[Recurrent urological cancer--diagnose and treatment].

PubMed

Takeshima, H; Akaza, H

1998-02-01

Clinical efforts to spare bladder function even in the case of muscle invasive recurrent bladder cancer is taking. Early detection of recurrence is essential for bladder sparing, and both urinary NMP22 and BTA are thought to have potency to detect recurrence of bladder cancer earlier than urinary cytology. Intravesical administration of BCG for superficial bladder cancer and intraarterial injection of chemoagents (Methotrexate and Cisplatin) with radiation for muscle invasive bladder cancer are thought to play important roles in sparing the bladder. Early detection of recurrent prostate cancer is becoming easier by ultrasensitive PSA assay. Though the value of early detection of recurrence is not proven since the benefits of early hormonal treatment have not yet been established, that should be a good indicator to evaluate new and coming treatments and play a important role to develop an effective treatment for recurrent prostate cancer.

Insights from animal models of bladder cancer: recent advances, challenges, and opportunities

PubMed Central

John, Bincy Anu; Said, Neveen

2017-01-01

Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with increasing incidence and mortality. Treatment of bladder cancer has not advanced in the past 30 years. Therefore, there is a crucial unmet need for novel therapies, especially for high grade/stage disease that can only be achieved by preclinical model systems that faithfully recapitulate the human disease. Animal models are essential elements in bladder cancer research to comprehensively study the multistep cascades of carcinogenesis, progression and metastasis. They allow for the investigation of premalignant phases of the disease that are not clinically encountered. They can be useful for identification of diagnostic and prognostic biomarkers for disease progression and for preclinical identification and validation of therapeutic targets/candidates, advancing translation of basic research to clinic. This review summarizes the latest advances in the currently available bladder cancer animal models, their translational potential, merits and demerits, and the prevalent tumor evaluation modalities. Thereby, findings from these model systems would provide valuable information that can help researchers and clinicians utilize the model that best answers their research questions. PMID:28915710

Management of Bladder Cancer After Renal Transplantation.

PubMed

Demirdag, C; Citgez, S; Talat, Z; Onal, B

2017-03-01

In renal transplant recipients, the risk of developing bladder cancer and rate of diagnosis of advanced staged bladder cancer are generally higher than the general population. Also, it is more challenging to treat renal transplant recipients than the regular patient population. We aimed to evaluate the efficacy and safety of radical cystectomy (RC) and urinary diversion with ileal conduit in renal transplant recipients. We identified 2 patients with prior history of renal transplantation who underwent RC and ileal conduit urinary diversion for bladder cancer. Preoperative clinical and demographic data were presented and outcomes were assessed. The RC and ileal conduit urinary diversion were performed in the first patient 56 months after renal transplantation and in the second patient 64 months after renal transplantation. Clinical staging was high-grade T2 transitional cell cancer of the bladder for patient 1 and T2 with pure squamous cell cancer of the bladder for patient 2. No perioperative or postoperative complication and no graft dysfunction occurred in either patient. Our experience demonstrated that RC with ileal conduit reconstruction in renal transplant recipients is safe and feasible. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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.

"Urgency tip": a portable patient-activated device for objective measurement of urinary urgency.

PubMed

Kobayashi, Hideki; Araki, Isao; Tsuchida, Takayuki; Zakoji, Hidenori; Mikami, Yuki; Takeda, Masayuki; Kiyohiro, Noriaki

2007-03-01

For clinical practice and research of overactive bladder syndrome, it is essential to evaluate urgency symptoms in daily life. We have developed a portable patient-activated device to record bladder sensations. This electronic device is pocket-size and light, with five grading buttons and another button for cancellation.

Prospective evaluation of the utility of routine postoperative cystogram after traumatic bladder injury.

PubMed

Inaba, Kenji; Okoye, Obi T; Browder, Timothy; Best, Charles; Branco, Bernardino C; Teixeira, Pedro G; Barmparas, Galinos; Reddy, Sravanthi; Demetriades, Demetrios

2013-12-01

The value of routinely testing bladder repair integrity with a cystogram before urinary catheter removal is unclear. The purpose of this study was to prospectively evaluate the utility of routine postoperative cystogram after traumatic bladder injury. All patients sustaining a bladder injury requiring operative repair at two Level I trauma centers were prospectively enrolled during a 62-month study period ending on January 2011. Injury demographics, imaging data, and outcomes were extracted. All patients were evaluated with either a plain or a computed tomography cystogram. A total of 127 patients were enrolled (mean [SD] age, 30.4 [13.5] years; blunt trauma, 63.8%, mean [SD] Injury Severity Score [ISS], 17.7 [10.6]). A total of 75 patients (59.1%) had an intraperitoneal (IP) bladder injury, 44 (34.6%) had an extraperitoneal (EP) bladder injury, and 8 had a (6.3%) combined IP/EP bladder injury. All patients with IP and IP/EP injuries (n = 83) underwent operative repair and a postoperative cystogram at 8.6 (1.8) days (range, 5-13 days). Sixty-nine IP injuries (83.1%) were simple (dome or body disruption/penetrating injury), while 14 (16.9%) were complex (trigone/requiring ureter implantation). There were no deaths during the follow-up period. With the exception of one patient (1.2%) with a complex injury requiring ureteric implantation, there were no leaks demonstrated on postoperative cystogram, and the urinary catheters were successfully removed. In this prospective evaluation of the role of bladder evaluation after operative repair, routine use of follow-up cystograms for simple injuries did not impact clinical management. For complex repairs to the trigone or those requiring ureter implantation, a follow-up cystogram should be obtained before catheter removal. Diagnostic study, level II.

An etiologic prediction model incorporating biomarkers to predict the bladder cancer risk associated with occupational exposure to aromatic amines: a pilot study.

PubMed

Mastrangelo, Giuseppe; Carta, Angela; Arici, Cecilia; Pavanello, Sofia; Porru, Stefano

2017-01-01

No etiological prediction model incorporating biomarkers is available to predict bladder cancer risk associated with occupational exposure to aromatic amines. Cases were 199 bladder cancer patients. Clinical, laboratory and genetic data were predictors in logistic regression models (full and short) in which the dependent variable was 1 for 15 patients with aromatic amines related bladder cancer and 0 otherwise. The receiver operating characteristics approach was adopted; the area under the curve was used to evaluate discriminatory ability of models. Area under the curve was 0.93 for the full model (including age, smoking and coffee habits, DNA adducts, 12 genotypes) and 0.86 for the short model (including smoking, DNA adducts, 3 genotypes). Using the "best cut-off" of predicted probability of a positive outcome, percentage of cases correctly classified was 92% (full model) against 75% (short model). Cancers classified as "positive outcome" are those to be referred for evaluation by an occupational physician for etiological diagnosis; these patients were 28 (full model) or 60 (short model). Using 3 genotypes instead of 12 can double the number of patients with suspect of aromatic amine related cancer, thus increasing costs of etiologic appraisal. Integrating clinical, laboratory and genetic factors, we developed the first etiologic prediction model for aromatic amine related bladder cancer. Discriminatory ability was excellent, particularly for the full model, allowing individualized predictions. Validation of our model in external populations is essential for practical use in the clinical setting.

Effect of spinal anaesthesia on the lower urinary tract in continent women.

PubMed

Haeusler, G; Sam, C; Chiari, A; Tempfer, C; Hanzal, E; Koelbl, H

1998-01-01

To evaluate the effect of spinal anaesthesia on the bladder neck position and the urethral closure function in the resting state and during clinical stress test in healthy, continent women. Controlled clinical trial. Department of Gynaecology and Obstetrics, Vienna University Medical School. Fourteen continent women, of which seven were nulliparous and seven parous, underwent minor gynaecological procedures under spinal anaesthesia. Urodynamics and ultrasound investigations were performed before and during spinal anaesthesia. Changes in the bladder neck position and the urethral closure function before and during spinal anaesthesia. Bladder neck position was found to be lower and more posterior during spinal anaesthesia as compared with pre-operative assessment. The posterior urethrovesical angle increased significantly both at rest and during maximum straining. We observed a significant increase in bladder compliance, and all parameters of the urethral pressure profile decreased significantly. While none of the nulliparous women had a positive clinical stress test during spinal anaesthesia, 4/7 parous women demonstrated leakage (Fisher's exact test, P = 0.003). Blockage of nerve supply to the pelvic floor muscles in continent women is associated with a significant loss of support of the bladder neck region confirming the theory of an active mechanism of muscular elements providing continence.

Bioadhesive drug delivery system using glyceryl monooleate for the intravesical administration of paclitaxel.

PubMed

Lee, Seung-Ju; Kim, Sae Woong; Chung, Hesson; Park, Yeong Taek; Choi, Young Wook; Cho, Yong-Hyun; Yoon, Moon Soo

2005-10-01

Many reports have shown that the efficacy of intravesical therapy for bladder cancer is in part limited by the poor penetration of drugs into the urothelium. The present study evaluated the effect of glyceryl monooleate (GMO) on the absorption of intravesically administered paclitaxel in a rabbit model of bladder cancer. Urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120 min with paclitaxel (500 microg/20 ml) by intravesical instillation. Two formulations of GMO/paclitaxel were evaluated using different proportions of water, 15 and 30%, and Taxol was used as a control. Animals were observed for clinical signs of toxicity and necropsy was performed. 120 min after instillation, the bladder was emptied and excised. In the urine, paclitaxel concentration was decreased by 39.6 and 41.2% in the two experimental groups and by 25.2% in the control group. The paclitaxel concentrations in the urothelium were 53 and 56% of the urine concentration in both experimental groups, but 11% in the control group. The concentration then declined exponentially in the underlying capillary-perfused tissues, reaching equilibrium at a depth of 1,400-1,700 microm. The plasma concentrations were extremely low compared with concentrations in urine and bladder tissues and were not associated with clinical toxicity. We conclude that GMO has a significantly increased bioadhesiveness to bladder mucosa. Therefore, intravesical administration of GMO/paclitaxel/water provides a significant advantage for drugs targeting the bladder tissue, and paclitaxel represents a viable option for intravesical bladder cancer therapy. Copyright 2005 S. Karger AG, Basel.

Trypanosoma cruzi infection induced changes in the innervation, structure and function of the murine bladder.

PubMed

Boczko, Judd; Tar, Moses; Melman, Arnold; Jelicks, Linda A; Wittner, Murray; Factor, Stephen M; Zhao, Dazhi; Hafron, Jason; Weiss, Louis M; Tanowitz, Herbert B; Christ, George J

2005-05-01

The involvement of the lower urinary tract in chronic Chagas' disease has received little attention. Therefore, we investigated pathology and functional alterations in the bladder of Trypanosoma cruzi infected mice. CD1 mice were infected with 5 x 10 T. cruzi trypomastigotes of the Brazil strain of T. cruzi. At day 100 after infection bladder structure and function were examined by pathological evaluation, magnetic resonance imaging and cystometric studies. The bladder in infected mice weighed more and were large, dilated, deformed, friable and thin walled compared with control mice. Magnetic resonance imaging confirmed these observations. Inflammation, fibrosis and ganglionitis was observed. Cystometric studies revealed that baseline, threshold and micturition pressures were increased in infected mice. Bladder overactivity and decreased bladder compliance were also noted in infected mice. There were no detectable differences in bladder capacity, micturition volume or residual volume between infected and uninfected mice. Bladder abnormalities may be a more common clinical sequelae of T. cruzi infection than previously appreciated.

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

PubMed

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.

Long-term effect of sphincteric fatigue during bladder neurostimulation.

PubMed

Li, J S; Hassouna, M; Sawan, M; Duval, F; Elhilali, M M

1995-01-01

Commercially available stimulators lack several features, including multiple channel capability and flexible stimulation parameters. These factors limit clinical application. A new computerized electrical stimulator system was developed by our team and evaluated for its efficacy in bladder evacuation in an animal model after spinal cord transection. The system can generate a wide range of stimulation characteristics and has the feature of being a programmable multichannel pacemaker. It has enabled us to induce a reversible fatigue to the external sphincter that results in proper bladder emptying on stimulation. Using this new bladder pacemaker, 8 dogs were studied. We applied the concept of fatiguing of the external sphincter via the pudendal nerve to avoid rhizotomy. We determined the optimal stimulation parameters that can reliably empty the dog's bladder for the duration of the experiment, which lasted for 8 months. The new computerized electrical stimulation system achieved the objective of reducing bladder outlet resistance without the need for sacral rhizotomy.

Morphological changes of bladder mucosa in patients who underwent instillation with combined sodium hyaluronic acid-chondroitin sulphate (Ialuril®).

PubMed

Costantini, E; Lazzeri, M; Pistolesi, D; Del Zingaro, M; Frumenzio, E; Boni, A; Pietropaolo, A; Fragalà, E; Porena, M

2013-01-01

To investigate what changes are endoscopically evident after glycosaminoglycans (GAGs) therapy by hyaluronic acid (HA) and chondroitin sulphate (CS) (Ialuril®) in female patients affected by bladder pain syndrome(BPS)/ interstitial cystitis (IC) or recurrent urinary tract infections (rUTIs). 21 female patients over 18 years affected by rUTIs or BPS/IC received intravesical instillation of HA and CS (4 weekly instillations followed by 2 instillations every 2 weeks and 2 instillation monthly). Post-treatment evaluation included cystoscopy and patient assessment of improvement in symptoms and satisfaction on a visual analogue scale (VAS) from 0 to 10. The post-treatment endoscopy showed a positive effect on bladder mucosa morphology. In 2 cases, treatment did not change endoscopic findings and clinical symptoms. In the other patients, when macroscopic features of the bladder mucosa normalized, the clinical picture improved. GAGs therapy by HA and CS (Ialuril) improves the morphology of bladder mucosa in patients with rUTI or BPS/IC. Copyright © 2013 S. Karger AG, Basel.

[Cystomanometric study of bladder sensation during sacral neuromodulation test].

PubMed

Leclers, François; Mourey, Eric; Galas, Jean Marie; Cormier, Luc; Mangin, Philippe

2005-04-01

Prospective clinical and urodynamic study evaluating modification of bladder sensation during sacral neuromodulation (SNM). 24 consecutive patients with non-neurological hyperactive bladder underwent an SNM test. Questioned about their symptoms before and during the test by the urinary handicap assessment scale, patients were divided into two groups: A (improved) and B (not improved). Group A consisted of patients obtaining 50% improvement of their symptoms with SNM followed by return of symptoms at the end of the test, while the other patients constituted group B. We then compared the cystomanometric results according to their clinical response. The mean age was 53 years: 10 patients with a good response constituted group A (n=10, i.e. 42%) and 14 patients with a poor response constituted group B (n=14, i.e. 58%). Clinically, in patients with a good response, SNM decreased urge incontinence by 100%, day-time frequency by 89% and protections by 55%. Urodynamic assessment in group A during the test demonstrated a significant increase of +23% of bladder capacity (p<0.01), +57% of the volume of onset of the first unstable contraction (p<0.004), +83% of bladder volume to the first urge to urinate BI (p<0.001) and +46% to urgency B3 (p<0.04). During SNM, cystometry revealed that 1 or 2 bladder filling volumes were increased at B1 and/or B3 in 100% of improved subjects. In contrast, 1 or 2 volumes decreased at B1 and/or B3 in 58% of non-improved subjects. No significant difference of intensity of unstable contractions was observed between the 2 groups during SNM (p=0.31). A significant correlation was observed between the two methods of clinical and urodynamic assessment. Our results suggest the use of the cystomanometric increase of bladder volume at B1 and B3 as selection criterion for candidates for SNM with non-neurological hyperactive bladder.

Bladder stones after bladder augmentation are not what they seem.

PubMed

Szymanski, Konrad M; Misseri, Rosalia; Whittam, Benjamin; Lingeman, James E; Amstutz, Sable; Ring, Joshua D; Kaefer, Martin; Rink, Richard C; Cain, Mark P

2016-04-01

Bladder and renal calculi after bladder augmentation are thought to be primarily infectious, yet few studies have reported stone composition. The primary aim was to assess bladder stone composition after augmentation, and renal stone composition in those with subsequent nephrolithiasis. The exploratory secondary aim was to screen for possible risk factors for developing infectious stones. Patients treated for bladder stones after bladder augmentation at the present institution between 1981 and 2012 were retrospectively reviewed. Data were collected on demographics, surgeries and stone composition. Patients without stone analysis were excluded. Stones containing struvite, carbonate apatite or ammonium acid ureate were classified as infectious. The following variables were analyzed for a possible association with infectious bladder stone composition: gender, history of cloacal exstrophy, ambulatory status, nephrolithiasis, recurrent urea-splitting urinary tract infections, first vs recurrent stones, timing of presentation with a calculus, history of bladder neck procedures, catheterizable channel and vesicoureteral reflux. Fisher's exact test was used for analysis. Of the 107 patients with bladder stones after bladder augmentation, 85 met inclusion criteria. Median age at augmentation was 8.0 years (follow-up 10.8 years). Forty-four patients (51.8%) recurred (14 multiple recurrences, 143 bladder stones). Renal calculi developed in 19 (22.4%) patients with a bladder stone, and 10 (52.6%) recurred (30 renal stones). Overall, 30.8% of bladder stones were non-infectious (Table). Among patients recurring after an infectious bladder stone, 30.4% recurred with a non-infectious one. Among patients recurring after a non-infectious stone, 84.6% recurred with a non-infectious one (P = 0.005). Compared with bladder stones, renal stones were more likely to be non-infectious (60.0%, P = 0.003). Of patients with recurrent renal calculi after an infectious stone, 40.0% recurred with a non-infectious one. No clinical variables were significantly associated with infectious stone composition on univariate (≥0.28) or bivariate analysis (≥0.36). This study had several limitations: it was not possible to accurately assess adherence with bladder irrigations, and routine metabolic evaluations were not performed. The findings may not apply to patients in all clinical settings. While stone analysis was available for 3/4 of the stones, similar rates of incomplete stone analyses have been reported in other series. In patients with bladder augmentation, 1/3 of bladder stones and >1/2 of renal stones were non-infectious. Furthermore, an infectious stone does not imply an infectious recurrent stone and no known clinical variables appear to be associated with stone composition, suggesting that there is a possible metabolic component in stone formation after bladder augmentation. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boutilier, Justin J., E-mail: j.boutilier@mail.utoronto.ca; Lee, Taewoo; Craig, Tim

Purpose: To develop and evaluate the clinical applicability of advanced machine learning models that simultaneously predict multiple optimization objective function weights from patient geometry for intensity-modulated radiation therapy of prostate cancer. Methods: A previously developed inverse optimization method was applied retrospectively to determine optimal objective function weights for 315 treated patients. The authors used an overlap volume ratio (OV) of bladder and rectum for different PTV expansions and overlap volume histogram slopes (OVSR and OVSB for the rectum and bladder, respectively) as explanatory variables that quantify patient geometry. Using the optimal weights as ground truth, the authors trained and appliedmore » three prediction models: logistic regression (LR), multinomial logistic regression (MLR), and weighted K-nearest neighbor (KNN). The population average of the optimal objective function weights was also calculated. Results: The OV at 0.4 cm and OVSR at 0.1 cm features were found to be the most predictive of the weights. The authors observed comparable performance (i.e., no statistically significant difference) between LR, MLR, and KNN methodologies, with LR appearing to perform the best. All three machine learning models outperformed the population average by a statistically significant amount over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and dose to the bladder, rectum, CTV, and PTV. When comparing the weights directly, the LR model predicted bladder and rectum weights that had, on average, a 73% and 74% relative improvement over the population average weights, respectively. The treatment plans resulting from the LR weights had, on average, a rectum V70Gy that was 35% closer to the clinical plan and a bladder V70Gy that was 29% closer, compared to the population average weights. Similar results were observed for all other clinical metrics. Conclusions: The authors demonstrated that the KNN and MLR weight prediction methodologies perform comparably to the LR model and can produce clinical quality treatment plans by simultaneously predicting multiple weights that capture trade-offs associated with sparing multiple OARs.« less

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

PubMed

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.

Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 [AEZS- 108].

PubMed

Szepeshazi, Karoly; Schally, Andrew V; Keller, Gunhild; Block, Norman L; Benten, Daniel; Halmos, Gabor; Szalontay, Luca; Vidaurre, Irving; Jaszberenyi, Miklos; Rick, Ferenc G

2012-07-01

Many bladder cancers progress to invasion with poor prognosis; new therapeutic methods are needed. We developed a cytotoxic LH-RH analog, AN-152 (AEZS-108) containing doxorubicin (DOX), for targeted therapy of cancers expressing LHRH receptors. We investigated the expression of LH-RH receptors in clinical bladder cancers and in HT-1376, J82, RT-4 and HT-1197 human bladder cancer lines. The effect of analog, AN-152, on growth of these tumor lines xenografted into nude mice was analyzed. Using molecular and functional assays, we also evaluated the differences between the effects of AN-152, and DOX alone. We demonstrated the expression of LH-RH receptors on 18 clinical bladder cancers by immunohistochemistry and on four human urinary bladder cancer lines HT-1376, J82, RT-4 and HT-1197 by Western blotting and binding assays. AN-152 powerfully inhibited growth of these bladder cancers in nude mice. AN-152 exerted greater effects than DOX and was less toxic. DOX activated strong multidrug resistance mechanisms in RT-4 and HT-1197 cancers, while AN-152 had no or less such effect. PCR assays and in vitro studies revealed differences in the action of AN-152 and DOX on the expression of genes involved in apoptosis. These results suggest that targeted cytotoxic LH-RH analog, AN-152 (AEZS- 108), should be examined for treatment of patients with LH-RH receptor positive invasive bladder cancers.

CIP2A is a predictor of survival and a novel therapeutic target in bladder urothelial cell carcinoma.

PubMed

Xue, Yijun; Wu, Gengqing; Wang, Xiaoning; Zou, Xiaofeng; Zhang, Guoxi; Xiao, Rihai; Yuan, Yuanhu; Long, Dazhi; Yang, Jun; Wu, Yuting; Xu, Hui; Liu, Folin; Liu, Min

2013-03-01

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified human oncoprotein that stabilizes the c-MYC protein. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in urothelial cell carcinoma (UCC) of the bladder. CIP2A expression was examined in 20 fresh bladder UCC tissues and paired adjacent normal bladder tissues by RT-PCR and Western blot. Immunohistochemistry for CIP2A was performed on additional 117 bladder UCC tissues. The clinical significance of CIP2A expression was analyzed. CIP2A downregulation was performed in bladder UCC cell line T24 with high abundance of CIP2A, and the effects of CIP2A silencing on cell proliferation, migration, invasion in vitro, and tumor growth in vivo were evaluated. We found that CIP2A expression was upregulated in bladder UCC tissues relative to adjacent normal bladder tissues. Clinicopathological analysis showed that CIP2A expression was significantly associated with tumor stage (P = 0.004), histological grade (P = 0.007), and lymph node status (P = 0.001). The Kaplan-Meier survival curves revealed that CIP2A expression was associated with poor prognosis in bladder UCC patients (log-rank value = 14.704, P < 0.001). CIP2A expression was an independent prognostic marker of overall patient survival in a multivariate analysis (P = 0.015). Knockdown of the CIP2A expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumor growth in xenograft model mice. Our findings suggest that CIP2A is an independent predictor of poor prognosis of bladder UCC patients, and inhibition of its expression might be of therapeutic significance.

Expression analysis and clinical significance of CXCL16/CXCR6 in patients with bladder cancer.

PubMed

Lee, Jun Taik; Lee, Sang Don; Lee, Jeong Zoo; Chung, Moon Kee; Ha, Hong Koo

2013-01-01

The interactions between chemokines and their receptors are closely involved in the progression and metastasis of cancer. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in bladder cancer progression. To evaluate this hypothesis, the expression levels of CXCL16 and CXCR6 were evaluated in 160 patients, including 155 patients with bladder cancer and 5 patients with benign bladder disease. The tissues were analyzed by immunohistochemical (IHC) staining and real-time reverse-transcription polymerase chain reaction. We compared the expression of CXCL16/CXCR6 in bladder cancer and benign bladder disease. The expression of CXCR6 was increased in patients with bladder cancer compared with benign bladder disease in RT-PCR. The mRNA expression levels of CXCL16 and CXCR6 were 1.75×10(-2) and 1.99×10(-2) in benign bladder tissue and 1.39×10(-2) and 2.32×10(-2) in bladder cancer tissue, respectively. In IHC staining, the expression of CXCL16/CXCR6 in bladder cancer tissues was higher compared with benign bladder tissues. On multivariate analysis, the IHC staining of CXCL16 was correlated with the 2004 WHO grade and lymphovascular invasion (P=0.021 and P=0.011, respectively). CXCR6 was correlated with the 1973 WHO grade (P=0.001), 2004 WHO grade (P<0.001), pathological T stage (P=0.002) and perineural invasion (P=0.031). However, Cox regression analysis revealed that the expression of CXCL16 and CXCR6 was not correlated with cancer recurrence and cancer-specific survival (P=0.142 and P=0.324, respectively). The expression of CXCL16/CXCR6 was higher in bladder cancer compared to benign disease and correlated with aggressive cancer behavior. Based on our results, the CXCL16/CXCR6 axis appears to be important in the progression of bladder cancer. Thus, CXCL16 and CXCR6 serve as potential therapeutic targets.

Treatment of Overactive Bladder Syndrome with Urethral Calibration in Women

PubMed Central

Sato, Renee L; Matsuura, Grace HK; Wei, David C; Chen, John J

2013-01-01

Our objective was to determine whether urethral calibration with Walther's urethral sounds may be an effective treatment for overactive bladder syndrome. The diagnosis of overactive bladder syndrome is a clinical one based on the presence of urgency, with or without urge incontinence, and is usually accompanied by frequency and nocturia in the absence of obvious pathologic or metabolic disease. These symptoms exert a profound effect on the quality of life. Pharmacologic treatment is generally used to relieve symptoms, however anticholinergic medications may be associated with several undesirable side effects. There are case reports of symptom relief following a relatively quick and simple office procedure known as urethral dilation. It is hypothesized that this may be an effective treatment for the symptoms of overactive bladder. Women with clinical symptoms of overactive bladder were evaluated. Eighty-eight women were randomized to either urethral calibration (Treatment), or placebo (Control) treatment. Women's clinical outcomes at two and eight weeks were assessed and compared between the two treatment arms. Eight weeks after treatment, 31.1% (n=14) of women who underwent urethral calibration were responsive to the treatment versus 9.3% (n=4) of the Control group. Also, 51.1% (n=23) of women within the Treatment group showed at least a partial response versus 20.9% (n=9) of the Control group. Our conclusion is that Urethral calibration significantly improves the symptoms of overactive bladder when compared to placebo and may be an effective alternative treatment method. PMID:24167769

Ultrasonographic evaluation of abdominal distension in 52 camels (Camelus dromedarius).

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Buczinski, Sébastien

2012-08-01

The purpose of this study was to assess the diagnostic value of ultrasonography in the evaluation of abdominal distension in 52 camels (Camelus dromedarius). The conditions included trypanosomiasis (n=35), intestinal obstruction (n=12) and ruptured urinary bladder (n=5). Fifteen clinically normal camels were included as controls. Transabdominal and transrectal ultrasonography was carried out on all camels. In animals with trypanosomiasis, ultrasonographic findings included accumulation of massive amounts of hypoechoic abdominal fluids where liver, intestine, kidney, spleen and urinary bladder were imaged floating. Except in two cases of bile duct calcification and one of hepatic abscessation, no detectable abnormal sonographic lesions were detected while imaging the hepatic and renal parenchyma, and the heart and its valves and major blood vessels. In camels with intestinal obstruction, ultrasonographic findings included distended intestinal loops with markedly reduced or absent motility. In one camel, the intestinal lumen contained localised hyperechoic material that was consistent with a foreign body. Hypoechoic fluid with or without fibrin was seen between intestinal loops. In camels with ruptured urinary bladder, ultrasonographic findings included collapsed and perforated bladder, echogenic blood clots within the urinary bladder and peritoneal cavity, increased thickness of the bladder wall, floating intestines in hypoechogenic fluid and echogenic calculi within the urethra. Ultrasonography was considered a useful tool for the evaluation of dromedary camels with abdominal distension. Copyright © 2011 Elsevier Ltd. All rights reserved.

Clinical and pathological implications of miRNA in bladder cancer.

PubMed

Braicu, Cornelia; Cojocneanu-Petric, Roxana; Chira, Sergiu; Truta, Anamaria; Floares, Alexandru; Petrut, Bogdan; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

2015-01-01

MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20-22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer.

Evaluation of atlas-based auto-segmentation software in prostate cancer patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greenham, Stuart, E-mail: stuart.greenham@ncahs.health.nsw.gov.au; Dean, Jenna; Fu, Cheuk Kuen Kenneth

2014-09-15

The performance and limitations of an atlas-based auto-segmentation software package (ABAS; Elekta Inc.) was evaluated using male pelvic anatomy as the area of interest. Contours from 10 prostate patients were selected to create atlases in ABAS. The contoured regions of interest were created manually to align with published guidelines and included the prostate, bladder, rectum, femoral heads and external patient contour. Twenty-four clinically treated prostate patients were auto-contoured using a randomised selection of two, four, six, eight or ten atlases. The concordance between the manually drawn and computer-generated contours were evaluated statistically using Pearson's product–moment correlation coefficient (r) and clinicallymore » in a validated qualitative evaluation. In the latter evaluation, six radiation therapists classified the degree of agreement for each structure using seven clinically appropriate categories. The ABAS software generated clinically acceptable contours for the bladder, rectum, femoral heads and external patient contour. For these structures, ABAS-generated volumes were highly correlated with ‘as treated’ volumes, manually drawn; for four atlases, for example, bladder r = 0.988 (P < 0.001), rectum r = 0.739 (P < 0.001) and left femoral head r = 0.560 (P < 0.001). Poorest results were seen for the prostate (r = 0.401, P < 0.05) (four atlases); however this was attributed to the comparison prostate volume being contoured on magnetic resonance imaging (MRI) rather than computed tomography (CT) data. For all structures, increasing the number of atlases did not consistently improve accuracy. ABAS-generated contours are clinically useful for a range of structures in the male pelvis. Clinically appropriate volumes were created, but editing of some contours was inevitably required. The ideal number of atlases to improve generated automatic contours is yet to be determined.« less

Clinical radiobiology of stage T2-T3 bladder cancer.

PubMed

Majewski, Wojciech; Maciejewski, Boguslaw; Majewski, Stanislaw; Suwinski, Rafal; Miszczyk, Leszek; Tarnawski, Rafal

2004-09-01

To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which included the treatment-related parameters and other clinical factors, revealed that the hemoglobin level and bladder capacity before RT and T-stage were statistically significant factors determining local control and overall survival. The total radiation dose was of borderline statistical significance for overall survival (p = 0.087), and OTT did not reach statistical significance. The results of our study showed that the treatment outcome after RT for bladder cancer depends mainly on clinical factors: hemoglobin level and bladder capacity before RT, and clinical T stage. An increase in the total radiation dose seemed to be associated with a better treatment outcome. The effect of the OTT was difficult to define, because it was influenced by other prognostic factors.

Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis.

PubMed

Dell'Atti, Lucio

2015-03-31

We retrospectively reviewed data of patients with incidental prostate cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. 11 out of 64 patients (17.2%) who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as significant PCa, while 8 cases (72.7%) were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79). During the follow-up, biochemical recurrence occurred in 1 patient (9%). Concerning the cancer specific survival there was no statistical significance (P = 0.326) between the clinically significant and clinical insignificant cancer group. In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

[Clinical study of bladder injury].

PubMed

Abe, Kazuhiro; Oishi, Yukihiko; Onodera, Syoichi; Ikemoto, Isao; Kiyota, Hiroshi; Asano, Koji; Ueda, Masataka; Wada, Tetsuro; Tashiro, Kazuya

2002-03-01

Since bladder injury has no specific clinical symptoms, accurate diagnosis at first consultation is relatively difficult. To elucidate the clinical characters type of injury, clinical symptoms, laboratory findings, methods of therapy and diagnosis, we reviewed 15 patients with bladder injury over a 9-year-period 1990-1998 (10 were traumatic injuries and 5 spontaneous injuries). We found no specific clinical symptom of bladder injury. Bladder injury may occur anywhere in the bladder wall, but most commonly occurred at the dome of the bladder (60.0%). Gross hematuria was not seen in 40.0% of the cases. The accuracy of diagnosis at first consultation was relatively low (46.7%) and the tendency to make a misdiagnosis as acute abdomen on digestive organs was found. Of the traumatic injuries 60% were afflicted in the drunken state, so alcohol intoxication was considered as an important enviromental factor of bladder injury. Surgical repair of injury sites was employed in 11 cases (73.3%: 7 were intraperitoneal injuries, 4 were extraperitoneal injuries), 4 cases were managed with indwelling urethral catheter. With appropriate treatment, the prognosis is excellent.

Novel Software-Assisted Hemodynamic Evaluation of Pelvic Flow During Chemoperfusion of Pelvic Arteries for Bladder Cancer: Double- Versus Single-Balloon Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, Kiyohito, E-mail: rad105@poh.osaka-med.ac.jp; Yamamoto, Kazuhiro, E-mail: rad043@poh.osaka-med.ac.jp; Nakai, Go, E-mail: rad091@poh.osaka-med.ac.jp

2016-06-15

PurposeApproximately 83 % of patients with bladder cancer have achieved a complete response after undergoing a novel bladder preservation therapy involving balloon-occluded intra-arterial infusion chemotherapy (BOAI) using a four-lumen double-balloon catheter, known as the Osaka Medical College regimen. This study aimed to show the quantitative difference in hemodynamics of the bladder arteries using syngo iFlow (Siemens Healthcare, Erlangen, Germany), which provides an automatic tool for quantitative blood flow analysis between double BOAI (D-BOAI) and conventional single BOAI (S-BOAI).Materials and MethodsFifty patients were included. The catheters were introduced into both posterior trunks of the internal iliac arteries via contralateral femoral artery access.more » A side hole between the distal and proximal balloons was placed at the origin of each bladder artery to allow clear visualization of angiographic flow of the injected agent into the urinary bladder. Digital subtraction angiography was used during analysis with the syngo iFlow to evaluate the hemodynamics of the contrast medium in the pelvic arteries during BOAI. The comparative change in the amount of contrast medium in the bladder arteries between D-BOAI and S-BOAI was assessed using syngo iFlow.ResultsOne-hundred pelvic sides were analyzed. The amount of contrast medium in the bladder arteries using D-BOAI was more than twice that using S-BOAI (right, 3.03-fold; left, 2.81-fold).ConclusionThe amount of contrast medium in the bladder arteries using D-BOAI was higher than that using conventional S-BOAI. This may increase the anticancer drug concentration in the affected bladder, leading to a good clinical response.« less

Safety of three sequential whole bladder photodynamic therapy (WBPDT) treatments in the management of resistant bladder cancer

NASA Astrophysics Data System (ADS)

Mejia, Maria C.; Nseyo, Unyime O.

2009-02-01

INTRODUCTION: WBPDT has been used to treat resistant superficial bladder cancer, with clinical benefits and associated dose-dependent side effects. OBJECTIVE: The objective of this study was to assess the safety of three sequential WBPDT treatments in patients with resistant non-muscle invasive (NMI) bladder cancer. MATERIALS AND METHODS: 12 males and one female provided written informed consent in this Phase II study. Each patient received intravenous injection of Photofrin® (AXCAN Parma Inc, Canada) at 1.5 mg/kg two days prior to whole bladder laser (630nm) treatment. Assessment of safety and efficacy included weekly urinary symptoms; cystoscopy, biopsy and cytology; and measurement of bladder volume quarterly after each treatment at baseline, six and 12 months. Treatment #2 and/or #3 occurred only in the absence of bladder contracture, and/or disease progression. RESULTS: 13 patients: 12 males and one female have been enrolled and average age of enrollees is 67.1(52 - 87) years. Four patients had Ta-T1/Grade I-III tumors; two patients had CIS associated with T1/GI-III; and seven patients had carcinoma in situ (CIS) only. Three patients received 3/3 treatments, and are evaluable for toxicity; three patients received two treatments only; and seven patients received one treatment only. There was no bladder contracture; transient mild to moderate bladder irritative voiding symptoms of dysuria, urinary frequency, nocturia and urgency occurred in all patients. The three evaluable patients were without evidence of disease at average of 13.1 (7-20) months. CONCLUSION: Three sequential WBPDT treatments might have a favorable toxicity profile in the management of recurrent/ refractory non-muscle invasive bladder cancer.

Large-Scale SRM Screen of Urothelial Bladder Cancer Candidate Biomarkers in Urine.

PubMed

Duriez, Elodie; Masselon, Christophe D; Mesmin, Cédric; Court, Magali; Demeure, Kevin; Allory, Yves; Malats, Núria; Matondo, Mariette; Radvanyi, François; Garin, Jérôme; Domon, Bruno

2017-04-07

Urothelial bladder cancer is a condition associated with high recurrence and substantial morbidity and mortality. Noninvasive urinary tests that would detect bladder cancer and tumor recurrence are required to significantly improve patient care. Over the past decade, numerous bladder cancer candidate biomarkers have been identified in the context of extensive proteomics or transcriptomics studies. To translate these findings in clinically useful biomarkers, the systematic evaluation of these candidates remains the bottleneck. Such evaluation involves large-scale quantitative LC-SRM (liquid chromatography-selected reaction monitoring) measurements, targeting hundreds of signature peptides by monitoring thousands of transitions in a single analysis. The design of highly multiplexed SRM analyses is driven by several factors: throughput, robustness, selectivity and sensitivity. Because of the complexity of the samples to be analyzed, some measurements (transitions) can be interfered by coeluting isobaric species resulting in biased or inconsistent estimated peptide/protein levels. Thus the assessment of the quality of SRM data is critical to allow flagging these inconsistent data. We describe an efficient and robust method to process large SRM data sets, including the processing of the raw data, the detection of low-quality measurements, the normalization of the signals for each protein, and the estimation of protein levels. Using this methodology, a variety of proteins previously associated with bladder cancer have been assessed through the analysis of urine samples from a large cohort of cancer patients and corresponding controls in an effort to establish a priority list of most promising candidates to guide subsequent clinical validation studies.

The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis.

PubMed

Tang, Xingxing; Du, Peng; Yang, Yong

2017-10-01

The aim of this study was to evaluate the evidence regarding the neutrophil-to-lymphocyte ratio (NLR) as a factor predictive of survival in bladder cancer patients. A search of PubMed and Embase for relevant studies between January 1, 1966 and November 10, 2016 was performed with the terms [NLR OR (neutrophil lymphocyte ratio)] AND [(bladder cancer) OR BCa OR NMIBC OR MIBC]. Inclusion required studies published in English containing bladder cancer patients and evaluating NLR as a predictive factor. Endpoints of NLR and survival data were extracted for pooled analysis. The pooled results showed that an elevated NLR was a predictor for poor overall survival (OS) [hazard ratio (HR) = 1.19, 95% confidence interval (CI) 1.07-1.31], cancer-specific survival (CSS) (HR = 1.40, 95% CI 1.17-1.69), recurrence-free survival (RFS) (HR = 1.58, 95% CI 1.24-2.03) and progression-free survival (PFS) (HR = 1.33, 95% CI 1.19-1.49) in patients with bladder cancer. Heterogeneity between studies was observed for OS, CSS and RFS, but not for PFS. Publication bias was detected for all these outcomes. Our results showed that elevated NLR might be valuable as a predictive factor of survival in bladder cancer patients.

Clinical significance and biological roles of CARMA3 in human bladder carcinoma.

PubMed

Man, Xiaojun; He, Jiani; Kong, Chuize; Zhu, Yuyan; Zhang, Zhe

2014-05-01

Caspase recruitment domain and membrane-associated guanylate kinase-like domain protein 3 (CARMA3) was reported as an oncoprotein overexpressed in several cancers. The expression pattern of CARMA3 and its clinical significance in human bladder cancer have not been well characterized. In the present study, CARMA3 expression was analyzed in 90 archived bladder cancer specimens using immunohistochemistry, and the correlation between CARMA3 expression and clinicopathological parameters was evaluated. We found that CARMA3 was overexpressed in 35 of 90 (38.8%) bladder cancer specimens. Significant association was observed between CARMA3 overexpression with tumor status (p = 0.081) and tumor grade (p = 0.027). To further explore the biological functions of CARMA3 in bladder cancer, we depleted CARMA3 in T24 and 5637 cell lines using small interfering RNA (siRNA). Using cell counting kit-8 (CCK8) assay and colony formation assay, we were able to show that CARMA3 depletion inhibited cell proliferation and colony number. Further study demonstrated that CARMA3 depletion decreased an expression of nuclear factor kappa B (NF-κB) targets cyclin D1 and Bcl-2 expression, as well as IκB phosphorylation. Luciferase reporter assay showed that CARMA3 depletion could downregulate NF-κB reporter activity. In conclusion, CARMA3 is overexpressed in bladder cancer and regulates malignant cell growth and NF-κB signaling, which makes CARMA3 a candidate therapeutic target for bladder cancer.

Case report of metastatic invasive breast lobular carcinoma to the urinary bladder.

PubMed

Al Ibraheemi, Ahmed A

2016-01-01

Breast cancer is the most common cancer in women except skin cancer. The common metastatic sites include lymph node, lung, liver and bone. However, metastasis to the bladder is extremely rare. To our knowledge, this is the first case of breast cancer metastasis to urinary bladder in Jordan which is reported. Nine years after the initial diagnosis of lobular breast carcinoma, the patient suffered from left side leg edema; Ultrasonography and Computed tomography scanning showed thickening of posterior bladder wall and bilateral hydronephrosis. The biopsy of the bladder confirmed metastatic lesion from the breast. In contrast to the primary tumor, bladder metastasis showed negative expression of estrogen (ER) and progesterone (PR) receptors. However, Her2neu test was negative in both. The reported case confirms that bladder metastasis from breast cancer tend to occur late after the diagnosis of the primary tumor. Furthermore, bladder metastasis can be asymptomatic and heterogeneous in ER and PR expression in comparison with the primary tumor. This report supports the need for careful follow-up and early intervention whenever such clinical situation is suspected. This report supports further evaluation of receptor status at time of metastasis.

Natural killer cell-based adoptive immunotherapy eradicates and drives differentiation of chemoresistant bladder cancer stem-like cells.

PubMed

Ferreira-Teixeira, Margarida; Paiva-Oliveira, Daniela; Parada, Belmiro; Alves, Vera; Sousa, Vitor; Chijioke, Obinna; Münz, Christian; Reis, Flávio; Rodrigues-Santos, Paulo; Gomes, Célia

2016-10-21

High-grade non-muscle invasive bladder cancer (NMIBC) has a high risk of recurrence and progression to muscle-invasive forms, which seems to be largely related to the presence of tumorigenic stem-like cell populations that are refractory to conventional therapies. Here, we evaluated the therapeutic potential of Natural Killer (NK) cell-based adoptive immunotherapy against chemoresistant bladder cancer stem-like cells (CSCs) in a pre-clinical relevant model, using NK cells from healthy donors and NMIBC patients. Cytokine-activated NK cells from healthy donors and from high-grade NMIBC patients were phenotypically characterized and assayed in vitro against stem-like and bulk differentiated bladder cancer cells. Stem-like cells were isolated from two bladder cancer cell lines using the sphere-forming assay. The in vivo therapeutic efficacy was evaluated in mice bearing a CSC-induced orthotopic bladder cancer. Animals were treated by intravesical instillation of interleukin-activated NK cells. Tumor response was evaluated longitudinally by non-invasive bioluminescence imaging. NK cells from healthy donors upon activation with IL-2 and IL-15 kills indiscriminately both stem-like and differentiated tumor cells via stress ligand recognition. In addition to cell killing, NK cells shifted CSCs towards a more differentiated phenotype, rendering them more susceptible to cisplatin, highlighting the benefits of a possible combined therapy. On the contrary, NK cells from NMIBC patients displayed a low density on NK cytotoxicity receptors, adhesion molecules and a more immature phenotype, losing their ability to kill and drive differentiation of CSCs. The local administration, via the transurethral route, of activated NK cells from healthy donors provides an efficient tumor infiltration and a subsequent robust tumoricidal activity against bladder cancer with high selective cytolytic activity against CSCs, leading to a dramatic reduction in tumor burden from 80 % to complete remission. Although pre-clinical, our results strongly suggest that an immunotherapeutic strategy using allogeneic activated NK cells from healthy donors is effective and should be exploited as a complementary therapeutic strategy in high-risk NMIBC patients to prevent tumor recurrence and progression.

Management of lower urinary tract symptoms in Parkinson's disease in the neurology clinic.

PubMed

Madan, Arina; Ray, Sudeshna; Burdick, Daniel; Agarwal, Pinky

2017-12-01

This clinical review aims to evaluate lower urinary tract symptoms (LUTS) in Parkinson's disease (PD) patients and the current treatment options available for these symptoms in a neurology setting. The review also addresses when referral to urology is appropriate. A literature search was conducted using the keywords 'LUTS', 'non-motor symptoms', 'overactive bladder', 'Parkinson's disease' and 'urinary symptoms' using the Medline/Pubmed search engine. Data collected ranged from 2000 to present with emphasis on recent publications. This review was conducted because LUTS in PD has a major impact on quality of life and is associated with early institutionalization. Emphasis is placed on treating overactive bladder with conservative strategies and medical management in the neurology setting. Quality of life can be improved and institutionalization can be delayed with a multimodal approach to bladder care.

Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition

PubMed Central

Cruz, Glaura Nisya de Oliveira; Fontes, Juliana Marin; Saad Salles, Tania Regina Dias; Boechat, Marcia Cristina Bastos; Monteiro, Ana Carolina; Moreira, Maria Elizabeth Lopes

2018-01-01

Introduction Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. Methods Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). Results Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. Conclusion Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we emphasize the importance of proactive management of neurogenic bladder and prompt referral so as to help mitigate CZS disease burden for patients and their families. PMID:29494684

Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition.

PubMed

Costa Monteiro, Lucia Maria; Cruz, Glaura Nisya de Oliveira; Fontes, Juliana Marin; Saad Salles, Tania Regina Dias; Boechat, Marcia Cristina Bastos; Monteiro, Ana Carolina; Moreira, Maria Elizabeth Lopes

2018-01-01

Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we emphasize the importance of proactive management of neurogenic bladder and prompt referral so as to help mitigate CZS disease burden for patients and their families.

Radiographer-performed abdominal and pelvic ultrasound: its value in a urology out-patient clinic.

PubMed

Nargund, V H; Lomas, K; Sapherson, D A; Flannigan, G M; Stewart, P A

1994-04-01

To assess the efficacy of radiographer-performed ultrasound examination as a routine investigative procedure in a urological out-patient clinic. A total of 151 patients attending a District General Hospital Urological Out-patient Department underwent an ultrasound examination in the clinic. Diagnosis by ultrasound was achieved in 93% of patients. The remaining patients underwent further investigations. Two (1%) patients with normal scans had small bladder tumours. Subsequent intravenous urography in these individuals showed normal upper tracts. Abdominal and pelvic ultrasound examination performed in the urological out-patient clinic on unprepared patients was the only investigation necessary for evaluation of common problems such as non-specific urinary symptoms, recurrent urinary tract infections and bladder outlet obstruction.

Occult Pelvic Lymph Node Involvement in Bladder Cancer: Implications for Definitive Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldsmith, Benjamin; Baumann, Brian C.; He, Jiwei

2014-03-01

Purpose: To inform radiation treatment planning for clinically staged, node-negative bladder cancer patients by identifying clinical factors associated with the presence and location of occult pathologic pelvic lymph nodes. Methods and Materials: The records of patients with clinically staged T1-T4N0 urothelial carcinoma of the bladder undergoing radical cystectomy and pelvic lymphadenectomy at a single institution were reviewed. Logistic regression was used to evaluate associations between preoperative clinical variables and occult pathologic pelvic or common iliac lymph nodes. Percentages of patient with involved lymph node regions entirely encompassed within whole bladder (perivesicular nodal region), small pelvic (perivesicular, obturator, internal iliac, andmore » external iliac nodal regions), and extended pelvic clinical target volume (CTV) (small pelvic CTV plus common iliac regions) were calculated. Results: Among 315 eligible patients, 81 (26%) were found to have involved pelvic lymph nodes at the time of surgery, with 38 (12%) having involved common iliac lymph nodes. Risk of occult pathologically involved lymph nodes did not vary with clinical T stage. On multivariate analysis, the presence of lymphovascular invasion (LVI) on preoperative biopsy was significantly associated with occult pelvic nodal involvement (odds ratio 3.740, 95% confidence interval 1.865-7.499, P<.001) and marginally associated with occult common iliac nodal involvement (odds ratio 2.307, 95% confidence interval 0.978-5.441, P=.056). The percentages of patients with involved lymph node regions entirely encompassed by whole bladder, small pelvic, and extended pelvic CTVs varied with clinical risk factors, ranging from 85.4%, 95.1%, and 100% in non-muscle-invasive patients to 44.7%, 71.1%, and 94.8% in patients with muscle-invasive disease and biopsy LVI. Conclusions: Occult pelvic lymph node rates are substantial for all clinical subgroups, especially patients with LVI on biopsy. Extended coverage of pelvic lymph nodes up to the level of the common iliac nodes may be warranted in subsets of patients.« less

Expression analysis and clinical significance of CXCL16/CXCR6 in patients with bladder cancer

PubMed Central

LEE, JUN TAIK; LEE, SANG DON; LEE, JEONG ZOO; CHUNG, MOON KEE; HA, HONG KOO

2013-01-01

The interactions between chemokines and their receptors are closely involved in the progression and metastasis of cancer. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in bladder cancer progression. To evaluate this hypothesis, the expression levels of CXCL16 and CXCR6 were evaluated in 160 patients, including 155 patients with bladder cancer and 5 patients with benign bladder disease. The tissues were analyzed by immunohistochemical (IHC) staining and real-time reverse-transcription polymerase chain reaction. We compared the expression of CXCL16/CXCR6 in bladder cancer and benign bladder disease. The expression of CXCR6 was increased in patients with bladder cancer compared with benign bladder disease in RT-PCR. The mRNA expression levels of CXCL16 and CXCR6 were 1.75×10−2 and 1.99×10−2 in benign bladder tissue and 1.39×10−2 and 2.32×10−2 in bladder cancer tissue, respectively. In IHC staining, the expression of CXCL16/CXCR6 in bladder cancer tissues was higher compared with benign bladder tissues. On multivariate analysis, the IHC staining of CXCL16 was correlated with the 2004 WHO grade and lymphovascular invasion (P=0.021 and P=0.011, respectively). CXCR6 was correlated with the 1973 WHO grade (P=0.001), 2004 WHO grade (P<0.001), pathological T stage (P=0.002) and perineural invasion (P=0.031). However, Cox regression analysis revealed that the expression of CXCL16 and CXCR6 was not correlated with cancer recurrence and cancer-specific survival (P=0.142 and P=0.324, respectively). The expression of CXCL16/CXCR6 was higher in bladder cancer compared to benign disease and correlated with aggressive cancer behavior. Based on our results, the CXCL16/CXCR6 axis appears to be important in the progression of bladder cancer. Thus, CXCL16 and CXCR6 serve as potential therapeutic targets. PMID:23255926

Proceedings of the 3rd Annual Albert Institute for Bladder Cancer Research Symposium.

PubMed

Flaig, Thomas W; Kamat, Ashish M; Hansel, Donna; Ingersoll, Molly A; Barton Grossman, H; Mendelsohn, Cathy; DeGraff, David; Liao, Joseph C; Taylor, John A

2017-07-27

The Third Annual Albert Institute Bladder Symposium was held on September 8-10th, 2016, in Denver Colorado. Participants discussed several critical topics in the field of bladder cancer: 1) Best practices for tissue analysis and use to optimize correlative studies, 2) Modeling bladder cancer to facilitate understanding and innovation, 3) Targeted therapies for bladder cancer, 4) Tumor phylogeny in bladder cancer, 5) New Innovations in bladder cancer diagnostics. Our understanding of and approach to treating urothelial carcinoma is undergoing rapid advancement. Preclinical models of bladder cancer have been leveraged to increase our basic and mechanistic understanding of the disease. With the approval of immune checkpoint inhibitors for the treatment of advanced urothelial carcinoma, the treatment approach for these patients has quickly changed. In this light, molecularly-defined subtypes of bladder cancer and appropriate pre-clinical models are now essential to the further advancement and appropriate application of these therapeutic improvements. The optimal collection and processing of clinical urothelial carcinoma tissues samples will also be critical in the development of predictive biomarkers for therapeutic selection. Technological advances in other areas including optimal imaging technologies and micro/nanotechnologies are being applied to bladder cancer, especially in the localized setting, and hold the potential for translational impact in the treatment of bladder cancer patients. Taken together, advances in several basic science and clinical areas are now converging in bladder cancer. These developments hold the promise of shaping and improving the clinical care of those with the disease.

