of the two putative therapies in which the minced graft is delivered at a dosage of 50% of the defect mass. Rats survived to 2 and 8 weeks post injury before functional (in vivo neuromuscular strength, histological, morphological, and biochemical analyses were performed. Rats treated with the expansion product exhibited improved neuromuscular function relative to untreated VML after an 8 week time period following injury. This improvement in functional capacity, however, was accompanied with a concomitant reduction in graft mediated regeneration, as evidenced cell lineage tracing enable by a transgenic GFP expressing donor, and a mixed histological outcome indicating coincident fibrous matrix deposition with interspersed islands of nascent muscle fibers. Furthermore, quantitative immunofluorescence and transcriptional analysis following the 2 week time point suggests an exacerbated immune response to the UBM as a possible nidus for the observed suboptimal regenerative outcome. Moving forward, efforts related to the development of a MG expansion product should carefully consider the effects of the host immune response to candidate biomaterials in order to avoid undesirable dysregulation of pro

  9. Concurrent chemoradiotherapy improves survival outcome in muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Byun, Sang Jun; Kim, Jin Hee; Oh, Young Kee; Kim, Byung Hoon

    2015-01-01

    To evaluate survival rates and prognostic factors related to treatment outcomes after bladder preserving therapy including transurethral resection of bladder tumor, radiotherapy (RT) with or without concurrent chemotherapy in bladder cancer with a curative intent. We retrospectively studied 50 bladder cancer patients treated with bladder-preserving therapy at Keimyung University Dongsan Medical Center from January 1999 to December 2010. Age ranged from 46 to 89 years (median, 71.5 years). Bladder cancer was the American Joint Committee on Cancer (AJCC) stage II, III, and IV in 9, 27, and 14 patients, respectively. Thirty patients were treated with concurrent chemoradiotherapy (CCRT) and 20 patients with RT alone. Nine patients received chemotherapy prior to CCRT or RT alone. Radiation was delivered with a four-field box technique (median, 63 Gy; range, 48.6 to 70.2 Gy). The follow-up periods ranged from 2 to 169 months (median, 34 months). Thirty patients (60%) showed complete response and 13 (26%) a partial response. All patients could have their own bladder preserved. Five-year overall survival (OS) rate was 37.2%, and the 5-year disease-free survival (DFS) rate was 30.2%. In multivariate analysis, tumor grade and CCRT were statistically significant in OS. Tumor grade was a significant prognostic factor related to OS. CCRT is also considered to improve survival outcomes. Further multi-institutional studies are needed to elucidate the impact of RT in bladder cancer

  10. Local control of muscle-invasive bladder cancer: preoperative radiotherapy and cystectomy versus cystectomy alone

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    Cole, Christopher J; Pollack, Alan; Zagars, Gunar K; Dinney, Colin P; Swanson, David A; Eschenbach, Andrew C. von

    1995-05-15

    Purpose: The role of preoperative radiotherapy for patients with muscle-invasive bladder cancer remains controversial. Since 1985, the primary modality for treatment of these patients at our institution has been radical cystectomy alone. Prior to that time, the use of preoperative radiotherapy and cystectomy had been the mainstay of treatment. In this retrospective review we compare the results of these treatments, focusing on local control. Methods and Materials: The preoperative radiotherapy and radical cystectomy (PREOP) group was comprised of 338 patients with muscle-invasive (Stages T2-T4) transitional cell carcinoma of the bladder treated between 1960 and 1983. A mean total dose of 49.3 {+-} 0.2 Gy ({+-} SE) was administered at 2 Gy per fraction 4-6 weeks prior to cystectomy. The radical cystectomy alone (CYST) group was comprised of 232 patients treated between 1985 and 1990. The median follow-up for the PREOP group was 91 months and for the CYST group was 54 months. Only those patients who completed planned PREOP (n = 301) and CYST (n = 220) treatments were included in the analyses described below. Results: The treatment groups were stratified by clinical stage and compared in terms of actuarial local control. There were no differences between the groups for Stage T2 or T3a patients, and there were not enough Stage T4 patients in the PREOP group with which to make a meaningful comparison. However, for those with T3b disease, actuarial 5 year local control for the PREOP group (n = 92) was 91%, compared to 72% for the CYST group (n = 43). This difference was significant at p = 0.003 (log rank). Patients with T3b disease who received PREOP also fared slightly better at 5 years in terms of freedom from distant metastasis (67% vs. 54%), disease freedom (59% vs. 47%), and overall survival (52% vs. 40%); although, these differences did not reach statistical significance. The distribution of prognostic factors in the groups was analyzed to determine if this could

  11. Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer.

    Science.gov (United States)

    Narayan, Vivek; Mamtani, Ronac; Keefe, Stephen; Guzzo, Thomas; Malkowicz, S Bruce; Vaughn, David J

    2016-07-01

    We sought to investigate the safety and efficacy of gemcitabine, cisplatin, and lapatinib (GCL) as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) planned for radical cystectomy. Four cycles of GCL were administered as neoadjuvant therapy for patients with MIBC. Although initially designed as a phase II efficacy study with a primary endpoint of pathologic complete response at the time of radical cystectomy, the dose selected for investigation proved excessively toxic. A total of six patients were enrolled. The initial four patients received gemcitabine 1,000 mg/m(2) intravenously on days 1 and 8 and cisplatin 70 mg/m(2) intravenously on day 1 of each 21-day treatment cycle. Lapatinib was administered as 1,000 mg orally daily starting one week prior to the initiation of cycle 1 of gemcitabine and cisplatin (GC) and continuing until the completion of cycle 4 of GC. These initial doses were poorly tolerated, and the final two enrolled patients received a reduced lapatinib dose of 750 mg orally daily. However, reduction of the lapatinib dose did not result in improved tolerance or drug-delivery, and the trial was terminated early due to excessive toxicity. Grade 3/4 toxicities included diarrhea (33%), nausea/vomiting (33%), and thrombocytopenia (33%). The addition of lapatinib to GC as neoadjuvant therapy for MIBC was limited by excessive treatment-related toxicity. These findings highlight the importance of thorough dose-escalation investigation of combination therapies prior to evaluation in the neoadjuvant setting, as well as the limitations of determination of maximum tolerated dose for novel targeted combination regimens.

  12. Endometrial stem cell differentiation into smooth muscle cell: a novel approach for bladder tissue engineering in women.

    Science.gov (United States)

    Shoae-Hassani, Alireza; Sharif, Shiva; Seifalian, Alexander M; Mortazavi-Tabatabaei, Seyed Abdolreza; Rezaie, Sassan; Verdi, Javad

    2013-10-01

    To investigate manufacturing smooth muscle cells (SMCs) for regenerative bladder reconstruction from differentiation of endometrial stem cells (EnSCs), as the recent discovery of EnSCs from the lining of women's uteri, opens up the possibility of using these cells for tissue engineering applications, such as building up natural tissue to repair prolapsed pelvic floors as well as building urinary bladder wall. Human EnSCs that were positive for cluster of differentiation 146 (CD146), CD105 and CD90 were isolated and cultured in Dulbecco's modified Eagle/F12 medium supplemented with myogenic growth factors. The myogenic factors included: transforming growth factor β, platelet-derived growth factor, hepatocyte growth factor and vascular endothelial growth factor. Differentiated SMCs on bioabsorbable polyethylene-glycol and collagen hydrogels were checked for SMC markers by real-time reverse-transcriptase polymerase chain reaction (RT-PCR), western blot (WB) and immunocytochemistry (ICC) analyses. Histology confirmed the growth of SMCs in the hydrogel matrices. The myogenic growth factors decreased the proliferation rate of EnSCs, but they differentiated the human EnSCs into SMCs more efficiently on hydrogel matrices and expressed specific SMC markers including α-smooth muscle actin, desmin, vinculin and calponin in RT-PCR, WB and ICC experiments. The survival rate of cultures on the hydrogel-coated matrices was significantly higher than uncoated cultures. Human EnSCs were successfully differentiated into SMCs, using hydrogels as scaffold. EnSCs may be used for autologous bladder wall regeneration without any immunological complications in women. Currently work is in progress using bioabsorbable nanocomposite materials as EnSC scaffolds for developing urinary bladder wall tissue. © 2013 The Authors. BJU International © 2013 BJU International.

  13. Induction Cisplatin and Fluorouracil-Based Chemotherapy Followed by Concurrent Chemoradiation for Muscle-Invasive Bladder Cancer

    International Nuclear Information System (INIS)

    Lin, C.-C.; Hsu, C.-H.; Cheng, Jason C.; Huang, C.-Y.; Tsai, Y.-C.; Hsu, F.-M.; Huang, K.-H.; Cheng, A.-L.; Pu, Y.-S.

    2009-01-01

    Purpose: To evaluate a multimodality bladder-preserving therapy in patients with muscle-invasive bladder cancer. Methods and Materials: Patients with stages T2-4aN0M0 bladder cancer suitable for cystectomy underwent radical transurethral resection and induction chemotherapy, followed by concurrent chemoradiotherapy (CCRT). Patients with a Karnofsky performance status (KPS) <80 or age ≥70 years underwent Protocol A: induction chemotherapy with three cycles of the cisplatin and 5-fluorouracil (CF) regimen, and CCRT with six doses of weekly cisplatin and 64.8 Gy radiotherapy given with the shrinking-field technique. Patients with KPS ≥80 and age <70 years underwent Protocol B: induction chemotherapy with three cycles of weekly paclitaxel plus the CF regimen, and CCRT with six doses of weekly paclitaxel and cisplatin plus 64.8 Gy radiotherapy. Interval cystoscopy was employed after induction chemotherapy and when radiotherapy reached 43.2 Gy. Patients without a complete response (CR) were referred for salvage cystectomy. Results: Among 30 patients (median, 66 years) enrolled, 17 and 13 patients underwent Protocol A and B, respectively. After induction chemotherapy, 23 patients achieved CR. Five (17%) of 7 patients without CR underwent salvage cystectomy. Overall, 28 patients (93%) completed the protocol treatment. Of 22 patients who completed CCRT, 1 had recurrence with carcinoma in situ and 3 had distant metastases. After a median follow-up of 47 months, overall and progression-free survival rate for all patients were 77% and 54% at 3 years, respectively. Of 19 surviving patients, 15 (79%) retained functioning bladders. Conclusions: Our protocols may be alternatives to cystectomy for selected patients who wish to preserve the bladder.

  14. Smooth Muscle-Like Cells Generated from Human Mesenchymal Stromal Cells Display Marker Gene Expression and Electrophysiological Competence Comparable to Bladder Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Juliane Brun

    Full Text Available The use of mesenchymal stromal cells (MSCs differentiated toward a smooth muscle cell (SMC phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs. Within 1-2 weeks of myogenic differentiation, differentiating MSCs significantly expressed alpha smooth muscle actin (αSMA; ACTA2, transgelin (TAGLN, calponin (CNN1, and smooth muscle myosin heavy chain (SM-MHC; MYH11 according to qRT-PCR and/or immunofluorescence and Western blot. Voltage-gated Na+ current levels also increased within the same time period following myogenic differentiation. In contrast to undifferentiated MSCs, differentiated MSCs and bladder SMCs exhibited elevated cytosolic Ca2+ transients in response to K+-induced depolarization and contracted in response to K+ indicating functional maturation of differentiated MSCs. Depolarization was suppressed by Cd2+, an inhibitor of voltage-gated Ca2+-channels. The expression of Na+-channels was pharmacologically identified as the Nav1.4 subtype, while the K+ and Ca2+ ion channels were identified by gene expression of KCNMA1, CACNA1C and CACNA1H which encode for the large conductance Ca2+-activated K+ channel BKCa channels, Cav1.2 L-type Ca2+ channels and Cav3.2 T-type Ca2+ channels, respectively. This protocol may be used to differentiate adult MSCs into smooth muscle-like cells with an intermediate-to-late SMC contractile phenotype exhibiting voltage-gated ion

  15. Smooth Muscle-Like Cells Generated from Human Mesenchymal Stromal Cells Display Marker Gene Expression and Electrophysiological Competence Comparable to Bladder Smooth Muscle Cells.

    Science.gov (United States)

    Brun, Juliane; Lutz, Katrin A; Neumayer, Katharina M H; Klein, Gerd; Seeger, Tanja; Uynuk-Ool, Tatiana; Wörgötter, Katharina; Schmid, Sandra; Kraushaar, Udo; Guenther, Elke; Rolauffs, Bernd; Aicher, Wilhelm K; Hart, Melanie L

    2015-01-01

    The use of mesenchymal stromal cells (MSCs) differentiated toward a smooth muscle cell (SMC) phenotype may provide an alternative for investigators interested in regenerating urinary tract organs such as the bladder where autologous smooth muscle cells cannot be used or are unavailable. In this study we measured the effects of good manufacturing practice (GMP)-compliant expansion followed by myogenic differentiation of human MSCs on the expression of a range of contractile (from early to late) myogenic markers in relation to the electrophysiological parameters to assess the functional role of the differentiated MSCs and found that differentiation of MSCs associated with electrophysiological competence comparable to bladder SMCs. Within 1-2 weeks of myogenic differentiation, differentiating MSCs significantly expressed alpha smooth muscle actin (αSMA; ACTA2), transgelin (TAGLN), calponin (CNN1), and smooth muscle myosin heavy chain (SM-MHC; MYH11) according to qRT-PCR and/or immunofluorescence and Western blot. Voltage-gated Na+ current levels also increased within the same time period following myogenic differentiation. In contrast to undifferentiated MSCs, differentiated MSCs and bladder SMCs exhibited elevated cytosolic Ca2+ transients in response to K+-induced depolarization and contracted in response to K+ indicating functional maturation of differentiated MSCs. Depolarization was suppressed by Cd2+, an inhibitor of voltage-gated Ca2+-channels. The expression of Na+-channels was pharmacologically identified as the Nav1.4 subtype, while the K+ and Ca2+ ion channels were identified by gene expression of KCNMA1, CACNA1C and CACNA1H which encode for the large conductance Ca2+-activated K+ channel BKCa channels, Cav1.2 L-type Ca2+ channels and Cav3.2 T-type Ca2+ channels, respectively. This protocol may be used to differentiate adult MSCs into smooth muscle-like cells with an intermediate-to-late SMC contractile phenotype exhibiting voltage-gated ion channel

  16. Urothelial Tumours of the Urinary Bladder: A Histopathological Study of Cystoscopic Biopsies

    Directory of Open Access Journals (Sweden)

    Sujan Vaidya

    2013-09-01

    Full Text Available ABSTRACT Introduction: Bladder tumours constitute one of the most common urological conditions. Urothelial (transitional cell carcinoma accounts for 90% of all primary tumours of the bladder. These tumours are an important cause of morbidity and mortality. The objective of this study was to present the histopathological patterns of urothelial tumours and to determine the grade and stage of these tumours. Methods: This is a 3 year retrospective study of urothelial tumours carried out in the Department of Pathology, Patan Academy of Health Sciences (PAHS, Lalitpur, Nepal. Data of all cystoscopic biopsies collected during this period were analyzed. Results: Urothelial (transitional cell tumours accounted for 97.59% (81 cases of all bladder tumours. Transitional cell carcinoma (TCC was the most common tumour which was present in 67 cases (80.72%. Of these, 32 (47.76% were low grade TCC while 35 (52.24% were high grade TCC. Maximum number of tumours (70.37% were superficial (pTa and pT1 while (29.63% were muscle invasive (pT2. Sixteen percent of low grade and 76.92% of high grade tumours showed muscle invasion. Detrusor muscle was absent in 23.88% cases (16/67. Conclusion: Transitional cell carcinoma was the most common bladder cancer. Most of these tumours were high grade. A large percentage of high grade carcinomas presented with muscle invasion. Pathological grade and muscle invasion are the most valuable prognostic predictors of survival. The importance of including smooth muscle in the biopsy specimens needs to be emphasized Key words: cancer, high grade, low grade, transitional, tumour, urinary bladder.

  17. Reduction of recurrence in non-muscle invasive bladder cancer using photodynamic diagnosis and immediate post-TUR-B chemoprophylaxis

    DEFF Research Database (Denmark)

    Risager, Malene Bøg

    2013-01-01

    (TUR-B), and one single instillation of 40 mg Mitomycin C (MMC) within 24 hours post-TUR-B were introduced at our institution by March 2008. For the study, patients were identified retrospectively using procedure codes for TUR-B and cystoscopy with biopsy and fulguration. Patients with muscle......-invasive bladder cancer were excluded. 190 consecutive patients, treated between 03-01-2008 and 28-02-2010, were included into the intervention group, while 216 patients, treated between 03-01-2006 and 29-02-2008, served as controls. Procedures and pathology results were registered. The groups were comparable...

  18. Bladder-sphincter dysfunction in myelomeningocele

    NARCIS (Netherlands)

    van Gool, J. D.; Dik, P.; de Jong, T. P.

    2001-01-01

    Pediatric urodynamics taught us that detrusor-sphincter dyssynergia creates a bladder outlet obstruction in about 50% of any population of children with myelomeningocele. This functional obstruction causes renal damage due to obstructive uropathy, exactly the same way as a congenital anatomical

  19. Full-thickness endometriosis of the bladder

    DEFF Research Database (Denmark)

    Kjer, Jens Jørgen; Kristensen, Jens; Hartwell, Dorthe

    2014-01-01

    referral centres in Denmark for surgical treatment of stage III and IV endometriosis. POPULATION: Thirty-one women with deep infiltrating bladder endometriosis. METHODS: All women presenting in the Department of Obstetrics and Gynaecology with deep infiltrating bladder endometriosis between March 2002...... and March 2011. We included only patients with symptomatic full-thickness bladder detrusor endometriosis and mucosal involvement. All patients had had bladder symptoms for two to seven years. MAIN OUTCOME MEASURES: Symptoms after surgery and recurrence rate. RESULTS: The main preoperative symptom...

  20. A role of multimodality bladder-preserving therapy in patients with muscle-invasive bladder cancer plus hydronephrosis with or without pelvic nodal involvement

    Directory of Open Access Journals (Sweden)

    Yun Chiang

    2017-09-01

    Conclusion: With trimodality treatment involving visually complete transurethral resection of bladder tumor, cisplatin-based induction chemotherapy, and CCRT, patients with unfavorable factors maintained satisfactory bladder preservation but not systemic control.

  1. Effectiveness of pelvic floor muscle training on symptoms and uroflowmetry parameters in female patients with overactive bladder.

    Science.gov (United States)

    Kulaksizoğlu, Haluk; Akand, Murat; Çakmakçi, Evrim; Gül, Murat; Seçkin, Bedreddin

    2015-01-01

    To evaluate the effects of pelvic floor muscle training (PFMT) on symptoms of overactive bladder (OAB) as well as uroflowmetry parameters and functional bladder capacity. Fifty-nine female patients with OAB symptoms were included. Patients were assessed by SEAPI-QMM, uroflowmetry, and abdominal ultrasound. A specially designed PFMT program using a Pilates ball was generated for patients. The training period was 1-h sessions twice a week for 6 weeks and aerobic home exercises to be performed at home 4 or 5 times every other day. Following training, subjects were reevaluated for body mass index, SEAPI questionnaire, and uroflowmetry. Initial mean SEAPI score, mean maximum and average flow rates, and mean voided volume were 9.8 ± 7.2, 29.8 ± 16.4 mL/s, 16.3 ± 8.7 mL/s, and 211.6 ± 173.5 mL, respectively. After completion of the training program, SEAPI scores improved significantly to 3.4 ± 6.4 (P < 0.05). Maximum and average flow rate results did not show significant changes, whereas voided volume seemed to have improved in conjunction with patients' symptom scores (Pearson correlation coefficient: 0.86). According to. our results, we think that proper PFMT results in increase of functional bladder capacity as well as improvement in OAB symptoms and can be recommended as first-line therapy or in conjunction with medical therapy in severe cases.

  2. Highly specific detection of muscarinic M3 receptor, G protein interaction and intracellular trafficking in human detrusor using Proximity Ligation Assay (PLA).

    Science.gov (United States)

    Berndt-Paetz, Mandy; Herbst, Luise; Weimann, Annett; Gonsior, Andreas; Stolzenburg, Jens-Uwe; Neuhaus, Jochen

    2018-05-01

    -subtype coupling patterns. Detection of M3 interactions with endocytic trafficking proteins by PLA resulted in object sizes correlating with well-documented vesicle sizes of the endocytosis pathway. PLA enabled highly specific detection of M3 receptor expression, demonstration of M3/GP differential coupling and intracellular M3 trafficking in human detrusor smooth muscle cells. This new approach minimized background fluorescence and antibody cross-reactions resulting from single antibody application, and enhanced specificity due to the use of two primary antibodies. Use of subcellular markers allowed visualization of subcellular receptor location. PLA/CLSM allows analyses of muscarinic "receptor - G protein - promiscuity" and intracellular trafficking even in bladder paraffin sections and may give new insights into the etiology and pathology of BPS/IC. Copyright © 2018 Elsevier GmbH. All rights reserved.

  3. Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder-preservation therapy for muscle-invasive bladder cancer.

    Science.gov (United States)

    Cahn, David B; Handorf, Elizabeth A; Ghiraldi, Eric M; Ristau, Benjamin T; Geynisman, Daniel M; Churilla, Thomas M; Horwitz, Eric M; Sobczak, Mark L; Chen, David Y T; Viterbo, Rosalia; Greenberg, Richard E; Kutikov, Alexander; Uzzo, Robert G; Smaldone, Marc C

    2017-11-15

    The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder-preservation therapy (BPT) for muscle-invasive urothelial carcinoma of the bladder. The authors reviewed the National Cancer Data Base to identify patients with AJCC stage II to III urothelial carcinoma of the bladder from 2004 through 2013. Patients receiving BPT were stratified as having received any external-beam radiotherapy (any XRT), definitive XRT (50-80 grays), and definitive XRT with chemotherapy (CRT). Treatment trends and OS outcomes for the BPT and RC cohorts were evaluated using Cochran-Armitage tests, unadjusted Kaplan-Meier curves, adjusted Cox multivariate regression, and propensity score matching, using increasingly stringent selection criteria. A total of 32,300 patients met the inclusion criteria and were treated with RC (22,680 patients) or BPT (9620 patients). Of the patients treated with BPT, 26.4% (2540 patients) and 15.5% (1489 patients), respectively, were treated with definitive XRT and CRT. Improved OS was observed for RC in all groups. After adjustments with more rigorous statistical models controlling for confounders and with more restrictive BPT cohorts, the magnitude of the OS benefit became attenuated on multivariate (any XRT: hazard ratio [HR], 2.115 [95% confidence interval [95% CI], 2.045-2.188]; definitive XRT: HR, 1.870 [95% CI, 1.773-1.972]; and CRT: HR, 1.578 [95% CI, 1.474-1.691]) and propensity score (any XRT: HR, 2.008 [95% CI, 1.871-2.154]; definitive XRT: HR, 1.606 [95% CI, 1.453-1.776]; and CRT: HR, 1.406 [95% CI, 1.235-1.601]) analyses. In the National Cancer Data Base, receipt of BPT was associated with decreased OS compared with RC in patients with stage II to III urothelial carcinoma. Increasingly stringent definitions of BPT and more rigorous statistical methods adjusting for selection biases attenuated observed survival differences. Cancer 2017;123:4337-45. © 2017

  4. Hydrostatic pressure and muscarinic receptors are involved in the release of inflammatory cytokines in human bladder smooth muscle cells.

    Science.gov (United States)

    Liang, Zhou; Xin, Wei; Qiang, Liu; Xiang, Cai; Bang-Hua, Liao; Jin, Yang; De-Yi, Luo; Hong, Li; Kun-Jie, Wang

    2017-06-01

    Abnormal intravesical pressure results in a series of pathological changes. We investigated the effects of hydrostatic pressure and muscarinic receptors on the release of inflammatory cytokines in rat and human bladder smooth muscle cells (HBSMCs). Animal model of bladder outlet obstruction was induced by urethra ligation. HBSMCs were subjected to elevated hydrostatic pressure and/or acetylcholine (Ach). Macrophage infiltration in the bladder wall was determined by immunohistochemical staining. The expression of inflammatory genes was measured by RT-PCR, ELISA and immunofluorescence. In obstructed bladder, inflammatory genes and macrophage infiltration were remarkably induced. When HBSMCs were subjected to 200-300 cm H 2 O pressure for 2-24 h in vitro, the expressions of IL-6 and RANTES were significantly increased. Hydrostatic pressure promoted the protein levels of phospho-NFκB p65 and phospho-ERK1/2 as well as muscarinic receptors. Moreover, NFκB or ERK1/2 inhibitors suppressed pressure-induced inflammatory genes mRNA. When cells were treated with 1 μM acetylcholine for 6 h, a significant increase in IL-6 mRNA expression was detected. Acetylcholine also enhanced pressure-induced phospho-NFκB p65 and IL-6 protein expression. Additionally, pressure-induced IL-6 was partially suppressed by muscarinic receptors antagonists. Hydrostatic pressure and muscarinic receptors were involved in the secretion of inflammatory cytokines in HBSMCs, indicating a pro-inflammatory effect of the two factors in the pathological process of BOO. © 2016 Wiley Periodicals, Inc.

  5. Expression and proliferation profiles of PKC, JNK and p38MAPK in physiologically stretched human bladder smooth muscle cells

    International Nuclear Information System (INIS)

    Wazir, Romel; Luo, De-Yi; Dai, Yi; Yue, Xuan; Tian, Ye; Wang, Kun-Jie

    2013-01-01

    Highlights: •Stretch induces proliferation in human bladder smooth muscle cells (HBSMC). •5% Equibiaxial elongation produces maximum proliferation. •Physiologic stretch decreases apoptotic cell death. •PKC is involved in functional modulation of bladder. •JNK and p38 are not involved in proliferating HBSMC. -- Abstract: Objective: To determine protein kinase C (PKC), c-Jun NH2-Terminal Kinase (JNK) and P38 mitogen-activated protein kinases (p38MAPK) expression levels and effects of their respective inhibitors on proliferation of human bladder smooth muscle cells (HBSMCs) when physiologically stretched in vitro. Materials and methods: HBSMCs were grown on silicone membrane and stretch was applied under varying conditions; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (frequency: 0.05, 0.1, 0.2, 0.5, 1 Hz). Optimal physiological stretch was established by assessing proliferation with 5-Bromo-2-deoxyuridine (BrdU) assay and flow cytometry. PKC, JNK and p38 expression levels were analyzed by Western blot. Specificity was maintained by employing specific inhibitors; (GF109203X for PKC, SP600125 for JNK and SB203580 for p38MAPK), in some experiments. Results: Optimum proliferation was observed at 5% equibiaxial stretch (BrdU: 0.837 ± 0.026 (control) to 1.462 ± 0.023)%, (P 0.05 SP600125) and (1.461 ± 0.01, P > 0.05 SB203580). These findings show that mechanical stretch can promote magnitude-dependent proliferative modulation through PKC and possibly JNK but not via p38MAPK in hBSMCs

  6. Clinical significance of serum and urinary HER2/neu protein levels in primary non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Ozgur Arikan

    2015-12-01

    Full Text Available Objective: We aimed to compare serum and urinary HER2/neu levels between healthy control group and patients with non-muscle invasive bladder cancer. Additionally, we evaluated relationship of HER2/neu levels with tumor stage, grade, recurrence and progression. Materials and Methods: Fourty-four patients with primary non-muscle invasive bladder tumors (Group 2 and 40 healthy control group (Group 1 were included the study. Blood and urinary samples were collected from all patients and HER2/neu levels were measured by ELISA method. Blood and urinary HER2/neu levels and additionally, ratio of urinary HER2/neu levels to urinary creatinine levels were recorded. Demographic data and tumor characteristics were recorded. Results: Mean serum HER2/neu levels were similar between two groups and statistically significant difference wasn't observed. Urinary HER2/neu levels were significantly higher in group 2 than group 1. Ratio of urinary HER2/neu to urinary creatinine was significantly higher in group 2 than group 1, (p=0,021. Serum and urinary HER2/ neu levels were not associated with tumor stage, grade, recurrence and progression while ratio of urinary HER2/neu to urinary creatinin levels were significantly higher in high-grade tumors. HER2/neu, the sensitivity of the test was found to be 20.5%, and the specificity was 97.5%, also for the urinary HER2/neu/urinary creatinine ratio, the sensitivity and specificity of the test were found to be 31.8% and 87.5%, respectively. Conclusions: Urinary HER2/neu and ratio of urinary creatinine urine were significantly higher in patients with bladder cancer compared to healthy subjects. Large series and controlled studies are needed for use as a tumor marker.

  7. Functional investigation of β-adrenoceptors in human isolated detrusor focusing on the novel selective β3-adrenoceptor agonist KUC-7322

    NARCIS (Netherlands)

    Igawa, Yasuhiko; Schneider, Tim; Yamazaki, Yoshinobu; Tatemichi, Satoshi; Homma, Yukio; Nishizawa, Osamu; Michel, Martin C.

    2012-01-01

    This study aimed to characterize the β-adrenoceptor (β-AR) subtype mediating relaxation of isolated human bladder strips and to explore relaxation by the novel β3-AR-selective agonist KUC-7322 for its relaxant effect on the human isolated detrusor and for its effect on the carbachol (CCh)-induced

  8. Clinical characteristics of bladder cancer in patients with spinal cord injury: the experience from a single centre.

    Science.gov (United States)

    Böthig, Ralf; Kurze, Ines; Fiebag, Kai; Kaufmann, Albert; Schöps, Wolfgang; Kadhum, Thura; Zellner, Michael; Golka, Klaus

    2017-06-01

    Life expectancy for people with spinal cord injury has shown a marked increase due to modern advances in treatment methods and in neuro-urology. However, since life expectancy of people with paralysis increases, the risk of developing of urinary bladder cancer is gaining importance. Single-centre retrospective evaluation of patient data with spinal cord injuries and proven urinary bladder cancer and summary of the literature. Between 1998 and 2014, 24 (3 female, 21 male) out of a total of 6599 patients with spinal cord injury were diagnosed with bladder cancer. The average age at bladder cancer diagnosis was 57.67 years, which is well below the average for bladder cancer cases in the general population (male: 73, female: 77). All but one patient had a latency period between the onset of the spinal paralysis and tumour diagnosis of more than 10 years. The median latency was 29.83 years. The median survival for these patients was 11.5 months. Of the 24 patients, 19 (79%) had muscle invasive bladder cancer at ≥T2 at the time of diagnosis. The type of neurogenic bladder (neurogenic detrusor overactivity or acontractility) and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients. The significantly younger age at onset and the frequency of invasive tumours at diagnosis indicate that spinal cord injury influences bladder cancer risk and prognosis as well. Early detection of bladder cancer in patients with spinal cord injury remains a challenge.

  9. Prognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health Organization Grading Classification Systems in Non-muscle-invasive Bladder Cancer: A European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review.

    Science.gov (United States)

    Soukup, Viktor; Čapoun, Otakar; Cohen, Daniel; Hernández, Virginia; Babjuk, Marek; Burger, Max; Compérat, Eva; Gontero, Paolo; Lam, Thomas; MacLennan, Steven; Mostafid, A Hugh; Palou, Joan; van Rhijn, Bas W G; Rouprêt, Morgan; Shariat, Shahrokh F; Sylvester, Richard; Yuan, Yuhong; Zigeuner, Richard

    2017-11-01

    Tumour grade is an important prognostic indicator in non-muscle-invasive bladder cancer (NMIBC). Histopathological classifications are limited by interobserver variability (reproducibility), which may have prognostic implications. European Association of Urology NMIBC guidelines suggest concurrent use of both 1973 and 2004/2016 World Health Organization (WHO) classifications. To compare the prognostic performance and reproducibility of the 1973 and 2004/2016 WHO grading systems for NMIBC. A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library. Studies were critically appraised for risk of bias (QUIPS). For prognosis, the primary outcome was progression to muscle-invasive or metastatic disease. Secondary outcomes were disease recurrence, and overall and cancer-specific survival. For reproducibility, the primary outcome was interobserver variability between pathologists. Secondary outcome was intraobserver variability (repeatability) by the same pathologist. Of 3593 articles identified, 20 were included in the prognostic review; three were eligible for the reproducibility review. Increasing tumour grade in both classifications was associated with higher disease progression and recurrence rates. Progression rates in grade 1 patients were similar to those in low-grade patients; progression rates in grade 3 patients were higher than those in high-grade patients. Survival data were limited. Reproducibility of the 2004/2016 system was marginally better than that of the 1973 system. Two studies on repeatability showed conflicting results. Most studies had a moderate to high risk of bias. Current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. Intra- and interobserver variability was slightly less in the 2004/2016 classification. We could not confirm that the 2004/2016 classification outperforms the 1973 classification in prediction of recurrence and progression. This article

  10. Capsaicin-Sensitive Sensory Nerves Indirectly Modulate Motor Function of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Hsi-Hsien Chang

    2018-06-01

    Full Text Available Purpose The urinary bladder (UB is innervated by both sensory and autonomic nerves. Recent studies have shown that sensory neuropeptides induced contractions in the detrusor muscle. Therefore, in a mouse model, we investigated the presence of interactions between the submucosal sensory nerves and the autonomic nerves that regulate the motor function of the detrusor muscle. Methods UB samples from male C57BL/6 mice were isolated, cut into strips, and mounted in an organ bath. Dose-response curves to norepinephrine and phenylephrine were studied in UB strips with and without mucosa, and the effects of preincubation with a receptor antagonist and various drugs on relaxation were also studied using tissue bath myography. Results Phenylephrine-induced relaxation of the UB strips showed concentration-related effects. This relaxation appeared in both mucosa-intact and mucosa-denuded UB strips, and was significantly inhibited by lidocaine, silodosin, and guanethidine (an adrenergic neuronal blocker. Meanwhile, phenylephrine-induced relaxation was inhibited by pretreatment with propranolol and calcitonin gene-related peptide (CGRP–depletory capsaicin in UB strips with and without mucosa. Conclusions The present study suggests that phenylephrine activates the α-1A adrenergic receptor (AR of the sensory nerve, and then activates capsaicin-sensitive sensory nerves to release an unknown substance that facilitates the release of norepinephrine from adrenergic nerves. Subsequently, norepinephrine stimulates β-ARs in the detrusor muscle in mice, leading to neurogenic relaxation of the UB. Further animal and human studies are required to prove this concept and to validate its clinical usefulness.

  11. Aging and recurrent urinary tract infections are associated with bladder dysfunction in type 2 diabetes.

    Science.gov (United States)

    Lin, Tzu-Li; Chen, Gin-Den; Chen, Yi-Ching; Huang, Chien-Ning; Ng, Soo-Cheen

    2012-09-01

    The objective of this study was to demonstrate the diversity of urodynamic findings and temporal effects on bladder dysfunction in diabetes as well as to evaluate the predisposing factors that attenuate the storage and voiding function of diabetic women. In this prospective study, 181 women with type 2 diabetes mellitus (DM) and lower urinary tract dysfunction underwent complete urogynecological evaluations and urodynamic studies. The patients' histories of DM and the treatment agents used were documented from chart records and interviews. The urodynamic diagnoses were recategorized into two groups for comparison, namely overactive detrusor (detrusor overactivity and/or increased bladder sensation as well as mixed incontinence) and voiding dysfunction (detrusor hyperactivity with insufficient contractility and detrusor underactivity with poor voiding efficiency) in order to evaluate the temporal effect of DM on diabetic bladder dysfunction. The development of bladder dysfunction showed a trend involving time-dependent progression, beginning with storage problems (i.e. advancing from urodynamic stress incontinence to detrusor overactivity and/or increased bladder sensation) and eventually led to impaired voiding function. The duration of DM relative to the urodynamic diagnoses of these women was longer in women with voiding dysfunction (6.8 ± 2.8 years with urodynamic stress incontinence, 7.3 ± 6.5 years with detrusor overactivity and/or increased bladder sensation, and 10.4 ± 8.3 years with women with voiding dysfunction). Notwithstanding these findings, stepwise logistic regression analysis indicated that age and recurrent urinary tract infections were the two independent factors associated with developing voiding dysfunction. The urodynamic study revealed a temporal effect on bladder function, and women with diabetic voiding dysfunction were found to have had a longer duration of DM than women with an overactive detrusor. However, aging and recurrent

  12. Treatment of muscle invasive bladder cancer. Is there a role for neoadjuvant chemotherapy?

    International Nuclear Information System (INIS)

    Kuten, A.; Baz, M.; Rubinov, R.; Dale, J.; Haim, N.; Robinson, E.; Cohen, Y.

    1994-01-01

    We compared the outcome of 3 different but widely accepted treatment protocols for bladder cancer in ordet to find which, if any, was superior, with particular emphasis upon the performance of the newest treatment, neoadjuvant chemotherapy. Data on 224 bladder patients treated at our institution (1975 to 1991) with 1 of the 3 protocols was analyzed. Those protocols were: 1. Radiotherapy >60 Gy (143 patients); 2. low dose radiotherapy followed by cystectomy (25 patients); 3. chemotherapy followed by either definitive radiotherapy or surgery (56 patients). Because the latter group was also a chronologically newer group with a shorter possible follow-up, we compared all treatments on the basis of 2-year survival, using Kaplan-Meier life tables. We briefly reviewed those modalities which are bladder-sparing because of the significance to quality of life of this factor. Two-year survival figures for the patients were: 63% for those wo received only radiotherapy; 72% for those undergoing cystectomy: 68% for the group to whom neoadjuvant chemotherapy was administered. The differences were not statistically significant. However, 23% of those patients treated neoadjuvantly were alive with intact bladders at 2 years. (orig./MG) [de

  13. Apoptosis and downstaging after preoperative radiotherapy for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Chyle, Valerian; Pollack, Alan; Czerniak, Bogdan A.; Stephens, L. Clifton; Zagars, Gunar K.; Terry, Nicholas H.A.; Meyn, Raymond E.

    1995-01-01

    Purpose/Objective: To determine the relationship between pretreatment (basal) apoptosis levels and clinical-to-pathologic downstaging resulting from preoperative radiotherapy. Materials and Methods: Between 1960-1983, 338 patients were dispositioned to receive preoperative radiotherapy and radical cystectomy for muscle-invasive transitional cell carcinoma of the bladder. Of these, adequate hematoxylin and eosin stained tissue sections for morphologic analysis of apoptosis were available in 158 patients. These patients were treated to a mean dose of 49.4 ± 3.0 Gy (± S.D.) and a median dose of 50 Gy. The average fractional dose was 2.0 ± 0.2 Gy with a median of 2.0 Gy. No patient had clinical or radiographic evidence of lymph nodal or distant metastasis, and none received neoadjuvant or adjuvant chemotherapy. The median follow-up for those living was 90 mo. The apoptotic index (AI) was calculated from the ratio of the number of apoptotic cells divided by the total counted and multiplied by 100. The apoptotic cells were counted from several random high powered fields. A minimum of 500 cells were counted from each patient. Results: The average AI for the whole group (n=158) was 2.0 ± 1.3 with a median of 1.8. The association of several potential prognostic factors to AI revealed that AI correlated strongly with clinical stage. The average AI for clinical stage T2 (n=56) was 1.8, for stage T3a (n=51) was 1.9, and for stage T3b (n=51) was 2.4 (p=0.036, Kendall Correlation). The relationship of AI to radiotherapy response also was significant with an average AI of 2.2 for those who were downstaged (n=103), 1.9 for those in whom the stage remained unchanged (n=20), and 1.7 for those who were upstaged (n=35, p=0.054, Kendall Correlation). The only other correlations with AI were for the factors gender (p=0.035) and pretreatment hemoglobin level (p=0.077). The AI was then categorized into 3 groups (≤1, >1 and ≤3, and >3) to examine the prognostic significance of this

  14. Apoptosis and downstaging after preoperative radiotherapy for muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chyle, Valerian; Pollack, Alan; Czerniak, Bogdan A; Stephens, L Clifton; Zagars, Gunar K; Terry, Nicholas H.A.; Meyn, Raymond E

    1995-07-01

    Purpose/Objective: To determine the relationship between pretreatment (basal) apoptosis levels and clinical-to-pathologic downstaging resulting from preoperative radiotherapy. Materials and Methods: Between 1960-1983, 338 patients were dispositioned to receive preoperative radiotherapy and radical cystectomy for muscle-invasive transitional cell carcinoma of the bladder. Of these, adequate hematoxylin and eosin stained tissue sections for morphologic analysis of apoptosis were available in 158 patients. These patients were treated to a mean dose of 49.4 {+-} 3.0 Gy ({+-} S.D.) and a median dose of 50 Gy. The average fractional dose was 2.0 {+-} 0.2 Gy with a median of 2.0 Gy. No patient had clinical or radiographic evidence of lymph nodal or distant metastasis, and none received neoadjuvant or adjuvant chemotherapy. The median follow-up for those living was 90 mo. The apoptotic index (AI) was calculated from the ratio of the number of apoptotic cells divided by the total counted and multiplied by 100. The apoptotic cells were counted from several random high powered fields. A minimum of 500 cells were counted from each patient. Results: The average AI for the whole group (n=158) was 2.0 {+-} 1.3 with a median of 1.8. The association of several potential prognostic factors to AI revealed that AI correlated strongly with clinical stage. The average AI for clinical stage T2 (n=56) was 1.8, for stage T3a (n=51) was 1.9, and for stage T3b (n=51) was 2.4 (p=0.036, Kendall Correlation). The relationship of AI to radiotherapy response also was significant with an average AI of 2.2 for those who were downstaged (n=103), 1.9 for those in whom the stage remained unchanged (n=20), and 1.7 for those who were upstaged (n=35, p=0.054, Kendall Correlation). The only other correlations with AI were for the factors gender (p=0.035) and pretreatment hemoglobin level (p=0.077). The AI was then categorized into 3 groups ({<=}1, >1 and {<=}3, and >3) to examine the prognostic

  15. A porcine model of bladder outlet obstruction incorporating radio-telemetered cystometry.

    Science.gov (United States)

    Shaw, Matthew B; Herndon, Claude D; Cain, Mark P; Rink, Richard C; Kaefer, Martin

    2007-07-01

    To present a novel porcine model of bladder outlet obstruction (BOO) with a standardized bladder outlet resistance and real-time ambulatory radio-telemetered cystometry, as BOO is a common condition with many causes in both adults and children, with significant morbidity and occasional mortality, but attempts to model this condition in many animal models have the fundamental problem of standardising the degree of outlet resistance. BOO was created in nine castrated male pigs by dividing the mid-urethra; outflow was allowed through an implanted bladder drainage catheter containing a resistance valve, allowing urine to flow across the valve only when a set pressure differential was generated across the valve. An implantable radio-telemetered pressure sensor monitored the pressure within the bladder and abdominal cavity, and relayed this information to a remote computer. Four control pigs had an occluded bladder drainage catheter and pressure sensor placed, but were allowed to void normally through the native urethra. Intra-vesical pressure was monitored by telemetry, while the resistance valve was increased weekly, beginning with 2 cmH2O and ultimately reaching 10 cmH2O. The pigs were assessed using conventional cystometry under anaesthesia before death, and samples conserved in formalin for haematoxylin and eosin staining. The pigs had radio-telemetered cystometry for a median of 26 days. All telemetry implants functioned well for the duration of the experiment, but one pig developed a urethral fistula and was excluded from the study. With BOO the bladder mass index (bladder mass/body mass x 10 000) increased from 9.7 to 20 (P = 0.004), with a significant degree of hypertrophy of the detrusor smooth muscle bundles. Obstructed bladders were significantly less compliant than control bladders (8.3 vs 22.1 mL/cmH2O, P = 0.03). Telemetric cystometry showed that there was no statistically significance difference in mean bladder pressure between obstructed and control pigs

  16. Hexaminolevulinate blue-light cystoscopy in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on appropriate use in the USA

    NARCIS (Netherlands)

    Daneshmand, S.; Schuckman, A.K.; Bochner, B.H.; Cookson, M.S.; Downs, T.M.; Gomella, L.G.; Grossman, H.B.; Kamat, A.M.; Konety, B.R.; Lee, C.T.; Pohar, K.S.; Pruthi, R.S.; Resnick, M.J.; Smith, N.D.; Witjes, J.A.; Schoenberg, M.P.; Steinberg, G.D.

    2014-01-01

    Hexaminolevulinate (HAL) is a tumour photosensitizer that is used in combination with blue-light cystoscopy (BLC) as an adjunct to white-light cystoscopy (WLC) in the diagnosis and management of non-muscle-invasive bladder cancer (NMIBC). Since being licensed in Europe in 2005, HAL has been used in

  17. Prediction model for recurrence probabilities after intravesical chemotherapy in patients with intermediate-risk non-muscle-invasive bladder cancer, including external validation

    NARCIS (Netherlands)

    Lammers, R.J.M.; Hendriks, J.C.M.; Rodriguez Faba, O.; Witjes, W.P.J.; Palou, J.; Witjes, J.A.