Evaluation of delivered dose for a clinical daily adaptive plan selection strategy for bladder cancer radiotherapy.

PubMed

Lutkenhaus, Lotte J; Visser, Jorrit; de Jong, Rianne; Hulshof, Maarten C C M; Bel, Arjan

2015-07-01

To account for variable bladder size during bladder cancer radiotherapy, a daily plan selection strategy was implemented. The aim of this study was to calculate the actually delivered dose using an adaptive strategy, compared to a non-adaptive approach. Ten patients were treated to the bladder and lymph nodes with an adaptive full bladder strategy. Interpolated delineations of bladder and tumor on a full and empty bladder CT scan resulted in five PTVs for which VMAT plans were created. Daily cone beam CT (CBCT) scans were used for plan selection. Bowel, rectum and target volumes were delineated on these CBCTs, and delivered dose for these was calculated using both the adaptive plan, and a non-adaptive plan. Target coverage for lymph nodes improved using an adaptive strategy. The full bladder strategy spared the healthy part of the bladder from a high dose. Average bowel cavity V30Gy and V40Gy significantly reduced with 60 and 69ml, respectively (p<0.01). Other parameters for bowel and rectum remained unchanged. Daily plan selection compared to a non-adaptive strategy yielded similar bladder coverage and improved coverage for lymph nodes, with a significant reduction in bowel cavity V30Gy and V40Gy only, while other sparing was limited. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Bladder outlet obstruction in women: definition and characteristics.

PubMed

Groutz, A; Blaivas, J G; Chaikin, D C

2000-01-01

The prevalence of bladder outlet obstruction in women is unknown and most probably has been underestimated. Moreover, there are no standard definitions for the diagnosis of bladder outlet obstruction in women. Our study was conducted to define as well as to examine the clinical and urodynamic characteristics of bladder outlet obstruction among women referred for evaluation of voiding symptoms. Bladder outlet obstruction was defined as a persistent, low, maximum "free" flow rate of <12 mL/s in repeated non-invasive uroflow studies, combined with high detrusor pressure at a maximum flow (p(det.Q)(max) >20 cm H(2)O) during detrusor pressure-uroflow studies. A urodynamic database of 587 consecutive women identified 38 (6.5%) women with bladder outlet obstruction. The mean age of the patients was 63.9 +/- 17.5 years. The mean maximum "free" flow, voided volume, and residual urinary volume were 9.4 +/-3.9 mL/s, 144. 9 +/- 72.7 mL, and 86.1 +/- 98.8 mL, respectively. The mean p(det. Q)(max) was 37.2 +/- 19.2 cm H(2)O. Previous anti-incontinence surgery and severe genital prolapse were the most common etiologies, accounting for half of the cases. Other, less common, etiologies included urethral stricture (13%), primary bladder neck obstruction (8%), learned voiding dysfunction (5%), and detrusor external sphincter dyssynergia (5%). Symptomatology was defined as mixed obstructive and irritative in 63% of the patients, isolated irritative in 29%, and isolated obstructive in other 8%. In conclusion, bladder outlet obstruction in women appears to be more common than was previously recognized, occurring in 6.5% of our patients. Micturition symptoms relevant to bladder outlet obstruction are non-specific, and a full urodynamic evaluation is essential in making the correct diagnosis and formulating a treatment plan.

Virtual 3D bladder reconstruction for augmented medical records from white light cystoscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lurie, Kristen L.; Zlatev, Dimitar V.; Angst, Roland; Liao, Joseph C.; Ellerbee, Audrey K.

2016-02-01

Bladder cancer has a high recurrence rate that necessitates lifelong surveillance to detect mucosal lesions. Examination with white light cystoscopy (WLC), the standard of care, is inherently subjective and data storage limited to clinical notes, diagrams, and still images. A visual history of the bladder wall can enhance clinical and surgical management. To address this clinical need, we developed a tool to transform in vivo WLC videos into virtual 3-dimensional (3D) bladder models using advanced computer vision techniques. WLC videos from rigid cystoscopies (1280 x 720 pixels) were recorded at 30 Hz followed by immediate camera calibration to control for image distortions. Video data were fed into an automated structure-from-motion algorithm that generated a 3D point cloud followed by a 3D mesh to approximate the bladder surface. The highest quality cystoscopic images were projected onto the approximated bladder surface to generate a virtual 3D bladder reconstruction. In intraoperative WLC videos from 36 patients undergoing transurethral resection of suspected bladder tumors, optimal reconstruction was achieved from frames depicting well-focused vasculature, when the bladder was maintained at constant volume with minimal debris, and when regions of the bladder wall were imaged multiple times. A significant innovation of this work is the ability to perform the reconstruction using video from a clinical procedure collected with standard equipment, thereby facilitating rapid clinical translation, application to other forms of endoscopy and new opportunities for longitudinal studies of cancer recurrence.

Clinical and pathological implications of miRNA in bladder cancer

PubMed Central

Braicu, Cornelia; Cojocneanu-Petric, Roxana; Chira, Sergiu; Truta, Anamaria; Floares, Alexandru; Petrut, Bogdan; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

2015-01-01

MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20–22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer. PMID:25653521

Influence of vestibulovaginal stenosis, pelvic bladder, and recessed vulva on response to treatment for clinical signs of lower urinary tract disease in dogs: 38 cases (1990-1999).

PubMed

Crawford, Jason T; Adams, William M

2002-10-01

To determine influence of vestibulovaginal stenosis, pelvic bladder, and recessed vulva on response to treatment for clinical signs of lower urinary tract disease in dogs. Retrospective study. 38 spayed female dogs. Medical records and client follow-up were reviewed for dogs evaluated via excretory urography because of clinical signs of lower urinary tract disease. Clinical signs, results of radiography, and response to surgical or medical treatment were analyzed. Clinical signs included urinary tract infection (n = 24), urinary incontinence (20), vaginitis (11), pollakiuria or stranguria (10), and perivulvar dermatitis (4). Vaginocystourethrographic findings included vestibulovaginal stenosis (n = 28), pelvic bladder (17), and ureteritis or pyelonephritis (4). Ten dogs had a vestibulovaginal ratio of < 0.20 (severe stenosis), 9 dogs had a ratio of 0.20 to 0.25 (moderate stenosis), 9 dogs had a ratio of 0.26 to 0.35 (mild stenosis), and 10 dogs had a ratio of > 0.35 (anatomically normal). Lower urinary tract infection, incontinence, and pelvic bladder were not associated with response to treatment for recessed vulva. Vestibulovaginal stenosis with a ratio < 0.20 was significantly associated negatively with response to treatment. Dogs without severe vestibulovaginal stenosis that received vulvoplasty for a recessed vulva responded well to treatment. Vestibulovaginal stenosis is likely an important factor in dogs with vestibulovaginal ratio < 0.20. Vaginectomy or resection and anastomosis should be considered in dogs with severe vestibulovaginal stenosis and signs of lower urinary tract disease.

Urgency in overactive bladder: translating experimental data into clinical practice.

PubMed

Wyndaele, Jean-Jacques; De Wachter, Stefan

2008-05-01

In overactive bladder (OAB) syndrome, urgency is considered to be the key symptom that generates or affects all other symptoms. Urgency has been defined by the latest International Continence Society (ICS) terminology report as "the complaint of a sudden compelling desire to pass urine, which is difficult to defer". This definition has caused some debate and a final terminology has not yet been agreed upon. However, many would agree that urgency is different from urge when describing bladder sensation, and "urgency" has become one of the leading topics in OAB diagnosis and a primary endpoint in evaluation of treatment. Despite the many potential targets for pharmacological treatment, few drugs other than antimuscarinic agents have passed the proof-of-concept stage. There are multiple mechanisms, some proven in concept but more theoretical, by which a pharmacological agent may facilitate lower urinary tract filling/urine storage, bladder sensation and bladder emptying, although organ selectivity is often a problem. Oxybutynin, tolterodine, darifenacin, solifenacin and trospium have shown superiority to placebo, with a different incidence of side effects among the different drugs. Larger randomized, controlled trials in clinical settings are required to further establish the role of these medications in the management of urgency and OAB syndrome. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer.

PubMed

Latz, Stefan; Umbach, Tine; Goltz, Diane; Kristiansen, Glen; Müller, Stephan C; Ellinger, Jörg

2016-01-01

Yes-associated protein 1 (YAP1), the nuclear effector of the Hippo pathway, plays an important role in many tumor entities. We evaluated staining and clinical significance of YAP1 and phosphorylated YAP1 (pYAP1) in urothelial bladder cancer (BCA). We used a tissue micorarray with samples of patients with muscle-invasive bladder cancer (MIBC, n = 192), non-muscle-invasive bladder cancer (NMIBC, n = 192) and normal urothelial bladder tissue (CTRL, n = 38) to determine the immunhistochemical staining of YAP1 and pYAP1. Cytoplasmatic and nuclear levels were evaluated. The t test was used for comparative analysis. Overall survival and progression-free survival were evaluated by Kaplan-Meier estimates and the Cox proportional hazard regression model. Nuclear YAP1 as well as cytoplasmatic pYAP1 levels were higher in CTRL than in BCA, whereby both--NMIBC and MIBC--had lower levels than CTRL. Among patients with MIBC, cytoplasmatic YAP1 and pYAP1 staining decreased with advanced stage. YAP1 and pYAP1 staining did not correlate with the recurrence rate, progression-free, cancer-specific or overall survival. Immunhistochemical staining and subcellular localization of YAP1 and pYAP1 are different for BCA, NMIBC, MIBC and CTRL, indicating that the Hippo pathway is involved in urothelial carcinogenesis. © 2015 S. Karger AG, Basel.

Current management of overactive bladder.

PubMed

Cartwright, Rufus; Renganathan, Arasee; Cardozo, Linda

2008-10-01

The concept of overactive bladder has helped us address the problem of urgency and urge incontinence from a symptomatic perspective. In this review, we provide a critical summary of clinically relevant recent publications, focusing in particular on advances in our understanding of assessment methods and therapeutic interventions for overactive bladder in women. According to current definitions, the prevalence of overactive bladder in western nations is now estimated as 13.0%. Although the prevalence increases with age, the symptoms of overactive bladder may follow a relapsing and remitting course. There has been a proliferation of validated symptom and quality of life measures and increasing sophistication in the analysis of bladder diaries. The role of urodynamics in the evaluation of urgency remains uncertain, with many trials showing limited benefit as a preoperative investigation. Fluid restriction and bladder retraining remain important first-line interventions. Many new anticholinergic medications have been licensed, with limited benefits compared with existing preparations. Intravesical botulinum toxin has become a popular alternative for patients who fail oral therapies. Although there have been few important therapeutic innovations, recent publications have led to greater sophistication in assessment methods and a clearer understanding of the role of existing interventions.

Gall bladder mucoceles and their association with endocrinopathies in dogs: a retrospective case-control study.

PubMed

Mesich, M L L; Mayhew, P D; Paek, M; Holt, D E; Brown, D C

2009-12-01

To investigate the relationship between endocrinopathies and diagnosis of gall bladder mucocele in dogs via a retrospective case-control study. Records of 78 dogs with a surgical or ultrasonographic diagnosis of gall bladder mucocele were examined for the presence or absence of hyperadrenocorticism, hypothyroidism and diabetes mellitus. Two age- and breed-matched controls for each gall bladder mucocele dog (156 total control dogs) were examined for the same concurrent diseases. A matched case-control analysis was performed using conditional logistic regression. The odds of mucocele in dogs with hyperadrenocorticism were 29 times that of dogs without hyperadrenocorticism (P=0.001; 95 per cent CI 3.8, 219.9). No difference was found between dogs with and without diabetes mellitus. Although a significant association was found between gall bladder mucocele and hypothyroidism, potential observation bias was also identifi ed. Hyperadrenocorticoid dogs that were presented for acute illness with laboratory evidence of hepatobiliary disease should undergo evaluation for the presence of a biliary mucocele. Dogs diagnosed with a gall bladder mucocele should be screened for concurrent hyperadrenocorticism if clinical suspicion exists.

Image-guided photo-therapeutic nanoporphyrin synergized HSP90 inhibitor in patient-derived xenograft bladder cancer model.

PubMed

Long, Qilai; Lin, Tzu-Yin; Huang, Yee; Li, Xiaocen; Ma, Ai-Hong; Zhang, Hongyong; Carney, Randy; Airhart, Susan; Lam, Kit S; deVere White, Ralph W; Pan, Chong-Xian; Li, Yuanpei

2018-04-01

Photodynamic therapy is a promising and effective non-invasive therapeutic approach for the treatment of bladder cancers. Therapies targeting HSP90 have the advantage of tumor cell selectivity and have shown great preclinical efficacy. In this study, we evaluated a novel multifunctional nanoporphyrin platform loaded with an HSP90 inhibitor 17AAG (NP-AAG) for use as a multi-modality therapy against bladder cancer. NP-AAG was efficiently accumulated and retained at bladder cancer patient-derived xenograft (PDX) over 7 days. PDX tumors could be synergistically eradicated with a single intravenous injection of NP-AAG followed by multiple light treatments within 7 days. NP-AAG mediated treatment could not only specifically deliver 17AAG and produce heat and reactive oxygen species, but also more effectively inhibit essential bladder cancer essential signaling molecules like Akt, Src, and Erk, as well as HIF-1α induced by photo-therapy. This multifunctional nanoplatform has high clinical relevance and could dramatically improve management for bladder cancers with minimal toxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

Antitumor effects of deracoxib treatment in 26 dogs with transitional cell carcinoma of the urinary bladder.

PubMed

McMillan, Sarah K; Boria, Pedro; Moore, George E; Widmer, William R; Bonney, Patty L; Knapp, Deborah W

2011-10-15

OBJECTIVE-To evaluate the antitumor activity and toxic effects of deracoxib, a selective cyclooxygenase-2 inhibitor, in dogs with transitional cell carcinoma (TCC) of the urinary bladder. DESIGN-Clinical trial. Animals-26 client-owned dogs with naturally occurring, histologically confirmed, measurableTCC of the urinary bladder. PROCEDURES-Dogs were treated PO with deracoxib at a dosage of 3 mg/kg/d (1.36 mg/lb/d) as a single-agent treatment for TCC. Tumor response was assessed via radiography, abdominal ultrasonography, and ultrasonographic mapping of urinary bladder masses. Toxic effects of deracoxib administration in dogs were assessed through clinical observations and hematologic and biochemical analyses. RESULTS-Of 24 dogs for which tumor response was assessed, 4 (17%) had partial remission, 17 (71%) had stable disease, and 3 (13%) had progressive disease; initial response could not be assessed in 2 of 26 dogs. The median survival time was 323 days. Median time to progressive disease was 133 days. Renal, hepatic, and gastrointestinal abnormalities attributed to deracoxib administration were noted in 4% (1/26), 4% (1/26), and 19% (5/26) of dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE-Results indicated that deracoxib was generally well tolerated by dogs and had antitumor activity against TCC.

Human urinary bladder regeneration through tissue engineering - an analysis of 131 clinical cases.

PubMed

Pokrywczynska, Marta; Adamowicz, Jan; Sharma, Arun K; Drewa, Tomasz

2014-03-01

Replacement of urinary bladder tissue with functional equivalents remains one of the most challenging problems of reconstructive urology over the last several decades. The gold standard treatment for urinary diversion after radical cystectomy is the ileal conduit or neobladder; however, this technique is associated with numerous complications including electrolyte imbalances, mucus production, and the potential for malignant transformation. Tissue engineering techniques provide the impetus to construct functional bladder substitutes de novo. Within this review, we have thoroughly perused the literature utilizing PubMed in order to identify clinical studies involving bladder reconstruction utilizing tissue engineering methodologies. The idea of urinary bladder regeneration through tissue engineering dates back to the 1950s. Many natural and synthetic biomaterials such as plastic mold, gelatin sponge, Japanese paper, preserved dog bladder, lyophilized human dura, bovine pericardium, small intestinal submucosa, bladder acellular matrix, or composite of collagen and polyglycolic acid were used for urinary bladder regeneration with a wide range of outcomes. Recent progress in the tissue engineering field suggest that in vitro engineered bladder wall substitutes may have expanded clinical applicability in near future but preclinical investigations on large animal models with defective bladders are necessary to optimize the methods of bladder reconstruction by tissue engineering in humans.

Ultrasound Thickness of Bladder Wall in Continent and Incontinent Women and Its Correlation with Cystometry

PubMed Central

Otsuki, Edney Norio; Oliveira, Emerson; Sartori, Marair Gracio Ferreira; Girão, Manoel João Batista Castelo; Jármy-Di Bella, Zsuzsanna Ilona Katalin

2014-01-01

Objective. To compare bladder wall thickness in two kinds of urinary incontinent women—stress urinary incontinence (SUI) and overactive bladder (OAB) with urodynamic detrusor overactivity (DO), and to compare them with continent patients by ultrasound, also, correlate with cystometric results in incontinent women. Methods. 91 women were divided into the following groups: continent (n = 31), SUI (n = 30), and DO (n = 30) groups after clinical evaluation and urodynamic test (only in incontinent women). Transvaginal ultrasound was performed to the bladder wall thickness (BWT) measurement. The mean of BWT was calculated and data were analyzed with ANOVA and Turkey's multiple comparison tests. Pearson's correlation coefficient (r) was used to compare two variables. Receiver operating characteristic (ROC) curve was performed to study BWT as a diagnostic parameter. Results. BWT in DO group was significantly higher than that in the other groups (P < 0.005). A moderate positive correlation was found between BWT and maximum bladder pressure during involuntary bladder contraction. There was no difference in BWT between SUI and continent groups. DO group had lower first desire to void and cystometric capacity. Maximum bladder pressure at detrusor contraction had a moderate positive correlation with BWT. The ROC revealed an area under the curve of 0.962 (95% CI, 0.90–1.01). Conclusions. DO patients have increased bladder wall thickness, lower first desire to void, and lower cystometric capacity. There was a moderate correlation between BWT and maximum bladder pressure during involuntary bladder contraction. PMID:25538959

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

PubMed

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.

Image guided adaptive external beam radiation therapy for cervix cancer: Evaluation of a clinically implemented plan-of-the-day technique.

PubMed

Buschmann, Martin; Majercakova, Katarina; Sturdza, Alina; Smet, Stephanie; Najjari, Dina; Daniel, Michaela; Pötter, Richard; Georg, Dietmar; Seppenwoolde, Yvette

2017-10-12

Radiotherapy for cervix cancer is challenging in patients exhibiting large daily changes in the pelvic anatomy, therefore adaptive treatments (ART) have been proposed. The aim of this study was the clinical implementation and subsequent evaluation of plan-of-the-day (POTD)-ART for cervix cancer in supine positioning. The described workflow was based on standard commercial equipment and current quality assurance (QA) methods. A POTD strategy, which employs a VMAT plan library consisting of an empty bladder plan, a full bladder plan and a motion robust backup plan, was developed. Daily adaption was guided by cone beam computed tomography (CBCT) imaging after which the best plan from the library was selected. Sixteen patients were recruited in a clinical study on ART, for nine POTD was applied due to their large organ motion derived from two computed tomography (CT) scans with variable bladder filling. All patients were treated to 45Gy in 25 fractions. Plan selection frequencies over the treatment course were analyzed. Daily doses in the rectum, bladder and cervix-uterus target (CTV-T) were derived and compared to a simulated non-adapted treatment (non-ART), which employed the robust plan for each fraction. Additionally, the adaption consistency was determined by repeating the plan selection procedure one month after treatment by a group of experts. ART-specific QA methods are presented. 225 ART fractions with CBCTs were analyzed. The empty bladder plan was delivered in 49% of the fractions in the first treatment week and this number increased to 78% in the fifth week. The daily coverage of the CTV-T was equivalent between ART and the non-ART simulation, while the daily total irradiated volume V42.75Gy (95% of prescription dose) was reduced by a median of 87cm 3 . The median delivered V42.75Gy was 1782cm 3 . Daily delivered doses (V42.75Gy, V40Gy, V30G) to the organs at risk were statistically significantly reduced by ART, with a median difference in daily V42.75Gy in rectum and bladder of 3.2% and 1.1%, respectively. The daily bladder V42.75Gy and V40Gy were decreased by more than 10 percent points in 30% and 24% of all fractions, respectively, through ART. The agreement between delivered plans and retrospective expert-group plan selections was 84%. A POTD-ART technique for cervix cancer was successfully and safely implemented in the clinic and evaluated. Improved normal tissue sparing compared to a simulated non-ART treatment could be demonstrated. Future developments should focus on commercial automated software solutions to allow for a more widespread adoption and to keep the increased workload manageable. Copyright © 2017. Published by Elsevier GmbH.

A Randomized Comparative Study Evaluating Various Cough Stress Tests and 24-Hour Pad Test with Urodynamics in the Diagnosis of Stress Urinary Incontinence.

PubMed

Henderson, Joseph W; Kane, Sarah M; Mangel, Jeffrey M; Kikano, Elias G; Garibay, Jorge A; Pollard, Robert R; Mahajan, Sangeeta T; Debanne, Sara M; Hijaz, Adonis K

2018-06-01

The cough stress test is a common and accepted tool to evaluate stress urinary incontinence but there is no agreement on how the test should be performed. We assessed the diagnostic ability of different cough stress tests performed when varying patient position and bladder volume using urodynamic stress urinary incontinence as the gold standard. The 24-hour pad test was also evaluated. We recruited women who presented to specialty outpatient clinics with the complaint of urinary incontinence and who were recommended to undergo urodynamic testing. A total of 140 patients were randomized to 4 cough stress test groups, including group 1-a comfortably full bladder, group 2-an empty bladder, group 3- a bladder infused with 200 cc saline and group 4-a bladder filled to half functional capacity. The sequence of standing and sitting was randomly assigned. The groups were compared by 1-way ANOVA or the generalized Fisher exact test. The κ statistic was used to evaluate agreement between the sitting and standing positions. The 95% CIs of sensitivity and specificity were calculated using the Wilson method. ROC analysis was done to evaluate the performance of the 24-hour pad test. The cough stress test performed with a bladder filled to half functional capacity was the best performing test with 83% sensitivity and 90% specificity. There was no statistically significant evidence that the sensitivity or specificity of 1 cough stress test differed from that of the others. The pad test had no significant predictive ability to diagnose urodynamic stress urinary incontinence (AUC 0.60, p = 0.08). Cough stress tests were accurate to diagnose urodynamic stress urinary incontinence. The 24-hour pad test was not predictive of urodynamic stress urinary incontinence and not helpful when used in conjunction with the cough stress test. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Wolfram (DIDMOAD) syndrome: a multidisciplinary clinical study in nine Turkish patients and review of the literature.

PubMed

Simsek, E; Simsek, T; Tekgül, S; Hosal, S; Seyrantepe, V; Aktan, G

2003-01-01

To study Wolfram syndrome (WFS) with multidisciplinary consultations and compare the results with the literature. Nine patients fulfilled the ascertainment criteria of WFS (insulin-dependent diabetes mellitus and optic atrophy). All patients were evaluated by the departments of paediatrics, ophthalmology, audiology, urology and medical biology. The earliest manifestation of WFS was insulin-dependent diabetes mellitus (at a median age of 6.9 y), followed by optic atrophy (8.9 y), diabetes insipidus (10.2 y) and deafness (10.5 y). Short stature was found in five cases, delayed puberty in two cases and hypergonadotropic hypogonadism in one case. Audiography disclosed hearing loss at high frequency in all patients (100%), but only five patients had clinical subjective hearing problems. Intravenous pyelography revealed hydroureteronephrosis in eight patients. Urodynamics revealed a normal bladder in only one patient. Three patients had a low-capacity, low-compliance bladder, detrusor external sphincteric dyssynergia and emptying problem, while five had an atonic bladder. Ocular findings were optic atrophy, low visual acuity and colour vision defects. Visual field tests revealed concentric and/or peripheral diminution in five patients. Visual evoked potentials were abnormal (reduced amplitude to both flash and pattern stimulation) in seven patients. Cranial magnetic resonance imaging showed mild or moderate atrophy of the optic nerves, chiasm, cerebellum, basal ganglia and brainstem in six patients; there was a partially empty sella in one case. There was no evidence of mitochondrial tRNA(Leu) (UUR) A to G (nucleotide 3243) mutation. Wolfram syndrome should be evaluated in a multidisciplinary manner. Some specific and dynamic tests are necessary to make a more precise estimate of the prevalence and median age of the components of WFS. Short stature is a common feature in WFS. Hypogonadism may be hypogonadotropic or hypergonadotropic. Bladder dysfunction does not always present as a large atonic bladder in WFS. A low-capacity, high-pressure bladder with sphincteric dyssynergia is also common.

A Prospective Blinded Evaluation of Urine-DNA Testing for Detection of Urothelial Bladder Carcinoma in Patients with Gross Hematuria.

PubMed

Dahmcke, Christina M; Steven, Kenneth E; Larsen, Louise K; Poulsen, Asger L; Abdul-Al, Ahmad; Dahl, Christina; Guldberg, Per

2016-12-01

Retrospective studies have provided proof of principle that bladder cancer can be detected by testing for the presence of tumor DNA in urine. We have conducted a prospective blinded study to determine whether a urine-based DNA test can replace flexible cystoscopy in the initial assessment of gross hematuria. A total of 475 consecutive patients underwent standard urological examination including flexible cystoscopy and computed tomography urography, and provided urine samples immediately before (n=461) and after (n=444) cystoscopy. Urine cells were collected using a filtration device and tested for eight DNA mutation and methylation biomarkers. Clinical evaluation identified 99 (20.8%) patients with urothelial bladder tumors. With this result as a reference and based on the analysis of all urine samples, the DNA test had a sensitivity of 97.0%, a specificity of 76.9%, a positive predictive value of 52.5%, and a negative predictive value of 99.0%. In three patients with a positive urine-DNA test without clinical evidence of cancer, a tumor was detected at repeat cystoscopy within 16 mo. Our results suggest that urine-DNA testing can be used to identify a large subgroup of patients with gross hematuria in whom cystoscopy is not required. We tested the possibility of using a urine-based DNA test to check for bladder cancer in patients with visible blood in the urine. Our results show that the test efficiently detects bladder cancer and therefore may be used to greatly reduce the number of patients who would need to undergo cystoscopy. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of bladder carcinoma.

PubMed

Kamat, Ashish M; Bellmunt, Joaquim; Galsky, Matthew D; Konety, Badrinath R; Lamm, Donald L; Langham, David; Lee, Cheryl T; Milowsky, Matthew I; O'Donnell, Michael A; O'Donnell, Peter H; Petrylak, Daniel P; Sharma, Padmanee; Skinner, Eila C; Sonpavde, Guru; Taylor, John A; Abraham, Prasanth; Rosenberg, Jonathan E

2017-08-15

The standard of care for most patients with non-muscle-invasive bladder cancer (NMIBC) is immunotherapy with intravesical Bacillus Calmette-Guérin (BCG), which activates the immune system to recognize and destroy malignant cells and has demonstrated durable clinical benefit. Urologic best-practice guidelines and consensus reports have been developed and strengthened based on data on the timing, dose, and duration of therapy from randomized clinical trials, as well as by critical evaluation of criteria for progression. However, these reports have not penetrated the community, and many patients do not receive appropriate therapy. Additionally, several immune checkpoint inhibitors have recently been approved for treatment of metastatic disease. The approval of immune checkpoint blockade for patients with platinum-resistant or -ineligible metastatic bladder cancer has led to considerations of expanded use for both advanced and, potentially, localized disease. To address these issues and others surrounding the appropriate use of immunotherapy for the treatment of bladder cancer, the Society for Immunotherapy of Cancer (SITC) convened a Task Force of experts, including physicians, patient advocates, and nurses, to address issues related to patient selection, toxicity management, clinical endpoints, as well as the combination and sequencing of therapies. Following the standard approach established by the Society for other cancers, a systematic literature review and analysis of data, combined with consensus voting was used to generate guidelines. Here, we provide a consensus statement for the use of immunotherapy in patients with bladder cancer, with plans to update these recommendations as the field progresses.

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

PubMed

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.

Portable Bladder Ultrasound

PubMed Central

2006-01-01

Executive Summary Objective The aim of this review was to assess the clinical utility of portable bladder ultrasound. Clinical Need: Target Population and Condition Data from the National Population Health Survey indicate prevalence rates of urinary incontinence are 2.5% in women and 1.4 % in men in the general population. Prevalence of urinary incontinence is higher in women than men and prevalence increases with age. Identified risk factors for urinary incontinence include female gender, increasing age, urinary tract infections (UTI), poor mobility, dementia, smoking, obesity, consuming alcohol and caffeine beverages, physical activity, pregnancy, childbirth, forceps and vacuum-assisted births, episiotomy, abdominal resection for colorectal cancer, and hormone replacement therapy. For the purposes of this review, incontinence populations will be stratified into the following; the elderly, urology patients, postoperative patients, rehabilitation settings, and neurogenic bladder populations. Urinary incontinence is defined as any involuntary leakage of urine. Incontinence can be classified into diagnostic clinical types that are useful in planning evaluation and treatment. The major types of incontinence are stress (physical exertion), urge (overactive bladder), mixed (combined urge and stress urinary incontinence), reflex (neurological impairment of the central nervous system), overflow (leakage due to full bladder), continuous (urinary tract abnormalities), congenital incontinence, and transient incontinence (temporary incontinence). Postvoid residual (PVR) urine volume, which is the amount of urine in the bladder immediately after urination, represents an important component in continence assessment and bladder management to provide quantitative feedback to the patient and continence care team regarding the effectiveness of the voiding technique. Although there is no standardized definition of normal PVR urine volume, measurements greater than 100 mL to 150 mL are considered an indication for urinary retention, requiring intermittent catheterization, whereas a PVR urine volume of 100 mL to 150 mL or less is generally considered an acceptable result of bladder training. Urinary retention has been associated with poor outcomes including UTI, bladder overdistension, and higher hospital mortality rates. The standard method of determining PVR urine volumes is intermittent catheterization, which is associated with increased risk of UTI, urethral trauma and discomfort. The Technology Being Reviewed Portable bladder ultrasound products are transportable ultrasound devices that use automated technology to register bladder volume digitally, including PVR volume, and provide three-dimensional images of the bladder. The main clinical use of portable bladder ultrasound is as a diagnostic aid. Health care professionals (primarily nurses) administer the device to measure PVR volume and prevent unnecessary catheterization. An adjunctive use of the bladder ultrasound device is to visualize the placement and removal of catheters. Also, portable bladder ultrasound products may improve the diagnosis and differentiation of urological problems and their management and treatment, including the establishment of voiding schedules, study of bladder biofeedback, fewer UTIs, and monitoring of potential urinary incontinence after surgery or trauma. Review Strategy To determine the effectiveness and clinical utility of portable bladder ultrasound as reported in the published literature, the Medical Advisory Secretariat used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases. Nonsystematic reviews, nonhuman studies, case reports, letters, editorials, and comments were excluded. Summary of Findings Of the 4 included studies that examined the clinical utility of portable bladder ultrasound in the elderly population, all found the device to be acceptable. One study reported that the device underestimated catheterized bladder volume In patients with urology problems, 2 of the 3 studies concerning portable bladder ultrasound found the device acceptable to use. However, one study did not find the device as accurate for small PVR volume as for catheterization and another found that the device overestimated catheterized bladder volume. In the remaining study, the authors reported that when the device’s hand-held ultrasound transducers (scanheads) were aimed improperly, bladders were missed, or lateral borders of bladders were missed resulting in partial bladder volume measurements and underestimation of PVR measurements. They concluded that caution should be used in interpreting PVR volume measured by portable bladder ultrasound machines and that catheterization may be the preferred assessment modality if an accurate PVR measurement is necessary. All 3 studies with post-operative populations found portable bladder ultrasound use to be reasonably acceptable. Two studies reported that the device overestimated catheter-derived bladder volumes, one by 7% and the other by 21 mL. The third study reported the opposite, that the device underestimated catheter bladder volume by 39 mL but that the results remained acceptable In rehabilitation settings, 2 studies found portable bladder ultrasound to underestimate catheter-derived bladder volumes; yet, both authors concluded that the mean errors were within acceptable limits. In patients with neurogenic bladder problems, 2 studies found portable bladder ultrasound to be an acceptable alternative to catheterization despite the fact that it was not as accurate as catheterization for obtaining bladder volumes. Lastly, examinations concerning avoidance of negative health outcomes showed that, after use of the portable bladder ultrasound, unnecessary catheterizations and UTIs were decreased. Unnecessary catheterizations avoided ranged from 16% to 47% in the selected articles. Reductions in UTI ranged from 38% to 72%. In sum, all but one study advocated the use of portable bladder ultrasound as an alternative to catheterization. Economic Analysis An economic analysis estimating the budget-impact of BladderScan in complex continuing care facilities was completed. The analysis results indicated a $192,499 (Cdn) cost-savings per year per facility and a cost-savings of $2,887,485 (Cdn) for all 15 CCC facilities. No economic analysis was completed for long-term care and acute care facilities due to lack of data. Considerations for Policy Development Rapid diffusion of portable bladder ultrasound technology is expected. Recently, the IC5 project on improving continence care in Ontario’s complex continuing care centres piloted portable bladder ultrasound at 12 sites. Preliminary results were promising. Many physicians and health care facilities already have portable bladder ultrasound devices. However, portable bladder ultrasound devices for PVR measurement are not in use at most health care facilities in Ontario and Canada. The Verathon Corporation (Bothell, Wisconsin, United States), which patents BladderScan, is the sole licensed manufacturer of the portable bladder ultrasound in Canada. Field monopoly may influence the rising costs of portable bladder ultrasound, particularly when faced with rapid expansion of the technology. Several thousand residents of Ontario would benefit from portable bladder ultrasound. The number of residents of Ontario that would benefit from the technology is difficult to quantify, because the incidence and prevalence of incontinence are grossly under-reported. However, long-term care and complex continuing care institutions would benefit greatly from portable bladder ultrasound, as would numerous rehabilitation units, postsurgical care units, and urology clinics. The cost of the portable bladder ultrasound devices ranges from $17,698.90 to $19,565.95 (Cdn) (total purchase price per unit as quoted by the manufacturer). Additional training packages, batteries and battery chargers, software, gel pads, and yearly warranties are additional costs. Studies indicate that portable bladder ultrasound is a cost-effective technology, because it avoids costs associated with catheterization equipment, saves nursing time, and reduces catheter-related complications and UTIs. The use of portable bladder ultrasound device will affect the patient directly in terms of health outcomes. Its use avoids the trauma related to the urinary tract that catheterization inflicts, and does not result in UTIs. In addition, patients prefer it, because it preserves dignity and reduces discomfort. PMID:23074481

Bladder Mucosal Graft Vaginoplasty: A Case Report.

PubMed

Chiaramonte, Cinzia; Vestri, Elettra; Tripi, Flavia; Giannone, Antonino Giulio; Cimador, Marcello; Cataliotti, Ferdinando

2018-06-18

Female vaginoplasty reconstruction, by choice, is usually performed with adjacent tissue. However in some clinical conditions such as high urogenital confluence sinus, cloacal malformation with extreme vaginal hypoplasia, local tissue may not be available. When vaginal replacement is performed in pediatric patients intestinal segments is preferred to non-operative procedures that require continuative dilations. However mucus production, malignant transformation risk and diversion colitis are important side effects. We present a nouvel technique for vaginoplasty in a female child presenting with an isolated urogenital sinus malformation without virilization. The patient at 20 months underwent vaginoplasty using tubularized bladder mucosal graft. Surgical procedure was devoid of complications. Pubertal development occurred at age of 15. She underwent regular follow up until 18 years of age. At this age we performed clinical evaluation: absence of vaginal introitus stenosis and good cosmetic results were observed. Then she underwent vaginoscopy with multiple biopsies. Pathology examination of the bladder mucosal graft evidenced a normal structure of the mucosa, with a stratified squamous epithelium. Different techniques are taken into account for vaginal reconstruction according to the severity and to the type of malformation. We describe the use of bladder mucosal graft with favorable results after long term follow-up. Copyright © 2018. Published by Elsevier Inc.

A Convex Hull-Based New Metric for Quantification of Bladder Wall Irregularity in Pediatric Patients With Congenital Anomalies of the Kidney and Urinary Tract.

PubMed

Stember, Joseph N; Newhouse, Jeffrey; Behr, Gerald; Alam, Shumyle

2017-11-01

Early identification and quantification of bladder damage in pediatric patients with congenital anomalies of the kidney and urinary tract (CAKUT) is crucial to guiding effective treatment and may affect the eventual clinical outcome, including progression of renal disease. We have developed a novel approach based on the convex hull to calculate bladder wall trabecularity in pediatric patients with CAKUT. The objective of this study was to test whether our approach can accurately predict bladder wall irregularity. Twenty pediatric patients, half with renal compromise and CAKUT and half with normal renal function, were evaluated. We applied the convex hull approach to calculate T, a metric proposed to reflect the degree of trabeculation/bladder wall irregularity, in this set of patients. The average T value was roughly 3 times higher for diseased than healthy patients (0.14 [95% confidence interval, 0.10-0.17] versus 0.05 [95% confidence interval, 0.03-0.07] for normal bladders). This disparity was statistically significant (P < .01). We have demonstrated that a convex hull-based procedure can measure bladder wall irregularity. Because bladder damage is a reversible precursor to irreversible renal parenchymal damage, applying such a measure to at-risk pediatric patients can help guide prompt interventions to avert disease progression. © 2017 by the American Institute of Ultrasound in Medicine.

Elective bladder-sparing treatment for muscle invasive bladder cancer.

PubMed

Lendínez-Cano, G; Rico-López, J; Moreno, S; Fernández Parra, E; González-Almeida, C; Camacho Martínez, E

2014-01-01

Radical cystectomy is the standard treatment for localised muscle invasive bladder cancer (MIBC). We offer a bladder-sparing treatment with TURB +/- Chemotherapy+Radiotherapy to selected patients as an alternative. We analyze, retrospectively, 30 patients diagnosed with MIBC from March 1991 to October 2010. The mean age was 62.7 years (51-74). All patients were candidates for a curative treatment, and underwent strict selection criteria: T2 stage, primary tumor, solitary lesion smaller than 5cm with a macroscopic disease-free status after TURB, negative random biopsy without hydronephrosis. Staging CT evaluation was normal. Restaging TURB or tumor bed biopsy showed a disease-free status or microscopic muscle invasion. 14 patients underwent TURB alone, 13 TURB+Chemotherapy and 3 TURB+Chemotherapy+Radiotherapy. The mean follow up was 88.7 months (19-220). 14 patients remained disease free (46.6%), 10 had recurrent non-muscle invasive bladder cancer (33%). 81.3% complete clinical response. 71% bladder preserved at 5-years. Overall, 5-years survival rate was 79% and 85% cancer-specific survival rate. Although radical cystectomy is the standard treatment for localised MIBC, in strictly selected cases, bladder-sparing treatment offers an alternative with good long term results. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Masaharu; Koga, Fumitaka, E-mail: f-koga@cick.jp; Yoshida, Soichiro

2014-10-01

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 TURBTmore » 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-sparing protocol. ERBB 2-targeting treatment may improve the outcomes of such patients.« less

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.

PubMed

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 of such patients. Copyright © 2014 Elsevier Inc. All rights reserved.

The impact of bladder neck mucosal eversion during open radical prostatectomy on bladder neck stricture and urinary extravasation.

PubMed

Schoeppler, Gita M; Zaak, Dirk; Clevert, Dirk-Andre; Schuhmann, Petra; Reich, Oliver; Seitz, Michael; Khoder, Wael Y; Staehler, Michael; Stief, Christian G; Buchner, Alexander

2012-10-01

To determine whether the bladder neck mucosal eversion (BNM-eversion) during radical retropubic prostatectomy (RRP) reduces the risk of bladder neck stricture (BNS) and of peri-anastomotic extravasation (PAE) in postoperative cystography. Two hundred and eleven patients with clinically localized prostate cancer underwent RRP and were prospectively randomized into patients with BNM-eversion (group I) and without BNM-eversion (group II). All patients underwent an evaluation of PAE by retrograde cystography on postoperative day 8. We assessed BNS after 6 months. Ninety-two patients with and 113 patients without BNM-eversion were included. There was no significant difference in baseline characteristics, including age, TNM-classification, Gleason score, PSA, prostate volume, and blood loss in both groups. A complete follow-up of 6 months for BNS was available for 188 patients (89.1 %). Sixteen BNS out of 188 patients were recorded, 4.7 % (n = 4) in group I and 11.7 % (n = 12) in group II (p = 0.09). Data from 205 out of 211 patients were available for the evaluation of the extravasation by cystography. Peri-anastomotic extravasation was detectable in 11.96 %, (11/205) in group I and in 21.24 % (24/205) in group II (p = 0.08). BNM-eversion does not have a positive influence on the prevention of bladder neck strictures. Peri-anastomotic extravasation detected by cystography does not correlate with a formation of bladder neck stricture.

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

PubMed Central

Lerner, Seth P.; Bajorin, Dean F.; Dinney, Colin P.; Efstathiou, Jason A.; Groshen, Susan; Hahn, Noah M.; Hansel, Donna; Kwiatkowski, David; O’Donnell, Michael; Rosenberg, Jonathan; Svatek, Robert; Abrams, Jeffrey S.; Al-Ahmadie, Hikmat; Apolo, Andrea B.; Bellmunt, Joaquim; Callahan, Margaret; Cha, Eugene K.; Drake, Charles; Jarow, Jonathan; Kamat, Ashish; Kim, William; Knowles, Margaret; Mann, Bhupinder; Marchionni, Luigi; McConkey, David; McShane, Lisa; Ramirez, Nilsa; Sharabi, Andrew; Sharpe, Arlene H.; Solit, David; Tangen, Catherine M.; Amiri, Abdul Tawab; Van Allen, Eliezer; West, Pamela J.; Witjes, J. A.; Quale, Diane Zipursky

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 NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations of BCG or radiotherapy and immunomodulatory agents in patients who recur after induction BCG (BCG failure). PMID:27376138

Towards nonionizing photoacoustic cystography

NASA Astrophysics Data System (ADS)

Kim, Chulhong; Jeon, Mansik; Wang, Lihong V.

2012-02-01

Normally, urine flows down from kidneys to bladders. Vesicoureteral reflux (VUR) is the abnormal flow of urine from bladders back to kidneys. VUR commonly follows urinary tract infection and leads to renal infection. Fluoroscopic voiding cystourethrography and direct radionuclide voiding cystography have been clinical gold standards for VUR imaging, but these methods are ionizing. Here, we demonstrate the feasibility of a novel and nonionizing process for VUR mapping in vivo, called photoacoustic cystography (PAC). Using a photoacoustic (PA) imaging system, we have successfully imaged a rat bladder filled with clinically being used methylene blue dye. An image contrast of ~8 was achieved. Further, spectroscopic PAC confirmed the accumulation of methylene blue in the bladder. Using a laser pulse energy of less than 1 mJ/cm2, bladder was clearly visible in the PA image. Our results suggest that this technology would be a useful clinical tool, allowing clinicians to identify bladder noninvasively in vivo.

Biomarkers in lower urinary tract symptoms/overactive bladder: a critical overview.

PubMed

Antunes-Lopes, Tiago; Cruz, Célia D; Cruz, Francisco; Sievert, Karl D

2014-07-01

Biomarkers constitute objectively measurable characteristics that can be evaluated as indicators of physiological and pathogenic processes and might be used as diagnostic, prognostic or predictive tools in clinical care. This review examines the availability of biomarkers to treat the dynamic and complex symptoms of overactive bladder (OAB). OAB biomarkers may contribute to reveal the origin of storage symptoms in otherwise healthy individuals. The research encompassing the changes that occur in the bladder or in the peripheral (and central) nervous system might be determined through blood or urinary molecules (neurotrophins, ATP, prostaglandins, C-reactive protein and cytokines) or the measurement of events occurring in the bladder wall (bladder wall or detrusor wall thickness, oxyhemoglobin and deoxyhemoglobin concentration). These biomarkers might contribute to a better understanding of the pathophysiologic mechanisms underlying OAB. The word biomarker to name all the parameters described above, from bladder wall thickness to urinary molecules, has been introduced to call the attention to a field wherein objective noninvasive parameters were nonexistent. OAB treatment based on a biomarker, in comparison to the treatment based on a diagnosis made from a careful history and exclusion of urinary tract infection, is not supported by current literature.

Male bladder outlet obstruction: Time to re-evaluate the definition and reconsider our diagnostic pathway? ICI-RS 2015.

PubMed

Rademakers, Kevin; Drake, Marcus J; Gammie, Andrew; Djurhuus, Jens C; Rosier, Peter F W M; Abrams, Paul; Harding, Christopher

2017-04-01

The diagnosis of bladder outlet obstruction (BOO) in the male is dependent on measurements of pressure and flow made during urodynamic studies. The procedure of urodynamics and the indices used to delineate BOO are well standardized largely as a result of the work of the International Continence Society. The clinical utility of the diagnosis of BOO is however, less well defined and there are several shortcomings and gaps in the currently available medical literature. Consequently the International Consultation on Incontinence Research Society (ICI-RS) held a think tank session in 2015 entitled "Male bladder outlet obstruction: Time to re-evaluate the definition and reconsider our diagnostic pathway?" This manuscript details the discussions that took place within that think tank setting out the pros and cons of the current definition of BOO and exploring alternative clinical tests (alone or in combination) which may be useful in the future investigation of male patients with lower urinary tract symptoms. The think tank panel concluded that pressure-flow studies remain the diagnostic gold-standard for BOO although there is still a lack of high quality evidence. Newer, less invasive, investigations have shown promise in terms of diagnostic accuracy for BOO but similar criticisms can be levelled against these tests. Therefore, the think tank suggests further research with regard to these alternative indicators to determine their clinical utility. © 2017 Wiley Periodicals, Inc.

A quantitative benefit-risk assessment approach to improve decision making in drug development: Application of a multicriteria decision analysis model in the development of combination therapy for overactive bladder.

PubMed

de Greef-van der Sandt, I; Newgreen, D; Schaddelee, M; Dorrepaal, C; Martina, R; Ridder, A; van Maanen, R

2016-04-01

A multicriteria decision analysis (MCDA) approach was developed and used to estimate the benefit-risk of solifenacin and mirabegron and their combination in the treatment of overactive bladder (OAB). The objectives were 1) to develop an MCDA tool to compare drug effects in OAB quantitatively, 2) to establish transparency in the evaluation of the benefit-risk profile of various dose combinations, and 3) to quantify the added value of combination use compared to monotherapies. The MCDA model was developed using efficacy, safety, and tolerability attributes and the results of a phase II factorial design combination study were evaluated. Combinations of solifenacin 5 mg and mirabegron 25 mg and mirabegron 50 (5+25 and 5+50) scored the highest clinical utility and supported combination therapy development of solifenacin and mirabegron for phase III clinical development at these dose regimens. This case study underlines the benefit of using a quantitative approach in clinical drug development programs. © 2015 The American Society for Clinical Pharmacology and Therapeutics.

An ex vivo investigation into the transurothelial permeability and bladder wall distribution of the nonsteroidal anti-inflammatory ketorolac.

PubMed

Williams, Nicholas A; Bowen, Jenna L; Al-Jayyoussi, Ghaith; Gumbleton, Mark; Allender, Chris J; Li, Jamie; Harrah, Tim; Raja, Aditya; Joshi, Hrishi B

2014-03-03

Transurothelial drug delivery continues to be an attractive treatment option for a range of urological conditions; however, dosing regimens remain largely empirical. Recently, intravesical delivery of the nonsteroidal anti-inflammatory ketorolac has been shown to significantly reduce ureteral stent-related pain. While this latest development provides an opportunity for advancing the management of stent-related pain, clinical translation will undoubtedly require an understanding of the rate and extent of delivery of ketorolac into the bladder wall. Using an ex vivo porcine model, we evaluate the urothelial permeability and bladder wall distribution of ketorolac. The subsequent application of a pharmacokinetic (PK) model enables prediction of concentrations achieved in vivo. Ketorolac was applied to the urothelium and a transurothelial permeability coefficient (Kp) calculated. Relative drug distribution into the bladder wall after 90 min was determined. Ketorolac was able to permeate the urothelium (Kp = 2.63 × 10(-6) cm s(-1)), and after 90 min average concentrations of 400, 141 and 21 μg g(-1) were achieved in the urothelium, lamina propria and detrusor respectively. An average concentration of 87 μg g(-1) was achieved across the whole bladder wall. PK simulations (STELLA) were then carried out, using ex vivo values for Kp and muscle/saline partition coefficient (providing an estimation of vascular clearance), to predict 90 min in vivo ketorolac tissue concentrations. When dilution of the drug solution with urine and vascular clearance were taken into account, a reduced ketorolac concentration of 37 μg g(-1) across the whole bladder wall was predicted. These studies reveal crucial information about the urothelium's permeability to agents such as ketorolac and the concentrations achievable in the bladder wall. It would appear that levels of ketorolac delivered to the bladder wall intravesically would be sufficient to provide an anti-inflammatory effect. The combination of such ex vivo data and PK modeling provides an insight into the likelihood of achieving clinically relevant concentrations of drug following intravesical administration.

Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM.

PubMed

Bryan, R T; Regan, H L; Pirrie, S J; Devall, A J; Cheng, K K; Zeegers, M P; James, N D; Knowles, M A; Ward, D G

2015-03-17

Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests. We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up. Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81-4.62, P<0.001). In multivariable models including both urinary EGFR and EpCAM, both biomarkers are predictive of bladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations. Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.

Endoscopic Optical Coherence Tomography in Urology

NASA Astrophysics Data System (ADS)

Pan, Yingtian; Waltzer, Wayne; Ye, Zhangqun

Clinical statistics has shown a stable prevalence of bladder cancer in recent years, which by far remains among the most common types of malignancy in the USA. With smoking as the most well-established risk factor, bladder cancer is the fourth most common cancer occurrences in male population [1]. In the year of 2014, an estimated 74,690 new cases are expected to occur with estimated 15,580 deaths. Bladder cancer often refers to transitional cell carcinoma (TCC) as it originates primarily from the epithelial cell layer (i.e., urothelium) of the bladder. Unlike prostate-specific antigen (PSA) for prostate cancer screening, there is currently no effective screening technique approved or recommended for the population at average risk [2-5]. As a result, hematuria (i.e., blood in the urine) is often the first clinical symptom of bladder cancer. Fortunately, urinary bladder is more accessible than prostate glands endoscopically; thus cytology following white-light cystoscopy has been the gold standard for current clinical detection of bladder cancer. This is important because bladder cancer if diagnosed prior to muscle invasion (e.g., superficial or at

Bladder Control Problems in Women: Lifestyle Strategies for Relief

MedlinePlus

Bladder control: Lifestyle strategies ease problems Simple lifestyle changes may improve bladder control or enhance response to medication. Find out what you can do to help with your bladder control problem. By Mayo Clinic Staff If you've ...

Prognostic Power of a Tumor Differentiation Gene Signature for Bladder Urothelial Carcinomas.

PubMed

Mo, Qianxing; Nikolos, Fotis; Chen, Fengju; Tramel, Zoe; Lee, Yu-Cheng; Hayashi, Kazukuni; Xiao, Jing; Shen, Jianjun; Chan, Keith Syson

2018-05-01

Muscle-invasive bladder cancers (MIBCs) cause approximately 150 000 deaths per year worldwide. Survival for MIBC patients is heterogeneous, with no clinically validated molecular markers that predict clinical outcome. Non-MIBCs (NMIBCs) generally have favorable outcome; however, a portion progress to MIBC. Hence, development of a prognostic tool that can guide decision-making is crucial for improving clinical management of bladder urothelial carcinomas. Tumor grade is defined by pathologic evaluation of tumor cell differentiation, and it often associates with clinical outcome. The current study extrapolates this conventional wisdom and combines it with molecular profiling. We developed an 18-gene signature that molecularly defines urothelial cellular differentiation, thus classifying MIBCs and NMIBCs into two subgroups: basal and differentiated. We evaluated the prognostic capability of this "tumor differentiation signature" and three other existing gene signatures including the The Cancer Genome Atlas (TCGA; 2707 genes), MD Anderson Cancer Center (MDA; 2252 genes/2697 probes), and University of North Carolina at Chapel Hill (UNC; 47 genes) using five gene expression data sets derived from MIBC and NMIBC patients. All statistical tests were two-sided. The tumor differentiation signature demonstrated consistency and statistical robustness toward stratifying MIBC patients into different overall survival outcomes (TCGA cohort 1, P = .03; MDA discovery, P = .009; MDA validation, P = .01), while the other signatures were not as consistent. In addition, we analyzed the progression (Ta/T1 progressing to ≥T2) probability of NMIBCs. NMIBC patients with a basal tumor differentiation signature associated with worse progression outcome (P = .008). Gene functional term enrichment and gene set enrichment analyses revealed that genes involved in the biologic process of immune response and inflammatory response are among the most elevated within basal bladder cancers, implicating them as candidates for immune checkpoint therapies. These results provide definitive evidence that a biology-prioritizing clustering methodology generates meaningful insights into patient stratification and reveals targetable molecular pathways to impact future therapeutic approach.