    2016-01-01

    PURPOSE: To develop a model to predict recurrence for patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) treated with intravesical chemotherapy which can be challenging because of the heterogeneous characteristics of these patients. METHODS: Data from three Dutch trials

  18. The effect of the time interval between diagnosis of muscle-invasive bladder cancer and radical cystectomy on staging and survival: A Netherlands Cancer Registry analysis

    NARCIS (Netherlands)

    Bruins, H.M.; Aben, K.K.H.; Arends, T.J.; Heijden, A.G. van der; Witjes, J.A.

    2016-01-01

    INTRODUCTION: Data from single-center series suggest that a delay in time to radical cystectomy (RC) more than 3 months after diagnosis of muscle-invasive bladder cancer (MIBC) is associated with pathological upstaging and decreased survival. However, limited data is available from population-based

  19. Pharmacokinetic, Pharmacodynamic, and Activity Evaluation of TMX-101 in a Multicenter Phase 1 Study in Patients With Papillary Non-Muscle-Invasive Bladder Cancer

    NARCIS (Netherlands)

    Arends, T.J.H.; Lammers, R.J.M.; Falke, J.; Heijden, A.G. van der; Rustighini, I.; Pozzi, R.; Ravic, M.; Eisenhardt, A.; Vergunst, H.; Witjes, J.A.

    2015-01-01

    INTRODUCTION/BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) has a strong tendency to recur despite adjuvant instillations. TMX-101 is a new liquid form of imiquimod for intravesical instillation and has activity in vitro against urothelial carcinoma. The purpose was to analyze the activity

  20. Physiotherapy Management of Idiopathic Detrusor Instability in elderly women is effective for continence rehabilitation

    International Nuclear Information System (INIS)

    Al-Gazzar, Samir A.

    2006-01-01

    The aim of this work was to give an overview of the conservative treatment of idiopathic detrusor instability (IDI) in elderly women, describe the clinical and urodynamic features of the over-active bladder and the role of physiotherapy as well as the various physiotherapeutic techniques in the management of this condition. A prospective, uncontrolled clinical trial was designed. Twenty elderly women aged 55-75 were participated for 8 weeks in this study. Therapeutic modalities including biofeedback training, bladder retraining, pelvic floor exercise and electrical stimulation were applied for all subjects. Each of 1st desire to void, maximum capacity, flow rate and voiding intervals were increased in its mean at the end of the study (p<0.0001), while the means of residual volume and frequency of micturation had significantly decreased at the end of the study (p<0.0001). The study showed that correctly taught pelvic floor exercise, biofeed back combined with bladder retaining, electrical stimulation and restriction of fluids intake are an effective treatment for the idiopathic detrusor instability in elderly women and should be considered effective approach for continence rehabilitation. (author)

  1. A pilot study of acotiamide hydrochloride hydrate in patients with detrusor underactivity

    Directory of Open Access Journals (Sweden)

    Sugimoto K

    2015-05-01

    Full Text Available Koichi Sugimoto,1 Takahiro Akiyama,2 Nobutaka Shimizu,3 Naoki Matsumura,1 Taiji Hayashi,1 Tsukasa Nishioka,1 Hirotsugu Uemura3 1Department of Urology, Sakai Hospital, Kinki University Faculty of Medicine, Sakai, Osaka, Japan; 2Department of Urology, Sakai-Onshinkai Hospital, Sakai, Osaka, Japan; 3Department of Urology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan Aim: To investigate the clinical efficacy of acotiamide hydrochloride hydrate in patients with detrusor underactivity. Methods: We measured the post-void residual urinary volume in 19 patients with underactive bladders. All these patients had been under treatment with distigmine bromide and were prescribed acotiamide hydrochloride hydrate at a dose of 100 mg three times daily for 2 weeks. Results: Compared with the post-void residual urinary volume value at baseline (161.4±90.0 mL a statistically significant reduction was observed at the end of treatment (116.3±63.1 mL (P=0.006. The drug was generally well tolerated by the majority of patients. Conclusion: Maybe, acotiamide hydrochloride hydrate showed clinical efficacy in patients with underactive bladders and may, therefore, be used alternatively in patients who do not respond sufficiently to distigmine bromide. Keywords: acotiamide hydrochloride hydrate, distigmine bromide, underactive bladder, detrusor underactive

  2. Brain SPECT study of detrusor overactivity and healthy men in urine withholding

    International Nuclear Information System (INIS)

    Yin Yafu; Li Xuena; Li Yaming; Noriyuki Shuke; Atsutaka Okizaki; Junichi Sato; Tamio Aburano

    2009-01-01

    The aim of the study is to identify the brain areas, which control the bladder storage by 99 Tc m -HMPAO SPECT with Neurological Statistical Image Analysis Software (NEUROSTAT). SPECT were performed on twenty-five patients with some storage symptoms of lower urinary tract, among which nineteen patients were with detrusor overactivity (DO) (Group II) and six patients were with normal detrusor function (Group III), and fifteen healthy volunteers (Group I). All the subjects were male and right-handed, and were scanned twice under two conditions: resting state and urine withholding state. NEUROSTAT was adopted to analyze the difference in rCBF between groups and states. The results were displayed on Z-score images at a significance threshold of P<0.05 with correction for multiple comparisons. No region reached significant threshold in comparison of Group II and III in resting state. There were significant increases in tracer activity in bilateral inferior frontal gyri and the right middle temporal gyrus in urine withholding state as compared with resting state in Group I and III (P<0.05 with correction for multiple comparisons, the corresponding Z value was more than 4.476 for Group I, more than 4.414 for Group III). Among the regions,the right inferior frontal gyrus was distinctly prominent at both Z-score and the extent. In Group II, only the left middle temporal gyrus and middle frontal gyrus were activated significantly in urine withholding state as compared with resting (P<0.05 with correction for multiple comparisons, the corresponding Z value was more than 4.35). The results indicated that bilateral inferior frontal gyri and the right middle temporal gyrus associated with the control of bladder storage.Especially, the right inferior frontal gyrus played a more important role in cerebral control of bladder storage, inhibiting the contraction of detrusor in urine storage. (authors)

  3. Risk estimation of multiple recurrence and progression of non muscle invasive bladder carcinoma using new mathematical models.

    Science.gov (United States)

    Luján, S; Santamaría, C; Pontones, J L; Ruiz-Cerdá, J L; Trassierra, M; Vera-Donoso, C D; Solsona, E; Jiménez-Cruz, F

    2014-12-01

    To apply new mathematical models according to Non Muscle Invasive Bladder Carcinoma (NMIBC) biological characteristics and enabling an accurate risk estimation of multiple recurrences and tumor progression. The classical Cox model is not valid for the assessment of this kind of events becausethe time betweenrecurrencesin the same patientmay be stronglycorrelated. These new models for risk estimation of recurrence/progression lead to individualized monitoring and treatment plan. 960 patients with primary NMIBC were enrolled. The median follow-up was 48.1 (3-160) months. Results obtained were validated in 240 patients from other center. Transurethral resection of the bladder (TURB) and random bladder biopsy were performed. Subsequently, adjuvant localized chemotherapy was performed. The variables analyzed were: number and tumor size, age, chemotherapy and histopathology. The endpoints were time to recurrence and time to progression. Cox model and its extensions were used as joint frailty model for multiple recurrence and progression. Model accuracy was calculated using Harrell's concordance index (c-index). 468 (48.8%) patients developed at least one tumor recurrence and tumor progression was reported in 52 (5.4%) patients. Variables for multiple-recurrence risk are: age, grade, number, size, treatment and the number of prior recurrences. All these together with age, stage and grade are the variables for progression risk. Concordance index was 0.64 and 0.85 for multiple recurrence and progression respectively. the high concordance reported besides to the validation process in external source, allow accurate multi-recurrence/progression risk estimation. As consequence, it is possible to schedule a follow-up and treatment individualized plan in new and recurrent NMCB cases. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

  4. A dosimetric comparison of 3D conformal vs intensity modulated vs volumetric arc radiation therapy for muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Foroudi Farshad

    2012-07-01

    Full Text Available Abstract Background To compare 3 Dimensional Conformal radiotherapy (3D-CRT with Intensity Modulated Radiotherapy (IMRT with Volumetric-Modulated Arc Therapy (VMAT for bladder cancer. Methods Radiotherapy plans for 15 patients with T2-T4N0M0 bladder cancer were prospectively developed for 3-DCRT, IMRT and VMAT using Varian Eclipse planning system. The same radiation therapist carried out all planning and the same clinical dosimetric constraints were used. 10 of the patients with well localised tumours had a simultaneous infield boost (SIB of the primary tumour planned for both IMRT and VMAT. Tumour control probabilities and normal tissue complication probabilities were calculated. Results Mean planning time for 3D-CRT, IMRT and VMAT was 30.0, 49.3, and 141.0 minutes respectively. The mean PTV conformity (CI index for 3D-CRT was 1.32, for IMRT 1.05, and for VMAT 1.05. The PTV Homogeneity (HI index was 0.080 for 3D-CRT, 0.073 for IMRT and 0.086 for VMAT. Tumour control and normal tissue complication probabilities were similar for 3D-CRT, IMRT and VMAT. The mean monitor units were 267 (range 250–293 for 3D-CRT; 824 (range 641–1083 for IMRT; and 403 (range 333–489 for VMAT (P  Conclusions VMAT is associated with similar dosimetric advantages as IMRT over 3D-CRT for muscle invasive bladder cancer. VMAT is associated with faster delivery times and less number of mean monitor units than IMRT. SIB is feasible in selected patients with localized tumours.

  5. NETUPITANT, A POTENT AND HIGHLY SELECTIVE NK1 RECEPTOR ANTAGONIST, ALLEVIATES ACETIC ACID-INDUCED BLADDER OVERACTIVITY IN ANESTHETIZED GUINEA-PIGS

    Directory of Open Access Journals (Sweden)

    Stefano Palea

    2016-08-01

    Full Text Available Introduction. Tachykinins potently contract the isolated urinary bladder from a number of animal species and play an important role in the regulation of the micturition reflex. On the guinea-pig isolated urinary bladder we examined the effects of a new potent and selective NK1 receptor antagonist (netupitant on the contractions induced by a selective NK1 receptor agonist, SP-methylester (SP-OMe. Moreover, the effects of netupitant and another selective NK1 antagonist (L-733,060 were studied in anesthetized guinea-pigs using two experimental models, the isovolumetric bladder contractions and a model of bladder overactivity induced by intravesical administration of acetic acid (AA. Methods and Results. Detrusor muscle strips were mounted in 5 mL organ baths and isometric contractions to cumulative concentrations of SP-OME were recorded before and after incubation with increasing concentrations of netupitant. In anesthetized female guinea-pigs, reflex bladder activity was examined under isovolumetric conditions with the bladder distended with saline or during cystometry using intravesical infusion of acetic acid (AA. After a 30 min stabilization period, netupitant (0.1-3 mg/kg, i.v. or L-733,060 (3-10 mg/kg, i.v. were administered. In the detrusor muscle, netupitant produced a concentration-dependent inhibition (mean pKB = 9.24 of the responses to SP-OMe. Under isovolumetric conditions, netupitant or L-733,060 reduced bladder contraction frequency in a dose-dependent manner, but neither drug changed bladder contraction amplitude. In the AA model, netupitant dose-dependently increased intercontraction interval (ICI but had no effect on the amplitude of micturition (AM. L-733,060 dose-dependently increased ICI also but this effect was paralleled by a significant reduction of AM. Conclusion. Netupitant decreases the frequency of reflex bladder contractions without altering their amplitude, suggesting that this drug targets the afferent limb of the

  6. ROLE OF ADJUVANT INTRAVESICAL CHEMOTHERAPY IN THE COMBINED ORGAN-SPARING TREATMENT OF NON-MUSCLE-INVASIVE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    A. Yu. Zubko

    2014-01-01

    Full Text Available Objective: to enhance the efficiency of combined treatment for non-muscle-invasive bladder cancer ((NMIBC and to assess the results of its treatment using transurethral resection (TUR as monotherapy and in combination with intravesical adjuvant chemotherapy (CT.Subjects and methods. The results of treatment were analyzed in 59 patients with NMIBC. Twenty-two patients underwent TUR in Group 1; TUR and single intravesical injection of drugs were performed in 19 patients in Group 2; 18 patients had TUR and long-term intravesical CT.Results and discussion. The recurrence rates were 59.1, 57.9, and 38.89 % in Groups 1, 2, and 3, respectively. Intravesical CT was found to appreciably affect the prevention of recurrence in the area of resection. The rate of this recurrence was 31.81, 26.32, and 5.56 % in Groups 1, 2, and 3, respectively. Conclusion. Adjuvant intravesical chemotherapy CT is an effective method to prevent recurrent bladder cancer.

  7. Contemporary management of patients with high-risk non-muscle-invasive bladder cancer who fail intravesical BCG therapy.

    Science.gov (United States)

    Yates, D R; Rouprêt, M

    2011-08-01

    It is advocated that patients with high-risk non-muscle-invasive bladder cancer (NMIBC) receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG, either early with persistent (refractory) disease or recur late after a long disease-free interval (relapsing). Guideline recommendation in the 'refractory' setting is radical cystectomy, but there are situations when extirpative surgery is not feasible due to competing co-morbidity, a patient's desire for bladder preservation or reluctance to undergo surgery. In this review, we discuss the contemporary management of NMIBC in patients who have failed prior BCG and are not suitable for radical surgery and highlight the potential options available. These options can be categorised as immunotherapy, chemotherapy, device-assisted therapy and combination therapy. However, the current data are still inadequate to formulate definitive recommendations, and data from ongoing trials and maturing studies will give us an insight into whether there is a realistic efficacious second-line treatment for patients who fail intravesical BCG but are not candidates for definitive surgery.

  8. Molecular markers in disease detection and follow-up of patients with non-muscle invasive bladder cancer.

    Science.gov (United States)

    Maas, Moritz; Walz, Simon; Stühler, Viktoria; Aufderklamm, Stefan; Rausch, Steffen; Bedke, Jens; Stenzl, Arnulf; Todenhöfer, Tilman

    2018-05-01

    Diagnosis and surveillance of non-muscle invasive bladder cancer (NMIBC) is mainly based on endoscopic bladder evaluation and urine cytology. Several assays for determining additional molecular markers (urine-, tissue- or blood-based) have been developed in recent years but have not been included in clinical guidelines so far. Areas covered: This review gives an update on different molecular markers in the urine and evaluates their role in patients with NMIBC in disease detection and surveillance. Moreover, the potential of recent approaches such as DNA methylation assays, multi-panel RNA gene expression assays and cell-free DNA analysis is assessed. Expert commentary: Most studies on various molecular urine markers have mainly focused on a potential replacement of cystoscopy. New developments in high throughput technologies and urine markers may offer further advantages as they may represent a non-invasive approach for molecular characterization of the disease. This opens new options for individualized surveillance strategies and may help to choose the best therapeutic option. The implementation of these technologies in well-designed clinical trials is essential to further promote the use of urine diagnostics in the management of patients with NMIBC.

  9. OVERACTIVE BLADDER SYNDROME IN CHILDREN

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    E.L. Vishnevskiy

    2007-01-01

    Full Text Available Overactive bladder is a specific syndrome characterized by bladder dysfunction that is clinically manifested by imperative urination (pollakiuria, urgency, urgent incontinence and nocturia. This state is very widely spread among children: every fifth child aged 4 to 7 shows typical bladder dysfunction. Quite often if urinary distresses are not studied well enough such children are falsely diagnosed with monosymptom enuresis, which, according to our information, actually happens in only 3,9% of cases. When examining children with urinary disorders it is reasonable to be geared to the protocol of European urologist association. According to this protocol, treatment should be started with antimuscarinimedications. The only antimuscarinic medication for treating children with hyperactive bladder that is legal in Russia is oxybutinin (Driptane, that is presently considered to be the «golden standard» of pharmaceutical treatment of overactive bladder for patients of any age. This statement is based on the modern idea of overactive bladder pathogenesis, that presupposes detrusorhypersensibility to acetylcholine. However, in some cases it might be reasonable to use some other medications, physiotherapy, sometimes as part of complex therapy. If individual dosage is observed, which will enable preventing or significantly lowering possible side effects, oxybutinin will be still considered «the golden standard» for treating overactive bladder for years to come in cases when detrusor hypersensibility to acetylcholine is the key component of bladder dysfunction pathogenesis.Key words: overactive bladder, oxybutinin, urination disorder, children.

  10. CD34-positive interstitial cells of the human detrusor

    DEFF Research Database (Denmark)

    Rasmussen, Helle; Hansen, Alastair; Smedts, Frank

    2007-01-01

    using a panel of antibodies directed against CD117/c-kit, CD34, CD31, S100, tryptase, neurofilament, NSE, Factor-VIII and GFAP. A striking finding was an interstitial type of cell which is CD34 immunoreactive (CD34-ir) but CD117/c-kit negative. The cells have a tentacular morphology, enveloping...... flattened processes, ramifying primarily in a bipolar fashion. Using immunoelectron microscopy (I-TEM) it was possible to view CD34 gold labelling of cells corresponding to interstitial cells. Although similar CD34-positive cells have been demonstrated in the bowel wall, they have never been described...... in the detrusor. The ontogeny and function of CD34-ir, a kit-negative cell, is unknown, but it may be involved in smooth muscle contraction....

  11. Effect of the SK/IK channel modulator 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591) on contractile force in rat, pig and human detrusor smooth muscle

    DEFF Research Database (Denmark)

    Nielsen, Jens Steen; Rode, Frederik; Rahbek, Mette

    2011-01-01

    • To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced by electri......• To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced...

  12. Pelvic floor muscle training in women with stress urinary incontinence causes hypertrophy of the urethral sphincters and reduces bladder neck mobility during coughing.

    Science.gov (United States)

    McLean, Linda; Varette, Kevin; Gentilcore-Saulnier, Evelyne; Harvey, Marie-Andree; Baker, Kevin; Sauerbrei, Eric

    2013-11-01

    The purpose of this study was to determine the effect of a 12-week pelvic floor muscle (PFM) training program on urethral morphology and mobility in women with stress urinary incontinence (SUI). Forty women with SUI were randomly assigned to one of two groups: the treatment group received 12 weekly physiotherapy sessions during which they learned how to properly contract their pelvic floor muscles (PFMs) and a home exercise program was prescribed, reviewed, and progressed; the control group received no treatment. Before and after the 12-week study period, ultrasound imaging was used to evaluate bladder neck position and mobility during coughing and Valsalva maneuver in supine and in standing, as well as urethral morphology. Secondary outcome measures included a 3-day bladder diary, 30-min pad test, the Incontinence Impact Questionnaire (IIQ-7) and the Urogenital Distress Inventory (UDI-6). The women in the treatment group demonstrated reduced bladder neck mobility during coughing and increased cross-sectional area of their urethra after as compared to before the training. These changes were not evident in the control group. No differences in the resting position of the bladder neck or in bladder neck excursion during Valsalva maneuver were noted in either group. Concomitantly the women in the treatment group demonstrated significant improvements in the 3-day bladder diary and IIQ-7 after the PFM training and improved significantly more than the control group. Physiotherapist-supervised PFM training reduces bladder neck motion during coughing, and results in hypertrophy of the urethral sphincter in women who present with SUI. © 2013 Wiley Periodicals, Inc.

  13. Immunoexpression of adrenergic receptors in detrusor from patients with prune belly syndrome: a digital quantification.

    Science.gov (United States)

    Schneider-Monteiro, Edison D; Dénes, Francisco T; Hampel, Christian; Leite, Katia R M; Thüroff, Joachim W; Srougi, Miguel

    2010-06-01

    Prune belly syndrome (PBS) presents with large-capacity bladders, high compliance and post-void residual volumes. Operative and conservative treatments are controversial. When histologically compared to normal bladder, bladder outlet obstruction results in an up- or down-regulation of adrenoceptors. Our goal was to study the immunoexpression of adrenoceptors in detrusor from patients with PBS. Bladder domes from PBS patients (n=14) were studied (PBG). For normal controls, bladder specimens were obtained at adult surgery (n=13) (CG1) and at child autopsy (n=5) (CG2). Staining was performed using antibodies to alpha1a, alpha1b, alpha1d and beta3 adrenoceptors. Five to 10 images were captured on an optic microscope with a digital camera and analysed with Photoshop. The immunocyhistochemical index with arbitrary units was calculated and compared. Mean age was 1.28, 64 and 1.41 years for PBG, CG1 and CG2, respectively. The immunohistochemical index with arbitrary units of alpha1a receptors was 0.06 in PBG, 0.16 in CG1 and 0.14 in CG2 (p=0.008); of alpha1b 0.06, 0.06 and 0.07 (p=0.781); and of alpha1d 0.04, 0.04 and 0.05 (p=0.618). Regarding beta3 the respective values were 0.07, 0.14 and 0.10 (p=0.378). Our results show a decrease in alpha1a-adrenoceptor immunostaining intensity in detrusor from children with PBS. Further in vitro studies are needed to determine whether these observations are physiologically significant. Copyright (c) 2010 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  14. Effect of the SK/IK channel modulator 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591) on contractile force in rat, pig and human detrusor smooth muscle

    DEFF Research Database (Denmark)

    Nielsen, Jens Steen; Rode, Frederik; Rahbek, Mette

    2011-01-01

    • To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced by electri...

  15. Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients.

    Directory of Open Access Journals (Sweden)

    Tatjana I Djukic

    Full Text Available OBJECTIVE: To examine the association of six glutathione transferase (GST gene polymorphisms (GSTT1, GSTP1/rs1695, GSTO1/rs4925, GSTO2/rs156697, GSTM1, GSTA1/rs3957357 with the survival of patients with muscle invasive bladder cancer and the genotype modifying effect on chemotherapy. PATIENTS AND METHODS: A total of 105 patients with muscle invasive bladder cancer were included in the study. The follow-up lasted 5 years. The effect of GSTs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier analysis was performed to assess differences in survival. RESULTS: GSTT1 active, GSTO1 Asp140Asp or GSTO2 Asp142Asp genotypes were independent predictors of a higher risk of death among bladder cancer patients (HR = 2.5, P = 0.028; HR = 2.9, P = 0.022; HR = 3.9, P = 0.001; respectively and significantly influenced the overall survival. There was no association between GSTP1, GSTM1 and GSTA1 gene variants with overall mortality. Only GSTO2 polymorphism showed a significant effect on the survival in the subgroup of patients who received chemotherapy (P = 0.006. CONCLUSION: GSTT1 active genotype and GSTO1 Asp140Asp and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive bladder cancer.

  16. New Aspects in the Differential Diagnosis and Therapy of Bladder Pain Syndrome/Interstitial Cystitis

    Directory of Open Access Journals (Sweden)

    Jochen Neuhaus

    2011-01-01

    Full Text Available Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical “columns”: (i clinical diagnostics, (ii histopathology, and (iii molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC.

  17. New Aspects in the Differential Diagnosis and Therapy of Bladder Pain Syndrome/Interstitial Cystitis

    Science.gov (United States)

    Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

    2011-01-01

    Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical “columns”: (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC. PMID:22028706

  18. New aspects in the differential diagnosis and therapy of bladder pain syndrome/interstitial cystitis.

    Science.gov (United States)

    Neuhaus, Jochen; Schwalenberg, Thilo; Horn, Lars-Christian; Alexander, Henry; Stolzenburg, Jens-Uwe

    2011-01-01

    Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical "columns": (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC.

  19. Botulinum toxin A for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    S. Deffontaines-Rufin

    2011-10-01

    Full Text Available PURPOSE: Neurogenic detrusor overactivity (NDO is common in patients who suffer from multiple sclerosis (MS. When the usual pharmacological treatment fails, botulinum toxin type A (BTX-A injections can be proposed. The safety and efficacy of this treatment are already well known, but only a few studies focus on its use in patients with MS. MATERIALS AND METHODS: Seventy-one patients with MS underwent their first BTX-A injection for refractory NDO. They had clinical and urodynamic cystometry assessment before and three months after injection. The patients were divided in three groups according to treatment efficacy: full success (total urinary continence, no overactive detrusor, improvement, or total failure (urge incontinence and overactive detrusor. RESULTS: 77% of the patients had clinical improvement or full success of the treatment with a reduction of their urgency and incontinence. Significant urodynamic improvement after treatment was shown on different parameters: volume at first involuntary bladder contraction (p = 0.0000001, maximum cystometric capacity (p = 0.0035, maximum detrusor pressure (p = 0.0000001. 46% of the patients were in the "full success" group. 31% of the patients had a partial improvement. 23% of the patients had no efficacy of the treatment. Duration of MS was a predictive factor of treatment failure (p = 0.015. CONCLUSIONS: Despite that a full success was obtained in 46% of the cases, BTX-A injection therapy failed to treat refractory NDO in 23% of patients suffering from MS. Duration of the disease was a predictive factor for an inefficient treatment. The injection therapy should be considered as soon as oral anticholinergic drugs fail to reduce NDO.

  20. Comparative immunohistochemical characterization of interstitial cells in the urinary bladder of human, guinea pig and pig.

    Science.gov (United States)

    Steiner, Clara; Gevaert, Thomas; Ganzer, Roman; De Ridder, Dirk; Neuhaus, Jochen

    2018-05-01

    Interstitial cells (ICs) are thought to play a functional role in urinary bladder. Animal models are commonly used to elucidate bladder physiology and pathophysiology. However, inter-species comparative studies on ICs are rare. We therefore analyzed ICs and their distribution in the upper lamina propria (ULP), the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human, guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry and 3D confocal immunofluorescence of the mesenchymal intermediate filament vimentin (VIM), alpha-smooth muscle actin (αSMA), platelet-derived growth factor receptor alpha (PDGFRα) and transient receptor potential cation channel A1 (TRPA1). Image stacks were processed for analysis using Huygens software; quantitative analysis was performed with Fiji macros. ICs were identified by immunoreactivity for VIM (excluding blood vessels). In all species ≥ 75% of ULP ICs were VIM + /PDGFRα + and ≥ 90% were VIM + /TRPA1 + . In human and pig ≥ 74% of ULP ICs were VIM + /αSMA + , while in GP the percentage differed significantly with only 37% VIM + /αSMA + ICs. Additionally, over 90% of αSMA + ICs were also TRPA1 + and PDGFRα + in human, GP and pig. In all three species, TRPA1 + and PDGFRα + ICs point to an active role for these cells in bladder physiology, regarding afferent signaling processes and signal modification. We hypothesize that decline in αSMA-positivity in GP reflects adaptation of bladder histology to smaller bladder size. In our experiments, pig bladder proved to be highly comparable to human urinary bladder and seems to provide safer interpretation of experimental findings than GP.

  1. Biochemical and functional correlates of an increased membrane density of caveolae in hypertrophic rat urinary bladder.

    Science.gov (United States)

    Shakirova, Yulia; Swärd, Karl; Uvelius, Bengt; Ekman, Mari

    2010-12-15

    Organ hypertrophy is often found to be associated with changes in the expression of caveolins and altered density of caveolae in the membrane. A plethora of signalling intermediaries are associated with caveolae and loss of caveolae has profound effects on contractility of the urinary bladder. We hypothesized that smooth muscle hypertrophy caused by bladder outflow obstruction (BOO) might lead to an altered caveola density with consequences for contractile regulation. Rat BOO for 6 weeks caused a 2.56-fold increase in the number of smooth muscle caveolae per μm membrane. No changes in the expression of caveolin-1 or cavin-1, normalized to β-actin were seen, but membrane area per unit muscle volume dropped to 0.346. Hypertrophy was associated with altered contraction in response to carbachol. The effect on contraction of cholesterol desorption, which disrupts lipid rafts and caveolae, was however not changed. Contraction in response to bradykinin resisted mβcd in control destrusor, but was inhibited by it after 6 weeks of obstruction. It is concluded that rat detrusor hypertrophy leads to an increased number of caveolae per unit membrane area. This change is due to a reduction of membrane area per volume muscle and it does not play a role for cholinergic activation, but promotes contraction in response to bradykinin after long-term obstruction. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Contractility of the guinea pig bladder measured in situ and in vitro

    NARCIS (Netherlands)

    J.M. Groen (Jan); R. van Mastrigt (Ron); J.L.H.R. Bosch (Ruud)

    1994-01-01

    textabstractTo study the relative importance of neurogenic factors in detrusor contractility and to relate a total bladder in vitro contractility model to a previously described bladder wall strip model, active intravesical pressure values were compared in situ and in vitro in eight male guinea

  3. Aging and recurrent urinary tract infections are associated with bladder dysfunction in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Tzu-Li Lin

    2012-09-01

    Conclusion: The urodynamic study revealed a temporal effect on bladder function, and women with diabetic voiding dysfunction were found to have had a longer duration of DM than women with an overactive detrusor. However, aging and recurrent urinary tract infections are the two independent factors that contribute to impaired voiding function and diabetic bladder dysfunction.

  4. Bladder compliance after posterior sacral root rhizotomies and anterior sacral root stimulation

    NARCIS (Netherlands)

    Koldewijn, E. L.; van Kerrebroeck, P. E.; Rosier, P. F.; Wijkstra, H.; Debruyne, F. M.

    1994-01-01

    To evaluate the effects of central detrusor denervation on bladder compliance, we studied 27 patients with complete suprasacral spinal cord injury in whom intradural posterior sacral root rhizotomies from S2 to S5 in combination with implantation of an intradural Finetech-Brindley bladder stimulator

  5. A panel of prognostic protein markers for progression in non-muscle invasive bladder cancer - a multicenter tissue microarray validation study

    DEFF Research Database (Denmark)

    Fristrup, Niels; Birkenkamp-Demtröder, Karin; Ulhøi, Benedicte Parm

    2012-01-01

    cohort of 283 patients with long-term follow-up. For validation of the results we used three independent patient cohorts with long-term follow-up from Sweden, Spain, and Taiwan. In total 649 primary NMIBC tissue-microarray specimens from patients with long-term follow-up were used. Protein expression......Bladder cancer is the fifth most common cancer in the Western world. The histopathological parameters used in the clinic cannot precisely predict the individual disease course. Bladder cancer patients are therefore monitored thoroughly for disease recurrence and progression by urine and cystoscopy...... Ta and T1 urothelial carcinomas. Transcripts from the five genes encoding these proteins were previously included in gene expression signatures for outcome prediction for non-muscle invasive bladder cancer (NMIBC). As a training-set, we used primary NMIBC tissue-microarray specimens from a Danish...

  6. Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

    International Nuclear Information System (INIS)

    Vashistha, Vishal; Wang, Hanzhang; Mazzone, Andrew; Liss, Michael A.; Svatek, Robert S.; Schleicher, Mary; Kaushik, Dharam

    2017-01-01

    Purpose: To perform a comprehensive comparison of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and treatment-related complications between radical cystectomy (RC) and combined modality treatment (CMT—radiation therapy, concurrent chemotherapy, and maximal transurethral resection of bladder tumor) in the setting of muscle-invasive bladder cancer. Methods and Materials: We searched 7 databases (PubMed, Scopus, EMBASE, Proquest, CINAHL, and (ClinicalTrials.gov)) for randomized, controlled trials and prospective and retrospective studies directly comparing RC with CMT from database inception to March 2016. We conducted meta-analyses evaluating OS, DSS, and PFS with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Nineteen studies evaluating 12,380 subjects were selected. For the 8 studies encompassing 9554 subjects eligible for meta-analyses, we found no difference in OS at 5 years (HR 0.96, favoring CMT, 95% CI 0.72-1.29; P=.778) or 10 years (HR 1.02, favoring cystectomy, 95% CI 0.73-1.42; P=.905). No difference was observed in DSS at 5 years (HR 0.83, favoring radiation, 95% CI 0.54-1.28; P=.390) or 10 years (HR 1.17, favoring cystectomy, 95% CI 0.89-1.55; P=.264), or PFS at 10 years (HR 0.85, favoring CMT, 95% CI 0.43-1.67; P=.639). The cystectomy arms had higher rates of early major complications, whereas rates of minor complications were similar between the 2 treatments. Conclusion: Current meta-analysis reveals no differences in OS, DSS, or PFS between RC and CMT. Further randomized, controlled trials are necessary to identify the optimal treatment for specific patients.

  7. The Prognostic Role of Circulating Tumor Cells (CTC) in High-risk Non-muscle-invasive Bladder Cancer.

    Science.gov (United States)

    Busetto, Gian Maria; Ferro, Matteo; Del Giudice, Francesco; Antonini, Gabriele; Chung, Benjamin I; Sperduti, Isabella; Giannarelli, Diana; Lucarelli, Giuseppe; Borghesi, Marco; Musi, Gennaro; de Cobelli, Ottavio; De Berardinis, Ettore

    2017-08-01

    The purpose of this study was to evaluate the impact of circulating tumor cells (CTCs) as a prognostic marker in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) and assess the efficacy and reliability of 2 different CTC isolation methods. Globally, 155 patients with a pathologically confirmed diagnosis of high-risk NMIBC were included (pT1G3 with or without carcinoma in situ) and underwent transurethral resection of bladder tumor (TURB) after a blood withdrawal for CTC evaluation. A total of 101 patients (Group A) had their samples analyzed with the CellSearch automated system, and 54 (Group B) had their samples analyzed with the CELLection Dynabeads manual system. Patients were followed for 28 months, and during this interval, there were a total of 65 (41.9%) recurrences, 27 (17.4%) disease progressions, and 9 (5.8%) lymph node and/or bone metastasis. In our CTC analysis, there were 20 (19.8%) positive patients in Group A and 24 in Group B (44.4%). In our analysis, we found a strong correlation between CTC presence and time to first recurrence; in Group A, we observed an incidence of recurrence in 75% of CTC-positive patients and in Group B of 83% of CTC-positive patients. The time to progression was also strongly correlated with CTCs: 65% and 29%, respectively, of those patients who progressed in those with CTCs in Group A and B. The study demonstrates the potential role of CTCs as a prognostic marker for risk stratification in patients with NMIBC, to predict both recurrence and progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Vashistha, Vishal [Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Wang, Hanzhang [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States); Mazzone, Andrew [Rush Medical College, Rush University Medical Center, Chicago, Illinois (United States); Liss, Michael A.; Svatek, Robert S. [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States); Schleicher, Mary [Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Kaushik, Dharam, E-mail: Kaushik@uthscsa.edu [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States)

    2017-04-01

    Purpose: To perform a comprehensive comparison of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and treatment-related complications between radical cystectomy (RC) and combined modality treatment (CMT—radiation therapy, concurrent chemotherapy, and maximal transurethral resection of bladder tumor) in the setting of muscle-invasive bladder cancer. Methods and Materials: We searched 7 databases (PubMed, Scopus, EMBASE, Proquest, CINAHL, and (ClinicalTrials.gov)) for randomized, controlled trials and prospective and retrospective studies directly comparing RC with CMT from database inception to March 2016. We conducted meta-analyses evaluating OS, DSS, and PFS with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Nineteen studies evaluating 12,380 subjects were selected. For the 8 studies encompassing 9554 subjects eligible for meta-analyses, we found no difference in OS at 5 years (HR 0.96, favoring CMT, 95% CI 0.72-1.29; P=.778) or 10 years (HR 1.02, favoring cystectomy, 95% CI 0.73-1.42; P=.905). No difference was observed in DSS at 5 years (HR 0.83, favoring radiation, 95% CI 0.54-1.28; P=.390) or 10 years (HR 1.17, favoring cystectomy, 95% CI 0.89-1.55; P=.264), or PFS at 10 years (HR 0.85, favoring CMT, 95% CI 0.43-1.67; P=.639). The cystectomy arms had higher rates of early major complications, whereas rates of minor complications were similar between the 2 treatments. Conclusion: Current meta-analysis reveals no differences in OS, DSS, or PFS between RC and CMT. Further randomized, controlled trials are necessary to identify the optimal treatment for specific patients.

  9. Feasibility of Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Patients With Diminished Renal Function.

    Science.gov (United States)

    Koshkin, Vadim S; Barata, Pedro C; Rybicki, Lisa A; Zahoor, Haris; Almassi, Nima; Redden, Alicia M; Fergany, Amr F; Kaouk, Jihad; Haber, Georges-Pascal; Stephenson, Andrew J; Ornstein, Moshe C; Gilligan, Timothy; Garcia, Jorge A; Rini, Brian I; Grivas, Petros

    2018-02-22

    Cisplatin-based neoadjuvant chemotherapy (NAC) before radical cystectomy is the standard of care in muscle-invasive bladder cancer. There are limited data regarding chemotherapy tolerability and outcomes for patients with low glomerular filtration rate (GFR) who receive cisplatin-based NAC. A retrospective analysis of patients who received cisplatin-based NAC at Cleveland Clinic (2005-2016) was undertaken. Patients with pre-NAC GFR < 60 mL/min by either Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) formula were compared to patients with GFR ≥ 60 mL/min for NAC tolerability, pathologic complete and partial response (pPR), and the ability to undergo radical cystectomy. Thirty patients with low GFR (34-59 mL/min) and 94 patients with normal GFR (≥ 60 mL/min) were identified. Low GFR patients were older (median, 71 vs. 65 years), but other demographic and transurethral resection of bladder tumor characteristics were comparable. Low GFR patients more frequently had early NAC discontinuation (30% vs. 13%), NAC modifications (delays, dose reduction, or discontinuation, 66% vs. 40%), and cisplatin-based NAC administered in split doses (37% vs. 16%). No differences in NAC tolerability or outcomes were noted among low GFR patients receiving split-dose versus standard regimens. No differences were noted between low and normal GFR patients in NAC cycles (median, 3 for each), cystectomy rates (93% for each), time to cystectomy, and GFR change from baseline to after NAC. Pathologic complete response was higher among normal GFR patients (24% vs. 14%). Patients with low GFR had more NAC discontinuations and modifications, but most completed planned NAC cycles. For carefully selected patients with GFR < 60 mL/min, cisplatin-based NAC remains a treatment option. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Significance of ERBB2 overexpression in therapeutic resistance and cancer-specific survival in muscle-invasive bladder cancer patients treated with chemoradiation-based selective bladder-sparing approach.

    Science.gov (United States)

    Inoue, Masaharu; Koga, Fumitaka; Yoshida, Soichiro; Tamura, Tomoki; Fujii, Yasuhisa; Ito, Eisaku; Kihara, Kazunori

    2014-10-01

    To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder-sparing protocol. ERBB 2-targeting treatment may improve the outcomes

  11. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    International Nuclear Information System (INIS)

    Inoue, Masaharu; Koga, Fumitaka; Yoshida, Soichiro; Tamura, Tomoki; Fujii, Yasuhisa; Ito, Eisaku; Kihara, Kazunori

    2014-01-01

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  12. Systemic Immunotherapy of Non–Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti–PD-L1 Immune Checkpoint Inhibitor

    Science.gov (United States)

    Vandeveer, Amanda J.; Fallon, Jonathan K.; Tighe, Robert; Sabzevari, Helen; Schlom, Jeffrey; Greiner, John W.

    2016-01-01

    Bacillus Calmette-Guerin (BCG) is the standard of care for intravesical therapy for carcinoma in situ and non–muscle invasive, nonmetastatic human urothelial carcinoma. While the responsiveness to this immunotherapeutic is believed to be linked with (i) a high number of somatic mutations and (ii) a large number of tumor-infiltrating lymphocytes, recent findings of the roles that inhibitory immune receptors and their ligands play in tumor evasion may provide insights into the limitations of the effectiveness of BCG and offer new targets for immune-based therapy. In this study, an aggressive, bioluminescent orthotopic bladder cancer model, MB49 tumor cells transfected with luciferase (MB49luc), was used to study the antitumor effects of avelumab, an antibody to PD-L1. MB49luc murine tumor cells form multifocal tumors on the mucosal wall of the bladder reminiscent of non–muscle invasive, nonmetastatic urothelial carcinomas. MB49luc bladder tumors are highly positive for the expression of PD-L1 and avelumab administration induced significant (P<0.05) antitumor effects. These antitumor effects were more dependent on the presence of CD4 than CD8 T cells, as determined by in vivo immune cell depletions. The findings suggest that in this bladder tumor model, interruption of the immune suppressive PD-1/PD-L1 complex releases a local adaptive immune response that, in turn, reduces tumor growth. This bladder tumor model can be used to further identify host antitumor immune mechanisms and evaluate combinations of immune-based therapies for carcinoma in situ and non–muscle invasive, nonmetastatic urothelial carcinoma, to provide the rationale for subsequent clinical studies. PMID:26921031

  13. Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor.

    Science.gov (United States)

    Vandeveer, Amanda J; Fallon, Jonathan K; Tighe, Robert; Sabzevari, Helen; Schlom, Jeffrey; Greiner, John W

    2016-05-01

    Bacillus Calmette-Guerin (BCG) is the standard of care for intravesical therapy for carcinoma in situ and non-muscle invasive, nonmetastatic human urothelial carcinoma. Although the responsiveness to this immunotherapeutic is believed to be linked with (i) a high number of somatic mutations and (ii) a large number of tumor-infiltrating lymphocytes, recent findings of the roles that inhibitory immune receptors and their ligands play in tumor evasion may provide insights into the limitations of the effectiveness of BCG and offer new targets for immune-based therapy. In this study, an aggressive, bioluminescent orthotopic bladder cancer model, MB49 tumor cells transfected with luciferase (MB49(luc)), was used to study the antitumor effects of avelumab, an antibody to PD-L1. MB49(luc) murine tumor cells form multifocal tumors on the mucosal wall of the bladder reminiscent of non-muscle invasive, nonmetastatic urothelial carcinomas. MB49(luc) bladder tumors are highly positive for the expression of PD-L1, and avelumab administration induced significant (P < 0.05) antitumor effects. These antitumor effects were more dependent on the presence of CD4 than CD8 T cells, as determined by in vivo immune cell depletions. The findings suggest that in this bladder tumor model, interruption of the immune-suppressive PD-1/PD-L1 complex releases a local adaptive immune response that, in turn, reduces tumor growth. This bladder tumor model can be used to further identify host antitumor immune mechanisms and evaluate combinations of immune-based therapies for carcinoma in situ and non-muscle invasive, nonmetastatic urothelial carcinoma, to provide the rationale for subsequent clinical studies. Cancer Immunol Res; 4(5); 452-62. ©2016 AACR. ©2016 American Association for Cancer Research.

  14. A dosimetric comparison of 3D conformal vs intensity modulated vs volumetric arc radiation therapy for muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Foroudi, Farshad; Kron, Tomas; Wilson, Lesley; Bressel, Mathias; Haworth, Annette; Hornby, Colin; Pham, Daniel; Cramb, Jim; Gill, Suki; Tai, Keen Hun

    2012-01-01

    To compare 3 Dimensional Conformal radiotherapy (3D-CRT) with Intensity Modulated Radiotherapy (IMRT) with Volumetric-Modulated Arc Therapy (VMAT) for bladder cancer. Radiotherapy plans for 15 patients with T2-T4N0M0 bladder cancer were prospectively developed for 3-DCRT, IMRT and VMAT using Varian Eclipse planning system. The same radiation therapist carried out all planning and the same clinical dosimetric constraints were used. 10 of the patients with well localised tumours had a simultaneous infield boost (SIB) of the primary tumour planned for both IMRT and VMAT. Tumour control probabilities and normal tissue complication probabilities were calculated. Mean planning time for 3D-CRT, IMRT and VMAT was 30.0, 49.3, and 141.0 minutes respectively. The mean PTV conformity (CI) index for 3D-CRT was 1.32, for IMRT 1.05, and for VMAT 1.05. The PTV Homogeneity (HI) index was 0.080 for 3D-CRT, 0.073 for IMRT and 0.086 for VMAT. Tumour control and normal tissue complication probabilities were similar for 3D-CRT, IMRT and VMAT. The mean monitor units were 267 (range 250–293) for 3D-CRT; 824 (range 641–1083) for IMRT; and 403 (range 333–489) for VMAT (P < 0.05). Average treatment delivery time were 2:25min (range 2:01–3:09) for 3D-CRT; 4:39 (range 3:41–6:40) for IMRT; and 1:14 (range 1:13–1:14) for VMAT. In selected patients, the SIB did not result in a higher dose to small bowel or rectum. VMAT is associated with similar dosimetric advantages as IMRT over 3D-CRT for muscle invasive bladder cancer. VMAT is associated with faster delivery times and less number of mean monitor units than IMRT. SIB is feasible in selected patients with localized tumours

  15. Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology.