Future directions in bladder cancer immunotherapy: towards adaptive immunity

PubMed Central

Smith, Sean G; Zaharoff, David A

2016-01-01

The clinical management of bladder cancer has not changed significantly in several decades. In particular, intravesical bacillus Calmette–Guérin (BCG) immunotherapy has been a mainstay for high-risk nonmuscle invasive bladder cancer since the late 1970s/early 1980s. This is despite the fact that bladder cancer has the highest recurrence rates of any cancer and BCG immunotherapy has not been shown to induce a tumor-specific immune response. We and others have hypothesized that immunotherapies capable of inducing tumor-specific adaptive immunity are needed to impact bladder cancer morbidity and mortality. This article summarizes the preclinical and clinical development of bladder cancer immunotherapies with an emphasis on the last 5 years. Expected progress in the near future is also discussed. PMID:26860539

Future directions in bladder cancer immunotherapy: towards adaptive immunity.

PubMed

Smith, Sean G; Zaharoff, David A

2016-01-01

The clinical management of bladder cancer has not changed significantly in several decades. In particular, intravesical bacillus Calmette-Guérin (BCG) immunotherapy has been a mainstay for high-risk nonmuscle invasive bladder cancer since the late 1970s/early 1980s. This is despite the fact that bladder cancer has the highest recurrence rates of any cancer and BCG immunotherapy has not been shown to induce a tumor-specific immune response. We and others have hypothesized that immunotherapies capable of inducing tumor-specific adaptive immunity are needed to impact bladder cancer morbidity and mortality. This article summarizes the preclinical and clinical development of bladder cancer immunotherapies with an emphasis on the last 5 years. Expected progress in the near future is also discussed.

Computed tomography findings of human polyomavirus BK (BKV)-associated cystitis in allogeneic hematopoietic stem cell transplant recipients.

PubMed

Schulze, M; Beck, R; Igney, A; Vogel, M; Maksimovic, O; Claussen, C D; Faul, C; Horger, M

2008-12-01

Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and increased mucosal enhancement. These findings are not specific for BKV cystitis, but awareness of this differential diagnosis should help in the early diagnosis and correct management of this infectious complication.

Involvement of the cystathionine-γ-lyase/Cav3.2 pathway in substance P-induced bladder pain in the mouse, a model for nonulcerative bladder pain syndrome.

PubMed

Tsubota, Maho; Okawa, Yasumasa; Irie, Yuhei; Maeda, Mariko; Ozaki, Tomoka; Sekiguchi, Fumiko; Ishikura, Hiroyasu; Kawabata, Atsufumi

2018-05-01

Hydrogen sulfide (H 2 S) formed by cystathionine-γ-lyase (CSE) enhances the activity of Ca v 3.2 T-type Ca 2+ channels, contributing to the bladder pain accompanying hemorrhagic cystitis caused by systemic administration of cyclophosphamide (CPA) in mice. Given clinical and fundamental evidence for the involvement of the substance P/NK 1 receptor systems in bladder pain syndrome (BPS)/interstitial cystitis (IC), we created an intravesical substance P-induced bladder pain model in mice and analyzed the possible involvement of the CSE/Ca v 3.2 pathway. Bladder pain/cystitis was induced by i.p. CPA or intravesical substance P in female mice. Bladder pain was evaluated by counting nociceptive behavior and by detecting referred hyperalgesia in the lower abdomen and hindpaw. The isolated bladder tissue was weighed to estimate bladder swelling and subjected to histological observation and Western blotting. Intravesical substance P caused profound referred hyperalgesia accompanied by little bladder swelling or edema 6-24 h after the administration, in contrast to i.p. CPA-induced nociceptive behavior/referred hyperalgesia with remarkable bladder swelling/edema and urothelial damage. The bladder pain and/or cystitis symptoms caused by substance P or CPA were prevented by the NK 1 receptor antagonist. CSE in the bladder was upregulated by substance P or CPA, and the NK 1 antagonist prevented the CPA-induced CSE upregulation. A CSE inhibitor, a T-type Ca 2+ channel blocker and gene silencing of Ca v 3.2 abolished the intravesical substance P-induced referred hyperalgesia. The intravesical substance P-induced pain in mice is useful as a model for nonulcerative BPS, and involves the activation of the NK 1 receptor/CSE/H 2 S/Ca v 3.2 cascade. Copyright © 2018 Elsevier Ltd. All rights reserved.

Portable bladder ultrasound: an evidence-based analysis.

PubMed

2006-01-01

The aim of this review was to assess the clinical utility of portable bladder ultrasound. TARGET POPULATION AND CONDITION Data from the National Population Health Survey indicate prevalence rates of urinary incontinence are 2.5% in women and 1.4 % in men in the general population. Prevalence of urinary incontinence is higher in women than men and prevalence increases with age. Identified risk factors for urinary incontinence include female gender, increasing age, urinary tract infections (UTI), poor mobility, dementia, smoking, obesity, consuming alcohol and caffeine beverages, physical activity, pregnancy, childbirth, forceps and vacuum-assisted births, episiotomy, abdominal resection for colorectal cancer, and hormone replacement therapy. For the purposes of this review, incontinence populations will be stratified into the following; the elderly, urology patients, postoperative patients, rehabilitation settings, and neurogenic bladder populations. Urinary incontinence is defined as any involuntary leakage of urine. Incontinence can be classified into diagnostic clinical types that are useful in planning evaluation and treatment. The major types of incontinence are stress (physical exertion), urge (overactive bladder), mixed (combined urge and stress urinary incontinence), reflex (neurological impairment of the central nervous system), overflow (leakage due to full bladder), continuous (urinary tract abnormalities), congenital incontinence, and transient incontinence (temporary incontinence). Postvoid residual (PVR) urine volume, which is the amount of urine in the bladder immediately after urination, represents an important component in continence assessment and bladder management to provide quantitative feedback to the patient and continence care team regarding the effectiveness of the voiding technique. Although there is no standardized definition of normal PVR urine volume, measurements greater than 100 mL to 150 mL are considered an indication for urinary retention, requiring intermittent catheterization, whereas a PVR urine volume of 100 mL to 150 mL or less is generally considered an acceptable result of bladder training. Urinary retention has been associated with poor outcomes including UTI, bladder overdistension, and higher hospital mortality rates. The standard method of determining PVR urine volumes is intermittent catheterization, which is associated with increased risk of UTI, urethral trauma and discomfort. Portable bladder ultrasound products are transportable ultrasound devices that use automated technology to register bladder volume digitally, including PVR volume, and provide three-dimensional images of the bladder. The main clinical use of portable bladder ultrasound is as a diagnostic aid. Health care professionals (primarily nurses) administer the device to measure PVR volume and prevent unnecessary catheterization. An adjunctive use of the bladder ultrasound device is to visualize the placement and removal of catheters. Also, portable bladder ultrasound products may improve the diagnosis and differentiation of urological problems and their management and treatment, including the establishment of voiding schedules, study of bladder biofeedback, fewer UTIs, and monitoring of potential urinary incontinence after surgery or trauma. To determine the effectiveness and clinical utility of portable bladder ultrasound as reported in the published literature, the Medical Advisory Secretariat used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases. Nonsystematic reviews, nonhuman studies, case reports, letters, editorials, and comments were excluded. Of the 4 included studies that examined the clinical utility of portable bladder ultrasound in the elderly population, all found the device to be acceptable. One study reported that the device underestimated catheterized bladder volume In patients with urology problems, 2 of the 3 studies concerning portable bladder ultrasound found the device acceptable to use. However, one study did not find the device as accurate for small PVR volume as for catheterization and another found that the device overestimated catheterized bladder volume. In the remaining study, the authors reported that when the device's hand-held ultrasound transducers (scanheads) were aimed improperly, bladders were missed, or lateral borders of bladders were missed resulting in partial bladder volume measurements and underestimation of PVR measurements. They concluded that caution should be used in interpreting PVR volume measured by portable bladder ultrasound machines and that catheterization may be the preferred assessment modality if an accurate PVR measurement is necessary. All 3 studies with post-operative populations found portable bladder ultrasound use to be reasonably acceptable. Two studies reported that the device overestimated catheter-derived bladder volumes, one by 7% and the other by 21 mL. The third study reported the opposite, that the device underestimated catheter bladder volume by 39 mL but that the results remained acceptable In rehabilitation settings, 2 studies found portable bladder ultrasound to underestimate catheter-derived bladder volumes; yet, both authors concluded that the mean errors were within acceptable limits. In patients with neurogenic bladder problems, 2 studies found portable bladder ultrasound to be an acceptable alternative to catheterization despite the fact that it was not as accurate as catheterization for obtaining bladder volumes. Lastly, examinations concerning avoidance of negative health outcomes showed that, after use of the portable bladder ultrasound, unnecessary catheterizations and UTIs were decreased. Unnecessary catheterizations avoided ranged from 16% to 47% in the selected articles. Reductions in UTI ranged from 38% to 72%. In sum, all but one study advocated the use of portable bladder ultrasound as an alternative to catheterization. An economic analysis estimating the budget-impact of BladderScan in complex continuing care facilities was completed. The analysis results indicated a $192,499 (Cdn) cost-savings per year per facility and a cost-savings of $2,887,485 (Cdn) for all 15 CCC facilities. No economic analysis was completed for long-term care and acute care facilities due to lack of data. Rapid diffusion of portable bladder ultrasound technology is expected. Recently, the IC5 project on improving continence care in Ontario's complex continuing care centres piloted portable bladder ultrasound at 12 sites. Preliminary results were promising. Many physicians and health care facilities already have portable bladder ultrasound devices. However, portable bladder ultrasound devices for PVR measurement are not in use at most health care facilities in Ontario and Canada. The Verathon Corporation (Bothell, Wisconsin, United States), which patents BladderScan, is the sole licensed manufacturer of the portable bladder ultrasound in Canada. Field monopoly may influence the rising costs of portable bladder ultrasound, particularly when faced with rapid expansion of the technology. Several thousand residents of Ontario would benefit from portable bladder ultrasound. The number of residents of Ontario that would benefit from the technology is difficult to quantify, because the incidence and prevalence of incontinence are grossly under-reported. However, long-term care and complex continuing care institutions would benefit greatly from portable bladder ultrasound, as would numerous rehabilitation units, postsurgical care units, and urology clinics. The cost of the portable bladder ultrasound devices ranges from $17,698.90 to $19,565.95 (Cdn) (total purchase price per unit as quoted by the manufacturer). Additional training packages, batteries and battery chargers, software, gel pads, and yearly warranties are additional costs. Studies indicate that portable bladder ultrasound is a cost-effective technology, because it avoids costs associated with catheterization equipment, saves nursing time, and reduces catheter-related complications and UTIs. The use of portable bladder ultrasound device will affect the patient directly in terms of health outcomes. Its use avoids the trauma related to the urinary tract that catheterization inflicts, and does not result in UTIs. In addition, patients prefer it, because it preserves dignity and reduces discomfort.

A microangiographic study of the effect of hyperthermia on the rabbit bladder

NASA Technical Reports Server (NTRS)

Hietala, S. O.; Howells, R.; Hazra, I. A.

1978-01-01

A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors.

Effect of bladder filling on doses to prostate and organs at risk: a treatment planning study

PubMed Central

Liu, Mitchell; Kristensen, Sarah; Gelowitz, Gerald; Berthelet, Eric

2007-01-01

In the present study, we aimed to evaluate effects of bladder filling on dose–volume distributions for bladder, rectum, planning target volume (PTV), and prostate in radiation therapy of prostate cancer. Patients (n=21) were scanned with a full bladder, and after 1 hour, having been allowed to void, with an empty bladder. Radiotherapy plans were generated using a four‐field box technique and dose of 70 Gy in 35 fractions. First, plans obtained for full‐ and empty‐bladder scans were compared. Second, situations in which a patient was planned on full bladder but was treated on empty bladder, and vice versa, were simulated, assuming that patients were aligned to external tattoos. Doses to the prostate [equivalent uniform dose (EUD)], bladder and rectum [effective dose (Deff)], and normal tissue complication probability (NTCP) were compared. Dose to the small bowel was examined. Mean bladder volume was 354.3 cm3 when full and 118.2 cm3 when empty. Median prostate EUD was 70 Gy for plans based on full‐ and empty‐bladder scans alike. The median rectal Deff was 55.6 Gy for full‐bladder anatomy and 56.8 Gy for empty‐bladder anatomy, and the corresponding bladder Deff was 29.0 Gy and 49.3 Gy respectively. In 1 patient, part of the small bowel (7.5 cm3) received more than 50 Gy with full‐bladder anatomy, and in 6 patients, part (2.5 cm3−30 cm3) received more than 50 Gy with empty‐bladder anatomy. Bladder filling had no significant impact on prostate EUD or rectal Deff. A minimal volume of the small bowel received more than 50 Gy in both groups, which is below dose tolerance. The bladder Deff was higher with empty‐bladder anatomy; however, the predicted complication rates were clinically insignificant. When the multileaf collimator pattern was applied in reverse, substantial underdosing of the planning target volume (PTV) was observed, particularly for patients with prostate shifts in excess of 0.5 cm in any one direction. However, the prostate shifts showed no correlation with bladder filling, and therefore the PTV underdosing also cannot be related to bladder filling. For some patients, bladder dose–volume constraints were not fulfilled in the worst‐case scenario—that is, when a patient planned with full bladder consistently arrived for treatment with an empty bladder. PACS numbers: 87.53.‐j, 87.53.Kn, 87.53.Tf PMID:17592448

Urinary bladder cancer T-staging from T2-weighted MR images using an optimal biomarker approach

NASA Astrophysics Data System (ADS)

Wang, Chuang; Udupa, Jayaram K.; Tong, Yubing; Chen, Jerry; Venigalla, Sriram; Odhner, Dewey; Guzzo, Thomas J.; Christodouleas, John; Torigian, Drew A.

2018-02-01

Magnetic resonance imaging (MRI) is often used in clinical practice to stage patients with bladder cancer to help plan treatment. However, qualitative assessment of MR images is prone to inaccuracies, adversely affecting patient outcomes. In this paper, T2-weighted MR image-based quantitative features were extracted from the bladder wall in 65 patients with bladder cancer to classify them into two primary tumor (T) stage groups: group 1 - T stage < T2, with primary tumor locally confined to the bladder, and group 2 - T stage < T2, with primary tumor locally extending beyond the bladder. The bladder was divided into 8 sectors in the axial plane, where each sector has a corresponding reference standard T stage that is based on expert radiology qualitative MR image review and histopathologic results. The performance of the classification for correct assignment of T stage grouping was then evaluated at both the patient level and the sector level. Each bladder sector was divided into 3 shells (inner, middle, and outer), and 15,834 features including intensity features and texture features from local binary pattern and gray-level co-occurrence matrix were extracted from the 3 shells of each sector. An optimal feature set was selected from all features using an optimal biomarker approach. Nine optimal biomarker features were derived based on texture properties from the middle shell, with an area under the ROC curve of AUC value at the sector and patient level of 0.813 and 0.806, respectively.

Protoporphyrin IX induced by 5-aminolevulinic acid in bladder cancer cells in voided urine can be extracorporeally quantified using a spectrophotometer.

PubMed

Nakai, Yasushi; Anai, Satoshi; Onishi, Sayuri; Masaomi, Kuwada; Tatsumi, Yoshihiro; Miyake, Makito; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

2015-06-01

We evaluated the feasibility of photodynamic diagnosis of bladder cancer by spectrophotometric analysis of voided urine samples after extracorporeal treatment with 5-aminolevulinic acid (ALA). Sixty-one patients with bladder cancer, confirmed histologically after the transurethral resection of a bladder tumor, were recruited as the bladder cancer group, and 50 outpatients without history of urothelial carcinoma or cancer-related findings were recruited as the control group. Half of the voided urine sample was incubated with ALA (ALA-treated sample), and the rest was incubated without treatment (ALA-untreated sample). For detecting cellular protoporphyrin IX levels, intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated and ALA-untreated samples at 635 nm was calculated. The differences in the bladder cancer group were significantly greater than those in the control group (p < 0.001). These differences were also significantly greater in patients with high-grade tumors than in those with low-grade tumors (p = 0.004), and also in patients with invasive bladder cancer than in those with noninvasive bladder cancer (p = 0.007). The area under the curve was 0.84. Sensitivity and specificity of the method were 82% and 80%, respectively. We demonstrated that protoporphyrin IX levels in urinary cells treated with ALA could be quantitatively detected by spectrophotometer in patients with bladder cancer. Therefore, this cancer detection system has a potential for clinical use. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of potential bladder cancer markers in urine by abundant-protein depletion coupled with quantitative proteomics.

PubMed

Chen, Chien-Lun; Lin, Tsung-Shih; Tsai, Cheng-Han; Wu, Chih-Ching; Chung, Ting; Chien, Kun-Yi; Wu, Maureen; Chang, Yu-Sun; Yu, Jau-Song; Chen, Yi-Ting

2013-06-24

In this study, we evaluated the reproducibility of abundant urine protein depletion by hexapeptide-based library beads and an antibody-based affinity column using the iTRAQ technique. The antibody-based affinity-depletion approach, which proved superior, was then applied in conjunction with iTRAQ to discover proteins that were differentially expressed between pooled urine samples from hernia and bladder cancer patients. Several proteins, including seven apolipoproteins, TIM, SAA4, and proEGF were further verified in 111 to 203 individual urine samples from patients with hernia, bladder cancer, or kidney cancer. Six apolipoproteins (APOA1, APOA2, APOB, APOC2, APOC3, and APOE) were able to differentiate bladder cancer from hernia. SAA4 was significantly increased in bladder cancer subgroups, whereas ProEGF was significantly decreased in bladder cancer subgroups. Additionally, the combination of SAA4 and ProEGF exhibited higher diagnostic capacity (AUC=0.80 and p<0.001) in discriminating bladder cancer from hernia than either marker alone. Using MetaCore software to interpret global changes of the urine proteome caused by bladder cancer, we found that the most notable alterations were in immune-response/alternative complement and blood-coagulation pathways. This study confirmed the clinical significance of the urine proteome in the development of non-invasive biomarkers for the detection of bladder cancer. In this study, we evaluated the reproducibility of abundant urine protein depletion by hexapeptide-based library beads and an antibody-based affinity column using the iTRAQ technique. The antibody-based affinity-depletion approach, which proved superior, was then applied in conjunction with iTRAQ to discover proteins that were differentially expressed between pooled urine samples from hernia and bladder cancer patients. Several proteins, including seven apolipoproteins, TIM, SAA4, and proEGF were further verified in 111 to 203 individual urine samples from patients with hernia, bladder cancer, or kidney cancer. SAA4 was significantly increased in bladder cancer subgroups, whereas ProEGF was significantly decreased in bladder cancer subgroups. Additionally, the combination of SAA4 and ProEGF exhibited higher diagnostic capacity in discriminating bladder cancer from hernia than either marker alone. A marker panel composed by two novel biomarker candidates, SAA4 and proEGF, was first discovered and verified successfully using Western blotting. To the best of our knowledge, the associations of urinary SAA4 and proEGF with bladder tumor and kidney cancer have not been mentioned before. In the present study, we discovered and verified SAA4 and proEGF as potential bladder cancer biomarker for the first time. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Sulforaphane for the chemoprevention of bladder cancer: molecular mechanism targeted approach

PubMed Central

Leone, Andrew; Diorio, Gregory; Sexton, Wade; Schell, Michael; Alexandrow, Mark; Fahey, Jed W.; Kumar, Nagi B.

2017-01-01

The clinical course for both early and late stage Bladder Cancer (BC) continues to be characterized by significant patient burden due to numerous occurrences and recurrences requiring frequent surveillance strategies, intravesical drug therapies, and even more aggressive treatments in patients with locally advanced or metastatic disease. For these reasons, BC is also the most expensive cancer to treat. Fortunately, BC offers an excellent platform for chemoprevention interventions with potential to optimize the systemic and local exposure of promising agents to the bladder mucosa. However, other than smoking cessation, there is a paucity of research that systematically examines agents for chemoprevention of bladder cancers. Adopting a systematic, molecular-mechanism based approach, the goal of this review is to summarize epidemiological, in vitro, and preclinical studies, including data regarding the safety, bioavailability, and efficacy of agents evaluated for bladder cancer chemoprevention. Based on the available studies, phytochemicals, specifically isothiocyanates such as sulforaphane, present in Brassicaceae or “cruciferous” vegetables in the precursor form of glucoraphanin are: (a) available in standardized formulations; (b) bioavailable- both systemically and in the bladder; (c) observed to be potent inhibitors of BC carcinogenesis through multiple mechanisms; and (d) without toxicities at these doses. Based on available evidence from epidemiological, in vitro, preclinical, and early phase trials, phytochemicals, specifically isothiocyanates (ITCs) such as sulforaphane (SFN) represent a promising potential chemopreventitive agent in bladder cancer. PMID:28423681

Spontaneous Urinary Bladder Leiomyoma in a Rhesus Macaque (Macaca mulatta).

PubMed

Scott, Kathleen E; Frydman, Galit; Fox, James G; Bakthavatchalu, Vasudevan

2018-06-01

Here we report the case of a urinary bladder leiomyoma in a rhesus macaque. The animal was clinically normal and had a lipoma localized to the stifle. Endovesicular leiomyomas are the most common form of urinary bladder leiomyoma in humans. In contrast, this macaque's tumor exhibited extravesicular localization in the bladder. Urinary bladder leiomyomas account for less than 0.5% of all bladder tumors in humans, with only 250 cases reported in total.

Are you experienced? Understanding bladder innate immunity in the context of recurrent urinary tract infection

PubMed Central

O’Brien, Valerie P.; Hannan, Thomas J.; Schaeffer, Anthony J.; Hultgren, Scott J.

2015-01-01

Purpose of review Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI. Recent findings Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naïve and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection. Summary The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact. PMID:25517222

Are you experienced? Understanding bladder innate immunity in the context of recurrent urinary tract infection.

PubMed

O'Brien, Valerie P; Hannan, Thomas J; Schaeffer, Anthony J; Hultgren, Scott J

2015-02-01

Recurrent urinary tract infection (rUTI) is a serious clinical problem, yet effective therapeutic options are limited, especially against multidrug-resistant uropathogens. In this review, we explore the development of a clinically relevant model of rUTI in previously infected mice and review recent developments in bladder innate immunity that may affect susceptibility to rUTI. Chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodelling that sensitizes the host to rUTI. Although constitutive defenses help prevent bacterial colonization of the urinary bladder, once infection occurs, induced cytokine and myeloid cell responses predominate and the balance of immune cell defense and bladder immunopathology is critical for determining disease outcome, in both naïve and experienced mice. In particular, the maintenance of the epithelial barrier appears to be essential for preventing severe infection. The innate immune response plays a key role in determining susceptibility to rUTI. Future studies should be directed towards understanding how the innate immune response changes as a result of bladder mucosal remodelling in previously infected mice, and validating these findings in human clinical specimens. New therapeutics targeting the immune response should selectively target the induced innate responses that cause bladder immunopathology, while leaving protective defenses intact.

A place for precision medicine in bladder cancer: targeting the FGFRs.

PubMed

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.

A place for precision medicine in bladder cancer: targeting the FGFRs

PubMed Central

di Martino, Erica; Tomlinson, Darren C; Williams, Sarah V; Knowles, Margaret A

2016-01-01

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. PMID:27381494

Immunotherapy: a new treatment paradigm in bladder cancer

PubMed Central

Davarpanah, Nicole N.; Yuno, Akira; Trepel, Jane B.; Apolo, Andrea B.

2017-01-01

Purpose of review T-cell checkpoint blockade has become a dynamic immunotherapy for bladder cancer. In 2016, atezolizumab, an immune checkpoint inhibitor, became the first new drug approved in metastatic urothelial carcinoma (mUC) in over 30 years. In 2017, nivolumab was also approved for the same indication. This overview of checkpoint inhibitors in clinical trials focuses on novel immunotherapy combinations, predictive biomarkers including mutational load and neoantigen identification, and an evaluation of the future of bladder cancer immunotherapy. Recent findings Programed cell death protein 1/programed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors have achieved durable clinical responses in a subset of previously treated and treatment-naïve patients with mUC. The combination of PD-1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) has successfully improved response rates in multiple malignancies, and combination studies are underway in many tumor types, including bladder cancer, combining T-cell checkpoint blockade with other checkpoint agents and immunomodulatory therapies. Strong tumor responses to checkpoint blockade have been reported to be positively associated with expression of PD-L1 on tumor and tumor-infiltrating immune cells and with increased mutation-associated neoantigen load, which may lead to the development of predictive biomarkers. Summary Recent clinical evidence suggests that mUC is susceptible to T-cell checkpoint blockade. A global effort is underway to achieve higher response rates and more durable remissions, accelerate the development of immunotherapies, employ combination therapies, and test novel immune targets. PMID:28306559

Bladder perforations in children.

PubMed

Bakal, U; Sarac, M; Tartar, T; Ersoz, F; Kazez, A

2015-01-01

Bladder perforations in children occur due to several different reasons. In this clinical series study, we focused on bladder perforations due to the pelvic injury, and our aim also was to create awareness for a rare type of bladder injuries. This was a retrospective study of the patients who were treated in our clinic for bladder perforation between 2006 and 2011. We reviewed the documents of childhood bladder perforations, and demographic and clinical characteristics of the patients were obtained. No statistical analyses were used because of the limited number of cases. There were ten patients who suffered from bladder perforation in 5-year period; 5 were male, and 5 were female. The mean age of the patients was 4.35 years. Four patients (40%) experienced iatrogenic perforation and six patients (60%) experienced perforation due to the accident. Common symptoms were hematuria, abdominal tenderness, and inability to urinate. Three patients were diagnosed via emergency laparotomy, without any radiological examinations performed before surgery. Four patients suffered from the intraperitoneal perforation, three patients suffered from extraperitoneal injury and three of them both of intraperitoneal and extraperitoneal injuries. Mean recovery time for patients was 15 days. One patient developed a urinary tract infection and one newborn died due to accompanying morbidities. Nine patients were discharged from the hospital. If the patients had a pelvic injury, surgeons must pay attention for the bladder perforation. Isolated bladder perforations are rare, and they are generally associated with iatrogenic injuries. Clinicians should pay attention to findings such as anuria, inability to insert a urinary catheter, and free fluid in the abdomen in order to diagnose the bladder perforation in newborns. Novice surgeons should pay more attention to avoid causing iatrogenic bladder perforation during inguinal hernia repair.

Treatment of Non-neurogenic Overactive Bladder with OnabotulinumtoxinA: Systematic Review and Meta-analysis of Prospective, Randomized, Placebo-controlled Clinical Trials.

PubMed

Arruda, Raquel Martins; Takano, Claudia Cristina; Girão, Manoel João Batista Castelo; Haddad, Jorge Milhem; Aleixo, Gabriel Francisco; Castro, Rodrigo Aquino

2018-04-01

We performed a systematic review and meta-analysis of randomized placebo-controlled trials that studied non-neurogenic overactive bladder patients who were treated with 100 units of onabotulinumtoxinA or placebo. The primary purpose of our study was to evaluate the clinical effectiveness with regard to urinary urgency, urinary frequency, nocturia, and incontinence episodes. Our secondary purpose consisted of evaluating the adverse effects. Our initial search yielded 532 entries. Of these, seven studies met all the inclusion criteria (prospective, randomized, placebo-controlled studies, ≥ 3 points on the Jadad scale) and were selected for analysis. For all primary endpoints, the toxin was more effective than placebo ( p  < 0.0001; 95% confidence interval [95CI]), namely: urgency (mean difference = -2.07; 95CI = [-2.55-1.58]), voiding frequency (mean difference = -1.64; 95CI = [-2.10-1.18]), nocturia (mean difference = -0.25; 95CI = [-0.39-0.11]) and incontinence episodes (mean difference = -2.06; 95CI= [-2.60-1.52]). The need for intermittent catheterization and the occurrence of urinary tract infection (UTI) were more frequent in patients treated with onabotulinumtoxinA than in patients treated with placebo ( p  < 0.0001). Compared with placebo, onabotulinumtoxinA had significantly and clinically relevant reductions in overactive bladder symptoms and is associated with higher incidence of intermittent catheterization and UTI. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

New clinical trial open for patients with muscle-invasive bladder cancer | Center for Cancer Research

Cancer.gov

Muscle-invasive bladder cancer is an aggressive form of bladder cancer in which the tumor invades deep into the musculature of the bladder wall, making it more likely to spread to other parts of the body. Standard treatment involves cisplatin-based chemotherapy followed by radical cystectomy, which is surgery to remove the bladder and nearby organs. However, many patients

Infiltrating T Cells Promote Bladder Cancer Progression via Increasing IL1→Androgen Receptor→HIF1α→VEGFa Signals.

PubMed

Tao, Le; Qiu, Jianxin; Jiang, Ming; Song, Wenbin; Yeh, Shuyuan; Yu, Hong; Zang, Lijuan; Xia, Shujie; Chang, Chawnshang

2016-08-01

The tumor microenvironment impacts tumor progression and individual cells, including CD4(+) T cells, which have been detected in bladder cancer tissues. The detailed mechanism of how these T cells were recruited to the bladder cancer tumor and their impact on bladder cancer progression, however, remains unclear. Using a human clinical bladder cancer sample survey and in vitro coculture system, we found that bladder cancer has a greater capacity to recruit T cells than surrounding normal bladder tissues. The consequences of higher levels of recruited T cells in bladder cancer included increased bladder cancer metastasis. Mechanism dissection revealed that infiltrating T cells might function through secreting the cytokine IL1, which increases the recruitment of T cells to bladder cancer and enhances the bladder cancer androgen receptor (AR) signaling that results in increased bladder cancer cell invasion via upregulation of hypoxia-inducible factor-1α (HIF1α)/VEGFa expression. Interruption of the IL1→AR→HIF1α→VEGFa signals with inhibitors of HIF1α or VEGFa partially reversed the enhanced bladder cancer cell invasion. Finally, in vivo mouse models of xenografted bladder cancer T24 cells with CD4(+) T cells confirmed in vitro coculture studies and concluded that infiltrating CD4(+) T cells can promote bladder cancer metastasis via modulation of the IL1→AR→HIF1α→VEGFa signaling. Future clinical trials using small molecules to target this newly identified signaling pathway may facilitate the development of new therapeutic approaches to better suppress bladder cancer metastasis. Mol Cancer Ther; 15(8); 1943-51. ©2016 AACR. ©2016 American Association for Cancer Research.

Biomarkers in bladder cancer: present status and perspectives.

PubMed

Kim, Wun-Jae; Park, Soongang; Kim, Yong-June

2007-03-27

Bladder cancers are a mixture of heterogeneous cell populations, and numerous factors are likely to be involved in dictating their recurrence, progression and the patient's survival. For any candidate prognostic marker to have considerable clinical relevance, it must add some predictive capacity beyond that offered by conventional clinical and pathologic parameters. Here, the current situation in bladder cancer research with respect to identification of suitable prognostic markers is reviewed. A number of individual molecular markers that might predict bladder cancer recurrence and progression have been identified but many are not sufficiently sensitive or specific for the whole spectrum of bladder cancer diseases seen in routine clinical practice. These limitations have led to interest in other molecular parameters that could enable more accurate prognosis for bladder cancer patients. Of particular interest is the epigenetic silencing of tumor suppressor genes. Since the methylation of these genes can correlate with a poor prognosis, the methylation profile may represent a new bio-marker that indicates the risk of transitional cell carcinoma development. In addition, bladder cancer research is likely to be revolutionized by high-throughput molecular technologies, which allow rapid and global gene expression analysis of thousands of tumor samples. Initial studies employing these technologies have considerably expanded our ability to classify bladder cancers with respect to their survivability. Future microarray analyses are likely to reveal particular gene expression signatures that predict the likelihood of bladder cancer progression and recurrence, as well as patient's survival and responsiveness to different anti-cancer therapies, with great specificity and sensitivity.

Significance of Random Bladder Biopsies in Non-Muscle Invasive Bladder Cancer

PubMed Central

Kumano, Masafumi; Miyake, Hideaki; Nakano, Yuzo; Fujisawa, Masato

2013-01-01

Background/Aims To evaluate retrospectively the clinical outcome of random bladder biopsies in patients with non-muscle invasive bladder cancer (NMIBC) undergoing transurethral resection (TUR). Patients and Method This study included 234 consecutive patients with NMIBC who underwent random biopsies from normal-appearing urothelium of the bladder, including the anterior wall, posterior wall, right wall, left wall, dome, trigone and/or prostatic urethra, during TUR. Result Thirty-seven patients (15.8%) were diagnosed by random biopsies as having urothelial cancer. Among several factors available prior to TUR, preoperative urinary cytology appeared to be independently related to the detection of urothelial cancer in random biopsies on multivariate analysis. Urinary cytology prior to TUR gave 50.0% sensitivity, 91.7% specificity, 56.8% positive predictive value and 89.3% negative predictive value for predicting the findings of the random biopsies. Conclusion Biopsies of normal-appearing urothelium resulted in the additional detection of urothelial cancer in a definite proportion of NMIBC patients, and it remains difficult to find a reliable alternative to random biopsies. Collectively, these findings suggest that it would be beneficial to perform random biopsies as part of the routine management of NMIBC. PMID:24917759

How to Measure Quality-of-Life Concerns in Patients with Neurogenic Lower Urinary Tract Dysfunction.

PubMed

Patel, Darshan P; Myers, Jeremy B; Lenherr, Sara M

2017-08-01

There is an evolving role for quality-of-life measures and patient-reported outcomes in the evaluation of neurogenic lower urinary tract dysfunction. We review available health-related quality-of-life instruments and patient-reported outcomes measures used in the assessment of patients with neurogenic bladder. We also discuss considerations for incorporation of these measures into clinical and patient-reported research. Emphasizing patient-reported outcomes in neurogenic bladder research will guide clinicians and other stakeholders to improve quality of life in this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

Multilayered disease-mimicking bladder phantom with realistic surface topology for optical coherence tomography

NASA Astrophysics Data System (ADS)

Smith, Gennifer T.; Lurie, Kristen L.; Khan, Saara A.; Liao, Joseph C.; Ellerbee, Audrey K.

2014-03-01

Optical coherence tomography (OCT) has shown potential as a complementary modality to white light cystoscopy (WLC), the gold standard for imaging bladder cancer. OCT can visualize sub-surface details of the bladder wall, which enables it to stage cancers and detect tumors that are otherwise invisible to WLC. Currently, OCT systems have too slow a speed and too small a field of view for comprehensive bladder imaging, which limits its clinical utility. Validation and feasibility testing of technological refinements aimed to provide faster imaging and wider fields of view necessitates a realistic bladder phantom. We present a novel process to fabricate the first such phantom that mimics both the optical and morphological properties of layers of the healthy and pathologic bladder wall as they characteristically appear with OCT. The healthy regions of the silicone-based phantom comprises three layers: the urothelium, lamina propria and muscularis propria, each containing an appropriate concentration of titanium dioxide to mimic its distinct scattering properties. As well, the layers each possess a unique surface appearance imposed by a textured mold. Within this phantom, pathologic tissue-mimicking regions are created by thickening specific layers or creating inclusions that disrupt the layered appearance of the bladder wall, as is characteristic of bladder carcinomas. This phantom can help to evaluate the efficacy of new OCT systems and software for tumor localization. Moreover, the procedure we have developed is highly generalizable for the creation of OCT-relevant, multi-layer phantoms for tissues that incorporate diseased states characterized by the loss of layered structures.

Pheochromocytoma of the Urinary Bladder - A Case Report of an Unusual Presentation.

PubMed

Nerli, Rajendra B; Magdum, Prasad V; Patil, Amey Y; Devraju, Shishir; Hiremath, M B

2015-09-01

Urinary bladder pheochromocytoma is rare. We report a case of bladder pheochromocytoma presenting with practically no obvious clinical symptoms in an adolescent who had undergone repair of mitral valve disease.

Role of Bladder Hydrodistention and Intravesical Sodium Hyaluronate in the Treatment of Interstitial Cystitis.

PubMed

Yang, Jin-Yi; Wei, Wei; Lan, Yu-Long; Liu, Jun-Qiang; Wang, Hai-Bo; Li, Shao

2015-12-23

To evaluate the clinical efficacy of bladder hydrodistention and intravesical sodium hyaluronate in the treatment of interstitial cystitis (IC). Twenty-one patients with IC received intravesical sodium hyaluronate therapy under nerve block or intravenous anesthesia. Bladders were perfused with 100 cmH2O perfusion pressure and expanded for 10 min and were later injected with 40 mg/50 mL sodium hyaluronate through the catheter. After 1 h, the perfusion fluid was released. Perfusion was applied once per week, 4 to 6 times as a course of treatment. Under anesthesia, the average bladder capacity was 191.62 ± 88.67 mL, and after bladder expansion, the bladder capacity reached 425.33 ± 79.83 mL (P = .000). There were 2 suspected bladder ruptures after bladder expansion at 6.5 min and 7.2 min. After 10 min of bladder expansion, there were 19 cases of significantly gross hematuria. After treatment, the catheters of 17 patients were removed at 24 h; for the 2 cases of hematuria, catheters were removed at 72 h and for the 2 cases of suspected bladder rupture, catheters were removed after 4 days. After catheter removal, the pain threshold significantly decreased, and the maximum urinary output increased slightly. Compared with values before treatment, the day before the second injection of sodium hyaluronate, the frequency of urination decreased significantly (32.8 vs. 18.5 times/24 h), the maximum urinary output increased significantly (86.7 vs. 151.9 mL), the pain decreased significantly (8.7 vs. 3.0), and the O'Leary-Sant IC score and quality of life score were significantly decreased (30.0 vs. 17.0 and 5.9 vs. 2.4, respectively) (P = .000). Bladder hydrodistention under anesthesia for patients with severe intractable IC produces immediate effectiveness; sodium hyaluronic infusion can alleviate frequent urination and pain, and the efficacy was positively correlated with the duration of treatment.

What is the role of combination drug therapy in the treatment of overactive bladder? ICI-RS 2014.

PubMed

Visco, Anthony G; Fraser, Matthew O; Newgreen, Donald; Oelke, Matthias; Cardozo, Linda

2016-02-01

The role of combination therapy using oral antimuscarinic medications for the treatment of overactive bladder was proposed at the 2014 International Consultation on Incontinence-Research Society in Bristol, UK to identify key factors to consider when making clinical decisions and to guide future research design. Combination therapy is justified if monotherapy is associated with suboptimal efficacy or bothersome side effects. Combination therapy has the potential to improve efficacy with fewer side effects than monotherapy. Two Phase 2 studies comparing combination therapy that included an antimuscarinic demonstrated improvement in mean voided volume, the primary outcome chosen, with some combinations showing improved micturition frequency and quality of life. The two studies found no evidence of an increased safety risk with combination therapy compared to monotherapy. Future studies should use clinically meaningful or patient reported outcomes such as incontinence episodes when comparing efficacy. If surrogate measures are used, a clear justification should be provided. Cost analyses should be planned for clinical research trials evaluating combination drug therapy. Combination therapy is reasonable when monotherapy has suboptimal efficacy or bothersome side effects. Future research studies evaluating combination therapy for urgency urinary incontinence should ideally(1) be performed as part of a randomized clinical trial,(2) evaluate non-responders to monotherapy,(3) evaluate combination therapy using medications with different mechanisms of action,(4) include clinically meaningful and patient reported outcomes when evaluating efficacy, and(5) include cost-effectiveness analyses to justify any increased cost by showing improvement in efficacy or reduction in side effects. © 2016 Wiley Periodicals, Inc.

Voiding diary might serve as a useful tool to understand differences between bladder pain syndrome/interstitial cystitis and overactive bladder.

PubMed

Kim, Sung Han; Oh, Shin Ah; Oh, Seung-June

2014-02-01

To identify the voiding characteristics of bladder pain syndrome/interstitial cystitis and overactive bladder. Between September 2005 and June 2010, 3-day voiding diaries of 49 consecutive bladder pain syndrome/interstitial cystitis patients and 301 overactive bladder patients were prospectively collected at an outpatient clinic and retrospectively analyzed. The characteristics of the two groups were not significantly different. However, all voiding variables including volume and frequency were significantly different except for the total voided volume: patients with bladder pain syndrome/interstitial cystitis showed significantly higher voiding frequencies, smaller maximal and mean voided volume, and more constant and narrower ranges of voided volume compared with overactive bladder patients (P < 0.005). Furthermore, mean intervals between voiding in bladder pain syndrome/interstitial cystitis were shorter and more consistent during the day and night (P < 0.001), although mean night-time variances were greater than daytime variances. Logistic regression analysis showed that total night-time frequency, maximal night-time voided volume and mean variance of daytime voiding intervals most significantly differentiated the two groups. Some voiding characteristics of bladder pain syndrome/interstitial cystitis and overactive bladder patients differ significantly according to 3-day voiding diary records. These findings provide additional information regarding the differences between these two diseases in the outpatient clinical setting. © 2013 The Japanese Urological Association.

Doing More for More: Unintended Consequences of Financial Incentives for Oncology Specialty Care.

PubMed

O'Neil, Brock; Graves, Amy J; Barocas, Daniel A; Chang, Sam S; Penson, David F; Resnick, Matthew J

2016-02-01

Specialty care remains a significant contributor to health care spending but largely unaddressed in novel payment models aimed at promoting value-based delivery. Bladder cancer, chiefly managed by subspecialists, is among the most costly. In 2005, Centers for Medicare and Medicaid Services (CMS) dramatically increased physician payment for office-based interventions for bladder cancer to shift care from higher cost facilities, but the impact is unknown. This study evaluated the effect of financial incentives on patterns of fee-for-service (FFS) bladder cancer care. Data from a 5% sample of Medicare beneficiaries from 2001-2013 were evaluated using interrupted time-series analysis with segmented regression. Primary outcomes were the effects of CMS fee modifications on utilization and site of service for procedures associated with the diagnosis and treatment of bladder cancer. Rates of related bladder cancer procedures that were not affected by the fee change were concurrent controls. Finally, the effect of payment changes on both diagnostic yield and need for redundant procedures were studied. All statistical tests were two-sided. Utilization of clinic-based procedures increased by 644% (95% confidence interval [CI] = 584% to 704%) after the fee change, but without reciprocal decline in facility-based procedures. Procedures unaffected by the fee incentive remained unchanged throughout the study period. Diagnostic yield decreased by 17.0% (95% CI = 12.7% to 21.3%), and use of redundant office-based procedures increased by 76.0% (95% CI = 59% to 93%). Financial incentives in bladder cancer care have unintended and costly consequences in the current FFS environment. The observed price sensitivity is likely to remain a major issue in novel payment models failing to incorporate procedure-based specialty physicians. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Individualized Nonadaptive and Online-Adaptive Intensity-Modulated Radiotherapy Treatment Strategies for Cervical Cancer Patients Based on Pretreatment Acquired Variable Bladder Filling Computed Tomography Scans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bondar, M.L., E-mail: m.bondar@erasmusmc.nl; Hoogeman, M.S.; Mens, J.W.

2012-08-01

Purpose: To design and evaluate individualized nonadaptive and online-adaptive strategies based on a pretreatment established motion model for the highly deformable target volume in cervical cancer patients. Methods and Materials: For 14 patients, nine to ten variable bladder filling computed tomography (CT) scans were acquired at pretreatment and after 40 Gy. Individualized model-based internal target volumes (mbITVs) accounting for the cervix and uterus motion due to bladder volume changes were generated by using a motion-model constructed from two pretreatment CT scans (full and empty bladder). Two individualized strategies were designed: a nonadaptive strategy, using an mbITV accounting for the full-rangemore » of bladder volume changes throughout the treatment; and an online-adaptive strategy, using mbITVs of bladder volume subranges to construct a library of plans. The latter adapts the treatment online by selecting the plan-of-the-day from the library based on the measured bladder volume. The individualized strategies were evaluated by the seven to eight CT scans not used for mbITVs construction, and compared with a population-based approach. Geometric uniform margins around planning cervix-uterus and mbITVs were determined to ensure adequate coverage. For each strategy, the percentage of the cervix-uterus, bladder, and rectum volumes inside the planning target volume (PTV), and the clinical target volume (CTV)-to-PTV volume (volume difference between PTV and CTV) were calculated. Results: The margin for the population-based approach was 38 mm and for the individualized strategies was 7 to 10 mm. Compared with the population-based approach, the individualized nonadaptive strategy decreased the CTV-to-PTV volume by 48% {+-} 6% and the percentage of bladder and rectum inside the PTV by 5% to 45% and 26% to 74% (p < 0.001), respectively. Replacing the individualized nonadaptive strategy by an online-adaptive, two-plan library further decreased the percentage of bladder and rectum inside the PTV (0% to 10% and -1% to 9%; p < 0.004) and the CTV-to-PTV volume (4-96 ml). Conclusions: Compared with population-based margins, an individualized PTV results in better organ-at-risk sparing. Online-adaptive radiotherapy further improves organ-at-risk sparing.« less

Safety and efficacy of fesoterodine fumarate in patients with overactive bladder: results of a post-marketing surveillance study in Korea.

PubMed

Kim, Tae Heon; Lee, Sang Eun; Lee, Hahn-Ey; Lee, Kyu-Sung

2016-08-01

The aim of this study was to evaluate the safety and efficacy of fesoterodine fumarate (fesoterodine; Toviaz ) in Korean patients with overactive bladder (OAB) in routine clinical practice. This was an open-label, non-interventional, prospective, post-marketing surveillance study submitted to the Korean Ministry of Food and Drug Safety. A total of 3109 patients aged ≥18 years with OAB symptoms were prescribed flexible doses of fesoterodine at the investigator's discretion. Safety was assessed based upon the reporting of adverse events (AEs). Efficacy was evaluated on the basis of patient self-assessment using a bladder diary as well as on the basis of investigator assessment in terms of overall clinical efficacy. A final analysis was performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy analysis, respectively. The mean treatment duration of fesoterodine was 83.2 days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107), constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI) per 24 hours decreased by 4.0, 2.4, and 0.8, respectively (all p < 0.001). At the final follow-up visit, the investigators found improvement in clinical efficacy for the majority of patients (90.1%, 2684/2978). Limitations of this study include the observational study design and the relatively short treatment duration. These results suggest that fesoterodine is a well tolerated and effective treatment for Korean patients with OAB in routine clinical practice.

Quality of life in women undergoing urinary diversion for bladder cancer: results of a multicenter study among long-term disease-free survivors.

PubMed

Gacci, Mauro; Saleh, Omar; Cai, Tommaso; Gore, John L; D'Elia, Carolina; Minervini, Andrea; Masieri, Lorenzo; Giannessi, Claudia; Lanciotti, Michele; Varca, Virginia; Simonato, Alchiede; Serni, Sergio; Carmignani, Giorgio; Carini, Marco

2013-03-12

Women undergoing radical cystectomy (RC) and urinary diversion for bladder cancer experience substantial limitations in health-related quality of life (HRQOL). However, the level of discomfort caused by different urinary diversion has been never evaluated in long term survivors. The aim of this multicenter study is to evaluate differences in HRQOL among recurrence-free women undergoing cutaneous ureterostomy (CUS), Bricker's ileal conduit (BK-IC) and Orthotopic neobladder VIP (ONB-VIP) in disease-free females treated with radical cystectomy (RC), with long-term follow up (mean 60.1 months; range 36-122 months). All consecutively treated female patients from two urological institutions who underwent RC and urinary diversion from January 2000 to December 2008, with no evidence of tumor recurrence at a minimum follow up of 36 months, were included. Patients received the European Organisation for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL). Clinical data and questionnaire results were analyzed in order to evaluate the HRQOL differences among diversion groups. We identified 37 females (median age: 68, range 45-82 years), including 12 status-post CUS, 16 who underwent BK-IC, and 9 who underwent ONB-VIP. Most were healthy (24/37 with no comorbidities, 4/37 Charlson 1-2, 9/37 Charlson 3 or greater - we didn't considered bladder cancer in Charlson evaluation because bladder cancer was the main inclusion criteria). Women undergoing CUS endorsed worse FACT-BL scores compared with BK-IC and ONB-VIP patients, worse HRQOL regarding physical and emotional well-being (p=0.008 and p=0.02, respectively), and a trend toward worse EORTC QLQ-C30 scores for appetite loss and fatigue (p=0.05 for both). In our study long-term disease-free females treated with CUS endorsed worse HRQOL compared with women who underwent BK-IC or ONB-VIP, mostly due to worse physical and emotional perception of their body image.

3D reconstruction of cystoscopy videos for comprehensive bladder records

PubMed Central

Lurie, Kristen L.; Angst, Roland; Zlatev, Dimitar V.; Liao, Joseph C.; Ellerbee Bowden, Audrey K.

2017-01-01

White light endoscopy is widely used for diagnostic imaging of the interior of organs and body cavities, but the inability to correlate individual 2D images with 3D organ morphology limits its utility for quantitative or longitudinal studies of disease physiology or cancer surveillance. As a result, most endoscopy videos, which carry enormous data potential, are used only for real-time guidance and are discarded after collection. We present a computational method to reconstruct and visualize a 3D model of organs from an endoscopic video that captures the shape and surface appearance of the organ. A key aspect of our strategy is the use of advanced computer vision techniques and unmodified, clinical-grade endoscopy hardware with few constraints on the image acquisition protocol, which presents a low barrier to clinical translation. We validate the accuracy and robustness of our reconstruction and co-registration method using cystoscopy videos from tissue-mimicking bladder phantoms and show clinical utility during cystoscopy in the operating room for bladder cancer evaluation. As our method can powerfully augment the visual medical record of the appearance of internal organs, it is broadly applicable to endoscopy and represents a significant advance in cancer surveillance opportunities for big-data cancer research. PMID:28736658

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiss, Christian; Roemer, Felix von; Capalbo, Gianni

Purpose: The objectives of this study were to investigate the expression of survivin in tumor samples from patients with high-risk T1 bladder cancer and to correlate its expression with clinicopathologic features as well as clinical outcomes after initial transurethral resection (TURBT) followed by radiotherapy (RT) or radiochemotherapy (RCT). Methods and Materials: Survivin protein expression was evaluated by immunohistochemistry on tumor specimen (n = 48) from the initial TURBT, and was correlated with clinical and histopathologic characteristics as well as with 5-year rates of local failure, tumor progression, and death from urothelial cancer after primary bladder sparring treatment with RT/RCT. Results:more » Survivin was not expressed in normal bladder urothelium but was overexpressed in 67% of T1 tumors. No association between survivin expression and clinicopathologic factors (age, gender, grading, multifocality, associated carcinoma in situ) could be shown. With a median follow-up of 27 months (range, 3-140 months), elevated survivin expression was significantly associated with an increased probability of local failure after TURBT and RCT/RT (p = 0.003). There was also a clear trend toward a higher risk of tumor progression (p = 0.07) and lower disease-specific survival (p = 0.10). Conclusions: High survivin expression is a marker of tumor aggressiveness and may help to identify a subgroup of patients with T1 bladder cancer at a high risk for recurrence when treated with primary organ-sparing approaches such as TURBT and RCT.« less

Health-related quality-of-life parameters as independent prognostic factors in advanced or metastatic bladder cancer.

PubMed

Roychowdhury, D F; Hayden, A; Liepa, A M

2003-02-15

This retrospective analysis examined prognostic significance of health-related quality-of-life (HRQoL) parameters combined with baseline clinical factors on outcomes (overall survival, time to progressive disease, and time to treatment failure) in bladder cancer. Outcome and HRQoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30) data were collected prospectively in a phase III study assessing gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in locally advanced or metastatic bladder cancer. Prespecified baseline clinical factors (performance status, tumor-node-metastasis staging, visceral metastases [VM], alkaline phosphatase [AP] level, number of metastatic sites, prior radiotherapy, disease measurability, sex, time from diagnosis, and sites of disease) and selected HRQoL parameters (global QoL; all functional scales; symptoms: pain, fatigue, insomnia, dyspnea, anorexia) were evaluated using Cox's proportional hazards model. Factors with individual prognostic value (P <.05) on outcomes in univariate models were assessed for joint prognostic value in a multivariate model. A final model was developed using a backward selection strategy. Patients with baseline HRQoL were included (364 of 405, 90%). The final model predicted longer survival with low/normal AP levels, no VM, high physical functioning, low role functioning, and no anorexia. Positive prognostic factors for time to progressive disease were good performance status, low/normal AP levels, no VM, and minimal fatigue; for time to treatment failure, they were low/normal AP levels, minimal fatigue, and no anorexia. Global QoL was a significant predictor of outcome in univariate analyses but was not retained in the multivariate model. HRQoL parameters are independent prognostic factors for outcome in advanced bladder cancer; their prognostic importance needs further evaluation.

Adenoviral receptor expression of normal bladder and transitional cell carcinoma of the bladder.

PubMed

Buscarini, Maurizio; Quek, Marcus L; Gilliam-Hegarich, Susan; Kasahara, Nori; Bochner, Bernard

2007-01-01

The insertion of absent or underexpressed genes into cancer cells to alter their malignant phenotype is an important potential application of available gene therapy technology. One of the more common viral vector systems that has been extensively studied for this purpose are the replication-deficient adenoviruses (Ad). Adenoviral infection of cells is mediated through a complex pathway, initiated following viral-cell attachment. Adenoviral-cell attachment occurs following interactions with a 46-kDa transmembrane protein with high affinity for both the Coxsackie and adenovirus, designated the CAR (Coxsackie and adenoviral receptor). Additional important cell-viral interactions that occur involve the alpha(v)-based integrins, specifically alpha(v)beta3 and alpha(v)beta5. The purpose of the present study was to determine the extent of expression and localization of the known Ad receptor proteins (CAR, alpha(v)beta3, and alpha(v)beta5) in normal and cancerous human bladders. Frozen tissue samples of normal bladder and invasive transitional cell cancers of the bladder were evaluated. Tissue blocks containing muscle-invasive transitional cell carcinoma (TCC) were obtained following radical cystectomy, which were performed at our institution. Thirty-two invasive transitional cell bladder tumors were evaluated, each with a matched sample of histologically normal-appearing bladder used as a control. Four additional samples of normal bladder were obtained from patients with no evidence of disease of the bladder and served as further controls. Three additional cases of invasive bladder cancer with no matching normal tissue were also evaluated. Identification of the CAR receptor was performed using the anti-CAR mouse monoclonal antibody designated RmBC. The integrins alpha(v)beta3 and alpha(v)beta5 were identified using the mouse monoclonal antibodies designated LM609 and P1F6 respectively. All slides were evaluated by two of the authors (M.B., B.B.) without knowledge of the clinical and pathological data. Normal bladder: Normal bladder mucosa demonstrated a marked positivity for CAR in 29/35 (82.8%) cases. In contrast, normal transitional epithelial cells were uniformly negative when tested for the integrins alpha(v)beta3 and alpha(v)beta5. Subepithelial tissues, specifically the connective tissue components of the lamina propria and deep muscle wall of the bladder, were positive for alpha(v)beta3 and for alpha(v)beta5 in 61 and 75% of samples, respectively. Endothelial cells associated with the various layers throughout the bladder uniformly expressed both integrins and served as a consistent internal control for both antibodies. An almost identical staining pattern of the endothelium was observed using LM609 and P1F6 in all samples tested. Bladder transitional cell carcinoma: CAR immunoreactivity against TCC cells was uniformly decreased compared to normal transitional cells. Nine tumors exhibited a weak positivity for CAR while the remaining samples were negative. In some cases, the absence of CAR positivity was associated with histological evidence of carcinoma in situ. In 6 cases, it led to the identification of small regions of carcinoma in situ that were not noted on primary pathological evaluation. Peritumoral connective tissue expressed both integrins in the majority of cases, similar to the pattern described above for normal bladder. Transitional cell cancers demonstrated a similar pattern of expression of alpha(v)beta5, in which all tumor cells exhibited minimal or no staining. The success of all viral-mediated gene therapy strategies relies on the ability of the vector to efficiently deliver its genetic material to a target cell population. In the current study, we demonstrate that the bladder epithelial layer consistently expresses high levels of CAR. Deeper layers of the epithelium also express CAR, including the basal layer cells. A decrease in the expression of CAR appears as an early event in bladder carcinogenesis. We observed that both alpha(v)beta3 and alpha(v)beta5 are strongly expressed in muscle cells surrounding the neoplastic cells, as well as within the peritumoral connective tissue. In cases of invasive bladder cancer that have lost CAR expression, an adenoviral vector may still be utilized through the less efficient interactions with the integrins. Bladder tumor tissue may be less susceptible to an adenoviral-mediated gene therapy approach in which a significant percentage of tumor cells require transduction. Adenoviral uptake by tumor or peritumoral cells with subsequent gene transfer could be predicted by the level of CAR and alpha(v)-based integrin expression. This would enhance our ability to identify those patients whose tumors would be more susceptible to Ad-mediated gene delivery as part of an antitumor treatment. 2007 S. Karger AG, Basel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heijkoop, Sabrina T., E-mail: s.heijkoop@erasmusmc.nl; Langerak, Thomas R.; Quint, Sandra

Purpose: To evaluate the clinical implementation of an online adaptive plan-of-the-day protocol for nonrigid target motion management in locally advanced cervical cancer intensity modulated radiation therapy (IMRT). Methods and Materials: Each of the 64 patients had four markers implanted in the vaginal fornix to verify the position of the cervix during treatment. Full and empty bladder computed tomography (CT) scans were acquired prior to treatment to build a bladder volume-dependent cervix-uterus motion model for establishment of the plan library. In the first phase of clinical implementation, the library consisted of one IMRT plan based on a single model-predicted internal targetmore » volume (mpITV), covering the target for the whole pretreatment observed bladder volume range, and a 3D conformal radiation therapy (3DCRT) motion-robust backup plan based on the same mpITV. The planning target volume (PTV) combined the ITV and nodal clinical target volume (CTV), expanded with a 1-cm margin. In the second phase, for patients showing >2.5-cm bladder-induced cervix-uterus motion during planning, two IMRT plans were constructed, based on mpITVs for empty-to-half-full and half-full-to-full bladder. In both phases, a daily cone beam CT (CBCT) scan was acquired to first position the patient based on bony anatomy and nodal targets and then select the appropriate plan. Daily post-treatment CBCT was used to verify plan selection. Results: Twenty-four and 40 patients were included in the first and second phase, respectively. In the second phase, 11 patients had two IMRT plans. Overall, an IMRT plan was used in 82.4% of fractions. The main reasons for selecting the motion-robust backup plan were uterus outside the PTV (27.5%) and markers outside their margin (21.3%). In patients with two IMRT plans, the half-full-to-full bladder plan was selected on average in 45% of the first 12 fractions, which was reduced to 35% in the last treatment fractions. Conclusions: The implemented online adaptive plan-of-the-day protocol for locally advanced cervical cancer enables (almost) daily tissue-sparing IMRT.« less

The Expression of Inflammatory Mediators in Bladder Pain Syndrome.

PubMed

Offiah, Ifeoma; Didangelos, Athanasios; Dawes, John; Cartwright, Rufus; Khullar, Vik; Bradbury, Elizabeth J; O'Sullivan, Suzanne; Williams, Dic; Chessell, Iain P; Pallas, Kenny; Graham, Gerry; O'Reilly, Barry A; McMahon, Stephen B

2016-08-01

Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life. We examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology. Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. We studied the expression of 96 inflammation-related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating these genes in BPS is a potential treatment strategy. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

MMP-1 and Pro-MMP-10 as potential urinary pharmacodynamic biomarkers of FGFR3-targeted therapy in patients with bladder cancer.

PubMed

Du, Xiangnan; Lin, Benjamin C; Wang, Qian-Rena; Li, Hao; Ingalla, Ellen; Tien, Janet; Rooney, Isabelle; Ashkenazi, Avi; Penuel, Elicia; Qing, Jing

2014-12-15

The aim of this study was to identify noninvasive pharmacodynamic biomarkers of FGFR3-targeted therapies in bladder cancer to facilitate the clinical development of experimental agent targeting FGFR3. Potential soluble pharmacodynamic biomarkers of FGFR3 were identified using a combination of transcriptional profiling and biochemical analyses in preclinical models. Two matrix metalloproteinases (MMP), MMP-1 and MMP-10, were selected for further studies in human bladder cancer xenograft models treated with a specific anti-FGFR3 monoclonal antibody, R3Mab. Serum and urinary levels of MMP-1 and MMP-10 were determined in healthy donors and patients with bladder cancer. The modulation of MMP-1 and MMP-10 by R3Mab in patients with bladder cancer was further evaluated in a phase I dose-escalation study. MMP-1 and MMP-10 mRNA and protein were downmodulated by FGFR3 shRNA and R3Mab in bladder cancer cell lines. FGFR3 signaling promoted the expression and secretion of MMP-1 and pro-MMP-10 in a MEK-dependent fashion. In bladder cancer xenograft models, R3Mab substantially blocked tumor progression and reduced the protein levels of human MMP-1 and pro-MMP-10 in tumor tissues as well as in mouse serum. Furthermore, both MMP-1 and pro-MMP-10 were elevated in the urine of patients with advanced bladder cancer. In a phase I dose-escalation trial, R3Mab administration resulted in an acute reduction of urinary MMP-1 and pro-MMP-10 levels in patients with bladder cancer. These findings reveal a critical role of FGFR3 in regulating MMP-1 and pro-MMP-10 expression and secretion, and identify urinary MMP-1 and pro-MMP-10 as potential pharmacodynamic biomarkers for R3Mab in patients with bladder cancer. ©2014 American Association for Cancer Research.

Cutaneous metastasis of transitional cell bladder carcinoma: a rare presentation and literature review.

PubMed

Salemis, Nikolaos S; Gakis, Christos; Zografidis, Andreas; Gourgiotis, Stavros

2011-01-01

Cutaneous metastasis from transitional cell bladder carcinoma is a rare clinical entity associated with poor prognosis. We present a case of cutaneous metastasis arising from a transitional cell bladder carcinoma in a male patient who had undergone a radical cystectomy and bilateral ureterostomy 17 months previously. The cutaneous metastasis became evident 3 months before the manifestations of generalized recurrent disease. An awareness of this rare clinical entity and high index of suspicion is needed to rule out metastatic spread in patients with a previous history of transitional cell bladder carcinoma presenting with cutaneous nodules. Definitive diagnosis requires a histological confirmation, but prognosis is generally poor.

Iatrogenic water intoxication during pelvic ultrasonography in a patient with diabetes insipidus.

PubMed

Derinöz, Okşan; Emeksiz, Hamdi Cihan; Kalkan, Gökhan; Camurdan, Orhun

2012-01-01

Pelvic ultrasonography (US) is a simple and non-invasive radiologic test to evaluate the pelvic organs. It requires a full bladder for better visualization. Our case is a 14-year-old female with diabetes insipidus (DI) who admitted to the pediatric emergency service with the complaints of seizure and agitation after drinking 4 liters of water in one hour for a pelvic US examination due to work-up for delayed puberty. Her biochemical and clinical evaluation revealed water intoxication (WI). To our knowledge, this is the first WI case developed in a patient with DI. Here, we discuss the underlying factors leading to this complication and recommended an approach to obtain a better sonographic image without necessitating oral water intake to fill the urinary bladder.

Unusual asymptomatic presentation of bladder cancer metastatic to the penis.

PubMed

Giunchi, Francesca; Vasuri, Francesco; Valerio, Vagnoni; Montagnani, Ilaria; Nelli, Federico; Fiorentino, Michelangelo; Raspollini, Maria Rosaria

2017-06-01

Penile metastasis is an extremely rare event and mainly originate from primary pelvic tumor sites such us urinary bladder, gastro-intestinal tract and prostate and more rarely from respiratory system, bone tumors and melanoma. Here we describe the unusual presentation of two bladder urothelial cancer metastatic to the penis with no relevant clinical symptoms. Namely, a 69 years-old man with a warthy lesions of the foreskin and the glans misunderstood for a condylomata that at histological and immunohistochemical analysis showed a bladder urothelial carcinoma; and a 71 years-old man with reddish skin lesion of the glans, a previous history of bladder and urethral carcinoma and histological pagetoid spread of urothelial cancer to the glans. Recurrent bladder urothelial carcinoma is usually a visceral disease that rarely presents as a superficial asymptomatic skin lesion. The two reported cases were asymptomatic superficial penis metastases with a relatively slow growth and a fairy good prognosis after conservative surgical approach. Accurate clinical examination of the penis is mandatory for males with history of bladder cancer. Copyright © 2016 Elsevier GmbH. All rights reserved.

How updating textual clinical practice guidelines impacts clinical decision support systems: a case study with bladder cancer management.

PubMed

Bouaud, Jacques; Séroussi, Brigitte; Brizon, Ambre; Culty, Thibault; Mentré, France; Ravery, Vincent

2007-01-01

Guideline-based clinical decision support systems (CDSSs) can be effective in increasing physician compliance with recommendations. However, the ever growing pace at which medical knowledge is produced requires that clinical practice guidelines (CPGs) be updated regularly. It is therefore mandatory that CDSSs be revised accordingly. The French Association for Urology publishes CPGs on bladder cancer management every 2 years. We studied the impact of the 2004 revision of these guidelines, with respect to the 2002 version with a CDSS, UroDoc. We proposed a typology of knowledge base modifications resulting from the update of CPGs making the difference between practice, clinical conditions and recommendations refinement as opposed to new practice and new recommendations. The number of formalized recommendations increased from 577 in 2002 to 1,081 in 2004. We evaluated the two versions of UroDoc on a randomized sample of patient records. A single new practice that modifies a decision taken in 49% of all recorded decisions leads to a fall from 67% to 46% of the compliance rate of decisions.

Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for urothelial cell carcinoma of the urinary bladder 2017.

PubMed

Alharbi, Hulayel; Alkhateeb, Sultan; Murshid, Esam; Alotaibi, Mohammed; Abusamra, Ashraf; Rabah, Danny; Almansour, Mubarak; Alghamdi, Abdullah; Aljubran, Ali; Eltigani, Amin; Alkushi, Hussein; Ahmed, Imran; Alsharm, Abdullah; Bazarbashi, Shouki

2018-01-01

This is an update to the previously published Saudi guidelines for the evaluation and medical/surgical management of patients diagnosed with urothelial cell carcinoma of the urinary bladder. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7 th edition. The guidelines are presented with their accompanying supporting evidence level, which is based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health-care policymakers in the management of patients diagnosed with urothelial cell carcinoma of the urinary bladder.

Whyever bladder tissue engineering clinical applications still remain unusual even though many intriguing technological advances have been reached?

PubMed

Alberti, C

2016-01-01

To prevent problematic outcomes of bowel-based bladder reconstructive surgery, such as prosthetic tumors and systemic metabolic complications, research works, to either regenerate and strengthen failing organ or build organ replacement biosubstitute, have been turned, from 90s of the last century, to both regenerative medicine and tissue engineering.Various types of acellular matrices, naturally-derived materials, synthetic polymers have been used for either "unseeded" (cell free) or autologous "cell seeded" tissue engineering scaffolds. Different categories of cell sources - from autologous differentiated urothelial and smooth muscle cells to natural or laboratory procedure-derived stem cells - have been taken into consideration to reach the construction of suitable "cell seeded" templates. Current clinically validated bladder tissue engineering approaches essentially consist of augmentation cystoplasty in patients suffering from poorly compliant neuropathic bladder. No clinical applications of wholly tissue engineered neobladder have been carried out to radical-reconstructive surgical treatment of bladder malignancies or chronic inflammation-due vesical coarctation. Reliable reasons why bladder tissue engineering clinical applications so far remain unusual, particularly imply the risk of graft ischemia, hence its both fibrous contraction and even worse perforation. Therefore, the achievement of graft vascular network (vasculogenesis) could allow, together with the promotion of host surrounding vessel sprouting (angiogenesis), an effective graft blood supply, so avoiding the ischemia-related serious complications.

[Comparative Study on Evaluating the Bladder Volume between BladderScan BVI9400 and Ultrasound System iU22].

PubMed

Luo, Huanli; Wang, Ying; Li, Fang; Ling, Yun; Yang, Dingyi; Jin, Fu

2015-07-01

To evaluate the accuracy of the latest BladderScan BVI9400 on measuring bladder volume. Two bladder phantoms were selected for investigating the accuracy of BVI9400. 341 patients with the iU22 ultrasound examinations were followed by BVI 9400. The difference and correlation between BVI9400 and iU22 were contrastively analyzed. The relative difference between results from BVI9400 and phantom volume was 2.5% and 1.36%. There was a strong correlation for patients between BVI9400 and iU22 (R = 0.96, P < 0.001). The relative difference between BVI9400 and iU22 decreased with the increasing of bladder volume and had no significant difference with patient's gender (P > 0.1). BladderScan BVI9400 had the ability of high accuracy and good stability of measured data. In view of quick and conveniences, BVI9400 could be as auxiliary equipment on pelvic tumor to evaluate whether the bladder volume during fractional radiotherapy was consistency with that during CT positioning.

A Pitfall in Transrectal Prostate Biopsy: Malakoplakia Evaluation of Two Cases Based on the Literature Review

PubMed Central

Solakoglu Kahraman, Dudu; Sayhan, Sevil; Diniz, Gulden; Ayaz, Duygu; Karadeniz, Tugba; Can, Ertan

2014-01-01

Malakoplakia is a rarely seen inflammatory condition that is considered to develop secondary to a chronic Escherichia coli infection. Although malakoplakia usually affects the genitourinary tract, it may also be observed in the colon, stomach, lungs, liver, bones, uterus, and skin. Malakoplakia of the genitourinary system usually involves the bladder, whereas it may also affect the prostate along with the bladder. Malakoplakia of the prostate is very rare, and it may be clinically mistaken for prostatic malignancies. Definitive diagnosis is only possible through histopathological examination. This study elaborates on two patients who presented to our hospital in 2013 with high PSA levels. The primary clinical consideration was prostate carcinoma. However, these two cases were diagnosed as malakoplakia based on the results of histopathological analysis of the transrectal prostate biopsy specimen. PMID:24868476

Primary Bladder Neurofibroma: A Rare Case with Clinical Implications and Diagnostic Challenges.

PubMed

Umakanthan, Srikanth; Naik, Ramadas; Bukelo, Maryann Margaret; Rai, Sharada; Prabhu, Laxman

2015-09-01

Neurofibroma of the genito-urinary tract is rare. Urinary bladder is the commonest organ involved in cases of urinary tract involvement. Patients present early in life and there is male preponderance. We discuss here a case of primary neurofibroma of the urinary bladder in a 52-year-male presenting with haematuria, irritative bladder symptoms and pelvic mass. Cystoscopy showed a swelling in the left lateral wall. A transurethral biopsy revealed neurofibroma of the urinary bladder. Immunohistochemical studies confirmed the diagnosis.

Primary Bladder Neurofibroma: A Rare Case with Clinical Implications and Diagnostic Challenges

PubMed Central

Naik, Ramadas; Bukelo, Maryann Margaret; Rai, Sharada; Prabhu, Laxman

2015-01-01

Neurofibroma of the genito-urinary tract is rare. Urinary bladder is the commonest organ involved in cases of urinary tract involvement. Patients present early in life and there is male preponderance. We discuss here a case of primary neurofibroma of the urinary bladder in a 52-year-male presenting with haematuria, irritative bladder symptoms and pelvic mass. Cystoscopy showed a swelling in the left lateral wall. A transurethral biopsy revealed neurofibroma of the urinary bladder. Immunohistochemical studies confirmed the diagnosis. PMID:26500913

Decision curve analysis assessing the clinical benefit of NMP22 in the detection of bladder cancer: secondary analysis of a prospective trial.

PubMed

Barbieri, Christopher E; Cha, Eugene K; Chromecki, Thomas F; Dunning, Allison; Lotan, Yair; Svatek, Robert S; Scherr, Douglas S; Karakiewicz, Pierre I; Sun, Maxine; Mazumdar, Madhu; Shariat, Shahrokh F

2012-03-01

• To employ decision curve analysis to determine the impact of nuclear matrix protein 22 (NMP22) on clinical decision making in the detection of bladder cancer using data from a prospective trial. • The study included 1303 patients at risk for bladder cancer who underwent cystoscopy, urine cytology and measurement of urinary NMP22 levels. • We constructed several prediction models to estimate risk of bladder cancer. The base model was generated using patient characteristics (age, gender, race, smoking and haematuria); cytology and NMP22 were added to the base model to determine effects on predictive accuracy. • Clinical net benefit was calculated by summing the benefits and subtracting the harms and weighting these by the threshold probability at which a patient or clinician would opt for cystoscopy. • In all, 72 patients were found to have bladder cancer (5.5%). In univariate analyses, NMP22 was the strongest predictor of bladder cancer presence (predictive accuracy 71.3%), followed by age (67.5%) and cytology (64.3%). • In multivariable prediction models, NMP22 improved the predictive accuracy of the base model by 8.2% (area under the curve 70.2-78.4%) and of the base model plus cytology by 4.2% (area under the curve 75.9-80.1%). • Decision curve analysis revealed that adding NMP22 to other models increased clinical benefit, particularly at higher threshold probabilities. • NMP22 is a strong, independent predictor of bladder cancer. • Addition of NMP22 improves the accuracy of standard predictors by a statistically and clinically significant margin. • Decision curve analysis suggests that integration of NMP22 into clinical decision making helps avoid unnecessary cystoscopies, with minimal increased risk of missing a cancer. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Catheterless Long-Term Ambulatory Urodynamic Measurement Using a Novel Three-Device System

PubMed Central

Wille, Sebastian; Schumacher, Pauline; Paas, Jenny; Tenholte, Dirk; Eminaga, Okyaz; Müller, Ute; Muthen, Noemi; Mehner, Jan; Cornely, Oliver; Engelmann, Udo

2014-01-01

Aims Long-term urodynamics are required because bladder-emptying disorders are often not clearly revealed by conventional urodynamics. Patients with severe clinical overactive bladder symptoms, for instance, often show normal results. This may be due to the short evaluation time and psychological factors that complicate conventional urodynamics. This study aimed to develop an ambulatory three-component urodynamic measurement system that is easy to operate, registers urodynamic parameters for several days, and has no negative impact on the patient. Methods We developed an intravesical capsule combined with a hand-held device to register voiding desire and micturition, and an alarm pad device that detects urine loss. Recently, the intravesical capsule and its proven function were detailed in the literature. Here, we present detailed in vitro results using a female bladder model. The flexible capsule was C-shaped to minimize the risk of expulsion from the bladder during micturition. Results of biocompatibility evaluation of the intravesical capsule, which is called Wille Capsule (WiCa) are described. Results The WiCa with an oval nose and a maximum outer diameter of 5.5 mm was easily inserted through a 25-French cystoscope. Removing the WiCa by grasping the nose using the female model with bladder was easily conducted. Expulsion of the WiCa during voiding was avoided through a novel C-shaped device design. Based on in vitro cytotoxicity studies, the capsule is a promising and safe device. Conclusion Our novel system is an innovative minimally-invasive tool for accurate long-term urodynamic measurement, and does not require inserting a transurethral catheter. PMID:24840482

Evaluation of cisplatin administered with piroxicam in dogs with transitional cell carcinoma of the urinary bladder.

PubMed

Greene, Shawna N; Lucroy, Michael D; Greenberg, Chelsea B; Bonney, Patty L; Knapp, Deborah W

2007-10-01

To evaluate the antitumor activity and toxic effects of a conservative dose of cisplatin administered in combination with piroxicam to dogs with transitional cell carcinoma (TCC) of the urinary bladder. Clinical trial (nonrandomized, noncontrolled). 14 client-owned dogs with histologically confirmed TCC of the urinary bladder. Each dog was treated with cisplatin (50 mg/m(2), i.v., q 21 d [reduced to 40 mg/m(2), i.v., q 21 d because of toxic effects]) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h). A CBC, serum biochemical analyses, and urinalysis were performed prior to each cisplatin treatment. Tumor staging (determined from thoracic and abdominal radiographic and urinary bladder ultrasonographic findings) was performed before treatment and at 6-week intervals during treatment. 5 dogs received only 1 dose of cisplatin because of the rapid progression of disease (n = 2) or toxic effects (3). With regard to the neoplastic disease among the other 9 dogs, 1 had partial remission, 5 had stable disease, and 3 had progressive disease after 6 weeks of treatment. Median progression-free interval was 78 days (range, 20 to 112 days). Median survival time was 307 days (range, 29 to 929 days). Moderate to severe renal toxicosis and moderate to severe gastrointestinal toxicosis developed in 5 and 8 dogs, respectively. Because of minimal efficacy and associated renal and gastrointestinal toxicosis, administration of cisplatin (40 to 50 mg/m(2)) with piroxicam cannot be recommended for treatment of dogs with TCC of the urinary bladder.

Bladder Carcinoma Data with Clinical Risk Factors and Molecular Markers: A Cluster Analysis

PubMed Central

Redondo-Gonzalez, Enrique; de Castro, Leandro Nunes; Moreno-Sierra, Jesús; Maestro de las Casas, María Luisa; Vera-Gonzalez, Vicente; Ferrari, Daniel Gomes; Corchado, Juan Manuel

2015-01-01

Bladder cancer occurs in the epithelial lining of the urinary bladder and is amongst the most common types of cancer in humans, killing thousands of people a year. This paper is based on the hypothesis that the use of clinical and histopathological data together with information about the concentration of various molecular markers in patients is useful for the prediction of outcomes and the design of treatments of nonmuscle invasive bladder carcinoma (NMIBC). A population of 45 patients with a new diagnosis of NMIBC was selected. Patients with benign prostatic hyperplasia (BPH), muscle invasive bladder carcinoma (MIBC), carcinoma in situ (CIS), and NMIBC recurrent tumors were not included due to their different clinical behavior. Clinical history was obtained by means of anamnesis and physical examination, and preoperative imaging and urine cytology were carried out for all patients. Then, patients underwent conventional transurethral resection (TURBT) and some proteomic analyses quantified the biomarkers (p53, neu, and EGFR). A postoperative follow-up was performed to detect relapse and progression. Clusterings were performed to find groups with clinical, molecular markers, histopathological prognostic factors, and statistics about recurrence, progression, and overall survival of patients with NMIBC. Four groups were found according to tumor sizes, risk of relapse or progression, and biological behavior. Outlier patients were also detected and categorized according to their clinical characters and biological behavior. PMID:25866762

The relationship between promoter methylation of p16 gene and bladder cancer risk: a meta-analysis

PubMed Central

Qi, Defeng; Li, Jinhui; Jiang, Mei; Liu, Chenli; Hu, Yuan; Li, Mengxi; Su, Jialin; Que, Biao; Ji, Weidong

2015-01-01

Purpose: Many scientific evidences suggested that the methylation of p16INK4a (p16) was associated with bladder cancer, but some existing studies have yielded inconclusive results about the relationship between p16 promoter methylation and pathological features or the tumor grade of bladder cancer. This meta-analysis of studies aims to evaluate the clinical and prognostic significance of p16 methylation in bladder carcinogenesis. Methods: Studies were systemically searched via PubMed and Google Scholar in English up to Sept 2015 and a total of ten appropriate studies (693 cases and 290 controls) with an average NOS score of 6.8 were included. The quality of the appropriate studies was measured by the Newcastle-Ottawa Scale (NOS) assessment. Results: The meta-analysis results revealed that the methylation state of p16 was statistically significantly associated with an increased risk of bladder cancer (OR=6.71, 95% CI=3.79-11.87) compared to control, and there is no statistically significantly association between the p16 methylation and the tumor pTNM staging (OR=0.59, 95% CI=0.22-1.60) or the tumor grade (OR=1.01, 95% CI=0.52-1.94) in p16 methylated patients compared to unmethylated patients. Conclusions: our meta-analysis indicates that p16 promoter methylation may be a promising biomarker for the diagnosis of bladder cancer and the inactivation of p16 may be an early event in bladder carcinogenesis. More studies with larger numbers of participants worldwide are needed to further identify the obvious association above. PMID:26884993

Association between cannabis use and the risk of bladder cancer: results from the California Men's Health Study.

PubMed

Thomas, Anil A; Wallner, Lauren P; Quinn, Virginia P; Slezak, Jeffrey; Van Den Eeden, Stephen K; Chien, Gary W; Jacobsen, Steven J

2015-02-01

To investigate the association of cannabis use and tobacco smoking on the incidence of bladder cancer within the California Men's Health Study cohort. We evaluated the records of 84,170 participants in a multiethnic cohort of men aged 45-69 years. Information on demographic and lifestyle factors including smoking history and cannabis use was collected using mailed questionnaires between 2002 and 2003. We linked the study data with clinical records including cancer data from electronic health records. Overall 34,000 (41%) cohort members reported cannabis use, 47,092 (57%) reported tobacco use, 22,500 (27%) reported using both, and 23,467 (29%) used neither. Men were followed over an 11-year period and 279 (0.3%) developed incident bladder tumors. Among cannabis users, 89 (0.3%) developed bladder cancer in comparison to 190 (0.4%) men who did not report cannabis use (P < .001). After adjusting for age, race or ethnicity, and body mass index, using tobacco only was associated with an increased risk of bladder cancer (hazard regression [HR], 1.52; 95% confidence interval [CI], 1.12-2.07), whereas cannabis use only was associated with a 45% reduction in bladder cancer incidence (HR, 0.55; 95% CI, 0.31-1.00). Using both cannabis and tobacco was associated with an HR of 1.28 (95% CI, 0.91-1.80). Although a cause and effect relationship has not been established, cannabis use may be inversely associated with bladder cancer risk in this population. Copyright © 2015 Elsevier Inc. All rights reserved.

Screening for Bladder and Other Urothelial Cancers

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... recovery . There is no standard or routine screening test for bladder cancer. Screening for bladder cancer is under study and there are screening clinical trials taking place ...

Photoacoustic cystography using handheld dual modal clinical ultrasound photoacoustic imaging system

NASA Astrophysics Data System (ADS)

Sivasubramanian, Kathyayini; Periyasamy, Vijitha; Austria, Dienzo Rhonnie; Pramanik, Manojit

2018-02-01

Vesicoureteral reflux is the abnormal flow of urine from your bladder back up the tubes (ureters) that connect your kidneys to your bladder. Normally, urine flows only down from your kidneys to your bladder. Vesicoureteral reflux is usually diagnosed in infants and children. The disorder increases the risk of urinary tract infections, which, if left untreated, can lead to kidney damage. X-Ray cystography is used currently to diagnose this condition which uses ionising radiation, making it harmful for patients. In this work we demonstrate the feasibility of imaging the urinary bladder using a handheld clinical ultrasound and photoacoustic dual modal imaging system in small animals (rats). Additionally, we demonstrate imaging vesicoureteral reflux using bladder mimicking phantoms. Urinary bladder imaging is done with the help of contrast agents like black ink and gold nanoparticles which have high optical absorption at 1064 nm. Imaging up to 2 cm was demonstrated with this system. Imaging was done at a framerate of 5 frames per second.

Nanotechnology and cancer: improving real-time monitoring and staging of bladder cancer with multimodal mesoporous silica nanoparticles.

PubMed

Sweeney, Sean K; Luo, Yi; O'Donnell, Michael A; Assouline, Jose

Despite being one of the most common cancers, bladder cancer is largely inefficiently and inaccurately staged and monitored. Current imaging methods detect cancer only when it has reached "visible" size and has significantly disrupted the structure of the organ. By that time, thousands of cells will have proliferated and perhaps metastasized. Repeated biopsies and scans are necessary to determine the effect of therapy on cancer growth. In this report, we describe a novel approach based on multimodal nanoparticle contrast agent technology and its application to a preclinical animal model of bladder cancer. The innovation relies on the engineering core of mesoporous silica with specific scanning contrast properties and surface modification that include fluorescence and magnetic resonance imaging (MRI) contrast. The overall dimensions of the nano-device are preset at 80-180 nm, depending on composition with a pore size of 2 nm. To facilitate and expedite discoveries, we combined a well-known model of bladder cancer and our novel technology. We exposed nanoparticles to MB49 murine bladder cancer cells in vitro and found that 70 % of the cells were labeled by nanoparticles as measured by flow cytometry. The in vivo mouse model for bladder cancer is particularly well suited for T1- and T2-weighted MRI. Under our experimental conditions, we demonstrate that the nanoparticles considerably improve tumor definition in terms of volumetric, intensity and structural characteristics. Important bladder tumor parameters can be ascertained, non-invasively, repetitively, and with great accuracy. Furthermore, since the particles are not biodegradable, repetitive injection is not required. This feature allows follow-up diagnostic evaluations during cancer treatment. Changes in MRI signals show that in situ uptake of free particles has predilection to tumor cells relative to normal bladder epithelium. The particle distribution within the tumors was corroborated by fluorescent microscopy of sections of excised bladders. In addition, MRI imaging revealed fibrous finger-like projections into the tumors where particles insinuated themselves deeply. This morphological characteristic was confirmed by fluorescence microscopy. These findings may present new options for therapeutic intervention. Ultimately, the combination of real-time and repeated MRI evaluation of the tumors enhanced by nanoparticle contrast may have the potential for translation into human clinical studies for tumor staging, therapeutic monitoring, and drug delivery.

Urothelium update: how the bladder mucosa measures bladder filling.

PubMed

Janssen, D A W; Schalken, J A; Heesakkers, J P F A

2017-06-01

This review critically evaluates the evidence on mechanoreceptors and pathways in the bladder urothelium that are involved in normal bladder filling signalling. Evidence from in vitro and in vivo studies on (i) signalling pathways like the adenosine triphosphate pathway, cholinergic pathway and nitric oxide and adrenergic pathway, and (ii) different urothelial receptors that are involved in bladder filling signalling like purinergic receptors, sodium channels and TRP channels will be evaluated. Other potential pathways and receptors will also be discussed. Bladder filling results in continuous changes in bladder wall stretch and exposure to urine. Both barrier and afferent signalling functions in the urothelium are constantly adapting to cope with these dynamics. Current evidence shows that the bladder mucosa hosts essential pathways and receptors that mediate bladder filling signalling. Intracellular calcium ion increase is a dominant factor in this signalling process. However, there is still no complete understanding how interacting receptors and pathways create a bladder filling signal. Currently, there are still novel receptors investigated that could also be participating in bladder filling signalling. Normal bladder filling sensation is dependent on multiple interacting mechanoreceptors and signalling pathways. Research efforts need to focus on how these pathways and receptors interact to fully understand normal bladder filling signalling. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

A new approach in the management of urothelial tumors using GM-CSF on marker lesions: an ultrastructural and immunohistochemical study on the macrophage population in bladder mucosa.

PubMed

Stravoravdi, P; Toliou, T; Kirtsis, P; Natsis, K; Konstandinidis, E; Barich, A; Gigis, P; Dimitriadis, K

1999-03-01

Our purpose was to investigate a new therapeutic model, GM-CSF-targeted immunomodulation on transitional cell carcinoma (TCC) marker lesions and to evaluate the immunologic response of the bladder mucosa. Eleven patients with pTa or pT1 bladder cancer were eligible for the study. All lesions were removed by transurethral resection (TUR) except for a marker lesion. All patients received 8 weekly instillations of 300 microg of GM-CSF, after which cystoscopy with bladder biopsies +/- TUR was repeated on adjacent urothelium or tumor or both. Paraffin-embedded sections were immunohistochemically stained with CD68, which labels monocytes and macrophages. The CD68+ cell population was evaluated as 1+ to 3+. Comparable specimens were routinely processed for ultrastructural analysis. Complete response was observed in 6 patients (55%), persistent tumor occurred in 4 patients (approximately 36.4%), and 1 patient (8.6%) showed recurrence. Immunohistochemically, an at least twofold increase in the number of the CD68+ cells was observed in all responders. Submicroscopically, migration of macrophages to the surface layer occurred. Macrophages showed an extensive lysosomal system and pseudopodia. This study indicates that the prophylactic treatment of TCC with GM-CSF may induce immunomodulatory effects on macrophage activities, which could be associated with the clinical evolution of the disease.

Lower urinary tract dysfunction in patients with dysautonomia.

PubMed

Aubin, Melissa St; Shridharani, Anand; Barboi, Alexandru C; Guralnick, Michael L; Jaradeh, Safwan S; Prieto, Thomas E; O'Connor, R Corey

2015-12-01

With the goal of better defining the types of bladder dysfunction observed in this population, we present the chief urologic complaints, results of urodynamic studies, and treatments of patients with dysautonomia-related urinary symptoms. All patients with dysautonomia referred to our neurourology clinic between 2005 and 2015 for management of lower urinary tract dysfunction were retrospectively reviewed. Each patient's chief urologic complaint was recorded and used to initially characterize the bladder storage or voiding symptoms. Patient evaluation included history and physical examination, urinalysis, post void bladder ultrasound, and urodynamic studies. Successful treatment modalities that subjectively or objectively improved symptoms were recorded. Of 815 patients with the diagnosis of dysautonomia, 82 (10 %) were referred for evaluation of lower urinary tract dysfunction. Mean age was 47 years (range 12-83) and 84 % were female. The chief complaint was urinary urgency ± incontinence in 61 % and hesitancy in 23 % of patients. Urodynamic findings demonstrated detrusor overactivity ± incontinence in 50 % of patients, although chief complaint did not reliably predict objective findings. Successful objective and subjective treatments were multimodal and typically non-operative. Lower urinary tract dysfunction may develop in at least 10 % of patients with dysautonomia, predominantly females. Bladder storage or voiding complaints do not reliably predict urodynamic findings. Urodynamically, most patients exhibited detrusor overactivity. The majority of patients were successfully managed with medical or physical therapy.

Challenges for Restoration of Lower Urinary Tract Innervation in Patients with Spinal Cord Injury: A European Single-center Retrospective Study with Long-term Follow-up.

PubMed

Sievert, Karl-Dietrich; Amend, Bastian; Roser, Florian; Badke, Andreas; Toomey, Patricia; Baron, Christopher; Kaminsky, Jan; Stenzl, Arnulf; Tatagiba, Marcos

2016-05-01

Xiao and colleagues in China reported successful restoration of bladder control in patients with spinal cord injury (SCI) by establishing a somatic-autonomic reflex pathway through lumbar-to-sacral ventral root nerve rerouting. We evaluated long-term results in eight patients who underwent this procedure at a German university clinic between 2005 and 2007. The primary outcome was the occurrence of voiding upon stimulation of the skin, with normalization of bladder pressure when filling, as assessed with videourodynamics at each visit. Videourodynamic variables, urinary tract infections, and bladder/stool events recorded in a patient diary were stored in a prospective database and reviewed retrospectively. Intraoperative testing indicated successful nerve rerouting in all eight patients. Duration of follow-up was 71 mo (range: 56-86). No patient reached the primary goal of voluntary voiding with normalization of detrusor pressure at any point during follow-up. No improvements in videourodynamic or diary variables regarding bladder function were observed. In view of the lack of short (12-18 mo) and long-term (71 mo) success in our patients and others, the risks of any surgical procedure using general anesthesia, and potential for unmet expectations to wreak havoc on patient emotional well-being, we cannot recommend this procedure for patients with SCI. Although the hope was to improve long-term outcomes of spinal cord injury patients, intraspinal nerve rerouting did not improve or normalize bladder function. In view of the lack of success, we cannot recommend this procedure until proven in clinical studies. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Gender Differences in Bladder Cancer Treatment Decision Making.

PubMed

Pozzar, Rachel A; Berry, Donna L

2017-03-01

To explore gender differences in bladder cancer treatment decision making.
. Secondary qualitative analysis of interview transcripts.
. One multidisciplinary genitourinary oncology clinic (Dana-Farber Cancer Institute) and two urology clinics (Brigham and Women's Hospital and Beth Israel Deaconess Medical Center) in Boston, MA.
. As part of the original study, 45 men and 15 women with bladder cancer participated in individual interviews. Participants were primarily Caucasian, and most had at least some college education.
. Word frequency reports were used to identify thematic differences between the men's and women's statements. Line-by-line coding of constructs prevalent among women was then performed on all participants in NVivo 9. Coding results were compared between genders using matrix coding queries.
. The role of family in the decision-making process was found to be a dominant theme for women but not for men. Women primarily described family members as facilitators of bladder cancer treatment-related decisions, but men were more likely to describe family in a nonsupportive role.
. The results suggest that influences on the decision-making process are different for men and women with bladder cancer. Family may play a particularly important role for women faced with bladder cancer treatment-related decisions.
. Clinical nurses who care for individuals with bladder cancer should routinely assess patients' support systems and desired level of family participation in decision making. For some people with bladder cancer, family may serve as a stressor. Nurses should support the decision-making processes of all patients and be familiar with resources that can provide support to patients who do not receive it from family.

Urothelial effects of oral agents for overactive bladder.

PubMed

Andersson, Karl-Erik; Fullhase, Claudius; Soler, Roberto

2008-11-01

The cholinergic system of the bladder includes muscarinic receptors distributed to detrusor myocytes and structures within mucosa including bladder afferent (sensory) nerves. The receptors have been shown to be involved in afferent signaling from the bladder, but it has not been established to what extent effects on this mucosal signaling pathway contribute to the therapeutic efficacy of the clinically used antimuscarinics. Mucosa can be influenced by antimuscarinics via the bloodstream. However, some antimuscarinics and their active metabolites are excreted in urine in amounts that may affect the mucosal muscarinic receptors from the luminal side. This has not yet been demonstrated to imply superior clinical efficacy. Nevertheless, mucosal afferent signaling pathways are therapeutically interesting targets that should be further explored.

Ultrasonography in the diagnosis of hemorrhagic cystitis – a complication of bone marrow transplantation in pediatric oncology patients

PubMed Central

Biel, Anna; Sokołowska-Dąbek, Dąbrówka; Olchowy, Cyprian; Łasecki, Mateusz

2014-01-01

Objective The aim of this study was to evaluate the usefulness of ultrasonography in the diagnosis of hemorrhagic cystitis following bone marrow transplantation in children. Material and methods The study involved an analysis of clinical material and the results of imaging tests performed in 334 patients who underwent hematopoietic cell transplantation. Ultrasonographic findings in 42 patients with hemorrhagic cystitis were analyzed in detail. The ultrasound images served to assess the severity of hemorrhagic cystitis and the results were compared with the clinical assessment of the disease on the Droller scale, as well as the laboratory and endoscopic tests. Results In the studied group of patients hemorrhagic cystitis following allogeneic transplantation was diagnosed in 12.5% cases. 73.8% patients received transplants from unrelated donors, 26.2% – from compatible siblings. The study revealed a higher incidence of hemorrhagic cystitis in children above 10 years of age. Grade 3 according to the Droller was diagnosed in 42.9%, grade 2 – in 30.9%, grade 4 – in 14.3%, and grade 1 – in 11.9% patients. The number of ultrasound examinations depended on the clinical symptoms, severity, duration and co-occurrence of other complications following the transplantation and was within the 1–15 range (average: 4.6). Grades 3 and 4 were related to the poor clinical condition of the patients and to their longer hospitalization. During this period there was an increased risk of renal malfunction and acute renal failure, post-inflammatory narrowing of the ureters, hydronephrosis, and in grade 4 the fibrosis of the bladder with reduced bladder capacity. Analyses demonstrated a significant correlation between the ultrasound image of the bladder wall and the clinical severity. Conclusions Ultrasound with Doppler options remains the primary diagnostic tool in the evaluation of hemorrhagic cystitis, and is useful in terms of its diagnosis, determination of the severity, and monitoring of the treatment. PMID:26675710

Research progress on bladder cancer molecular genetics.

PubMed

Kang, Zhengjun; Li, Yuhui; Yu, Yang; Guo, Zhan

2014-11-01

Bladder cancer is a common malignant urinary tumor with a high rate of recurrence and quick progression, which threats human health. With the research on bladder cancer molecular genetics, the knowledge of gene modification and the development of molecular detection methods, more tumor markers have been discovered, which may have potential for early diagnosis, clinical examination and prognosis. This article reviews the research progress on bladder cancer molecular genetics.

Impact of database quality in knowledge-based treatment planning for prostate cancer.

PubMed

Wall, Phillip D H; Carver, Robert L; Fontenot, Jonas D

2018-03-13

This article investigates dose-volume prediction improvements in a common knowledge-based planning (KBP) method using a Pareto plan database compared with using a conventional, clinical plan database. Two plan databases were created using retrospective, anonymized data of 124 volumetric modulated arc therapy (VMAT) prostate cancer patients. The clinical plan database (CPD) contained planning data from each patient's clinically treated VMAT plan, which were manually optimized by various planners. The multicriteria optimization database (MCOD) contained Pareto-optimal plan data from VMAT plans created using a standardized multicriteria optimization protocol. Overlap volume histograms, incorporating fractional organ at risk volumes only within the treatment fields, were computed for each patient and used to match new patient anatomy to similar database patients. For each database patient, CPD and MCOD KBP predictions were generated for D 10 , D 30 , D 50 , D 65 , and D 80 of the bladder and rectum in a leave-one-out manner. Prediction achievability was evaluated through a replanning study on a subset of 31 randomly selected database patients using the best KBP predictions, regardless of plan database origin, as planning goals. MCOD predictions were significantly lower than CPD predictions for all 5 bladder dose-volumes and rectum D 50 (P = .004) and D 65 (P < .001), whereas CPD predictions for rectum D 10 (P = .005) and D 30 (P < .001) were significantly less than MCOD predictions. KBP predictions were statistically achievable in the replans for all predicted dose-volumes, excluding D 10 of bladder (P = .03) and rectum (P = .04). Compared with clinical plans, replans showed significant average reductions in D mean for bladder (7.8 Gy; P < .001) and rectum (9.4 Gy; P < .001), while maintaining statistically similar planning target volume, femoral head, and penile bulb dose. KBP dose-volume predictions derived from Pareto plans were more optimal overall than those resulting from manually optimized clinical plans, which significantly improved KBP-assisted plan quality. This work investigates how the plan quality of knowledge databases affects the performance and achievability of dose-volume predictions from a common knowledge-based planning approach for prostate cancer. Bladder and rectum dose-volume predictions derived from a database of standardized Pareto-optimal plans were compared with those derived from clinical plans manually designed by various planners. Dose-volume predictions from the Pareto plan database were significantly lower overall than those from the clinical plan database, without compromising achievability. Copyright © 2018 Elsevier Inc. All rights reserved.

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis.

PubMed

Towner, Rheal A; Wisniewski, Amy B; Wu, Dee H; Van Gordon, Samuel B; Smith, Nataliya; North, Justin C; McElhaney, Rayburt; Aston, Christopher E; Shobeiri, S Abbas; Kropp, Bradley P; Greenwood-Van Meerveld, Beverley; Hurst, Robert E

2016-03-01

Interstitial cystitis/bladder pain syndrome is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated as patients present with a wide range of symptoms, physical examination findings and clinical test responses. One hypothesis is that interstitial cystitis symptoms arise from increased bladder permeability to urine solutes. This study establishes the feasibility of using contrast enhanced magnetic resonance imaging to quantify bladder permeability in patients with interstitial cystitis. Permeability alterations in bladder urothelium were assessed by intravesical administration of the magnetic resonance imaging contrast agent Gd-DTPA (Gd-diethylenetriaminepentaacetic acid) in a small cohort of patients. Magnetic resonance imaging signal intensity in patient and control bladders was compared regionally and for entire bladders. Quantitative assessment of magnetic resonance imaging signal intensity indicated a significant increase in signal intensity in anterior bladder regions compared to posterior regions in patients with interstitial cystitis (p <0.01) and significant increases in signal intensity in anterior bladder regions (p <0.001). Kurtosis (shape of probability distribution) and skewness (measure of probability distribution asymmetry) were associated with contrast enhancement in total bladders in patients with interstitial cystitis vs controls (p <0.05). Regarding symptomatology interstitial cystitis cases differed significantly from controls on the SF-36®, PUF (Pelvic Pain and Urgency/Frequency) and ICPI (Interstitial Cystitis Problem Index) questionnaires with no overlap in the score range in each group. ICSI (Interstitial Cystitis Symptom Index) differed significantly but with a slight overlap in the range of scores. Data suggest that contrast enhanced magnetic resonance imaging provides an objective, quantifiable measurement of bladder permeability that could be used to stratify bladder pain patients and monitor therapy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Dosimetric impact in the dose-volume histograms of rectal and vesical wall contouring in prostate cancer IMRT treatments.

PubMed

Gómez, Laura; Andrés, Carlos; Ruiz, Antonio

2017-01-01

The main purpose of this study was to evaluate the differences in dose-volume histograms of IMRT treatments for prostate cancer based on the delineation of the main organs at risk (rectum and bladder) as solid organs or by contouring their wall. Rectum and bladder have typically been delineated as solid organs, including the waste material, which, in practice, can lead to an erroneous assessment of the risk of adverse effects. A retrospective study was made on 25 patients treated with IMRT radiotherapy for prostate adenocarcinoma. 76.32 Gy in 36 fractions was prescribed to the prostate and seminal vesicles. In addition to the delineation of the rectum and bladder as solid organs (including their content), the rectal and bladder wall were also delineated and the resulting dose-volume histograms were analyzed for the two groups of structures. Data analysis shows statistically significant differences in the main parameters used to assess the risk of toxicity of a prostate radiotherapy treatment. Higher doses were received on the rectal and bladder walls compared to doses received on the corresponding solid organs. The observed differences in terms of received doses to the rectum and bladder based on the method of contouring could gain greater importance in inverse planning treatments, where the treatment planning system optimizes the dose in these volumes. So, one should take into account the method of delineating of these structures to make a clinical decision regarding dose limitation and risk assessment of chronic toxicity.

Are Interferential Electrical Stimulation and Diaphragmatic Breathing Exercises Beneficial in Children With Bladder and Bowel Dysfunction?

PubMed

Zivkovic, Vesna D; Stankovic, Ivona; Dimitrijevic, Lidija; Kocic, Mirjana; Colovic, Hristina; Vlajkovic, Marina; Slavkovic, Andjelka; Lazovic, Milica

2017-04-01

To evaluate the effects of interferential current (IC) stimulation and diaphragmatic breathing exercises (DBEs) in children with bladder and bowel dysfunction. Seventy-nine children with dysfunctional voiding and chronic constipation who were failures of primary care interventions were included in the prospective clinical study. All the children were checked for their medical history regarding lower urinary tract symptoms and bowel habits. Physical examination, including abdominal and anorectal digital examination, was performed. Children kept a bladder and bowel diary, and underwent urinalyses and urine culture, ultrasound examination of bladder and kidneys, and uroflowmetry with pelvic floor electromyography. Eligible children were divided into 3 groups (A, B, and C). All groups were assigned education and behavioral modifications. Additionally, group A underwent DBEs and IC stimulation, whereas group B received only DBEs. The treatment was conducted for 2 weeks in the clinic in all 3 groups,. The behavioral modifications and DBEs were continued at home for 1 month. Clinical manifestations, uroflowmetry parameters, and postvoided residual urine were analyzed before and after 6 weeks of therapy. After the treatment, significant improvement in defecation frequency and fecal incontinence was noticed only in group A (P < .001 and P < .05, respectively). These children demonstrated significant improvement in lower urinary tract symptoms and postvoided residual urine (P < .001 and P < .05, respectively). Bell-shaped uroflowmetry curve was observed in 73.3% of group A patients (P < .001). IC stimulation and DBEs are beneficial in chronically constipated dysfunctional voiders. Further trials are needed to define the long-term effects of this program. Copyright © 2016 Elsevier Inc. All rights reserved.

Emerging Endoscopic Imaging Technologies for Bladder Cancer Detection

PubMed Central

Lopez, Aristeo; Liao, Joseph C.

2014-01-01

Modern urologic endoscopy is the result of continuous innovations since early 19th century. White light cystoscopy is the primary strategy for identification, resection, and local staging of bladder cancer. While highly effective, white light cystoscopy has several well-recognized shortcomings. Recent advances in optical imaging technologies and device miniaturization hold the potential to improve bladder cancer diagnosis and resection. Photodynamic diagnosis and narrow band imaging are the first to enter the clinical arena. Confocal laser endomicroscopy, optical coherence tomography, Raman spectroscopy, UV autofluorescence, and others have shown promising clinical and pre-clinical feasibility. We review their mechanisms of action, highlight their respective advantages, and propose future directions. PMID:24658832

Treatment May Help Prevent Bladder Cancer Recurrences

Cancer.gov

Flushing the bladder with the chemotherapy drug gemcitabine after tumors have been removed surgically may reduce the risk of the cancer returning, according to the results of a large clinical trial. As this Cancer Currents blog post explains, the treatment approach is for patients with low-grade bladder cancer.

[Evaluation and clinical management of urination disorders in 1,025 patients in a geriatric department].

PubMed

Abrahamik, A; Leblond, J B; Perilliat, I; Henry, O; Loison, M; De Madet, M; Cotteret, R

1993-01-01

Evaluation of voluntary urination and measurement of the post-voiding residue enabled the identification of 6 groups among 1,025 patients 83 +/- 7 years old: 400 normal patients (N); 97 with retention but without incontinence (R); 133 incontinent without retention (I); 50 incontinent with retention (IR); 236 who failed to urinate voluntarily (MO); 109 with indwelling catheters (SAD). Incontinence and indwelling catheters were more common in women; men more frequently failed to urinate voluntarily (p < 0.01). The IR and SAD groups had more urinary infections (p < 0.01) and included more invalids (p < 0.001). The MO and SAD groups had more demented members (p < 0.001) and a higher death rate (p < 0.001). Management consisted of a 48-hour diary of urinations (R and IR groups), scheduled micturitions (I and MO groups) and treatment of urinary infections. Evaluation of bladder sphincter function (n = 291) showed that bladder hypoesthesia was prevalent in groups R and IR and that bladder hyperactivity was predominant in groups I, MO and SAD. Among the 314 patients discharged from the hospital, 181 were reevaluated: good results were obtained for 43% of the initially incontinent and for 53% of those with retention. The indwelling catheters were removed from 82% of the SAD group.