    Science.gov (United States)

    Vetterlein, Malte W; Wankowicz, Stephanie A M; Seisen, Thomas; Lander, Richard; Löppenberg, Björn; Chun, Felix K-H; Menon, Mani; Sun, Maxine; Barletta, Justine A; Choueiri, Toni K; Bellmunt, Joaquim; Trinh, Quoc-Dien; Preston, Mark A

    2017-11-15

    Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, to the authors' knowledge, it is unknown whether this benefit persists in histological variants. The objective of the current study was to assess the effect of neoadjuvant chemotherapy on the probability of non-organ-confined disease and overall survival after radical cystectomy (RC) in patients with histological variants. Querying the National Cancer Data Base, the authors identified 2018 patients with histological variants who were undergoing RC for bladder cancer between 2003 and 2012. Variants were categorized as micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other histology. Logistic regression models estimated the odds of non-organ-confined disease at the time of RC for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup. Patients with neuroendocrine tumors (odds ratio [OR], 0.16; 95% confidence interval [95% CI], 0.08-0.32 [Pchemotherapy. An overall survival benefit for neoadjuvant chemotherapy was only found in patients with neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]). Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better overall survival and lower rates of non-organ-confined disease at the time of RC. For tumors with micropapillary differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant chemotherapy decreased the frequency of non-organ-confined disease at the time of RC. However, this favorable effect did not translate into a statistically significant overall survival benefit for these patients, potentially due to the aggressive tumor biology. Cancer 2017;123:4346-55. © 2017 American Cancer Society. © 2017 American Cancer Society.

  16. Urofacial syndrome: A subset of neurogenic bladder dysfunction syndromes?

    Directory of Open Access Journals (Sweden)

    K N Stamatiou

    2010-01-01

    Full Text Available The urofacial syndrome is probably a subset of neurogenic bladder dysfunction syndromes characterized by detrusor-sphincter discoordination along with a characteristic inversion of facial expression with laughing. This characteristic facial expression can facilitate early detection of this disorder, which leads to poor bladder emptying with high residual urine, hydro-nephrosis with vesico-ureteral reflux and potentially renal failure if left untreated. The etiology of the urofacial syndrome is unknown. In our case, a 12-year-old boy of Middle-Eastern origin presented to the Outpatient Department of our hospital with left pyelonephritis, hydronephrosis and bladder dilatation. Voiding cystourethrography performed 15 days later revealed left vesicoureteral reflux. Cystoscopy revealed bladder trabeculation however an anatomic urethral obstruction was not noticed. Both, neurological examination and radiography of the lumbosacral spine were normal. Urodynamic evaluation revealed the typical findings of detrusor-sphincter discoordination.

  17. Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Seiler, Roland; Ashab, Hussam Al Deen; Erho, Nicholas; van Rhijn, Bas W G; Winters, Brian; Douglas, James; Van Kessel, Kim E; Fransen van de Putte, Elisabeth E; Sommerlad, Matthew; Wang, Natalie Q; Choeurng, Voleak; Gibb, Ewan A; Palmer-Aronsten, Beatrix; Lam, Lucia L; Buerki, Christine; Davicioni, Elai; Sjödahl, Gottfrid; Kardos, Jordan; Hoadley, Katherine A; Lerner, Seth P; McConkey, David J; Choi, Woonyoung; Kim, William Y; Kiss, Bernhard; Thalmann, George N; Todenhöfer, Tilman; Crabb, Simon J; North, Scott; Zwarthoff, Ellen C; Boormans, Joost L; Wright, Jonathan; Dall'Era, Marc; van der Heijden, Michiel S; Black, Peter C

    2017-10-01

    An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). Gene expression analysis was used to assign subtypes. Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. Different molecular

  18. Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Jonathan A Ewald

    Full Text Available The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta, superficial (T1 and muscle-invasive (≥T2 bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and

  19. A droplet-based building block approach for bladder smooth muscle cell (SMC) proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Xu, F; Moon, S J; Emre, A E; Turali, E S; Song, Y S; Hacking, S A; Demirci, U [Department of Medicine, Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Nagatomi, J, E-mail: udemirci@rics.bwh.harvard.ed [Department of Bioengineering, Clemson University, Clemson, SC (United States)

    2010-03-15

    Tissue engineering based on building blocks is an emerging method to fabricate 3D tissue constructs. This method requires depositing and assembling building blocks (cell-laden microgels) at high throughput. The current technologies (e.g., molding and photolithography) to fabricate microgels have throughput challenges and provide limited control over building block properties (e.g., cell density). The cell-encapsulating droplet generation technique has potential to address these challenges. In this study, we monitored individual building blocks for viability, proliferation and cell density. The results showed that (i) SMCs can be encapsulated in collagen droplets with high viability (>94.2 +- 3.2%) for four cases of initial number of cells per building block (i.e. 7 +- 2, 16 +- 2, 26 +- 3 and 37 +- 3 cells/building block). (ii) Encapsulated SMCs can proliferate in building blocks at rates that are consistent (1.49 +- 0.29) across all four cases, compared to that of the controls. (iii) By assembling these building blocks, we created an SMC patch (5 mm x 5 mm x 20 mum), which was cultured for 51 days forming a 3D tissue-like construct. The histology of the cultured patch was compared to that of a native rat bladder. These results indicate the potential of creating 3D tissue models at high throughput in vitro using building blocks.

  20. Prostaglandin D2 effects and DP1 /DP2 receptor distribution in guinea pig urinary bladder out-flow region.

    Science.gov (United States)

    Guan, Na N; Svennersten, Karl; de Verdier, Petra J; Wiklund, N Peter; Gustafsson, Lars E

    2017-02-01

    The proximal urethra and urinary bladder trigone play important roles in continence. We have previously shown that PGD 2 is released from guinea pig bladder urothelium/suburothelium and can inhibit detrusor contractile responses. We presently wished to investigate PGD 2 actions in guinea pig out-flow region and the distribution of DP 1 /DP 2 receptors. The effects of PGD 2 on urothelium-intact trigone and proximal urethra contractility were studied in organ bath experiments. Expression of DP 1 /DP 2 receptor proteins was analysed by western blot. Immunohistochemistry was used to identify distribution of DP 1 /DP 2 receptors. PGD 2 in a dose-dependent manner inhibited trigone contractions induced by electrical field stimulation (EFS) and inhibited spontaneous contractions of the proximal urethra. PGD 2 was equally (trigone) or slightly less potent (urethra) compared with PGE 2 . Expression of DP 1 and DP 2 receptors was found in male guinea pig bladder trigone, neck and proximal urethra. In the trigone and proximal urethra, DP 1 receptors were found on the membrane of smooth muscle cells and weak immunoreactivty was observed in the urothelium. DP 2 receptors were distributed more widespread, weakly and evenly in the urothelium and smooth muscles. Inhibitory effects by PGD 2 on motor activity of guinea pig trigone and proximal urethra are consistent with finding DP 1 and DP 2 receptors located in the urothelium and smooth muscle cells of the trigone and proximal urethra, and PGD 2 may therefore be a modulator of the bladder out-flow region, possibly having a function in regulation of micturition and a role in overactive bladder syndrome. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  1. Toward Self-Control Systems for Neurogenic Underactive Bladder: A Triboelectric Nanogenerator Sensor Integrated with a Bistable Micro-Actuator.

    Science.gov (United States)

    Arab Hassani, Faezeh; Mogan, Roshini P; Gammad, Gil G L; Wang, Hao; Yen, Shih-Cheng; Thakor, Nitish V; Lee, Chengkuo

    2018-04-24

    Aging, neurologic diseases, and diabetes are a few risk factors that may lead to underactive bladder (UAB) syndrome. Despite all of the serious consequences of UAB, current solutions, the most common being ureteric catheterization, are all accompanied by serious shortcomings. The necessity of multiple catheterizations per day for a physically able patient not only reduces the quality of life with constant discomfort and pain but also can end up causing serious complications. Here, we present a bistable actuator to empty the bladder by incorporating shape memory alloy components integrated on flexible polyvinyl chloride sheets. The introduction of two compression and restoration phases for the actuator allows for repeated actuation for a more complete voiding of the bladder. The proposed actuator exhibits one of the highest reported voiding percentages of up to 78% of the bladder volume in an anesthetized rat after only 20 s of actuation. This amount of voiding is comparable to the common catheterization method, and its one time implantation onto the bladder rectifies the drawbacks of multiple catheterizations per day. Furthermore, the scaling of the device for animal models larger than rats can be easily achieved by adjusting the number of nitinol springs. For neurogenic UAB patients with degraded nerve function as well as degenerated detrusor muscle, we integrate a flexible triboelectric nanogenerator sensor with the actuator to detect the fullness of the bladder. The sensitivity of this sensor to the filling status of the bladder shows its capability for defining a self-control system in the future that would allow autonomous micturition.

  2. Risk factor assessment in high-risk, bacillus Calmette–Guérin-treated, non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Holz S

    2017-09-01

    Full Text Available Serge Holz,* Simone Albisinni,* Jacques Gilsoul, Michel Pirson, Véronique Duthie, Thierry Quackels, Marc Vanden Bossche, Thierry Roumeguère Department of Urology, Erasme Hospital, Université libre de Bruxelles, Belgium *These authors contributed equally to this work Objective: To assess the risk factors associated with recurrence, progression and survival in high-risk non-muscle-invasive bladder cancer (NMIBC patients treated with bacillus Calmette–Guérin (BCG and validate the European Organization for Research and Treatment of Cancer (EORTC and Spanish Urological Club for Oncological Treatment (CUETO scores.Patients and methods: We retrospectively analyzed all BCG-treated NMIBC patients from 1998 to 2012. Multiple variables were tested as risk factors for recurrence-free survival and progression-free survival (PFS. Variables included age, sex, grade, stage, tumor size, number of tumors, carcinoma in situ (CIS, recurrence status, BCG strain used, smoking status, use of re-staging transurethral resection and use of single immediate postoperative instillation. We also tested the accuracy of EORTC and CUETO scores in predicting recurrence and progression.Results: Overall, 123 patients were analyzed. Median (interquartile range follow-up was 49 months. The 5-year overall survival, cancer-specific survival, recurrence-free survival and PFS were 75.0%, 89.3%, 59.4% and 79.2%, respectively. On univariate analysis, multiple tumors (≥3, concomitant CIS and smoking influenced recurrence. Regarding progression, multiple tumors, concomitant CIS and Connaught strain (vs Tice negatively influenced PFS on univariate and multivariate analyses were independent prognostic factors. CUETO scores were accurate, with a slight overestimation, while EORTC score was not predictive of recurrence or progression.Conclusion: In this study, CIS and tumor multiplicity were unfavorable predictors of recurrence and progression in patients with NMIBC receiving BCG

  3. Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

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    Elizabeth A Guancial

    Full Text Available Platinum (Pt-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC. However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our group previously demonstrated a significant correlation between tissue Pt concentration and tumor response to Pt-based neoadjuvant chemotherapy (NAC in lung cancer. We hypothesized that increased Pt concentration in radical cystectomy (RC specimens would correlate with improved pathologic response to Pt-based NAC in MIBC.A cohort of 19 clinically annotated, archived, fresh frozen RC specimens from patients with MIBC treated with Pt-based NAC was identified [ypT0 (pathologic complete response, pCR, N = 4; ≤ypT1N0M0 (pathologic partial response, pPR, N = 6; ≥ypT2 (minimal pathologic response/progression, N = 9]. RC specimens from 2 patients with MIBC who did not receive NAC and 1 treated with a non-Pt containing NAC regimen were used as negative controls. Total Pt concentration in normal adjacent urothelial tissue and bladder tumors from RC specimens was measured by flameless atomic absorption spectrophotometry.Total Pt concentration in normal urothelium differed by tumor pathologic response (P = 0.011. Specimens with pCR had the highest Pt concentrations compared to those with pPR (P = 0.0095 or no response/progression (P = 0.020. There was no significant difference in Pt levels in normal urothelium and tumor between pPR and no response/progression groups (P = 0.37; P = 0.25, respectively.Our finding of increased intracellular Pt in RC specimens with pCR following NAC for MIBC compared to those with residual disease suggests that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Factors that modulate intracellular Pt concentration, such as expression of Pt transporters, warrant further investigation as predictive biomarkers of response to Pt-based NAC in MIBC.

  4. The association between smoking cessation before and after diagnosis and non-muscle-invasive bladder cancer recurrence: a prospective cohort study.

    Science.gov (United States)

    van Osch, Frits H M; Jochems, Sylvia H J; Reulen, Raoul C; Pirrie, Sarah J; Nekeman, Duncan; Wesselius, Anke; James, Nicholas D; Wallace, D Michael A; Cheng, K K; van Schooten, Frederik J; Bryan, Richard T; Zeegers, Maurice P

    2018-07-01

    Smoking is a major risk factor for bladder cancer, but the relationship between smoking cessation after initial treatment and bladder cancer recurrence has been investigated less frequently and not prospectively yet. 722 non-muscle-invasive bladder cancer (NMIBC) patients (pTa, pT1, and CIS) from the prospective Bladder Cancer Prognosis Programme (BCPP) cohort, selected in the UK between 2005 and 2011, provided complete data on smoking behavior before and up to 5 years after diagnosis. The impact of smoking behavior on NMIBC recurrence was explored by multivariable Cox regression models investigating time-to-first NMIBC recurrence. Over a median follow-up period of 4.21 years, 403 pathologically confirmed NMIBC recurrences occurred in 210 patients. Only 25 current smokers at diagnosis quit smoking (14%) during follow-up and smoking cessation after diagnosis did not decrease risk of recurrence compared to continuing smokers (p = 0.352). Although quitting smoking after diagnosis might reduce the risk of recurrence based on retrospective evidence, this is not confirmed in this prospective study because the number of NMIBC patients quitting smoking before their first recurrence was too low. Nevertheless, this indicates an important role for urologists and other health care professionals in promoting smoking cessation in NMIBC.

  5. Sensory dysfunction of bladder mucosa and bladder oversensitivity in a rat model of metabolic syndrome.

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    Wei-Chia Lee

    Full Text Available PURPOSE: To study the role of sensory dysfunction of bladder mucosa in bladder oversensitivity of rats with metabolic syndrome. MATERIALS AND METHODS: Female Wistar rats were fed a fructose-rich diet (60% or a normal diet for 3 months. Based on cystometry, the fructose-fed rats (FFRs were divided into a group with normal detrusor function or detrusor overactivity (DO. Acidic adenosine triphosphate (ATP solution (5mM, pH 3.3 was used to elicit reflex micturition. Cystometric parameters were evaluated before and after drug administration. Functional proteins of the bladder mucosa were assessed by western blotting. RESULTS: Compared to the controls, intravesical acidic ATP solution instillation induced a significant increase in provoked phasic contractions in both FFR groups and a significant decrease in the mean functional bladder capacity of group DO. Pretreatment with capsaicin for C-fiber desentization, intravesical liposome for mucosal protection, or intravenous pyridoxal 5-phosphate 6-azophenyl-2',4'-disulfonic acid for antagonized purinergic receptors can interfere with the urodynamic effects of intravesical ATP in FFRs and controls. Over-expression of TRPV1, P2X(3, and iNOS proteins, and down-regulation of eNOS proteins were observed in the bladder mucosa of both fructose-fed groups. CONCLUSIONS: Alterations of sensory receptors and enzymes in the bladder mucosa, including over-expression of TRPV1, P2X(3, and iNOS proteins, can precipitate the emergence of bladder phasic contractions and oversensitivity through the activation of C-afferents during acidic ATP solution stimulation in FFRs. The down-regulation of eNOS protein in the bladder mucosa of FFRs may lead to a failure to suppress bladder oversensitivity and phasic contractions. Sensory dysfunction of bladder mucosa and DO causing by metabolic syndrome are easier to elicit bladder oversensitivity to certain urothelium stimuli.

  6. Clinical results of conformal versus intensity-modulated radiotherapy using a focal simultaneous boost for muscle-invasive bladder cancer in elderly or medically unfit patients.

    Science.gov (United States)

    Lutkenhaus, Lotte J; van Os, Rob M; Bel, Arjan; Hulshof, Maarten C C M

    2016-03-18

    For elderly or medically unfit patients with muscle-invasive bladder cancer, cystectomy or chemotherapy are contraindicated. This leaves radical radiotherapy as the only treatment option. It was the aim of this study to retrospectively analyze the treatment outcome and associated toxicity of conformal versus intensity-modulated radiotherapy (IMRT) using a focal simultaneous tumor boost for muscle-invasive bladder cancer in patients not suitable for cystectomy. One hundred eighteen patients with T2-4 N0-1 M0 bladder cancer were analyzed retrospectively. Median age was 80 years. Treatment consisted of either a conformal box technique or IMRT and included a simultaneous boost to the tumor. To enable an accurate boost delivery, fiducial markers were placed around the tumor. Patients were treated with 40 Gy in 20 fractions to the elective treatment volumes, and a daily tumor boost up to 55-60 Gy. Clinical complete response was seen in 87 % of patients. Three-year overall survival was 44 %, with a locoregional control rate of 73 % at 3 years. Toxicity was low, with late urinary and intestinal toxicity rates grade ≥ 2 of 14 and 5 %, respectively. The use of IMRT reduced late intestinal toxicity, whereas fiducial markers reduced acute urinary toxicity. Radical radiotherapy using a focal boost is feasible and effective for elderly or unfit patients, with a 3-year locoregional control of 73 %. Toxicity rates were low, and were reduced by the use of IMRT and fiducial markers.

  7. Experimental model of bladder instability in rabbits

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    Balasteghin K.T.

    2003-01-01

    Full Text Available OBJECTIVE: Propose a new experimental model of bladder instability in rabbits after partial bladder obstruction. MATERIALS AND METHODS: Thirty North Folk male rabbits, weighting 1,700 to 2,820 g (mean: 2,162 g were studied. The animals were distributed in 2 experimental groups, formed by 15 rabbits each: Group 1 - clinical control. In this group there was no surgical intervention; Group 2 - bladder outlet obstruction. In this group, after anesthetizing the animal, urethral cannulation with Foley catheter 10F was performed and then an adjustable plastic bracelet was passed around the bladder neck. It was then adjusted in order to not constrict the urethra. The following parameters were studied in M1 - pre-operative period; M2 - 4 weeks post-operatively moments: 1- urine culture; 2- cystometric study; 3- serum creatinine and BUN. RESULTS: Bladder weight was 2.5 times larger in the group with obstruction than in the control group. Cystometric evaluation showed a significant increase in maximal vesical volume in the final moment at Group G2. However, there was no statistically significant difference among the groups studied. There was no statistically significant difference between maximal detrusor pressure and vesical compliance in the different moments or in the studied groups. There was an absence of uninhibited detrusor contractions in all the animals in group 1, and involuntary contractions were detected in 93% of group 2 animals. There was no significant variation in BUN and serum creatinine either among the groups or in the same group. CONCLUSIONS: We observed in the group with obstruction a bladder weight 2.5 higher than normal bladders. We detected involuntary contractions in 93% of the animals in group 2, establishing this experimental model as appropriate to secondary bladder instability and partial bladder outlet obstruction.

  8. Retinoblastoma protein expression and radiation response in muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    Pollack, Alan; Czerniak, Bogdan; Zagars, Gunar K.; Hu Shixue; Wu, Catherine S.; Dinney, Colin P.N.; Chyle, Valerian; Benedict, William F.

    1997-01-01

    survival in Stage T3b patients. Patient outcome was best when RB negative and p53 negative staining were seen. Conclusion: Our results indicate that loss of RB function as measured by immunohistochemical staining is the strongest correlate of radiation response thus far recognized. Loss of RB expression also predicted for poor outcome in Stage T3b patients, which appeared to compliment the finding of normal p53 expression. While normal RB protein expression is usually associated with better patient outcome, other series have not examined patients treated with radiotherapy. The absence of pRB may be a useful marker for selecting patients for bladder preservation with radiotherapy, particularly when wild-type p53 is present

  9. Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Galsky, Matthew D; Pal, Sumanta K; Chowdhury, Simon

    2015-01-01

    ). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P = .48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved......BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had...... clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients...

  10. Platelet-derived growth factor receptor beta: a novel urinary biomarker for recurrence of non-muscle-invasive bladder cancer.

    Science.gov (United States)

    Feng, Jiayu; He, Weifeng; Song, Yajun; Wang, Ying; Simpson, Richard J; Zhang, Xiaorong; Luo, Gaoxing; Wu, Jun; Huang, Chibing

    2014-01-01

    Non-muscle-invasive bladder cancer (NMIBC) is one of the most common malignant tumors in the urological system with a high risk of recurrence, and effective non-invasive biomarkers for NMIBC relapse are still needed. The human urinary proteome can reflect the status of the microenvironment of the urinary system and is an ideal source for clinical diagnosis of urinary system diseases. Our previous work used proteomics to identify 1643 high-confidence urinary proteins in the urine from a healthy population. Here, we used bioinformatics to construct a cancer-associated protein-protein interaction (PPI) network comprising 16 high-abundance urinary proteins based on the urinary proteome database. As a result, platelet-derived growth factor receptor beta (PDGFRB) was selected for further validation as a candidate biomarker for NMIBC diagnosis and prognosis. Although the levels of urinary PDGFRB showed no significant difference between patients pre- and post-surgery (n = 185, P>0.05), over 3 years of follow-up, urinary PDGFRB was shown to be significantly higher in relapsed patients (n = 68) than in relapse-free patients (n = 117, P<0.001). The levels of urinary PDGFRB were significantly correlated with the risk of 3-year recurrence of NMIBC, and these levels improved the accuracy of a NMIBC recurrence risk prediction model that included age, tumor size, and tumor number (area under the curve, 0.862; 95% CI, 0.809 to 0.914) compared to PDGFR alone. Therefore, we surmise that urinary PDGFRB could serve as a non-invasive biomarker for predicting NMIBC recurrence.

  11. Whole-exome sequencing of muscle-invasive bladder cancer identifies recurrent mutations of UNC5C and prognostic importance of DNA repair gene mutations on survival.

    Science.gov (United States)

    Yap, Kai Lee; Kiyotani, Kazuma; Tamura, Kenji; Antic, Tatjana; Jang, Miran; Montoya, Magdeline; Campanile, Alexa; Yew, Poh Yin; Ganshert, Cory; Fujioka, Tomoaki; Steinberg, Gary D; O'Donnell, Peter H; Nakamura, Yusuke

    2014-12-15

    Because of suboptimal outcomes in muscle-invasive bladder cancer even with multimodality therapy, determination of potential genetic drivers offers the possibility of improving therapeutic approaches and discovering novel prognostic indicators. Using pTN staging, we case-matched 81 patients with resected ≥pT2 bladder cancers for whom perioperative chemotherapy use and disease recurrence status were known. Whole-exome sequencing was conducted in 43 cases to identify recurrent somatic mutations and targeted sequencing of 10 genes selected from the initial screening in an additional 38 cases was completed. Mutational profiles along with clinicopathologic information were correlated with recurrence-free survival (RFS) in the patients. We identified recurrent novel somatic mutations in the gene UNC5C (9.9%), in addition to TP53 (40.7%), KDM6A (21.0%), and TSC1 (12.3%). Patients who were carriers of somatic mutations in DNA repair genes (one or more of ATM, ERCC2, FANCD2, PALB2, BRCA1, or BRCA2) had a higher overall number of somatic mutations (P = 0.011). Importantly, after a median follow-up of 40.4 months, carriers of somatic mutations (n = 25) in any of these six DNA repair genes had significantly enhanced RFS compared with noncarriers [median, 32.4 vs. 14.8 months; hazard ratio of 0.46, 95% confidence interval (CI), 0.22-0.98; P = 0.0435], after adjustment for pathologic pTN staging and independent of adjuvant chemotherapy usage. Better prognostic outcomes of individuals carrying somatic mutations in DNA repair genes suggest these mutations as favorable prognostic events in muscle-invasive bladder cancer. Additional mechanistic investigation into the previously undiscovered role of UNC5C in bladder cancer is warranted. ©2014 American Association for Cancer Research.

  12. The outcome of a multi-centre feasibility study of online adaptive radiotherapy for muscle-invasive bladder cancer TROG 10.01 BOLART

    International Nuclear Information System (INIS)

    Foroudi, Farshad; Pham, Daniel; Rolfo, Aldo; Bressel, Mathias; Tang, Colin I.; Tan, Alex; Turner, Sandra; Hruby, George; Williams, Stephen; Hayne, Dickon; Lehman, Margot; Skala, Marketa; Jose, Chakiath C.; Gogna, Kumar; Kron, Tomas

    2014-01-01

    Purpose: To assess whether online adaptive radiotherapy for bladder cancer is feasible across multiple Radiation Oncology departments using different imaging, delivery and recording technology. Materials and methods: A multi-centre feasibility study of online adaptive radiotherapy, using a choice of three “plan of the day”, was conducted at 12 departments. Patients with muscle-invasive bladder cancer were included. Departments were activated if part of the pilot study or after a site-credentialing visit. There was real time review of the first two cases from each department. Results: 54 patients were recruited, with 50 proceeding to radiotherapy. There were 43 males and 7 females with a mean age of 78 years. The tumour stages treated included T1 (1 patient), T2 (35), T3 (10) and T4 (4). One patient died of an unrelated cause during radiotherapy. The three adaptive plans were created before the 10th fraction in all cases. In 8 (16%) of the patients, a conventional plan using a ‘standard’ CTV to PTV margin of 1.5 cm was used for one or more fractions where the pre-treatment bladder CTV was larger than any of the three adaptive plans. The bladder CTV extended beyond the PTV on post treatment imaging in 9 (18%) of the 49 patients. Conclusions: From a technical perspective an online adaptive radiotherapy technique can be instituted in a multi-centre setting. However, without further bladder filling control or imaging, a CTV to PTV margin of 7 mm is insufficient

  13. Prognostic value of p53 in patients with muscle-invasive bladder cancer treated with preoperative radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Catherine S; Pollack, Alan; Czerniak, Bogdan A; Chyle, Valerian; Zagars, Gunar K; Dinney, Colin P; Benedict, William F

    1995-07-01

    Purpose/Objective: The overexpression of mutated and/or wild type p53 has been associated with poorer prognosis in patients with bladder cancer. However, most studies have involved a mixed patient population, including those with superficial and muscle-invasive disease, and some patients treated with adjuvant chemotherapy. In this study we examine the prognostic significance of p53 detected immunohistochemically in a cohort of patients with muscle-invasive transitional cell carcinoma of the bladder treated relatively uniformly with preoperative radiotherapy 4-6 weeks prior to radical cystectomy. Materials and Methods: Of 301 patients treated with preoperative radiotherapy (50 Gy in 25 fractions over 5 weeks) for muscle-invasive bladder cancer between 1960-1983, adequate material for immunohistochemical analysis of p53 was obtained in 107. Formalin-fixed paraffin-embedded archival tissue was stained using monoclonal anti-p53 antibody D01 (Oncogene Science, Manhasset, NY). The immunostaining of p53 was considered positive if greater than 20% of the tumor nuclei were stained. There were 82 men and 25 women with a mean age of 61 yr and no patient received neoadjuvant or adjuvant chemotherapy. All patients were without distant metastasis prior to treatment initiation. The median follow-up for those living (n=32) was 88 mo. The number of patients by clinical stage was 48 for T2, 30 for T3a, and 29 for T3b. Results: Overall, 46% of the patients were p53 positive, with 42% in Stage T2, 57% in Stage T3a, and 41% in Stage T3b. The distributions of potential patient prognostic factors by p53 positivity were investigated and the only association was with lymphatic-vascular invasion (p=0.04, chi-square). No correlation was seen between p53 staining and pathologic complete response (seen in 47%), clinical-to-pathologic downstaging (seen in 69%), clinical stage, tumor grade, tumor morphology, tumor number, tumor size, gender, patient age, pretreatment hemoglobin levels, BUN

  14. Impact of age and gender on the clinicopathological characteristics of bladder cancer

    Directory of Open Access Journals (Sweden)

    Parag Gupta

    2009-01-01

    Full Text Available Purpose: To determine the impact of age and gender on the clinicopathological characteristics of histologically confirmed bladder cancer in India. Materials and Methods: From January 2001 to June 2008, records of patients with bladder cancer were evaluated for age and gender at presentation, clinical symptoms, cystoscopic finding, history of smoking, and histopathological characteristics. A total of 561 patients were identified from the computer-based hospital information system and the case files of patients. Results: A total of 97% of the patients presented with painless hematuria. The mean age was 60.2 ± 4.4 years old (range: 18-90 years old and the male to female ratio was 8.6:1. Transitional cell carcinoma (TCC was the most common histological variety, which was present in 97.71% (470 of 481 of the patients. A total of 26% of the patients had muscle invasive disease at the time of presentation. However, 34.5% (166 of 481 of the patients did not show any evidence of detrusor muscle in their biopsy specimen. In patients with nonmuscle-invasive bladder carcinoma, 55% had p Ta while 45% had p T1. Overall, 44.7% (215 of 481 of the patients had low-grade disease. Among patients younger than 60 years old, low-grade (51.0% vs. 38.1%; P = 0.006 and low-stage (77.1% vs. 70.8%; P = 0.119 disease were more prevalent than in patients older than 60 years old. The incidence of smoking was much higher among males compared with females (74% vs. 22%. Conclusion: TCC is the predominant cancer, with significant male preponderance among Indian patients. Younger-aged patients have low-grade disease. Hematuria is the most common presentation and greater awareness is needed not to overlook bladder cancer.

  15. Is [F-18]-fluorodeoxyglucose FDG-PET/CT better than CT alone for the preoperative lymph node staging of muscle invasive bladder cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Uttam, Mete; Pravin, Nayak; Anish, Bhattacharya; Nandita, Kakkar; Arup, Mandal, E-mail: uttam_mete@yahoo.com [PGIMER, Chandigarh, (India)

    2016-03-15

    Objective: To evaluate whether the use of [F-18]-FDG-PET/CT can accurately predict pelvic lymph node metastasis in patients with muscle invasive TCC of the bladder undergoing radical cystectomy. Materials and methods: Fifteen patients with muscle invasive bladder cancer had undergone FDG-PET/CT scan from the skull base to the mid-thighs after IV injection of 6.5MBq (Mega-Becquerel)/Kg of FDG. After intravenous hydration IV furosemide was given to overcome the difficulties posed by urinary excretion of {sup 18}F-FDG. PET/ CT data were analyzed as PET and CT images studied separately as well as fused PET/ CT images. The imaging findings were correlated with the histopathology of the nodes (gold standard). Results: CT and FDG-PET had demonstrated positive lymph nodes in 9 & 8 patients respectively. Among the 15 patients 3 had documented metastasis on histopathology. Both CT and PET could detect the nodes in all these 3 patients (100% sensitivity). Nodes were histologically negative amongst 6&5 patients who had node involvement by CT and PET respectively. Therefore, specificity, positive predictive value (PPV) & negative predictive value (NPV) for CT and PET/CT were 50%, 33.3%, 100% and 58.3%, 37.5%, 100% respectively. Conclusion: The theoretical advantage of this cutting edge technology for whole body imaging has not been translated into clinical practice as we found minimal advantage of combined FDG-PET/CT over CT alone for nodal staging of muscle invasive bladder cancer. This may be due to substantial overlap between standardized uptake values (SUVs) from active inflammatory processes with those of malignant lesion. (author)

  16. Initial Results of Bladder Preserving Approach by Chemo-Radiotherapy in Patients with Muscle Invading Transitional Cell Carcinoma

    International Nuclear Information System (INIS)

    Aboziada, M.A.; Hamza, H.; Abdlrahem, A.M.

    2009-01-01

    This study was conducted to test the efficacy and tolerability of trimodality treatment for invasive bladder cancer and to test the possibility of bladder sparing. Methods: This study had been carried out on 50 patients with transitional cell carcinoma (TCC) stage T2- T3 tumors with adequate performance status and renal function. All patients were subjected to maximum transurethral resection of bladder tumors (TURBT). Patients were then subjected to chemo-radiation that was executed in two treatment phases. Phase I was external radiotherapy in the form of 46 Gy /23 fractions /5 weeks to whole pelvis with concurrent cisplatin 40 mg/m 2 weekly. Phase II was 20 Gy /10 fractions /2 weeks to the bladder tumor with concurrent cisplatin 40 mg/m2 weekly. After phase I, patients who had complete response (CR) or partial response (PR) were subjected to phase II and patients who had stationary disease (SD) were subjected to salvage cystectomy. After the end of treatment, patients who had CR were subjected to bladder preservation. Radiological and cystoscopic reevaluation was done to assess the tumor response after phase I and phase II. After completion of the scheduled treatment, patients were under follow up for clinical examination, radiological, and cystoscopic assessment. Results: The treatment schedule was tolerable and was associated with infrequent incidence of moderate toxicity that was easily controlled without interruption of treatment. Bladder preservation was achieved in 72% of patients. The actuarial relapse free survival and overall survival at a median follow up 18 months for patients who were candidate for bladder preservation were 81% and 100%; respectively. Invasive recurrence (16%) sal-Jvaged with cystectomy and superficial recurrence (6%) successfully treated with Bacilles bilie de Calmette- Guerin. Conclusions: This study indicates that in spite of a relatively small number of patients and short follow-up period; the trimodality treatment could be an

  17. Copy Number Analysis of 24 Oncogenes: MDM4 Identified as a Putative Marker for Low Recurrence Risk in Non Muscle Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Samanta Salvi

    2014-07-01

    Full Text Available Patients with non-muscle invasive bladder cancer (NMIBC generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy number variations (CNVs of 24 oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR and BRAF using multiplex ligation probe amplification technique to verify their role as predictive markers of recurrence. Formalin-fixed paraffin-embedded tissue samples from 43 patients who underwent transurethral resection of the bladder (TURB were used; 23 patients had relapsed and 20 were disease-free after 5 years. Amplification frequencies were analyzed for all genes and MDM4 was the only gene that showed significantly higher amplification in non recurrent patients than in recurrent ones (0.65 vs. 0.3; Fisher’s test p = 0.023. Recurrence-free survival analysis confirmed the predictive role of MDM4 (log-rank test p = 0.041. Our preliminary results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. Confirmation of this hypothesis is needed in a larger cohort of NMIBC patients.

  18. The awareness of patients with non - muscle invasive bladder cancer regarding the importance of smoking cessation and their access to smoking cessation programs

    Directory of Open Access Journals (Sweden)

    Emrah Yuruk

    Full Text Available ABSTRACT Objectives Smoking is the most important risk factor for bladder cancer and smoking cessation is associated with reduced risk of tumor recurrence and progression. The aim of this study is to assess the awareness of non-muscle invasive bladder cancer (NMIBC patients regarding the importance of smoking cessation, determine their access to smoking cessation programs and the effects of smoking cessation on recurrence rates of NMIBC. Materials and Methods NMIBC patients who were followed with cystoscopy were included in the study. Their demographic properties were recorded, along with their smoking habits, awareness regarding the effects of smoking on bladder cancer and previous attempts for smoking cessation. Moreover, the patients were asked whether they applied for a smoking cessation program. Recurrence of bladder cancer during the follow-up period was also noted. Results A total of 187 patients were included in the study. The mean age was 64.68±12.05 (range: 15-90 and the male to female ratio was 167/20. At the time of diagnosis, 114 patients (61.0% were active smokers, 35 patients (18.7% were ex-smokers and 38 patients (20.3% had never smoked before. After the diagnosis, 83.3% of the actively smoking patients were advised to quit smoking and 57.9% of them quit smoking. At the time of the study, 46.52% of the NMIBC patients were aware of the link between smoking and bladder cancer, whereas only 4.1% of the smoking patients were referred to smoking cessation programs. After a mean follow-up of 32.28±11.42 months, 84 patients (44.91% had recurrence; however, current smoking status or awareness of the causative role of smoking on NMIBC did not affect the recurrence. Conclusion In our study group, the majority of the NMIBC patients were not aware of the association between smoking and bladder cancer. Although most of the physicians advised patients to quit smoking, a significant amount of the patients were still active smokers during

  19. ErbB2 and NFκB overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer.

    Directory of Open Access Journals (Sweden)

    Fumitaka Koga

    Full Text Available Radical cystectomy for muscle-invasive bladder cancer (MIBC patients frequently impairs their quality of life (QOL due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS were investigated. Of the 35 patients, 11 (31% achieved pathological CR, while tumors in the remaining 24 patients (69% were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014, 15.4 (P = 0.024 and 14.3 (P = 0.038. The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001. The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056 along with chemoradiation resistance (P = 0.003 and hydronephrosis (P = 0.018. The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with

  20. Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer.

    Science.gov (United States)

    Gözen, Ali Serdar; Umari, Paolo; Scheitlin, Walter; Su, Fuat Ernis; Akin, Yigit; Rassweiler, Jens

    2017-06-30

    Background&Aim: High grade non-muscle invasive bladder cancer (NMIBC) is common in urological practice. Most of these cancers are or become refractory to intravesical immunotherapy and chemotherapy. Here we evaluated the efficacy of combined local bladder hyperthermia and intravesical mitomycin-C (MMC) instillation in patients with high-risk recurrent NMIBC. Between February 2014 and December 2015, 18 patients with high risk NMIBC were enrolled. Patients were treated in an outpatient basis with 6 weekly induction sessions followed by monthly maintenance sessions with intravesical MMC in local hyperthermia with bladder wall thermo-chemotherapy (BWT) system (PelvixTT system, Elmedical Ltd., Hod Hasharon, Israel). The follow-up regimen included cystoscopy after the induction cycle and thereafter with regular intervals. Time to disease recurrence was defined as time from the first intravesical treatment to endoscopic or histological documentation of a new bladder tumour. Adverse events were recorded according to CTC 4.0 (Common Toxicity Criteria) score system. Mean age was 72 (32-87) years. 10 patients had multifocal disease, 9 had CIS, 6 had recurrent disease and 2 had highly recurrent disease (> 3 recurrences in a 24 months period). 6 patients underwent previous intravesical chemotherapy with MMC. The average number of maintenance sessions per patient was 7.6. After a mean follow-up of 433 days, 15 patients (83.3%) were recurrence-free. 3 patients had tumour recurrence after a mean period of 248 days without progression. Side effects were limited to grade 1 in 2 patients and grade 2 in 1 patient. BWT seems to be feasible and safe in high grade NMIBC. More studies are needed to identify the subgroup of patients who may benefit more from this treatment.

  1. Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Ali Serdar Gözen

    2017-06-01

    Full Text Available Background&Aim: High grade non-muscle invasive bladder cancer (NMIBC is common in urological practice. Most of these cancers are or become refractory to intravesical immunotherapy and chemotherapy. Here we evaluated the efficacy of combined local bladder hyperthermia and intravesical mitomycin-C (MMC instillation in patients with high-risk recurrent NMIBC. Materials and methods: Between February 2014 and December 2015, 18 patients with high risk NMIBC were enrolled. Patients were treated in an outpatient basis with 6 weekly induction sessions followed by monthly maintenance sessions with intravesical MMC in local hyperthermia with bladder wall thermo-chemotherapy (BWT system (PelvixTT system, Elmedical Ltd., Hod Hasharon, Israel. The follow-up regimen included cystoscopy after the induction cycle and thereafter with regular intervals. Time to disease recurrence was defined as time from the first intravesical treatment to endoscopic or histological documentation of a new bladder tumour. Adverse events were recorded according to CTC 4.0 (Common Toxicity Criteria score system. Results: Mean age was 72 (32-87 years. 10 patients had multifocal disease, 9 had CIS, 6 had recurrent disease and 2 had highly recurrent disease (> 3 recurrences in a 24 months period. 6 patients underwent previous intravesical chemotherapy with MMC. The average number of maintenance sessions per patient was 7.6. After a mean follow-up of 433 days, 15 patients (83.3% were recurrence-free. 3 patients had tumour recurrence after a mean period of 248 days without progression. Side effects were limited to grade 1 in 2 patients and grade 2 in 1 patient. Conclusions: BWT seems to be feasible and safe in high grade NMIBC. More studies are needed to identify the subgroup of patients who may benefit more from this treatment.

  2. Definition and symptoms of underactive bladder.

    Science.gov (United States)

    Uren, Alan D; Drake, Marcus J

    2017-12-01

    Underactive bladder (UAB) is a symptom syndrome reflecting the urodynamic observation of detrusor underactivity (DU), a voiding contraction of reduced strength and/or duration, leading to prolonged or incomplete bladder emptying. An International Continence Society Working Group has described UAB as characterised by a slow urinary stream, hesitancy and straining to void, with or without a feeling of incomplete bladder emptying and dribbling, often with storage symptoms. Since DU often coexists with bladder outlet obstruction, or storage dysfunction (detrusor overactivity or incontinence), the exact contribution of the DU to the presenting complaints can be difficult to establish. The presence of voiding and post voiding lower urinary tract symptoms (LUTS) is implicitly expected in UAB, but a reduced sensation of fullness is reported by some patients, and storage LUTS are also an important factor in many affected patients. These may result from a postvoid residual, but often they do not. The storage LUTS are often the key driver in leading the patient to seek healthcare input. Nocturia is particularly common and bothersome, but what the role of DU is in all the range of influences on nocturia has not been established. Qualitative research has established a broad impact on everyday life as a result of these symptoms. In general, people appear to manage the voiding LUTS relatively well, but the storage LUTS may be problematic.

  3. Herpes zoster induced neuropathic bladder--a case report.

    Science.gov (United States)

    Tsai, Hsiu-Nan; Wu, Wen-Jeng; Huang, Shu-Pin; Su, Chin-Ming; Chen, Chung-Chin; Wang, Chii-Jye; Chou, Yii-Her; Huang, Chun-Hsiung

    2002-01-01

    Herpes zoster infection involving the sacral dermatomes has been associated with bladder dysfunction and, although rarely, with acute urinary retention. Less than 150 cases have been reported in the literature. After reviewing our institute's chart records covering a period of time dating from 1991 to 2001, we found that three of our patients had developed acute urinary retention following herpes zoster skin lesions of the S2-4 dermatomes. Herein we report our findings. These three patients had previously been found to have normal voiding status. However, at the time of complaint urodynamic studies revealed detrusor areflexia or detrusor hyporeflexia with decreased sensation of bladder filling. After micturation recovery, repeat urodynamic studies revealed detrusor pressure and bladder sensation recovery. After one to six weeks of treatment, all three patients could void spontaneously without catheterization. We found that, when treated with antiviral medication, supportive analgesics, and temporary urinary drainage, which included urethral catheterization and suprapubic cystostomy, acute urinary retention associated with herpes zoster has a generally favorable prognosis. In other words, we found that in spite of its rarity, herpes zoster induced neuropathic bladder dysfunction is reversible when treated appropriately.

  4. Preoperative prognostic nutritional index and nomogram predicting recurrence-free survival in patients with primary non-muscle-invasive bladder cancer without carcinoma in situ

    Directory of Open Access Journals (Sweden)

    Cui J

    2017-11-01

    Full Text Available Jianfeng Cui,1,* Shouzhen Chen,1,* Qiyu Bo,2 Shiyu Wang,1 Ning Zhang,1 Meng Yu,1 Wenfu Wang,1 Jie Han,3 Yaofeng Zhu,1 Benkang Shi1 1Department of Urology, 2Department of First Operating Room, Qilu Hospital of Shandong University, 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background and objectives: Among the cancers of the urogenital system, bladder cancer is ranked second both in incidence and mortality, and hence, a more accurate estimate of the prognosis for individual patients with non-muscle-invasive bladder cancer (NMIBC is urgently needed. Prognostic nutritional index (PNI which is based on serum albumin levels and peripheral lymphocyte count has been confirmed to have prognostic value in various cancers. The aim of this study was to clarify the prognostic value of PNI in patients with NMIBC.Methods: Data of 329 patients with NMIBC were evaluated retrospectively. Recurrence-free survival (RFS was assessed using the Kaplan–Meier method, and the equivalences of survival curves were tested by log-rank tests. The univariate and multivariate analyses were performed using the Cox proportional hazards regression model. Discrimination of the nomogram was measured by the concordance index. A p-value of <0.05 was considered statistically significant.Results: In univariate analysis, age, tumor focality, tumor size, tumor grade, pathological T stage and preoperative PNI were significantly associated with RFS. Multivariate analysis identified PNI as an independent predictor of RFS in patients with NMIBC. According to these independent predictors, a nomogram for the prediction of recurrence was developed.Conclusion: PNI can be regarded as an independent prognostic factor for predicting RFS in NMIBC. The nomogram could be useful to improve personalized therapy for patients with NMIBC. Keywords: non-muscle

  5. [(18)F]Fluorodeoxyglucose - positron emission tomography/computed tomography improves staging in patients with high-risk muscle-invasive bladder cancer scheduled for radical cystectomy.

    Science.gov (United States)

    Kollberg, Petter; Almquist, Helen; Bläckberg, Mats; Cronberg, Carin; Garpered, Sabine; Gudjonsson, Sigurdur; Kleist, Jakob; Lyttkens, Kerstin; Patschan, Oliver; Liedberg, Fredrik

    2015-01-01

    The aim of this study was to evaluate the clinical use of [(18)F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in addition to conventional preoperative radiological investigations in a defined group of patients with high-risk muscle-invasive bladder cancer. In total, 103 patients with high-risk muscle-invasive bladder cancer defined as stage T3/T4 disease or as stage T2 with hydronephrosis or high-risk histological features, who were provisionally scheduled to undergo cystectomy, were prospectively recruited to the study. The patients were referred to FDG-PET/CT in addition to standard preoperative investigation with computed tomography (CT). The final treatment decision was reached at a multidisciplinary conference based on all available information including the FDG-PET/CT findings. Compared to CT alone, FDG-PET/CT provided more supplemental findings suggesting malignant manifestations in 48 (47%) of the 103 patients. The additional FDG-PET/CT findings led to an altered provisional treatment plan in 28 out of 103 patients (27%), detection of disseminated bladder cancer and subsequent cancellation of the initially intended cystectomy in 16 patients, and identification of disseminated disease and treatment with induction chemotherapy before radical cystectomy in 12 patients. Preoperative FDG-PET/CT changed the treatment plan for a considerable proportion (27%) of the present patients. Accordingly, such examination can potentially improve the preoperative staging of cystectomy patients with high-risk features, and may also reduce the number of futile operations in patients with advanced disease who are beyond cure.

  6. Clinical results of conformal versus intensity-modulated radiotherapy using a focal simultaneous boost for muscle-invasive bladder cancer in elderly or medically unfit patients

    International Nuclear Information System (INIS)

    Lutkenhaus, Lotte J.; Os, Rob M. van; Bel, Arjan; Hulshof, Maarten C. C. M.

    2016-01-01

    For elderly or medically unfit patients with muscle-invasive bladder cancer, cystectomy or chemotherapy are contraindicated. This leaves radical radiotherapy as the only treatment option. It was the aim of this study to retrospectively analyze the treatment outcome and associated toxicity of conformal versus intensity-modulated radiotherapy (IMRT) using a focal simultaneous tumor boost for muscle-invasive bladder cancer in patients not suitable for cystectomy. One hundred eighteen patients with T2-4 N0-1 M0 bladder cancer were analyzed retrospectively. Median age was 80 years. Treatment consisted of either a conformal box technique or IMRT and included a simultaneous boost to the tumor. To enable an accurate boost delivery, fiducial markers were placed around the tumor. Patients were treated with 40 Gy in 20 fractions to the elective treatment volumes, and a daily tumor boost up to 55–60 Gy. Clinical complete response was seen in 87 % of patients. Three-year overall survival was 44 %, with a locoregional control rate of 73 % at 3 years. Toxicity was low, with late urinary and intestinal toxicity rates grade ≥ 2 of 14 and 5 %, respectively. The use of IMRT reduced late intestinal toxicity, whereas fiducial markers reduced acute urinary toxicity. Radical radiotherapy using a focal boost is feasible and effective for elderly or unfit patients, with a 3-year locoregional control of 73 %. Toxicity rates were low, and were reduced by the use of IMRT and fiducial markers. The online version of this article (doi:10.1186/s13014-016-0618-6) contains supplementary material, which is available to authorized users

  7. Bladder Management

    Science.gov (United States)

    ... Catheterization • Urinary Tract Infections: Indwelling (Foley) Catheter Bladder Management [ Download this pamphlet: "Bladder Management" - (PDF, 499KB) ] The ... and medication or surgery may be helpful. Bladder Management Foley or Suprapubic Catheter A tube is inserted ...

  8. Bladder Cancer

    Science.gov (United States)

    ... organ in your lower abdomen that stores urine. Bladder cancer occurs in the lining of the bladder. It ... urinate Low back pain Risk factors for developing bladder cancer include smoking and exposure to certain chemicals in ...

  9. Overactive bladder – 18 years – Part II

    Directory of Open Access Journals (Sweden)

    Jose Carlos Truzzi

    2016-04-01

    Full Text Available ABSTRACT Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics – pillars of the overactive bladder pharmacotherapy – started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning – as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder – 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder.

  10. Detrusor overactivity in diabetic and non-diabetic patients: is there a difference?

    LENUS (Irish Health Repository)

    Golabek, Tomasz

    2013-07-22

    To compare urodynamic characteristics in patients with idiopathic detrusor overactivity (IDO) with those of an age matched cohort with diabetes mellitus (DM) and detrusor overactivity (DO). Secondly, to determine whether urodynamic features could help distinguish these two groups of patients.

  11. Near-infrared spectroscopy of the bladder: a new technique for studying lower urinary tract function in health and disease

    Science.gov (United States)

    Shadgan, Babak; Afshar, Kourosh; Stothers, Lynn; Macnab, Andrew

    2010-02-01

    Background: Continuous wave near-infrared spectroscopy (NIRS) can monitor chromophore change in the bladder detrusor muscle during voiding; oxygenation and hemodynamic data derived differ in health and disease. Application of wireless NIRS for evaluation of voiding dysfunction would benefit children. Methods: Subjects: 20 children (4-17 yrs) [5 normal, 15 with urinary tract pathology]. Instrumentation: self-contained device weight 84 gm; 3 paired light emitting diodes (760/850 nm) in a spatially resolved configuration; source-detector separation distances (30, 35 and 40 mm); silicon photodiode detector; and Bluetooth®. Procedure: Transcutaneous monitoring (midline abdominal skin 2 cm above pubis) during spontaneous voiding (bladder contraction) of oxygenated (O2Hb), deoxygenated (HHb) and total hemoglobin (tHb) and tissue oxygen saturation index (TSI %) at 10 Hz. Results: All 20 trials produced clear graphic data with no movement effect evident. Comparison of patterns of chromophore change between normal and symptomatic subjects revealed trend differences in O2Hb and tHb. (Normal positive; Symptomatic negative, and TSI% fell in symptomatic group). Conclusions: Wireless NIRS is technically feasible in ambulant children. Negative trends in chromophore concentration and falls in TSI% suggest a hemodynamic impairment may underlie some forms of voiding dysfunction, with abnormal physiology involving the microcirculation possibly resulting in muscle fatigue during voiding.

  12. Predictive Value of NRAMP1 and HGPX1 Gene Polymorphism for Maintenance BCG Response in Non-muscle-invasive Bladder Cancer.

    Science.gov (United States)

    Lenormand, Claire; Couteau, Jérôme; Nouhaud, François-Xavier; Maillet, Géraldine; Bou, Jacqueline; Gobet, Françoise; Pfister, Christian

    2016-04-01

    To assess the potential predictive value of natural resistance-associated macrophage protein 1 (NRAMP1) and human glutathione peroxidase 1 (hGPX1) polymorphism in non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin (BCG) instillation, we conducted an original ancillary multicenter study. We evaluated patients included in the multicenter URO-BCG 4 trial, who received three weekly instillations of one-third dose BCG every 6 months (group I) or two weekly instillations every 3 months (group II) for 3 years. For clinical evaluation we also evaluated tumor recurrence and muscle progression. NRAMP1 and hGPX1 polymorphism analyses were performed on blood DNA. NRAMP1 exon 15 and hGPX1 exon 1c were amplified using Type-it Microsatellite PCR Kit® for multiplex polymerase chain reaction. From June 2004 to April 2010, 146 randomized patients were included in this retrospective study. Blood samples were obtained from 107 patients. With 36 months of follow-up, 13.6% of patients had a tumor recurrence and muscle-invasive progression was observed in 4.3% of patients. Concerning NRAMP1 D543N polymorphism, patients with allele A had no tumor recurrence or muscle-invasive progression. No significant difference was observed in gene polymorphism distribution between groups I and II. Moreover, we did not observe any significant association of gene polymorphisms, tumor recurrence or muscle-invasive progression, event time and disease-free survival. Our results suggest that no significant difference was found for NRAMP1 and hGPX1 gene polymorphisms associated with recurrence time, muscle invasion frequency and disease-free survival, nevertheless, we observed that the NRAMP1 D543N GG genotype group had a shorter time to tumor recurrence. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. UroVysion compared with cytology and quantitative cytology in the surveillance of non-muscle-invasive bladder cancer.

    NARCIS (Netherlands)

    Moonen, P.M.J.; Merkx, G.F.M.; Peelen, P.; Karthaus, H.F.M.; Smeets, D.F.C.M.; Witjes, J.A.

    2007-01-01

    OBJECTIVES: The multitarget fluorescence in situ hybridization probe set Vysis UroVysion, consisting of probes for chromosomes 3, 7, and 17 and for the 9p21 band, was studied to evaluate its value in the follow-up of patients with bladder cancer. The results were compared with conventional cytology

  14. Retinoblastoma protein expression is an independent predictor of both radiation response and survival in muscle invasive bladder cancer

    DEFF Research Database (Denmark)

    Agerbæk, Mads; Alsner, Jan; Marcussen, Niels

    2003-01-01

    The objective of the study was to investigate the predictive value of various clinical, biochemical, and histopathological parameters, with special emphasis on the expression of the retinoblastoma protein (pRB), on the radiation response in bladder cancer. In order to obtain a truly objective...

  15. Isolation and individual electrical stimulation of single smooth-muscle cells from the urinary bladder of the pig

    NARCIS (Netherlands)

    J.J. Glerum (Jacobus); R. van Mastrigt (Ron); J.C. Romijn (Johannes); D.J. Griffiths (Derek)

    1987-01-01

    textabstractIn contrast to striated muscle, measurements on strips of smooth muscle cannot be uniquely interpreted in terms of an array of contractile units. Therefore scaling down to the single-cell level is necessary to gain detailed understanding of the contractile process in this type of muscle.

  16. Concomitant alteration in number and affinity of P2X and muscarinic receptors are associated with bladder dysfunction in early stage of diabetic rats.

    Science.gov (United States)

    Yoshizawa, Tsuyoshi; Hayashi, Yukio; Yoshida, Akira; Yoshida, Shohei; Ito, Yoshihiko; Yamaguchi, Kenya; Yamada, Shizuo; Takahashi, Satoru

    2018-03-01

    To investigate time course of bladder dysfunction and concurrent changes in number and affinity of the muscarinic and P 2 X receptor in the early stage of streptozotocin (STZ)-induced diabetic rats. Diabetic rats were prepared by the intraperitoneal injection of 50 mg/kg of STZ to 7-week-old female Wistar rats. We performed recording of 24-h voiding behavior and cystometry at 1, 4, 8, and 12 weeks after the induction of diabetes. A muscle strip experiments with electrical field stimulation (EFS), carbachol, and α,β-methylene adenosine 5'-triphosphate (α,β-MeATP) were also performed at the same time-points. Additionally, concurrent changes in number and affinity of bladder muscarinic and P 2 X receptor were measured by a radioreceptor assay using [N-methyl- 3 H] scopolamine methyl chloride ([ 3 H]NMS) and α,β-methylene-ATP (2,8- 3 H) tetrasodium salt ([ 3 H]α,β-MeATP). In STZ-induced diabetic rats, polydipsic polyuric pollakiuria were noted on recording of 24-h voiding behavior from early stage. Also, the residual urine volume markedly increased in diabetic rats on cystometry. In the muscle strip experiment, the detrusor contractions induced by EFS, carbachol, and α,β-MeATP were enhanced in STZ-induced diabetic rats. Based on the radioreceptor assay, the maximum number of sites (Bmax) for the specific binding of [ 3 H]NMS and [ 3 H]α,β-MeATP was concurrently increased in the bladder from diabetic rats. Increased bladder contractility is found in early stage of diabetic rats. Then, bladder dysfunction is associated with increased number of muscarinic and P 2 X receptors in STZ-induced diabetic rats.

  17. Mitochondrial stress and activation of PI3K and Akt survival pathway in bladder ischemia

    Directory of Open Access Journals (Sweden)

    Yang JH

    2017-06-01

    Full Text Available Jing-Hua Yang,1 Mike B Siroky,1 Subbarao V Yalla,2 Kazem M Azadzoi3,4 1Department of Urology, VA Boston Healthcare System, Boston University School of Medicine, 2Department of Urology, VA Boston Healthcare System, Harvard Medical School, 3Department of Urology, 4Department of Pathology, VA Boston Healthcare System, Boston University School of Medicine, Boston, MA, USA Purpose: Detrusor overactivity contributes to bothersome constellation of lower urinary tract symptoms (LUTS in men and women as they age. However, the underlying mechanisms of non-obstructive detrusor overactivity and LUTS remain largely unknown. Growing evidence suggests that ischemia may be an independent factor in the development of non-obstructive bladder dysfunction. Our goal was to determine the effects of ischemia on detrusor function and voiding behavior and define redox-mediated cellular stress and cell survival signaling in the ischemic bladder. Materials and methods: Male Sprague Dawley rats were randomly divided into treatment (n=8 and control (n=8 groups. In the treatment group, iliac artery atherosclerosis and chronic bladder ischemia were induced. At 8 weeks after bladder ischemia, voiding patterns were examined in metabolic cages, cystometrograms were recorded in conscious animals, and then bladder blood flow was measured under general anesthesia. Bladder tissues were processed for assessment of transcription factors, markers of cellular and mitochondrial stress, mitochondrial respiration, and cell survival signaling pathway.Results: Atherosclerotic occlusive disease spread from the common iliac arteries to the internal iliac and vesical arteries and produced sustained bladder ischemia. Studies in metabolic cages showed increased micturition frequency and decreased voided volume in bladder ischemia. Conscious cystometrograms produced consistent data showing significant increase in micturition frequency and decreased voided volume and bladder capacity. Voiding

  18. Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette-Guerin (BCG): results of an international individual patient data survey (IPDS)

    NARCIS (Netherlands)

    Witjes, J.A.; Palou, J.; Soloway, M.; Lamm, D.; Kamat, A.M.; Brausi, M.; Persad, R.; Buckley, R.; Colombel, M.; Bohle, A.

    2013-01-01

    OBJECTIVES: To examine the management of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), particularly with regard to the use of bacillus Calmette-Guerin (BCG) therapy, in North America and Europe. To compare NMIBC management practices to European Association of Urology (EAU)

  19. Prognostic factors in non-muscle-invasive bladder tumors - I. Clinical prognostic factors: A review of the experience of the EORTC genito-urinary group - II. Biologic prognostic markers

    NARCIS (Netherlands)

    Kurth, Karl-Heinz; Sylvester, Richard J.

    2007-01-01

    Objectives: To summarize the most important clinical prognostic factors of non-muscle-invasive bladder cancer, as assessed by the European organization for Research and Treatment of Cancer (EORTC) Genito-Urinary Group, to present biologic markers involved in urothelial cell carcinoma, and to address

  20. Can we predict detrusor overactivity in women with lower urinary tract symptoms? The King's Detrusor Overactivity Score (KiDOS).

    Science.gov (United States)

    Giarenis, Ilias; Musonda, Patrick; Mastoroudes, Heleni; Robinson, Dudley; Cardozo, Linda

    2016-10-01

    Traditionally, urodynamic studies (UDS) have been used to assess lower urinary tract symptoms (LUTS), but their routine use is now discouraged. While urodynamic stress incontinence is strongly associated with the symptom of stress urinary incontinence (SUI) and a positive cough test, there is a weak relationship between symptoms of overactive bladder and detrusor overactivity (DO). The aim of our study was to develop a model to predict DO in women with LUTS. This prospective study included consecutive women with LUTS attending a urodynamic clinic. All women underwent a comprehensive clinical and urodynamic assessment. The effect of each variable on the odds of DO was estimated both by univariate analysis and adjusted analysis using logistic regression. 1006 women with LUTS were included in the study with 374 patients (37%) diagnosed with DO. The factors considered to be the best predictors of DO were urgency urinary incontinence, urge rating/void and parity (p-value<0.01). The absence of SUI, vaginal bulging and previous continence surgery were also good predictors of DO (p-value<0.01). We have created a prediction model for DO based on our best predictors. In our scoring system, presence of UUI scores 5; mean urge rating/void≥3 scores 3; parity≥2 scores 2; previous continence surgery scores -1; presence of SUI scores -1; and the complaint of vaginal bulging scores -1. If a criterion is absent, then the score is 0 and the total score can vary from a value of -3 to +10. The Receiver Operating Characteristic (ROC) analysis for the overall cut-off points revealed an area under the curve of 0.748 (95%CI 0.741, 0.755). This model is able to predict DO more accurately than a symptomatic diagnosis alone, in women with LUTS. The introduction of this scoring system as a screening tool into clinical practice may reduce the need for expensive and invasive tests to diagnose DO, but cannot replace UDS completely. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Muscle-invasive bladder cancer treated with external beam radiation: influence of total dose, overall treatment time, and treatment interruption on local control

    International Nuclear Information System (INIS)

    Moonen, L.; Voet, H. van der; Nijs, R. de; Horenblas, S.; Hart, A.A.M.; Bartelink, H.

    1998-01-01

    Purpose: To evaluate and eventually quantify a possible influence of tumor proliferation during the external radiation course on local control in muscle invasive bladder cancer. Methods and Materials: The influence of total dose, overall treatment time, and treatment interruption has retrospectively been analyzed in a series of 379 patients with nonmetastasized, muscle-invasive transitional cell carcinoma of the urinary bladder. All patients received external beam radiotherapy at the Netherlands Cancer Institute between 1977 and 1990. Total dose varied between 50 and 75 Gy with a mean of 60.5 Gy and a median of 60.4 Gy. Overall treatment time varied between 20 and 270 days with a mean of 49 days and a median of 41 days. Number of fractions varied between 17 and 36 with a mean of 27 and a median of 26. Two hundred and forty-four patients had a continuous radiation course, whereas 135 had an intended split course or an unintended treatment interruption. Median follow-up was 22 months for all patients and 82 months for the 30 patients still alive at last follow-up. A stepwise procedure using proportional hazard regression has been used to identify prognostic treatment factors with respect to local recurrence as sole first recurrence. Results: One hundred and thirty-six patients experienced a local recurrence and 120 of these occurred before regional or distant metastases. The actuarial local control rate was 40.3% at 5 years and 32.3% at 10 years. In a multivariate analysis total dose showed a significant association with local control (p 0.0039), however in a markedly nonlinear way. In fact only those patients treated with a dose below 57.5 Gy had a significant higher bladder relapse rate, whereas no difference in relapse rate was found among patients treated with doses above 57.5 Gy. This remained the case even after adjustment for overall treatment time and all significant tumor and patient characteristics. The Normalized Tumor Dose (NTD) (α/β = 10) and NTD (

  2. Overexpression of long non-coding RNA TUG1 predicts poor prognosis and promotes cancer cell proliferation and migration in high-grade muscle-invasive bladder cancer.

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    Iliev, Robert; Kleinova, Renata; Juracek, Jaroslav; Dolezel, Jan; Ozanova, Zuzana; Fedorko, Michal; Pacik, Dalibor; Svoboda, Marek; Stanik, Michal; Slaby, Ondrej

    2016-10-01

    Long non-coding RNA TUG1 is involved in the development and progression of a variety of tumors. Little is known about TUG1 function in high-grade muscle-invasive bladder cancer (MIBC). The aims of our study were to determine expression levels of long non-coding RNA TUG1 in tumor tissue, to evaluate its relationship with clinico-pathological features of high-grade MIBC, and to describe its function in MIBC cells in vitro. TUG1 expression levels were determined in paired tumor and adjacent non-tumor bladder tissues of 47 patients with high-grade MIBC using real-time PCR. Cell line T-24 and siRNA silencing were used to study the TUG1 function in vitro. We observed significantly increased levels of TUG1 in tumor tissue in comparison to adjacent non-tumor bladder tissue (P TUG1 levels were significantly increased in metastatic tumors (P = 0.0147) and were associated with shorter overall survival of MIBC patients (P = 0.0241). TUG1 silencing in vitro led to 34 % decrease in cancer cell proliferation (P = 0.0004) and 23 % reduction in migration capacity of cancer cells (P TUG1 silencing on cell cycle distribution and number of apoptotic cells. Our study confirmed overexpression of TUG1 in MIBC tumor tissue and described its association with worse overall survival in high-grade MIBC patients. Together with in vitro observations, these data suggest an oncogenic role of TUG1 and its potential usage as biomarker or therapeutic target in MIBC.

  3. Potential therapeutic strategies for non - muscle invasive bladder cancer based on association of intravesical immunotherapy with p - mapa and systemic administration of cisplatin and doxorubicin.

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    Dias, Queila Cristina; Nunes, Iseu da Silva; Garcia, Patrick Vianna; Favaro, Wagner Jose

    2016-01-01

    The present study describes the histopathological and molecular effects of P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) intravesical immunotherapy combined with systemic doxorubicin or cisplatin for treatment of non-muscle invasive bladder cancer (NMIBC) in an appropriate animal model. Our results showed an undifferentiated tumor, characterizing a tumor invading mucosa or submucosa of the bladder wall (pT1) and papillary carcinoma in situ (pTa) in the Cancer group. The histopathological changes were similar between the combined treatment with intravesical P-MAPA plus systemic Cisplatin and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions progression and histopathological recovery in 80% of the animals. The animals treated systemically with cisplatin or doxorubicin singly, showed 100% of malignant lesions in the urinary bladder. Furthemore, the combined treatment with P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments than other groups. In contrast, PTEN protein levels were significantly higher in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it could be concluded that combination of intravesical P-MAPA immunotherapy and systemic cisplatin in the NMIBC animal model was effective, well tolerated and showed no apparent signs of antagonism between the drugs. In addition, intravesical P-MAPA immunotherapy may be considered as a valuable option for treatment of BCG unresponsive patients that unmet the criteria for early cystectomy. Copyright® by the International Brazilian Journal of Urology.

  4. Bladder Cancer—Health Professional Version

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    Transitional cell carcinoma of the bladder can be low-grade or high-grade. Bladder cancer is also divided into muscle-invasive and nonmuscle-invasive disease. Find evidence-based information on bladder cancer including treatment, screening, research, and statistics.

  5. Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1.

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    Meng-Chuan Chen

    Full Text Available Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM or gemcitabine (TGM, markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC. The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1 production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis.

  6. Development of oxybutynin chloride topical gel for overactive bladder

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    Lucente VR

    2011-04-01

    Full Text Available Vincent R Lucente1, David R Staskin2, Elise De31Institute of Female Pelvic Medicine and Reconstructive Surgery, Allentown, PA, USA; 2Division of Urology, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, MA, USA; 3Urological Institute of Northeastern New York, Albany, NY, USAAbstract: Overactive bladder (OAB is an age-related syndrome often associated with urinary incontinence. Symptoms of OAB, such as urgency, frequency, and nocturia, can be treated effectively with inhibitors of muscarinic acetylcholine receptors. Antimuscarinic agents promote relaxation of the detrusor muscle and may modulate afferent neuronal signals involved in the regulation of the micturition reflex. Despite the availability of an increasing number of oral antimuscarinic agents, treatment persistence among patients with OAB generally appears to be low. This may be attributed, at least in part, to the common occurrence of anticholinergic adverse effects, such as dry mouth, constipation, and dizziness. Oxybutynin is a well-established antimuscarinic agent that is available in a variety of formulations. Transdermal formulations have been developed to avoid the first-pass hepatic and gastrointestinal drug metabolism responsible for the anticholinergic adverse effects often observed with oral delivery of oxybutynin. Oxybutynin chloride topical gel (OTG is a formulation of oxybutynin that was approved by the US Food and Drug Administration in January 2009. OTG was the result of a systematic evidence-based effort to develop a formulation that preserves the efficacy of oral oxybutynin formulations while eliminating most of their anticholinergic adverse effects. Additional emphasis was put on creating a transdermal formulation with minimal potential for application-site skin reactions. The formulation and pharmacokinetic properties of OTG are reviewed in the context of recently published efficacy and tolerability data from a large multicenter, placebo

  7. Can the neutrophil-to-lymphocyte ratio be used to predict recurrence and progression of non-muscle-invasive bladder cancer?

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    Sebahattin Albayrak

    2016-06-01

    Full Text Available The aim of our study was to evaluate whether neutrophil-to-lymphocyte ratio (NLR is a predictor of disease progression and recurrence in patients with primary non-muscle-invasive bladder cancer (NMIBC. This was a prospective study of 86 patients with newly diagnosed NMIBC. The patients were classified by the number of points assigned by the European Organization for Research and Treatment of Cancer risk tables. The correlation between progression score, recurrence score, age, mean platelet volume, red blood cell distribution width and NLR was assessed statistically. The same parameters were compared between the risk groups. A significant difference in NLR and age values was observed between recurrence and progression risk score groups. The relationships between NLR and recurrence and progression risk scores were no longer significant after correcting for the statistical effect of age on scores. Age was significantly different between groups after adjusting for NLR. Our study revealed that NLR and age were associated with patient age and bladder tumor progression and recurrence risk scores. After correcting for age, the significant relationship with NLR was lost, in contrast to some previous studies. We recommend that patient age should be corrected to avoid misleading results in NLR studies.

  8. Ten Years of Complete Remission of Pulmonary Metastasis after Post-Cystectomy Palliative Cisplatin-Gemcitabine Chemotherapy with Gefitinib for Muscle Invasive Bladder Cancer: A Case Report.

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    Fahmy, Omar; Scharpf, Marcus; Schubert, Tina; Feyerabend, Susan; Stenzl, Arnulf; Schwentner, Christian; Fend, Falko; Gakis, Georgios

    2016-01-01

    Muscle-invasive bladder cancer (MIBC) is considered one of the most lethal malignancies with high metastatic potential. Usually, metastatic bladder cancer carries worse prognosis with a median survival rate of approximately 6 months, which can be prolonged for up to 14 months with palliative systemic chemotherapy. We present the case of a 61-year-old male patient diagnosed with localized MIBC 10 years ago. He underwent nerve-sparing radical cystectomy with ileal neobladder, but developed pulmonary metastatic disease 7 months postoperatively. Six cycles of gemcitabine/cisplatin combination chemotherapy with an addition of gefitinib as daily oral medication were administered within a randomized phase II clinical trial; this resulted in complete remission of the pulmonary metastases. Until now, the patient is still on gefitinib daily without any side effects. Although, the addition of gefitinib to standard systemic chemotherapy has not been shown to improve the survival in metastatic urothelial cancer, this case represents a very pleasant albeit uncommon long-term outcome. © 2016 S. Karger AG, Basel.

  9. Clinicopathological Profiling of LC3B, an Autophagy Marker, and ESRRA (Estrogen-related Receptor-alpha) in Muscle-invasive Bladder Cancer.

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    Kim, Sup; Lee, Adam Jaehyeok; Yeo, Min-Kyung; Na, Yong Gil; Kim, Ji-Yeon; Cho, Moon-June; Kim, Jun-Sang; Jo, Eun-Kyeong; Kim, Jin-Man

    2018-04-01

    Microtubule-associated protein 1 light chain 3B (LC3B), an autophagy marker, has been used as a promising marker in various cancer types. However, the expression of LC3B in muscle-invasive bladder cancer (MIBC) and its prognostic significance have not been investigated. Recent studies pointed to the involvement of ESRRA in regulating autophagy via both transcriptional and post-translational control. In the current study, prognostic importance of LC3B and ESRRA in MIBC was investigated. We immunohistochemically studied the expression of LC3B and ESRRA in 56 MIBC samples. LC3B was stained high in 16 patients (28.6%) and low or negative in 40 patients (71.4%). ESRRA expression was high for 20 patients (35.7%) and low for 36 patients (64.3%). Both LC3B (p=0.003) and ESRRA (p=0.026) expression correlated significantly with disease-free survival rates. Double-positive LC3B and ESRRA correlated with poor overall survival (p=0.007) and disease-free survival (p=0.001) in MIBC patients. LC3B and ESRRA might be a useful prognostic factor in patients with MIBC. The co-expression of LC3B and ESRRA might be a prognostic and therapeutic target for patients with bladder cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Overexpression of Aquaporin-1 and Caveolin-1 in the Rat Urinary Bladder Urothelium Following Bladder Outlet Obstruction

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    Sun-Ouck Kim

    2013-12-01

    Full Text Available Purpose This study was designed to investigate the effect of detrusor overactivity induced by partial bladder outlet obstruction (BOO on the expression of aquaporin 1 (AQP1 and caveolin 1 (CAV1 in the rat urinary bladder, and to determine the role of these molecules in detrusor overactivity. Methods Female Sprague-Dawley rats were divided into control (n=30 and experimental (n=30 groups. The BOO group underwent partial BOO, and the control group underwent a sham operation. After 4 weeks, an urodynamic study was performed to measure the contraction interval and contraction pressure. The expression and cellular localization of AQP1 and CAV1 were determined by western blot and immunofluorescence experiments in the rat urinary bladder. Results In cystometrograms, the contraction interval was significantly lower in the BOO group (2.9±1.5 minutes than in the control group (6.7±1.0 minutes (P<0.05. Conversely, the average contraction pressure was significantly higher in the BOO group (21.2±3.3 mmHg than in the control group (13.0±2.5 mmHg (P<0.05. AQP1 and CAV1 were coexpressed in the capillaries, arterioles, and venules of the suburothelial layer. AQP1 and CAV1 protein expression was significantly increased in the BOO rats compared to the control rats (P<0.05. Conclusions Detrusor overactivity induced by BOO causes a significant increase in the expression of AQP1 and CAV1, which were coexpressed in the suburothelial microvasculature. This finding suggests that AQP1 and CAV1 might be closely related to bladder signal activity and may have a functional role in BOO-associated detrusor overactivity.

  11. Percutaneous tibial nerve stimulation versus electrical stimulation with pelvic floor muscle training for overactive bladder syndrome in women: results of a randomized controlled study

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    Carlo Vecchioli Scaldazza

    Full Text Available ABSTRACT Introduction This study compared percutaneous tibial nerve stimulation (PTNS versus electrical stimulation with pelvic floor muscle training (ES + PFMT in women with overactive bladder syndrome (OAB. Materials and Methods 60 women with OAB were enrolled. Patients were randomized into two groups. In group A, women underwent ES with PFMT, in group B women underwent PTNS. Results A statistically significant reduction in the number of daily micturitions, episodes of nocturia and urge incontinence was found in the two groups but the difference was more substantial in women treated with PTNS; voided volume increased in both groups. Quality of life improved in both groups, whereas patient perception of urgency improved only in women treated with PTNS. Global impression of improvement revealed a greater satisfaction in patients treated with PTNS. Conclusion This study demonstrates the effectiveness of PTNS and ES with PFMT in women with OAB, but greater improvements were found with PTNS.

  12. Urodynamic Bladder Patterns in Spinal Cord Injury Patients

    International Nuclear Information System (INIS)

    Aziz, T.; Khan, A. A.; Iqbal, S.; Aziz, U.; Jilani, S.; Ayyub, A.

    2017-01-01

    Objective: To determine the frequency of various neurogenic bladder patterns in patients with traumatic spinal cord injury presenting at Armed Forces Institute of Rehabilitation Medicine Rawalpindi based on urodynamic studies. Study Design: Descriptive cross sectional study. Place and Duration of Study: Armed Forces Institute of Rehabilitation Medicine (AFIRM) Rawalpindi, from Jul 2014 to Jun 2016. Material and Methods: One hundred and forty traumatic spinal cord injury patients fulfilling the inclusion criteria were included both from indoor and outdoor departments through non-probability purposive sampling. Urodynamic studies were performed using the urodynamic equipment at urodynamic laboratory. Data were collected and recorded on specialized proforma by the principal investigator. Results: Among 140 study participants detrusor overactivity was found in 100 patients out of which 76 (76 percent) had thoracic level of injury, 20 (20 percent) had cervical level and 4 (4 percent) had lumbar level of injury. Detrusor areflexia was the bladder pattern in 40 patients out of which 26 (65 percent) had thoracic level of injury, 10 (25 percent) had cervical level, and 4 (10 percent) had lumbar level of injury. Conclusion: Detrusor overactivity was the commonest neurogenic bladder pattern among the traumatic spinal cord injury patients. (author)

  13. Neuromodulation: urodynamic effects of sacral (S3) spinal nerve stimulation in patients with detrusor instability or detrusor hyperflexia.

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    Bosch, J L; Groen, J

    1998-05-01

    The aim of this study was to determine the urodynamic effects of sacral (S3) nerve stimulation in patients with urge incontinence due to detrusor overactivity which has been refractory to conservative treatment. A total of 24 patients with idiopathic detrusor instability and five with neurogenic hyperreflexia were studied urodynamically before and 6 months after a permanent S3 foramen electrode implant. The urodynamic studies at follow-up were done with the stimulus on. Clinically, the average voiding frequency, the number of leakage episodes and pad use per 24 h decreased significantly. Improvement in several urodynamic parameters was noted. In the idiopathic as well as in the neurogenic group, the correlation between symptomatic and urodynamic improvement was incomplete. Neuromodulation leads to improvement of several urodynamic parameters in patients with urge incontinence due to detrusor overactivity which has been refractory to conservative treatment and appears to be a valuable treatment option in these patients.

  14. Assessment of the Radiation-Equivalent of Chemotherapy Contributions in 1-Phase Radio-chemotherapy Treatment of Muscle-Invasive Bladder Cancer

    International Nuclear Information System (INIS)

    Plataniotis, George A.; Dale, Roger G.

    2014-01-01

    Purpose: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. Methods and Materials: A standard logistic dose–response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. Results: The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval −0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. Conclusion: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy

  15. Recommended oral sodium bicarbonate administration for urine alkalinization did not affect the concentration of mitomycin-C in non-muscle invasive bladder cancer patients.

    Science.gov (United States)

    Seo, Ho Kyung; Kim, Sung Han; Ahn, Kyung-Ohk; Lee, Sang-Jin; Park, Weon Seo; Kim, Sohee; Hwang, Sang-Hyun; Lee, Do Hoon; Joung, Jae Young; Chung, Jinsoo; Joo, Jungnam; Jeong, Kyung-Chae

    2017-11-10

    Sodium bicarbonate has been reported to maximize the efficacy of intravesical instillation of mitomycin-C (IVI-MMC) therapy by urine alkalinization in non-muscle-invasive bladder cancer (NMIBC). This study aimed to analyze the changes in MMC concentration according to urinary pH and evaluate the efficacy of sodium bicarbonate to maintain the concentration of active form of MMC during IVI-MMC. We prospectively enrolled 26 patients with NMIBC after transurethral resection of bladder tumor. Patients with very high-risk and low-risk NMIBC were excluded. Urinary creatinine, volume, pH, and concentrations of MMC and its degraded form were measured immediately before and after IVI-MMC. The patients were administered 1.5 g of oral sodium bicarbonate during the preceding evening, in the morning, and immediately before the fourth cycle of the six-cycle IVI-MMC. The correlation between MMC concentration and urinary pH changes was explored with or without oral bicarbonate therapy. Recurrence without progression to muscle-invasive disease was noted in 4 of 26 patients in a 23.7-month follow-up. The mean urinary pH before and after the therapy increased from 6.03 to 6.50, and 6.46 to 7.24, without or with oral SB therapy, respectively. Despite this increase, the concentration of active form of MMC did not change significantly. No correlation was found between urinary pH and MMC concentration. Urine alkalinization by SB administration did not maintain the high concentration of urinary MMC. Urine alkalinization by sodium bicarbonate administration for IVI-MMC did not maintain the high concentration of active urinary MMC in NMIBC.

  16. Optical diagnosis of interstitial cystitis / painful bladder syndrome

    Science.gov (United States)

    Shadgan, Babak; Macnab, Andrew; Stothers, Lynn

    2013-03-01

    Background: Painful bladder syndrome/interstitial cystitis (PBS/IC) is defined as a syndrome of urgency, frequency, and suprapubic pain in the absence of positive urine culture or obvious bladder pathology. As no specific etiology has been identified yet, no specific methodology exists for diagnosis of this condition. One potential etiology of PBS/IC is inflammation of the bladder mucosa associated with abnormal angiogenesis and ulcerative lesions. The purpose of this study was to examine the feasibility of using transcutaneous near infrared spectroscopy (NIRS) of the bladder to monitor tissue oxygenation and hemodynamics as a means of differentiating subjects diagnosed with PBS/IC from those with other bladder conditions. Methods: Twenty-four adult patients with lower urinary tract dysfunction were divided into 2 groups, PBS/IC and non-PBS/IC after standard diagnostic investigations. Detrusor oxygen saturation percentage (TSI%) was measured in all subjects while they were at rest in a supine position, using a spatially resolved (SR) NIRS instrument. Mean values of detrusor TSI% were significantly different between the two groups (74.2%+/-4.9 in PBS/IC vs. 63.6%+/-5.5 in non-PBS/IC, P<0.0005). Results: Noninvasive NIRS interrogation of the bladder demonstrated that patients diagnosed as having PBS/IC had significantly higher detrusor oxygen saturation at rest. Conclusions: SR-NIRS as a feasible non-noninvasive entity for use in the evaluation of patients for the presence or absence of physiologic changes associated with PBS/IC.

  17. Molecular biology of bladder cancer.

    Science.gov (United States)

    Martin-Doyle, William; Kwiatkowski, David J

    2015-04-01

    Classic as well as more recent large-scale genomic analyses have uncovered multiple genes and pathways important for bladder cancer development. Genes involved in cell-cycle control, chromatin regulation, and receptor tyrosine and PI3 kinase-mammalian target of rapamycin signaling pathways are commonly mutated in muscle-invasive bladder cancer. Expression-based analyses have identified distinct types of bladder cancer that are similar to subsets of breast cancer, and have prognostic and therapeutic significance. These observations are leading to novel therapeutic approaches in bladder cancer, providing optimism for therapeutic progress. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Efficacy of peripheral lidocaine application (neural therapy) in the treatment of neurogenic detrusor overactivity in multiple sclerosis patients.

    Science.gov (United States)

    Tamam, Yusuf; Özdemir, Hasan Hüseyin; Gedik, Abdullah; Tamam, Cüneyt; Nazlıkul, Hüseyin

    2017-09-01

    Many agents and treatments are used in the treatment of neurogenic detrusor overactivity (NDO) in MS patients, but no study has been conducted on the use of peripheric lidocaine (neural therapy-NT) on MS patients. We evaluated the effects of local administration of lidocaine on NDO in Multiple Sclerosis (MS) patients. For each patient local anesthetic lidocaine was injected at each session. Sessions were held once a week for 5 weeks. At each session, Th 10-L1, urogenital segment intradermal injections, Frankenhauser, and sacral epidural injections were given. The patients had clinical and urodynamic assessment 1 month before and 3, 9, and 12 months after NT. In addition, multiple sclerosis quality of life inventory (MSQL-54) and bladder control scale (BLCS) was performed for patients. Twenty-eight patients were included in the study (8 males, 20 females). The patients' average age was 31.7 ± 8.1 years. The injection therapy significantly improved volume at first involuntary bladder contraction (FCV), maximal detrusor pression during filling (P det. max.), maximal cystometric bladder capacity (MCC) after 3 months. Also, the MSQL-54 and BLCS scores were improved with treatment. However, these improvements reached a maximum 3 months after treatment, but from the 9 month a regression was seen in the parameters, and after 12 months the findings were seen to be slightly above their basal levels. These results suggest that NDO treatment in MS patients could be an effective treatment which is easy and has very few side effects, and is cost effective. © 2017 Wiley Periodicals, Inc.

  19. Combined treatment with a β3 -adrenergic receptor agonist and a muscarinic receptor antagonist inhibits detrusor overactivity induced by cold stress in spontaneously hypertensive rats.

    Science.gov (United States)

    Imamura, Tetsuya; Ogawa, Teruyuki; Minagawa, Tomonori; Nagai, Takashi; Suzuki, Toshiro; Saito, Tetsuichi; Yokoyama, Hitoshi; Nakazawa, Masaki; Ishizuka, Osamu

    2017-04-01

    This study determined if combined treatment with the muscarinic receptor (MR) antagonist solifenacin and the β 3 -adrenergic receptor (AR) agonist mirabegron could inhibit detrusor overactivity induced by cold stress in spontaneously hypertensive rats (SHRs). Thirty-two female 10-week-old SHRs were fed an 8% NaCl-supplemented diet for 4 weeks. Cystometric measurements of the unanesthetized, unrestricted rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then intravenously administered vehicle, 0.1 mg/kg solifenacin alone, 0.1 mg/kg mirabegron alone, or the combination of 0.1 mg/kg mirabegron and 0.1 mg/kg solifenacin (n = 8 each group). Five minutes later, the treated rats were exposed to low temperature (LT, 4 ± 2°C) for 40 min. Finally, the rats were returned to RT. After the cystometric investigations, the β 3 -ARs and M 3 -MRs expressed within the urinary bladders were analyzed. Just after transfer from RT to LT, vehicle-, solifenacin-, and mirabegron-treated SHRs exhibited detrusor overactivity that significantly decreased voiding interval and bladder capacity. However, treatment with the combination of solifenacin and mirabegron partially inhibited the cold stress-induced detrusor overactivity patterns. The decreases of voiding interval and bladder capacity in the combination-treated rats were significantly inhibited compared to other groups. Within the urinary bladders, there were no differences between expression levels of M 3 -MR and β 3 -AR mRNA. The tissue distribution of M 3 -MRs was similar to that of the β 3 -ARs. This study suggested that the combination of solifenacin and mirabegron act synergistically to inhibit the cold stress-induced detrusor overactivity in SHRs. Neurourol. Urodynam. 36:1026-1033, 2017. © 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc. © 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

  20. Trends in the Use of Chemotherapy before and after Radical Cystectomy in Patients with Muscle-invasive Bladder Cancer in Korea

    Science.gov (United States)

    Kim, Sung Han; Seo, Ho Kyung; Shin, Hee Chul; Chang, Sung Ja; Yun, Sooin; Joo, Jungnam; Ku, Ja Hyeon; Kim, Hyung Suk; Jeon, Hwang Gyun; Jeong, Byong Chang; Jeong, In Gab; Kang, Seok Ho

    2015-01-01

    We investigated trends in perioperative chemotherapy use, and determined factors associated with neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) use in Korean patients with muscle-invasive bladder cancer (MIBC). We recruited 1,324 patients who had MIBC without nodal invasion or metastases and had undergone radical cystectomies (RC) between 2003 and 2013. The study's cut-off time for AC was three months after surgery, and the study's timespan was divided into three periods based on NAC use, namely, 2003-2005, 2006-2009, and 2010-2013. Complete remission was defined as histologically confirmed T0N0M0 after RC. NAC and AC were administered to 7.3% and 18.1% of the patients, respectively. The median time interval between completing NAC and undergoing RC was 32 days and the mean number of cycles was 3.2. The median time interval between RC and AC was 43 days and the mean number of cycles was 4.1. Gemcitabine and cisplatin were most frequently used in combination for NAC (49.0%) and AC (74.9%). NAC use increased significantly from 4.6% between 2003 and 2005 to 8.4% between 2010 and 2013 (P < 0.05), but AC use did not increase. Only 1.9% of patients received NAC and AC. Complete remission after NAC was achieved in 12 patients (12.5%). Multivariable modeling revealed that an advanced age, the earliest time period analyzed, and clinical tumor stage ≤ cT2 bladder cancer were negatively associated with NAC use (P < 0.05). While NAC use has slowly increased over time, it remains an underutilized therapeutic approach in Korean clinical practice. PMID:26240494

  1. Clinical usefulness of random biopsies in diagnosis and treatment of non-muscle invasive bladder cancer: Systematic review and meta-analysis.

    Science.gov (United States)

    Subiela, J D; Palou, J; Esquinas, C; Fernández Gómez, J M; Rodríguez Faba, O

    2017-11-20

    This systematic review of the literature has been focused on determining the clinical usefulness of random bladder biopsies (RB) in the diagnosis of carcinoma in situ. A meta-analysis was performed to establish the clinic and pathological factors associated to positive biopsies. A systematic review was performed using Pubmed/Medline database according to the PRISMA guidelines. Thirty-seven articles were included, recruiting a total of 12,657 patients, 10,975 were submitted to RB. The overall incidence of positive RB was 21.91%. Significant differences were found in the incidence of positive RB when patients were stratified according to urine cytology result, tumor multiplicity, tumor appearance, stage and grade. The results of the meta-analysis revealed that the presence of positive cytology, tumor multiplicity, non-papillary appearance tumors, stage T1 and histological grades G2 and G3 represent the risk factors to predict abnormalities in RB. The incidence of positive RB in patients with non-muscle invasive bladder cancer was 21.91%. The maximum usefulness of RB was observed when these are performed in a standardized way. The results of the meta-analysis showed that besides positive cytology and non-papillary appearance tumors, tumor multiplicity and histological grades G2 and G3 represent risk factors associated to positive RB, suggesting that the use of RB might be extensive to the intermediate risk group of the European Organization for Research and Treatment of Cancer (EORTC). Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Teardrop bladder: additional considerations

    International Nuclear Information System (INIS)

    Wechsler, R.J.; Brennan, R.E.