Long-term safety, efficacy, and tolerability of imidafenacin in the treatment of overactive bladder: a review of the Japanese literature

PubMed Central

Masumori, Naoya

2013-01-01

Imidafenacin is an antimuscarinic agent with high affinity for the M3 and M1 muscarinic receptor subtypes and low affinity for the M2 subtype, and is used to treat overactive bladder. Several animal studies have demonstrated that imidafenacin has organ selectivity for the bladder over the salivary glands, colon, heart, and brain. In Phase I studies in humans, the approximately 2.9-hour elimination half-life of imidafenacin was shorter than that of other antimuscarinics such as tolterodine and solifenacin. Imidafenacin was approved for clinical use in overactive bladder in Japan in 2007 after a randomized, double-blind, placebo-controlled Phase II study and a propiverine-controlled Phase III study conducted in Japanese patients demonstrated that imidafenacin 0.1 mg twice daily was clinically effective for treating overactive bladder and was not inferior to propiverine for reduction of episodes of incontinence, with a better safety profile than propiverine. Several short-term clinical studies have demonstrated that imidafenacin also improves sleep disorders, nocturia, and nocturia-related quality of life. In addition, it is speculated that addon therapy with imidafenacin is beneficial for men with benign prostatic hyperplasia whose overactive bladder symptoms are not controlled by alpha-1 adrenoceptor antagonists. No cognitive impairment or influence of imidafenacin on the QTc interval has been observed. Although there have been very few relevant long-term clinical studies, the available information suggests the long-term efficacy, safety, and tolerability of imidafenacin, with less frequent severe adverse events, such as dry mouth and constipation. In addition, imidafenacin can be used safely for a long time even for cognitively vulnerable elderly patients with symptoms of overactive bladder. Thus, it is highly likely that imidafenacin is safe, efficacious, and tolerable to control symptoms of overactive bladder even over the long term. However, it remains unknown if the practical effectiveness of imidafenacin is applicable to ethnic groups other than Japanese. PMID:23390360

Urodynamic investigation by telemetry in Beagle dogs: validation and effects of oral administration of current urological drugs: a pilot study

PubMed Central

2013-01-01

Background Vesico-urethral function may be evaluated in humans and dogs by conventional urodynamic testing (cystometry and urethral pressure profilometry) or by electromyography. These techniques are performed under general anaesthesia in dogs. However, anaesthesia can depress bladder and urethral pressures and inhibit the micturition reflex. The primary objective of this pilot study was to evaluate the use of telemetry for urodynamic investigation in dogs. We also aimed to determine the applicability of telemetry to toxicologic studies by assessing the repeatability of telemetric recordings. Results Conventional diuresis cystometry was performed in six continent adult female Beagle dogs prior to surgical implantation of telemetric and electromyographic devices. In the first phase of the telemetric study, continuous recordings were performed over 8 days and nights. Abdominal, intravesical and detrusor threshold pressures (Pdet th), voided volume (Vv), urethral smooth muscle electrical activity and involuntary detrusor contractions (IDC) were measured during the bladder filling phase and during micturition episodes. Vv recorded during telemetry was significantly lower than bladder volume obtained by diuresis cystometry. Repeatability of telemetric measurements was greater for observations recorded at night. IDC frequency and Pdet th were both lower and Vv was higher at night compared to values recorded during daytime. In the second phase of the telemetric study, phenylpropanolamine, oestriol, bethanechol, oxybutynin or duloxetine were administered orally for 15 days. For each drug, continuous recordings were performed overnight for 12 hours on days 0, 1, 8 and 15. Electromyographic urethral activity was significantly increased 8 days after oestriol or duloxetine administration. No significant changes in bladder function were observed at any time point. Conclusions In dogs, the high repeatability of nocturnal telemetric recordings indicates that this technique could provide more informative results for urologic research. Urethral smooth muscle electrical activity appears to be modified by administration of drugs with urethral tropism. In this pilot telemetric study, bladder function was not affected by oral administration of urological drugs at their recommended clinical dosages. Experimental studies, (pharmacokinetic and pharmacodynamic) and clinical studies are warranted to further define the effects of these drugs on vesico-urethral function in dogs. PMID:24099564

SU-E-J-83: CBCT Based Rectum and Bladder Dose Tracking in the Prostate Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Z; Wang, J; Yang, Z

2015-06-15

Purpose: The aim of this study is to monitor the volume changes of bladder and rectum and evaluate the dosimetric changes of bladder and rectum using daily cone-beam CT for prostate radiotherapy. Methods: The data of this study were obtained from 12 patients, totally 222 CBCTs. All the volume of the bladder and the rectum on the CBCT were normalized to the bladder and the rectum on their own original CT to monitory the volume changes. To evaluate dose delivered to the OARs, volumes that receive 70Gy (V70Gy), 60Gy, 50Gy, 40Gy and 30Gy are calculated for the bladder and themore » rectum, V20Gy and V10Gy for rectum additionally. And the deviation of the mean dose to the bladder and the rectum are also chosen as the evaluation parameter. Linear regression analysis was performed to identify the mean dose change of the volume change using SPSS 19. Results: The results show that the variances of the normalize volume of the bladder and the rectum are 0.15–0.58 and 0.13–0.50. The variances of V70Gy, V60Gy, V50Gy, V40Gy and V30Gy of bladder are bigger than rectum for 11 patients. The linear regression analysis indicated a negative correlation between the volume and the mean dose of the bladder (p < 0.05). A 10% increase in bladder volume will cause 5.1% (±4.3%) reduction in mean dose. Conclusion: The bladder volume change is more significant than that for rectum for the prostate cancer patient. The volume changes of rectum are not significant except air gap in the rectum. Bladder volume varies will cause significant dose change. The bladder volume monitoring before fractional treatment delivery would be crucial for accuracy dose delivery.« less

Transurethral resection and degeneration of bladder tumour

PubMed Central

Li, Aihua; Fang, Wei; Zhang, Feng; Li, Weiwu; Lu, Honghai; Liu, Sikuan; Wang, Hui; Zhang, Binghui

2013-01-01

Introduction: We evaluate the efficacy and safety of transurethral resection and degeneration of bladder tumour (TURD-Bt). Methods: In total, 56 patients with bladder tumour were treated by TURD-Bt. The results in these patients were compared with 32 patients treated by current transurethral resection of bladder tumour (TUR-Bt). Patients with or without disease progressive factors were respectively compared between the 2 groups. The factors included recurrent tumour, multiple tumours, tumour ≥3 cm in diameter, clinical stage T2, histological grade 3, adenocarcinoma, and ureteral obstruction or hydronephrosis. Results: Follow-up time was 48.55 ± 23.74 months in TURD-Bt group and 56.28 ± 17.61 months in the TUR-Bt group (p > 0.05). In patients without progressive factors, no tumour recurrence was found and overall survival was 14 (100%) in the TURD-Bt group; 3 (37.50%) patients had recurrence and overall survival was 5 (62.5%) in the TUR-Bt group. In patients with progressive factors, 8 (19.05%) patients had tumour recurrence, overall survival was 32 (76.19%) and cancer death was 3 (7.14%) in TURD-Bt group; 18 (75.00%) patients had tumour recurrence (p < 0.05), overall survival was 12 (50.00%) (p < 0.01) and cancer death was 8 (33.33%) (p < 0.05) in TUR-Bt group. No significant complication was found in TURD-Bt group. Conclusion: This study suggests that complete resection and degeneration of bladder tumour can be expected by TURD-Bt. The surgical procedure is safe and efficacious, and could be predictable and controllable before and during surgery. We would conclude that for bladder cancers without lymph node metastasis and distal metastasis, TURD-Bt could be performed to replace radical TUR-Bt and preserve the bladder. PMID:24475002

Comparative analysis of the effect of prostatic invasion patterns on cancer-specific mortality after radical cystectomy in pT4a urothelial carcinoma of the bladder.

PubMed

Vallo, Stefan; Gilfrich, Christian; Burger, Maximilian; Volkmer, Björn; Boehm, Katharina; Rink, Michael; Chun, Felix K; Roghmann, Florian; Novotny, Vladimir; Mani, Jens; Brisuda, Antonin; Mayr, Roman; Stredele, Regina; Noldus, Joachim; Schnabel, Marco; May, Matthias; Fritsche, Hans-Martin; Pycha, Armin; Martini, Thomas; Wirth, Manfred; Roigas, Jan; Bastian, Patrick J; Nuhn, Philipp; Dahlem, Roland; Haferkamp, Axel; Fisch, Margit; Aziz, Atiqullah

2016-10-01

To evaluate the prognostic relevance of different prostatic invasion patterns in pT4a urothelial carcinoma of the bladder (UCB) after radical cystectomy. Our study comprised a total of 358 men with pT4a UCB. Patients were divided in 2 groups-group A with stromal infiltration of the prostate via the prostatic urethra with additional muscle-invasive UCB (n = 121, 33.8%) and group B with continuous infiltration of the prostate through the entire bladder wall (n = 237, 66.2%). The effect of age, tumor grade, carcinoma in situ, lymphovascular invasion, soft tissue surgical margin, lymph node metastases, administration of adjuvant chemotherapy, and prostatic invasion patterns on cancer-specific mortality (CSM) was evaluated using competing-risk regression analysis. Decision curve analysis was used to evaluate the net benefit of including the variable invasion pattern within our model. The estimated 5-year CSM-rates for group A and B were 50.1% and 66.0%, respectively. In multivariable competing-risk analysis, lymph node metastases (hazard ratio [HR] = 1.73, P<0.001), lymphovascular invasion (HR = 1.62, P = 0.0023), soft tissue surgical margin (HR = 1.49, P = 0.026), absence of adjuvant chemotherapy (HR = 2.11, P<0.001), and tumor infiltration of the prostate by continuous infiltration of the entire bladder wall (HR = 1.37, P = 0.044) were significantly associated with a higher risk for CSM. Decision curve analysis showed a net benefit of our model including the variable invasion pattern. Continuous infiltration of the prostate through the entire bladder wall showed an adverse effect on CSM. Besides including these patients into clinical trials for an adjuvant therapy, we recommend including prostatic invasion patterns in predictive models in pT4a UCB in men. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic Relevance of Urinary Bladder Cancer Susceptibility Loci

PubMed Central

Grotenhuis, Anne J.; Dudek, Aleksandra M.; Verhaegh, Gerald W.; Witjes, J. Alfred; Aben, Katja K.; van der Marel, Saskia L.; Vermeulen, Sita H.; Kiemeney, Lambertus A.

2014-01-01

In the last few years, susceptibility loci have been identified for urinary bladder cancer (UBC) through candidate-gene and genome-wide association studies. Prognostic relevance of most of these loci is yet unknown. In this study, we used data of the Nijmegen Bladder Cancer Study (NBCS) to perform a comprehensive evaluation of the prognostic relevance of all confirmed UBC susceptibility loci. Detailed clinical data concerning diagnosis, stage, treatment, and disease course of a population-based series of 1,602 UBC patients were collected retrospectively based on a medical file survey. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed, and log-rank tests calculated, to evaluate the association between 12 confirmed UBC susceptibility variants and recurrence and progression in non-muscle invasive bladder cancer (NMIBC) patients. Among muscle-invasive or metastatic bladder cancer (MIBC) patients, association of these variants with overall survival was tested. Subgroup analyses by tumor aggressiveness and smoking status were performed in NMIBC patients. In the overall NMIBC group (n = 1,269), a statistically significant association between rs9642880 at 8q24 and risk of progression was observed (GT vs. TT: HR = 1.08 (95% CI: 0.76–1.54), GG vs. TT: HR = 1.81 (95% CI: 1.23–2.66), P for trend = 2.6×10−3). In subgroup analyses, several other variants showed suggestive, though non-significant, prognostic relevance for recurrence and progression in NMIBC and survival in MIBC. This study provides suggestive evidence that genetic loci involved in UBC etiology may influence disease prognosis. Elucidation of the causal variant(s) could further our understanding of the mechanism of disease, could point to new therapeutic targets, and might aid in improvement of prognostic tools. PMID:24586564

Adenocarcinoma of the urinary bladder

PubMed Central

Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

2015-01-01

Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma. PMID:26309895

Optogenetic Modulation of Urinary Bladder Contraction for Lower Urinary Tract Dysfunction

NASA Astrophysics Data System (ADS)

Park, Jae Hong; Hong, Jin Ki; Jang, Ja Yun; An, Jieun; Lee, Kyu-Sung; Kang, Tong Mook; Shin, Hyun Joon; Suh, Jun-Kyo Francis

2017-01-01

As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method. The results showed that depolarizing ChR2-SMCs with blue light induced bladder contraction, whereas hyperpolarizing NpHR-SMCs with yellow light suppressed PGE2-induced overactive contraction. We also confirmed that optogenetic contraction of bladder smooth muscles in this study is not neurogenic, but solely myogenic, and that optogenetic light stimulation can modulate the urination in vivo. This study thus demonstrated the utility of optogenetic modulation of smooth muscle as a means to actively control the urinary bladder contraction with spatial and temporal accuracy. These features would increase the efficacy of bladder control in LUT dysfunctions without the side effects of conventional clinical therapies.

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

PubMed

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.

Incidence and location of lymph node metastases in patients undergoing radical cystectomy for clinical non-muscle invasive bladder cancer: results from a prospective lymph node mapping study.

PubMed

Bruins, Harman M; Skinner, Eila C; Dorin, Ryan P; Ahmadi, Hamed; Djaladat, Hooman; Miranda, Gus; Cai, Jie; Daneshmand, Siamak

2014-01-01

The objective of this study is to investigate the incidence and location of lymph node metastases (LNMs) in patients undergoing radical cystectomy (RC) and lymph node dissection (LND) for clinical non-muscle invasive bladder cancer (NMIBC). Prospectively collected data of 637 patients who underwent RC and 'superextended' LND with intent-to-cure for urothelial carcinoma of the bladder between 2002 and 2008 were examined. Inclusion criteria were (a) clinical stage Ta, Tis-only, or T1, (b) muscle presence at diagnostic transurethral resection in clinical T1 patients, (c) no prior diagnosis of ≥ T2 disease, (d) no neoadjuvant therapy, and (e) lymphatic tissue sample submitted from all 13 predesignated locations. Lymph node mapping was performed in all patients to determine the location of metastatic lymph nodes. Median follow-up time was 4.7 years. Recurrence-free survival and overall survival were reported. A total of 114 patients were included of whom 9 patients (7.9%) had LNM. Stratified by clinical stage, LNM was present in 6/67 (9.0%) patients with cT1, 3/25 (12.0%) patients with cTis-only, and none of the 22 patients with cTa. Of the 9 node-positive patients (33.3%), 3 had LNM proximal to the aortic bifurcation. No skip metastases were found. After RC, 27 patients (23.7%) were upstaged to muscle invasive disease; of whom 16.7% had cT1, 2.6% had cTa, and 4.4% had cTis-only. Of the remaining 87 patients with pathologic NMIBC, 1 patient (1.1%) had LNM, limited to the true pelvis. Five-year RFS was 82.3%, 81.5%, and 62.0% in patients with pathologic NMIBC, clinical NMIBC, and pathologic muscle invasive bladder cancer, respectively. Routine LND is important in patients with cT1 and cTis-only bladder cancer, but may have limited value in patients with cTa. LNM beyond the boundaries of a standard LND occurred in up to one-third of node-positive patients. In the absence of skip metastases, however, performing a standard LND would correctly identify all node-positive patients. Whether removal of LNM proximal to the common iliac vessels provides a survival benefit remains to be evaluated in future prospective studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

SU-F-BRD-01: A Logistic Regression Model to Predict Objective Function Weights in Prostate Cancer IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boutilier, J; Chan, T; Lee, T

2014-06-15

Purpose: To develop a statistical model that predicts optimization objective function weights from patient geometry for intensity-modulation radiotherapy (IMRT) of prostate cancer. Methods: A previously developed inverse optimization method (IOM) is applied retrospectively to determine optimal weights for 51 treated patients. We use an overlap volume ratio (OVR) of bladder and rectum for different PTV expansions in order to quantify patient geometry in explanatory variables. Using the optimal weights as ground truth, we develop and train a logistic regression (LR) model to predict the rectum weight and thus the bladder weight. Post hoc, we fix the weights of the leftmore » femoral head, right femoral head, and an artificial structure that encourages conformity to the population average while normalizing the bladder and rectum weights accordingly. The population average of objective function weights is used for comparison. Results: The OVR at 0.7cm was found to be the most predictive of the rectum weights. The LR model performance is statistically significant when compared to the population average over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and mean voxel dose to the bladder, rectum, CTV, and PTV. On average, the LR model predicted bladder and rectum weights that are both 63% closer to the optimal weights compared to the population average. The treatment plans resulting from the LR weights have, on average, a rectum V70Gy that is 35% closer to the clinical plan and a bladder V70Gy that is 43% closer. Similar results are seen for bladder V54Gy and rectum V54Gy. Conclusion: Statistical modelling from patient anatomy can be used to determine objective function weights in IMRT for prostate cancer. Our method allows the treatment planners to begin the personalization process from an informed starting point, which may lead to more consistent clinical plans and reduce overall planning time.« less

Management of congenital bladder diverticulum in children: A report of seven cases.

PubMed

Khemakhem, Rachid; Ghorbel, Sofiane; Jlidi, Said; Nouira, Faouzi; Louati, Héla; Douira, Wiem; Chennoufi, Faouzia; Bellagha, Ibtisem; Chaouachi, Béji

2013-01-01

The purpose of the study is to present the author's experience with congenital bladder diverticula in seven pediatric patients at a developing world tertiary care center. Records of seven patients diagnosed and treated as congenital bladder diverticulum, from January 1998 to December 2009 were retrospectively reviewed for age, sex, clinical symptoms, investigative work-up, operative notes, and postoperative follow-up. All patients were males. Age at presentation ranged from six months to six years (mean three years and six months). All were manifested postnatally by urinary tract infection in four cases, bladder retention in three cases and abdominal pain in two cases. Diagnosis was suggested by ultrasound and confirmed by voiding cystourethrography (VCUG) in all cases and urethrocystoscopy in three cases. Open surgical excision of diverticulum was done in all the patients associated with ureteral reimplantation in four patients with VCUG-documented high-grade vesicoureteral reflux (VUR). Average follow-up was four years; there is a resolution of symptoms and no diverticulum recurrence at the defined mean follow-up. Recurrent urinary tract infections and voiding dysfunction in pediatric population should always be evaluated for congenital bladder diverticulum. Investigations such as abdominal ultrasound, VCUG and nuclear renal scanning, form an important part of preoperative diagnostic work-up and postoperative follow up. Diverticulectomy with ureteral reimplantation in case of high-grade reflux, provides good results without recurrence.

Bladder Leiomyoma.

PubMed

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.

Biomarker in Cisplatin-Based Chemotherapy for Urinary Bladder Cancer.

PubMed

Ecke, Thorsten H

2015-01-01

The treatment of metastasized bladder cancer has been evolving during recent years. Cisplatin based chemotherapy combinations are still gold standard in the treatment of advanced and metastasized bladder cancer. But new therapies are approaching. Based to this fact biological markers will become more important for decisions in bladder cancer treatment. A systematic MEDLINE search of the key words "cisplatin", "bladder cancer", "DNA marker", "protein marker", "methylation biomarker", "predictive marker", "prognostic marker" has been made. This review aims to highlight the most relevant clinical and experimental studies investigating markers for metastasized transitional carcinoma of the urothelium treated by cisplatin based regimens.

78 FR 52824 - Proposed Information Collection (Bowel and Bladder Care Billing Form) Activity: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-26

... and Bladder Care Billing Form) Activity: Comment Request AGENCY: Veterans Health Administration.... This notice solicits comments on the information needed to evaluate the Bowel and Bladder Care Billing... specifically to bowel and bladder care. DATES: Written comments and recommendations on the proposed collection...

Pathobiology and Chemoprevention of Bladder Cancer

PubMed Central

Tanaka, Takuji; Miyazawa, Katsuhito; Tsukamoto, Tetsuya; Kuno, Toshiya; Suzuki, Koji

2011-01-01

Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer. PMID:21941546

Multi-center randomized controlled trial of cognitive treatment, placebo, oxybutynin, bladder training, and pelvic floor training in children with functional urinary incontinence.

PubMed

van Gool, Jan D; de Jong, Tom P V M; Winkler-Seinstra, Pauline; Tamminen-Möbius, Tytti; Lax, Hildegard; Hirche, Herbert; Nijman, Rien J M; Hjälmås, Kelm; Jodal, Ulf; Bachmann, Hannsjörg; Hoebeke, Piet; Walle, Johan Vande; Misselwitz, Joachim; John, Ulrike; Bael, An

2014-06-01

Functional urinary incontinence causes considerable morbidity in 8.4% of school-age children, mainly girls. To compare oxybutynin, placebo, and bladder training in overactive bladder (OAB), and cognitive treatment and pelvic floor training in dysfunctional voiding (DV), a multi-center controlled trial was designed, the European Bladder Dysfunction Study. Seventy girls and 27 boys with clinically diagnosed OAB and urge incontinence were randomly allocated to placebo, oxybutynin, or bladder training (branch I), and 89 girls and 16 boys with clinically diagnosed DV to either cognitive treatment or pelvic floor training (branch II). All children received standardized cognitive treatment, to which these interventions were added. The main outcome variable was daytime incontinence with/without urinary tract infections. Urodynamic studies were performed before and after treatment. In branch I, the 15% full response evolved to cure rates of 39% for placebo, 43% for oxybutynin, and 44% for bladder training. In branch II, the 25% full response evolved to cure rates of 52% for controls and 49% for pelvic floor training. Before treatment, detrusor overactivity (OAB) or pelvic floor overactivity (DV) did not correlate with the clinical diagnosis. After treatment these urodynamic patterns occurred de novo in at least 20%. The mismatch between urodynamic patterns and clinical symptoms explains why cognitive treatment was the key to success, not the added interventions. Unpredictable changes in urodynamic patterns over time, the response to cognitive treatment, and the gender-specific prevalence suggest social stress might be a cause for the symptoms, mediated by corticotropin-releasing factor signaling pathways. © 2013 Wiley Periodicals, Inc.

Clinical Guideline for Female Lower Urinary Tract Symptoms.

PubMed

Takahashi, Satoru; Takei, Mineo; Nishizawa, Osamu; Yamaguchi, Osamu; Kato, Kumiko; Gotoh, Momokazu; Yoshimura, Yasukuni; Takeyama, Masami; Ozawa, Hideo; Shimada, Makoto; Yamanishi, Tomonori; Yoshida, Masaki; Tomoe, Hikaru; Yokoyama, Osamu; Koyama, Masayasu

2016-01-01

The "Japanese Clinical Guideline for Female Lower Urinary Tract Symptoms," published in Japan in November 2013, contains two algorithms (a primary and a specialized treatment algorithm) that are novel worldwide as they cover female lower urinary tract symptoms other than urinary incontinence. For primary treatment, necessary types of evaluation include querying the patient regarding symptoms and medical history, examining physical findings, and performing urinalysis. The types of evaluations that should be performed for select cases include evaluation with symptom/quality of life (QOL) questionnaires, urination records, residual urine measurement, urine cytology, urine culture, serum creatinine measurement, and ultrasonography. If the main symptoms are voiding/post-voiding, specialized treatment should be considered because multiple conditions may be involved. When storage difficulties are the main symptoms, the patient should be assessed using the primary algorithm. When conditions such as overactive bladder or stress incontinence are diagnosed and treatment is administered, but sufficient improvement is not achieved, the specialized algorithm should be considered. In case of specialized treatment, physiological re-evaluation, urinary tract/pelvic imaging evaluation, and urodynamic testing are conducted for conditions such as refractory overactive bladder and stress incontinence. There are two causes of voiding/post-voiding symptoms: lower urinary tract obstruction and detrusor underactivity. Lower urinary tract obstruction caused by pelvic organ prolapse may be improved by surgery. © 2015 Wiley Publishing Asia Pty Ltd.

Methylation status as a predictor of intravesical Bacillus Calmette-Guérin (BCG) immunotherapy response of high grade non-muscle invasive bladder tumor.

PubMed

Husek, Petr; Pacovsky, Jaroslav; Chmelarova, Marcela; Podhola, Miroslav; Brodak, Milos

2017-06-01

Genetic and epigenetic alterations play an important role in urothelial cancer pathogenesis. Deeper understanding of these processes could help us achieve better diagnosis and management of this life-threatening disease. The aim of this research was to evaluate the methylation status of selected tumor suppressor genes for predicting BCG response in patients with high grade non-muscle-invasive bladder tumor (NMIBC). We retrospectively evaluated 82 patients with high grade non-muscle-invasive bladder tumor (stage Ta, T1, CIS) who had undergone BCG instillation therapy. We compared epigenetic methylation status in BCG-responsive and BCG-failure groups. We used the MS-MLPA (Methylation-Specific Multiplex Ligation-Dependent Probe Amplification probe sets ME001 and ME004. The control group was 13 specimens of normal urotel (bladder tissue)). Newly identified methylations in high grade NMIBC were found in MUS81a, NTRK1 and PCCA. The methylation status of CDKN2B (P=0.00312 ** ) and MUS81a (P=0.0191 * ) is associated with clinical outcomes of BCG instillation therapy response. CDKN2B and MUS81a unmethylation was found in BCG failure patients. The results show that the methylation status of selected tumor suppressor genes (TSGs) has the potential for predicting BCG response in patients with NMIBC high grade tumors. Tumor suppressor genes such as CDKN2b, MUS81a, PFM-1, MSH6 and THBS1 are very promising for future research.

Spontaneous puerperal extraperitoneal bladder wall rupture in young woman with diagnostic dilemma

PubMed Central

Sabat, Debabrat Kumar; Panigrahi, Pradeep Kumar; Sahoo, Ranjan Kumar; Acharya, Mousumi; Sahu, Mahesh Ch

2015-01-01

A young female presented with an acute abdominal pain and oliguria for 1 week following normal vaginal delivery. No history of hematuria was present. Patient was having lochia rubra. Sealed uterine rupture was suspected clinically. Initial ultrasound of the patient showed distended urinary bladder containing Foley catheter ballon with clamping of Foley catheter and particulate ascites. Abdominal paracentesis revealed hemorrhagic fluid. Contrast-enhanced computed tomography of abdomen revealed ascites, distended urinary bladder and no extraluminal contrast extravasation in delayed scan. As patient condition deteriorated, repeat ultrasound guided abdominal paracentesis was done which revealed transudative peritoneal collection with distended bladder. Cystoscopy revealed urinary bladder ruptures with exudate sealing the rupture site. Exploratory laparotomy was done and a diagnosis of extraperitoneal bladder rupture was confirmed. The rent was repaired in layers. She was put on continuous bladder drainage for 3 weeks followed by bladder training. It presented in a unique way as there was hemorrhagic peritoneal tap, no macroscopic hematuria and urinary bladder was distended in spite of urinary bladder wall rupture which delayed the diagnosis and treatment. Complete emptying of urinary bladder before second stage of labor and during postpartum period with perineal repair is mandatory to prevent urinary bladder rupture. PMID:26985426

Spontaneous puerperal extraperitoneal bladder wall rupture in young woman with diagnostic dilemma.

PubMed

Sabat, Debabrat Kumar; Panigrahi, Pradeep Kumar; Sahoo, Ranjan Kumar; Acharya, Mousumi; Sahu, Mahesh Ch

2015-01-01

A young female presented with an acute abdominal pain and oliguria for 1 week following normal vaginal delivery. No history of hematuria was present. Patient was having lochia rubra. Sealed uterine rupture was suspected clinically. Initial ultrasound of the patient showed distended urinary bladder containing Foley catheter ballon with clamping of Foley catheter and particulate ascites. Abdominal paracentesis revealed hemorrhagic fluid. Contrast-enhanced computed tomography of abdomen revealed ascites, distended urinary bladder and no extraluminal contrast extravasation in delayed scan. As patient condition deteriorated, repeat ultrasound guided abdominal paracentesis was done which revealed transudative peritoneal collection with distended bladder. Cystoscopy revealed urinary bladder ruptures with exudate sealing the rupture site. Exploratory laparotomy was done and a diagnosis of extraperitoneal bladder rupture was confirmed. The rent was repaired in layers. She was put on continuous bladder drainage for 3 weeks followed by bladder training. It presented in a unique way as there was hemorrhagic peritoneal tap, no macroscopic hematuria and urinary bladder was distended in spite of urinary bladder wall rupture which delayed the diagnosis and treatment. Complete emptying of urinary bladder before second stage of labor and during postpartum period with perineal repair is mandatory to prevent urinary bladder rupture.

Work Capacity of the Bladder During Voiding: A Novel Method to Evaluate Bladder Contractile Function and Bladder Outlet Obstruction

PubMed Central

Liu, Ning; Man, Li-Bo; He, Feng; Huang, Guang-Lin; Zhou, Ning; Zhu, Xiao-Fei

2015-01-01

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 (Pdet Qmax) of ≥40 cmH2O 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 Pdet Qmax 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 Pdet Qmax (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 Pdet Qmax 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. PMID:26668148

Clinical significance of CDH13 promoter methylation as a biomarker for bladder cancer: a meta-analysis.

PubMed

Chen, Feng; Huang, Tao; Ren, Yu; Wei, Junjun; Lou, Zhongguan; Wang, Xue; Fan, Xiaoxiao; Chen, Yirun; Weng, Guobin; Yao, Xuping

2016-08-30

Methylation of the tumor suppressor gene H-cadherin (CDH13) has been reported in many cancers. However, the clinical effect of the CDH13 methylation status of patients with bladder cancer remains to be clarified. A systematic literature search was performed to identify eligible studies in the PubMed, Embase, EBSCO, CKNI and Wanfang databases. The pooled odds ratio (OR) and the corresponding 95 % confidence interval (95 % CI) was calculated and summarized. Nine eligible studies were included in the present meta-analysis consisting of a total of 1017 bladder cancer patients and 265 non-tumor controls. A significant association was found between CDH13 methylation levels and bladder cancer (OR = 21.71, P < 0.001). The results of subgroup analyses based on sample type suggested that CDH13 methylation was significantly associated with bladder cancer risk in both the tissue and the urine (OR = 53.94, P < 0.001; OR = 7.71, P < 0.001; respectively). A subgroup analysis based on ethnic population showed that the OR value of methylated CDH13 was higher in Asians than in Caucasians (OR = 35.18, P < 0.001; OR = 8.86, P < 0.001; respectively). The relationships between CDH13 methylation and clinicopathological features were also analyzed. A significant association was not observed between CDH13 methylation status and gender (P = 0.053). Our results revealed that CDH13 methylation was significantly associated with high-grade bladder cancer, multiple bladder cancer and muscle invasive bladder cancer (OR = 2.22, P < 0.001; OR = 1.45, P = 0.032; OR = 3.42, P < 0.001; respectively). Our study indicates that CDH13 methylation may play an important role in the carcinogenesis, development and progression of bladder cancer. In addition, CDH13 methylation has the potential to be a useful biomarker for bladder cancer screening in urine samples and to be a prognostic biomarker in the clinic.

Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murthy, Vedang, E-mail: vmurthy@actrec.gov.in; Masodkar, Renuka; Kalyani, Nikhil

Purpose: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. Methods and Materials: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gymore » in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2]{sub 10} = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). Results: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. Conclusions: Adaptive IGRT using plan-of-the-day approach for bladder preservation is clinically feasible, with good oncological outcomes and low rates of acute and late toxicities. Dose escalation is safe and possibly improves outcomes in bladder preservation.« less

Evaluation of urovysion and cytology for bladder cancer detection: a study of 1835 paired urine samples with clinical and histologic correlation.

PubMed

Dimashkieh, Haythem; Wolff, Daynna J; Smith, T Michael; Houser, Patricia M; Nietert, Paul J; Yang, Jack

2013-10-01

Urine cytology has been used for screening of bladder cancer but has been limited by its low sensitivity. UroVysion is a multiprobe fluorescence in situ hybridization (FISH) assay that detects common chromosome abnormalities in bladder cancers. For this study, the authors evaluated the effectiveness of multiprobe FISH and urine cytology in detecting urothelial cell carcinoma (UCC) in the same urine sample. In total, 1835 cases with the following criteria were selected: valid results from both the multiprobe FISH assay and urine cytology in the same urine sample, histologic and/or cystoscopic follow-up within 4 months of the original tests, or at least 3 years of clinical follow-up information. The results of FISH and cytology were correlated with clinical outcomes derived from a combination of histologic, cystoscopic, and clinical follow-up information. Of 1835 cases, 1045 cases were from patients undergoing surveillance of recurrent UCC, and 790 were for hematuria. The overall sensitivity, specificity, positive predictive value, and negative predictive value in detecting UCC were 61.9%, 89.7%, 53.9%, and 92.4%, respectively, for FISH and 29.1%, 96.9%, 64.4%, and 87.5%, respectively, for cytology. The performance of both FISH and cytology generally was better in the surveillance population and in samples with high-grade UCC. In 95 of 296 cases with atypical cytology that were proven to have UCC, 61 cases, mostly high-grade UCC, were positive using the multiprobe FISH assay. The UroVysion multiprobe FISH assay was more sensitive than urine cytology in detecting UCC, but it produced more false-positive results. The current data suggest that the use of FISH as a reflex test after an equivocal cytologic diagnosis may play an effective role in detecting UCC. © 2013 American Cancer Society.

Technique of Antireflux Procedure without Creating Submucosal Tunnel for Surgical Correction of Vesicoureteric Reflux during Bladder Closure in Exstrophy.

PubMed

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.

[Continuous bladder irrigation following transurethral resection of the prostate (TURP)].

PubMed

Nojiri, Yoshikatsu; Okamura, Kikuo; Kinukawa, Tsuneo; Ozawa, Hideo; Saito, Shiro; Okumura, Kazuhiro; Terai, Akito; Takei, Mineo

2007-09-01

We investigated whether continuous bladder irrigation after Transurethral Resection of the Prostate (TURP) would prevent catheter obstruction by the clot. We analyzed data from 761 patients registered in "a multi-institutional study of TURP clinical pathway" sponsored by the Ministry of Health, Labor and Welfare between 2001 and 2003. The difference of clinical backgrounds of the cases, resected weight, operating time, risk of being feverish, risk of catheter obstruction and chance of postoperative Transurethral Fulguration (TUF) between each institution were investigated. The risk factor of catheter obstruction is characterized and the significance of continuous bladder irrigation is discussed. The incidence of catheter obstruction in the four institutions, in which 90% or more of patients underwent continuous bladder irrigation, was significantly lower than that in the three institutions, in which continuous bladder irrigation was performed in selected patients whose hematuria was severe (4.4% VS 12.9%, p<0.001). There was no difference in the frequency of either pyrexia or postoperative TUF. Logistic regression analysis showed that significant factors for catheter obstruction are continuous bladder irrigation, resected tissue weight and preoperative urinary infection. Routine continuous bladder irrigation achieved a lower incidence of catheter obstruction. However, we recommend that urologists should decide whether to perform routine continuous irrigation, considering the frequency of catheter obstruction, safety, labor and cost.

[Clinical experience on the use of total parenteral nutrition in patients subjected to radical cystectomy intervention for infiltrating neoplasms of the bladder].

PubMed

Del Boca, C; Furiosi, D; Bolis, C; Ferrari, C

1989-03-01

The Authors report their 7 year follow-up on the use of T.P.N. in 28 patients treated surgically for infiltrating cancer of the bladder. They consider the pathogenetic mechanisms that influence the organism's adaptation to surgical stress with particular reference to the multiple neuroendocrinal and biochemical interconnections. The procedures to define the nutritional/metabolic levels, of the patients undergoing operation are exposed. The T.P.N. is given according to the personal requirements of each patient and is a function of the "performance status", caloric need and to the presence of sepsis. Problems concerning the radical cistectomy such as: time of surgery, extention of exeresis, uroentheroanastomosis, metabolic variations, sepsis, etc., are evaluated. Considering the positive results obtained with this nutritional procedure, the Authors underline the importance of a systematic use of T.P.N. wich should be included, in their opinion, in a multidisciplinar treatment of advanced bladder neoplasms.

Sixteen-slice multidetector computed tomographic virtual cystoscopy in the evaluation of a patient with suspected bladder tumor and history of bladder carcinoma operation.

PubMed

Basak, Muzaffer; Ozkurt, Huseyin; Tanriverdi, Orhan; Cay, Esra; Aydin, Mustafa; Miroglu, Cengiz

2009-01-01

The purpose of this study was to evaluate the use of virtual cystoscopy performed with multidetector computed tomography (CT) in patients with suspected bladder tumors and histories of bladder carcinoma operation. Thirty-six patients (29 men and 7 women) with a mean age of 66 years (range, 24-88 years) with suspected bladder tumors and histories of bladder carcinoma operation were included in this prospective study. Virtual cystoscopy was performed by 16-slice multidetector CT scanner. The bladder was filled with diluted contrast material solution through a Foley catheter. Then, all patients underwent conventional cystoscopy examination. Two reviewers found 18 lesions detected by virtual cystoscopy by consensus, whereas 19 lesions were depicted by conventional cystoscopy. At virtual and conventional cystoscopies, the conditions of 3 patients, 2 with chronic inflammations and 1 with foreign body reaction, were wrongly diagnosed as tumors. At conventional cystoscopy, one patient's result was wrongly interpreted as normal. In pathologic evaluation, all tumors were diagnosed as transitional cell carcinoma. Bladder tumor can be noninvasively diagnosed using virtual cystoscopy. Use of virtual cystoscopy should be considered inpatients who present with hematuria or have histories of bladder carcinoma operation and are for follow-up because of its lesser complication risk and its being a less invasive, easily applied procedure without need of anesthesia. In the future, owing to the development of the CT technology and image processing technique, virtual cystoscopy may have a part in the detection of bladder cancer.

What are the origins and relevance of spontaneous bladder contractions? ICI-RS 2017.

PubMed

Drake, Marcus J; Fry, Christopher H; Hashitani, Hikaru; Kirschner-Hermanns, Ruth; Rahnama'i, Mohammad S; Speich, John E; Tomoe, Hikaru; Kanai, Anthony J; McCloskey, Karen D

2018-01-23

Storage phase bladder activity is a counter-intuitive observation of spontaneous contractions. They are potentially an intrinsic feature of the smooth muscle, but interstitial cells in the mucosa and the detrusor itself, as well as other muscular elements in the mucosa may substantially influence them. They are identified in several models explaining lower urinary tract dysfunction. A consensus meeting at the International Consultation on Incontinence Research Society (ICI-RS) 2017 congress considered the origins and relevance of spontaneous bladder contractions by debating which cell type(s) modulate bladder spontaneous activity, whether the methodologies are sufficiently robust, and implications for healthy and abnormal lower urinary tract function. The identified research priorities reflect a wide range of unknown aspects. Cellular contributions to spontaneous contractions in detrusor smooth muscle are still uncertain. Accordingly, insight into the cellular physiology of the bladder wall, particularly smooth muscle cells, interstitial cells, and urothelium, remains important. Upstream influences, such as innervation, endocrine, and paracrine factors, are particularly important. The cellular interactions represent the key understanding to derive the integrative physiology of organ function, notably the nature of signalling between mucosa and detrusor layers. Indeed, it is still not clear to what extent spontaneous contractions generated in isolated preparations mirror their normal and pathological counterparts in the intact bladder. Improved models of how spontaneous contractions influence pressure generation and sensory nerve function are also needed. Deriving approaches to robust evaluation of spontaneous contractions and their influences for experimental and clinical use could yield considerable progress in functional urology. © 2018 Wiley Periodicals, Inc.

Vascular endothelial growth factor-C (VEGF-C) expression predicts lymph node metastasis of transitional cell carcinoma of the bladder.

PubMed

Suzuki, Kazumi; Morita, Tatsuo; Tokue, Akihiko

2005-02-01

It has been found that expression of vascular endothelial growth factor-C (VEGF-C) in several carcinomas is significantly associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis. However, VEGF-C expression in bladder transitional cell carcinoma (TCC) has not yet been reported. To elucidate the role of VEGF-C in bladder TCC, we examined VEGF-C expression in bladder TCC and pelvic lymph node metastasis specimens obtained from patients who underwent radical cystectomy. Eighty-seven patients who underwent radical cystectomy for clinically organ-confined TCC of the bladder were enrolled in the present study. No neoadjuvant treatments, except transurethral resection of the tumor, were given to these patients. The VEGF-C expressions of 87 bladder tumors and 20 pelvic lymph node metastasis specimens were examined immunohistochemically and the association between VEGF-C expression and clinicopathological factors, including angiogenesis as evaluated by microvessel density (MVD), was also examined. Vascular endothelial growth factor-C expression was found in the cytoplasm of tumor cells, but not in the normal transitional epithelium. Vascular endothelial growth factor-C expression was significantly associated with the pathological T stage (P = 0.0289), pelvic lymph node metastasis (P < 0.0001), lymphatic involvement (P = 0.0008), venous involvement (P = 0.0002) and high MVD (P = 0.0043). The multivariate analysis demonstrated that VEGF-C expression and high MVD in bladder TCC were independent risk factors influencing the pelvic lymph node metastasis. Moreover, the patients with VEGF-C-positive tumors had significantly poorer prognoses than those with the VEGF-C-negative tumors (P = 0.0087) in the univariate analysis. The multivariate analysis based on Cox proportional hazard model showed that the independent prognostic factors were patient age (P = 0.0132) and pelvic lymph node metastasis (P = 0.0333). The present study suggests that VEGF-C expression is an important predictive factor of pelvic lymph node metastasis in bladder cancer patients.

Recovery of storage and emptying functions of the urinary bladder after spinal anesthesia with lidocaine and with bupivacaine in men.

PubMed

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 for spinal anesthesia seems to be preferable.

Cytological Diagnosis of Small Cell Carcinoma of Urinary Bladder in a Patient with CLL

PubMed Central

Şimşek, Gülçin Güler; Güreşçi, Servet; Oğuz, Ural; Ünsal, Ali

2014-01-01

Small cell carcinoma of the urinary bladder (SCCUB) is an extremely rare bladder malignancy characterized by an aggressive clinical behavior. So, it is important to diagnose this high grade disease by urinary cytology. We report a case of SCCUB in an old man with chronic lymphocytic leukemia (CLL) in remission, while bladder tumor was diagnosed by cytology. With this article, we aimed to review and to update the literature concerning this tumor. PMID:24518979

Bladder Cancer Mortality in the United States: A Geographic and Temporal Analysis of Socioeconomic and Environmental Factors.

PubMed

Smith, Norm D; Prasad, Sandip M; Patel, Amit R; Weiner, Adam B; Pariser, Joseph J; Razmaria, Aria; Maene, Chieko; Schuble, Todd; Pierce, Brandon; Steinberg, Gary D

2016-02-01

We assessed the association of temporal, socioeconomic and environmental factors with bladder cancer mortality in the United States. Our hypothesis was that bladder cancer mortality is associated with distinct environmental and socioeconomic factors with effects varying by region, race and gender. NCI (National Cancer Institute) age adjusted, county level bladder cancer mortality data from 1950 to 2007 were analyzed to identify clusters of increased bladder cancer death using the Getis-Ord Gi* statistic. Socioeconomic, clinical and environmental data were assessed using geographically weighted spatial regression analysis adjusting for spatial autocorrelation. County level socioeconomic, clinical and environmental data were obtained from national databases, including the United States Census, CDC (Centers for Disease Control and Prevention), NCHS (National Center for Health Statistics) and County Health Rankings. Bladder cancer mortality hot spots and risk factors for bladder cancer death differed significantly by gender, race and geographic region. From 1996 to 2007 smoking, unemployment, physically unhealthy days, air pollution ozone days, percent of houses with well water, employment in the mining industry and urban residences were associated with increased rates of bladder cancer mortality (p <0.05). Model fit was significantly improved in hot spots compared to all American counties (R(2) = 0.20 vs 0.05). Environmental and socioeconomic factors affect bladder cancer mortality and effects appear to vary by gender and race. Additionally there were temporal trends of bladder cancer hot spots which, when persistent, should be the focus of individual level studies of occupational and environmental factors. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Catheter-related bladder discomfort after urological surgery: importance of the type of surgery and efficiency of treatment by clonazepam].

PubMed

Maro, S; Zarattin, D; Baron, T; Bourez, S; de la Taille, A; Salomon, L

2014-09-01

Bladder catheter can induce a Catheter-Related Bladder Discomfort (CRBD). Antagonist of muscarinic receptor is the gold standard treatment. Clonazepam is an antimuscarinic, muscle relaxing oral drug. The aim of this study is to look for a correlation between the type of surgical procedure and the existence of CRBD and to evaluate the efficiency of clonazepam. One hundred patients needing bladder catheter were evaluated. Sexe, age, BMI, presence of diabetes, surgical procedure and existence of CRBD were noted. Pain was evaluated with analogic visual scale. Timing of pain, need for specific treatment by clonazepam and its efficiency were noted. Correlation between preoperative data, type of surgical procedure, existence of CRBD and efficiency of treatment were evaluated. There were 79 men and 21 women (age: 65.9 years, BMI: 25.4). Twelve patients presented diabetes. Surgical procedure concerned prostate in 39 cases, bladder in 19 cases (tumor resections), endo-urology in 20 cases, upper urinary tract in 12 cases (nephrectomy…) and lower urinary tract in 10 cases (sphincter, sub-uretral tape). Forty patients presented CRBD, (pain 4.5 using VAS). This pain occurred 0.6 days after surgery. No correlation was found between preoperative data and CRBD. Bladder resection and endo-urological procedures were surgical procedures which procured CRBD. Clonazepam was efficient in 30 (75 %) out of 40 patients with CRBD. However, it was less efficient in case of bladder tumor resection. CRBD is frequent and occurred immediately after surgery. Bladder resection and endo-urology were the main surgical procedures which induced CRBD. Clonazepam is efficient in 75 %. Bladder resection is the surgical procedure which is the most refractory to treatment. 5. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Traces: making sense of urodynamics testing--Part 8: Evaluating sensations of bladder filling.

PubMed

Gray, Mikel

2011-01-01

The "Traces" series discusses how the urodynamic clinician generates usable data from a filling cystometrogram (CMG). Part 8 focuses on the question, "What are the sensations of bladder filling?" Recent research suggests that sensations of bladder filling wax and wane from consciousness in healthy persons free of bothersome lower urinary tract symptoms. Because of its invasive and atypical nature when compared to daily life, multichannel urodynamics testing cannot reproduce the numerous and complex variables that influence bladder sensation in the healthy individual, making the evaluation of sensations of bladder filling a particularly challenging component of the filling CMG. Routine assessment of bladder sensations focuses on identification of three landmarks--first sensation of bladder filling, first desire to void, and a strong desire to void. A fourth sensation, bladder fullness or a compelling desire to void, is recommended. In addition to assessing these sensations, the urodynamic clinician must assess sensations indicating associated disease or disorders affecting lower urinary tract function, including urgency, pain, and atypical sensations. This assessment should be completed in the context of the results of one or more validated instruments used to measure bladder sensations.

Bladder sensation measures and overactive bladder.

PubMed

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 <0.01). A weak negative correlation was seen between Urgency Perception Score and bladder capacity (-0.25, p <0.05). No correlation was noted for the other urodynamics parameters. First 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.

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

PubMed Central

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

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

PubMed

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.

Effects of Physiotherapy in the Treatment of Neurogenic Bladder in Patients Infected with Human T-Lymphotropic Virus 1 (HTLV-1)

PubMed Central

Andrade, Rosana C.P.; Neto, José A.; Andrade, Luciana; Oliveira, Tatiane S. S.; Santos, Dislene N.; Oliveira, Cassius J.V.; Prado, Márcio J.; Carvalho, Edgar M.

2016-01-01

Objective To evaluate the efficacy of physiotherapy for urinary manifestations in patients with HTLV-1-associated lower urinary tract dysfunction. Methods Open clinical trial with 21 patients attending the physiotherapy clinic of the Hospital Universitário, Bahia, Brazil. Combinations of behavioral therapy, perineal exercises and intravaginal/intra-anal electrical stimulation were used. Results The mean age was 54±12 years and 67% were female. After treatment, there was an improvement in symptoms of urinary urgency, frequency, incontinence, nocturia and in the sensation of incomplete emptying (p<0.001). There was also a reduction in the overactive bladder symptom score from 10±4 to 6±3 (p<0.001) and an increasing in the perineal muscle strength (p<0.001). The urodynamic parameters improved, with reduction in the frequency of patients with detrusor hyperactivity from 57.9% to 42.1%; detrusor-sphincter dyssynergia (DSD) from 31.6% to 5.3%; detrusor hypocontractility from 15.8% to 0% and detrusor areflexia from 10.5% to 0%, with positive repercussions in the quality of life in all patients. Conclusion Physiotherapy was effective in cases of HTLV-1-associated neurogenic bladder, reducing symptoms, increasing perineal muscle strength, improving urodynamic parameters and quality of life. PMID:26724409

Is radical oncosurgery justified for the treatment of primary malignant fibrous histiocytoma of the urinary bladder? Report of two cases and analyses of disease-specific survival rates based on a review of the literature.

PubMed

Gunia, Sven; May, Matthias; Koch, Stefan; Erbersdobler, Andreas

2011-01-01

Disease-specific survival (DSS) rates were evaluated in 20 patients with primary malignant fibrous histiocytoma (MFH) of the bladder. The most common pathologic finding was the pleomorphic subtype of MFH (55%) with a mean tumor size of 6.8 cm. 10 patients underwent surgery without and 6 patients with adjuvant therapy. Local and systemic rates of progression were 30 and 60% after surgery only compared with 16.7 and 50% after surgery with adjuvant therapy. Although none of the patients showed metastatic dissemination at the time of diagnosis, overall 1- and 2-year DSS rates of only 47.8 and 31.9% were observed. Hence, after the onset of clinical symptoms, the disease runs a very aggressive course regardless of the therapeutic options employed. Although distant dissemination seems to be rare at the time of diagnosis, the prognostic outcome is dismal. The rarity and inconsistency of the currently available case reports on MFH of the bladder hampers the development of therapeutic guidelines. Advanced studies enrolling a larger number of patients with appropriate clinical and pathological data are needed to compare the beneficial effects of various treatment options. Copyright © 2011 S. Karger AG, Basel.

Cerebrospinal fluid leakage in intracranial hypotension syndrome: usefulness of indirect findings in radionuclide cisternography for detection and treatment monitoring.

PubMed

Morioka, Tomoaki; Aoki, Takatoshi; Tomoda, Yoshinori; Takahashi, Hiroyuki; Kakeda, Shingo; Takeshita, Iwao; Ohno, Masato; Korogi, Yukunori

2008-03-01

To evaluate indirect findings of cerebrospinal fluid (CSF) leakage on radionuclide cisternography and their changes after treatment. This study was approved by the hospital's institutional review board and informed consent was obtained before each examination. A total of 67 patients who were clinically suspected of spontaneous intracranial hypotension (SIH) syndrome underwent radionuclide cisternography, and 27 patients who had direct findings of CSF leakage on radionuclide cisternography were selected for this evaluation. They were 16 males and 11 females, aged between 26 and 58 years. Sequential images of radionuclide cisternography were acquired at 1, 3, 5, and 24 hours after injection. We assessed the presence or absence of 4 indirect findings; early visualization of bladder activity, no visualization of activity over the brain convexities, rapid disappearance of spinal activity, and abnormal visualization of the root sleeves. Changes of the direct and indirect findings after treatment were also evaluated in 14 patients who underwent epidural blood patch treatment. Early visualization of bladder activity was found in all 27 patients. Seven of 27 (25.9%) patients showed no activity over the brain convexities. Rapid disappearance of spinal activity and abnormal root sleeve visualization were present in 2 (7.4%) and 5 (18.5%) patients, respectively. After epidural blood patch, both direct CSF leakage findings and indirect findings of early visualization of bladder activity had disappeared or improved in 12 of 14 patients (85.7%). The other indirect findings also disappeared after treatment in all cases. Indirect findings of radionuclide cisternography, especially early visualization of bladder activity, may be useful in the diagnosis and posttreatment follow-up of CSF leakage.

Validation of Fully Automated VMAT Plan Generation for Library-Based Plan-of-the-Day Cervical Cancer Radiotherapy.