    1982-01-01

    Nine cases of teardrop bladder (TDB) seen at excretory urography are presented. In some of these patients, the iliopsoas muscles were at the upper limit of normal in size, and additional evaluation of the perivesical structures with computed tomography (CT) was necessary. CT demonstrated only hypertrophied muscles with or without perivesical fat. The psoas muscles and pelvic width were measured in 8 patients and compared with the measurements of a control group of males without TDB. Patients with TDB had large iliopsoas muscles and narrow pelves compared with the control group. The psoas muscle width/pelvic width ratio was significantly greater (p < 0.0005) in patients with TDB than in the control group, with values of 1.04 + 0.05 and 0.82 + 0.09, respectively. It is concluded that TDB is not an uncommon normal variant in black males. Both iliopsoas muscle hypertrophy and a narrow pelvis are factors that predispose a patient to TDB

  3. Dynamic contrast-enhanced MRI in patients with muscle-invasive transitional cell carcinoma of the bladder can distinguish between residual tumour and post-chemotherapy effect

    International Nuclear Information System (INIS)

    Donaldson, Stephanie B.; Bonington, Suzanne C.; Kershaw, Lucy E.; Cowan, Richard; Lyons, Jeanette; Elliott, Tony; Carrington, Bernadette M.

    2013-01-01

    Introduction: Treatment of muscle-invasive bladder cancer with chemotherapy results in haemorrhagic inflammation, mimicking residual tumour on conventional MR images and making interpretation difficult. The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to estimate descriptive and tracer kinetic parameters post-neoadjuvant chemotherapy and to investigate whether parameters differed in areas of residual tumour and chemotherapy-induced haemorrhagic inflammation (treatment effect, Tr-Eff). Methods and materials: Twenty-one patients underwent DCE-MRI scans with 2.5 s temporal resolution before and following neoadjuvant chemotherapy. Regions-of-interest (ROIs) were defined in areas suspicious of residual tumour on T 2 -weighted MRI scans. Data were analysed semi-quantitatively and with a two-compartment exchange model to obtain parameters including relative signal intensity (rSI 80s ) and plasma perfusion (F p ) respectively. The bladder was subsequently examined histologically after cystectomy for evidence of residual tumour and/or Tr-Eff. Differences in parameters measured in areas of residual tumour and Tr-Eff were examined using Student's t-test. Results: Twenty-four abnormal sites were defined after neoadjuvant chemotherapy. On pathology, 10 and 14 areas were identified as residual tumour and Tr-Eff respectively. Median rSI 80s and F p were significantly higher in areas of residual tumour than Tr-Eff (rSI 80s = 2.9 vs 1.7, p < 0.001; F p = 20.7 vs 9.1 ml/100 ml/min, p = 0.03). The sensitivity and specificity for differentiating residual tumour from Tr-Eff were 70% and 100% (rSI 80s ), 60% and 86% (F p ), and 75% and 100% when combined. Conclusion: DCE-MRI parameters obtained post-treatment are capable of distinguishing between residual tumour and treatment effect in patients treated for bladder cancer with neoadjuvant chemotherapy

  4. A bladder-free, non-fluidic, conductive McKibben artificial muscle operated electro-thermally

    Science.gov (United States)

    Sangian, Danial; Foroughi, Javad; Farajikhah, Syamak; Naficy, Sina; Spinks, Geoffrey M.

    2017-01-01

    Fluidic McKibben artificial muscles that operate pneumatically or hydraulically provide excellent performance, but require bulky pumps/compressors, valves and connecting lines. Use of a pressure generating material, such as thermally expanding paraffin wax, can eliminate the need for these pumps and associated infrastructure. Here we further develop this concept by introducing the first bladderless McKibben muscle wherein molten paraffin is contained by surface tension within a tailored braid. Incorporation of electrically conductive wires in the braid allows for convenient Joule heating of the paraffin. The muscle is light (0.14 g) with a diameter of 1.4 mm and is capable of generating a tensile stress of 50 kPa (0.039 N) in 20 s. The maximum contraction strain of 10% (7.6 kPa given load) was achieved in 60 s with an applied electrical power of 0.35 W.

  5. Trends in the use of perioperative chemotherapy for localized and locally advanced muscle-invasive bladder cancer: a sign of changing tides.

    Science.gov (United States)

    Reardon, Zachary D; Patel, Sanjay G; Zaid, Harras B; Stimson, C J; Resnick, Matthew J; Keegan, Kirk A; Barocas, Daniel A; Chang, Sam S; Cookson, Michael S

    2015-01-01

    Despite the documented survival benefit conferred by neoadjuvant (NAC) and adjuvant chemotherapy (AC), there has been a slow adoption of guideline recommendations for the use of perioperative chemotherapy (POC) in patients with muscle-invasive bladder cancer (MIBC). To evaluate temporal trends in POC utilization and identify factors influencing POC delivery in a representative cohort of patients with MIBC. Retrospective cohort study identifying factors associated with receipt of POC and evaluating temporal changes in NAC and AC utilization. We included patients from the National Cancer Data Base (NCDB) with no prior malignancy who ultimately underwent radical cystectomy for ≥ cT2/cN0/cM0 MIBC between 2006 and 2010. Relationships between demographic and hospital factors and the likelihood of receiving POC were evaluated using Pearson chi-square and Wilcoxon rank-sum tests, and multivariable logistic regression. Temporal changes in NAC and AC use were detected using a linear test of trend. A total of 5692 patients met our inclusion criteria. POC use increased from 29.5% in 2006 to 39.8% in 2010 (p < 0.001). NAC use increased from 10.1% in 2006 to 20.8% in 2010 (p = 0.005); AC remained stable between 18.1% and 21.3% (p = 0.68). Multivariable modeling revealed advanced age, increasing comorbidity, lack of insurance, increased travel distance, geographic location outside the northeastern United States, and lower income as negatively associated with POC receipt (all p < 0.05). Limitations include retrospective design and potential sampling bias, excluding patients treated at non-NCDB facilities. POC use for MIBC increased from 2006 to 2010, with this increase disproportionately due to rising NAC utilization. Nonetheless, there is persistent variation in the likelihood of receiving POC secondary to nonclinical factors. When retrospectively analyzing a representative cohort of patients undergoing radical cystectomy for muscle-invasive bladder cancer between 2006 and 2010

  6. Experimental electrical stimulation of the bladder using a new device

    DEFF Research Database (Denmark)

    Petersen, T.; Christiansen, P.; Nielsen, B.

    1986-01-01

    Repeated bladder contractions were evoked during a six month period in three unanaesthetized female minipigs by using unipolar carbon fiber electrodes embedded in the bladder wall adjacent to the ureterovesical junction. In contrast to bipolar and direct bladder muscle stimulation unipolar...... electrodes at each ureterovesical junction evoked bladder pressure increase similar to those produced in previous investigations in dogs. Sacral nerve stimulation of S2 evoked bladder contraction at a minimal current. Microscopic examination revealed no cellular reactions to the carbon fibers...

  7. The Patient Deficit Model Overturned: a qualitative study of patients' perceptions of invitation to participate in a randomized controlled trial comparing selective bladder preservation against surgery in muscle invasive bladder cancer (SPARE, CRUK/07/011

    Directory of Open Access Journals (Sweden)

    Moynihan Clare

    2012-11-01

    Full Text Available Abstract Background Evidence suggests that poor recruitment into clinical trials rests on a patient ‘deficit’ model – an inability to comprehend trial processes. Poor communication has also been cited as a possible barrier to recruitment. A qualitative patient interview study was included within the feasibility stage of a phase III non-inferiority Randomized Controlled Trial (RCT (SPARE, CRUK/07/011 in muscle invasive bladder cancer. The aim was to illuminate problems in the context of randomization. Methods The qualitative study used a ‘Framework Analysis’ that included ‘constant comparison’ in which semi-structured interviews are transcribed, analyzed, compared and contrasted both between and within transcripts. Three researchers coded and interpreted data. Results Twenty-four patients agreed to enter the interview study; 10 decliners of randomization and 14 accepters, of whom 2 subsequently declined their allocated treatment. The main theme applying to the majority of the sample was confusion and ambiguity. There was little indication that confusion directly impacted on decisions to enter the SPARE trial. However, confusion did appear to impact on ethical considerations surrounding ‘informed consent’, as well as cause a sense of alienation between patients and health personnel. Sub-optimal communication in many guises accounted for the confusion, together with the logistical elements of a trial that involved treatment options delivered in a number of geographical locations. Conclusions These data highlight the difficulty of providing balanced and clear trial information within the UK health system, despite best intentions. Involvement of multiple professionals can impact on communication processes with patients who are considering participation in RCTs. Our results led us to question the ‘deficit’ model of patient behavior. It is suggested that health professionals might consider facilitating a context in which patients

  8. Pain during ice water test distinguishes clinical bladder hypersensitivity from overactivity disorders

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    Bountra Chas

    2006-12-01

    Full Text Available Abstract Background The Bladder cooling reflex (BCR i.e. uninhibited detrusor contractions evoked by intravesical instillation of cold saline, is a segmental reflex believed to be triggered by menthol sensitive cold receptors in the bladder wall, with the afferent signals transmitted by C fibres. The BCR is a neonatal reflex that becomes suppressed by descending signals from higher centres at approximately the time when the child gains full voluntary control of voiding. It re-emerges in adults with neurogenic detrusor overactivity as a consequence of loss of central descending inhibition, resulting from conditions such as spinal cord injury or multiple sclerosis. We have recently shown an increase of nerve fibres expressing the cool and menthol receptor TRPM8 in both overactive (IDO and painful bladder syndrome (PBS, but its functional significance is unknown. We have therefore studied the bladder cooling reflex and associated sensory symptoms in patients with PBS and overactivity disorders. Methods The BCR, elicited by ice water test (IWT was performed in patients with painful bladder syndrome (PBS, n = 17, idiopathic detrusor overactivity (IDO, n = 22, neurogenic detrusor overactivity (NDO, n = 4 and stress urinary incontinence (as controls, n = 21. The IWT was performed by intravesical instillation of cold saline (0 – 4°C. A positive IWT was defined as presence of uninhibited detrusor contraction evoked by cold saline, associated with urgency or with fluid expulsion. Patients were asked to report and rate any pain and cold sensation during the test. Results A positive IWT was observed in IDO (6/22, 27.3% and NDO (4/4, 100% patients, but was negative in all control and PBS patients. Thirteen (76.5% PBS patients reported pain during the IWT, with significantly higher pain scores during ice water instillation compared to the baseline (P = 0.0002, or equivalent amount of bladder filling (100 mls with saline at room temperature (P = 0.015. None

  9. Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

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    Franklin C. Lee

    2013-01-01

    Full Text Available Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0 and any response (≤pT1. Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64, P=0.03 and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64, P=0.01. Seventy-two patients received GC (n=41 or MVAC (n=31. CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58. Any response (≤pT1 was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71. Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC. Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

  10. Urinary incontinence at orgasm: relation to detrusor overactivity and treatment efficacy.

    Science.gov (United States)

    Serati, Maurizio; Salvatore, Stefano; Uccella, Stefano; Cromi, Antonella; Khullar, Vik; Cardozo, Linda; Bolis, Pierfrancesco

    2008-10-01

    To understand the pathophysiological mechanism of incontinence during orgasm and to compare women affected by symptomatic detrusor overactivity (DO) with and without incontinence at orgasm in terms of efficacy of antimuscarinic treatment. All consecutive sexually active women with incontinence during intercourse were prospectively included and divided into two groups: women with coital incontinence at orgasm or at penetration. The two forms of coital incontinence were correlated to the urodynamic finding of DO. Women complaining of overactive bladder (OAB) symptoms, with urinary incontinence at orgasm and urodynamically proven DO (cases), were prescribed tolterodine 4 mg extended release for at least 12 wk. The cases were compared in terms of efficacy of treatment on OAB symptoms to consecutive patients with symptomatic DO without coital incontinence (control group). Among the 1133 women who underwent urodynamic testings during the study period, 132 patients were eligible for final analysis. A significant difference in DO was observed in women with incontinence at orgasm (34 of 49; 69.4%) compared with women with incontinence during penetration (24 of 83; 28.9%) (porgasm associated with DO were given antimuscarinics treatment and were compared with 53 controls. Fourteen of 34 (41.2%) and 9 of 53 (17%) women did not respond to antimuscarinics in the cases and in the control group, respectively (p=0.023). Incontinence at orgasm is associated with DO in the majority of cases. This is the first study showing an inferior efficacy of antimuscarinic treatment in women with DO complaining of incontinence at orgasm.

  11. Characterization of prejunctional serotonin receptors modulating [3H]acetylcholine release in the human detrusor.

    Science.gov (United States)

    D'Agostino, Gianluigi; Condino, Anna M; Gallinari, Paola; Franceschetti, Gian P; Tonini, Marcello

    2006-01-01

    Bladder overactivity (OAB) is a chronic and debilitating lower urinary tract (LUT) disorder that affects millions of individuals worldwide. LUT symptoms associated with OAB, such as urgency and urinary incontinence, cause a hygienic and social concern to patients, but their current pharmacological treatment is largely inadequate due to the lack of uroselectivity. Although OAB etiology remains multifactorial and poorly understood, increasing evidence indicates that serotonin [5-hydroxytryptamine (5-HT)] is an endogenous substance involved in the control of micturition at central and peripheral sites. In this study, we demonstrated the presence of three distinct 5-HT receptors localized at parasympathetic nerve terminals of the human bladder by measuring electrically evoked tritiated acetylcholine release in isolated detrusor strips. These prejunctional receptors, involved in both positive and negative feedback mechanisms regulating cholinergic transmission, have been characterized by means of three highly selective 5-HT antagonists for 5-HT(4), 5-HT(7), and 5-HT(1A) receptors, namely GR113808A ([1-[2-[(-methylsulphonyl) amino] ethyl]4-piperinidyl]methyl1-methyl-1H-indole-3-carboxylate succinate), SB269970 [(R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)pyrrolidine-1-sulfonyl)phenol hydrochloride], and WAY100635 [N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)-cyclohexane-carboxamide trichloride]. Under these conditions, we confirmed the facilitatory role of 5-HT(4) heteroreceptors on acetylcholine release and revealed for the first time the occurrence of 5-HT(7) and 5-HT(1A) heteroreceptors with a facilitatory and an inhibitory action, respectively. Our findings strengthen the novel concept for the use of recently patented selective 5-HT agonists and antagonists for the control of OAB dysfunctions associated with inflammatory conditions, although their therapeutic efficacy needs to be explored in the clinical setting.

  12. Bethanechol chloride for the prevention of bladder dysfunction after radical hysterectomy in gynecologic cancer patients: a randomized controlled trial study.

    Science.gov (United States)

    Manchana, Tarinee; Prasartsakulchai, Chalisa

    2011-05-01

    Bethanechol chloride is considered as a treatment in patients with high postvoid residual urine (PVR). It enhances detrusor muscle contraction, resulting in higher maximum flow rate, higher detrusor pressure at maximum flow, and lower PVR. The efficacy of this agent in patients after radical hysterectomy is unclear. We aim to evaluate the efficacy of bethanechol chloride compared with placebo for the prevention of bladder dysfunction after type III radical hysterectomy. Gynecologic cancer patients who underwent type III radical hysterectomy were randomized by computer-generated schedule to assign patients in a 1:1 ratio into 2 groups. The treatment group received bethanechol chloride (Ucholine 20 mg 3 times a day on the third to seventh postoperative day), and the control group received placebo. Patients and physicians were masked to treatment allocation. The primary end point was the rate of urethral catheter removal at 1 week postoperatively. If PVR was more than 30% of voided volume, the urethral catheter was reinserted, and medication would be continued but not for more than 1 month. This study was registered as ISRCTN92687416. There were 31 patients in each group without significant difference in baseline characteristics. Twenty-one patients (67.7%) in the treatment group and 12 patients (38.7%) in the control group had the urethral catheter removed at 1 week postoperatively (P = 0.04). Median duration of urethral catheterization was shorter in the treatment group (7 and 14 days, P = 0.03). However, the PVR and the incidence of urinary tract infection at 1 month postoperatively were not significantly different. Nine patients (29%) in the treatment group had adverse events such as nausea, abdominal distension, and abdominal cramping, which was higher than the control group (1 patient, 3.2%; P = 0.01). However, no patients required any medical treatments. Bethanechol chloride decreases the duration of urethral catheterization in patients who underwent type III

  13. Bladder Leiomyoma.

    Science.gov (United States)

    Caliskan, Selahattin; Sungur, Mustafa

    2017-03-01

    Leiomyoma of the bladder is a very rare disorder that accounts for 0.43% of all bladder neoplasms. Although the pathophysiology of the bladder leiomyoma is unknown, there are some theories in it. The patients can be asymptomatic; and clinical symptoms, when present, are associated with the tumor size and location. Imaging techniques such as ultrasonography, intravenous urography, computed tomography, and magnetic resonance imaging are helpful but definitive diagnosis is made by histopathological examination. Surgical resection of tumor with transurethral, open, laparoscopic and robotic approaches is the main treatment. We present a case of leiomyoma of the bladder in an adult male patient.

  14. Clinical variability of target volume description and treatment plans in conformal radiotherapy in muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Logue, John P; Sharrock, Carole L; Cowan, Richard A.; Read, Graham; Marrs, Julie; Mott, David

    1996-01-01

    Purpose/Objective: The delineation of tumor and the production of a treatment plan to encompass this is the prime step in radiotherapy planning. Conformal radiotherapy is developing rapidly and although plentiful research has addressed the implementation of the radiotherapy prescription, scant attention has been made to the fundamental step of production, by the clinician, of an appropriate target volume. As part of an ongoing randomized trial of conformal radiotherapy, in bladder cancer, we have therefore assessed the interphysician variability of radiologists and radiation oncologists (RO) in assessing Gross Tumor Volume(GTV) (ICRU 50) and the adherence of the radiation oncologists to the study protocol of producing a Planning Target Volume (PTV). Materials and Methods: Four patients with T3 carcinoma of bladder who had been entered into the trial were identified. The clinical details, MR scans and CT scans were made available. Eight RO and 3 dedicated diagnostic oncology radiologists were invited to directly outline the GTV onto CT images on a planning computer consul. The RO in addition created a PTV following the trial protocol of 15mm margin around the GTV. Three RO sub-specialized in Urological radiotherapy; all RO had completed training. Volumes were produced, for each clinician, and comparison of these volumes and their isocenters were analyzed. In addition the margins allowed were measured and compared. Results: There was a maximum variation ratio (largest to smallest volume outlined) of the GTV in the four cases of 1.74 among radiologists and 3.74 among oncologists. There was a significant difference (p=0.01) in mean GTV between RO and the radiologists. The mean GTV of the RO exceeded the radiologists by a factor of 1.29 with a mean difference of 13.4 cm 3 The between observer variance within speciality comprised only 9.9% of the total variance in the data having accounted for case and observers speciality. The variation ratio in PTV among oncologists

  15. Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency.

    Science.gov (United States)

    Regadas, Rommel Prata; Reges, Ricardo; Cerqueira, João Batista Gadelha; Sucupira, Daniel Gabrielle; Jamacaru, Francisco Vagnaldo F; Moraes, Manoel Odorico de; Gonzaga-Silva, Lúcio Flávio

    2014-01-01

    The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO) induced by chronic nitric oxide deficiency. Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME); 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days), all animals were submitted to urodynamic study. The administration of L-NAME increased the number of non-voiding contractions (NVC) (1.04 ± 0.22), volume threshold (VT) (1.86 ± 0.35), and micturition cycle (MC) (1.34 ± 0.11) compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30), respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42) and VT (0.76 ± 0.24 ) compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53) and MC (0.76 ± 0.22) compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18), VT (0.97 ± 0.52) and MC (0.68 ± 0.30) compared with L-NAME group. In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles.

  16. Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

    Directory of Open Access Journals (Sweden)

    Rommel Prata Regadas

    2014-08-01

    Full Text Available Purpose The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO induced by chronic nitric oxide deficiency. Materials and Methods Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME; 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days, all animals were submitted to urodynamic study. Results The administration of L-NAME increased the number of non-voiding contractions (NVC (1.04 ± 0.22, volume threshold (VT (1.86 ± 0.35, and micturition cycle (MC (1.34 ± 0.11 compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30, respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42 and VT (0.76 ± 0.24 compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53 and MC (0.76 ± 0.22 compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18, VT (0.97 ± 0.52 and MC (0.68 ± 0.30 compared with L-NAME group. Conclusion In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles.

  17. A 3D Printed Implantable Device for Voiding the Bladder Using Shape Memory Alloy (SMA) Actuators.

    Science.gov (United States)

    Hassani, Faezeh Arab; Peh, Wendy Yen Xian; Gammad, Gil Gerald Lasam; Mogan, Roshini Priya; Ng, Tze Kiat; Kuo, Tricia Li Chuen; Ng, Lay Guat; Luu, Percy; Yen, Shih-Cheng; Lee, Chengkuo

    2017-11-01

    Underactive bladder or detrusor underactivity (DU) is defined as a reduction of contraction strength or duration of the bladder wall. Despite the serious healthcare implications of DU, there are limited solutions for affected individuals. A flexible 3D printed implantable device driven by shape memory alloys (SMA) actuators is presented here for the first time to physically contract the bladder to restore voluntary control of the bladder for individuals suffering from DU. This approach is used initially in benchtop experiments with a rubber balloon acting as a model for the rat bladder to verify its potential for voiding, and that the operating temperatures are safe for the eventual implantation of the device in a rat. The device is then implanted and tested on an anesthetized rat, and a voiding volume of more than 8% is successfully achieved for the SMA-based device without any surgical intervention or drug injection to relax the external sphincter.

  18. [Systematic review on conservative treatment options in non-muscle-invasive bladder cancer patients refractory to Bacillus Calmette-Guérin instillation therapy].

    Science.gov (United States)

    Martini, Thomas; Wezel, Felix; Löbig, Niklas; Mitterberger, Michael J; Colleselli, Daniela

    2017-08-01

    Background Adjuvant Bacillus Calmette-Guérin (BCG) intravesical instillation is the recommended standard treatment in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). However, a significant proportion of patients fail treatment, and radical cystectomy (RC) is the subsequent gold standard. On the other hand, there is an unmet need for conservative alternatives for patients who are unfit or unwilling to undergo surgery. This study aimed to identify conservative treatment options in NMIBC patients after BCG failure. Material and Methods We performed a systematic search in the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, including all randomised controlled trials (RCTs), quasi-RCTs and single-arm studies, in which patients with NMIBC were treated with second-line intravesical or systemic therapy after BCG failure. A minimum of eight patients were included in each treatment arm. Full papers were restricted to English language. Literature research and data analysis were assessed independently by two reviewers. Data on treatment response, recurrence, time to recurrence, progression and rate of cystectomy were collected and analysed. Results  This systematic review included 42 publications with a total of 3521 patients (2371 BCG failures). Valrubicin, taxanes, gemcitabine, combination chemotherapy, thermochemotherapy, photodynamic therapy, combination of BCG and interferon and immunotherapies or targeted therapies were identified as conservative treatment options. For taxanes, gemcitabine and thermochemotherapy there is the highest evidence for a clinical meaningful response with minor toxicities. Conclusions Despite some promising response rates for taxanes, gemcitabine or thermochemotherapy, an evidence-based recommendation for treatment options superior to RC in patients failing BCG therapy cannot be made. The definition of BCG failure is still inconsistent and heterogeneous outcomes in patients with BCG

  19. p53 Status correlates with the risk of recurrence in non-muscle invasive bladder cancers treated with Bacillus Calmette-Guérin: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xiaofeng Zhou

    Full Text Available Published studies have yielded inconsistent results on the relationship between p53 status and the prognosis of non-muscle invasive bladder cancer (NMIBC treated with Bacillus Calmette-Guérin (BCG intravesical therapy. Therefore, we performed a meta-analysis to evaluate the prognostic value of p53 in NMIBC treated with BCG.We systematically searched for relevant literature in PubMed, EMBASE, CNKI, and Chinese Wanfang databases. Hazard ratios (HRs with 95% confidence intervals (CIs were combined as the effect size (ES across studies for recurrence-free survival (RFS and progression-free survival (PFS.A total of 11 studies, consisting of 1,049 participants, met the criteria. Overall, there was no clear relationship between p53 status and RFS or PFS for NMIBC patients treated with BCG (HR: 1.40, 95% CI: 0.91-2.16; HR: 1.37, 95% CI: 0.90-2.09, respectively. Obvious heterogeneity was observed across the studies (I2 = 69.5%, P = 0.001; I2 = 44.7%, P = 0.081, respectively. In stratified analysis by region, p53 overexpression was a predictor of poor RFS in Asian populations (HR: 1.57, 95% CI: 1.08-2.27. In addition, after excluding the studies that possibly contributed to the heterogeneity by the Galbraith plot, the overall association for RFS became statistically significant (HR: 1.38 95% CI: 1.08-1.77 without evidence of heterogeneity (I2 = 0.0%, P = 0.499.This meta-analysis suggests that p53 overexpression in NMIBC patients treated with BCG may be associated with RFS, especially in Asian populations. Because of the heterogeneity and other limitations, further studies with rigid criteria and large populations are still warranted to confirm our findings.

  20. HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Mark O Kitchen

    2018-01-01

    Full Text Available Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.

  1. Lymphovascular invasion, ureteral reimplantation and prior history of urothelial carcinoma are associated with poor prognosis after partial cystectomy for muscle-invasive bladder cancer with negative pelvic lymph nodes.

    Science.gov (United States)

    Ma, B; Li, H; Zhang, C; Yang, K; Qiao, B; Zhang, Z; Xu, Y

    2013-10-01

    To identify predictive factors underlying recurrence and survival after partial cystectomy for pelvic lymph node-negative muscle-invasive bladder cancer (MIBC) (urothelial carcinoma) and to report the results of partial cystectomy among select patients. We retrospectively reviewed 101 cases that received partial cystectomy for MIBC (pT2-3N0M0) between 2000 and 2010. The log-rank test and a Cox regression analyses were performed to identify factors that were predictive of recurrence and survival. With a median follow-up of 53.0 months (range 9-120), the 5-year overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) rates were 58%, 65% and 50%, respectively. A total of 33 patients died of bladder cancer and 52 patients survived with intact bladder. Of the 101 patients included, 55 had no recurrence, 12 had non-muscle-invasive recurrence in the bladder that was treated successfully, and 34 had recurrence with advanced disease. The multivariate analysis showed that prior history of urothelial carcinoma (PH.UC) was associated with both CSS and RFS and weakly associated with OS; lymphovascular invasion (LVI) and ureteral reimplantation (UR) were associated with OS, CSS and RFS. Among patients with pelvic lymph node-negative MIBC, PH.UC and UR should be considered as contraindications for partial cystectomy, and LVI is predictive of poor outcomes after partial cystectomy. Highly selective partial cystectomy is a rational alternative to radical cystectomy for the treatment of MIBC with negative pelvic lymph nodes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Combined Chemoradiation Therapy With Twice-Weekly Gemcitabine and Cisplatin for Organ Preservation in Muscle-Invasive Bladder Cancer: Long-Term Results of a Phase 1 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Azria, David, E-mail: david.azria@icm.unicancer.fr [Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier (France); INSERM, U896, IRCM, Montpellier (France); Riou, Olivier [Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier (France); Rebillard, Xavier [Department of Urology, Clinique Beausoleil, Montpellier (France); Thezenas, Simon [Biostatistics Unit, Montpellier Cancer Institute, Montpellier (France); Thuret, Rodolphe [Department of Urology, Montpellier University Hospital, Montpellier (France); Fenoglietto, Pascal [Department of Radiation Oncology and Radiophysics Unit, Montpellier Cancer Institute (ICM), Montpellier (France); Pouessel, Damien; Culine, Stephane [Department of Medical Oncology, AP-HP Saint-Louis, Paris (France)

    2014-03-15

    Purpose: Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting. Methods and Materials: Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabine twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control. Results: Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months. Conclusions: This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing.

  3. Contemporary management of low-risk bladder cancer

    NARCIS (Netherlands)

    Falke, J.; Witjes, J.A.

    2011-01-01

    Bladder cancer comprises a heterogeneous group of tumors, the majority of which are non-muscle-invasive bladder cancer (NMIBC) at initial presentation. Low-risk bladder cancer--defined as pTa low-grade papillary tumors--is the type of NMIBC with the most favorable oncologic outcome. Although the

  4. Overactive Bladder

    Science.gov (United States)

    ... especially if your symptoms disrupt your work schedule, social interactions and everyday activities. Causes Normal bladder function The ... fills, nerve signals sent to your brain eventually trigger the need to urinate. When you urinate, nerve ...

  5. Neurogenic bladder

    Science.gov (United States)

    ... cause skin to break down and lead to pressure sores Kidney damage if the bladder becomes too full, ... dysfunction; NBSD Patient Instructions Multiple sclerosis - discharge Preventing pressure ulcers Images Voiding cystourethrogram References Chapple CR, Osman NI. ...

  6. Bladder cancer

    Science.gov (United States)

    ... Dye workers, rubber workers, aluminum workers, leather workers, truck drivers, and pesticide applicators are at the highest ... examining the inside of the bladder with a camera), with biopsy Intravenous pyelogram - IVP Pelvic CT scan ...

  7. Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury

    Science.gov (United States)

    2014-12-01

    propria, between detrusor muscle bundles (intra- muscular ), within muscle bundles (inter- muscular )27 and around blood vessels (perivascular)6 (Fig. 1...osmotic distension , signals propagated from the urothelial to smooth muscle. When the ICs were removed, the smooth muscle did not respond to stretch...calcium channels. Br J Pharmacol 1995;115:1020–6. 37. Ghoneim MA, Fretin JA, Gagnon DJ, et al. The influence of vesical distension on the urethral

  8. Selective stimulation of sacral nerve roots for bladder control: a study by computer modeling

    NARCIS (Netherlands)

    Rijkhoff, N. J.; Holsheimer, J.; Koldewijn, E. L.; Struijk, J. J.; van Kerrebroeck, P. E.; Debruyne, F. M.; Wijkstra, H.

    1994-01-01

    The aim of this study was to investigate theoretically the conditions for the activation of the detrusor muscle without activation of the urethral sphincter and afferent fibers, when stimulating the related sacral roots. Therefore, the sensitivity of excitation and blocking thresholds of nerve

  9. [Bladder-conserving treatment for bladder cancer: potential of and developments in radiotherapy].

    Science.gov (United States)

    Hulshof, Maarten C C M; Pieters, Bradley R; Koning, Caro C E

    2013-01-01

    The standard treatment for muscle-invasive bladder cancer is surgical removal of the bladder and construction of a neobladder. Recently, important improvements have been made in the potential for bladder-conserving treatment using radiotherapy. External beam radiotherapy has undergone technological improvements, as a result of which it is possible to radiate the tumour more precisely while decreasing radiation to healthy tissue. Radiochemotherapy improves local recurrence-free and overall survival compared with radiotherapy alone. The results of this combined treatment are comparable with those of surgery. Additionally, Dutch radiotherapy departments have collected data in a national database of 1040 selected patients with confined bladder cancer. These patients were treated with external beam radiation, limited surgery and brachytherapy. The 5-year local recurrence-free survival was 75%. Bladder conserving treatment options for muscle-invasive bladder cancer should be discussed during the multidisciplinary meeting.

  10. Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

    Directory of Open Access Journals (Sweden)

    Dozmorov Igor

    2007-05-01

    Full Text Available Abstract Background Tachykinins (TK, such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs. Methods An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2. In the absence of

  11. [Economic impact of overactive bladder symptoms in Japan].

    Science.gov (United States)

    Inoue, Sachie; Kobayashi, Makoto; Sugaya, Kimio

    2008-11-01

    Overactive bladder (OAB) is characterized by involuntary contractions of the detrusor muscles of the bladder. The primary symptoms of OAB include urinary urgency and frequency, with or without urge incontinence. Despite the growing awareness of OAB as a chronic medical condition, little is known about the disease's economic burden. Therefore, in the present study, the costs associated with the management of OAB symptoms in Japan were estimated, and the potential cost saving by increasing the rate of physician visits in OAB population was analyzed. To estimate the costs of OAB symptoms in Japan, we collected a variety of epidemiologic and economic literatures about OAB or urinary incontinence published by June, 2007. Three types of costs were considered in this estimation: 1. OAB treatment cost (pharmacological treatment cost, diagnostic cost and cost for physician visits), 2. direct cost (OAB-related cost [urinary tract infections, skin infections and fractures] and incontinence care cost [costs of pads, diapers and cleaning]), and 3. indirect cost (work loss due to absence from work and decrease in productivity). The analysis was conducted on community dwelling Japanese persons aged > or = 40 years, and assumed that OAB patients visited a hospital or a clinic once every four weeks. For the estimation of pharmacological treatment cost, four anticholinergic drugs (immediate-release oxybutynin (Pollakisu), propiverine (BUP-4), extended-release tolterodine (Detrusitol) and solifenacin (Vesicare)) were referred. Potential cost saving was estimated on the assumption that the hospital visit rate would increase from the current 22.7% to 35% and 50%, respectively. The number of persons with OAB symptoms and OAB patients was estimated at 8.6 million (4.6 million men, 4.0 million women) and 2.0 million (1.7 million men, 0.3 million women), respectively. The annual cost for OAB was estimated to be 956.2 billion yen (112,000 yen per one person with OAB symptoms). This cost

  12. Bladder Cancer Advocacy Network

    Science.gov (United States)

    ... Grants Bladder Cancer Think Tank Bladder Cancer Research Network Bladder Cancer Genomics Consortium Get Involved Ways to ... us? Who we are The Bladder Cancer Advocacy Network (BCAN) is a community of patients, caregivers, survivors, ...

  13. Researchers studying alternative to bladder removal for bladder cancer patients | Center for Cancer Research

    Science.gov (United States)

    A new phase I clinical trial conducted by researchers at the Center for Cancer Research (CCR) is evaluating the safety and tolerability, or the degree to which any side effects can be tolerated by patients, of a two-drug combination as a potential alternative to bladder removal for bladder cancer patients. The trial targets patients with non-muscle invasive bladder cancer (NMIBC) whose cancers have stopped responding to traditional therapies. Read more...

  14. Work Capacity of the Bladder During Voiding: A Novel Method to Evaluate Bladder Contractile Function and Bladder Outlet Obstruction

    Directory of Open Access Journals (Sweden)

    Ning Liu

    2015-01-01

    Full Text Available Background: Work in voiding (WIV of the bladder may be used to evaluate bladder status throughout urination rather than at a single time point. Few studies, however, have assessed WIV owing to the complexity of its calculations. We have developed a method of calculating work capacity of the bladder while voiding and analyzed the associations of bladder work parameters with bladder contractile function and bladder outlet obstruction (BOO. Methods: The study retrospectively evaluated 160 men and 23 women, aged >40 years and with a detrusor pressure at maximal flow rate (P det Q max of ≥40 cmH 2 O in men, who underwent urodynamic testing. The bladder power integration method was used to calculate WIV; WIV per second (WIV/t and WIV per liter of urine voided (WIV/v were also calculated. In men, the relationships between these work capacity parameters and P det Q max and Abrams-Griffiths (AG number were determined using linear-by-linear association tests, and relationships between work capacity parameters and BOO grade were investigated using Spearman′s association test. Results: The mean WIV was 1.15 ± 0.78 J and 1.30 ± 0.88 J, mean WIV/t was 22.95 ± 14.45 mW and 23.78 ± 17.02 mW, and mean WIV/v was 5.59 ± 2.32 J/L and 2.83 ± 1.87 J/L in men and women, respectively. In men, WIV/v showed significant positive associations with P det Q max (r = 0.845, P = 0.000, AG number (r = 0.814, P = 0.000, and Schafer class (r = 0.726, P = 0.000. Conversely, WIV and WIV/t showed no associations with P det Q max or AG number. In patients with BOO (Schafer class > II, WIV/v correlated positively with increasing BOO grade. Conclusions: WIV can be calculated from simple urodynamic parameters using the bladder power integration method. WIV/v may be a marker of BOO grade, and the bladder contractile function can be evaluated by WIV and WIV/t.

  15. Are patients with bladder oversensitivity different from those with urodynamically proven detrusor overactivity in female overactive bladder syndrome?

    Directory of Open Access Journals (Sweden)

    Sung-Lang Chen

    2017-10-01

    Conclusion: Patients with BO seemed to be on a different spectrum compared to those with DO and also had different symptom-specific and associative factors. It was also found that FDV could be good predictive indicator for detecting DO at a low filling rate.

  16. Applications of Nanotechnology in Bladder Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jong-Wei Hsu

    2012-01-01

    Full Text Available Effective therapies can prevent superficial bladder cancer from developing into muscle-invasive stage or more severe stages which require radical cystectomy and negatively affect life quality. In terms of therapeutic approaches against superficial bladder cancer, intravesical (regional therapy has several advantages over oral (systemic therapy. Though urologists can directly deliver drugs to bladder lesions by intravesical instillation after transurethral resection, the efficacy of conventional drug delivery is usually low due to the bladder permeability barrier and bladder periodical discharge. Nanoparticles have been well developed as pharmaceutical carriers. By their versatile properties, nanoparticles can greatly improve the interactions between urothelium and drugs and also enhance the penetration of drugs into urothelium with lesions, which dramatically improves therapeutic efficacy. In this review, we discuss the advances of nanotechnology in bladder cancer therapy by different types of nanoparticles with different encapsulating materials.

  17. The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer.

    Science.gov (United States)

    Witjes, J Alfred; Dalbagni, Guido; Karnes, Robert J; Shariat, Shahrokh; Joniau, Steven; Palou, Joan; Serretta, Vincenzo; Larré, Stéphane; di Stasi, Savino; Colombo, Renzo; Babjuk, Marek; Malmström, Per-Uno; Malats, Nuria; Irani, Jacques; Baniel, Jack; Cai, Tommaso; Cha, Eugene; Ardelt, Peter; Varkarakis, John; Bartoletti, Riccardo; Spahn, Martin; Pisano, Francesca; Gontero, Paolo; Sylvester, Richard

    2016-11-01

    Potential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients. Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011. Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival. Information on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20-1.82; PTICE was more effective than Connaught for the time to first recurrence (HR = 0.66; 95% CI: 0.47-0.93; P = 0.019) with a trend for cancer specific survival (HR = 0.36; 95% CI: 0.14-0.92; P = 0.033). For time to progression and overall survival, Connaught and TICE had a similar efficacy. Compared to no maintenance therapy, maintenance BCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught. We found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given. As there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate

  18. [Effect of hydrostatic pressure on intracellular free calcium concentration and transient receptor potential vanilloid expression in human bladder smooth muscle cells].

    Science.gov (United States)

    Han, Zhenwei; Wang, Kunjie; Chen, Lin; Wei, Tangqiang; Luo, Deyi; Li, Shengfu

    2012-04-01

    To explore the effect of hydrostatic pressure on intracellular free calcium concentration ([Ca2+]i) and the gene expression of transient receptor potential vanilloid (TRPV) in cultured human bladder smooth muscle cells (hb-SMCs), and to preliminarily probe into the possible molecular mechanism of hb-SMCs proliferation stimulated by hydrostatic pressure. The passage 6-7 hb-SMCs were loaded with Ca2+ indicator Fluo-3/AM. When the hb-SMCs were under 0 cm H2O (1cm H2O = 0.098 kPa) (group A) or 200 cm H2O hydrostatic pressure for 30 minutes (group B) and then removing the 200 cm H2O hydrostatic pressure (group C), the [Ca2+]i was measured respectively by inverted laser scanning confocal microscope. When the hb-SMCs were given the 200 cm H2O hydrostatic pressure for 0 hour, 2 hours, 6 hours, 12 hours, and 24 hours, the mRNA expressions of TRPV1, TRPV2, and TRPV4 were detected by RT-PCR technique. The [Ca2+]i of group A, group B, and group C were (100.808 +/- 1.724), (122.008 +/- 1.575), and (99.918 +/- 0.887) U, respectively; group B was significantly higher than groups A and C (P pressure (t = 0.919, P = 0.394). The TRPV1, TRPV2, and TRPV4 genes expressed in hb-SMCs under 200 cm H2O hydrostatic pressure at 0 hour, 2 hours, 6 hours, 12 hours, and 24 hours, but the expressions had no obvious changes with time. There was no significant difference in the expressions of TRPV1, TRPV2, and TRPV4 among 3 groups (P > 0.05). The [Ca2+]i of hb-SMCs increases significantly under high hydrostatic pressure. As possible genes in stretch-activated cation channel, the TRPV1, TRPV2, and TRPV4 express in hb-SMCs under 200 cm H2O hydrostatic pressure. It is possible that the mechanical pressure regulates the [Ca2+]i of hb-SMCs by opening the stretch-activated cation channel rather than up-regulating its expression.

  19. Suburothelial Bladder Contraction Detection with Implanted Pressure Sensor.

    Directory of Open Access Journals (Sweden)

    Steve J A Majerus

    Full Text Available Managing bladder pressure in patients with neurogenic bladders is needed to improve rehabilitation options, avoid upper tract damage, incontinence, and their associated co-morbidities and mortality. Current methods of determining bladder contractions are not amenable to chronic or ambulatory settings. In this study we evaluated detection of bladder contractions using a novel piezoelectric catheter-free pressure sensor placed in a suburothelial bladder location in animals.Wired prototypes of the pressure monitor were implanted into 2 nonsurvival (feline and canine and one 13-day survival (canine animal. Vesical pressures were obtained from the device in both suburothelial and intraluminal locations and simultaneously from a pressure sensing catheter in the bladder. Intravesical pressure was monitored in the survival animal over 10 days from the suburothelial location and necropsy was performed to assess migration and erosion.In the nonsurvival animals, the average correlation between device and reference catheter data was high during both electrically stimulated bladder contractions and manual compressions (r = 0.93±0.03, r = 0.89±0.03. Measured pressures correlated strongly (r = 0.98±0.02 when the device was placed in the bladder lumen. The survival animal initially recorded physiologic data, but later this deteriorated. However, endstage intraluminal device recordings correlated (r = 0.85±0.13 with the pressure catheter. Significant erosion of the implant through the detrusor was found.This study confirms correlation between suburothelial pressure readings and intravesical bladder pressures. Due to device erosion during ambulatory studies, a wireless implant is recommended for clinical rehabilitation applications.

  20. THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study.

    Science.gov (United States)

    Maniscalco, Giorgia Teresa; Aponte, R; Bruzzese, D; Guarcello, G; Manzo, V; Napolitano, M; Moreggia, O; Chiariello, F; Florio, C

    2018-01-01

    Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB). The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by means of clinical and instrumental tools. Twenty-one MS patients were screened, and 15 cases have been evaluated. They underwent a specific clinical assessment (overactive bladder symptom score, OABSS) and a urodynamic assessment evaluating the maximal cystometric capacity (CCmax), bladder compliance (Qmax), maximum detrusor pressure (Pdet max), detrusor pressure at the first desire (Pdet first), bladder volume at the first desire (BVFD), leakage volume (LV), and post-void residual volume (PVR), before and after 4 weeks of THC/CBD administration. A complete neurological evaluation, including the assessment of their spasticity using the Modified Ashworth Scale (MAS) and the spasticity 0-10 numerical rating scale (NRS), was performed at the same times. Mobility was evaluated through the 25-ft walking-time test (T25-WT). The THC/CBD treatment successfully reduced the OAB symptoms (p = 0.001). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016), while BVFD and CCmax were increased although the difference was not statistically significant. THC/CBD oromucosal spray has shown to be effective in improving overactive bladder symptoms in MS patients demonstrating a favorable impact on detrusor overactivity.

  1. Neurogenic Bladder in Lyme Disease

    Directory of Open Access Journals (Sweden)

    Mi-hwa Kim

    2012-12-01

    Full Text Available Lyme disease is a multi-systemic, tick-borne infectious disease caused by a spirochete, Borrelia burgdorferi. Various urologic symptoms are associated with Lyme disease, which can be primary or late manifestations of the disease. Although voiding dysfunction is a rarely reported symptom in patients with Lyme disease, it is one of the most disabling complications of Lyme disease. Korea is not an endemic area of Lyme disease, thus, fewer cases have been reported. Herein, we report a case of a 32-year-old man with rapidly progressive bilateral ptosis, dysphagia, spastic paraparesis, and voiding difficulty in whom Lyme disease was diagnosed through serologic tests for antibodies and Western blot testing. A urodynamic study demonstrated detrusor areflexia and bulbocavernosus reflex tests showed delayed latency, indicating demyelination at S2-S4 levels. He received a 4-week course of intravenous ceftriaxone (2 g/day. The patient has recovered from the bilateral ptosis and spastic paraparesis but still suffers from neurogenic bladder.

  2. Implantation of In Vitro Tissue Engineered Muscle Repair Constructs and Bladder Acellular Matrices Partially Restore In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss Injury

    Science.gov (United States)

    2014-01-01

    onto a custom designed seeding chamber made of silicon ( McMaster Carr, Cleveland, OH). Scaffolds and silicon seeding chambers were then individually...TRAUMATIZED SKELETAL MUSCLE 707 observations in an effort to reduce the variability within this group. Ultimately, the coefficient of variation (CV

  3. Efficacy of holmium laser enucleation of the prostate (HoLEP) in men with bladder outlet obstruction (BOO) and non-neurogenic bladder dysfunction.

    Science.gov (United States)

    Pyun, Jong Hyun; Kang, Sung Gu; Kang, Seok Ho; Cheon, Jun; Kim, Je Jong; Lee, Jeong Gu

    2017-09-01

    We aimed to compare the short-term outcomes of men who had urodynamic evidence of detrusor underactivity (DU) or detrusor overactivity (DO) of a non-neurogenic etiology as well as bladder outlet obstruction (BOO) and who underwent Holmium Laser Enucleation of the prostate (HoLEP). A database of 322 patients who underwent HoLEP between 2010 and 2014 was analyzed. Patients were classified into three groups according to the results of a preoperative urodynamic study. Preoperative parameters such as International Prostate Symptom Score (IPSS), Quality of Life (QoL) index, IPSS grade, uroflowmetry were compared with postoperative parameters measured at 6 months. There were 138 patients with BOO-only and 89 patients with BOO and detrusor dysfunction including 56 with DO and 33 with DU. The degree of improvement in IPSS-total (BOO: 10.7, DO: 8.3, DU: 7.0; p = 0.023) was greater in the BOO-only group than in the DU group. There were more patients whose IPSS grade improved in the BOO-only group (71%) than in the detrusor dysfunction group (DO: 53.6% and DU: 45.5%). Postoperative IPSS-voiding (4.5 vs 7.0), and Qmax (18 vs 13.7) in the BOO-only group were significantly better than those in the DU group. Additionally, postoperative IPSS-storage (4.7 vs 6.7), and IPSS-total (9.1 vs 12.3) in the BOO-only group were significantly better than in the DO group (all p < 0.05). In conclusion, early surgical management for men with severe LUTS and associated BPH before secondary degeneration occurs may be beneficial for preserving detrusor function and yield better treatment outcomes. Copyright © 2017. Published by Elsevier Taiwan.

  4. Bladder stones

    Science.gov (United States)

    The health care provider will perform a physical exam. This will also include a rectal exam. The exam may reveal an enlarged prostate or other problems. The following tests may be done: Bladder or pelvic x-ray Cystoscopy Urinalysis Urine culture (clean catch)

  5. Technique of Antireflux Procedure without Creating Submucosal Tunnel for Surgical Correction of Vesicoureteric Reflux during Bladder Closure in Exstrophy.

    Science.gov (United States)

    Sunil, Kanoujia; Gupta, Archika; Chaubey, Digamber; Pandey, Anand; Kureel, Shiv Narain; Verma, Ajay Kumar

    2018-01-01

    To report the clinical application of the new surgical technique of antireflux procedure without creating submucosal tunnel for surgical correction of vesicoureteric reflux during bladder closure in exstrophy. Based on the report of published experimental technique, the procedure was clinically executed in seven patients of classic exstrophy bladder with small bladder plate with polyps, where the creation of submucosal tunnel was not possible, in last 18 months. Ureters were mobilized. A rectangular patch of bladder mucosa at trigone was removed exposing the detrusor. Mobilized urteres were advanced, crossed and anchored to exposed detrusor parallel to each other. Reconstruction included bladder and epispadias repair with abdominal wall closure. The outcome was measured with the assessment of complications, abolition of reflux on cystogram and upper tract status. At 3-month follow-up cystogram, reflux was absent in all. Follow-up ultrasound revealed mild dilatation of pelvis and ureter in one. The technique of extra-mucosal ureteric reimplantation without the creation of submucosal tunnel is simple to execute without risk and complications and effectively provides an antireflux mechanism for the preservation of upper tract in bladder exstrophy. With the use of this technique, reflux can be prevented since the very beginning of exstrophy reconstruction.

  6. Quantifying mast cells in bladder pain syndrome by immunohistochemical analysis

    DEFF Research Database (Denmark)

    Larsen, M.S.; Mortensen, S.; Nordling, J.

    2008-01-01

    OBJECTIVES To evaluate a simple method for counting mast cells, thought to have a role in the pathophysiology of bladder pain syndrome (BPS, formerly interstitial cystitis, a syndrome of pelvic pain perceived to be related to the urinary bladder and accompanied by other urinary symptoms, e. g....... frequency and nocturia), as > 28 mast cells/mm(2) is defined as mastocytosis and correlated with clinical outcome. PATIENTS AND METHODS The current enzymatic staining method (naphtolesterase) on 10 mu m sections for quantifying mast cells is complicated. In the present study, 61 patients had detrusor...... sections between, respectively. Mast cells were counted according to a well-defined procedure. RESULTS The old and the new methods, on 10 and 3 mu m sections, showed a good correlation between mast cell counts. When using tryptase staining and 3 mu m sections, the mast cell number correlated well...

  7. Botulinum toxin A for the Treatment of Overactive Bladder.

    Science.gov (United States)

    Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung

    2016-02-29

    The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.

  8. Is the male dog comparable to human? A histological study of the muscle systems of the lower urinary tract.

    Science.gov (United States)

    Stolzenburg, Jens-Uwe; Schwalenberg, Thilo; Do, Minh; Dorschner, Wolfgang; Salomon, Franz-Viktor; Jurina, Konrad; Neuhaus, Jochen

    2002-08-01

    Because of their superficial anatomical resemblance, the male dog seems to be suitable for studying the physiologic and pathological alterations of the bladder neck of human males. The present study was carried out to compare and contrast the muscular anatomy of the male dog lower urinary tract with that of humans. The complete lower urinary tract, including the surrounding organs (bulb of penis, prostate, rectum and musculature of the pelvic floor) were removed from adult and newborn male dogs and histologically processed using serial section technique. Based on our own histological investigations, three-dimensional (3D)-models of the anatomy of the lower urinary tract were constructed to depict the corresponding structures and the differences between the species. The results of this study confirm that the lower urinary tract of the male dog bears some anatomical resemblance (musculus detrusor vesicae, prostate, prostatic and membranous urethra) to man. As with human males, the two parts of the musculus sphincter urethrae (glaber and transversostriatus) are evident in the canine bladder neck. Nevertheless, considerable differences in formation of individual muscles should be noted. In male dogs, no separate anatomic entity can be identified as vesical or internal sphincter. The individual course of the ventral and lateral longitudinal musculature and of the circularly arranged smooth musculature of the urethra is different to that of humans. Differences in the anatomy of individual muscles of the bladder neck in the male dog and man suggest that physiological interpretations of urethral functions obtained in one species cannot be attributed without qualification to the other.

  9. Efficacy and tolerability of concurrent weekly low dose cisplatin during radiation treatment of localised muscle invasive bladder transitional cell carcinoma: A report of two sequential Phase II studies from the Trans Tasman Radiation Oncology Group

    International Nuclear Information System (INIS)

    Gogna, Nirdosh Kumar; Matthews, John H.L.; Turner, Sandra L.; Mameghan, Heidi; Duchesne, Gillian M.; Spry, Nigel; Berry, Martin P.; Keller, Jacqui; Tripcony, Lee

    2006-01-01

    Background and purpose: To determine the feasibility, toxicity, and clinical effectiveness of concurrent weekly cisplatin chemotherapy in conjunction with definitive radiation in the treatment of localised muscle invasive bladder cancer. Patients and methods: In January 1997 the Trans Tasman Radiation Oncology Group embarked on a Phase II study (TROG 97.01) of weekly cisplatin (35 mg/m 2 x 7 doses) plus radiation to a dose of 63 Gy over 7 weeks. Following an interim toxicity analysis, the dose intensity of cisplatin was reduced to 6 cycles and the radiation schedule changed to 64 Gy over 6.5 weeks leading to the second study (TROG 99.06). A total of 113 patients were enrolled. Results: Acute grade 3 urinary toxicity occurred in 23% of the patients. Acute grade 4 pelvic toxicity was not seen. Thirty-eight patients (33%) experienced grade 3 or 4 cisplatin related toxicities with 15 patients (12%) requiring significant dose modification. The reduced dose intensity in Study 99.06 improved tolerability. Incidence of significant late morbidity was low (6%). Seventy-nine patients (70%) achieved complete remission at the 6 month cystoscopic assessment. Local invasive recurrence was seen in 11 of the 79 patients (14%). In 18 patients (16%) isolated superficial TCC/CIS were detected (6 months and beyond).The local control rate was 45% with a functional bladder being retained in 69 of the 113 patients (61%). RFS and DSS at 5 years were 33% and 50%, respectively. Conclusion: Our two sequential Phase II studies have shown that concurrent chemoradiation using weekly cisplatin in the management of localised invasive bladder TCC is feasible and reasonably well tolerated. This approach is currently being investigated further in a randomised study

  10. BCG+MMC trial: adding mitomycin C to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer: a randomised phase III trial (ANZUP 1301)

    International Nuclear Information System (INIS)

    Hayne, Dickon; Stockler, Martin; McCombie, Steve P.; Chalasani, Venu; Long, Anne; Martin, Andrew; Sengupta, Shomik; Davis, Ian D.

    2015-01-01

    Despite adequate trans-urethral resection of the bladder tumour (TURBT), non-muscle-invasive bladder cancer (NMIBC) is associated with high rates of recurrence and progression. Instillation of Bacillus Calmette-Guérin (BCG) into the urinary bladder after TURBT (adjuvant intravesical administration) reduces the risk of both recurrence and progression, and this is therefore the standard of care for high-risk tumours. However, over 30 % of people still recur or progress despite optimal delivery of BCG. Our meta-analysis suggests that outcomes might be improved further by using an adjuvant intravesical regimen that includes both mitomycin and BCG. These promising findings require corroboration in a definitive, large scale, randomised phase III trial using standard techniques for intravesical administration. The BCG + MMC trial (ANZUP 1301) is an open-label, randomised, stratified, two-arm multi-centre phase III trial comparing the efficacy and safety of standard intravesical therapy (BCG alone) against experimental intravesical therapy (BCG and mitomycin) in the treatment of adults with resected, high-risk NMIBC. Participants in the control group receive standard treatment with induction (weekly BCG for six weeks) followed by maintenance (four-weekly BCG for ten months). Participants in the experimental group receive induction (BCG weeks 1, 2, 4, 5, 7, and 8; mitomycin weeks 3, 6, and 9) followed by four-weekly maintenance (mitomycin weeks 13, 17, 25, 29, 37, and 41; BCG weeks 21, 33, and 45). The trial aims to include 500 participants who will be centrally randomised to one of the two treatment groups in a 1:1 ratio stratified by T-stage, presence of CIS, and study site. The primary endpoint is disease-free survival; secondary endpoints are disease activity, time to recurrence, time to progression, safety, health-related quality of life, overall survival, feasibility, and resource use

  11. Augmentation enterocystoplasty is effective in relieving refractory ketamine-related bladder pain.

    Science.gov (United States)

    Chung, Shiu-Dong; Wang, Chung-Cheng; Kuo, Hann-Chorng

    2014-11-01

    To report our early results of augmentation enterocystoplasty (AE) for severe bladder pain associated with chronic ketamine cystitis (KC). We performed AE for 14 patients with refractory KC-related bladder pain, which is based on the criteria including severe bladder pain, urgency and frequency and/or upper urinary tract damage such as bilateral hydronephrosis, and contracted bladder. Every patient had been treated conservatively with medication or cystoscopic hydrodistention for at least 1 year before they had received surgical intervention. Video-urodynamic studies were obtained before AE and 3-6 months after surgery. Outcome measurements included visual analogue score (VAS) for pain, cystometric bladder capacity (CBC), maximum urinary flow rate (Qmax), post-void residual, and maximal detrusor pressure (Pdet). The patients' general satisfaction with regard to treatment outcome was also assessed by the Patient Perception of Bladder Condition (PPBC). A total of 4 men and 10 women underwent this procedure as indicated. The mean age was 26.7 (ranged 20-38) years old and the duration of ketamine abuse was 3.82 years (ranged 2-7). Contracted bladder was noted in all patients, hydronephrosis in nine and vesicoureteral reflux (VUR) in eight. At 3-6 months after AE, VAS was remarkably improved from baseline to the end-point (8.29 ± 1.54 vs. 2.14 ± 1.51, P ketamine-related bladder pain and lower urinary tract symptoms. © 2013 Wiley Periodicals, Inc.

  12. Effects of electrotherapy in treatment of neurogenic bladder in children with occult spinal dysraphism

    Directory of Open Access Journals (Sweden)

    Ćirović Dragana

    2009-01-01

    Full Text Available Introduction Neurogenic bladder can develop as a result of various degrees of neurogenic lesion in spina bifida. The degree of bladder dysfunction depends on the level and type of spina bifida. Due to results upon complete diagnostic protocols, treatment options are applied. Objective Comparison of therapy results of patients with occult spinal dysraphism with neurogenic bladder that under-went medicamentous therapy and medicamentous with electrotherapy treatment. Methods We had 49 patients with neurogenic bladder that were treated at the University Children's Hospital in Belgrade in the period 2003-2008. The first group of children received medicamentous therapy and the second group received medicamentous therapy with transcutaneous electric nerve stimulation. In both groups we evaluated 4 symptoms: daily enuresis, enuresis nocturna, urgency and frequency and 4 urodynamic parameters: lower bladder capacity, unstable contractions and residual urine and detrusor sphincter dyssynergia. Follow-up urodynamic evaluation was done after 3, 6 and 12 months respectively. Results Our findings pointed out a high statistical significance of improvement in all evaluated urodynamic parameters of neurogenic bladder (predominantly in bladder capacity in the group of children with combined therapy as well in resolution of symptoms (predominantly enuresis nocturna, urgency and frequency. Conclusion Combined therapy is more efficient in treatment of children with neurogenic bladder. Electrotherapy is non-invasive, easily applicable and has had a significant place in treatment of children with dysfunctional voiding.

  13. Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations

    Directory of Open Access Journals (Sweden)

    Benham Christopher D

    2006-03-01

    Full Text Available Abstract Background The recent identification of the cold-menthol sensory receptor (TRPM8; CMR1, provides us with an opportunity to advance our understanding of its role in the pathophysiology of bladder dysfunction, and its potential mediation of the bladder cooling reflex. In this study, we report the distribution of the cool and menthol receptor TRPM8 in the urinary bladder in patients with overactive and painful bladder syndromes, and its relationship with clinical symptoms. Methods Bladder specimens obtained from patients with painful bladder syndrome (PBS, n = 16, idiopathic detrusor overactivity (IDO, n = 14, and asymptomatic microscopic hematuria (controls, n = 17, were immunostained using specific antibodies to TRPM8; nerve fibre and urothelial immunostaining were analysed using fibre counts and computerized image analysis respectively. The results of immunohistochemistry were compared between the groups and correlated with the Pain, Frequency and Urgency scores. Results TRPM8-immunoreactive staining was observed in the urothelium and nerve fibres scattered in the suburothelium. The nerve fibre staining was seen in fine-calibre axons and thick (myelinated fibres. There was marked increase of TRPM8-immunoreactive nerve fibres in IDO (P = 0.0249 and PBS (P Conclusion This study demonstrates increased TRPM8 in nerve fibres of overactive and painful bladders, and its relationship with clinical symptoms. TRPM8 may play a role in the symptomatology and pathophysiology of these disorders, and may provide an additional target for future overactive and painful bladder pharmacotherapy.

  14. Perioperative complications of radical cystectomy after induction chemoradiotherapy in bladder-sparing protocol against muscle-invasive bladder cancer. A single institutional retrospective comparative study with primary radical cystectomy

    International Nuclear Information System (INIS)

    Iwai, Aki; Koga, Fumitaka; Fujii, Yasuhisa; Masuda, Hitoshi; Saito, Kazutaka; Numao, Noboru; Sakura, Mizuaki; Kawakami, Satoru; Kihara, Kazunori

    2011-01-01

    The objective of this study was to compare rates of early morbidity after radical cystectomy in patients treated with or without induction chemoradiotherapy (CRT) using a standardized reporting methodology. All 193 consecutive patients undergoing radical cystectomy for bladder cancer between 1989 and 2010 were retrospectively reviewed. Induction chemoradiotherapy consists of radiation at 40 Gy to the small pelvis and two cycles of concurrent cisplatin at 20 mg/day for 5 days. Deaths within 90 days after radical cystectomy and complications arising within 30 days were recorded and graded according to the Clavien-Dindo classification. Grades 1-2 were considered minor; Grades 3-5 were considered major. Eighty-seven patients underwent radical cystectomy following chemoradiotherapy (chemoradiotherapy group) while the remaining 106 primarily underwent radical cystectomy (no chemoradiotherapy group). No Grade 4-5 complication was observed. Overall, 118 patients (61%) experienced 36 major and 122 minor complications. There was no significant difference in the incidence of overall complications between the chemoradiotherapy and no chemoradiotherapy groups (67 vs. 57%). Overall urinary anastomosis-related complications and major gastrointestinal complications, most of which were Grade 3 ileus, were more frequent in the chemoradiotherapy group than the no chemoradiotherapy group (11 vs. 2%, P=0.007; and 14 vs. 4%, P=0.02; respectively). Multivariate analysis identified induction chemoradiotherapy as an independent risk factor for overall urinary anastomosis-related complications (relative risk 6.0, P=0.01) but not for major gastrointestinal complications. Induction chemoradiotherapy at 40 Gy in bladder-sparing protocols against MIBC is unlikely to increase the rate of severe complications of radical cystectomy. (author)

  15. Bladder exstrophy: current management and postoperative imaging

    International Nuclear Information System (INIS)

    Pierre, Ketsia; Borer, Joseph; Phelps, Andrew; Chow, Jeanne S.

    2014-01-01

    Bladder exstrophy is a rare malformation characterized by an infra-umbilical abdominal wall defect, incomplete closure of the bladder with mucosa continuous with the abdominal wall, epispadias, and alterations in the pelvic bones and muscles. It is part of the exstrophy-epispadias complex, with cloacal exstrophy on the severe and epispadias on the mild ends of the spectrum. Bladder exstrophy is the most common of these entities and is more common in boys. The goal of this paper is to describe common methods of repair and to provide an imaging review of the postoperative appearances. (orig.)

  16. Bladder exstrophy: current management and postoperative imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pierre, Ketsia [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Borer, Joseph [Boston Children' s Hospital, Department of Urology, Boston, MA (United States); Phelps, Andrew [University of California, San Francisco, Department of Pediatric Radiology, San Francisco, CA (United States); Chow, Jeanne S. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Boston Children' s Hospital, Department of Urology, Boston, MA (United States)

    2014-07-15

    Bladder exstrophy is a rare malformation characterized by an infra-umbilical abdominal wall defect, incomplete closure of the bladder with mucosa continuous with the abdominal wall, epispadias, and alterations in the pelvic bones and muscles. It is part of the exstrophy-epispadias complex, with cloacal exstrophy on the severe and epispadias on the mild ends of the spectrum. Bladder exstrophy is the most common of these entities and is more common in boys. The goal of this paper is to describe common methods of repair and to provide an imaging review of the postoperative appearances. (orig.)

  17. Bladder overdistension with polyuria in a hypertensive rat model.

    Science.gov (United States)

    Velasquez Flores, Monica; Mossa, Abubakr H; Cammisotto, Philippe; Campeau, Lysanne

    2018-03-31

    Polyuria can lead to progressive chronic bladder overdistension. The impact of polyuria on the bladder has been extensively studied in settings of either diabetes or sucrose diuresis in animals. The goal of this study was to investigate the outcomes of polyuria in a hypertension setting. Male Dahl/SS rats, a hypertension model, received a high-salt or normal diet for 6 weeks. Twenty-four-hour water intake, micturition patterns, and blood pressures were recorded biweekly. Conscious cystometry was carried out at the end of this period. Bladders were collected to measure contractile force and for histological analysis. Paired t-tests were used to compare changes between Week 0 and Week 6 within each group. Unpaired t-tests were used for comparisons between groups for all parameters at Week 6. Six weeks of high-salt diet significantly increased water intake and total urine. Blood pressures and volume of urine per micturition was higher in rats on high-salt diet. Bladder overdistension in the high-salt diet group was confirmed by cystometry, shown by a significantly higher bladder capacity, and compliance. No difference in detrusor contractility was observed between both groups. Collagen content was significantly higher in the lamina propria of the high-salt group compared to the normal group, while the opposite was observed in the muscularis. Polyuria, in a hypertension context, leads to changes in bladder morphology and function. These findings help clarify the deleterious clinical impact of polyuria on voiding function, highlighting the variable consequences of bladder overdistension according to the underlying pathology. © 2018 Wiley Periodicals, Inc.

  18. Application of 2-Micron Laser to Outpatients with Non-Muscle-Invasive Bladder Cancer%2 μm激光治疗非肌层浸润性膀胱肿瘤30例

    Institute of Scientific and Technical Information of China (English)

    陈文政; 李宏召; 杨勇

    2013-01-01

    Objective To investigate the security and feasibility of 2-micron laser to treat outpatients with non-muscle-invasive bladder cancer under local anesthesia. Methods Altogether 30 cases of single and thin-pedicle bladder tumors with a diameter less than 3 cm were directly resected with 2-micron laser during the cystoscopy. NRS pain scores were taken separately during the cystoscopy and resection. Bladder epirubicin irrigation was given in 2 hours after the operation. Follow-up visits were conducted regularly. Results The pathological results showed 25 cases of GradeⅠ urothelial carcinoma, 3 cases of GradeⅠ -Ⅱ urothelial carcinoma and 2 cases of inverted papilloma. As to the NRS pain score related to the cystoscopy, 12 cases got a score of 2, and 18 cases a score of 3. For the resection, the NRS pain scores were 4 in 5 cases, 5 in 13 cases and 6 in 12 cases. No obturator nerve reflex or bladder perforation was found. The postoperative follow-up lasted for 6-24 months, and none of the patients was observed with tumor recurrence in si- Conclusions It is safe and feasible to treat non-muscle-invasive bladder cancer of outpatients with 2-micron laser, which alleviated greatly the patients'pain and economic burden.%目的 探讨局部麻醉下门诊膀胱镜检查中2 μm激光气化切除单发非肌层浸润性膀胱肿瘤的安全性和可行性.方法 在尿道局部麻醉下,经膀胱镜检查发现的单发、带蒂、直径小于3 cm的膀胱肿瘤患者30例,直接采用2μm激光气化切除.并在膀胱镜检查及激光气化切除过程中对患者进行NRS疼痛评分.术后2h给予表阿霉素膀胱灌注,定期灌注随访.结果 组织病理学检查结果显示,尿路上皮癌Ⅰ级25例,尿路上皮癌Ⅰ~Ⅱ级3例,内翻性乳头状瘤2例.膀胱镜检查时NRS疼痛评分:2分12例,3分18例;激光切除时疼痛评分:4分5例,5分13例,6分12例.术中无闭孔神经反射及膀胱穿孔等手术并发症.术后6~24个月随访,所有

  19. A urodynamic study of surface neuromodulation versus sham in detrusor instability and sensory urgency.

    Science.gov (United States)

    Bower, W F; Moore, K H; Adams, R D; Shepherd, R

    1998-12-01

    We studied the effect of surface neuromodulation on cystometric pressure and volume parameters in women with detrusor instability or sensory urgency. Electrical current was delivered to the suprapubic region and third sacral foramina via a transcutaneous electrical nerve stimulator with sham neuromodulation control. A consecutive series of women with proved detrusor instability or sensory urgency were randomized to 3 surface neuromodulation groups. Volume and pressure parameters were the main outcomes of transcutaneous electrical nerve stimulation applied during second cystometric fill. Sham transcutaneous electrical nerve stimulation did not alter the outcome measures. However, neuromodulation delivered across the suprapubic and sacral skin effected a reduction in mean maximum height of detrusor contraction. A current which inhibits motor activity was not superior to that which inhibits sensory perception in reducing detrusor pressure. Response in sensory urgency was poor. Results from our sham controlled study suggest that short-term surface neuromodulation via transcutaneous electrical nerve stimulation may have a role in the treatment of detrusor instability. Future studies must examine the clinical effect of long-term surface neuromodulation.

  20. [Consensus document on overactive bladder in older patients].

    Science.gov (United States)

    Verdejo-Bravo, Carlos; Brenes-Bermúdez, Francisco; Valverde-Moyar, Maria Victoria; Alcántara-Montero, Antonio; Pérez-León, Noemí

    2015-01-01

    Overactive nladder (OAB) is a clinical entity with a high prevalence in the population, having a high impact on quality of life, especially when it occurs with urge urinary incontinence. It is very important to highlight the low rate of consultation of this condition by the older population. This appears to depend on several factors (educational, cultural, professional), and thus leads to the low percentage of older patients who receive appropriate treatment and, on the other hand, a large percentage of older patients with a significant deterioration in their quality of life. Therefore, Scientific societies and Working Groups propose the early detection of OAB in their documents and clinical guidelines. Its etiology is not well known, but is influenced by cerebrovascular processes and other neurological problems, abnormalities of the detrusor muscle of bladder receptors, and obstructive and inflammatory processes of the lower urinary tract. Its diagnosis is clinical, and in the great majority of the cases it can be possible to establish its diagnosis and etiopathogenic orientation, without the need for complex diagnostic procedures. Currently, there are effective treatments for OAB, and we should decide the most appropriate for each elderly patient, based on their individual characteristics. Based on the main clinical practice guidelines, a progressive treatment is proposed, with the antimuscarinics being the most recommended drug treatment. Therefore, a group of very involved professionals in clinical practice for the elderly, and representing two scientific Societies (Spanish Society of Geriatrics and Gerontology [SEGG], and the Spanish Society of Primary Care Physicians [SEMERGEN]) developed this consensus document with the main objective of establishing practices and valid strategies, focused to simplify the management of this clinical entity in the elderly population, and especially to improve their quality of life. The recommendations presented in this

  1. Botulinum toxin A for treatment of neurogenic detrusor overactivity and incontinence in patients with spinal cord lesions

    DEFF Research Database (Denmark)

    Bagi, Per; Biering-Sørensen, Fin

    2004-01-01

    To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs).......To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs)....

  2. Effects of vitamin D analog on bladder function and sensory signaling in animal models of cystitis.

    Science.gov (United States)

    Shapiro, Bennett; Redman, T Lawton; Zvara, Peter

    2013-02-01

    To measure the effects of nonhypercalcemic vitamin D receptor agonist elocalcitol on bladder function in rats with cyclophosphamide-induced cystitis and on bladder function and sensory nerve activity in a mouse with acetic acid-evoked bladder irritation. Female Wistar rats and male Balb/C mice were gavaged once daily with elocalcitol diluted in miglyol 812 (treatment group) or miglyol alone (control group). On experimental day 12, polyethylene tubing was implanted into the urinary bladder in all the animals. In the mice, a bipolar electrode was positioned under a single postganglionic bladder nerve. At 48 hours after surgery, bladder function was measured in awake, freely moving rats during bladder filling with 0.9% NaCl and both bladder function and sensory nerve activity was measured in awake, restrained mice during continuous intravesical infusion of 0.9% NaCl followed by 0.25% acetic acid. In rats, the treatment group showed a significant increase in bladder capacity and decrease in number of nonvoiding bladder contractions. In mice, the filling pressure during saline infusion was similar in both groups; however, during acetic acid infusion, the average filling pressure was significantly increased (47%) in the control group but not in the elocalcitol treatment group. The firing rate at filling pressure for the treatment group was 3.6-fold and 2.7-fold lower than that in the control group during the saline and acetic acid infusion, respectively. Oral treatment with elocalcitol suppressed signs of detrusor overactivity in both animal models and exerted strong suppressive effect on urinary bladder sensory signaling during filling in mice. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Leiomyoma of urinary bladder with bladder stone

    International Nuclear Information System (INIS)

    Farouk, K.; Gondal, M.; Khan, A.

    2008-01-01

    Leiomyoma of the urinary bladder is a rare benign mesenchymal tumour. We describe here a case of leiomyoma of the urinary bladder in a 65-year-old gentleman who presented with haematuria, passage of clots and combined obstructive and irritative urinary symptoms. The investigations revealed a vesical calculus and a mass on the left lateral wall of the urinary bladder. Cystolitholapaxy and transurethral resection of the tumour was performed. Histopathological report of the resected tumour revealed a leiomyoma of the urinary bladder. So far, a leiomyoma of the urinary bladder and a concomitant vesical calculus have not been described in literature. (author)

  4. Does the Compliance of the Bladder Affect the Grade of Vesicoureteral Reflux?

    Directory of Open Access Journals (Sweden)

    Ferhat Kilinc

    2013-10-01

    Full Text Available Aim: We retrospectively reviewed videourodynamic outcomes in children with primary vesicoureteral reflux. The aim of this study to evaluate the relationship between vesicoureteral reflux grade and bladder compliance. Material and Method: Videourodynamic traces of 53 children with primary vesicoureteral reflux investigated between January 2004 and January 2012 were reviewed. The detrusor pressures of the point when the reflux started were recorded. The detrusor pressures 10 cmH2O or less at that point was accepted as normal compliance (Group 1, the detrusor pressures more than10 cm H2O was accepted as hipocompliance (Group 2. The reflux grades were divided into two grades, low-grade reflux (grades 1 and 2, high-grade reflux (grades 3, 4 and 5. Data were analyzed using the chi-square test. Results: Patients’ ages ranged between 5 and 11 years (mean 7.09±1.81 years. Of the 53 patients, 29 (54.7% had normal compliance (Group 1, 24 (45.3% had hipocompliance (Group 2. Twenty-four (82.8% patients in-group 1 had a low-grade reflux, 5 (17.2% patients had a high-grade reflux. In group 2, 8 (33.3% patients had a low-grade reflux, 16 (66.7% patients had a high-grade reflux. The detected high-grade reflux in-group 2 was significantly higher than in-group 1 (p<0.001. Discussion: The physicians should be considering the bladder compliance at the point when the reflux started in primary vesicoureteral reflux cases. The bladder hipocompliance may play a secondary role in reflux grade.

  5. A network meta-analysis of therapeutic outcomes after new image technology-assisted transurethral resection for non-muscle invasive bladder cancer: 5-aminolaevulinic acid fluorescence vs hexylaminolevulinate fluorescence vs narrow band imaging

    International Nuclear Information System (INIS)

    Lee, Joo Yong; Cho, Kang Su; Kang, Dong Hyuk; Jung, Hae Do; Kwon, Jong Kyou; Oh, Cheol Kyu; Ham, Won Sik; Choi, Young Deuk

    2015-01-01

    This study included a network meta-analysis of evidence from randomized controlled trials (RCTs) to assess the therapeutic outcome of transurethral resection (TUR) in patients with non-muscle-invasive bladder cancer assisted by photodynamic diagnosis (PDD) employing 5-aminolaevulinic acid (5-ALA) or hexylaminolevulinate (HAL) or by narrow band imaging (NBI). Relevant RCTs were identified from electronic databases. The proceedings of relevant congresses were also searched. Fifteen articles based on RCTs were included in the analysis, and the comparisons were made by qualitative and quantitative syntheses using pairwise and network meta-analyses. Seven of 15 RCTs were at moderate risk of bias for all quality criteria and two studies were classified as having a high risk of bias. The recurrence rate of cancers resected with 5-ALA-based PDD was lower than of those resected using HAL-based PDD (odds ratio (OR) = 0.48, 95 % confidence interval (CI) [0.26–0.95]) but was not significantly different than those resected with NBI (OR = 0.53, 95 % CI [0.26–1.09]). The recurrence rate of cancers resected using HAL-based PDD versus NBI did not significantly differ (OR = 1.11, 95 % CI [0.55–2.1]). All cancers resected using 5-ALA-based PDD, HAL-based PDD, or NBI recurred at a lower rate than those resected using white light cystoscopy (WLC). No difference in progression rate was observed between cancers resected by all methods investigated. The recurrence rate of some bladder cancers can be decreased by the implementation of either PDD- and NBI-assisted TUR; in real settings, clinicians should consider replacing WLC as the standard imaging technology to guide TUR

  6. Alterations in ubiquitin ligase Siah-2 and its corepressor N-CoR after P-MAPA immunotherapy and anti-androgen therapy: new therapeutic opportunities for non-muscle invasive bladder cancer.

    Science.gov (United States)

    Garcia, Patrick Vianna; Apolinário, Letícia Montanholi; Böckelmann, Petra Karla; da Silva Nunes, Iseu; Duran, Nelson; Fávaro, Wagner José

    2015-01-01

    The present study describes the role of the ubiquitin ligase Siah-2 and corepressor N-CoR in controlling androgen receptor (AR) and estrogen receptors (ERα and ERβ) signaling in an appropriate animal model (Fischer 344 female rats) of non-muscle invasive bladder cancer (NMIBC), especially under conditions of anti-androgen therapy with flutamide. Furthermore, this study describes the mechanisms of a promising therapeutic alternative for NMIBC based on Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) intravesical immunotherapy combined with flutamide, involving the interaction among steroid hormone receptors, their regulators and Toll-like receptors (TLRs). Our results demonstrated that increased Siah-2 and AR protein levels and decreased N-CoR, cytochrome P450 (CYP450) and estrogen receptors levels played a critical role in the urothelial carcinogenesis, probably leading to escape of urothelial cancer cells from immune system attack. P-MAPA immunotherapy led to distinct activation of innate immune system TLRs 2 and 4-mediated, resulting in increase of interferon signaling pathway, which was more effective in recovering the immunosuppressive tumor immune microenvironment and in recovering the bladder histology features than BCG (Bacillus Calmette-Guerin) treatments. The AR blockade therapy was important in the modulating of downstream molecules of TLR2 and TLR4 signaling pathway, decreasing the inflammatory cytokines signaling and enhancing the interferon signaling pathway when associated with P-MAPA. Taken together, the data obtained suggest that interferon signaling pathway activation and targeting AR and Siah-2 signals by P-MAPA intravesical immunotherapy alone and/ or in combination with AR blockade may provide novel therapeutic approaches for NMIBC.

  7. Outpatient diagnostic of bladder tumours in flexible cystoscopes

    DEFF Research Database (Denmark)

    Hermann, Gregers G; Mogensen, Karin; Toft, Birgitte Grønkær

    2012-01-01

    The aim of this study was to evaluate photodynamic diagnosis (PDD) in flexible cystoscopes and the diagnostic quality of biopsies for diagnosis of non-muscle-invasive bladder cancer in the outpatients department (OPD).......The aim of this study was to evaluate photodynamic diagnosis (PDD) in flexible cystoscopes and the diagnostic quality of biopsies for diagnosis of non-muscle-invasive bladder cancer in the outpatients department (OPD)....

  8. Treatment changes and long-term recurrence rates after hexaminolevulinate (HAL) fluorescence cystoscopy: does it really make a difference in patients with non-muscle-invasive bladder cancer (NMIBC)?

    Science.gov (United States)

    Geavlete, Bogdan; Multescu, Razvan; Georgescu, Dragos; Jecu, Marian; Stanescu, Florin; Geavlete, Petrisor

    2012-02-01

    •  To evaluate in a prospective, randomized study the impact of hexaminolevulinate blue-light cystoscopy (HAL-BLC) on the diagnostic accuracy and treatment changes in cases of non-muscle invasive bladder cancer (NMIBC) compared with standard white-light cystoscopy (WLC). •  To compare the long-term recurrence rates in the two study arms. •  In all, 362 patients suspected of NMIBC were included in the trial based on positive urinary cytology and/or ultrasonographic suspicion of bladder tumours and underwent transurethral resection of bladder tumours. •  A single postoperative mytomicin-C instillation was performed in all cases, intravesical chemotherapy for intermediate-risk patients and BCG instillations for high-risk cases. •  The follow-up protocol consisted of urinary cytology and WLC every 3 months for 2 years. •  Only first-time recurrences after the initial diagnosis were considered. •  In the 142 patients with NMIBC in the HAL-BLC series, tumour detection rates significantly improved for carcinoma in situ, pTa andoverall cases. •  In 35.2% of the cases, additional malignant lesions were found by HAL-BLC and consequently, the recurrence- and progression-risk categories of patients and subsequent treatment improved in 19% of the cases due to fluorescence cystoscopy. •  In all, 125 patients in the HAL-BLC group and 114 of the WLC group completed the follow-up. •  The recurrence rate at 3 months was lower in the HAL-BLC series (7.2% vs 15.8%) due to fewer 'other site' recurrences when compared with the WLC series (0.8% vs 6.1%). •  The 1 and 2 years recurrence rates were significantly decreased in the HAL-BLC group compared with the WLC group (21.6% vs 32.5% and 31.2% vs 45.6%, respectively). •  HAL-BLC was better than WLC for detecting NMIBC cases and improved tumour detection rates. •  HAL-BLC significantly modified the postoperative treatment of cases. •  The 3 months, 1 and 2 years recurrence rates were

  9. Prospective Study Delivering Simultaneous Integrated High-dose Tumor Boost (≤70 Gy) With Image Guided Adaptive Radiation Therapy for Radical Treatment of Localized Muscle-Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hafeez, Shaista, E-mail: Shaista.Hafeez@icr.ac.uk [The Institute of Cancer Research, London (United Kingdom); The Royal Marsden National Health Service Foundation Trust, London (United Kingdom); Warren-Oseni, Karole [The Royal Marsden National Health Service Foundation Trust, London (United Kingdom); McNair, Helen A.; Hansen, Vibeke N.; Jones, Kelly; Tan, Melissa; Khan, Attia [The Institute of Cancer Research, London (United Kingdom); The Royal Marsden National Health Service Foundation Trust, London (United Kingdom); Harris, Victoria; McDonald, Fiona; Lalondrelle, Susan; Mohammed, Kabir; Thomas, Karen; Thompson, Alan; Kumar, Pardeep [The Royal Marsden National Health Service Foundation Trust, London (United Kingdom); Dearnaley, David; Horwich, Alan; Huddart, Robert [The Institute of Cancer Research, London (United Kingdom); The Royal Marsden National Health Service Foundation Trust, London (United Kingdom)

    2016-04-01

    Purpose: Image guided adaptive radiation therapy offers individualized solutions to improve target coverage and reduce normal tissue irradiation, allowing the opportunity to increase the radiation tumor dose and spare normal bladder tissue. Methods and Materials: A library of 3 intensity modulated radiation therapy plans were created (small, medium, and large) from planning computed tomography (CT) scans performed at 30 and 60 minutes; treating the whole bladder to 52 Gy and the tumor to 70 Gy in 32 fractions. A “plan of the day” approach was used for treatment delivery. A post-treatment cone beam CT (CBCT) scan was acquired weekly to assess intrafraction filling and coverage. Results: A total of 18 patients completed treatment to 70 Gy. The plan and treatment for 1 patient was to 68 Gy. Also, 1 patient's plan was to 70 Gy but the patient was treated to a total dose of 65.6 Gy because dose-limiting toxicity occurred before dose escalation. A total of 734 CBCT scans were evaluated. Small, medium, and large plans were used in 36%, 48%, and 16% of cases, respectively. The mean ± standard deviation rate of intrafraction filling at the start of treatment (ie, week 1) was 4.0 ± 4.8 mL/min (range 0.1-19.4) and at end of radiation therapy (ie, week 5 or 6) was 1.1 ± 1.6 mL/min (range 0.01-7.5; P=.002). The mean D{sub 98} (dose received by 98% volume) of the tumor boost and bladder as assessed on the post-treatment CBCT scan was 97.07% ± 2.10% (range 89.0%-104%) and 99.97% ± 2.62% (range 96.4%-112.0%). At a median follow-up period of 19 months (range 4-33), no muscle-invasive recurrences had developed. Two patients experienced late toxicity (both grade 3 cystitis) at 5.3 months (now resolved) and 18 months after radiation therapy. Conclusions: Image guided adaptive radiation therapy using intensity modulated radiation therapy to deliver a simultaneous integrated tumor boost to 70 Gy is feasible, with acceptable toxicity, and will be

  10. LDH-A promotes malignant progression via activation of epithelial-to-mesenchymal transition and conferring stemness in muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Fujin [Department of Urinary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu (China); Department of Urinary Surgery, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Ma, Song [Department of Urinary Surgery, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Xue, Yubao [Department of Medical Oncology, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Hou, Jianquan, E-mail: Jianquanhou@aliyun.com [Department of Urinary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu (China); Zhang, Yongjie, E-mail: zhangyj0818@126.com [Department of Medical Oncology, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China)

    2016-01-22

    Lactate dehydrogenase-A(LDH-A) is an important rate-limiting enzyme in the Warburg effect. Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. The results of in vitro experiment indicated that LDH-A promotes MIBC cells proliferation, invasion and migration. The positive relationship between LDH-A expression and CSC/EMT markers was confirmed both in invasive bladder cell line and in 136 MIBC specimens. Thus, we conclude that LDH-A may be a promising target for MIBC. - Highlights: • Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. • IHC analysis of 136 MIBC specimens revealed increased LDH-A is correlated with positive Oct4 and negative E-cadherin. • In vitro experiments demonstrated LDH-A promotes MIBC progression by positive regulation of EMT/CSC.

  11. Urinary bladder cancer: role of MR imaging.

    Science.gov (United States)

    Verma, Sadhna; Rajesh, Arumugam; Prasad, Srinivasa R; Gaitonde, Krishnanath; Lall, Chandana G; Mouraviev, Vladimir; Aeron, Gunjan; Bracken, Robert B; Sandrasegaran, Kumaresan

    2012-01-01

    Urinary bladder cancer is a heterogeneous disease with a variety of pathologic features, cytogenetic characteristics, and natural histories. It is the fourth most common cancer in males and the tenth most common cancer in females. Urinary bladder cancer has a high recurrence rate, necessitating long-term surveillance after initial therapy. Early detection is important, since up to 47% of bladder cancer-related deaths may have been avoided. Conventional computed tomography (CT) and magnetic resonance (MR) imaging are only moderately accurate in the diagnosis and local staging of bladder cancer, with cystoscopy and pathologic staging remaining the standards of reference. However, the role of newer MR imaging sequences (eg, diffusion-weighted imaging) in the diagnosis and local staging of bladder cancer is still evolving. Substantial advances in MR imaging technology have made multiparametric MR imaging a feasible and reasonably accurate technique for the local staging of bladder cancer to optimize treatment. In addition, whole-body CT is the primary imaging technique for the detection of metastases in bladder cancer patients, especially those with disease that invades muscle. © RSNA, 2012.

  12. Conformal radiotherapy of urinary bladder cancer

    International Nuclear Information System (INIS)

    Muren, Ludvig Paul; Smaaland, Rune; Dahl, Olav

    2004-01-01

    Recent advances in radiotherapy (RT) are founded on the enhanced tumour visualisation capabilities of new imaging modalities and the precise deposition of individualised radiation dose distributions made possible with the new systems for RT planning and delivery. These techniques have a large potential to also improve the results of RT of urinary bladder cancer. Major challenges to take full advantage of these advances in the management of bladder cancer are to control, and, as far as possible, reduce bladder motion, and to reliably account for the related intestine and rectum motion. If these obstacles are overcome, it should be possible in the near future to offer selected patients with muscle invading bladder cancer an organ-sparing, yet effective combined-modality treatment as an alternative to radical surgery

  13. Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin.

    Science.gov (United States)

    Peyronnet, Benoit; Castel-Lacanal, Evelyne; Manunta, Andréa; Roumiguié, Mathieu; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

    2015-12-01

    To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results. © 2015 The Japanese Urological Association.

  14. Recovery of storage and emptying functions of the urinary bladder after spinal anesthesia with lidocaine and with bupivacaine in men.