PubMed

Sharfo, Abdul Wahab M; Breedveld, Sebastiaan; Voet, Peter W J; Heijkoop, Sabrina T; Mens, Jan-Willem M; Hoogeman, Mischa S; Heijmen, Ben J M

2016-01-01

To develop and validate fully automated generation of VMAT plan-libraries for plan-of-the-day adaptive radiotherapy in locally-advanced cervical cancer. Our framework for fully automated treatment plan generation (Erasmus-iCycle) was adapted to create dual-arc VMAT treatment plan libraries for cervical cancer patients. For each of 34 patients, automatically generated VMAT plans (autoVMAT) were compared to manually generated, clinically delivered 9-beam IMRT plans (CLINICAL), and to dual-arc VMAT plans generated manually by an expert planner (manVMAT). Furthermore, all plans were benchmarked against 20-beam equi-angular IMRT plans (autoIMRT). For all plans, a PTV coverage of 99.5% by at least 95% of the prescribed dose (46 Gy) had the highest planning priority, followed by minimization of V45Gy for small bowel (SB). Other OARs considered were bladder, rectum, and sigmoid. All plans had a highly similar PTV coverage, within the clinical constraints (above). After plan normalizations for exactly equal median PTV doses in corresponding plans, all evaluated OAR parameters in autoVMAT plans were on average lower than in the CLINICAL plans with an average reduction in SB V45Gy of 34.6% (p<0.001). For 41/44 autoVMAT plans, SB V45Gy was lower than for manVMAT (p<0.001, average reduction 30.3%), while SB V15Gy increased by 2.3% (p = 0.011). AutoIMRT reduced SB V45Gy by another 2.7% compared to autoVMAT, while also resulting in a 9.0% reduction in SB V15Gy (p<0.001), but with a prolonged delivery time. Differences between manVMAT and autoVMAT in bladder, rectal and sigmoid doses were ≤ 1%. Improvements in SB dose delivery with autoVMAT instead of manVMAT were higher for empty bladder PTVs compared to full bladder PTVs, due to differences in concavity of the PTVs. Quality of automatically generated VMAT plans was superior to manually generated plans. Automatic VMAT plan generation for cervical cancer has been implemented in our clinical routine. Due to the achieved workload reduction, extension of plan libraries has become feasible.

PET/CT in renal, bladder and testicular cancer

PubMed Central

Bouchelouche, Kirsten; Physician, Chief; Choyke, Peter L.

2015-01-01

Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/CT is having a broad impact in oncology, and in recent years PET/CT is beginning to have an impact in uro-oncology as well. In both bladder and renal cancer there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with only limited renal excretion. Thus, new tracers are being introduced in these malignancies. This review focuses on the clinical role of FDG and other PET agents in renal, bladder and testicular cancer. PMID:26099672

Gene expression signature in urine for diagnosing and assessing aggressiveness of bladder urothelial carcinoma.

PubMed

Mengual, Lourdes; Burset, Moisès; Ribal, María José; Ars, Elisabet; Marín-Aguilera, Mercedes; Fernández, Manuel; Ingelmo-Torres, Mercedes; Villavicencio, Humberto; Alcaraz, Antonio

2010-05-01

To develop an accurate and noninvasive method for bladder cancer diagnosis and prediction of disease aggressiveness based on the gene expression patterns of urine samples. Gene expression patterns of 341 urine samples from bladder urothelial cell carcinoma (UCC) patients and 235 controls were analyzed via TaqMan Arrays. In a first phase of the study, three consecutive gene selection steps were done to identify a gene set expression signature to detect and stratify UCC in urine. Subsequently, those genes more informative for UCC diagnosis and prediction of tumor aggressiveness were combined to obtain a classification system of bladder cancer samples. In a second phase, the obtained gene set signature was evaluated in a routine clinical scenario analyzing only voided urine samples. We have identified a 12+2 gene expression signature for UCC diagnosis and prediction of tumor aggressiveness on urine samples. Overall, this gene set panel had 98% sensitivity (SN) and 99% specificity (SP) in discriminating between UCC and control samples and 79% SN and 92% SP in predicting tumor aggressiveness. The translation of the model to the clinically applicable format corroborates that the 12+2 gene set panel described maintains a high accuracy for UCC diagnosis (SN = 89% and SP = 95%) and tumor aggressiveness prediction (SN = 79% and SP = 91%) in voided urine samples. The 12+2 gene expression signature described in urine is able to identify patients suffering from UCC and predict tumor aggressiveness. We show that a panel of molecular markers may improve the schedule for diagnosis and follow-up in UCC patients. Copyright 2010 AACR.

Bladder Cancer Advocacy Network

MedlinePlus

... Event No Repeat Daily Weekly Monthly Yearly Repeat gap Repeat by day SU MO TU WE TH ... is Bladder Cancer? Newly Diagnosed Treatments Clinical Trials Research Research Grants Think Tank Research Network Genomics Consortium ...

Differential Diagnosis and Treatment of Impaired Bladder Emptying

PubMed Central

Yoshimura, Naoki; Chancellor, Michael B

2004-01-01

Although much attention is paid to urinary incontinence, the condition of incomplete bladder emptying is becoming more common with the aging of the US population and the widespread use of anticholinergic drugs to treat overactive bladder. This disorder can often be silent until end-stage presentation of overflow incontinence. In this article, we review the pathophysiologic conditions of the bladder and urethra that can cause impaired bladder emptying and discuss how to evaluate and screen the patient with a bladder that does not empty. In addition, we provide an overview of treatment options available for impaired bladder emptying and consider the research that is under way to find the best therapies for the failing bladder. PMID:16985851

[Recommendations for the urodynamic examination in the investigation of non-neurological female urinary incontinence].

PubMed

Hermieu, Jean François

2007-11-01

INDICATIONS FOR URODYNAMIC ASSESSMENT IN WOMEN: Urodynamic assessment is not useful for the diagnosis of female urinary incontinence which remains a clinical diagnosis. Before any form of surgery for pure stress urinary incontinence, evaluation of bladder emptying by determination of maximum flow rate and residual urine is recommended. In the presence of pure stress urinary incontinence with no other associated clinical symptoms, a complete urodynamic assessment is not mandatory, but can be helpful to define the prognosis and inform the patient about her vesicosphincteric function. On the other hand, a complete urodynamic assessment is recommended to investigate complex or complicated urinary incontinence, mainly in the case of: history of surgery for urinary incontinence. urgency with or without urine leakage, severe urinary incontinence, voiding abnormalities, negative cough test, decreased bladder capacity, suspected obstruction or decreased bladder contractility, failure of first-line treatment. PATIENT PREPARATION: The patient should be thoroughly informed about the examination procedure and its possible consequences. The patient should be advised to attend the examination with a normal desire to urinate. Urodynamic assessment must not be performed in the presence of untreated urinary tract infection. Antibiotic prophylaxis is not recommended. UROFLOWMETRY: The flowmeter must be regularly calibrated and must be installed in a quiet room. Whenever possible, uroflowmetry should be performed before cystometry with a normal desire to urinate. The patient should be advised to urinate normally without straining and by staying as relaxed as possible. During voiding, all of the stream must enter the flowmeter. The main parameters recorded are Qmax (expressed in ml/s), the voided volume (expressed in ml), and the appearance of the curve. The examination must be interpreted manually without taking into account the automated interpretation. GUIDELINES CONCERNING CYSTOMETRY EQUIPMENT: A three pressure line configuration is recommended. Bladder filling must be performed with a sterile liquid; filling with gas is no longer recommended. Bladder filling is ideally performed by a pump ensuring a sufficiently slow flow rate to avoid modifying bladder behaviour (< 50 ml/min). It is essential to determine and check the volume infused into the bladder. When a peristaltic pump is used, the bladder filling catheter must be adapted to the pump. Water or electronic transducers can be used to measure bladder pressure. Balloon catheters filled with air appear to be sufficiently precise to perform pressure measurements in a manometric chamber (during cystometry) but not in a virtual cavity such as the urethra (during the urethral pressure profile). Measurement of abdominal pressure is recommended, either via the infusion catheter or preferably by a rectal balloon catheter. GUIDELINES ON THE PRACTICAL CONDITIONS OF CYSTOMETRY: The equipment must be regularly calibrated. Make sure that the bladder is empty before starting cystometry. Transducers are zeroed at the superior extremity of the pubic symphysis for infused transducers and at atmospheric pressure for electronic and air transducers. Tubings must be correctly connected without kinks, bubbles or leaks. The catheter must be selected according to its technical characteristics, particularly its pressure loss. After filling for one or two minutes, the patient is asked to cough to ensure a similar increase in both abdominal pressure and bladder pressure. The following parameters are recorded: baseline detrusor pressure, first desire to void, detrusor activity, bladder capacity and bladder compliance. Measurement of bladder pressure during voiding is used to confirm whether or not the bladder is contractile, assess obstruction in the case of low urine flow rate with high bladder pressure, and detect abdominal straining. Good test conditions must be ensured in order to obtain good quality voiding. In the case of incoherent results, the bladder should be re-filled after checking the equipment. MEASUREMENT AND INTERPRETATION OF URETHRAL PRESSURE: To obtain a reliable measurement of urethral pressure, it is recommended to: Define the normal values used. Use a catheter smaller than 12 F. Perform a circumferential measurement. Use a catheter with an infusion rate of 2 ml/min. Remove the catheter at a rate of 1 mm/s. Perform the examination in the seating or supine position with a half-full bladder after reducing any prolapse. Repeat the measurements. THE FOLLOWING ELEMENTS MUST BE TAKEN INTO ACCOUNT WHEN INTERPRETING AN URETHRAL PRESSURE PROFILE: The functional urethral length is neither a diagnostic criterion nor a prognostic criterion of urinary incontinence. The urethral pressure profile cannot be considered to be a useful test for the diagnosis of female urinary incontinence. However, in combination with clinical criteria, it is predictive of the results of female stress urinary incontinence surgical repair techniques. The pressure transmission ratio is neither a diagnostic criterion nor a prognostic criterion of urinary incontinence.

Acute gall bladder perforation--a dilemma in early diagnosis.

PubMed Central

Ong, C L; Wong, T H; Rauff, A

1991-01-01

Gall bladder perforation is a rare complication of cholecystitis. A definitive diagnosis is uncommon before surgery and the morbidity and mortality associated with this condition are high. We report six patients with gall bladder perforation to show the difficulty of making an early diagnosis. The history and the clinical findings of these patients are reviewed to highlight diagnostic pitfalls. PMID:1885081

[Using of cell biocomposite material in tissue engineering of the urinary bladder].

PubMed

Glybochko, P V; Olefir, Yu V; Alyaev, Yu G; Butnaru, D V; Bezrukov, E A; Chaplenko, A A; Zharikova, T M

2017-06-01

In a systematic review, to present an overview of the current situation in the field of tissue engineering of urinary bladder related to the use of cell lines pre-cultured on matrices. The selection of eligible publications was conducted according to the method described in the article Glybochko P.V. et al. "Tissue engineering of urinary bladder using acellular matrix." At the final stage, studies investigating the application of matrices with human and animal cell lines were analyzed. Contemporary approaches to using cell-based tissue engineering of the bladder were analyzed, including the formation of 3D structures from several types of cells, cell layers and genetic modification of injected cells. The most commonly used cell lines are urothelial cells, mesenchymal stem cells and fibroblasts. The safety and efficacy of any types of composite cell structures used in the cell-based bladder tissue engineering has not been proven sufficiently to warrant clinical studies of their usefulness. The results of cystoplasty of rat bladder are almost impossible to extrapolate to humans; besides, it is difficult to predict possible side effects. For the transition to clinical trials, additional studies on relevant animal models are needed.

Bladder irrigation and urothelium disruption: a reminder apropos of a case of fatal fluid absorption.

PubMed

Di Paolo, Marco; Bugelli, Valentina; Di Luca, Alessandro; Turillazzi, Emanuela

2014-11-20

Irrigation or washouts of the bladder are usually performed in various clinical settings. In the 1980s Elliot and colleagues argued that urothelial damage could occur after washouts and irrigations of the bladder. The exact mechanism underlying urothelial damage has not yet been discovered. To our knowledge, this is the first report of fatal fluid overload and pulmonary edema, due to urothelium disruption occurring during bladder irrigation, approached performing complete histological and immunohistochemical investigation on bladder specimens. The exposed case deserves attention since it demonstrates that, although very rarely, irrigation or washouts of the bladder may have unexpected serious clinical consequences. An 85 year-old Caucasian man, unable to eat independently and whose fluid intake was controlled, underwent continuous bladder irrigation with a 3-way catheter due to a severe episode of macrohematuria. During the third day of hospitalization, while still undergoing bladder irrigation, he suddenly experienced extreme shortness of breath, breathing difficulties, and cough with frothy sputum. His attending nurse immediately noted that there was no return of the fluid (5 liters) introduced through bladder irrigation. He was treated urgently with hemodialysis. At the beginning of the dialysis treatment, the patient had gained 7.4 kg since the previous measurement (24 hours prior) without any clear explanation. Although a significant weight loss (from 81 to 76 kg) due to the dialysis procedure, the patient died shortly after the final treatment. The autopsy revealed that the brain and the lungs were heavily edematous. Microscopic examination of bladder specimens revealed interstitial and mucosal swelling, and loss of the superficial cell layer. Intermediate and basal urothelial cells were preserved. Altogether the above mentioned findings were suggestive of a diffuse disruption of the urothelium. In conclusion the death of the man was attributed to an acute severe pulmonary edema due to massive fluid absorption. Our case demonstrates that urothelium disruption may occur during irrigation and washouts of the bladder, also in the absence of other well-known predisposing conditions. Inappropriate use of bladder irrigation should be avoided and a close attention is required of the fluid balance is mandatory when irrigating the bladder.

Expression of parathyroid hormone/parathyroid hormone-related peptide receptor 1 in normal and diseased bladder detrusor muscles: a clinico-pathological study.

PubMed

Nishikawa, Nobuyuki; Yago, Rie; Yamazaki, Yuichiro; Negoro, Hiromitsu; Suzuki, Mari; Imamura, Masaaki; Toda, Yoshinobu; Tanabe, Kazunari; Ogawa, Osamu; Kanematsu, Akihiro

2015-01-21

To investigate the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor 1 (PTH1R) in clinical specimens of normal and diseased bladders. PTHrP is a unique stretch-induced endogenous detrusor relaxant that functions via PTH1R. We hypothesized that suppression of this axis could be involved in the pathogenesis of bladder disease. PTH1R expression in clinical samples was examined by immunohistochemistry. Normal kidney tissue from a patient with renal cancer and bladder specimens from patients undergoing ureteral reimplantation for vesicoureteral reflux or partial cystectomy for urachal cyst were examined as normal control organs. These were compared with 13 diseased bladder specimens from patients undergoing bladder augmentation. The augmentation patients ranged from 8 to 31 years old (median 15 years), including 9 males and 4 females. Seven patients had spinal disorders, 3 had posterior urethral valves and 3 non-neurogenic neurogenic bladders (Hinman syndrome). Renal tubules, detrusor muscle and blood vessels in normal control bladders stained positive for PTH1R. According to preoperative urodynamic studies of augmentation patients, the median percent bladder capacity compared with the age-standard was 43.6% (range 1.5-86.6%), median intravesical pressure at maximal capacity was 30 cmH2O (range 10-107 cmH2O), and median compliance was 3.93 ml/cmH2O (range 0.05-30.3 ml/cmH2O). Detrusor overactivity was observed in five cases (38.5%). All augmented bladders showed negative stainings in PTH1R expression in the detrusor tissue, but positive staining of blood vessels in majority of the cases. Downregulation of PTH1R may be involved in the pathogenesis of human end-stage bladder disease requiring augmentation.

Cystoscopic diagnosis of polypoid cystitis in two pet rabbits.

PubMed

Di Girolamo, Nicola; Bongiovanni, Laura; Ferro, Silvia; Melidone, Raffaele; Nicoletti, Annalisa; Duca, Valeria Del; Donnelly, Thomas M; Selleri, Paolo

2017-07-01

CASE DESCRIPTION AS-year-old male Dwarf rabbit and 4-year-old female Mini-Rex rabbit were evaluated because of anorexia and urine scalding of the perineum. CLINICAL FINDINGS Abdominal radiography revealed a diffuse increase in the opacity of the urinary bladder attributable to urinary sludge. In 1 rabbit, abdominal ultrasonography revealed several mass-like lesions protruding from the mucosal surface into the lumen of the urinary bladder. Rabbits were anesthetized, and cystoscopy was performed with a rigid 2.7-mm, 30° endoscope. Histologic analysis of tissue samples obtained through the cystoscope operating channel revealed findings consistent with polypoid cystitis. TREATMENT AND OUTCOME To remove the urinary sludge from each rabbit, the urinary bladder was filled with sterile saline (0.9% NaCl) solution and emptied with a gentle massage several times until the ejected fluid was transparent. Rabbits were treated with NSAIDs, antimicrobials (chosen following microbial culture of urine and antimicrobial susceptibility testing), bathing of the perineum, and a low-calcium diet. The male rabbit died of unrelated causes 18 months later; postmortem examination findings confirmed the polypoid cystitis. The female rabbit remained disease free through to last follow-up (12 months after initial evaluation). CLINICAL RELEVANCE This was the first report of polypoid cystitis in pet rabbits. Although ultrasonographic findings supported this diagnosis, a definitive diagnosis was achieved through cystoscopy and lesion biopsy. Treatments administered were intended to reduce the potential sources of irritation. Research is needed to investigate the effectiveness of the applied interventions and the association between excessive urinary calcium excretion and polyploid cystitis in rabbits.

Overactive and Underactive Bladder Dysfunction is Reflected by Alterations in Urothelial ATP and NO Release

PubMed Central

Munoz, Alvaro; Smith, Christopher P.; Boone, Timothy B.; Somogyi, George T.

2011-01-01

ATP and NO are released from the urothelium in the bladder. Detrusor Overactivity (DO) following spinal cord injury results in higher ATP and lower NO release from the bladder urothelium. Our aim was to study the relationship between ATP and NO release in 1) early diabetic bladders, an overactive bladder model; and 2) in “diuretic” bladders, an underactive bladder model. To induce diabetes mellitus female rats received 65 mg/kg streptozocin (i.v.). To induce chronic diuresis rats were fed with 5% sucrose. At 28 days, in vivo open cystometry was performed. Bladder wash was collected to analyze the amount of ATP and NO released into the bladder lumen. For in vitro analysis of ATP and NO release, a Ussing chamber was utilized and hypoosmotic Krebs was perfused on the urothelial side of the chamber. ATP was analyzed with luminometry or HPLC-fluorometry while NO was measured with a Sievers NO-analyzer. In vivo ATP release was increased in diabetic bladders and unchanged in diuretic bladders. In vitro release from the urothelium followed the same pattern. NO release was unchanged both in vitro and in vivo in overactive bladders whereas it was enhanced in underactive bladders. We found that the ratio of ATP/NO, representing sensory transmission in the bladder, was high in overactive and low in underactive bladder dysfunction. In summary, ATP release has a positive correlation while NO release has a negative correlation with the bladder contraction frequency. The urinary ATP/NO ratio may be a clinically relevant biomarker to characterize the extent of bladder dysfunction. PMID:21145365

Classification of bladder cancer cell lines using Raman spectroscopy: a comparison of excitation wavelength, sample substrate and statistical algorithms

NASA Astrophysics Data System (ADS)

Kerr, Laura T.; Adams, Aine; O'Dea, Shirley; Domijan, Katarina; Cullen, Ivor; Hennelly, Bryan M.

2014-05-01

Raman microspectroscopy can be applied to the urinary bladder for highly accurate classification and diagnosis of bladder cancer. This technique can be applied in vitro to bladder epithelial cells obtained from urine cytology or in vivo as an optical biopsy" to provide results in real-time with higher sensitivity and specificity than current clinical methods. However, there exists a high degree of variability across experimental parameters which need to be standardised before this technique can be utilized in an everyday clinical environment. In this study, we investigate different laser wavelengths (473 nm and 532 nm), sample substrates (glass, fused silica and calcium fluoride) and multivariate statistical methods in order to gain insight into how these various experimental parameters impact on the sensitivity and specificity of Raman cytology.

A review of plan library approaches in adaptive radiotherapy of bladder cancer.

PubMed

Collins, Shane D; Leech, Michelle M

2018-05-01

Large variations in the shape and size of the bladder volume are commonly observed in bladder cancer radiotherapy (RT). The clinical target volume (CTV) is therefore frequently inadequately treated and large isotropic margins are inappropriate in terms of dose to organs at risk (OAR); thereby making adaptive radiotherapy (ART) attractive for this tumour site. There are various methods of ART delivery, however, for bladder cancer, plan libraries are frequently used. A review of published studies on plan libraries for bladder cancer using four databases (Pubmed, Science Direct, Embase and Cochrane Library) was conducted. The endpoints selected were accuracy and feasibility of initiation of a plan library strategy into a RT department. Twenty-four articles were included in this review. The majority of studies reported improvement in accuracy with 10 studies showing an improvement in planning target volume (PTV) and CTV coverage with plan libraries, some by up to 24%. Seventeen studies showed a dose reduction to OARs, particularly the small bowel V45Gy, V40Gy, V30Gy and V10Gy, and the rectal V30Gy. However, the occurrence of no suitable plan was reported in six studies, with three studies showing no significant difference between adaptive and non-adaptive strategies in terms of target coverage. In addition, inter-observer variability in plan selection appears to remain problematic. The additional resources, education and technology required for the initiation of plan library selection for bladder cancer may hinder its routine clinical implementation, with eight studies illustrating increased treatment time required. While there is a growing body of evidence in support of plan libraries for bladder RT, many studies differed in their delivery approach. The advent of the clinical use of the MRI-linear accelerator will provide RT departments with the opportunity to consider daily online adaption for bladder cancer as an alternate to plan library approaches.

Automatic bladder segmentation from CT images using deep CNN and 3D fully connected CRF-RNN.

PubMed

Xu, Xuanang; Zhou, Fugen; Liu, Bo

2018-03-19

Automatic approach for bladder segmentation from computed tomography (CT) images is highly desirable in clinical practice. It is a challenging task since the bladder usually suffers large variations of appearance and low soft-tissue contrast in CT images. In this study, we present a deep learning-based approach which involves a convolutional neural network (CNN) and a 3D fully connected conditional random fields recurrent neural network (CRF-RNN) to perform accurate bladder segmentation. We also propose a novel preprocessing method, called dual-channel preprocessing, to further advance the segmentation performance of our approach. The presented approach works as following: first, we apply our proposed preprocessing method on the input CT image and obtain a dual-channel image which consists of the CT image and an enhanced bladder density map. Second, we exploit a CNN to predict a coarse voxel-wise bladder score map on this dual-channel image. Finally, a 3D fully connected CRF-RNN refines the coarse bladder score map and produce final fine-localized segmentation result. We compare our approach to the state-of-the-art V-net on a clinical dataset. Results show that our approach achieves superior segmentation accuracy, outperforming the V-net by a significant margin. The Dice Similarity Coefficient of our approach (92.24%) is 8.12% higher than that of the V-net. Moreover, the bladder probability maps performed by our approach present sharper boundaries and more accurate localizations compared with that of the V-net. Our approach achieves higher segmentation accuracy than the state-of-the-art method on clinical data. Both the dual-channel processing and the 3D fully connected CRF-RNN contribute to this improvement. The united deep network composed of the CNN and 3D CRF-RNN also outperforms a system where the CRF model acts as a post-processing method disconnected from the CNN.

Dosimetric evaluation of planning target volume margin reduction for prostate cancer via image-guided intensity-modulated radiation therapy

NASA Astrophysics Data System (ADS)

Hwang, Taejin; Kang, Sei-Kwon; Cheong, Kwang-Ho; Park, Soah; Yoon, Jai-Woong; Han, Taejin; Kim, Haeyoung; Lee, Meyeon; Kim, Kyoung-Joo; Bae, Hoonsik; Suh, Tae-Suk

2015-07-01

The aim of this study was to quantitatively estimate the dosimetric benefits of the image-guided radiation therapy (IGRT) system for the prostate intensity-modulated radiation therapy (IMRT) delivery. The cases of eleven patients who underwent IMRT for prostate cancer without a prostatectomy at our institution between October 2012 and April 2014 were retrospectively analyzed. For every patient, clinical target volume (CTV) to planning target volume (PTV) margins were uniformly used: 3 mm, 5 mm, 7 mm, 10 mm, 12 mm, and 15 mm. For each margin size, the IMRT plans were independently optimized by one medical physicist using Pinnalce3 (ver. 8.0.d, Philips Medical System, Madison, WI) in order to maintain the plan quality. The maximum geometrical margin (MGM) for every CT image set, defined as the smallest margin encompassing the rectum at least at one slice, was between 13 mm and 26 mm. The percentage rectum overlapping PTV (%V ROV ), the rectal normal tissue complication probability (NTCP) and the mean rectal dose (%RD mean ) increased in proportion to the increase of PTV margin. However the bladder NTCP remained around zero to some extent regardless of the increase of PTV margin while the percentage bladder overlapping PTV (%V BOV ) and the mean bladder dose (%BD mean ) increased in proportion to the increase of PTV margin. Without relatively large rectum or small bladder, the increase observed for rectal NTCP, %RDmean and %BD mean per 1-mm PTV margin size were 1.84%, 2.44% and 2.90%, respectively. Unlike the behavior of the rectum or the bladder, the maximum dose on each femoral head had little effect on PTV margin. This quantitative study of the PTV margin reduction supported that IG-IMRT has enhanced the clinical effects over prostate cancer with the reduction of normal organ complications under the similar level of PTV control.

In vivo diode dosimetry vs. computerized tomography and digitally reconstructed radiographs for critical organ dose calculation in high-dose-rate brachytherapy of cervical cancer.

PubMed

Hassouna, Ashraf H; Bahadur, Yasir A; Constantinescu, Camelia; El Sayed, Mohamed E; Naseem, Hussain; Naga, Adly F

2011-01-01

To investigate the correlation between the dose predicted by the treatment planning system using digitally reconstructed radiographs or three-dimensional (3D)-reconstructed CT images and the dose measured by semiconductor detectors, under clinical conditions of high-dose-rate brachytherapy of the cervix uteri. Thirty-two intracavitary brachytherapy applications were performed for 12 patients with cancer of the cervix uteri. The prescribed dose to Point A was 7 Gy. Dose was calculated for both International Commissioning on Radiation Units and Measurements (ICRU) bladder and rectal points based on digitally reconstructed radiographs and for 3D CT images-based volumetric calculation of the bladder and rectum. In vivo diode dosimetry was performed for the bladder and rectum. The ICRU reference point and the volumes of 1, 2, and 5cm(3) received 3.6±0.9, 5.6±2.0, 5.1±1.7, 4.3±1.4 and 5.0±1.2, 5.3±1.3, 4.9±1.1, and 4.2±0.9 Gy for the bladder and rectum, respectively. The ratio of the 1cm(3) and the ICRU reference point dose to the diode dose was 1.8±0.7 and 1.2±0.5 for the bladder and 1.9±0.6 and 1.7±0.5 for the rectum, respectively. 3D image-based dose calculation is the most accurate and reliable method to evaluate the dose given to critical organs. In vivo diode dosimetry is an important method of quality assurance, but clinical decisions should be made based on 3D-reconstructed CT image calculations. Copyright © 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome.

PubMed

Lashinger, Erin S R; Steiginga, Matthew S; Hieble, J Paul; Leon, Lisa A; Gardner, Scott D; Nagilla, Rakesh; Davenport, Elizabeth A; Hoffman, Bryan E; Laping, Nicholas J; Su, Xin

2008-09-01

The activation of the TRPM8 channel, a member of the large class of TRP ion channels, has been reported to be involved in overactive bladder and painful bladder syndrome, although an endogenous activator has not been identified. In this study, N-(3-aminopropyl)-2-{[(3-methylphenyl) methyl]oxy}-N-(2-thienylmethyl)benzamide hydrochloride salt (AMTB) was evaluated as a TRPM8 channel blocker and used as a tool to evaluate the effects of this class of ion channel blocker on volume-induced bladder contraction and nociceptive reflex responses to noxious bladder distension in the rat. AMTB inhibits icilin-induced TRPM8 channel activation as measured in a Ca(2+) influx assay, with a pIC(50) of 6.23. In the anesthetized rat, intravenous administration of AMTB (3 mg/kg) decreased the frequency of volume-induced bladder contractions, without reducing the amplitude of contraction. The nociceptive response was measured by analyzing both visceromotor reflex (VMR) and cardiovascular (pressor) responses to urinary bladder distension (UBD) under 1% isoflurane. AMTB (10 mg/kg) significantly attenuated reflex responses to noxious UBD to 5.42 and 56.51% of the maximal VMR response and pressor response, respectively. The ID50 value on VMR response was 2.42 +/- 0.46 mg/kg. These results demonstrate that TRPM8 channel blocker can act on the bladder afferent pathway to attenuate the bladder micturition reflex and nociceptive reflex responses in the rat. Targeting TRPM8 channel may provide a new therapeutic opportunity for overactive bladder and painful bladder syndrome.

SU-F-T-433: Evaluation of a New Dose Mimicking Application for Clinical Flexibility and Reliability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoffman, D; Nair, C Kumaran; Wright, C

2016-06-15

Purpose: Clinical workflow and machine down time occasionally require patients to be temporarily treated on a system other than the initial treatment machine. A new commercial dose mimicking application provides automated cross-platform treatment planning to expedite this clinical flexibility. The aim of this work is to evaluate the feasibility of automatic plan creation and establish a robust clinical workflow for prostate and pelvis patients. Methods: Five prostate and five pelvis patients treated with helical plans were selected for re-planning with the dose mimicking application, covering both simple and complex scenarios. Two-arc VMAT and 7- and 9-field IMRT plans were generatedmore » for each case, with the objective function of achieving similar dose volume histogram from the initial helical plans. Dosimetric comparisons include target volumes and organs at risk (OARs) (rectum, bladder, small bowel, femoral heads, etc.). Dose mimicked plans were evaluated by a radiation oncologist, and patient-specific QAs were performed to validate delivery. Results: Overall plan generation and transfer required around 30 minutes of dosimetrist’s time once the dose-mimicking protocol is setup for each site. The resulting VMAT and 7- and 9-field IMRT plans achieved equivalent PTV coverage and homogeneity (D99/DRx = 97.3%, 97.2%, 97.2% and HI = 6.0, 5.8, and 5.9, respectively), compared to helical plans (97.6% and 4.6). The OAR dose discrepancies were up to 6% in rectum Dmean, but generally lower in bladder, femoral heads, bowel and penile bulb. In the context of 1–5 fractions, the radiation oncologist evaluated the dosimetric changes as not clinically significant. All delivery QAs achieved >90% pass with a 3%/3mm gamma criteria. Conclusion: The automated dose-mimicking workflow offers a strategy to avoid missing treatment fractions due to machine down time with non-clinically significant changes in dosimetry. Future work will further optimize dose mimicking plans and investigate other cross-platform treatment delivery options.« less

Current status of tissue engineering applied to bladder reconstruction in humans.

PubMed

Gasanz, C; Raventós, C; Morote, J

2018-01-11

Bladder reconstruction is performed to replace or expand the bladder. The intestine is used in standard clinical practice for tissue in this procedure. The complications of bladder reconstruction range from those of intestinal resection to those resulting from the continuous contact of urine with tissue not prepared for this contact. In this article, we describe and classify the various biomaterials and cell cultures used in bladder tissue engineering and reviews the studies performed with humans. We conducted a review of literature published in the PubMed database between 1950 and 2017, following the principles of the PRISM declaration. Numerous in vitro and animal model studies have been conducted, but only 18 experiments have been performed with humans, with a total of 169 patients. The current evidence suggests that an acellular matrix, a synthetic polymer with urothelial and autologous smooth muscle cells attached in vitro or stem cells would be the most practical approach for experimental bladder reconstruction. Bladder replacement or expansion without using intestinal tissue is still a challenge, despite progress in the manufacture of biomaterials and the development of cell therapy. Well-designed studies with large numbers of patients and long follow-up times are needed to establish an effective clinical translation and standardisation of the check-up functional tests. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Metastatic signet-ring cell cancer of the bladder responding to chemotherapy with capecitabine: case report and review of literature

PubMed Central

Michels, Jorg; Barbour, Sean; Cavers, Douglas; Chi, Kim N.

2010-01-01

Signet-ring cell cancers deriving from the bladder are rare entities and usually present with advanced incurable disease and associated poor outlook. No standard effective chemotherapeutic option has been described largely due to the rarity of this malignancy. We report a case of a patient with metastatic bladder cancer, signet-ring cell variant. The patient progressed rapidly on standard first-line bladder cancer chemotherapy with gemcitabine and carboplatin. He responded well to second-line capecitabine with a clinically meaningful progression-free survival. PMID:20368884

Functional, histological structure and mastocytes alterations in rat urinary bladders following acute and [corrected] chronic cyclophosphamide treatment.

PubMed

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.

Tadalafil attenuates hypotonicity-induced Ca2+ influx via TRPV2 and TRPV4 in primary rat bladder urothelial cell cultures.

PubMed

Dong, Xiao; Nakagomi, Hiroshi; Miyamoto, Tatsuya; Ihara, Tatsuya; Kira, Satoru; Sawada, Norifumi; Mitsui, Takahiko; Takeda, Masayuki

2018-03-22

To investigate the localization of phosphodiesterase 5 (PDE5) and the molecular mechanism underlying the effect of the PDE5 inhibitor tadalafil in signal transduction in the bladder urothelium. PDE5 expression in rat bladder tissues and cultured primary rat bladder urothelial cells was evaluated using immunochemistry and western blot assays. Ca 2+ influx in cells exposed to isotonic solution, hypotonic solution, a selective transient receptor potential vanilloid 2 (TRPV2) channel agonist (cannabidiol), a selective TRPV4 channel agonist (GSK1016790A), a TRP cation channel melastatin 7 (TRPM7) channel agonist (PIP2), or a purinergic receptor agonist (ATP) in the presence or absence of 10 µM tadalafil was evaluated using calcium imaging techniques. We also evaluated stretch-induced changes in ATP concentration in the mouse bladder in the presence or absence of 100 µM tadalafil. Immunochemistry and western blot analyses demonstrated that PDE5 is abundantly expressed in the bladder urothelium and in primary rat urothelial cells. Ca 2+ influx induced by hypotonic stimulation, GSK1016790A, or cannabidiol was significantly inhibited by tadalafil, whereas ATP-induced Ca 2+ influx was unaffected by tadalafil. PIP2 did not induce Ca2+ influx. ATP release in tadalafil-pretreated bladders significantly decreased compared to control bladders. Tadalafil attenuates Ca 2+ influx via TRPV4 and TRPV2, and inhibits ATP release in the bladder urothelium. These findings indicate that tadalafil functions as an inhibitor of urothelial signal transduction. © 2018 Wiley Periodicals, Inc.

An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer

PubMed Central

Liang, Li-Guo; Kong, Meng-Qi; Zhou, Sherry; Sheng, Ye-Feng; Wang, Ping; Yu, Tao; Inci, Fatih; Kuo, Winston Patrick; Li, Lan-Juan; Demirci, Utkan; Wang, ShuQi

2017-01-01

Extracellular vesicles (EVs), including exosomes and microvesicles, are present in a variety of bodily fluids, and the concentration of these sub-cellular vesicles and their associated biomarkers (proteins, nucleic acids, and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for isolation of EVs, it is highly time-consuming, labor-intensive and instrument-dependent for both research laboratories and clinical settings. Here, we developed an integrated double-filtration microfluidic device that isolated and enriched EVs with a size range of 30–200 nm from urine, and subsequently quantified the EVs via a microchip ELISA. Our results showed that the concentration of urinary EVs was significantly elevated in bladder cancer patients (n = 16) compared to healthy controls (n = 8). Receiver operating characteristic (ROC) analysis demonstrated that this integrated EV double-filtration device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and 8 healthy controls). Thus, this integrated device has great potential to be used in conjunction with urine cytology and cystoscopy to improve clinical diagnosis of bladder cancer in clinics and at point-of-care (POC) settings. PMID:28436447

Basal and stress-activated hypothalamic pituitary adrenal axis function in postmenopausal women with overactive bladder.

PubMed

Smith, Ariana L; Hantsoo, Liisa; Malykhina, Anna P; File, Daniel W; Valentino, Rita; Wein, Alan J; Sammel, Mary D; Epperson, C Neill

2016-09-01

The aim of this study was to measure physiologic and psychologic stress reactivity in women with overactive bladder (OAB). There is growing evidence in preclinical models that central nervous system dysregulation, particularly in response to psychological stress, may contribute to lower urinary tract symptoms in women with OAB. Postmenopausal women with OAB and healthy controls underwent Structured Clinical Interview for DSM-IV Axis I disorders (SCID) to identify those without identifiable psychiatric disease. Eligible participants underwent physiologic measures including basal (cortisol-awakening response; CAR) and stress-activated salivary cortisol levels, heart rate (HR), urinary metanephrines and neurotrophins, as well as validated symptom assessment for stress, anxiety, depression, and bladder dysfunction at baseline and during, and following an acute laboratory stressor, the Trier Social Stress Test (TSST). Baseline measures of cortisol reactivity measured by CAR showed blunted response among women with OAB (p = 0.015), while cortisol response to the TSST was greater in the OAB group (p = 0.019). Among OAB patients, bladder urgency as measured by visual analog scale (VAS) increased from pre- to post-TSST (p = 0.04). There was a main effect of TSST on HR (p < 0.001), but no group interaction. Preliminary findings suggest that women with OAB have greater physiologic and psychologic stress reactivity than healthy controls. Importantly for women with OAB, acute stress appears to exacerbate bladder urgency. Evaluation of the markers of stress response may suggest targets for potential diagnostic and therapeutic interventions.

Spatial and temporal profile of cisplatin delivery by ultrasound-assisted intravesical chemotherapy in a bladder cancer model.

PubMed

Sasaki, Noboru; Ishi, Kazuhiro; Kudo, Nobuki; Nakayama, Shouta M M; Nakamura, Kensuke; Morishita, Keitaro; Ohta, Hiroshi; Ishizuka, Mayumi; Takiguchi, Mitsuyoshi

2017-01-01

Non-muscle invasive bladder cancer is one of the most common tumors of the urinary tract. Despite the current multimodal therapy, recurrence and progression of disease have been challenging problems. We hereby introduced a new approach, ultrasound-assisted intravesical chemotherapy, intravesical instillation of chemotherapeutic agents and microbubbles followed by ultrasound exposure. We investigated the feasibility of the treatment for non-muscle invasive bladder cancer. In order to evaluate intracellular delivery and cytotoxic effect as a function to the thickness, we performed all experiments using a bladder cancer mimicking 3D culture model. Ultrasound-triggered microbubble cavitation increased both the intracellular platinum concentration and the cytotoxic effect of cisplatin at the thickness of 70 and 122 μm of the culture model. The duration of enhanced cytotoxic effect of cisplatin by ultrasound-triggered microbubble cavitation was approximately 1 hr. Based on the distance and duration of delivery, we further tested the feasibility of repetition of the treatment. Triple treatment increased the effective distance by 1.6-fold. Our results clearly showed spatial and temporal profile of delivery by ultrasound-triggered microbubble cavitation in a tumor-mimicking structure. Furthermore, we demonstrated that the increase in intracellular concentration results in the enhancement of the cytotoxic effect in a structure with the certain thickness. Repetition of ultrasound exposure would be treatment of choice in future clinical application. Our results suggest ultrasound-triggered microbubble cavitation can be repeatable and is promising for the local control of non-muscle invasive bladder cancer.

Management of Neurogenic Bladder.

PubMed

Sripathi, Venkataramani; Mitra, Aparajita

2017-07-01

This article provides a comprehensive summary of the clinical approach, investigative modalities and management of a child with neurogenic bladder disease due to myelodysplasia. It is aimed at pediatric physicians and surgeons working in developing nations. The methodologies suggested are simple and can be practised even in resource poor regions. The goal of management is avoidance of Chronic kidney disease and for this, meticulous bladder management is the key.

Blind urethral catheterization in trauma patients suffering from lower urinary tract injuries.

PubMed

Shlamovitz, Gil Z; McCullough, Lynne

2007-02-01

The goals of our study were to review all cases of urethral and bladder trauma that presented to the University of California, Los Angeles (UCLA) Medical Center between January 1998 and August 2005 and determine (1) the clinical characteristics of patients with urethral and/or bladder injuries as well as the sensitivities of those clinical characteristics; (2) whether or not a blind attempt to insert a urethral catheter was performed; and (3) whether there is any evidence that a blind attempt to insert a urethral catheter worsened the initial urinary tract injury. This is a retrospective chart review. The study cohort comprised 46 patients with a mean age of 30 years, including 36 men (78.2%) and 10 women (21.8%). Bladder tears were found in 33 patients, 10 patients had urethral lacerations, and 3 patients had combined bladder and urethral lacerations. The most sensitive finding for urinary bladder or urethral injury was the presence of gross hematuria in the urethral catheter (100%, 95% confidence interval [CI] 0.63-0.89). Blinded insertion of a urethral catheter was attempted in 30 (90.9%, 95% CI 0.75-0.98) patients who suffered from urinary bladder injury, 6 (50%, 95% CI 0.26-0.87) patients who suffered from urethral injury and 1 (33%, 95% CI 0.0-0.9) patient who suffered from a combined urinary bladder and urethral injuries. We did not find evidence that a blind attempt to insert a urethral catheter worsened the initial urinary injury. Gross hematuria in the urethral catheter was the most sensitive sign for the presence of a urethral or urinary bladder injury in our study cohort, and often the only sign of such an injury. We found no evidence that a blind attempt to insert a urethral catheter in patients suffering from urethral and or urinary bladder injuries worsened the initial injury. Larger studies will be needed to determine the safety of blind urethral catheterization in patients that are suspected to suffer from a lower urological trauma. It is our opinion that the current guidelines should be revised to better reflect the current knowledge, technologies, and clinical practice.

18F-FDG PET/CT Findings of Metastasis to Spongy Body of Penis From Urothelial Carcinoma of Bladder.

PubMed

Wang, Yan-li; Fang, Na; Zeng, Lei; Wu, Zeng-jie; Cui, Xin-jian

2016-05-01

The spongy body of the penis metastasis from other primary sites is a rare clinical entity. It is frequently associated with widespread metastatic disease and poor prognosis clinically. We report a case of a 61-year-old man with a previous history of cystectomy due to infiltrating urothelial carcinoma of the bladder 12 months ago and presented with penile shaft swelling pain and hematuria for 3 months. The restaging F-FDG PET/CT scan demonstrated a hypermetabolic mass at his penile shaft. This lesion was confirmed on phallectomy to be infiltrating urothelial carcinoma metastasis from the known primary bladder tumor.

New clinical trial open for patients with muscle-invasive bladder cancer | Center for Cancer Research

Cancer.gov

Muscle-invasive bladder cancer is an aggressive form of bladder cancer in which the tumor invades deep into the musculature of the bladder wall, making it more likely to spread to other parts of the body. Standard treatment involves cisplatin-based chemotherapy followed by radical cystectomy, which is surgery to remove the bladder and nearby organs. However, many patients don’t receive chemotherapy before surgery or may not respond to it. Other patients are ineligible for cisplatin treatment due to poor kidney function. CCR investigators are leading a phase III trial to determine whether an immunotherapy drug given shortly after cystectomy can help these patients. Read more…

Superficial and muscle-invasive bladder cancer: principles of management for outcomes assessments.

PubMed

Parekh, Dipen J; Bochner, Bernard H; Dalbagni, Guido

2006-12-10

Bladder cancer is a heterogeneous disease. Non-muscle-invasive bladder cancer embraces a spectrum of tumors with varying degrees of clinical behavior. Transurethral resection remains the surgical mainstay for the treatment of non-muscle-invasive bladder cancer. In an attempt to decrease the recurrence or progression rate, intravesical chemotherapy or immunotherapy is also used. Radical cystectomy with bilateral pelvic lymph node dissection remains the gold standard for treating muscle-invasive bladder cancer. Over the last decade, the orthotopic neobladder has gained widespread popularity as the preferred mode of urinary diversion in both males and females with similar oncologic and functional outcomes. Well-designed trials with effective chemotherapy have shown a beneficial role for neoadjuvant chemotherapy.

Relationship among bacterial virulence, bladder dysfunction, vesicoureteral reflux and patterns of urinary tract infection in children.

PubMed

Storm, Douglas W; Patel, Ashay S; Horvath, Dennis J; Li, Birong; Koff, Stephen A; Justice, Sheryl S

2012-07-01

We hypothesized that virulence levels of Escherichia coli isolates causing pediatric urinary tract infections differ according to severity of infection and also among various uropathies known to contribute to pediatric urinary tract infections. We evaluated these relationships using in vitro cytokine interleukin-6 elicitation. E. coli isolates were cultured from children presenting with urinary tract infections. In vitro cytokine (interleukin-6) elicitation was quantified for each isolate and the bacteria were grouped according to type of infection and underlying uropathy (neurogenic bladder, nonneurogenic bowel and bladder dysfunction, primary vesicoureteral reflux, no underlying etiology). A total of 40 E. coli isolates were collected from children with a mean age of 61.5 months (range 1 to 204). Mean level of in vitro cytokine elicitation from febrile urinary tract infection producing E. coli was significantly lower than for nonfebrile strains (p = 0.01). The interleukin-6 response to E. coli in the neurogenic bladder group was also significantly higher than in the vesicoureteral reflux (p = 0.01) and no underlying etiology groups (p = 0.02). In vitro interleukin-6 elicitation, an established marker to determine bacterial virulence, correlates inversely with clinical urinary tract infection severity. Less virulent, high cytokine producing E. coli were more likely to cause cystitis and were more commonly found in patients with neurogenic bladder and nonneurogenic bowel and bladder dysfunction, whereas higher virulence isolates were more likely to produce febrile urinary tract infections and to affect children with primary vesicoureteral reflux and no underlying etiology. These findings suggest that bacteria of different virulence levels may be responsible for differences in severity of pediatric urinary tract infections and may vary among different underlying uropathies. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

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

PubMed

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.

Successful adenovirus-mediated wild-type p53 gene transfer in patients with bladder cancer by intravesical vector instillation.

PubMed

Kuball, Jürgen; Wen, Shu Fen; Leissner, Joachim; Atkins, Derek; Meinhardt, Patricia; Quijano, Erlinda; Engler, Heidrun; Hutchins, Beth; Maneval, Daniel C; Grace, Michael J; Fritz, Mary Ann; Störkel, Stefan; Thüroff, Joachim W; Huber, Christoph; Schuler, Martin

2002-02-15

To study safety, feasibility, and biologic activity of adenovirus-mediated p53 gene transfer in patients with bladder cancer. Twelve patients with histologically confirmed bladder cancer scheduled for cystectomy were treated on day 1 with a single intratumoral injection of SCH 58500 (rAd/p53) at cystoscopy at one dose level (7.5 x 10(11) particles) or a single intravesical instillation of SCH 58500 with a transduction-enhancing agent (Big CHAP) at three dose levels (7.5 x 10(11) to 7.5 x 10(13) particles). Cystectomies were performed in 11 patients on day 3, and transgene expression, vector distribution, and biologic markers of transgene activity were assessed by molecular and immunohistochemical methods in tumors and normal bladder samples. Specific transgene expression was detected in tissues from seven of eight assessable patients treated with intravesical instillation of SCH 58500 but in none of three assessable patients treated with intratumoral injection of SCH 58500. Induction of RNA and protein expression of the p53 target gene p21/WAF1 was demonstrated in samples from patients treated with SCH 58500 instillation at higher dose levels. Distribution studies after intravesical instillation of SCH 58500 revealed both high transduction efficacy and vector penetration throughout the whole urothelium and into submucosal tumor cells. No dose-limiting toxicity was observed, and side effects were local and of transient nature. Intravesical instillation of SCH 58500 combined with a transduction-enhancing agent is safe, feasible, and biologically active in patients with bladder cancer. Studies to evaluate the clinical efficacy of this treatment in patients with localized high-risk bladder cancer are warranted.

Experimental results on mechanisms of action of electrical neuromodulation in chronic urinary retention.

PubMed

Schultz-Lampel, D; Jiang, C; Lindström, S; Thüroff, J W

1998-01-01

Sacral foramen neuromodulation--initially applied for the treatment of urinary incontinence--has proved to be effective in patients with chronic urinary retention. Thus far, the underlying neurophysiological mechanisms have not been elucidated. In an experimental study on the neurophysiological basis of sacral neurostimulation, one objective was to investigate the mechanisms responsible for initiation of micturition in chronic urinary retention. In ten female cats anesthetized with alpha-chloralose the clinical situation of sacral foramen stimulation was experimentally reproduced by isolated S2 nerve stimulation after L6-S3 laminectomy. Stimulation responses were recorded from the bladder, peripheral nerves, and striated muscles of the foot and pelvic floor. The effect of sudden cessation of prolonged S2 stimulation, during which the bladder was completely inhibited, was evaluated in 70 stimulation sequences in 5 cats. Sacral nerve stimulation induced excitatory and inhibitory effects on the bladder, depending on the frequency and intensity of stimulation. With unilateral S2 stimulation, bladder excitation was best at frequencies of 2-5 Hz and at intensities ranging between 0.8 and 1.4 times the threshold for the M-response of the foot muscle. Inhibition was the dominating effect at frequencies of 7-10 Hz and at intensities exceeding 1.4 times the threshold. Prolonged S2 stimulation above the threshold produced complete bladder inhibition during stimulation but induced strong bladder contractions after sudden interruption of stimulation, with amplitudes being significantly higher than that of spontaneous contractions preceding the stimulation. These results confirm the hypothesis of a "rebound" phenomenon as the mechanism of action for induction of spontaneous voiding in patients with chronic urinary retention.

Bladder symptoms assessed with overactive bladder questionnaire in Parkinson's disease.

PubMed

Iacovelli, Elisa; Gilio, Francesca; Meco, Giuseppe; Fattapposta, Francesco; Vanacore, Nicola; Brusa, Livia; Giacomelli, Elena; Gabriele, Maria; Rubino, Alfonso; Locuratolo, Nicoletta; Iani, Cesare; Pichiorri, Floriana; Colosimo, Carlo; Carbone, Antonio; Palleschi, Giovanni; Inghilleri, Maurizio

2010-07-15

In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB-q) is a measure designed to assess the impact of OAB symptoms on health-related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB-q short form. Possible correlations between the OAB-q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB-q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Hoehn-Yahr (H-Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age-matched healthy subjects. The OAB-q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB-q scores, UPDRS-III scores, and H-Y staging. A multiple linear regression analysis showed that OAB-q values were significantly influenced by age and UPDRS-III. No statistical correlations were found between OAB-q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB-q mainly correlates with UPDRS-III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB-q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD.

Novel bifunctional anthracycline and nitrosourea chemotherapy for human bladder cancer: analysis in a preclinical survival model.

PubMed

Glaves, D; Murray, M K; Raghavan, D

1996-08-01

A hybrid drug [N-2-chloroethylnitrosoureidodaunorubicin (AD312)] that combines structural and functional features of both anthracyclines and nitrosoureas was evaluated in a preclinical survival model of human bladder cancer. To measure the therapeutic activity of AD312, UCRU-BL13 transitional cell carcinoma cells were grown as xenografts in nude mice, and tumor growth rates were compared after i.v. administration of the drug at three dose levels. AD312 treatment at 45 and 60 mg/kg achieved 7-10-fold inhibition of tumor growth and increased host survival by 156 and 249%, respectively. Doses of 60 mg/kg showed optimal therapeutic efficacy, with sustained tumor growth inhibition, an over 2-fold increase in life span, and 40% of mice tumor free ("cured") at 120 days. Tumors were unresponsive to maximum tolerated doses of doxorubicin, a standard anthracycline used as a single agent and in combination therapies for bladder cancer. 1,3-Bis-[2-chloroethyl]-1-nitrosourea was used as a control for the apparently enhanced response of human tumors in murine hosts to nitrosoureas. 1, 3-Bis-[2-chloroethyl]-1-nitrosourea administered in three injections of 20 mg/kg did not cure mice but temporarily inhibited tumor growth by 70% and prolonged survival by 55%; its activity in this model suggests that it may be included in the repertoire of alkylating agents currently used for treatment of bladder cancers. AD312 showed increased antitumor activity with less toxicity than doxorubicin, and its bifunctional properties provide the opportunity for simultaneous treatment of individual cancer cells with two cytotoxic modalities as well as treatment of heterogeneous populations typical of bladder cancers. This novel cytotoxic drug cured doxorubicin-refractory disease and should be investigated for the clinical management of bladder cancer.

Arctigenin anti-tumor activity in bladder cancer T24 cell line through induction of cell-cycle arrest and apoptosis.