    Science.gov (United States)

    Kamphuis, E T; Ionescu, T I; Kuipers, P W; de Gier, J; van Venrooij, G E; Boon, T A

    1998-02-01

    The aim of this study was to evaluate and compare the effects of spinal anesthesia with lidocaine and with bupivacaine on urinary bladder function in healthy men who were scheduled for minor orthopaedic surgical procedures. Twenty men were randomly allocated to receive either bupivacaine or lidocaine. Before spinal anesthesia, filling cystometry was performed with the patient in the supine position and a pressure flow study was done with the patient in the standing position. After operation, cystometric measurements were continued until the patient could void urine spontaneously. The levels of analgesia and of motor blockade were recorded. The urge to void disappeared immediately after injection of the local anesthetics. There was no difference in the duration of lower extremity motor blockade between bupivacaine and lidocaine. Detrusor blockade lasted significantly longer in the bupivacaine group (means +/- SD, 460 +/- 60 min) than in the lidocaine group (235 +/- 30 min). Total fluid intake and urine volume accumulated during the detrusor blockade were significantly higher in the bupivacaine group than in the lidocaine group. In the bupivacaine group, the total volume of accumulated urine (875 +/- 385 ml) was also significantly higher than cystometric bladder capacity (505 +/- 120 ml) with the risk of over distension of the bladder. Spontaneous voiding of urine did not occur until segmental sensory analgesia had regressed to the third sacral segment. Spinal anesthesia with lidocaine and with bupivacaine causes a clinically significant disturbance of bladder function due to interruption of the micturition reflex. The urge to void disappears quickly and bladder function remains impaired until the block has regressed to the third sacral segment in all patients. With long-acting local anesthetics, the volume of accumulated urine may exceed the cystometric bladder capacity. With respect to recovery of urinary bladder function, the use of short-acting local anesthetics

  15. Radical radiotherapy for urinary bladder cancer

    DEFF Research Database (Denmark)

    Fokdal, Lars; Høyer, Morten; von der Maase, Hans

    2006-01-01

    The exact value of radiotherapy in the treatment of muscle-invasive       bladder cancer is difficult to establish, as most studies exploring this       issue are retrospective with different procedures for selecting patients       for treatment, as well as varying treatment strategies. An estima...

  16. Bladder sensation measures and overactive bladder.

    Science.gov (United States)

    Rapp, David E; Neil, Nancy J; Govier, Fred E; Kobashi, Kathleen C

    2009-09-01

    We performed a prospective multicomponent study to determine whether subjective and objective bladder sensation instruments may provide data on sensory dysfunction in patients with overactive bladder. We evaluated 70 prospectively enrolled patients with urodynamics and questionnaires on validated urgency (Urgency Perception Score), general overactive bladder (Urogenital Distress Inventory) and quality of life (Incontinence Impact Questionnaire). We first sought a correlation between sensory specific (Urgency Perception Score) and quality of life questionnaire scores. We then assessed a correlation between sensory questionnaire scores and urodynamic variables, exploring the hypothesis that certain urodynamic parameters may be bladder sensation measures. We evaluated 2 urodynamic derivatives (first sensation ratio and bladder urgency velocity) to increase sensory finding discrimination. We noted a moderate correlation between the Urgency Perception Score (0.56) and the Urogenital Distress Inventory (0.74) vs the Incontinence Impact Questionnaire (each p Perception Score and bladder capacity (-0.25, p sensation ratio and bladder urgency velocity statistically significantly correlated with the Urgency Perception Score despite the lesser or absent correlation associated with the individual components of these derivatives. Bladder sensation questionnaires may be valuable to identify patients with sensory dysfunction and provide additional data not obtained in generalized symptom questionnaires. Urodynamic variables correlated with bladder sensation questionnaire scores and may be an objective method to assess sensory dysfunction.

  17. Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)

    Science.gov (United States)

    Häggström, Christel; Liedberg, Fredrik; Hagberg, Oskar; Aljabery, Firas; Ströck, Viveka; Hosseini, Abolfazl; Gårdmark, Truls; Sherif, Amir; Malmström, Per-Uno; Garmo, Hans; Jahnson, Staffan; Holmberg, Lars

    2017-01-01

    Purpose To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). Participants The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death. Findings to date Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival. Future plans The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding

  18. Treatment of non muscle invasive bladder tumor related to the problem of bacillus Calmette-Guerin availability. Consensus of a Spanish expert's panel. Spanish Association of Urology.

    Science.gov (United States)

    Fernández-Gómez, J M; Carballido-Rodríguez, J; Cozar-Olmo, J M; Palou-Redorta, J; Solsona-Narbón, E; Unda-Urzaiz, J M

    2013-01-01

    Since June 2012, the has been a worldwide lack of available of the Connaught strain. In December 2012, a group of experts met in the Spanish Association of Urology to analyze this situation and propose alternatives. To present the work performed by said committee and the resulting recommendations. An update has been made of the principal existing evidence in the treatment of middle and high risk tumors. Special mention has been made regarding the those related with the use of BCG and their possible alternative due to the different availability of BCG. In tumors with high risk of progression, immediate cystectomy should be considered when BCG is not available, with dose reduction or alternating with chemotherapy as methods to economize on the use of BCG when availability is reduced. In tumors having middle risk of progression, chemotherapy can be used, although when it is associated to a high risk of relapse, BCG would be indicated if available with the mentioned savings guidelines. BCG requires maintenance to maintain its effectiveness, it being necessary to optimize the application of endovesical chemotherapy and to use systems that increase its penetration into the bladder wall (EMDA) if they are available. Due to the scarcity of BCG, it has been necessary to agree on a series of recommendations that have been published on the web page of the Spanish Association of Urology. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  19. The paediatric neuropathic bladder

    African Journals Online (AJOL)

    pathophysiological terms, a neurogenic bladder is caused by a spinal reflex arc that occurs when ... and potential progressive renal damage because of high bladder ... creatinine level, can also be used to assess kidney function. Urodynamic ...

  20. Intraoperative radiation therapy in patients with bladder cancer. A review of techniques allowing improved tumor doses and providing high cure rates without loss of bladder function

    International Nuclear Information System (INIS)

    Shipley, W.U.; Kaufman, S.D.; Prout, G.R. Jr.

    1987-01-01

    Conventional external beam irradiation, using modern megavoltage techniques and doses that do not harm bladder function, will permanently eradicate local bladder cancer in 30% to 50% of patients, compared with 70% to 90% with cystectomy. In appropriately chosen patients, open surgery can safely provide excellent exposure for the selective delivery of more radiant energy directly to the tumor and less to the uninvolved portion of the bladder. Intraoperative radiation therapy, by either a removable radium or iridium implant or a large single dose of electrons, has been reported to be safe and can permanently cure the bladder of cancer and also preserve bladder function in more than 75% of patients with solitary tumors that invade into but not beyond the bladder muscle. With the increasing interest in and availability of intraoperative radiation therapy in the US, this curative and bladder-sparing treatment for operable patients with bladder cancer invading the trigone is appropriate for careful clinical trial. 13 references

  1. A Phase 1/2 Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation After Transurethral Surgery for Noncystectomy Candidates With Muscle-Invasive Bladder Cancer (Trial NRG Oncology RTOG 0524)

    Energy Technology Data Exchange (ETDEWEB)

    Michaelson, M. Dror, E-mail: dmichaelson1@partners.org [Massachusetts General Hospital Cancer Center, Boston, Massachusetts (United States); Hu, Chen [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Pham, Huong T. [Virginia Mason CCOP, Seattle, Washington (United States); Dahl, Douglas M.; Lee-Wu, Chin [Massachusetts General Hospital Cancer Center, Boston, Massachusetts (United States); Swanson, Gregory P. [University of Texas at San Antonio, San Antonio, Texas (United States); Vuky, Jacqueline [Virginia Mason CCOP, Seattle, Washington (United States); Lee, R. Jeffrey [Intermountain Medical Center, Murray, Utah (United States); Souhami, Luis [McGill University, Montréal, Quebec (Canada); Chang, Brian [Parkview Cancer Center, Parkview Hospital, Fort Wayne, Indiana (United States); George, Asha [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Sandler, Howard [Cedars-Sinai Medical Center, Los Angeles, California (United States); Shipley, William [Massachusetts General Hospital Cancer Center, Boston, Massachusetts (United States)

    2017-04-01

    Purpose: Bladder preservation therapy is an effective treatment for muscle-invasive urothelial carcinoma (UC). In this study we treated noncystectomy candidates with daily radiation and weekly paclitaxel for 7 weeks. Patients whose tumors showed her2/neu overexpression were additionally treated with weekly trastuzumab. Methods and Materials: Sixty-eight evaluable patients were treated with radiation therapy and either paclitaxel + trastuzumab (group 1) or paclitaxel alone (group 2). Groups were assigned on the basis of her2/neu immunohistochemistry results. Patients received 1.8-Gy fractions to a total dose of 64.8 Gy. The primary endpoint of the study was treatment-related toxicity, and secondary endpoints included complete response (CR) rate, protocol completion rate, and survival. Results: A total of 20 evaluable patients were treated in group 1 and 46 patients in group 2. Acute treatment-related adverse events (AEs) were observed in 7 of 20 patients in group 1 (35%) and 14 of 46 patients in group 2 (30.4%). Protocol therapy was completed by 60% (group 1) and 74% (group 2) of patients. Most incompletions were due to toxicity, and the majority of AEs were gastrointestinal, including 1 grade 5 AE (group 1). Two other deaths (both in group 2) were unrelated to protocol therapy. No unexpected cardiac, hematologic, or other toxicities were observed. The CR rate at 1 year was 72% for group 1 and 68% for group 2. Conclusions: In patients with muscle-invasive UC who are not candidates for cystectomy, daily radiation combined with paclitaxel is an effective treatment strategy with a high completion rate and moderate toxicity. In patients with her2/neu-positive tumors, a group generally considered to have worse outcomes, the addition of trastuzumab appears to result in comparable efficacy and toxicity. Further biomarker-driven trials should be undertaken in advancing treatment of this challenging disease.

  2. The brain stem function in patients with brain bladder

    International Nuclear Information System (INIS)

    Takahashi, Toshihiro

    1990-01-01

    A syndrome of detrusor-sphincter dyssynergia (DSD) is occasionally found in patients with brain bladder. To evaluate the brain stem function in cases of brain bladder, urodynamic study, dynamic CT scan of the brain stem (DCT) and auditory brainstem response (ABR) were performed. The region of interest of DCT aimed at the posterolateral portion of the pons. The results were analysed in contrast with the presense of DSD in urodynamic study. DCT studies were performed in 13 cases with various brain diseases and 5 control cases without neurological diseases. Abnormal patterns of the time-density curve consisted of low peak value, prolongation of filling time and low rapid washout ratio (low clearance ratio) of the contrast medium. Four of 6 cases with DSD showed at least one of the abnormal patterns of the time-density curve bilaterally. In 7 cases without DSD none showed bilateral abnormality of the curve and in 2 of 7 cases only unilateral abnormality was found. ABR was performed in 8 patients with brain diseases. The interpeak latency of the wave I-V (I-V IPL) was considered to be prolonged in 2 cases with DSD compared to that of 4 without DSD. In 2 cases with DSD who had normal DCT findings, measurement of the I-V IPL was impossible due to abnormal pattern of the ABR wave. Above mentioned results suggests the presence of functional disturbance at the posterolateral portion of the pons in cases of brain bladder with DSD. (author)

  3. Overactive bladder, differential diagnosis, and clinical utility of fesoterodine

    Directory of Open Access Journals (Sweden)

    Wyndaele J-J

    2012-11-01

    Full Text Available Jean-Jacques WyndaeleDepartment of Urology, Antwerp University, Antwerp, BelgiumAbstract: Overactive bladder is a symptom syndrome with urgency, frequency and, in many cases, nocturia. Urge incontinence is not present in all. There is no direct correlation with detrusor overactivity, an objective finding during urodynamic testing where involuntary contractions can be noticed. In the pathophysiology, much more attention has been given to the afferent/sensory arm of the micturition reflex in the last decade. Anatomical and infectious causes have to be diagnosed or ruled out. Diagnosis of overactive bladder is made mostly by history-taking, but other tests can be necessary in specific patients. Treatment consists of behavioral measures, a good explanation of the condition, training, and pelvic floor physiotherapy. Drugs are often used. Until recently, antimuscarinic drugs have been the mainstay of pharmacological therapy. Fesoterodine is a newer antimuscarinic agent which is more pharmacodynamically stable then tolterodine. Fesoterodine has been extensively researched using different dosages and compared with placebo and tolterodine, in different age groups, and under different conditions. Fesoterodine is superior to placebo and to tolterodine in the short term and long term. Its safety is very acceptable.Keywords: overactive bladder, fesoterodine, incontinence, urgency, lower urinary tract

  4. Establishment and antitumor effects of dasatinib and PKI-587 in BD-138T, a patient-derived muscle invasive bladder cancer preclinical platform with concomitant EGFR amplification and PTEN deletion.

    Science.gov (United States)

    Chang, Nakho; Lee, Hye Won; Lim, Joung Eun; Jeong, Da Eun; Song, Hye Jin; Kim, Sudong; Nam, Do-Hyun; Sung, Hyun Hwan; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

    2016-08-09

    Muscle-invasive bladder cancer (MIBC) consists of a heterogeneous group of tumors with a high rate of metastasis and mortality. To facilitate the in-depth investigation and validation of tailored strategies for MIBC treatment, we have developed an integrated approach using advanced high-throughput drug screening and a clinically relevant patient-derived preclinical platform. We isolated patient-derived tumor cells (PDCs) from a rare MIBC case (BD-138T) that harbors concomitant epidermal growth factor receptor (EGFR) amplification and phosphatase and tensin homolog (PTEN) deletion. High-throughput in vitro drug screening demonstrated that dasatinib, a SRC inhibitor, and PKI-587, a dual PI3K/mTOR inhibitor, exhibited targeted anti-proliferative and pro-apoptotic effects against BD-138T PDCs. Using established patient-derived xenograft models that successfully retain the genomic and molecular characteristics of the parental tumor, we confirmed that these anti-tumor responses occurred through the inhibition of SRC and PI3K/AKT/mTOR signaling pathways. Taken together, these experimental results demonstrate that dasatinib and PKI-587 might serve as promising anticancer drug candidates for treating MIBC with combined EGFR gene amplification and PTEN deletion.

  5. Bladder leiomyoma presenting as dyspareunia: Case report and literature review.

    Science.gov (United States)

    Xin, Jun; Lai, Hai-Ping; Lin, Shao-Kun; Zhang, Qing-Quan; Shao, Chu-Xiao; Jin, Lie; Lei, Wen-Hui

    2016-07-01

    Leiomyoma of the bladder is a rare tumor arising from the submucosa. Most patients with bladder leiomyoma may present with urinary frequency or obstructive urinary symptoms. However, there are a few cases of bladder leiomyoma coexisting with uterine leiomyoma presenting as dyspareunia. We herein report an unusual case of coexisting bladder leiomyoma and uterine leiomyoma presenting as dyspareunia. A 44-year-old Asian female presented to urologist and complained that she had experienced dyspareunia over the preceding several months. A pelvic ultrasonography revealed a mass lesion located in the trigone of urinary bladder. The mass lesion was confirmed on contrast-enhanced computed tomography (CT). The CT scan also revealed a lobulated and enlarged uterus consistent with uterine leiomyoma. Then, the biopsies were then taken with a transurethral resection (TUR) loop and these biopsies showed a benign proliferation of smooth muscle in a connective tissue stroma suggestive of bladder leiomyoma. An open local excision of bladder leiomyoma and hysteromyomectomy were performed successfully. Histological examination confirmed bladder leiomyoma coexisting with uterine leiomyoma. This case highlights a rare presentation of bladder leiomyoma, dyspareunia, as the chief symptom in a patient who had coexisting uterine leiomyoma. Bladder leiomyomas coexisting with uterine leiomyomas are rare and can present with a wide spectrum of complaints including without symptoms, irritative symptoms, obstructive symptoms, or even dyspareunia.

  6. Orthotopic neo- bladder in women.

    Science.gov (United States)

    Schettini, Manlio

    2010-12-01

    Radical cystectomy is the most effective treatment madality for high grade urinary bladder carcinoma and orthotopic reconstruction is the better urinary diversion modality also in women. From 2002 to 2007 we performed 14 radical cystectomies followed by orthotopic reconstruction in women aged between 47 and 68 years (mean age 56) affected by urinary bladder carcinoma. Our reconstructive technique requires the preparation of two strips of the recti muscles fascia, the sectioning of the bladder neck and, when the uterus is present, hysteroannessiectomy and cystectomy en block leaving intact the lateral and inferior vaginal walls. The pelvic floor is stabilized by a colposacropexis with a prosthesis and placing an omental flap over the prosthesis. The orthotopic reconstruction is achieved via a neobladder according to the Padovana technique. The ureters are anastomized to the neobladder and splinted with single J stents. The pathological examination demonstrated in all patients the presence of a high grade carcinoma (G3): more specifically 4 patients had a full thickness intramural infiltration (T2), 2 patients had involvment of the perivescical fat (T3) ad 8 patients were in T1 stage. Lymphnodes were negative for tumour (NO). In 8 patients blood transfusions were necessary to treat post surgical anemia. No significant intra-, peri- or post operative complications were noted. The mean follow-up was 45 months: a patient died for diffuse metastatic disease after 11 months. The remaining patients are still alive and report normal lifestyle: 10 with normal micturition and 4 with urinary retention treated with intermittent self-catetherization. Two patients report nocturnal incontinence treated with hourly micturition and one pad. The five patients who had normal preoperative sexual intercourse resumed a normal sexual activity. The possibility to orthotopically recontruct the female urinary bladder has been established long time after the introduction of orthotopic

  7. A novel bioreactor to simulate urinary bladder mechanical properties and compliance for bladder functional tissue engineering.

    Science.gov (United States)

    Wei, Xin; Li, Dao-bing; Xu, Feng; Wang, Yan; Zhu, Yu-chun; Li, Hong; Wang, Kun-jie

    2011-02-01

    Bioreactors are pivotal tools for generating mechanical stimulation in functional tissue engineering study. This study aimed to create a bioreactor that can simulate urinary bladder mechanical properties, and to investigate the effects of a mechanically stimulated culture on urothelial cells and bladder smooth muscle cells. We designed a bioreactor to simulate the mechanical properties of bladder. A pressure-record system was used to evaluate the mechanical properties of the bioreactor by measuring the pressure in culture chambers. To test the biocompatibility of the bioreactor, viabilities of urothelial cells and smooth muscle cells cultured in the bioreactor under static and mechanically changed conditions were measured after 7-day culture. To evaluate the effect of mechanical stimulations on the vital cells, urethral cells and smooth muscle cells were cultured in the simulated mechanical conditions. After that, the viability and the distribution pattern of the cells were observed and compared with cells cultured in non-mechanical stimulated condition. The bioreactor system successfully generated waveforms similar to the intended programmed model while maintaining a cell-seeded elastic membrane between the chambers. There were no differences between viabilities of urothelial cells ((91.90 ± 1.22)% vs. (93.14 ± 1.78)%, P > 0.05) and bladder smooth muscle cells ((93.41 ± 1.49)% vs. (92.61 ± 1.34)%, P > 0.05). The viability of cells and tissue structure observation after cultured in simulated condition showed that mechanical stimulation was the only factor affected cells in the bioreactor and improved the arrangement of cells on silastic membrane. This bioreactor can effectively simulate the physiological and mechanical properties of the bladder. Mechanical stimulation is the only factor that affected the viability of cells cultured in the bioreactor. The bioreactor can change the growth behavior of urothelial cells and bladder smooth muscle cells, resulting in

  8. Chromium in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Golabek, Tomasz; Socha, Katarzyna; Kudelski, Jacek; Darewicz, Barbara; Markiewicz-Zukowska, Renata; Chlosta, Piotr; Borawska, Maria

    2017-12-23

    Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, the involvement of heavy metals in tumourigenesis of urothelial carcinoma of the bladder has been poorly investigated. Therefore, the aim of this study was to examine the relationship between chromium (Cr) and bladder cancer. Chromium concentration in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of a control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage. While the median chromium concentration levels reached statistically higher values in the bladder cancer tissue, compared with the non-cancer tissue (99.632ng/g and 33.144ng/g, respectively; p<0.001), the median Cr levels in the sera of the patients with this carcinoma showed no statistical difference when compared to those of the control group (0.511μg/l and 0.710μg/l, respectively; p=0.408). The median levels of Cr in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p<0.001 and p<0.01, respectively). This study shows that patients with urothelial carcinoma of the bladder had higher tissue Cr levels than people without tumour, while no difference was found in the Cr serum levels between the two groups of patients under investigation.

  9. Urodynamic assessment of bladder and urethral function among men with lower urinary tract symptoms after radical prostatectomy: A comparison between men with and without urinary incontinence.

    Science.gov (United States)

    Lee, Hansol; Kim, Ki Bom; Lee, Sangchul; Lee, Sang Wook; Kim, Myong; Cho, Sung Yong; Oh, Seung-June; Jeong, Seong Jin

    2015-12-01

    We compared bladder and urethral functions following radical prostatectomy (RP) between men with and without urinary incontinence (UI), using a large-scale database from SNU-experts-of-urodynamics-leading (SEOUL) Study Group. Since July 2004, we have prospectively collected data on urodynamics from 303 patients with lower urinary tract symptoms (LUTS) following RP at three affiliated hospitals of SEOUL Study Group. After excluding 35 patients with neurogenic abnormality, pelvic irradiation after surgery, or a history of surgery on the lower urinary tract, 268 men were evaluated. We compared the urodynamic findings between men who had LUTS with UI (postprostatectomy incontinence [PPI] group) and those who had LUTS without UI (non-PPI group). The mean age at an urodynamic study was 68.2 years. Overall, a reduced bladder compliance (≤20 mL/cmH2O) was shown in 27.2% of patients; and 31.3% patients had idiopathic detrusor overactivity. The patients in the PPI group were older (p=0.001) at an urodynamic study and had a lower maximum urethral closure pressure (MUCP) (p<0.001), as compared with those in the non-PPI group. Bladder capacity and detrusor pressure during voiding were also significantly lower in the PPI group. In the logistic regression, only MUCP and maximum cystometric capacity were identified as the related factor with the presence of PPI. In our study, significant number of patients with LUTS following RP showed a reduced bladder compliance and detrusor overactivity. PPI is associated with both impairment of the urethral closuring mechanism and bladder storage dysfunction.

  10. [Definition of botulinum toxin failure in neurogenic detrusor overactivity: Preliminary results of the DETOX survey].

    Science.gov (United States)

    Peyronnet, B; Sanson, S; Amarenco, G; Castel-Lacanal, E; Chartier-Kastler, E; Charvier, K; Damphousse, M; Denys, P; de Seze, M; Egon, G; Even, A; Forin, V; Karsenty, G; Kerdraon, J; le Normand, L; Loche, C-M; Manunta, A; Mouracade, P; Phe, V; Previnaire, J-G; Ruffion, A; Saussine, C; Schurch, B; Game, X

    2015-12-01

    There is currently no guideline regarding the management of neurogenic detrusor overactivity (NDO) refractory to intra-detrusor botulinum toxin injections. The primary objective of the present study was to find a consensus definition of failure of botulinum toxin intra-detrusor injections for NDO. The secondary objective was to report current trends in the managment of NDO refractory to botulinum toxin. A survey was created, based on data drawn from current literature, and sent via e-mail to all the experts form the Group for research in neurourology in french language (GENULF) and from the comittee of neurourology of the French urological association (AFU). The experts who did not answer to the first e-mail were contacted again twice. Main results from the survey are presented and expressed as numbers and proportions. Out of the 42 experts contacted, 21 responded to the survey. Nineteen participants considered that the definition of failure should be a combination of clinical and urodynamics criteria. Among the urodynamics criteria, the persistence of a maximum detrusor pressure>40 cm H2O was the most supported by the experts (18/21, 85%). According to the vast majority of participants (19/21, 90.5%), the impact of injections on urinary incontinence should be included in the definition of failure. Regarding the management, most experts considered that the first line treatment in case of failure of a first intra-detrusor injection of Botox(®) 200 U should be a repeat injection of Botox(®) at a higher dosage (300 U) (15/20, 75%), regardless of the presence or not of urodynamics risk factors of upper tract damage (16/20, 80%). This work has provided a first overview of the definition of failure of intra-detrusor injections of botulinum toxin in the management of NDO. For 90.5% of the experts involved, the definition of failure should be clinical and urodynamic and most participants (75%) considered that, in case of failure of a first injection of Botox(®) 200 U

  11. Bladder Cancer Stem-Like Cells: Their Origin and Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Tomokazu Ohishi

    2015-12-01

    Full Text Available Bladder cancer (BC, the most common cancer arising from the human urinary tract, consists of two major clinicopathological phenotypes: muscle-invasive bladder cancer (MIBC and non-muscle-invasive bladder cancer (NMIBC. MIBC frequently metastasizes and is associated with an unfavorable prognosis. A certain proportion of patients with metastatic BC can achieve a remission with systemic chemotherapy; however, the disease relapses in most cases. Evidence suggests that MIBC comprises a small population of cancer stem cells (CSCs, which may be resistant to these treatments and may be able to form new tumors in the bladder or other organs. Therefore, the unambiguous identification of bladder CSCs and the development of targeted therapies are urgently needed. Nevertheless, it remains unclear where bladder CSCs originate and how they are generated. We review recent studies on bladder CSCs, specifically focusing on their proposed origin and the possible therapeutic options based on the CSC theory.

  12. Developments in diagnosis and prognosis of superficial bladder cancer.

    NARCIS (Netherlands)

    Moonen, P.M.J.

    2007-01-01

    Non-muscle invasive bladder encompasses the relatively innocent low risk tumours, but also the potentially lethal high risk tumours. Low risk tumours have a high chance of recurrence, but high risk tumours have both a high risk of recurrence and progression. Progression to muscle-invasive disease

  13. Tibial nerve stimulation for overactive bladder syndrome unresponsive to medical therapy.

    Science.gov (United States)

    Ridout, A E; Yoong, W

    2010-02-01

    Overactive bladder syndrome is defined as a symptom syndrome which includes urinary urgency, with or without urge incontinence, usually accompanied by frequency (>8 micturitions/24 h) and nocturia. Conservative treatment usually comprises behavioural techniques, bladder retraining, pelvic floor re-education and pharmacotherapy but up to 30% of patients will remain refractory to treatment. Although second-line treatment options such as sacral nerve stimulation and intravesical botulinum A injections are valuable additions to the therapeutic arsenal, they are relatively invasive and can have serious side-effects. Inhibition of detrusor activity by peripheral neuromodulation of the posterior tibial nerve was first described in 1983, with recent authors further confirming a 60-80% positive response rate. This review was undertaken to examine published literature on percutaneous tibial nerve stimulation and to discuss outcome measures, maintenance therapy and prognostic factors of this technique.

  14. Bladder metastases of appendiceal mucinous adenocarcinoma: a case presentation

    Directory of Open Access Journals (Sweden)

    Giusti Guido

    2010-02-01

    Full Text Available Abstract Background Appendiceal adenocarcinoma is rare with a frequency of 0.08% of all surgically removed appendices. Few cases of appendiceal carcinoma infiltrating the bladder wall for spatial contiguity have been documented. Case Presentation A case is reported of a 45-years old woman with mucinous cystadenocarcinoma of the appendix with bladder metastasis. Although ultrasonography and voided urinary cytology were negative, abdomen computed tomography (CT scan and cystoscopy and subsequent pathological examination revealed a mass exclusively located in the anterior wall of the bladder. Histopathology of the transurethral bladder resection revealed a bladder adenocarcinoma [6 cm (at the maximum diameter × 2,5 cm; approximate weight: 10 gr] with focal mucinous aspects penetrating the muscle and perivisceral fat. Laparotomy evidenced the presence of a solid mass of the appendix (2,5 cm × 3 cm × 2 cm extending to the loco-regional lymph nodes. Appendectomy and right hemicolectomy, linfoadenectomy and partial cystectomy were performed. The subsequent pathological examination revealed a mucinous cystadenocarcinoma of the appendix with metastatic cells colonising the anterior bladder wall and several colic lymph nodes. Conclusions The rarity of the appendiceal carcinoma invading the urinary bladder and its usual involvement of nearest organs and the posterior bladder wall, led us to describe this case which demonstrates the ability of the appendiceal cancer to metastasize different regions of urinary bladder.

  15. Bladder metastases of appendiceal mucinous adenocarcinoma: a case presentation

    International Nuclear Information System (INIS)

    Taverna, Gianluigi; Graziotti, Pierpaolo; Corinti, Matteo; Colombo, Piergiuseppe; Grizzi, Fabio; Severo, Mauro; Piccinelli, Alessando; Giusti, Guido; Benetti, Alessio; Zucali, Paolo A

    2010-01-01

    Appendiceal adenocarcinoma is rare with a frequency of 0.08% of all surgically removed appendices. Few cases of appendiceal carcinoma infiltrating the bladder wall for spatial contiguity have been documented. A case is reported of a 45-years old woman with mucinous cystadenocarcinoma of the appendix with bladder metastasis. Although ultrasonography and voided urinary cytology were negative, abdomen computed tomography (CT) scan and cystoscopy and subsequent pathological examination revealed a mass exclusively located in the anterior wall of the bladder. Histopathology of the transurethral bladder resection revealed a bladder adenocarcinoma [6 cm (at the maximum diameter) × 2,5 cm; approximate weight: 10 gr] with focal mucinous aspects penetrating the muscle and perivisceral fat. Laparotomy evidenced the presence of a solid mass of the appendix (2,5 cm × 3 cm × 2 cm) extending to the loco-regional lymph nodes. Appendectomy and right hemicolectomy, linfoadenectomy and partial cystectomy were performed. The subsequent pathological examination revealed a mucinous cystadenocarcinoma of the appendix with metastatic cells colonising the anterior bladder wall and several colic lymph nodes. The rarity of the appendiceal carcinoma invading the urinary bladder and its usual involvement of nearest organs and the posterior bladder wall, led us to describe this case which demonstrates the ability of the appendiceal cancer to metastasize different regions of urinary bladder

  16. Urinary Incontinence due to Overactive Detrusor Muscle: A Rare Side Effect of Venlafaxine

    Directory of Open Access Journals (Sweden)

    Vithyalakshmi Selvaraj

    2015-01-01

    Full Text Available We report a case of reemergence of urinary incontinence (UI in a patient with benign prostatic hyperplasia (BPH after starting treatment with venlafaxine who was stabilized on tamsulosin and finasteride for about 6 years. A 66-year-old Caucasian male with prior history of major depressive disorder developed UI within a week of starting venlafaxine 75 mg per day. He described symptoms in the form of involuntary leakage of urine both during the day and at night. His symptoms of UI resolved after stopping the venlafaxine. To the best of our knowledge, there are only four case reports of venlafaxine induced urinary incontinence which have been published.

  17. Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway.

    Science.gov (United States)

    Chen, Shulian; Peng, Chuandu; Wei, Xin; Luo, Deyi; Lin, Yifei; Yang, Tongxin; Jin, Xi; Gong, Lina; Li, Hong; Wang, Kunjie

    2017-08-01

    To investigate the effect of simulated physiological stretch on the expression of extracellular matrix (ECM) proteins and the role of integrin α4/αv, focal adhesion kinase (FAK), extracellular regulated protein kinases 1/2 (ERK1/2) in the stretch-induced ECM protein expression of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to simulated physiological stretch at the range of 5, 10, and 15% elongation. Expression of primary ECM proteins in HBSMCs was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the FAK and ERK1/2 was determined by Western blot with FAK inhibitor and ERK1/2 inhibitor (PD98059). Specificity of integrin α4 and integrin αv was determined with small interfering ribonucleic acid (siRNA) transfection. The expression of collagen I (Col1), collagen III (Col3), and fibronectin (Fn) was increased significantly under the simulated physiological stretch of 10 and 15%. Integrin α4 and αv, FAK, ERK1/2 were activated by 10% simulated physiological stretch compared with the static condition. Pretreatment of ERK1/2 inhibitor, FAK inhibitor, integrin α4 siRNA, or integrin αv siRNA reduced the stretch-induced expression of ECM proteins. And FAK inhibitor decreased the stretch-induced ERK1/2 activity and ECM protein expression. Integrin α4 siRNA or integrin αv siRNA inhibited the stretch-induced activity of FAK. Simulated physiological stretch increases the expression of ECM proteins in HBSMCs, and integrin α4/αv-FAK-ERK1/2 signaling pathway partly modulates the mechano-transducing process.

  18. Study of kidney damage in paediatric patients with neurogenic bladder and its relationship with the pattern of bladder function and treatment received.

    Science.gov (United States)

    Rodríguez-Ruiz, M; Somoza, I; Curros-Mata, N

    2016-01-01

    Kidney failure is the main cause of morbidity and mortality in patients with myelodysplasia. We analysed the presence of renal lesions in these patients using dimercaptosuccinic acid scintigraphy and related their presence with the type of vesical function and the delay in receiving appropriate management. We performed a retrospective study of patients with myelodysplasia treated in our hospital since 2004. We analysed the epidemiological and clinical data and the pattern of bladder function according to urodynamic studies. We classified the patients into 4 urodynamic patterns according to detrusor and sphincter behaviour. We linked this behaviour to renal function in the scintigraphy and the care received since birth. The study included 39 patients with myelodysplasia. The most common bladder pattern was type A (61.5%), with sphincter and detrusor hyperactivity, followed by type D (20.5%), C (7.8%) and B (5.1%). Some 38% of our patients (n=15) had some type of nephropathy. Some 92.9% of the children who were properly treated during the first year of their life had no renal lesions in the scintigraphy. We found some type of nephropathy in 56% of the patients for whom appropriate treatment was delayed for more than a year. The nephropathy was more severe the later the management was started. There is a statistically significant relationship between a delay in treatment and impairment in renal scintigraphy in patients with neurogenic bladders. The early study and treatment of patients is essential for decreasing renal impairment, reducing the need for surgery and improving the continence options. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Bladder pain syndrome

    DEFF Research Database (Denmark)

    Hanno, Philip; Nordling, Jørgen; Fall, Magnus

    2011-01-01

    Bladder pain syndrome is a deceptively intricate symptom complex that is diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder, accompanied by at least one other urinary symptom. It is a diagnosis of exclusion in a patient who has ex...... can be challenging, and misdiagnosis as a psychological problem, overactive bladder, or chronic urinary infection has plagued patients with the problem....

  20. Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes.

    Science.gov (United States)

    Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

    2013-03-01

    Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats. A total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder. Diabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes. Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative

  1. Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: A report from the Radiation Therapy Oncology Group

    International Nuclear Information System (INIS)

    Chakravarti, Arnab; Winter, Kathryn M.S.; Wu, C.-L.; Kaufman, Donald; Hammond, Elizabeth; Parliament, Matthew; Tester, William; Hagan, Michael; Grignon, David; Heney, Niall; Pollack, Alan; Sandler, Howard; Shipley, William

    2005-01-01

    Purpose: Erb-1 (epidermal growth factor receptor, EGFR) and Erb-2 (Her-2) are two of the best characterized members in the EGFR pathway. In many tumor types, overexpression of these proteins is associated with enhanced malignant potential. Our objective in this study was to investigate the clinical relevance of EGFR and Her-2 expression in bladder cancer cases from four prospective Radiation Therapy Oncology Group (RTOG) bladder preservation trials using cisplatin-containing chemoradiation (RTOG 8802, 8903, 9506, and 9706). Methods and materials: Tumors from 73 cases from patients with muscle-invading T2-T4a bladder cancers had slides interpretable for EGFR staining; 55 cases had slides interpretable for Her-2 staining. Additionally, the respective prognostic values of p53, pRB, and p16 immunostaining were concomitantly examined. Staining and interpretation of staining were done in a blinded manner, without knowledge of clinical outcome. Staining was judged as positive or negative. Subsequently, staining was correlated with clinical outcome. Results: On univariate analysis, EGFR positivity was significantly associated with improved overall survival (p = 0.044); disease-specific survival (DSS) (p = 0.042); and DSS with intact bladder (p = 0.021). There was also a trend for association between EGFR expression and reduced frequency of distant metastasis (p = 0.06). On multivariate analysis adding tumor stage, tumor grade, whether a visibly complete transurethral resection of bladder tumor (TURBT) was done or not, and patient age to the model, EGFR positivity was significantly associated with improved DSS. On univariate analysis, Her-2 positivity was significantly associated with reduced complete response (CR) rates (50% vs. 81%, p = 0.026) after chemoradiation which remained significant on multivariate analysis. The other markers examined in this study were not found to have any prognostic value in this setting. Conclusion: Epidermal growth factor receptor expression

  2. Acid and stretch, but not capsaicin, are effective stimuli for ATP release in the porcine bladder mucosa: Are ASIC and TRPV1 receptors involved?

    Science.gov (United States)

    Sadananda, Prajni; Kao, Felicity C L; Liu, Lu; Mansfield, Kylie J; Burcher, Elizabeth

    2012-05-15

    Stretch-evoked ATP release from the bladder mucosa is a key event in signaling bladder fullness. Our aim was to examine whether acid and capsaicin can also release ATP and to determine the receptors involved, using agonists and antagonists at TRPV1 and acid-sensing ion channels (ASICs). Strips of porcine bladder mucosa were exposed to acid, capsaicin or stretch. Strip tension was monitored. Bath fluid was collected for ATP measurement. Gene expression of ASICs and TRPV1 in porcine bladders was quantified using quantitative real-time PCR (qRT-PCR). Stretch stimulus (150% of original length) repeatedly and significantly increased ATP release to approximately 45 times basal release. Acid (pH 6.5, 6.0, 5.6) contracted mucosal strips and also increased ATP release up to 30-fold, without evidence of desensitization. Amiloride (0.3 μM) reduced the acid-evoked ATP release by approximately 70%, while capsazepine (10 μM) reduced acid-evoked ATP release at pH 6.0 and pH 5.6 (by 68% and 61%, respectively). Capsaicin (0.1-10 μM) was ineffective in causing ATP release, and also failed to contract porcine mucosal or detrusor strips. Gene expression for ASIC1, ASIC2, ASIC3 and TRPV1 was seen in the lateral wall, dome, trigone and neck of both detrusor and mucosa. In conclusion, stretch and acid induce ATP release in the porcine bladder mucosa, but capsaicin is ineffective. The pig bladder is a well-known model for the human bladder, however these data suggest that it should be used with caution, particularly for TRPV1 related studies. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Radiotherapy for bladder cancer and kidney cancer

    International Nuclear Information System (INIS)

    Ishikawa, Hitoshi; Tanaka, Keiichi; Iizumi, Takashi; Shimizu, Shosei; Okumura, Toshiyuki; Sakurai, Hideyuki; Kimura, Tomokazu; Nishiyama, Hiroyuki

    2017-01-01

    This paper explained the current state of radiotherapy for bladder cancer and kidney cancer, and discussed the role of radiotherapy in curative treatment and the future development. In the diagnosis and treatment of bladder cancer, it is important to judge the existence of pathological muscular layer invasion based on transurethral resection of bladder tumor (TUR-BT). In surgical results in Japan, the U.S., and Switzerland, 5-year survival rate is about 60 to 70%. Standard treatment for bladder cancer with muscle layer invasion had been surgery, and radiotherapy had been applied to the cases without resistance to surgery. Three combined therapy with TUR-BT and simultaneous chemoradiotherapy is the current standard bladder conserving therapy. The 5-year survival rate is approximately 60%, which is superior to the treatment with irradiation alone. Radiotherapy for kidney cancer is most often used as perioperative treatment for locally advanced cancer or as symptomatic treatment for metastatic lesions. However, due to recent improvement in radiotherapy technology, correspondence to respiratory movement and high dose administration associated with improvement in dose concentration have been realized, and stereotactic irradiation using a high single dose for inoperable disease cases or surgery refusal disease cases has come to be clinically applied. (A.O.)

  4. Urology and nephrology update: bladder and kidney cancer.

    Science.gov (United States)

    Fiore, David C; Fox, Cara-Louise

    2014-01-01

    It has been estimated that bladder and kidney cancers would be diagnosed in approximately 140,000 Americans in 2013, with approximately 30,000 dying from these cancers. Urinary tract cancers affect men more commonly than they do women, and the median age at diagnosis is 65 years. Major risk factors for these cancers include tobacco smoking, certain chemical exposures, family history, age, and obesity. Unexplained hematuria in adults should be evaluated to exclude bladder and kidney cancer. Staging of bladder and kidney cancer should be based on the TNM staging system, which, along with tumor grade, provides important treatment and prognostic information. Urothelial cell carcinoma is the most common type of bladder cancer; it also can occur in the kidneys or ureters. Renal cell carcinoma is the most common type of kidney cancer. Treatment options for bladder cancer vary widely, depending on the grade of the cancer. Early non-muscle-invasive bladder cancer may be removed cystoscopically and/or treated with intravesical immunotherapy or chemotherapy, whereas patients with muscle-invasive bladder tumors typically require surgery. Management of kidney cancer is almost always surgical, unless the patient is too ill to undergo surgery or chooses palliative care. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  5. Overview of bladder heating technology: matching capabilities with clinical requirements

    Science.gov (United States)

    Stauffer, Paul R.; van Rhoon, Gerard C.

    2016-01-01

    Moderate temperature hyperthermia (40–450°C for one hour) is emerging as an effective treatment to enhance best available chemotherapy strategies for bladder cancer. A rapidly increasing number of clinical trials have investigated the feasibility and efficacy of treating bladder cancer with combined intravesical chemotherapy and moderate temperature hyperthermia. To date, most studies have concerned treatment of non-muscle invasive bladder cancer (NMIBC) limited to the interior wall of the bladder. Following the promising results of initial clinical trials, investigators are now considering protocols for treatment of muscle invasive bladder cancer (MIBC). This paper provides a brief overview of the devices and techniques used for heating bladder cancer. Systems are described for thermal conduction heating of bladder wall via circulation of hot fluid, intravesical microwave antenna heating, capacitively coupled RF current heating, and radiofrequency phased array deep regional heating of the pelvis. Relative heating characteristics of the available technologies are compared based on published feasibility studies, and the systems correlated with clinical requirements for effective treatment of MIBC and NMIBC. PMID:26939993

  6. The Danish Bladder Cancer Database

    Directory of Open Access Journals (Sweden)

    Hansen E

    2016-10-01

    Full Text Available Erik Hansen,1–3 Heidi Larsson,4 Mette Nørgaard,4 Peter Thind,3,5 Jørgen Bjerggaard Jensen1–3 1Department of Urology, Hospital of West Jutland-Holstebro, Holstebro, 2Department of Urology, Aarhus University Hospital, Aarhus, 3The Danish Bladder Cancer Database Group, 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, 5Department of Urology, Copenhagen University Hospital, Copenhagen, Denmark Aim of database: The aim of the Danish Bladder Cancer Database (DaBlaCa-data is to monitor the treatment of all patients diagnosed with invasive bladder cancer (BC in Denmark. Study population: All patients diagnosed with BC in Denmark from 2012 onward were included in the study. Results presented in this paper are predominantly from the 2013 population. Main variables: In 2013, 970 patients were diagnosed with BC in Denmark and were included in a preliminary report from the database. A total of 458 (47% patients were diagnosed with non-muscle-invasive BC (non-MIBC and 512 (53% were diagnosed with muscle-invasive BC (MIBC. A total of 300 (31% patients underwent cystectomy. Among the 135 patients diagnosed with MIBC, who were 75 years of age or younger, 67 (50% received neoadjuvent chemotherapy prior to cystectomy. In 2013, a total of 147 patients were treated with curative-intended radiation therapy. Descriptive data: One-year mortality was 28% (95% confidence interval [CI]: 15–21. One-year cancer-specific mortality was 25% (95% CI: 22–27%. One-year mortality after cystectomy was 14% (95% CI: 10–18. Ninety-day mortality after cystectomy was 3% (95% CI: 1–5 in 2013. One-year mortality following curative-intended radiation therapy was 32% (95% CI: 24–39 and 1-year cancer-specific mortality was 23% (95% CI: 16–31 in 2013. Conclusion: This preliminary DaBlaCa-data report showed that the treatment of MIBC in Denmark overall meet high international academic standards. The database is able to identify Danish BC patients and

  7. Primary congenital bladder diverticula: Where does the ureter drain?

    Directory of Open Access Journals (Sweden)

    Antonio Macedo

    2015-01-01

    Full Text Available Background: Primary congenital bladder diverticulum (PCBD is related to a deficient detrusor layer allowing out-pouching of the bladder mucosa through the inadequate muscularis wall. We aimed to review our experience with symptomatic PCBD in order to correlate clinical findings with anatomical aspects and to present late outcome. Materials and Methods: We reviewed all patients operated in our institution since 2004. We evaluated the charts for complaints, radiological exams, method of treatment, complications and length of follow-up. Results: We treated 10 cases (11 renal units - [RU], predominantly males (9/10, mean age at surgery of 5.3 years. All patients had significant urological complaints presenting either with antenatal hydronephrosis (4 or febrile urinary tract infection (5 and urinary retention in one. The ureter was found implanted inside the diverticulum in 8/11 RU. An extravesical psoas-hitch ureteroneocystostomy and diverticulum resection was performed in 10/11 cases, whereas 1 case was treated intravesically based on surgeon′s preference without performing cystoscopy. Mean follow-up was 34.1 months (1-120 without complications. Conclusions: PCBD is an uncommon diagnosis and has a high probability of drainage inside the diverticulum (72.7%. We recommend the extravesical approach associated with diverticulectomy and ureteroneocystostomy as the preferred technique to treat this abnormality.

  8. Bladder necrosis: 'A man without a bladder'.

    Science.gov (United States)

    Bosschieter, Judith; Oudshoorn, Frederik H K; Meuleman, Eric J H; Nieuwenhuijzen, Jakko A

    2018-02-17

    Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Artificial intelligence and bladder cancer arrays.

    Science.gov (United States)

    Wild, P J; Catto, J W F; Abbod, M F; Linkens, D A; Herr, A; Pilarsky, C; Wissmann, C; Stoehr, R; Denzinger, S; Knuechel, R; Hamdy, F C; Hartmann, A

    2007-01-01

    Non-muscle invasive bladder cancer is a heterogenous disease whose management is dependent upon the risk of progression to muscle invasion. Although the recurrence rate is high, the majority of tumors are indolent and can be managed by endoscopic means alone. The prognosis of muscle invasion is poor and radical treatment is required if cure is to be obtained. Progression risk in non-invasive tumors is hard to determine at tumor diagnosis using current clinicopathological means. To improve the accuracy of progression prediction various biomarkers have been evaluated. To discover novel biomarkers several authors have used gene expression microarrays. Various statistical methods have been described to interpret array data, but to date no biomarkers have entered clinical practice. Here, we describe a new method of microarray analysis using neurofuzzy modeling (NFM), a form of artificial intelligence, and integrate it with artificial neural networks (ANN) to investigate non-muscle invasive bladder cancer array data (n=66 tumors). We develop a predictive panel of 11 genes, from 2800 expressed genes, that can significantly identify tumor progression (average Logrank p = 0.0288) in the analyzed cancers. In comparison, this panel appears superior to those genes chosen using traditional analyses (average Logrank p = 0.3455) and tumor grade (Logrank, p = 0.2475) in this non-muscle invasive cohort. We then analyze panel members in a new non-muscle invasive bladder cancer cohort (n=199) using immunohistochemistry with six commercially available antibodies. The combination of 6 genes (LIG3, TNFRSF6, KRT18, ICAM1, DSG2 and BRCA2) significantly stratifies tumor progression (Logrank p = 0.0096) in the new cohort. We discuss the benefits of the transparent NFM approach with respect to other reported methods.

  10. Image-Guided Radiation Therapy for Muscle-Invasive Carcinoma of the Urinary Bladder with Cone Beam CT Scan: Use of Individualized Internal Target Volumes for a Single Patient

    Directory of Open Access Journals (Sweden)

    Gagan Saini

    2012-09-01

    Full Text Available Introduction: While planning radiation therapy (RT for a carcinoma of the urinary bladder (CaUB, the intra-fractional variation of the urinary bladder (UB volume due to filling-up needs to be accounted for. This internal target volume (ITV is obtained by adding internal margins (IM to the contoured bladder. This study was planned to propose a method of acquiring individualized ITVs for each patient and to verify their reproducibility. Methods: One patient with CaUB underwent simulation with the proposed ‘bladder protocol’. After immobilization, a planning CT scan on empty bladder was done. He was then given 300 ml of water to drink and the time (T was noted. Planning CT scans were performed after 20 min (T+20, 30 min (T+30 and 40 min (T+40. The CT scan at T+20 was co-registered with the T+30 and T+40 scans. The bladder volumes at 20, 30 and 40 min were then contoured as CTV20, CTV30 and CTV40 to obtain an individualized ITV for our patient. For daily treatment, he was instructed to drink water as above, and the time was noted; treatment was started after 20 min. Daily pre- and post-treatment cone beam CT (CBCT scans were done. The bladder visualized on the pre-treatment CBCT scan was compared with CTV20 and on the post-treatment CBCT scan with CTV30. Results: In total, there were 65 CBCT scans (36 pre- and 29 post-treatment. Individualized ITVs were found to be reproducible in 93.85% of all instances and fell outside in 4 instances. Conclusions: The proposed bladder protocol can yield a reproducible estimation of the ITV during treatment; this can obviate the need for taking standard IMs.

  11. Developments in bladder cancer

    International Nuclear Information System (INIS)

    Denis, L.; Niijima, T.; Prout, G.; Schroder, F.H.

    1986-01-01

    This book contains 20 selections. Some of the titles are: Guidelines for Radiation Therapy in Clinical Research on Bladder Cancer; Transitional Cell Carcinoma in Situ; Policy on Monitoring and Reporting Results; Standardization of Protocol Formnd The Role of Cytology in the Diagnosis, Detection and Follow-up of Bladder Cancer

  12. Bladder pain syndrome

    DEFF Research Database (Denmark)

    Hanno, Philip; Nordling, Jørgen; Fall, Magnus

    2011-01-01

    Bladder pain syndrome is a deceptively intricate symptom complex that is diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder, accompanied by at least one other urinary symptom. It is a diagnosis of exclusion in a patient who has...

  13. Ultrasound: Bladder (For Parents)

    Science.gov (United States)

    ... If You Have Questions Print en español Ultrasonido: vejiga What It Is A bladder ultrasound is a safe and painless test that ... Exam: Voiding Cystourethrogram (VCUG) Ultrasound: Renal (Kidneys, Ureters, Bladder) Urinary ... only. For specific medical advice, diagnoses, and treatment, consult your doctor. © 1995- The Nemours Foundation. All ...

  14. The hyperactive urinary bladder in female patients with multiple sclerosis as seen by a physiotherapist

    OpenAIRE

    Havlíčková, Michaela

    2008-01-01

    The aim of the thesis " A Physiotherapist's View of Overactive Bladder function in Multiple Sclerosis Patients" and the influence of physiotherapy on the symptoms of the overactive bladder. This thesis deals with exert influence on symptoms of an overactive bladder by physiotherapy. Therapy is based on the fact that guarding reflexes that maintains continence at the level of spine and subcortical (micturition centre in pons) are activated by the contraction of the pelvic floor muscles. Physio...

  15. Surgical technique for en bloc transurethral resection of bladder tumour with a Hybrid Knife(®).

    Science.gov (United States)

    Islas-García, J J O; Campos-Salcedo, J G; López-Benjume, B I; Torres-Gómez, J J; Aguilar-Colmenero, J; Martínez-Alonso, I A; Gil-Villa, S A

    2016-05-01

    Bladder cancer is the second most common malignancy of the urinary tract and the 9th worldwide. Latin American has an incidence of 5.6 per 100,000 inhabitants per year. Seventy-five percent of newly diagnosed cases are nonmuscle invasive bladder cancer, and 25% of cases present as muscle invasive. The mainstay of treatment for nonmuscle invasive bladder cancer is loop transurethral resection. In 2013, the group led by Dr Mundhenk of the University Hospital of Tübingen, Germany, was the first to describe the Hybrid Knife(®) equipment for performing en bloc bladder tumour resection, with favourable functional and oncological results. To describe the surgical technique of en bloc bladder tumour resection with a Hybrid Knife(®) as an alternative treatment for nonmuscle invasive bladder tumours. A male patient was diagnosed by urotomography and urethrocystoscopy with a bladder tumour measuring 2×1cm on the floor. En bloc transurethral resection of the bladder tumour was performed with a Hybrid Knife(®). Surgery was performed for 35min, with 70 watts for cutting and 50 watts for coagulation, resecting and evacuating en bloc the bladder tumour, which macroscopically included the muscle layer of the bladder. There were no complications. The technique of en bloc bladder tumour resection with Hybrid Knife(®) is an effective alternative to bipolar loop transurethral resection. Resection with a Hybrid Knife(®) is a procedure with little bleeding and good surgical vision and minimises the risk of bladder perforation and tumour implants. The procedure facilitates determining the positivity of the neoplastic process, vascular infiltration and bladder muscle invasion in the histopathology study. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. [En bloc resection and vaporization techniques for the treatment of bladder cancer].

    Science.gov (United States)

    Struck, J P; Karl, A; Schwentner, C; Herrmann, T R W; Kramer, M W

    2018-04-12

    Modifications in resection techniques may overcome obvious limitations of conventionally performed transurethral resection (e. g., tumor fragmentation) of bladder tumors or provide an easier patient treatment algorithm (e. g., tumor vaporization). The present review article summarizes the current literature in terms of en bloc resection techniques, histopathological quality, complication rates, and oncological outcomes. A separate data search was performed for en bloc resection (ERBT, n = 27) and vaporization (n = 15) of bladder tumors. In most cases, ERBT is performed in a circumferential fashion. Alternatively, ERBT may be performed by undermining the tumor base via antegrade application of short energy impulses. Based on high rates of detrusor in specimens of ERBT (90-100%), a better histopathological quality is assumed. Significant differences in perioperative complication rates have not been observed, although obturator-nerve-based bladder perforations are not seen when laser energy is used. There is a nonstatistically significant trend towards lower recurrence rates in ERBT groups. Tumor vaporization may provide a less invasive technique for older patients with recurrences of low-risk bladder cancer. It can be performed in an outpatient setting. ERBT may provide better histopathological quality. Tumor vaporization is performed in health care systems where reimbursement is adequate.

  17. Increased toll-like receptors and p53 levels regulate apoptosis and angiogenesis in non-muscle invasive bladder cancer: mechanism of action of P-MAPA biological response modifier

    International Nuclear Information System (INIS)

    Garcia, Patrick Vianna; Seiva, Fábio Rodrigues Ferreira; Carniato, Amanda Pocol; Mello Júnior, Wilson de; Duran, Nelson; Macedo, Alda Maria; Oliveira, Alexandre Gabarra de; Romih, Rok; Nunes, Iseu da Silva; Nunes, Odilon da Silva; Fávaro, Wagner José

    2016-01-01

    The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom BCG (Bacillus Calmette-Guerin) has failed or is contraindicated are recently increasing due to the development of new drugs. Although agents like mitomycin C and BCG are routinely used, there is a need for more potent and/or less-toxic agents. In this scenario, a new perspective is represented by P-MAPA (Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride), developed by Farmabrasilis (non-profit research network). This study detailed and characterized the mechanisms of action of P-MAPA based on activation of mediators of Toll-like Receptors (TLRs) 2 and 4 signaling pathways and p53 in regulating angiogenesis and apoptosis in an animal model of NMIBC, as well as, compared these mechanisms with BCG treatment. Our results demonstrated the activation of the immune system by BCG (MyD88-dependent pathway) resulted in increased inflammatory cytokines. However, P-MAPA intravesical immunotherapy led to distinct activation of TLRs 2 and 4-mediated innate immune system, resulting in increased interferons signaling pathway (TRIF-dependent pathway), which was more effective in the NMIBC treatment. Interferon signaling pathway activation induced by P-MAPA led to increase of iNOS protein levels, resulting in apoptosis and histopathological recovery. Additionally, P-MAPA immunotherapy increased wild-type p53 protein levels. The increased wild-type p53 protein levels were fundamental to NO-induced apoptosis and the up-regulation of BAX. Furthermore, interferon signaling pathway induction and increased p53 protein levels by P-MAPA led to important antitumor effects, not only suppressing abnormal cell proliferation, but also by preventing continuous expansion of tumor mass through suppression of angiogenesis, which was characterized by decreased VEGF and increased endostatin protein levels. Thus, P-MAPA immunotherapy could be considered an important therapeutic

  18. Increased toll-like receptors and p53 levels regulate apoptosis and angiogenesis in non-muscle invasive bladder cancer: mechanism of action of P-MAPA biological response modifier.

    Science.gov (United States)

    Garcia, Patrick Vianna; Seiva, Fábio Rodrigues Ferreira; Carniato, Amanda Pocol; de Mello Júnior, Wilson; Duran, Nelson; Macedo, Alda Maria; de Oliveira, Alexandre Gabarra; Romih, Rok; Nunes, Iseu da Silva; Nunes, Odilon da Silva; Fávaro, Wagner José

    2016-07-07

    The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom BCG (Bacillus Calmette-Guerin) has failed or is contraindicated are recently increasing due to the development of new drugs. Although agents like mitomycin C and BCG are routinely used, there is a need for more potent and/or less-toxic agents. In this scenario, a new perspective is represented by P-MAPA (Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride), developed by Farmabrasilis (non-profit research network). This study detailed and characterized the mechanisms of action of P-MAPA based on activation of mediators of Toll-like Receptors (TLRs) 2 and 4 signaling pathways and p53 in regulating angiogenesis and apoptosis in an animal model of NMIBC, as well as, compared these mechanisms with BCG treatment. Our results demonstrated the activation of the immune system by BCG (MyD88-dependent pathway) resulted in increased inflammatory cytokines. However, P-MAPA intravesical immunotherapy led to distinct activation of TLRs 2 and 4-mediated innate immune system, resulting in increased interferons signaling pathway (TRIF-dependent pathway), which was more effective in the NMIBC treatment. Interferon signaling pathway activation induced by P-MAPA led to increase of iNOS protein levels, resulting in apoptosis and histopathological recovery. Additionally, P-MAPA immunotherapy increased wild-type p53 protein levels. The increased wild-type p53 protein levels were fundamental to NO-induced apoptosis and the up-regulation of BAX. Furthermore, interferon signaling pathway induction and increased p53 protein levels by P-MAPA led to important antitumor effects, not only suppressing abnormal cell proliferation, but also by preventing continuous expansion of tumor mass through suppression of angiogenesis, which was characterized by decreased VEGF and increased endostatin protein levels. Thus, P-MAPA immunotherapy could be considered an important therapeutic

  19. Genomic Alterations in Liquid Biopsies from Patients with Bladder Cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Nordentoft, Iver Kristiansen; Christensen, Emil

    2016-01-01

    Background: At least half of the patients diagnosed with non–muscle-invasive bladder cancer (NMIBC) experience recurrence and approximately 15% will develop progression to muscle invasive or metastatic disease. Biomarkers for disease surveillance are urgently needed. Objective: Development......-invasive or metastatic bladder cancer; t test for ddPCR data. Results and limitations: We developed from one to six personalised assays per patient. Patients with progressive disease showed significantly higher levels of tumour DNA in plasma and urine before disease progression, compared with patients with recurrent...

  20. Bladder Cancer—Patient Version

    Science.gov (United States)

    The most common type of bladder cancer is transitional cell carcinoma, also called urothelial carcinoma. Smoking is a major risk factor for bladder cancer. Bladder cancer is often diagnosed at an early stage. Start here to find information on bladder cancer treatment, screening, research, and statistics.

  1. SU-F-J-05: The Effect of Air Pockets in the Urinary Bladder During Bladder Hyperthermia Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Schooneveldt, G.; Kok, H.P.; Bakker, A.; Geijsen, E.D.; Reijke, T.M. de; Crezee, J. [Academisch Medisch Centrum / Universiteit van Amsterdam, Amsterdam (Netherlands)

    2016-06-15

    Purpose: Hyperthermia combined with Mitomycin C is used for the treatment of non-muscle invasive bladder cancer (NMIBC), using a phased array system of microwave antennas for bladder heating. Often some air is present in the bladder, which effectively blocks the microwave radiation, potentially preventing proper treatment of that part of the bladder. Air can be a relevant fraction of the bladder content and large air pockets are expected to have a noticeable influence on achieved temperatures. Methods: We analysed 14 NMIBC patients treated at our institute with our AMC-4 hyperthermia device with four 70MHz antennas around the pelvis. A CT scan was made after treatment and a physician delineated the bladder on the CT scan. On the same scan, the amount of air present in the bladder was delineated. Using our in-house developed hyperthermia treatment planning system, we simulated the treatment using the clinically applied device settings. We did this once with the air pocket delineated on the CT scan, and once with the same volume filled with bladder tissue. Results: The patients had on average 4.2ml (range 0.8–10.1ml) air in the bladder. The bladder volume was delineated by the physician, that is including air pocket and bladder wall, was on average 253ml (range 93–452ml). The average volume in which changes exceeded 0.25°C was 22ml (range 0–108 ml), with the bladder being up to 2°C cooler when an air pocket was present. Except for extreme cases, there was no evident relation between the quantity of air and the difference in temperature. Conclusion: The effect of an air pocket in the bladder during bladder hyperthermia treatment varies strongly between patients. Generally, this leads to lower temperatures in the bladder, potentially affecting treatment quality, and suggesting that care need be taken to minimise the size of air pockets during hyperthermia treatments. The KWF Dutch Cancer Society financially supported this work, grant UVA 2012-5539.

  2. Biofabricated Structures Reconstruct Functional Urinary Bladders in Radiation-injured Rat Bladders.

    Science.gov (United States)

    Imamura, Tetsuya; Shimamura, Mitsuru; Ogawa, Teruyuki; Minagawa, Tomonori; Nagai, Takashi; Silwal Gautam, Sudha; Ishizuka, Osamu

    2018-05-08

    The ability to repair damaged urinary bladders through the application of bone marrow-derived cells is in the earliest stages of development. We investigated the application of bone marrow-derived cells to repair radiation-injured bladders. We used a three-dimensional (3D) bioprinting robot system to biofabricate bone marrow-derived cell structures. We then determined if the biofabricated structures could restore the tissues and functions of radiation-injured bladders. The bladders of female 10-week-old Sprague-Dawley (SD) rats were irradiated with 2-Gy once a week for 5 weeks. Adherent and proliferating bone marrow-derived cells harvested from the femurs of male 17-week-old green fluorescence protein-transfected Tg-SD rats were cultured in collagen-coated flasks. Bone marrow-derived cell spheroids were formed in 96-well plates. Three layers of spheroids were assembled by the bioprinter onto a 9x9 microneedle array. The assembled spheroids were perfusion cultured for 7 days, and then the microneedle array was removed. Two weeks after the last radiation treatment, the biofabricated structures were transplanted into an incision on the anterior wall of the bladders (n=10). Control rats received the same surgery but without the biofabricated structures (sham-structure, n=12). At 2 and 4 weeks after surgery, the sham-structure control bladder tissues exhibited disorganized smooth muscle layers, decreased nerve cells, and significant fibrosis with increased presence of fibrosis-marker P4HB-positive cells and hypoxia-marker HIF1α-positive cells. The transplanted structures survived within the recipient tissues, and blood vessels extended within them from the recipient tissues. The bone marrow-derived cells in the structures differentiated into smooth muscle cells and formed smooth muscle clusters. The recipient tissues near the transplanted structures had distinct smooth muscle layers and reconstructed nerve cells, and only minimal fibrosis with decreased presence of P4

  3. Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe).

    Science.gov (United States)

    Häggström, Christel; Liedberg, Fredrik; Hagberg, Oskar; Aljabery, Firas; Ströck, Viveka; Hosseini, Abolfazl; Gårdmark, Truls; Sherif, Amir; Malmström, Per-Uno; Garmo, Hans; Jahnson, Staffan; Holmberg, Lars

    2017-09-27

    To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death. Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival. The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author. © Article author(s) (or their employer

  4. Functional, histological structure and mastocytes alterations in rat urinary bladders following acute and [corrected] chronic cyclophosphamide treatment.

    Science.gov (United States)

    Juszczak, K; Gil, K; Wyczolkowski, M; Thor, P J

    2010-08-01

    Neurogenic inflammation is linked to urinary bladder overactivity development. Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and induces cystitis with overactivity. The aim of this study was to estimate the effect of CYP on rat urinary bladder function, histological structure and mastocytes numbers following acute and chronic CYP treatment. Fourty two female rats were divided into four groups: I (control), II (acute cystitis), III (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively. In group I-III the cystometric evaluation was performed. Sections of the bladder were stained with HE and toluidine blue for the detection of mastocytes. The severity of inflammation was examined according to mucosal abrasion, haemorrhage, leukocyte infiltration and oedema. Acute and chronic CYP treatment caused inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage, oedema) and increased infiltration of inflammatory cells in urinary bladder. Acute treatment induced the infiltration of mastocytes within bladder wall contrary to chronic one decrement. Acute treatment caused more severe mucosal abrasion, whereas chronic one revealed more developed haemorrhage changes. Additionally, cystometric evaluation revealed urinary bladder overactivity development in both types of cystitis. Basal pressure and detrusor overactivity index after acute treatment increased considerably in comparison with the increase obtained after chronic one. Our results proved that acute model of CYP-induced cystitis in rats is more credible for further evaluation of neurogenic inflammation response in pathogenesis of overactive bladder as compared to chronic one.

  5. Neuronal Activation in the Periaqueductal Gray Matter Upon Electrical Stimulation of the Bladder

    Directory of Open Access Journals (Sweden)

    Céline Meriaux

    2018-05-01

    Full Text Available Reflexes, that involve the spinobulbospinal pathway control both storage and voiding of urine. The periaqueductal gray matter (PAG, a pontine structure is part of the micturition pathway. Alteration in this pathway could lead to micturition disorders and urinary incontinence, such as the overactive bladder symptom complex (OABS. Although different therapeutic options exist for the management of OABS, these are either not effective in all patients. Part of the pathology of OABS is faulty sensory signaling about the filling status of the urinary bladder, which results in aberrant efferent signaling leading to overt detrusor contractions and the sensation of urgency and frequent voiding. In order to identify novel targets for therapy (i.e., structures in the central nervous system and explore novel treatment modalities such as neuromodulation, we aimed at investigating which areas in the central nervous system are functionally activated upon sensory afferent stimulation of the bladder. Hence, we designed a robust protocol with multiple readout parameters including immunohistological and behavioral parameters during electrical stimulation of the rat urinary bladder. Bladder stimulation induced by electrical stimulation, below the voiding threshold, influences neural activity in: (1 the caudal ventrolateral PAG, close to the aqueduct; (2 the pontine micturition center and locus coeruleus; and (3 the superficial layers of the dorsal horn, sacral parasympathetic nucleus and central canal region of the spinal cord. In stimulated animals, a higher voiding frequency was observed but was not accompanied by increase in anxiety level and locomotor deficits. Taken together, this work establishes a critical role for the vlPAG in the processing of sensory information from the urinary bladder and urges future studies to investigate the potential of neuromodulatory approaches for urological diseases.

  6. Randomized controlled trial of foot reflexology for patients with symptomatic idiopathic detrusor overactivity.

    Science.gov (United States)

    Mak, Ho-Leung Jimmy; Cheon, Willy Cecilia; Wong, To; Liu, Yu Sun John; Tong, Wai Mei Anny

    2007-06-01

    The aim of this study was to examine whether foot reflexology has beneficial effects on patients with idiopathic detrusor overactivity. One hundred and nine women with symptomatic idiopathic detrusor overactivity were randomized into either foot reflexology treatment group or nonspecific foot massage control group. The primary outcome measure was the change in the diurnal micturition frequency. There was significant change in the number of daytime frequency in the reflexology group when compared with the massage group (-1.90 vs -0.55, p = 0.029). There was also a decrease in the 24-h micturition frequency in both groups, but the change was not statistically significant (-2.80 vs -1.04 p = 0.055). In the reflexology group, more patients believed to have received "true" reflexology (88.9 vs 67.4%, p = 0.012). This reflects the difficulty of blinding in trials of reflexology. Larger scale studies with a better-designed control group and an improved blinding are required to examine if reflexology is effective in improving patients' overall outcome.

  7. Robotic Extramucosal Excision of Bladder Wall Leiomyoma

    Directory of Open Access Journals (Sweden)

    Khalid E. Al-Othman

    2014-01-01

    Full Text Available Introduction: Multiple case reports and reviews have been described in the literature for bladder wall leiomyoma resection via different approaches. The minimally invasive partial cystectomy remains the most widely accepted technique; however, case reports for enucleation of bladder wall leiomyoma have also been described. The purpose of this video is to demonstrate the robotic extramucosal excision of a bladder wall leiomyoma, without cystotomy, but with complete removal of the muscular layer. Materials and Methods: A 35-year old male present with lower urinary tract symptoms and imaging showed bladder wall mass with histopathology showed leiomyoma. The patient consented for mass excision with the possibility of a partial cystectomy. The patient was placed in the supine, 30-degree Trendelenburg position during the procedure. A total of 4 ports were inserted. A 3-arm da Vinci robotic surgical system was docked, and the arms were connected. Extramucosal excision was accomplished without cystotomy and muscle approximation was achieved by 2 0 Vicryle. Result: The operative time was 90 minutes, blood loss of approximately 50mL and the patient was discharged after 72 hours with no immediate complications and a 6 months follow-up showed no recurrence. Conclusion: Such a technique results in complete excision of the tumor, without cystotomy, and also maintains an intact mucosa. These steps, in addition to decreasing the risk of local recurrence, also shorten the period of postoperative catheterization and hospitalization.

  8. Stages of Bladder Cancer

    Science.gov (United States)

    ... above the waist. Tiny tubules in the kidneys filter and clean the blood . They take out waste ... to bladder cancer. Being exposed to paints, dyes, metals, or petroleum products in the workplace. Past treatment ...

  9. Bladder Diseases - Multiple Languages

    Science.gov (United States)

    ... PDF Health Information Translations Spanish (español) Expand Section Bladder Diseases: MedlinePlus Health Topic - English Enfermedades de la vejiga: Tema de salud de MedlinePlus - español (Spanish) National ...

  10. Bladder perforations in children

    African Journals Online (AJOL)

    2014-11-20

    Nov 20, 2014 ... Mean recovery time for patients was 15 days. ... fracture.[1,2] Isolated bladder perforations are rare, and they .... PA, perineal injury, pelvic fracture. Trauma .... Lower genitourinary injury and pelvic fractures in pediatric patients.

  11. HPLC assisted Raman spectroscopic studies on bladder cancer

    Science.gov (United States)

    Zha, W. L.; Cheng, Y.; Yu, W.; Zhang, X. B.; Shen, A. G.; Hu, J. M.

    2015-04-01

    We applied confocal Raman spectroscopy to investigate 12 normal bladder tissues and 30 tumor tissues, and then depicted the spectral differences between the normal and the tumor tissues and the potential canceration mechanism with the aid of the high-performance liquid chromatographic (HPLC) technique. Normal tissues were demonstrated to contain higher tryptophan, cholesterol and lipid content, while bladder tumor tissues were rich in nucleic acids, collagen and carotenoids. In particular, β-carotene, one of the major types of carotenoids, was found through HPLC analysis of the extract of bladder tissues. The statistical software SPSS was applied to classify the spectra of the two types of tissues according to their differences. The sensitivity and specificity of 96.7 and 66.7% were obtained, respectively. In addition, different layers of the bladder wall including mucosa (lumps), muscle and adipose bladder tissue were analyzed by Raman mapping technique in response to previous Raman studies of bladder tissues. All of these will play an important role as a directive tool for the future diagnosis of bladder cancer in vivo.

  12. Current trends in the management of bladder cancer.

    Science.gov (United States)

    Patel, Amit R; Campbell, Steven C

    2009-01-01

    This article provides a review of bladder cancer etiology, diagnosis, and management for WOC nurses. Bladder cancer incidence continues to rise yearly in the United States, and patients with bladder cancer comprise some of the most challenging cases in urologic oncology. Nurses are involved with all aspects of the processes of care for the patient with bladder cancer, from initial diagnosis and treatment to postsurgical care and follow-up. For nonmuscle invasive bladder cancer, treatment includes transurethral resection followed by intravesical chemotherapy or immunotherapy to prevent recurrence or progression. Radical cystectomy along with chemotherapy protocols provides a survival advantage for muscle invasive bladder cancer, although the timing of chemotherapy remains controversial. Numerous factors are considered when determining the type of urinary diversion used at the time of radical cystectomy, but patient, family, surgeon, and nursing input are essential for preserving an optimal health-related quality of life and reducing morbidity. Patients with metastatic bladder cancer are generally treated with a cisplatin-based chemotherapy but continue to have a poor prognosis. Newer therapies involving novel molecular-targeted agents provide hope for the future for patients with metastatic disease.

  13. Trimodality therapy in bladder cancer: Who, what and when?

    Science.gov (United States)

    Premo, Christopher; Apolo, Andrea B.; Agarwal, Piyush K.

    2015-01-01

    Summary Radical cystectomy is a standard treatment for non-metastatic, muscle-invasive bladder cancer. Treatment with trimodality therapy consisting of maximal transurethral resection of the bladder tumor (TURBT) followed by concurrent chemotherapy and radiation has emerged as a method to preserve the native bladder in highly motivated patients. A number of factors can impact the likelihood of long term bladder preservation after trimodality therapy, and therefore should be taken into account when selecting patients. New radiation techniques such as intensity modulated radiation therapy and image guided radiation therapy may decrease the toxicity of radiotherapy in this setting, but remain an area of active study. Novel chemotherapy regimens may improve response rates and minimize toxicity. PMID:25882559

  14. Bladder cancer: what’s new in 2017

    Directory of Open Access Journals (Sweden)

    O. B. Karyakin

    2018-01-01

    Full Text Available Treatment of bladder cancer has been a complicated problem. Low survival for regional and metastatic disease remains. In recent years,  the efforts of doctors, biologists, diagnosticians were aimed at development of new technologies in these spheres and improvement of treatment results for this pathology. In this review, current views on diagnosis, the role of repeated surgical interventions in non-muscle-invasive bladder cancer, etc. are presented. Advances in molecular biology allowed to differentiate subtypes of urothelial bladder cancer. Importantly, the results of biomolecular studies allowed to identify different responses to drug treatment. Moreover, in some cases these results have a follow-up period of up to 3 years. Based on other data characterizing the tumor, the effectiveness of new drugs for treatment of regional, metastatic and post-cisplatin therapy bladder cancer was evaluated. These results allow to hope for increased life span and quality of life for patients with this severe disease.

  15. Bladder cancer and schistosomiasis

    International Nuclear Information System (INIS)

    Zaghloul, M.S.

    2012-01-01

    Schistosoma-associated bladder cancer was believed, for several decades, to be a completely unique entity of disease, different from urothelial cancer. This was probably due to its distinct clinico pathologic and demographic features that varied from those of urothelial entity. The carcinogenesis is an extremely complex process resulting from the accumulation of many genetic and epigenetic changes leading to alterations in the cell proliferation regulation process. In bladder cancer, many of these carcinogenic cascades were not fully documented or somewhat conflicting. In spite of the efforts performed, much is still needed to explore the presence or absence of the carcinogenic difference with a different etiology. The control of schistosomiasis in certain countries and the subsequent decrease in the intensity of infestation showed changing of features approaching that of urothelial tumors. However the schistosoma-associated bladder cancer presented in more advanced stages than schistosoma-non associated urothelial cancer. More recently, data are gathered that, upon applying the same treatment protocol and management care, stage by stage comparison of the treatment end-results were found to be similar in bladder cancer patients with a different etiology. All treatment options; including radical cystectomy with or without adjuvant or neoadjuvant chemo- or radiotherapy or tri modality bladder preserving treatment seem to lead to similar end-results regardless of etiologic factor(s) implicated in bladder cancer development.

  16. Roles of Polyuria and Hyperglycemia on Bladder Dysfunction in Diabetes

    Science.gov (United States)

    Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

    2014-01-01

    Purpose Diabetes mellitus (DM) causes diabetic bladder dysfunction (DBD). We aimed to identify the pathogenic roles of polyuria and hyperglycemia on DBD in rats. Materials and Methods Seventy-two female Sprague-Dawley rats were divided: age-matched controls (control), sham urinary diversion (sham), urinary diversion (UD), streptozotocin-induced diabetes after sham UD (DM), streptozotocin-induced diabetes after UD (UD+DM), and 5% sucrose-induced diuresis after sham UD (DIU). UD was performed by ureterovaginostomy 10d before DM induction. Animals were evaluated 20 wks after DM or diuresis induction. We measured 24-hr drinking and voiding volumes and cystometry (CMG). Bladders were harvested for quantification of smooth muscle, urothelium, and collagen. We measured nitrotyrosine and manganese superoxide dismutase (MnSOD) in bladder. Results Diabetes and diuresis caused increases in drinking volume, voiding volume and bladder weight. Bladder weights decreased in the UD and UD+DM groups. Intercontractile intervals, voided volume, and compliance increased in the DIU and DM groups, decreased in the UD, and further decreased in the UD+DM group. The total cross-sectional tissue, smooth muscle and urothelium areas increased in the DIU and DM groups, and decreased in the UD and UD+DM groups. As percentages of total tissue area, collagen decreased in the DIU and DM groups, and increased in the UD and UD+DM groups, and smooth muscle and urothelium decreased in the UD and UD+DM groups. Nitrotyrosine and MnSOD increased in DM and UD+DM rats. Conclusions Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may play a pathogenic role in late stage DBD. PMID:22999997

  17. Neurostimulation for bladder evacuation: is sacral root stimulation a substitute for microstimulation?

    Science.gov (United States)

    Probst, M; Piechota, H J; Hohenfellner, M; Gleason, C A; Tanagho, E A

    1997-04-01

    To determine by anatomical and functional studies whether stimulation of sacral rootlets might permit selective stimulation of autonomic fibres, thus avoiding the detrusor/sphincter dyssynergia characteristic of current techniques of neurostimulation for bladder evacuation. In 10 male mongrel dogs, the S2 root was isolated and its constituent rootlets followed from their origin in the spinal cord to the point of exit from the dura. The entire root and the individual rootlets were then stimulated, including intra- and extra-dural stimulation and at proximal, mid and distal levels. Neuroanatomical and histological findings showed that rootlets of ventral S2 maintain their identity throughout their intradural course; some carry predominantly autonomic fibres, some predominantly somatic and some a mixture of the two. It appears surgically feasible to identify, isolate and sever the predominantly somatic rootlets intradurally, sparing the predominantly autonomic rootlets for inclusion in extradural electrode placement around the entire sacral root, thus eliminating sphincteric interference with detrusor contraction for voiding at low pressure.

  18. Electrical stimulation of the sacral dorsal gray commissure evokes relaxation of the external urethral sphincter in the cat

    NARCIS (Netherlands)

    Blok, Bertil F.M.; Maarseveen, Jos T.P.W.; Holstege, Gert

    1998-01-01

    Stimulation of the pontine micturition center (PMC) results in micturition, i.e. an immediate relaxation of the urethral sphincter and a contraction of the detrusor muscle of the bladder. The PMC generates the bladder contraction by way of a direct excitatory pathway to the parasympathetic bladder

  19. High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

    International Nuclear Information System (INIS)

    Egerod, Frederikke Lihme; Bartels, Annette; Fristrup, Niels; Borre, Michael; Ørntoft, Torben F; Oleksiewicz, Martin B; Brünner, Nils; Dyrskjøt, Lars

    2009-01-01

    Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer

  20. Does phosphorylation of cofilin affect the progression of human bladder cancer?

    International Nuclear Information System (INIS)

    Chung, Hong; Kim, Hong Sup; Kim, Bokyung; Jung, Seung-Hyo; Won, Kyung-Jong; Jiang, Xiaowen; Lee, Chang-Kwon; Lim, So Dug; Yang, Sang-Kuk; Song, Ki Hak

    2013-01-01

    We determined the differently expressed protein profiles and their functions in bladder cancer tissues with the aim of identifying possible target proteins and underlying molecular mechanisms for taking part in their progression. We examined the expression of proteins by proteomic analysis and western blot in normal urothelium, non-muscle-invasive bladder cancers (NMIBCs), and muscle-invasive bladder cancers (MIBCs). The function of cofilin was analyzed using T24 human bladder cancer cells. The expression levels of 12 proteins were altered between bladder cancers and normal bladder tissues. Of these proteins, 14-3-3σ was upregulated in both NMIBCs and MIBCs compared with controls. On the other hand, myosin regulatory light chain 2, galectin-1, lipid-binding AI, annexin V, transthyretin, CARD-inhibitor of NF-κB-activating ligand, and actin prepeptide were downregulated in cancer samples. Cofilin, an actin-depolymerizing factor, was prominent in both NMIBCs and MIBCs compared with normal bladder tissues. Furthermore, we confirmed that cofilin phosphorylation was more prominent in MIBCs than in NMIBCs using immunoblotting and immunohistochemcal analyses. Epidermal growth factor (EGF) increased the phosphorylation of cofilin and elevated the migration in T24 cells. Knockdown of cofilin expression with small interfering RNA attenuated the T24 cell migration in response to EGF. These results demonstrate that the increased expression and phosphorylation of cofilin might play a role in the occurrence and invasiveness of bladder cancer. We suspected that changes in cofilin expression may participate in the progression of the bladder cancer

  1. A place for precision medicine in bladder cancer: targeting the FGFRs.

    Science.gov (United States)

    di Martino, Erica; Tomlinson, Darren C; Williams, Sarah V; Knowles, Margaret A

    2016-10-01

    Bladder tumors show diverse molecular features and clinical outcome. Muscle-invasive bladder cancer has poor prognosis and novel approaches to systemic therapy are urgently required. Non-muscle-invasive bladder cancer has good prognosis, but high recurrence rate and the requirement for life-long disease monitoring places a major burden on patients and healthcare providers. Studies of tumor tissues from both disease groups have identified frequent alterations of FGFRs, including mutations of FGFR3 and dysregulated expression of FGFR1 and FGFR3 that suggest that these may be valid therapeutic targets. We summarize current understanding of the molecular alterations affecting these receptors in bladder tumors, preclinical studies validating them as therapeutic targets, available FGFR-targeted agents and results from early clinical trials in bladder cancer patients.

  2. Role of hexaminolevulinate-guided fluorescence cystoscopy in bladder cancer

    DEFF Research Database (Denmark)

    Malmström, Per-Uno; Grabe, Magnus; Haug, Erik Skaaheim

    2012-01-01

    Hexaminolevulinate (HAL) is an optical imaging agent used with fluorescence cystoscopy (FC) for the detection of non-muscle-invasive bladder cancer (NMIBC). Guidelines from the European Association of Urology (EAU) and a recent, more detailed European expert consensus statement agree that HAL...

  3. Abdominal wall closure in bladder exstrophy complex repair by ...

    African Journals Online (AJOL)

    Background and Objectives: The Exstrophy Complex (EC) is a serious malformation of midline abdominal wall. Wide pubis prevents approximating the lateralized rectus muscle and leads to dehiscence and fi stula formation. Our aim was to recommend an easier method for abdominal wall closure in the Bladder Exstrophy ...

  4. Spontaneous Bladder Perforation in an Infant Neurogenic Bladder: Laparoscopic Management

    Directory of Open Access Journals (Sweden)

    Daniel Cabezalí Barbancho

    2013-01-01

    Full Text Available Spontaneous bladder perforation is an uncommon event in childhood. It is usually associated with bladder augmentation. We are presenting a case of bladder rupture in an infant with neurogenic bladder without prior bladder surgery. Three days after lipomyelomeningocele excision the patient showed signs and symptoms of acute abdomen. The ultrasound exploration revealed significant amount of intraperitoneal free fluid and therefore a laparoscopic exploration was performed. A posterior bladder rupture was diagnosed and repaired laparoscopically. Currently, being 3 years old, she keeps successfully dry with clean intermittent catheterization. Neurogenic bladder voiding function can change at any time of its evolution and lead to complications. Early diagnosis of spontaneous bladder rupture is of paramount importance, so it is essential to think about it in the differential diagnosis of acute abdomen.

  5. Solifenacin objectively decreases urinary sensation in women with overactive bladder syndrome.

    Science.gov (United States)

    Lowenstein, Lior; Kenton, Kimberly; Mueller, Elizabeth R; Brubaker, Linda; Sabo, Edmond; Durazo-Arivzu, Ramón A; Fitzgerald, Mary P

    2012-04-01

    To evaluate the test-retest reliability of a device that measures urinary sensation during cystometry, and to use that device to determine whether treatment of overactive bladder syndrome (OAB) with solifenacin is associated with a change in urinary sensation. Overall 15 women were recruited for this study, ten women with OAB and urodynamically demonstrated detrusor overactivity and five controls without OAB underwent filling cystometry twice with contemporaneous, continuous recording of urinary sensation. Women with OAB received solifenacin 10 mg daily during the weeks between testing. We compared the areas under the initial and repeat sensation-volume curves. While taking solifenacin, the maximum cystometric capacity increased from 329 ± 168 ml to 464 ± 123 ml (P sensation curve decreased (P sensation during the treatment of OAB with solifenacin. If clinical correlations are confirmed by future study, such urinary sensation measures may prove useful as assessment, treatment predictor, or outcome measures in OAB research and/or clinical care.

  6. Genetics Home Reference: bladder cancer

    Science.gov (United States)

    ... Testing Registry: Malignant tumor of urinary bladder Other Diagnosis and Management Resources (1 link) MedlinePlus Encyclopedia: Bladder Cancer General Information from MedlinePlus (5 links) Diagnostic Tests ...

  7. Intra- and Intersexual swim bladder dimorphisms in the plainfin midshipman fish (Porichthys notatus): Implications of swim bladder proximity to the inner ear for sound pressure detection.

    Science.gov (United States)

    Mohr, Robert A; Whitchurch, Elizabeth A; Anderson, Ryan D; Forlano, Paul M; Fay, Richard R; Ketten, Darlene R; Cox, Timothy C; Sisneros, Joseph A

    2017-11-01

    The plainfin midshipman fish, Porichthys notatus, is a nocturnal marine teleost that uses social acoustic signals for communication during the breeding season. Nesting type I males produce multiharmonic advertisement calls by contracting their swim bladder sonic muscles to attract females for courtship and spawning while subsequently attracting cuckholding type II males. Here, we report intra- and intersexual dimorphisms of the swim bladder in a vocal teleost fish and detail the swim bladder dimorphisms in the three sexual phenotypes (females, type I and II males) of plainfin midshipman fish. Micro-computerized tomography revealed that females and type II males have prominent, horn-like rostral swim bladder extensions that project toward the inner ear end organs (saccule, lagena, and utricle). The rostral swim bladder extensions were longer, and the distance between these swim bladder extensions and each inner-ear end organ type was significantly shorter in both females and type II males compared to that in type I males. Our results revealed that the normalized swim bladder length of females and type II males was longer than that in type I males while there was no difference in normalized swim bladder width among the three sexual phenotypes. We predict that these intrasexual and intersexual differences in swim bladder morphology among midshipman sexual phenotypes will afford greater sound pressure sensitivity and higher frequency detection in females and type II males and facilitate the detection and localization of conspecifics in shallow water environments, like those in which midshipman breed and nest. © 2017 Wiley Periodicals, Inc.

  8. Detrusor instability in children with recurrent urinary tract infection and/or enuresis. II

    DEFF Research Database (Denmark)

    Qvist, N; Nielsen, K K; Kristensen, E S

    1986-01-01

    Of 41 children, aged 5-15 years, referred consecutively because of recurrent urinary tract infections (UTIs) and/or enuresis, 18 (44%) showed detrusor instability (DI) in at least 2 of 6 CO2 cystometries. One child was excluded from the study because of lack of follow-up. Four children with less...... pronounced DI (instability during less than or equal to 50% of the cystometries performed) and frequent UTIs were given antibiotics prophylactically for 3 months. In the remaining 13 children, DI was found during more than half the cystometries performed, and 11 of these children, who also had urge...... incontinence, were treated with emepronium bromide, 400-600 mg daily (10-12 mg/kg) for 3 months. In 7 of the patients this treatment was supplemented by antibiotics prophylactically because of frequent UTIs. Two children with special problems received other types of treatment. All children were free from...

  9. Transcutaneous electrical nerve stimulation and temporary S3 neuromodulation in idiopathic detrusor instability.

    Science.gov (United States)

    Hasan, S T; Robson, W A; Pridie, A K; Neal, D E

    1996-06-01

    We studied the effects of electrical stimulation on idiopathic detrusor instability. Between January 1993 and December 1994, 30 men and 41 women (mean age plus or minus standard deviation 48 +/- 16 years) underwent transcutaneous electrical nerve stimulation (TENS) of the S2-S3 dermatomes, and 13 men and 22 women (mean age 48 +/- 12