PubMed

Yang, Shucai; Ma, Jing; Xiao, Jianbing; Lv, Xiaohong; Li, Xinlei; Yang, Huike; Liu, Ying; Feng, Sijia; Zhang, Yafang

2012-08-01

Bladder cancer is the most common neoplasm in the urinary system. This study assesses arctigenin anti-tumor activity in human bladder cancer T24 cells in vitro and the underlying molecular events. The flow cytometry analysis was used to detect cell-cycle distribution and apoptosis. Western blotting was used to detect changes in protein expression. The data showed that arctigenin treatment reduced viability of bladder cancer T24 cells in a dose- and time-dependent manner after treatment with arctigenin (10, 20, 40, 80, and 100 μmol/L) for 24 hr and 48 hr. Arctigenin treatment clearly arrested tumor cells in the G1 phase of the cell cycle. Apoptosis was detected by hoechst stain and flow cytometry after Annexin-V-FITC/PI double staining. Early and late apoptotic cells were accounted for 2.32-7.01% and 3.07-7.35%, respectively. At the molecular level, arctigenin treatment decreased cyclin D1 expression, whereas CDK4 and CDK6 expression levels were unaffected. Moreover, arctigenin selectively altered the phosphorylation of members of the MAPK superfamily, decreasing phosphorylation of ERK1/2 and activated phosphorylation of p38 significantly in a dose-dependent manner. These results suggest that arctigenin may inhibit cell viability and induce apoptosis by direct activation of the mitochondrial pathway, and the mitogen-activated protein kinase pathway may play an important role in the anti-tumor effect of arctigenin. The data from the current study demonstrate the usefulness of arctigenin in bladder cancer T24 cells, which should further be evaluated in vivo before translation into clinical trials for the chemoprevention of bladder cancer. Copyright © 2012 Wiley Periodicals, Inc.

Effectiveness of platinum-based adjuvant chemotherapy for muscle-invasive bladder cancer: A weighted propensity score analysis.

PubMed

Shimizu, Fumitaka; Muto, Satoru; Taguri, Masataka; Ieda, Takeshi; Tsujimura, Akira; Sakamoto, Yoshiro; Fujita, Kazuhiko; Okegawa, Takatsugu; Yamaguchi, Raizo; Horie, Shigeo

2017-05-01

To evaluate the clinical benefit of adjuvant platinum-based chemotherapy after radical cystectomy for muscle-invasive bladder cancer in routine clinical practice. The present observational study was carried out to compare the effectiveness of adjuvant chemotherapy versus observation post-radical cystectomy in patients with clinically muscle-invasive bladder cancer. Cancer-specific survival and overall survival between the adjuvant chemotherapy group and radical cystectomy alone group were compared using Kaplan-Meier method and log-rank test. After adjusting for background factors using propensity score weighting, differences in cancer-specific survival and overall survival between these two groups were compared. Subgroup analyses by the pathological characteristics were carried out. In total, 322 patients were included in the present study. Of these, 23% received adjuvant chemotherapy post-radical cystectomy. Clinicopathological characteristics showed that patients in the adjuvant chemotherapy group were pathologically more advanced and were at higher risk than the radical cystectomy alone group. In the unadjusted population, although it is not significant, the adjuvant chemotherapy group had lower overall survival (3-year overall survival; 61.5% vs 73.6%, HR 1.33, P = 0.243, log-rank test, adjuvant chemotherapy vs radical cystectomy alone). In the weighted propensity score analysis, although it is not significant, the adjuvant chemotherapy group were superior to radical cystectomy alone groups (overall survival: HR 0.65, 95% CI 0.39-1.09, P = 0.099, log-rank test, adjuvant chemotherapy vs radical cystectomy alone). Subgroup analyses showed that adjuvant chemotherapy significantly reduced the hazard ratio of overall survival and cancer-specific survival in the ≥pT3, pN+, ly+ and v+ subgroups. Platinum-based adjuvant chemotherapy might be associated with increased cancer-specific survival and overall survival in patients with high-risk invasive bladder cancer. © 2017 The Japanese Urological Association.

Initial experimental evaluation of wireless capsule endoscopes in the bladder: implications for capsule cystoscopy.

PubMed

Gettman, Matthew T; Swain, Paul

2009-05-01

Cystoscopy remains one of the most important diagnostic procedures for the lower urinary tract. Wireless capsule endoscopy was introduced in the 1990s but use to date is limited to gastroenterology. We evaluated the feasibility in the pig model of using wireless capsule endoscopes (WCEs) for cystoscopy. Experimental evaluation of capsule cystoscopy was performed in a 50-kg farm pig. The capsule was deployed into the bladder through a custom access sheath. Images were continuously transmitted at a rate of four frames per second to a laptop computer and processed using proprietary software. Manipulation of the WCE within the bladder was performed using a set protocol. The animal was then euthanized and gross inspection was performed. We measured the ability to deploy and manipulate the capsule within the bladder. Feasibility of capturing and retrieving images in real time was also assessed. The WCE was efficiently deployed and manipulated within the bladder passively and with the use of external magnets. The entire bladder mucosa was visualized. Real-time image transmission and capture were successful. No complications were seen during capsule cystoscopy. Minor urethral bleeding was observed after the experiment, likely related to placement of the access sheath required for deployment of the WCE. Limitations are that the evaluation of WCE was performed in the pig model, in only one female animal, using a nonsurvival approach. Furthermore, the study was not designed to differentiate normal from abnormal mucosal findings and focused solely on inspection of the bladder. This report suggests that cystoscopy with a WCE is feasible. With this device, all aspects of the bladder mucosa could be visualized, and ongoing technologic and procedural developments are warranted for this new approach.

Fluorescein angiography of the bladder: technique and relevance to bladder cancer and interstitial cystitis patients.

PubMed

Zimmern, P E; Laub, D; Leach, G E

1995-07-01

Fluorescein angiography has been used in the study of bleeding vessels, neovascularity, tumors and ischemic tissues in a variety of disorders. This pilot study was designed to evaluate the feasibility, safety and relevance of this interesting technology for the evaluation of bladder wall vessels in patients with interstitial cystitis and bladder cancer. Five patients with National Institutes of Health defined interstitial cystitis symptoms and 10 with bladder cancer were studied during cytoscopy while they were under general anesthesia. A yellow-green barrier filter (520 nm.) was placed over the cystoscope eyepiece and a blue exciter filter (465 nm.) was attached to the light source. Patients received a 5 ml. bolus of 10% fluorescein intravenously. After hydrodistension, glomerulations in interstitial cystitis patients were more prominent with fluorescein angiography and occurred in the venule phase. Areas of papillary transitional cell tumor and carcinoma in situ developed a brilliant yellow-green fluorescence. Adjacent normal urothelium was nonfluorescent and provided a contrasting dark background facilitating the detection of all lesions. No allergic reaction or other adverse effect related to the fluorescein injection was observed. These unique observations in a limited number of patients suggest that fluorescein angiography of the bladder is a safe and simple procedure. This preliminary report underscores the relevance of fluorescein angiography in the detection of bladder tumor and offers a new approach to the evaluation of bladder wall vessels in interstitial cystitis patients.

Bladder cancer in patients with spinal cord injury.

PubMed

Hess, Marika J; Zhan, Ellen H; Foo, Dominic K; Yalla, Subbarao V

2003-01-01

The incidence of bladder cancer in spinal cord injury (SCI) is 16 to 28 times higher than that in the general population. The objective of this study was to investigate the characteristics of bladder cancer that are unique to the SCI population. Retrospective review. The charts of 16 patients diagnosed with bladder cancer from 1982 to 2001 were reviewed for type of cancer, exposure to risk factors, presenting symptoms, and survival time. The presenting manifestations were gross hematuria in 14 patients, papillary urethral growth in 1 patient, and acute obstructive renal failure in 1 patient. The diagnosis was made on initial cystoscopic evaluation in 16 patients; 3 patients required further evaluation. Eight of the 11 screening cytologies were suspicious for a malignancy prior to the diagnosis. Seven patients had transitional cell carcinoma, 6 patients had squamous cell carcinoma (SCCA), and 3 patients had both. The bladder wasmanaged with chronic indwelling catheter in 12 patients. Nine patients died of bladder cancer metastases and the remaining 3 patients died of other causes. Six patients survived 5 years or more; 4 were still alive at the completion of this study. Gross hematuria in individuals with SCI warrants aggressive assessment for bladder cancer. Chronic indwelling catheter, smoking, and renal and bladder stones are important risk factors for cancer. The incidence of SCCA in the SCI popullation is much higher than in the general population. Cystoscopic and cytologic evaluation in patients with advanced disease may fail to confirm the diagnosis in a high proportion of patients.

Primary malignant melanoma of the urinary bladder: clinical, morphological, and molecular analysis of five cases.

PubMed

Karabulut, Yasemin Y; Erdogan, Seyda; Sayar, Hamide; Ergen, Ali; Ertoy Baydar, Dilek

2016-12-01

The aim of our study was to evaluate the clinical and morphological features of primary malignant melanomas of the urinary bladder. We obtained information on five such cases from three different institutions. These were three men and two women between 52 and 76 years of age. Three tumors presented with hematuria, one with dysuria, and one was discovered incidentally on imaging studies. All were invasive to muscularis propria on transuretral resections performed for diagnosis. Neoplastic cells showed variable patterns (large cell epithelioid, small cell diffuse, storiform, or mixed) in different tumors. Pigmentation was prominent in all except one case. Each case was labeled diffusely for S-100, HMB-45, and Melan-A. Pan-cytokeratin showed a perinuclear dot-like reaction in two tumors. Three cases showed the BRAF mutation in molecular studies. Two patients were already metastatic at the time of diagnosis. Two patients died, one is alive with disease after 15 months, and two patients are disease free at 1 and 5 years of surveillance.

Clinical staging: its importance in therapeutic decisions and clinical trials.

PubMed

Denis, L J

1992-02-01

International collaboration has resulted in a revised and unified 1987 formulation for the TNM classification in solid tumors. The simplification and eliminations of most variables caused difficulties for the clinical use of the system in some tumors such as bladder cancer. The approval of the proposed adaptation covering the tumor mass, subdividing the T4 category and adapting the stage grouping, resolves these difficulties. Published reports demonstrate support for the TNM system as a clinical base for treatment decisions and prognosis. The TNMG stage and grade are important basic prognostic factors, but other prognostic factors, especially biologic tumor activity, are under clinical investigation. The TNM classification is the initial evaluation after histologic confirmation of cancer to guide treatment and prognosis. The quality of the evaluation is enhanced by precise communication on the employed methodology.

Fetal bladder catheterization in severe obstructive uropathy before the 24th week of pregnancy.

PubMed

Szaflik, K; Kozarzewski, M; Adamczewski, D

1998-01-01

Fetal obstructive uropathy is simple to diagnose before the 24th week of life. Drainage of the pathologically enlarged fetal bladder avoids development of hydronephrosis and destruction of kidneys and, obviously, prevents development of secondary oligohydramnios and pulmonary hypoplasia. The aim of our study was to evaluate the usefulness of a fetal bladder shunt in cases of obstructive uropathy before the 24th week of gestation. From January 1997 we diagnosed 6 cases of fetal obstructive uropathy before the 24th week of gestation. In all cases oligohydramnios or ahydramnios was also observed. After evaluation of the renal function on the basis of fetal urine samples, we shunted 5 fetuses. After routine preparation of the operative field, a special puncture needle was inserted through the abdominal wall of mother and fetus into the fetal bladder. Through the needle a fetal bladder catheter was inserted between the fetal bladder and the amniotic sac. After shunt placement, fetal urine fills the amniotic sac and the fetal bladder is decompressed. After the procedure, the patients were hospitalized and serial sonographic examinations were performed to evaluate shunt function. Bladder size, presence and size of hydronephrosis, and volume of amniotic fluid were evaluated. The Rocket Medical catheters have an excellent 'shape memory'. All but 1 newborns had a good perinatal outcome. Mean Apgar score was 8 at 1 min, weight at delivery was between 1,700 and 3,100 g. No pulmonary hypoplasia was observed. All deliveries were after the 33rd week of gestation (range 33-38 weeks). The minimum drainage time was 11 weeks, maximum 18 weeks. In 2 cases premature delivery occurred because of premature rupture of the membranes. One newborn died of respiratory distress syndrome. Early bladder drainage (before the 24th week of gestation) enables delivery of newborns with a good perinatal outcome, without pulmonary hypoplasia. This method of therapy limits renal damage and allows time for normal development of the fetal lungs.

OK-432 Suppresses Proliferation and Metastasis by Tumor Associated Macrophages in Bladder Cancer.

PubMed

Tian, Yuan-Feng; Tang, Kun; Guan, Wei; Yang, Tao; Xu, Hua; Zhuang, Qian-Yuan; Ye, Zhang-Qun

2015-01-01

OK-432, a Streptococcus-derived anticancer immunotherapeutic agent, has been applied in clinic for many years and achieved great progress in various cancers. In the present study, we investigated its anticancer effect on bladder cancer through tumor associated macrophages (TAMs). MTS assay validated OK-432 could inhibit proliferation in both T24 and EJ bladder cell lines. OK-432 also induced apoptosis of bladder cancer cells in vitro. Consequently, we demonstrated that OK-432 could suppress the bladder cancer cells migration and invasion by altering the EMT-related factors. Furthermore, using SD rat model, we revealed that OK-432 inhibited tumor growth, suppressed PCNA expression and inhibited metastasis in vivo. Taken together, these findings strongly suggest that OK-432 inhibits cell proliferation and metastasis through inducing macrophages to secret cytokines in bladder cancer.

Single Versus Customized Treatment Planning for Image-guided High-Dose-Rate Brachytherapy for Cervical Cancer: Dosimetric Comparison and Predicting Factor for Organs at Risk Overdose With Single Plan Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, Alexander; Gao Mingcheng; Sinacore, James

2009-09-01

Purpose: To compare the dose distribution between customized planning (CP) and adopting a single plan (SP) in multifractionated high-dose-rate brachytherapy and to establish predictors for the necessity of CP in a given patient. Methods and Materials: A total of 50 computed tomography-based plans for 10 patients were evaluated. Each patient had received 6 Gy for five fractions. The clinical target volume and organs at risk (i.e., rectum, bladder, sigmoid, and small bowel) were delineated on each computed tomography scan. For the SP approach, the same dwell position and time was used for all fractions. For the CP approach, the dwellmore » position and time were reoptimized for each fraction. Applicator position variation was determined by measuring the distance between the posterior bladder wall and the tandem at the level of the vaginal fornices. Results: The organs at risk D{sub 2cc} (dose to 2 cc volume) was increased with the SP approach. The dose variation was statistically similar between the tandem and ring and tandem and ovoid groups. The bladder D{sub 2cc} dose was 81.95-105.42 Gy{sub 2} for CP and 82.11-122.49 Gy{sub 2} for SP. In 5 of the 10 patients, the bladder would have been significantly overdosed with the SP approach. The variation of the posterior bladder wall distance from that in the first fraction was correlated with the increase in the bladder D{sub 2cc} (SP/CP), with a correlation coefficient of -0.59. Conclusion: Our results support the use of CP instead of the SP approach to help avoid a significant overdose to the bladder. This is especially true for a decrease in the posterior wall distance of {>=}0.5 cm compared with that in the first fraction.« less

Early treatment improves urodynamic prognosis in neurogenic voiding dysfunction: 20 years of experience.

PubMed

Costa Monteiro, Lucia M; Cruz, Glaura O; Fontes, Juliana M; Vieira, Eliane T R C; Santos, Eloá N; Araújo, Grace F; Ramos, Eloane G

To evaluate the association between early treatment and urodynamic improvement in pediatric and adolescent patients with neurogenic bladder. Retrospective longitudinal and observational study (between 1990 and 2013) including patients with neurogenic bladder and myelomeningocele treated based on urodynamic results. The authors evaluated the urodynamic follow-up (bladder compliance and maximum bladder capacity and pressure) considering the first urodynamic improvement in two years as the outcome variable and early referral as the exposure variable, using a descriptive and multivariate analysis with logistic regression model. Among 230 patients included, 52% had an early referral. The majority were diagnosed as overactive bladder with high bladder pressure (≥40cm H 2 O) and low bladder compliance (3mL/cmH 2 O) and were treated with oxybutynin and intermittent catheterization. Urodynamic follow-up results showed 68% of improvement at the second urodynamic examination decreasing bladder pressure and increasing bladder capacity and compliance. The percentage of incontinence and urinary tract infections decreased over treatment. Early referral (one-year old or less) increased by 3.5 the probability of urodynamic improvement in two years (95% CI: 1.81-6.77). Treatment onset within the first year of life improves urodynamic prognosis in patients with neurogenic bladder and triplicates the probability of urodynamic improvement in two years. The role of neonatologists and pediatricians in early referral is extremely important. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Long-term complications following bladder augmentations in patients with spina bifida: bladder calculi, perforation of the augmented bladder and upper tract deterioration.

PubMed

Husmann, Douglas A

2016-02-01

We desire to review our experience with bladder augmentation in spina bifida patients followed in a transitional and adult urologic practice. This paper will specifically focus on three major complications: bladder calculi, the most frequent complication found following bladder augmentation, perforation of the augmentation, its most lethal complication and finally we will address loss of renal function as a direct result of our surgical reconstructive procedures. We reviewed a prospective data base maintained on patients with spina bifida followed in our transitional and adult urology clinic from 1986 to date. Specific attention was given to patients who had developed bladder calculi, sustained a spontaneous perforation of the augmented bladder or had developed new onset of renal scarring or renal insufficiency (≥ stage 3 renal failure) during prolonged follow-up. The development of renal stones (P<0.05) and symptomatic urinary tract infections (P<0.0001) were found to be significantly reduced by the use of high volume (≥240 mL) daily bladder wash outs. Individuals who still developed bladder calculi recalcitrant to high volume wash outs were not benefited by the correction of underlying metabolic abnormalities or mucolytic agents. Spontaneous bladder perforations in the adult patient population with spina bifida were found to be directly correlated to substance abuse and noncompliance with intermittent catheterization, P<0.005. Deterioration of the upper tracts as defined by the new onset of renal scars occurred in 40% (32/80) of the patients managed by a ileocystoplasty and simultaneous bladder neck outlet procedure during a median follow-up interval 14 years (range, 8-45 years). Development of ≥ stage 3 chronic renal failure occurred within 38% (12/32) of the patients with scarring i.e., 15% (12/80) of the total patient population. Prior to the development of the renal scarring, 69% (22/32) of the patients had been noncompliant with intermittent catheterization. The onset of upper tract deterioration (i.e., new scar formation, hydronephrosis, calculus development, decrease in renal function) was silent, that is, clinically asymptomatic in one third (10/32 pts). This paper documents the need for high volume bladder irrigations to both prevent the most common complication following bladder augmentation, which is the development of bladder calculi and to reduce the incidence of symptomatic urinary tract infections. It provides a unique perspective regarding the impact of substance abuse and patient non-compliance with medical directives as being both the most common cause for both spontaneous bladder rupture following augmentation cystoplasty and for deterioration of the upper tracts. These findings should cause the surgeon to reflect on his/her assessment of a patient prior to performing a bladder augmentation procedure and stress the need for close follow-up.

A systematic review and comparison of questionnaires in the management of spinal cord injury, multiple sclerosis and the neurogenic bladder.

PubMed

Tsang, B; Stothers, L; Macnab, A; Lazare, D; Nigro, M

2016-03-01

Validated questionnaires are increasingly the preferred method used to obtain historical information. Specialized questionnaires exist validated for patients with neurogenic disease including neurogenic bladder. Those currently available are systematically reviewed and their potential for clinical and research use are described. A systematic search via Medline and PubMed using the key terms questionnaire(s) crossed with Multiple Sclerosis (MS) and Spinal Cord Injury (SCI) for the years 1946 to January 22, 2014 inclusive. Additional articles were selected from review of references in the publications identified. Only peer reviewed articles published in English were included. 18 questionnaires exist validated for patients with neurogenic bladder; 14 related to MS, 3 for SCI, and 1 for neurogenic bladder in general; with 4 cross-validated in both MS and SCI. All 18 are validated for both male and female patients; 59% are available only in English. The domains of psychological impact and physical function are represented in 71% and 76% of questionnaires, respectively. None for the female population included elements to measure symptoms of prolapse. The last decade has seen an expansion of validated questionnaires to document bladder symptoms in neurogenic disease. Disease specific instruments are available for incorporation into the clinical setting for MS and SCI patients with neurogenic bladder. The availability of caregiver and interview options enhances suitability in clinical practice as they can be adapted to various extents of disability. Future developments should include expanded language validation to the top 10 global languages reported by the World Health Organization. © 2015 Wiley Periodicals, Inc.

Implantable Bladder Sensors: A Methodological Review

PubMed Central

Dakurah, Mathias Naangmenkpeong; Koo, Chiwan; Choi, Wonseok; Joung, Yeun-Ho

2015-01-01

The loss of urinary bladder control/sensation, also known as urinary incontinence (UI), is a common clinical problem in autistic children, diabetics, and the elderly. UI not only causes discomfort for patients but may also lead to kidney failure, infections, and even death. The increase of bladder urine volume/pressure above normal ranges without sensation of UI patients necessitates the need for bladder sensors. Currently, a catheter-based sensor is introduced directly through the urethra into the bladder to measure pressure variations. Unfortunately, this method is inaccurate because measurement is affected by disturbances in catheter lines as well as delays in response time owing to the inertia of urine inside the bladder. Moreover, this technique can cause infection during prolonged use; hence, it is only suitable for short-term measurement. Development of discrete wireless implantable sensors to measure bladder volume/pressure would allow for long-term monitoring within the bladder, while maintaining the patient’s quality of life. With the recent advances in microfabrication, the size of implantable bladder sensors has been significantly reduced. However, microfabricated sensors face hostility from the bladder environment and require surgical intervention for implantation inside the bladder. Here, we explore the various types of implantable bladder sensors and current efforts to solve issues like hermeticity, biocompatibility, drift, telemetry, power, and compatibility issues with popular imaging tools such as computed tomography and magnetic resonance imaging. We also discuss some possible improvements/emerging trends in the design of an implantable bladder sensor. PMID:26620894

[Unfixed Mesh Plug Migration from Inguinal Ring to Urinary Bladder].

PubMed

Okada, Koichi; Nakayama, Jiro; Adachi, Shiro; Miyake, Osamu

2018-02-01

A 65-year-old man presented to a clinic with a chief complaint of macrohematuria and frequent urination. The computed tomographic scan and cystoscopy revealed a dome of bladder tumor. He was referred to our hospital with the diagnosis of bladder tumor. He had undergone bilateral inguinal hernia repair and magnetic resonance imaging suggested mesh plug migration on the urinary bladder inserted into the right inguinal lesion 11 years previously. Under the diagnosis of mesh plug migration, partial cystectomy with extraction of the foreign body was performed. After the surgery he was well and symptoms had disappeared.

Effects of Physiotherapy in the Treatment of Neurogenic Bladder in Patients Infected With Human T-Lymphotropic Virus 1.

PubMed

Andrade, Rosana C P; Neto, José A; Andrade, Luciana; Oliveira, Tatiane S; Santos, Dislene N; Oliveira, Cassius J V; Prado, Márcio J; Carvalho, Edgar M

2016-03-01

To evaluate the efficacy of physiotherapy for urinary manifestations in patients with human T-lymphotropic virus 1-associated lower urinary tract dysfunction. Open clinical trial was conducted with 21 patients attending the physiotherapy clinic of the Hospital Universitário, Bahia, Brazil. Combinations of behavioral therapy, perineal exercises, and intravaginal or intra-anal electrical stimulation were used. The mean age was 54 ± 12 years and 67% were female. After treatment, there was an improvement in symptoms of urinary urgency, frequency, incontinence, nocturia, and in the sensation of incomplete emptying (P < .001). There was also a reduction in the overactive bladder symptom score from 10 ± 4 to 6 ± 3 (P < .001) and an increase in the perineal muscle strength (P <.001). The urodynamic parameters improved, with reduction in the frequency of patients with detrusor hyperactivity from 57.9% to 42.1%, detrusor-sphincter dyssynergia from 31.6% to 5.3%, detrusor hypocontractility from 15.8% to 0%, and detrusor areflexia from 10.5% to 0%, with positive repercussions in the quality of life in all patients. Physiotherapy was effective in cases of human T-lymphotropic virus 1-associated neurogenic bladder, reducing symptoms, increasing perineal muscle strength, and improving urodynamic parameters and quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

Voiding dysfunction: another etiology of vulvovaginitis in young girls.

PubMed

Romero, P; Rodríguez, E; Muñoz, M; Delucchi, A; Guerrero, J L; Lillo, A M; Cano, F; Matilde Osses, Sra; Romero, M I; Gonzalez Roca, C

2011-08-01

To determine the prevalence of voiding dysfunction (VD) in patients with persistent vulvovaginitis (PVV), and to evaluate the clinical response of PVV in the treatment of VD. Girls four years or older who consulted for PVV for at least one month and who did not respond to general measures. A physical examination was performed with visual inspection and colposcopy; vaginal samples for culture and vaginoscopy were carried out. On every patient urodynamic studies were performed. Girls who were diagnosed with VD were treated. A pediatric gynecologist did the follow-up; a successful response was considered when inflammatory symptoms and vaginal discharge ceased. Twenty patients were included, mean age 8.6 years (range: 4.6-14 years); 75% prepubertal symptoms lasted for 1.8 years; 19 (95%) had urodynamia, 10 (52.6%) had an overactive bladder, 8 (42.1%) external bladder sphincter dyssynergia, 1 (5.2%) hypotonic bladder, and 13 (65%) showed improvement. VD is an important cause when considering the etiology of PVV. 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Different HER2 protein expression profiles aid in the histologic differential diagnosis between urothelial carcinoma in situ (CIS) and non-CIS conditions (dysplasia and reactive atypia) of the urinary bladder mucosa.

PubMed

Gunia, Sven; Koch, Stefan; Hakenberg, Oliver W; May, Matthias; Kakies, Christoph; Erbersdobler, Andreas

2011-12-01

We evaluated HER2 expression profiles in 32 carcinoma in situ (CIS) and 31 non-CIS conditions (5 dysplasia and 26 reactive atypia) of the urinary bladder mucosa by applying breast cancer scoring rules. In situ hybridization was performed on tissue microarrays to assess HER2 gene amplification status. Our immunoprofiling data disclosed moderate to strong HER2 expression in CIS, including the basal layer of the urothelium, and absent to weak HER2 expression in non-CIS conditions. From the histologic differential diagnostic standpoint, immunostaining for HER2 protein represents a useful adjunct to aid in the delineation between CIS and non-CIS conditions of the bladder mucosa. Pathogenically, aberrant HER2 protein expression in CIS seems to be more commonly associated with polysomy than with gene amplification. From a therapeutic viewpoint, prospective clinical studies should investigate the potential benefit of HER2-targeted therapies in CIS, particularly in cases unresponsive to conventional therapeutic regimens.

Nanotechnology in bladder cancer: current state of development and clinical practice

PubMed Central

Tomlinson, Ben; Lin, Tzu-yin; Dall'Era, Marc; Pan, Chong-Xian

2015-01-01

Nanotechnology is being developed for the diagnosis and treatment of both nonmyoinvasive bladder cancer (NMIBC) and invasive bladder cancer. The diagnostic applications of nanotechnology in NMIBC mainly focus on tumor identification during endoscopy to increase complete resection of bladder cancer while nanotechnology to capture malignant cells or their components continues to be developed. The therapeutic applications of nanotechnology in NMIBC are to reformulate biological and cytotoxic agents for intravesical instillation, combine both diagnostic and therapeutic application in one nanoformulation. In invasive and advanced bladder cancer, magnetic resonance imaging with supraparamagnetic iron oxide nanoparticles can improve the sensitivity and specificity in detecting small metastasis to lymph nodes. Nanoformulation of cytotoxic agents can potentially decrease the toxicity while increasing efficacy. PMID:25929573

Neurogenic bladder in spinal cord injury patients

PubMed Central

Taweel, Waleed Al; Seyam, Raouf

2015-01-01

Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury. PMID:26090342

Large sliding inguino-scrotal hernia of the urinary bladder

PubMed Central

Wang, Ping; Huang, Yonggang; Ye, Jing; Gao, Guodong; Zhang, Fangjie; Wu, Hao

2018-01-01

Abstract Rationale: Sliding inguinal hernias of the urinary bladder are protrusions of the bladder through the internal inguinal ring, most of which are insignificant and diagnosed intra-operatively. Large inguino-scrotal bladder hernias commonly present with lower urinary tract symptoms and may cause severe complications, including bladder incarceration or necrosis, bladder hemorrhage, obstructive or neurogenic bladder dysfunction, and even renal failure. Patient concerns: We describe and discuss the clinical findings and management of a 59-year-old man who complained of a decrease in scrotal size after voiding and 2-stage voiding requiring pressure to the scrotum. Diagnoses: The patient was diagnosed preoperatively as massive, bilateral, inguinoscrotal hernias, and a large, left-sided, sliding bladder hernia. Interventions: The patient underwent a timely open re-peritoneal inguinal herniorrhaphy using a mesh. Outcomes: The surgical outcomes were good, and no surgical site infection, chronic postoperative inguinal pain or recurrence were recorded during the follow-up. Lessons: Better knowledge of this rare condition of large inguino-scrotal sliding bladder hernia could help in making a correct diagnosis preoperatively and provide proper surgical management timely, so as to reduce delay in treatment and avoid potential complications. PMID:29595706

Mast Cell IL-10 Drives Localized Tolerance in Chronic Bladder Infection

PubMed Central

Chan, Cheryl Y.; St. John, Ashley L.; Abraham, Soman N.

2013-01-01

The lower urinary tract’s virtually inevitable exposure to external microbial pathogens warrants efficient tissue-specialized defenses to maintain sterility. The observation that the bladder can become chronically infected in combination with clinical observations that antibody responses following bladder infections are not detectable, suggest defects in the formation of adaptive immunity and immunological memory. We have identified a broadly immunosuppressive transcriptional program specific to the bladder, but not the kidney, during infection of the urinary tract that is dependent on tissue-resident mast cells (MCs). This involves localized production of interleukin-10 and results in suppressed humoral and cell mediated responses and bacterial persistence. Therefore, in addition to the previously described role of MCs orchestrating the early innate immunity during bladder infection, they subsequently play a tissue-specific immunosuppressive role. These findings may explain the prevalent recurrence of bladder infections and suggest the bladder as a site exhibiting an intrinsic degree of MC-maintained immune privilege. PMID:23415912

Optimal Timing of Chemotherapy and Surgery in Patients with Muscle-Invasive Bladder Cancer and Upper Urinary Tract Urothelial Carcinoma.

PubMed

Tabayoyong, William; Li, Roger; Gao, Jianjun; Kamat, Ashish

2018-05-01

Radical cystectomy with bilateral pelvic lymph node dissection is the standard of care for patients with clinically localized muscle-invasive bladder cancer. Survival after radical cystectomy is associated with final pathologic staging. Survival decreases with increasing pT stage because of the presence of occult micrometastases, indicating the need for systemic chemotherapy. Systemic chemotherapy is delivered as either neoadjuvant therapy preoperatively, or as adjuvant therapy postoperatively. This article reviews the evidence for neoadjuvant and adjuvant chemotherapy for the treatment of muscle-invasive bladder and upper tract urothelial cancer and offers recommendations based on these data and recently updated clinical guidelines. Copyright © 2018 Elsevier Inc. All rights reserved.

How should bladder sensation be measured? ICI-RS 2011.

PubMed

De Wachter, S; Smith, Philip P; Smith, P; Tannenbaum, C; Van Koeveringe, G; Drake, M; Wyndaele, J J; Chapple, C

2012-03-01

Disturbed bladder sensations, or in broader terms, sensory dysfunctions are increasingly recognized as key elements in the origin and manifestation of symptom syndromes of urinary dysfunction. Adequate assessment of bladder sensation is crucial to improve our understanding of the pathophysiology and treatment of urinary dysfunction. This manuscript summarizes the discussions of a think tank on "How to measure bladder sensation" held at the ICI-RS meeting in 2011. Based upon literature reviews on bladder sensation presented at the think tank in the ICI-RS meeting, discussions evolved which were summarized in the ICI-RS report. Different physicians/researchers further elaborated on this report, which is presented in this manuscript. Bladder sensations are not merely the result of bladder distension. Other factors inside the bladder or bladder wall: central processing and/or cognitive manipulation may play an important role. Current methods to measure sensations such as urodynamics, voiding diaries, forced diuresis, electrical stimulation and brain imaging are likely sub-optimal as they only consider part of these factors in isolation. Different methods to measure bladder sensations have been described and are used in clinical practice. Current methods only address part of the parameters responsible for the generation and perception of urinary sensations. Further focused research is required, and several recommendations are provided. Copyright © 2012 Wiley Periodicals, Inc.

Assessment of accuracy and efficiency of atlas-based autosegmentation for prostate radiotherapy in a variety of clinical conditions.

PubMed

Simmat, I; Georg, P; Georg, D; Birkfellner, W; Goldner, G; Stock, M

2012-09-01

The goal of the current study was to evaluate the commercially available atlas-based autosegmentation software for clinical use in prostate radiotherapy. The accuracy was benchmarked against interobserver variability. A total of 20 planning computed tomographs (CTs) and 10 cone-beam CTs (CBCTs) were selected for prostate, rectum, and bladder delineation. The images varied regarding to individual (age, body mass index) and setup parameters (contrast agent, rectal balloon, implanted markers). Automatically created contours with ABAS(®) and iPlan(®) were compared to an expert's delineation by calculating the Dice similarity coefficient (DSC) and conformity index. Demo-atlases of both systems showed different results for bladder (DSC(ABAS) 0.86 ± 0.17, DSC(iPlan) 0.51 ± 0.30) and prostate (DSC(ABAS) 0.71 ± 0.14, DSC(iPlan) 0.57 ± 0.19). Rectum delineation (DSC(ABAS) 0.78 ± 0.11, DSC(iPlan) 0.84 ± 0.08) demonstrated differences between the systems but better correlation of the automatically drawn volumes. ABAS(®) was closest to the interobserver benchmark. Autosegmentation with iPlan(®), ABAS(®) and manual segmentation took 0.5, 4 and 15-20 min, respectively. Automatic contouring on CBCT showed high dependence on image quality (DSC bladder 0.54, rectum 0.42, prostate 0.34). For clinical routine, efforts are still necessary to either redesign algorithms implemented in autosegmentation or to optimize image quality for CBCT to guarantee required accuracy and time savings for adaptive radiotherapy.

An in-vitro urinary catheterization model that approximates clinical conditions for evaluation of innovations to prevent catheter-associated urinary tract infections.

PubMed

Chua, R Y R; Lim, K; Leong, S S J; Tambyah, P A; Ho, B

2017-09-01

Catheter-associated urinary tract infections (CAUTI) account for approximately 25% of nosocomial infections globally, and often result in increased morbidity and healthcare costs. An additional concern is the presence of microbial biofilms which are major reservoirs of bacteria, especially antibiotic-resistant bacteria, in catheters. Since introduction of the use of closed drainage systems, innovations to combat CAUTI have not led to significant improvements in clinical outcomes. The lack of a robust laboratory platform to test new CAUTI preventive strategies may impede development of novel technologies. To establish an in-vitro catheterization model (IVCM) for testing of technological innovations to prevent CAUTI. The IVCM consists of a continuous supply of urine medium flowing into a receptacle (bladder) where the urine is drained through a urinary catheter connected to an effluent collection vessel (drainage bag). Test organism(s) can be introduced conveniently into the bladder via a rubber septa port. Development of bacteriuria and microbial biofilm on the catheter can be determined subsequently. With an initial inoculum of Escherichia coli [∼5×10 5  colony-forming units (cfu)/mL] into the bladder, a 100% silicone catheter and a commercially available silver-hydrogel catheter showed heavy biofilm colonization (∼10 8  cfu/cm and ∼10 7  cfu/cm, respectively) with similar bacterial populations in the urine (bacteriuria) (∼10 8  cfu/mL and ∼10 7  cfu/mL, respectively) within three days. Interestingly, an antimicrobial peptide (CP11-6A)-coated catheter showed negligible biofilm colonization and no detectable bacteriuria. The IVCM is a useful preclinical approach to evaluate new strategies for the prevention of CAUTI. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Evaluation of educational content of YouTube videos relating to neurogenic bladder and intermittent catheterization.

PubMed

Ho, Matthew; Stothers, Lynn; Lazare, Darren; Tsang, Brian; Macnab, Andrew

2015-01-01

Many patients conduct internet searches to manage their own health problems, to decide if they need professional help, and to corroborate information given in a clinical encounter. Good information can improve patients' understanding of their condition and their self-efficacy. Patients with spinal cord injury (SCI) featuring neurogenic bladder (NB) require knowledge and skills related to their condition and need for intermittent catheterization (IC). Information quality was evaluated in videos accessed via YouTube relating to NB and IC using search terms "neurogenic bladder intermittent catheter" and "spinal cord injury intermittent catheter." Video content was independently rated by 3 investigators using criteria based on European Urological Association (EAU) guidelines and established clinical practice. In total, 71 videos met the inclusion criteria. Of these, 12 (17%) addressed IC and 50 (70%) contained information on NB. The remaining videos met inclusion criteria, but did not contain information relevant to either IC or NB. Analysis indicated poor overall quality of information, with some videos with information contradictory to EAU guidelines for IC. High-quality videos were randomly distributed by YouTube. IC videos featuring a healthcare narrator scored significantly higher than patient-narrated videos, but not higher than videos with a merchant narrator. About half of the videos contained commercial content. Some good-quality educational videos about NB and IC are available on YouTube, but most are poor. The videos deemed good quality were not prominently ranked by the YouTube search algorithm, consequently user access is less likely. Study limitations include the limit of 50 videos per category and the use of a de novo rating tool. Information quality in videos with healthcare narrators was not higher than in those featuring merchant narrators. Better material is required to improve patients' understanding of their condition.

[Concomitant oncopathological changes in the prostate of urinary bladder cancer patients undergoing radical cystoprostateectomy].

PubMed

Komyakov, B K; Sergeev, A V; Fadeev, V A; Ismailov, K I; Ulyanov, A Yu; Shmelev, A Yu; Onoshko, M V

2017-09-01

To determine the incidence of spreading bladder transitional cell carcinoma and primary adenocarcinoma to the prostate in patients with bladder cancer undergoing radical cystectomy. From 1995 to 2016, 283 men underwent radical cystectomy with removal of the bladder, perivesical tissue, prostate, seminal vesicles and pelvic lymph nodes. Prostate sparing cystectomy was performed in 45 (13.7%) patients. The whole prostate and the apex of the prostate were preserved in 21 (6.4%) and 24 (7.3%) patients, respectively. The spread of transitional cell cancer of the bladder to the prostate occurred in 50 (15.2%) patients. Twelve (3.6%) patients were found to have primary prostate adenocarcinoma. Clinically significant prostate cancer was diagnosed in 4 (33.3%) patients. We believe that the high oncological risk of prostate sparing cystectomy, despite some functional advantages, dictates the need for complete removal of the prostate in the surgical treatment of bladder cancer.

Long-term persistence with mirabegron in a real-world clinical setting.

PubMed

Wada, Naoki; Watanabe, Masaki; Banjo, Hiroko; Tsuchida, Miyu; Hori, Junichi; Tamaki, Gaku; Azumi, Makoto; Kita, Masafumi; Kakizaki, Hidehiro

2018-05-01

To examine the long-term persistence rate with mirabegron in a real-world clinical setting. We retrospectively collected the data of patients who were prescribed mirabegron. We investigated the persistence rate and the reason for the discontinuation. The analysis included patient's age, diagnosis, Overactive Bladder Symptom Score, prostatic volume, the prescription by specialists for lower urinary tract dysfunction, drug-naïve patients, replacement of antimuscarinics or add-on therapy to antimuscarinics. A total of 556 patients were included. Among them, 401 patients (72%) had overactive bladder and the other 155 (28%) were categorized as having other storage symptoms. During the observation period, 170 patients (42%) with overactive bladder discontinued mirabegron. The reasons for discontinuation in patients with overactive bladder included unmet expectation of treatment (45 patients, 26%), any adverse events (38 patients, 22%) or symptom improvement (37 patients, 22%). The persistence or discontinuation was not related with age, Overactive Bladder Symptom Score, prostatic volume or the prescription by specialists, while older male patients tended to continue mirabegron. The 3-year persistence rates in female and male overactive bladder patients were 46% and 51%, respectively, and these were better than those in patients with storage symptoms without urgency. In female overactive bladder patients, the persistence rate with mirabegron used as add-on therapy to antimuscarinics was higher than that in the drug-naïve patients on the Kaplan-Meier curve. The present study shows a relatively good long-term persistence rate with mirabegron in overactive bladder patients, notwithstanding the retrospective study in an academic hospital. The combined treatment with antimuscarinics could result in a good persistence rate with mirabegron. © 2018 The Japanese Urological Association.

Combined cystometrography and electromyography of the external urethral sphincter following complete primary repair of bladder exstrophy.

PubMed

Borer, Joseph G; Strakosha, Ruth; Bauer, Stuart B; Diamond, David A; Pennison, Melanie; Rosoklija, Ilina; Khoshbin, Shahram

2014-05-01

Concern in patients with bladder exstrophy after reconstruction regarding potential injury to pelvic neurourological anatomy and a resultant functional deficit prompted combined (simultaneous) cystometrography and electromyography after complete primary repair of bladder exstrophy. We determined whether complete primary repair of bladder exstrophy would adversely affect the innervation controlling bladder and external urethral sphincter function. Complete primary repair of bladder exstrophy was performed via a modified Mitchell technique in newborns without osteotomy. Postoperative evaluation included combined cystometrography and needle electrode electromyography via the perineum, approximating the external urethral sphincter muscle complex. Electromyography was done to evaluate the external urethral sphincter response to sacral reflex stimulation and during voiding. Nine boys and 4 girls underwent combined cystometrography/electromyography after complete primary repair of bladder exstrophy. Age at study and time after complete primary repair of bladder exstrophy was 3 months to 10 years (median 11.5 months). Cystometrography revealed absent detrusor overactivity and the presence of a sustained detrusor voiding contraction in all cases. Electromyography showed universally normal individual motor unit action potentials of biphasic pattern, amplitude and duration. The external urethral sphincter sacral reflex response was intact with a normal caliber with respect to Valsalva, Credé, bulbocavernosus and anocutaneous (bilateral) stimulation. Synergy was documented by abrupt silencing of external urethral sphincter electromyography activity during voiding. After complete primary repair of bladder exstrophy combined cystometrography/electromyography in patients with bladder exstrophy showed normal neurourological findings, including sacral reflex responses, sustained detrusor voiding contraction and synergic voiding, in all patients postoperatively. These findings confirm the safety of complete primary repair of bladder exstrophy. Based on our results we have discontinued routine electromyography in these patients. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer.

PubMed

Nakai, Yasushi; Tatsumi, Yoshihiro; Miyake, Makito; Anai, Satoshi; Kuwada, Masaomi; Onishi, Sayuri; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

2016-03-01

The mechanism underlying the increased levels of protoporphyrin IX in bladder cancer remains unclear. Here, we focus on proteins associated with protoporphyrin IX accumulation in bladder cancer cells and investigate the protein that plays a key role in increased protoporphyrin IX accumulation in bladder cancer cells. Western blotting was used to determine the expression of peptide transporter 1, hydroxymethylbilane synthase, ferrochelatase, ATP-binding cassette 2, and heme oxygenase-1 in bladder cancer cell line cells. We evaluated the correlation between the expression of each protein and accumulated protoporphyrin IX in these cells using Pearson's correlation analysis. Immunohistochemistry was used to estimate the expression of the same five proteins in samples from 75 patients who underwent transurethral resection of bladder tumors. The correlation between the expression of each protein in cells from resected bladder specimens and accumulated protoporphyrin IX in bladder cancer cells in voided urine was evaluated using Pearson's correlation analysis. The expression of ferrochelatase showed a significant negative correlation with protoporphyrin IX accumulation in vitro (p=0.04). The expression of peptide transporter 1 (p<0.01, R=0.39), heme oxygenase-1 (p<0.01, R=0.33), and ferrochelatase (p<0.01, R=0.75) in resected bladder specimens by immunohistochemistry was correlated with protoporphyrin IX accumulation in bladder cancer cells in voided urine. On multivariate analysis, the expression of ferrochelatase (p=0.03) was significant factors to predict positive 5-aminolevulinic acid-induced fluorescent cytology. The expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of a Pelvic Floor Training Program Among Women with Multiple Sclerosis: A Controlled Clinical Trial.

PubMed

Ferreira, Ana Paula Silva; Pegorare, Ana Beatriz Gomes de Souza; Salgado, Pedro Rippel; Casafus, Filemón Silva; Christofoletti, Gustavo

2016-01-01

The objective of this study was to investigate the effects of two programs for strengthening the pelvic floor on the urinary incontinence of patients with multiple sclerosis (MS). This is a prospective study of the clinical trial type, monitored for 6 mos, in which 24 women in the moderate stage of MS participated in a program of exercises for strengthening the pelvic floor-associated (experimental group) or not (control group) with electrotherapy. The variables analyzed were as follows: quality-of-life, overactivity of the bladder, perineal contraction, and level of anxiety and depression. The statistical procedures involved multivariate analyses of repeated measurements, with a significance of 5%. Initial homogeneity being observed in the anthropometric and clinical variables, both protocols resulted in improvements in quality-of-life (P = 0.001), overactive bladder (P = 0.001), perineal contraction (P = 0.004), and level of anxiety (P = 0.001) and depression (P = 0.001), in relation to the initial comparison. The association of electrotherapy with strengthening exercises increased the improvement of the patients regarding overactive bladder (P = 0.039) and perineal contraction (P = 0.001), in comparison with the control group. The results reinforce the benefit of exercises for strengthening the musculature of the pelvic floor in women with overactive bladder in MS and demonstrate a potential of the action when associated with electrotherapy. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES:: Upon completion of this article, the reader should be able to: (1) Identify common dysfunctions of the lower urinary tract in women with multiple sclerosis; (2) Discuss the relationship between quality-of-life, level of anxiety and depression, degree of perineal contraction, and overactive bladder; and (3) Recognize the benefits promoted by physical therapy for strengthening the pelvic floor in patients with multiple sclerosis. Advanced : The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity.

Optical improvements in the diagnosis of bladder cancer: implications for clinical practice.

PubMed

Schubert, Tina; Rausch, Steffen; Fahmy, Omar; Gakis, Georgios; Stenzl, Arnulf

2017-11-01

For over 100 years white-light cystoscopy has remained the gold-standard technique for the detection of bladder cancer (BCa). Some limitations in the detection of flat lesions (CIS), the differentiation between inflammation and malignancy, the inaccurate determination of the tumor margin status as well as the tumor depth, have led to a variety of technological improvements. The aim of this review is to evaluate the impact of these improvements in the diagnosis of BCa and their effectiveness in clinical practice. A systematic literature search was conducted according to the PRISMA statement to identify studies reporting on imaging modalities in the diagnosis of NMIBC between 2000 and 2017. A two-stage selection process was utilized to determine eligible studies. A total of 74 studies were considered for final analysis. Optical imaging technologies have emerged as an adjunct to white-light cystoscopy and can be classified according to their scope as macroscopic, microscopic and molecular. Macroscopic techniques including photodynamic diagnosis (PDD), narrow-band imaging (NBI) and the Storz Professional Image Enhancement System (IMAGE1 S, formerly known as SPIES) are similar to white-light cystoscopy, but are superior in the detection of bladder tumors by means of contrast enhancement. Especially the detection rate of very mute lesions in the bladder mucosa (CIS) could be significantly increased by the use of these methods. Microscopic imaging techniques like confocal laser endomicroscopy and optical coherence tomography permit a real-time high-resolution assessment of the bladder mucosa at a cellular and sub-cellular level with spatial resolutions similar to histology, enabling the surgeon to perform an 'optical biopsy'. Molecular techniques are based on the combination of optical imaging technologies with fluorescence labeling of cancer-specific molecular agents like antibodies. This labeling is intended to favor an optical distinction between benign and malignant tissue. Optical improvements of the standard white-light cystoscopy have proven their benefit in the detection of BCa and have found their way into clinical practice. Especially the combination of macroscopic and microscopic techniques may improve diagnostic accuracy. Nevertheless, HAL-PDD guided cystoscopy is the only approach approved for routine use in the diagnosis of BCa by most urological associations in the EU and USA to date.

Evidence of bladder oversensitivity in the absence of an infection in premenopausal women with a history of recurrent urinary tract infections.

PubMed

Arya, Lily A; Northington, Gina M; Asfaw, Tirsit; Harvie, Heidi; Malykhina, Anna

2012-07-01

Study Type - Prevalence (case control) Level of Evidence 4. What's known on the subject? and What does the study add? Urinary tract infections (UTIs) have been implicated in the aetiology of interstitial cystitis/painful bladder syndrome (IC/PBS). Prior studies have described symptoms and laboratory tests suggestive of UTI at the onset of IC/PBS as well as a significant history of childhood recurrent UTIs. However, the mechanism by which recurrent UTIs contribute to the development of IC/PBS is not clear. Our study shows that women with recurrent UTI suffer from bladder oversensitivity. Our findings have useful clinical implications. Women with bladder oversensitivity complain of urinary frequency which is often misdiagnosed as an infection and treated with unnecessary antibiotics. Additionally, there are no effective therapies for bladder oversensitivity. Therefore, women with recurrent UTI should undergo prompt evaluation and treatment of episodes of infection to prevent the development of bladder oversensitivity. Our findings also provide a possible mechanism for the development of IC/PBS. Whether women with recurrent UTI are at increased risk for developing IC/PBS in the future will need to be confirmed in future studies. • To compare the mean voided volume and bladder sensation during filling cystometry in women with a history of recurrent urinary tract infection (UTI) and controls. • This was a case-control study including adult women seen in the urogynaecology clinic. • The cases were 49 women with at least three documented positive urine cultures >105 colonies/mL in the previous 12 months and no active infection at the time of data collection. • Controls were 53 women with stress urinary incontinence and no history of recurrent UTI or coexistent urge urinary incontinence. • We compared bladder diary variables and filling cystometry data in the absence of an active infection. • There was no significant difference in the median age, parity and body mass index of women with a history of recurrent UTI and controls. • The median number of voids per day and median number of voids per litre of fluid intake was significantly greater in women with recurrent UTI than controls (12 vs 7 voids/day and 6 vs 4 voids/L, P= 0.005 and P= 0.004 respectively). • The median average voided volume was significantly lower in women with recurrent UTI than controls (155 vs 195 mL, P= 0.008). • On filling cystometry, median volumes of strong desire to void and maximum cystometric capacity were significantly lower in women with recurrent UTI than controls (all P < 0.05). • In the absence of an infection, premenopausal women with a history of recurrent UTI have significantly greater urinary frequency, lower average voided volume and a lower threshold of bladder sensitivity than controls. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

The Potential Role of Polymethyl Methacrylate as a New Packaging Material for the Implantable Medical Device in the Bladder

PubMed Central

Kim, Su Jin; Choi, Bumkyoo; Kim, Kang Sup; Bae, Woong Jin; Hong, Sung Hoo; Lee, Ji Youl; Hwang, Tae-Kon; Kim, Sae Woong

2015-01-01

Polydimethylsiloxane (PDMS) is used in implantable medical devices; however, PDMS is not a completely biocompatible material for electronic medical devices in the bladder. To identify novel biocompatible materials for intravesical implanted medical devices, we evaluated the biocompatibility of polymethyl methacrylate (PMMA) by analyzing changes in the levels of macrophages, macrophage migratory inhibitory factor (MIF), and inflammatory cytokines in the bladder. A ball-shaped metal coated with PMMA or PDMS was implanted into the bladders of rats, and after intravesical implantation, the inflammatory changes induced by the foreign body reaction were evaluated. In the early period after implantation, increased macrophage activity and MIF in the urothelium of the bladder were observed. However, significantly decreased macrophage activity and MIF in the bladder were observed after implantation with PMMA- or PDMS-coated metal in the later period. In addition, significantly decreased inflammatory cytokines such as IL-1β, IL-6, and TNF-α were observed with time. Based on these results, we suggest that MIF plays a role in the foreign body reaction and in the biocompatible packaging with PMMA for the implanted medical devices in the bladder. PMID:25705692

Evaluation of the biocompatibility of a coating material for an implantable bladder volume sensor.

PubMed

Kim, Su-Jin; Lee, Dong-Sup; Kim, In-Gul; Sohn, Dong-Wan; Park, Jung-Yul; Choi, Bum-Kyoo; Kim, Sae-Woong

2012-03-01

As the applications for implantable medical devices have increased, the need for biocompatible packaging materials has become important. Recently, we reported an implantable sensor for real-time monitoring of the changes in bladder volume, which necessitated finding a safe coating material for use in bladder tissue. At present, materials like polyethylene glycol (PEG), polydimethylsiloxane (PDMS) and parylene-C are used in biomedical devices or as coating materials, owing to their excellent safety in various medical fields. However, few studies have assessed their safety in bladder tissue, therefore, we evaluated the biocompatibility of PEG, PDMS and parylene-C in the bladder. All three materials turned out to be safe in in vitro tests of live/dead staining and cell viability. In vivo tests with hematoxylin and eosin and immunofluorescence staining with MAC387 showed no persistent inflammation. Therefore, we consider that the three materials are biocompatible in bladder tissue. Despite this safety, however, PEG has biodegradable characteristics and thus is not suitable for use as packaging. We suggest that PDMS and parylene-C can be used as safe coating materials for the implantable bladder volume sensor reported previously. Copyright © 2012. Published by Elsevier B.V.

Validation of Fully Automated VMAT Plan Generation for Library-Based Plan-of-the-Day Cervical Cancer Radiotherapy

PubMed Central

Breedveld, Sebastiaan; Voet, Peter W. J.; Heijkoop, Sabrina T.; Mens, Jan-Willem M.; Hoogeman, Mischa S.; Heijmen, Ben J. M.

2016-01-01

Purpose To develop and validate fully automated generation of VMAT plan-libraries for plan-of-the-day adaptive radiotherapy in locally-advanced cervical cancer. Material and Methods Our framework for fully automated treatment plan generation (Erasmus-iCycle) was adapted to create dual-arc VMAT treatment plan libraries for cervical cancer patients. For each of 34 patients, automatically generated VMAT plans (autoVMAT) were compared to manually generated, clinically delivered 9-beam IMRT plans (CLINICAL), and to dual-arc VMAT plans generated manually by an expert planner (manVMAT). Furthermore, all plans were benchmarked against 20-beam equi-angular IMRT plans (autoIMRT). For all plans, a PTV coverage of 99.5% by at least 95% of the prescribed dose (46 Gy) had the highest planning priority, followed by minimization of V45Gy for small bowel (SB). Other OARs considered were bladder, rectum, and sigmoid. Results All plans had a highly similar PTV coverage, within the clinical constraints (above). After plan normalizations for exactly equal median PTV doses in corresponding plans, all evaluated OAR parameters in autoVMAT plans were on average lower than in the CLINICAL plans with an average reduction in SB V45Gy of 34.6% (p<0.001). For 41/44 autoVMAT plans, SB V45Gy was lower than for manVMAT (p<0.001, average reduction 30.3%), while SB V15Gy increased by 2.3% (p = 0.011). AutoIMRT reduced SB V45Gy by another 2.7% compared to autoVMAT, while also resulting in a 9.0% reduction in SB V15Gy (p<0.001), but with a prolonged delivery time. Differences between manVMAT and autoVMAT in bladder, rectal and sigmoid doses were ≤ 1%. Improvements in SB dose delivery with autoVMAT instead of manVMAT were higher for empty bladder PTVs compared to full bladder PTVs, due to differences in concavity of the PTVs. Conclusions Quality of automatically generated VMAT plans was superior to manually generated plans. Automatic VMAT plan generation for cervical cancer has been implemented in our clinical routine. Due to the achieved workload reduction, extension of plan libraries has become feasible. PMID:28033342

[Virtual CT-pneumocystoscopy: indications, advantages and limitations. Our experience].

PubMed

Regine, Giovanni; Atzori, Maurizio; Buffa, Vitaliano; Miele, Vittorio; Ialongo, Pasquale; Adami, Loredana

2003-09-01

The use of CT volume-rendering techniques allows the evaluation of visceral organs without the need for endoscopy. Conventional endoscopic evaluation of the bladder is limited by the invasiveness of the technique and the difficulty exploring the entire bladder. Virtual evaluation of the bladder by three-dimensional CT reconstruction offers potential advantages and can be used in place of endoscopy. This study investigates the sensitivity of virtual CT in assessing lesion of the bladder wall to compare it with that of conventional endoscopy, and outlines the indications, advantages and disadvantages of virtual CT-pneumocystography. Between September 2001 and May 2002, 21 patients with haematuria and positive cystoscopic findings were studied. After an initial assessment by ultrasound, the patients underwent pelvic CT as a single volumetric scan after preliminary air distension of the bladder by means of 12 F Foley catheter. The images were processed on an independent workstation (Advantage 3.0 GE) running dedicated software for endoluminal navigation. The lesions detected by endoscopy were classified as sessile or pedunculated, and according to size (more or less than 5 mm). Finally, the results obtained at virtual cystoscopy were evaluated by two radiologists blinded to the conventional cystoscopy results. Thirty lesions (24 pedunculated, 6 sessile) were detected at conventional cystoscopy in 16 patients (multiple polyposis in 3 cases). Virtual cystoscopy identified 23 lesions (19 pedunculated and 4 sessile). The undetected lesions were pedunculated <5 mm (5 cases) and sessile (2 cases). One correctly identified pedunculated lesion was associated with a bladder stone. Good quality virtual images were obtained in all of the patients. In only one patient with multiple polyposis the quality of the virtual endoscopic evaluation was limited by the patient's intolerance to bladder distension, although identification of the lesions was not compromised. The overall sensitivity was 77%; this was higher for pedunculated lesions (79%) than for sessile lesions (50%). The virtual technique is less invasive and tends to be associated with fewer complications than is conventional cystoscopy. It also demonstrated a good sensitivity for evaluating pedunculated lesions, allowing evaluation of the bladder base and anterior wall, sites that are commonly poorly accessible at conventional cystoscopy. Further advantages of the virtual technique include the possibility of accurately measuring the extent of the lesion and obtaining virtual images even in patients with severe urethral obstruction and active bleeding. The limitations include the inability to obtain tissue for histologic examination or to perform endoscopic resection of pedunculated lesions. The technique is less sensitive than conventional cystoscopy in the detection of sessile lesions or very small polyps (<5 mm). Furthermore, diffuse wall thickening reduces bladder distension thereby preventing optimal evaluation. The most valuable indication appears to be the follow-up of treated wall lesions. Virtual CT-pneumocystoscopy can replace conventional cystoscopy in cases with pedunculated lesions when there is no need for biopsy, when the lesions are located at the bladder base or when cystoscopic instrumentation cannot be introduced into the bladder due to stenosis. Virtual pneumocystoscopy can also be used in the follow-up of treated polypoid lesions in association with pelvic CT-angiography.

Tolerance of the canine bladder to intraoperative radiation therapy: an experimental study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kinsella, T.J.; Sindelar, W.F.; DeLuca, A.M.

1988-05-01

An experimental study of bladder tolerance to intraoperative radiotherapy (IORT) was designed using a large animal model (adult American Foxhounds, weight 25-30 kg) to access acute and late radiation effects. Dogs were subjected to laparotomy where the bladder was mobilized and IORT was delivered using a 5 cm circular cone through a cystotomy incision with 12 MeV electrons. The bladder trigone including both ureteral orifices and the proximal urethra was irradiated in groups of 3 dogs with doses of 0, 20, 25, 30, 35, and 40 Gy. Dogs were followed clinically with repeat urinalysis, intravenous pyelogram (IVP), and cystometrogram atmore » 1 month and then Q6 months for up to 4 years. One dog from each dose group was sacrificed electively at 1 and 2 years, whereas the other dog is being followed clinically for a minimum of 4 years. Complete autopsies were performed with particular attention to genitourinary and pelvic structures. No clinically detectable acute toxicity resulted from IORT to the bladder. Three of 15 IORT dogs (1 each at 25, 35, and 40 Gy) showed obstruction of a ureteral orifice with 2 dogs dying of renal failure secondary to bilateral hydronephrosis within 1-2 years of treatment. The remaining 12 IORT dogs and 3 control dogs have normal repeat IVP's and renal function with up to 4 years of follow-up. Serial cystometry demonstrates no major loss of bladder contractility or volume. At autopsy, histological changes of mucosal thinning and telangiectasia with submucosal fibrosis were confined to the IORT field and appeared dose-related. However, the bladder epithelium remained intact at all doses. The ureterovesical junction in animals receiving 20 Gy showed mild fibrosis of the lamina propria and moderate chronic inflammation. Above 20 Gy, these histological changes at the U-V junction were more pronounced with gross stenosis in 3 animals as predicted by the IVP.« less

Impact of urinary incontinence on healthcare resource utilization, health-related quality of life and productivity in patients with overactive bladder.

PubMed

Tang, Derek H; Colayco, Danielle C; Khalaf, Kristin M; Piercy, James; Patel, Vaishali; Globe, Denise; Ginsberg, David

2014-03-01

To evaluate the impact of urinary incontinence (UI) on healthcare resource utilization (HRU), health-related quality of life (HRQoL) and productivity measures in patients with overactive bladder (OAB). This retrospective, cross-sectional study used data from the Adelphi OAB/UI Disease Specific Programme, a multinational survey of patient- and physician-reported data, fielded between November 2010 and February 2011. The primary patient groups of interest were those with OAB, both with and without UI. Health-related quality of life and productivity measures were derived from the EuroQoL-5D, the Incontinence Quality of Life questionnaire, the Overactive Bladder Questionnaire, and the Work Productivity and Activity Impairment Questionnaire. Measures of HRU included OAB-related surgeries, OAB-related hospitalizations, incontinence pads, anticholinergic use and physician visits. Multivariate linear regression models and literature-based minimal clinically important differences were used to assess statistically significant and clinically meaningful differences in HRQoL and productivity measures between patients with OAB with UI and those without UI. A total of 1 730 patients were identified, with a mean age of 60.7 years, and 77.0% of them were women, 84.2% were non-Hispanic whites, and 71% were incontinent. Bivariate analyses showed that HRU was significantly higher among patients with OAB with UI than among those without UI in all categories except for the number of OAB-related physician visits. In both bivariate and multivariate analyses, incontinent patients presented with clinically and statistically significantly lower HRQoL and productivity measures with respect to all study endpoints, except for percentage of work time missed due to their OAB/UI. Urinary incontinence was associated with significantly higher HRU and lower HRQoL and productivity in this population of patients with OAB from five different countries. In addition to clinical considerations, the economic and humanistic impact of UI should be taken into account when evaluating treatment options for patients with OAB. © 2013 The Authors. BJU International © 2013 BJU International.

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The role of matrix metalloproteinase MMP-9 and TIMP-2 tissue inhibitor of metalloproteinases as serum markers of bladder cancer.

PubMed

Ramón de Fata, F; Ferruelo, A; Andrés, G; Gimbernat, H; Sánchez-Chapado, M; Angulo, J C

2013-09-01

The diagnosis and molecular staging of bladder cancer based on the detection of gelatinases mRNA (MMP-2 and MMP-9) in peripheral blood circulating and mononuclear cells have shown promising results. We analyze if the determination of the corresponding protein synthesis products makes it possible to diagnose and characterize patients with bladder cancer. Quantification of the serum levels of MMP-2, MMP-9 and TIMP-2 in a series of 42 individuals (31 patients with bladder cancer in different stages and 11 healthy controls) using the ELISA technique was carried out. The determinations were compared between cases and controls (Mann-Whitney U) and between different groups of tumors (Mann-Whitney U or Kruskal-Wallis), according to the clinical-pathological characteristics (age, gender, T category, M category or grade). Diagnostic yield of these markers was evaluated by analysis of the ROC curves. There is a correlation between the determinations of MMP-2 and TIMP-2 (R=.699; P>.0001) and MMP-9 and TIMP-2 (R=.305; P=.049). Patients with bladder cancer have higher levels of MMP-9 (p<0.0001) and TIMP-2 (P=.047) than the controls. Furthermore, the MMP-9/TIMP-2 ratio is also superior in cancer patients (P<.001). Differences were not detected between cancer and controls regarding age (P=.64) or gender (P=.64). Differences were also not detected regarding MMP-2 (P=.35) or MMP-2/TIMP-2 rate (P=.45). Within the cancer patient population, the MMP-2 and MMP-9 values differ according to T category (P=.022 and P=.038, respectively) and those of the TIMP-2 according to M category (P=.036). ROC curve analysis showed that both MMP-9 and the MMP-9/TIMP-2 ratio discriminate patients with cancer and controls, with equivalent diagnostic accuracy (ABC 0.953) and cut offs of 3.93 ng/mL (S 90%; Sp 81%) and 0.053 ng/mL (S 96%; Sp 84%), respectively. The results obtained suggest that both serum MMP-9 and TIMP-2 would have an application in the prediction of the development and progression of bladder cancer, and a potential utility as clinical markers of the disease. Multicenter, prospective studies that confirm their preliminary results are necessary. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

The cytostatic effect of 9-cis-retinoic acid, tretinoin, and isotretinoin on three different human bladder cancer cell lines in vitro.

PubMed

Laaksovirta, S; Rajala, P; Nurmi, M; Tammela, T L; Laato, M

1999-01-01

Retinoids have been shown to have activity in both preclinical and clinical bladder cancer studies but their exact role in its treatment and prevention remains obscure. In this study cytostatic activity of a novel 9-cis-retinoic acid (9-cis-RA) was compared with two other retinoids: tretinoin and isotretinoin, in three different bladder cancer cell lines: RT4 (well differentiated), 5637 (moderately differentiated) and T24 (poorly differentiated). The three retinoids were incubated at concentrations of 0.3, 3 and 30 microg/ml with bladder cancer cells in microtitre plates for 3 and 6 days. The cytostatic effect was estimated by using luminometric measuring of ATP activity of viable cells in suspension. Compared with the older retinoids, tretinoin and isotretinoin, the highest concentration of 9-cis-RA had a cytostatic efficacy in all three bladder cancer cell lines tested. A clear dose response relationship was observed in isotretinoin-treated cultures after 6 days and in all 9-cis-RA-treated cultures. Tretinoin was either ineffective or had a stimulating effect on poorly differentiated tumour cells. To conclude, isotretinoin and 9-cis-RA had a cytostatic effect on human bladder cancer cells in vitro. However, the possibility of stimulating cancer growth at small doses, at least with tretinoin, and toxicity at high doses must be considered when planning clinical trials.

An adaptive radiotherapy planning strategy for bladder cancer using deformation vector fields.

PubMed

Vestergaard, Anne; Kallehauge, Jesper Folsted; Petersen, Jørgen Breede Baltzer; Høyer, Morten; Søndergaard, Jimmi; Muren, Ludvig Paul

2014-09-01

Adaptive radiotherapy (ART) has considerable potential in treatment of bladder cancer due to large inter-fractional changes in shape and size of the target. The aim of this study was to compare our clinically applied method for plan library creation that involves manual bladder delineations (Clin-ART) with a method using the deformation vector fields (DVFs) resulting from intensity-based deformable image registrations (DVF-based ART). The study included thirteen patients with urinary bladder cancer who had daily cone beam CTs (CBCTs) acquired for set-up. In both ART strategies investigated, three plan selection volumes were generated using the CBCTs from the first four fractions; in Clin-ART boolean combinations of delineated bladders were used, while the DVF-based strategy applied combinations of the mean and standard deviation of patient-specific DVFs. The volume ratios (VRs) of the course-averaged PTV for the two ART strategies relative the non-adaptive PTV were calculated. Both Clin-ART and DVF-based ART considerably reduced the course-averaged PTV, compared to non-adaptive RT. The VR for DVF-based ART was lower than for Clin-ART (0.65 vs. 0.73; p<0.01). DVF-based ART for bladder irradiation has a considerable normal tissue sparing potential surpassing our already highly conformal clinically applied ART strategy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Presence of Cleaved Synaptosomal-Associated Protein-25 and Decrease of Purinergic Receptors P2X3 in the Bladder Urothelium Influence Efficacy of Botulinum Toxin Treatment for Overactive Bladder Syndrome.

PubMed

Liu, Hsin-Tzu; Chen, Sung-Ho; Chancellor, Michael B; Kuo, Hann-Chorng

2015-01-01

To evaluate whether botulinum toxin A (BoNT-A) injection and Lipotoxin (liposomes with 200 U of BoNT-A) instillation target different proteins, including P2X3, synaptic vesicle glycoprotein 2A, and SNAP-25, in the bladder mucosa, leading to different treatment outcomes. This was a retrospective study performed in a tertiary teaching hospital. We evaluated the clinical results of 27 OAB patients treated with intravesical BoNT-A injection (n = 16) or Lipotoxin instillation (n = 11). Seven controls were treated with saline. Patients were injected with 100 U of BoNT-A or Lipotoxinin a single intravesical instillation. The patients enrolled in this study all had bladder biopsies performed at baseline and one month after BoNT-A therapy. Treatment outcome was measured by the decreases in urgency and frequency episodes at 1 month. The functional protein expressions in the urothelium were measured at baseline and after 1 month. The Wilcoxon signed-rank test and ordinal logistic regression were used to compare the treatment outcomes. Both BoNT-A injection and Lipotoxin instillation treatments effectively decreased the frequency of urgency episodes in OAB patients. Lipotoxin instillation did not increase post-void residual volume. BoNT-A injection effectively cleaved SNAP-25 (p < 0.01). Liposome encapsulated BoNT-A decreased urothelial P2X3 expression in the five responders (p = 0.04), while SNAP-25 was not significantly cleaved. The results of this study provide a possible mechanism for the therapeutic effects of BoNT-A for the treatment of OAB via different treatment forms. BoNT-A and Lipotoxin treatments effectively decreased the frequency of urgency episodes in patients with OAB.

Bladder function after sacrospinous hysteropexy and vaginal wall repair in women with uterovaginal prolapse.

PubMed

Sayed Ahmed, Waleed A; Taha, Omima T; Hamdy, Mostafa A; Ibrahim, Zakia M; Elshahat, Amal M

2018-05-01

To evaluate the impact of repair of uterovaginal prolapse using sacrospinous hysteropexy and vaginal wall repair on the bladder function. The study was conducted at the urogynecology clinic of Suez Canal University Hospitals, Ismailia from January 2014 to March 2016. This study included women with a diagnosis of uterovaginal prolapse and wishing to preserve their uteri. Bladder function was evaluated through assessment of urological symptoms using a standardized questionnaire - the urogenital distress inventory (UDI-6) - in addition to urodynamic studies just before and six-months after the sacrospinous hysteropexy ± associated vaginal wall repair operation. Twenty-seven patients completed the study with a mean age of 36.5 ± 4 years. Only 3 women had sacrospinous hysteropexy with no additional procedures. Other procedures included anterior colporrhaphy (12), posterior colporrhaphy (9) and perineorrhaphy (15). Based on UDI-6, there was no significant difference between the pre- and post-operative symptoms of stress urinary incontinence (SUI) [8/27 (29.6%) vs. 9/27 (33.3%) respectively; p value = 0.7]. The pre- and post-operative symptoms of urge urinary incontinence were also insignificantly different [13/27 (48.1%) vs. 15/27 (55.5%); p value = 0.5]. The total score of UDI-6 increased from 24.5 ± (14.2) to 32.8 ± (29.4) which was not statistically significant (p value = 0.12). Urodynamically, voiding dysfunction was found less frequently after the operation, however the difference was statistically insignificant [9/27 (33.3%) vs. 8/27 (29.6%); p value = 0.7]. Sacrospinous hysteropexy and associated vaginal wall repair do not affect the bladder function either subjectively or objectively. Copyright © 2018. Published by Elsevier B.V.

Long-term complications following bladder augmentations in patients with spina bifida: bladder calculi, perforation of the augmented bladder and upper tract deterioration

PubMed Central

2016-01-01

Background We desire to review our experience with bladder augmentation in spina bifida patients followed in a transitional and adult urologic practice. This paper will specifically focus on three major complications: bladder calculi, the most frequent complication found following bladder augmentation, perforation of the augmentation, its most lethal complication and finally we will address loss of renal function as a direct result of our surgical reconstructive procedures. Methods We reviewed a prospective data base maintained on patients with spina bifida followed in our transitional and adult urology clinic from 1986 to date. Specific attention was given to patients who had developed bladder calculi, sustained a spontaneous perforation of the augmented bladder or had developed new onset of renal scarring or renal insufficiency (≥ stage 3 renal failure) during prolonged follow-up. Results The development of renal stones (P<0.05) and symptomatic urinary tract infections (P<0.0001) were found to be significantly reduced by the use of high volume (≥240 mL) daily bladder wash outs. Individuals who still developed bladder calculi recalcitrant to high volume wash outs were not benefited by the correction of underlying metabolic abnormalities or mucolytic agents. Spontaneous bladder perforations in the adult patient population with spina bifida were found to be directly correlated to substance abuse and noncompliance with intermittent catheterization, P<0.005. Deterioration of the upper tracts as defined by the new onset of renal scars occurred in 40% (32/80) of the patients managed by a ileocystoplasty and simultaneous bladder neck outlet procedure during a median follow-up interval 14 years (range, 8–45 years). Development of ≥ stage 3 chronic renal failure occurred within 38% (12/32) of the patients with scarring i.e., 15% (12/80) of the total patient population. Prior to the development of the renal scarring, 69% (22/32) of the patients had been noncompliant with intermittent catheterization. The onset of upper tract deterioration (i.e., new scar formation, hydronephrosis, calculus development, decrease in renal function) was silent, that is, clinically asymptomatic in one third (10/32 pts). Conclusions This paper documents the need for high volume bladder irrigations to both prevent the most common complication following bladder augmentation, which is the development of bladder calculi and to reduce the incidence of symptomatic urinary tract infections. It provides a unique perspective regarding the impact of substance abuse and patient non-compliance with medical directives as being both the most common cause for both spontaneous bladder rupture following augmentation cystoplasty and for deterioration of the upper tracts. These findings should cause the surgeon to reflect on his/her assessment of a patient prior to performing a bladder augmentation procedure and stress the need for close follow-up. PMID:26904407

Targeting fibroblast growth factor receptors and immune checkpoint inhibitors for the treatment of advanced bladder cancer: New direction and New Hope.

PubMed

Morales-Barrera, Rafael; Suárez, Cristina; de Castro, Ana Martínez; Racca, Fabricio; Valverde, Claudia; Maldonado, Xavier; Bastaros, Juan Maria; Morote, Juan; Carles, Joan

2016-11-01

Bladder cancer is one of the leading causes of death in Europe and the United States. About 25% of patients with bladder cancer have advanced disease (muscle-invasive or metastatic disease) at presentation and are candidates for systemic chemotherapy. In the setting of metastatic disease, use of cisplatin-based regimens improves survival. However, despite initial high response rates, the responses are typically not durable leading to recurrence and death in the vast majority of these patients with median overall survival of 15months and a 5-year survival rate of ⩽10%. Furthermore, unfit patients for cisplatin have no standard of care for first line therapy in advance disease Most second-line chemotherapeutic agents tested have been disappointing. Newer targeted drugs and immunotherapies are being studied in the metastatic setting, their usefulness in the neoadjuvant and adjuvant settings is also an intriguing area of ongoing research. Thus, new treatment strategies are clearly needed. The comprehensive evaluation of multiple molecular pathways characterized by The Cancer Genome Atlas project has shed light on potential therapeutic targets for bladder urothelial carcinomas. We have focused especially on emerging therapies in locally advanced and metastatic urothelial carcinoma with an emphasis on immune checkpoints inhibitors and FGFR targeted therapies, which have shown great promise in early clinical studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Readability of American online patient education materials in urologic oncology: a need for simple communication.

PubMed

Pruthi, Amanda; Nielsen, Matthew E; Raynor, Mathew C; Woods, Michael E; Wallen, Eric M; Smith, Angela B

2015-02-01

To determine the readability levels of reputable cancer and urologic Web sites addressing bladder, prostate, kidney, and testicular cancers. Online patient education materials (PEMs) for bladder, prostate, kidney, and testicular malignancies were evaluated from the American Cancer Society, American Society of Clinical Oncology, National Cancer Institute, Urology Care Foundation, Bladder Cancer Advocacy Network, Prostate Cancer Foundation, Kidney Cancer Association, and Testicular Cancer Resource Center. Grade level was determined using several readability indices, and analyses were performed on the basis of cancer type, Web site, and content area (general, causes, risk factors and prevention, diagnosis and staging, treatment, and post-treatment). Estimated grade level of online PEMs ranged from 9.2 to 14.2 with an overall mean of 11.7. Web sites for kidney cancer had the least difficult readability (11.3) and prostate cancer had the most difficult readability (12.1). Among specific Web sites, the most difficult readability levels were noted for the Urology Care Foundation Web site for bladder and prostate cancer and the Kidney Cancer Association and Testicular Cancer Resource Center for kidney and testes cancer. Readability levels within content areas varied on the basis of the disease and Web site. Online PEMs in urologic oncology are written at a level above the average American reader. Simplification of these resources is necessary to improve patient understanding of urologic malignancy. Copyright © 2015 Elsevier Inc. All rights reserved.

Advances in intravesical therapy for urinary tract disorders

PubMed Central

Tyagi, Pradeep; Kashyap, Mahendra; Hensley, Harvey; Yoshimura, Naoki

2016-01-01

Introduction Intravesical therapy is a valuable option in the clinical management of urinary tract disorders such as interstitial cystitis/ painful bladder syndrome (IC/PBS) and refractory overactive bladder. This review will cover the latest advances in this field using polymer and liposomes as delivery platform for drugs, protein and nucleic acids. Areas covered This review summarizes the significance of intravesical therapy for lower urinary tract disorders. The recent advancement of liposomes as a drug delivery platform for botulinum toxin, tacrolimus and small interfering RNA is discussed. The importance of polymers forming indwelling devices and hydrogels are also discussed, where all preparations improved efficacy parameters in rodent models. Clinical experience of treating IC/PBS with indwelling devices and liposomes are summarized and preclinical evidence about the downregulation of target gene expression in rodent bladder with liposomes complexed with siRNA is also reviewed. Expert opinion There have been several advances in the field of intravesical therapy for improving clinical outcomes. One of the most promising research avenues is the repurposing of drugs, given previously by other routes of administration, such as tacrolimus. Intravesical therapy also opens up novel therapeutic targets with improved efficacy and safety for underactive bladder. PMID:26479968

Who, where, and why are patients lost to follow-up? A 20-year study of bladder exstrophy patients at a single institution.

PubMed

Haddad, Emily; Sancaktutar, Ahmet Ali; Palmer, Blake W; Aston, Christopher; Kropp, Bradley P

2018-03-19

Individuals with bladder and cloacal exstrophy are at increased risk for kidney disease, renal failure, and bladder complications. Given the social implications and sensitive nature of the disease, these patients are also at risk for psychosocial problems. Lack of regular medical follow-up visits may pose serious risks to their long-term health status. The aim of this study is determine what factors place an affected individual at risk for limited long term follow up. We identified all patients with bladder or cloacal exstrophy seen by the pediatric urology department at the Oklahoma University Health Sciences Center (OUHSC) between January 1996 and August 2016. Patient data included demographics, insurance coverage, distance from patient's home to the clinic, medical and surgical history, and the date of their last clinic visit. Two groups for comparison were (1) those that had been seen within the last 2 years, and (2) those that were counted as failing to maintain follow-up because 2 or more years had passed since their last clinic visit. These groups were compared using the Student t-test, the chi-square test, or the Fisher exact test and p < 0.05 was treated as significant for the purposes of discussion. Ninety-one patients with bladder or cloacal exstrophy were seen by the pediatric urology department between January 1996 and August 2016. Of the 91 patients, 24 left the clinic for known reasons thus leaving 67 patients that were considered for analyses: 51 had been seen within the last 2 years while 16 were counted as lost to follow-up. These two groups (active and lost to follow-up) did not differ significantly for age at last clinic visit, distance between family's home and clinic, history of bladder reconstruction, sex, or insurance status. There was a significant difference between the two groups in the medical complexity of their condition. The group active in urological care had more patients with cloacal exstrophy and additional anomalies than the group lost to follow-up. Patients with bladder exstrophy and cloacal exstrophy are less likely to maintain annual follow-up visits with their urologist if they have a simpler diagnosis requiring fewer surgical interventions. For patients with exstrophy, regular clinic visits prioritizing education and psychosocial support may prevent hospitalizations, emergency interventions, and poor overall health outcomes. To maintain contact with the medical team and promote optimal health outcomes, a social worker or care coordinator/educator may play an integral part in addressing the unique needs of this population. Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Gene Discovery in Bladder Cancer Progression using cDNA Microarrays

PubMed Central

Sanchez-Carbayo, Marta; Socci, Nicholas D.; Lozano, Juan Jose; Li, Wentian; Charytonowicz, Elizabeth; Belbin, Thomas J.; Prystowsky, Michael B.; Ortiz, Angel R.; Childs, Geoffrey; Cordon-Cardo, Carlos

2003-01-01

To identify gene expression changes along progression of bladder cancer, we compared the expression profiles of early-stage and advanced bladder tumors using cDNA microarrays containing 17,842 known genes and expressed sequence tags. The application of bootstrapping techniques to hierarchical clustering segregated early-stage and invasive transitional carcinomas into two main clusters. Multidimensional analysis confirmed these clusters and more importantly, it separated carcinoma in situ from papillary superficial lesions and subgroups within early-stage and invasive tumors displaying different overall survival. Additionally, it recognized early-stage tumors showing gene profiles similar to invasive disease. Different techniques including standard t-test, single-gene logistic regression, and support vector machine algorithms were applied to identify relevant genes involved in bladder cancer progression. Cytokeratin 20, neuropilin-2, p21, and p33ING1 were selected among the top ranked molecular targets differentially expressed and validated by immunohistochemistry using tissue microarrays (n = 173). Their expression patterns were significantly associated with pathological stage, tumor grade, and altered retinoblastoma (RB) expression. Moreover, p33ING1 expression levels were significantly associated with overall survival. Analysis of the annotation of the most significant genes revealed the relevance of critical genes and pathways during bladder cancer progression, including the overexpression of oncogenic genes such as DEK in superficial tumors or immune response genes such as Cd86 antigen in invasive disease. Gene profiling successfully classified bladder tumors based on their progression and clinical outcome. The present study has identified molecular biomarkers of potential clinical significance and critical molecular targets associated with bladder cancer progression. PMID:12875971

EVALUATION OF CONTRAST-ENHANCED ULTRASONOGRAPHY AS A METHOD FOR DETECTING GALLBLADDER NECROSIS OR RUPTURE IN DOGS.

PubMed

Bargellini, Paolo; Orlandi, Riccardo; Paloni, Chiara; Rubini, Giuseppe; Fonti, Paolo; Peterson, Mark E; Rishniw, Mark; Boiti, Cristiano

2016-11-01

Gall bladder necrosis and rupture are life-threatening conditions in dogs requiring surgical intervention and early diagnosis is essential. Human patients with suspected gall bladder necrosis/rupture are commonly evaluated with contrast-enhanced ultrasonography (CEUS), however this procedure has not been described in dogs with suspected gall bladder necrosis/rupture. In a prospective diagnostic cohort study, CEUS (using SonoVue contrast medium) was performed in 93 dogs with gallbladder lesions identified by abdominal conventional ultrasonography. Necrosis/rupture was identified by CEUS as a focal lack of enhancement of the gallbladder wall. Dogs with positive CEUS finding for necrosis/rupture (complete lack of regional wall enhancement) underwent immediate surgery as did dogs with other biliary disorders requiring surgery. Dogs with negative CEUS findings or those not requiring surgery were managed medically. In cases undergoing surgery, necrosis/rupture was confirmed intraoperatively (and via histopathology). Absence of necrosis/rupture was confirmed either intraoperatively (via histopathology) or was assumed to be absent by complete recovery with medical management. Forty-nine dogs underwent surgery and cholecystectomy: 24 had necrosis/rupture. CEUS was more accurate (100% sensitive and specific) in diagnosing gallbladder wall necrosis/rupture than conventional ultrasonography (75% sensitive and 81% specific) (P < 0.03). In conclusion, CEUS provides accurate characterization of gallbladder wall integrity that can impact decisions regarding clinical management, either surgical or medical. © 2016 American College of Veterinary Radiology.

Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-2-0132 TITLE: Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury...Sept 2015 4. TITLE AND SUBTITLE Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury 5a...evaluate the restoration of bladder and bowel function using electrical stimulation and block after spinal cord injury in human subjects. All staff

FGF2-mediated reciprocal tumor cell-endothelial cell interplay contributes to the growth of chemoresistant cells: a potential mechanism for superficial bladder cancer recurrence.

PubMed

Chen, Yule; Zhu, Guodong; Wu, Kaijie; Gao, Yang; Zeng, Jin; Shi, Qi; Guo, Peng; Wang, Xinyang; Chang, Luke S; Li, Lei; He, Dalin

2016-04-01

Patients with superficial bladder cancer can be definitively cured by one single transurethral resection (TUR) with additional intravesical chemotherapy; however, up to 75 % of cases display frequent and multiple recurrences. One of the major causes of recurrence is that chemotherapeutic drugs used in intravesical regimens may induce chemoresistance. However, the mechanisms by which these chemoresistant cells develop into recurrent tumors remain unclear. Recent clinical evidence revealed that the expression of pro-angiogenic factor FGF2 was associated with early local relapse in patients with superficial bladder cancer. In this study, we conducted a preliminary investigation of the mechanisms of chemoresistant cells mediated bladder cancer recurrence, focusing on FGF2-initiated tumor cell-endothelial cell interaction on chemoresistant cancer cell growth. We found that the expression of FGF2 was increased in chemoresistant bladder cell lines and in bladder tissues after intravesical chemotherapy. Although chemoresistant bladder cells grow slower than parental cells, chemoresistant bladder cancer cells had stronger ability than parental cells to stimulate endothelial cell migration, growth, and tube formation by producing FGF2. Inversely, endothelial cells significantly promoted chemoresistant bladder cancer growth in vitro and in vivo. Thus, targeting chemotherapy-induced FGF2 upregulation may provide a promising approach to manage the recurrence of superficial bladder cancer.

[Anterior urethral valves and anterior urethral diverticulum, are they same entity?

PubMed

Calleja Aguayo, E; Hernández Calvarro, A E; Bregante Ucedo, J; Marhuenda Irastorza, C

2015-04-15

We present our experience in the diagnosis and management of anterior urethral valves (AUV) and anterior urethral diverticula (AUD) as well as review of the bibliography. We retrospectively evaluated all the cases of the AUV and AUD treated in our hospital during the last 10 years. The clinical exploration, renal function study and renal and bladder ultrasound were evaluated in all the children. The diagnosis was completed with voiding cystography (VCUG) and cystoscopy as well as nuclear study in the relevant patients. Four patients have been treated in our center. AUV was suspected in those children with narrowing of the anterior urethra and thickened bladder with trabeculations at the VCUG. These findings were noticed in 50% of the patients, which also had a neonatal presentation. The diagnosis was confirmed by cystoscopy that allowed the endoscopic resection at the same procedure. The boys with AUD were managed by excision of the diverticulum with urethroplasty. On the follow up, one patient who had AUV, presented renal involvement in the nuclear scans with normal renal function. In our experience, the AUV and AUD behave as two different entities in terms of clinical presentation and treatment. The AUV have been effectively treated with endoscopic surgery and the AUD have pointed out open surgery, as described in the literature.

Parameters of two-dimensional perineal ultrasonography for evaluation of urinary incontinence after Radical Prostatectomy.

PubMed

Costa Cruz, Danilo Souza Lima da; D'Ancona, Carlos Arturo Levi; Baracat, Jamal; Alves, Marco Antonio Dionisio; Cartapatti, Marcelo; Damião, Ronaldo

2014-01-01

Urinary incontinence remains a major concern for patients undergoing radical prostatectomy. Its prevalence can reach 20% in the late postoperative period. This clinical study investigated the differences of a dynamic evaluation of the urethra and pelvic floor contraction using perineal ultrasound in men without prostate surgery and in men submitted to radical prostatectomy with and without stress urinary incontinence. Ninety two male patients were included, which 70% of them underwent radical prostatectomy (RP) for more than one year. Thirty one men with clinically post prostatectomy incontinence were compared by two-dimensional (2D) perineal ultrasound to 34 patients without post prostatectomy incontinence and to 27 men without surgery in two centers in Brazil. Our results showed that the continent group presented the urethral angle at rest significantly lower than the prostate group (p = 0.0002). We also observed that the incontinent group showed the displacement of the anterior bladder neck during contraction significantly lower than the continent group (p = 0.008). We found that the continent group presented the urethral angle at rest significantly lower than the prostate group. The incontinent group also showed the anterior bladder neck displacement during contraction significantly lower than the continent group. It was more evident when the severe incontinent group and the continent group were compared.

Evaluation of the axonics modulation technologies sacral neuromodulation system for the treatment of urinary and fecal dysfunction.

PubMed

Cohn, Joshua A; Kowalik, Casey G; Kaufman, Melissa R; Reynolds, W Stuart; Milam, Douglas F; Dmochowski, Roger R

2017-01-01

Sacral neuromodulation (SNM) remains one of the few effective treatments for refractory bladder and bowel dysfunction. However, SNM is associated with frequent need for surgical intervention, in many cases because of a failed battery. A rechargeable SNM system, with a manufacturer-reported battery life of 15 years or more, has entered post-market clinical testing in Europe but has not yet been approved for clinical testing in the United States. Areas covered: We review existing neuromodulation technologies for the treatment of lower urinary tract and bowel dysfunction and explore the limitations of available technology. In addition, we discuss implantation technique and device specifications and programming of the rechargeable SNM system in detail. Lastly, we present existing evidence for the use of SNM in bladder and bowel dysfunction and evaluate the anticipated trajectory of neuromodulation technologies over the next five years. Expert commentary: A rechargeable system for SNM is a welcome technological advance. However surgical revision not related to battery changes is not uncommon. Therefore, while a rechargeable system would be expected to reduce costs, it will not eliminate the ongoing maintenance associated with neuromodulation. No matter the apparent benefits, all new technologies require extensive post-market monitoring to ensure safety and efficacy.

A Methylation Panel for Bladder Cancer — EDRN Public Portal

Cancer.gov

Participate in a prevalidation study for methylation based detection of bladder cancer. In addition, a panel of three markers identified will be evaluated for their ability to a) identify bladder cancer patients from those with benign urologic disease; b) identify patients with superficial (papillary) cancers from those with high grade invasive cancers

Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples.

PubMed

Karavitakis, Markos; Msaouel, Pavlos; Michalopoulos, Vassilis; Koutsilieris, Michael

2014-06-01

Known risks factors for bladder cancer progression and recurrence are limited regarding their prognostic ability. Therefore identification of molecular determinants of disease progression could provide with more specific prognostic information and could be translated into new approaches for biomarker development. In the present study we evaluated, the expression patterns of somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. The expression of SSTR1-5 was characterized in 45 normal and bladder cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT-PCR). SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4 in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed lower levels of SSTR3. Co-expression of SSTRs was associated with superficial disease. Our results demonstrate, for the first time, that there is expression of SSTR in normal and bladder cancer urothelium. Further studies are required to evaluate the prognostic and therapeutic significance of these findings. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Muscarinic Receptor Binding in Rat Bladder Urothelium and Detrusor Muscle by Intravesical Solifenacin.

PubMed

Ito, Yoshihiko; Kashiwabara, Michishi; Yoshida, Akira; Hikiyama, Eriko; Onoue, Satomi; Yamada, Shizuo

2016-01-01

Solifenacin is an antimuscarinic agent used to treat symptoms of overactive bladder. Pharmacologically significant amounts of solifenacin were excreted in the urine of humans taking a clinical dose of this drug. The aim of this study is to measure muscarinic receptor binding in the bladder urothelium and detrusor muscles of rats following the intravesical instillation of solifenacin. Muscarinic receptors were measured by radioreceptor assay using [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS), a selective radioligand of muscarinic receptors. Solifenacin showed concentration-dependent inhibition of specific [(3)H]NMS binding in the bladder urothelium and detrusor muscle of rats, with no significant difference in Ki values or Hill coefficients between these tissues. Following the intravesical instillation of solifenacin, there was significant muscarinic receptor binding (increase in Kd for specific [(3)H]NMS binding) in the bladder urothelium and detrusor muscle of rats. Similar bladder muscarinic receptor binding was observed by the intravesical instillation of oxybutynin, but not with trospium. In conclusion, the present study has demonstrated that solifenacin binds muscarinic receptors not only in the detrusor muscle but also in the bladder urothelium with high affinity. These bladder muscarinic receptors may be significantly affected by solifenacin excreted in the urine.

Analysis on pathogenesis of 50 cases of bladder proliferative lesions.

PubMed

Chen, Zhiqiang; Lan, Ruzhu; Ye, Zhangqun; Yang, Weimin

2003-01-01

In order to study the pathogenesis, clinical and pathological characteristics of proliferative lesions of the bladder, 50 cases of proliferative lesions of the bladder from 150 patients with complaints of frequency, urgency, hematuria and dysuria were subjected to cystoscopic biopsy of the suspicious foci in the bladder. In combination with the symptoms, urine and urodynamics, the relationship of proliferative lesions of the bladder to the inflammation and obstruction of the lower urinary tract was analyzed. Of the 50 cases of proliferative bladder lesions, 44 cases (88%) had lower urinary tract infection and 29 (58%) lower urinary tract obstruction. The patients with lower urinary tract obstruction were all complicated with infection. Three cases were associated with transitional cell carcinoma. Malignant cells were detected in 1 case by urinary cytologic examination. Proliferative lesions of the bladder, especially those without other obvious mucosa changes under cystoscopy, are common histological variants of urothelium in the patients with chronic inflammation and obstruction of the lower urinary tract. Chronic inflammation and obstruction of the lower urinary tract might be the causes for proliferative lesions of the bladder. It is suggested that different treatments should be applied according to the scope and histological type of the proliferative lesions.

Urothelial cancer of bladder in young versus older adults: clinical and pathological characteristics and outcomes.

PubMed

Telli, Onur; Sarici, Hasmet; Ozgur, Berat Cem; Doluoglu, Omer Gokhan; Sunay, Mehmet Melih; Bozkurt, Selen; Eroglu, Muzaffer

2014-09-01

Bladder urothelial carcinoma is rare in young adults and occurs more commonly in older individuals. The aim of this study was to compare the clinical behavior, pathologic characteristics, and prognosis of urothelial carcinoma of urinary bladder in young versus older adults. A retrospective review of our records between 2007 and 2013 identified 56 patients (42 males and 14 females) with transitional cell carcinoma of the bladder who were less than 40 years old. Clinical and pathological parameters of patients who were less than 40 years of age were compared with those of a series of patients older than 40 years of age (the control group) during the same period. A survival analysis was performed using the Kaplan-Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinical outcomes. The mean age was 29.21 years (range, 5-40 years) for patients less than 40 years old and 61.66 years (range, 41-75) for those older than 40 years. The mean follow-up was 40.26 months (range, 12-65 months) for young patients and 42.57 months (range, 12-72 months) for the older patients. Young bladder cancer patients had smaller-sized tumors (less than 3 cm), less high-grade cancers, higher papillary urothelial neoplasms of low malignant potential, and low-grade tumors than patients older than 40 years. Multivariate logistic regression analysis predicted tumor recurrence in young patients with high-grade tumors [odds ratio (OR), 1.959; 95% confidence interval (CI), 1.235-2.965; p = 0.046] and tumors larger than 3 cm (OR, 1.772; 95% CI, 1.416-1.942; p = 0.032). The 5-year overall survival rate was 100% for young patients and 88.1% for older patients. No difference was observed in the recurrence-free (p = 0.321) and progression-free (p = 0.422) survival rates between the two groups. We concluded that although the clinical stage distribution, natural history, and outcomes of bladder urothelial cancer in young adults are similar to those in their older counterparts, clinicians must be aware that patients under 40 years of age presented with higher-grade and larger (>3 cm) tumors and are more likely to experience tumor recurrence. Copyright © 2014. Published by Elsevier B.V.

Correlation between messenger RNA expression and protein expression of immune checkpoint-associated molecules in bladder urothelial carcinoma: A retrospective study.

PubMed

Le Goux, Constance; Damotte, Diane; Vacher, Sophie; Sibony, Mathilde; Delongchamps, Nicolas Barry; Schnitzler, Anne; Terris, Benoit; Zerbib, Marc; Bieche, Ivan; Pignot, Géraldine

2017-05-01

Immunotherapy for bladder cancer seems to have promising results. Here, we evaluated the association between messenger RNA (mRNA) and protein levels and possible prognostic value of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) immune checkpoint pathways during bladder carcinogenesis. Tumor samples were obtained from 155 patients (84 with muscle-invasive bladder cancer [MIBC], and 71 non-muscle-invasive bladder cancer [NMIBC]) and normal bladder tissue from 15 patients. We evaluated the mRNA expression of 3 genes in the PD-1 pathway (PD-1, PD-L1, and PD-L2) and 4 in the CTLA4 pathway (CTLA4, CD28, CD80, and CD86) in normal and tumoral human bladder samples by quantitative real-time reverse transcription polymerase chain reaction, with immunohistochemistry used to evaluate the protein expression of PD-1 and PD-L1 in tumor and immune cells. Results of molecular analyses were compared with survival analyses. As compared with normal bladder tissue, MIBC tissue showed PD-1, PD-L1, CTLA4, and CD80 overexpression (59.5%, 60.7%, 84.5%, and 92.9%, respectively), whereas overexpression was lower in NMIBC tissue (22.5%, 4.2%, 35.2%, and 46.5%, respectively). The results of reverse transcription polymerase chain reaction analysis were confirmed by immunohistochemistry, with a high correlation between mRNA and protein expression. On multivariate analyses, overexpression of the studied genes was not associated with prognosis in relapse or progression of NMIBC or in recurrence-free and overall survival of MIBC. The CTLA4 pathway appears to be deregulated along with the PD-1/PD-L1 pathway in bladder carcinogenesis, with good correlation between mRNA and protein expression endorsing the useful role of immune checkpoints, especially for a large subgroup of MIBC. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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 urinary tract infections are the two independent factors that contribute to impaired voiding function and diabetic bladder dysfunction. Copyright © 2012. Published by Elsevier B.V.

Unexpected complication after cystometry in the hypocompliant urinary bladder: formation of a knot in the double lumen urethral catheter--a case report.

PubMed

Ayyildiz, Ali; Huri, Emre; Nuhoğlu, Bariş; Germiyanoğlu, Cankon

2006-01-01

Urodynamic evaluation is frequently used in the follow-up of the treatment and diagnosis of incontinence, which develops in connection with a neurogenic or non-neurogenic reason. There is no identified serious complication during or after urodynamic evaluation, present in the literature up to date. Hematuria, due to the urethral catheter, the development of oedema in the urinary bladder wall and the development of urinary bladder spasm as a result of catheter irritation, are some of the complications, which may occur. In this paper, twist and knot formation in the double lumen urethral catheter after cystometry of a patient with a hypocompliant urinary bladder, has been presented.

Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hata, Masaharu; Miyanaga, Naoto; Tokuuye, Koichi

Purpose: To present outcomes of bladder-preserving therapy with proton beam irradiation in patients with invasive bladder cancer. Methods and Materials: Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT2-3N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and cisplatin. Upon completion of these treatments, patients were evaluated by transurethral resection biopsy. Patients with no residual tumor received proton irradiation boost to the primary sites, whereas patients demonstrating residual tumors underwent radical cystectomy. Results: Of 25 patients, 23 (92%) were free of residual tumor at the time of re-evaluation; consequently,more » proton beam therapy was applied. The remaining 2 patients presenting with residual tumors underwent radical cystectomy. Of the 23 patients treated with proton beam therapy, 9 experienced recurrence at the median follow-up time of 4.8 years: local recurrences and distant metastases in 6 and 2 patients, respectively, and both situations in 1. The 5-year overall, disease-free, and cause-specific survival rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder-preservation rates were 73% and 96%, respectively, in the patients treated with proton beam therapy. Therapy-related toxicities of Grade 3-4 were observed in 9 patients: hematologic toxicities in 6, pulmonary thrombosis in 1, and hemorrhagic cystitis in 2. Conclusions: The present bladder-preserving regimen for invasive bladder cancer was feasible and effective. Proton beam therapy might improve local control and facilitate bladder preservation.« less

Dose evaluation of organs at risk (OAR) cervical cancer using dose volume histogram (DVH) on brachytherapy

NASA Astrophysics Data System (ADS)

Arif Wibowo, R.; Haris, Bambang; Inganatul Islamiyah, dan

2017-05-01

Brachytherapy is one way to cure cervical cancer. It works by placing a radioactive source near the tumor. However, there are some healthy tissues or organs at risk (OAR) such as bladder and rectum which received radiation also. This study aims to evaluate the radiation dose of the bladder and rectum. There were 12 total radiation dose data of the bladder and rectum obtained from patients’ brachytherapy. The dose of cervix for all patients was 6 Gy. Two-dimensional calculation of the radiation dose was based on the International Commission on Radiation Units and Measurements (ICRU) points or called DICRU while the 3-dimensional calculation derived from Dose Volume Histogram (DVH) on a volume of 2 cc (D2cc). The radiation dose of bladder and rectum from both methods were analysed using independent t test. The mean DICRU of bladder was 4.33730 Gy and its D2cc was4.78090 Gy. DICRU and D2cc bladder did not differ significantly (p = 0.144). The mean DICRU of rectum was 3.57980 Gy and 4.58670 Gy for D2cc. The mean DICRU of rectum differed significantly from D2cc of rectum (p = 0.000). The three-dimensional method radiation dose of the bladder and rectum was higher than the two-dimensional method with ratios 1.10227 for bladder and 1.28127 for rectum. The radiation dose of the bladder and rectum was still below the tolerance dose. Two-dimensional calculation of the bladder and rectum dose was lower than three-dimension which was more accurate due to its calculation at the whole volume of the organs.

Gall-bladder and colonic retention of SeHCAT: a re-evaluation.

PubMed

Merrick, M V

1994-09-01

A number of suggested alternatives and emendations to the 7-day SeHCAT retention test have been compared with whole-body counting. It was found that correction for colonic retention is an unnecessary complication in patients with diarrhoea and that imaging either of the gall-bladder or of the distribution of activity in the intestines at 24 h does not add useful information to the standard 7-day retention measurement. Neither could the patterns of colonic uptake identified in patients following extensive ideal resection or radiotherapy be reproduced in patients with idiopathic diarrhoea. Sadly it must be concluded that neither of these shortened techniques is of clinical value in patients with intact small bowel and that there remains no reliable alternative to the 7-day Se HCAT retention test. The simplest technique the best.

Development of an overactive bladder assessment tool (BAT): A potential improvement to the standard bladder diary.

PubMed

Kelleher, Con; Chapple, Christopher; Johnson, Nathan; Payne, Christopher; Homma, Yukio; Hakimi, Zalmai; Siddiqui, Emad; Evans, Christopher; Egan, Shayna; Kopp, Zoe

2018-01-23

To develop a comprehensive patient-reported bladder assessment tool (BAT) for assessing overactive bladder (OAB) symptoms, bother, impacts, and satisfaction with treatment. Subjects were consented and eligibility was confirmed by a recruiting physician; subjects were then scheduled for in-person interviews. For concept elicitation and cognitive interviews, 30 and 20 subjects, respectively, were targeted for recruitment from US sites. All interviews were conducted face-to-face, audio-recorded, transcribed verbatim, anonymized, and analyzed using a qualitative data analysis software program. A draft BAT was created based on the results of the concept elicitation interviews and further revised based on cognitive interviews as well as feedback from an advisory board of clinical and patient-reported outcome (PRO) experts. Nocturia, daytime frequency, and urgency were reported by all subjects (n = 30, 100.0%), and incontinence was reported by most subjects (n = 25, 83.3%). The most frequently reported impacts were waking up to urinate (n = 30, 100.0%), embarrassment/shame (n = 24, 80.0%), stress/anxiety (n = 23, 76.7%), and lack of control (n = 23, 76.7%). Following analysis, item generation, cognitive interviews, and advisory board feedback, the resulting BAT contains four hypothesized domains (symptom frequency, symptom bother, impacts, and satisfaction with treatment) and 17 items with a 7-day recall period. The BAT has been developed in multiple stages with input from both OAB patients and clinical experts following the recommended processes included in the FDA PRO Guidance for Industry. Once fully validated, we believe it will offer a superior alternative to use of the bladder diary and other PROs for monitoring OAB patients in clinical trials and clinical practice. © 2018 Wiley Periodicals, Inc.

Effects of acetylic salicylic acid and pentoxifylline on the efficacy of intravesical BCG therapy in orthotopic murine bladder cancer (MB49).

PubMed

Günther, J H; Frambach, M; Deinert, I; Brandau, S; Jocham, D; Böhle, A

1999-05-01

Intravesical immunotherapy with bacillus Calmette-Guerin (BCG), which has become the gold standard in the adjuvant treatment of superficial bladder cancer, is hampered by local side effects. Anti-inflammatory drugs may be helpful, but as an undesired side effect, therapeutic efficacy of BCG might be impaired. Therefore, we investigated the effects of anti-inflammatory drugs on the efficacy of intravesical BCG in an animal model. Syngenic tumor cells were implanted into the bladders of 75 mice according to our modification of the method. Mice were randomized to 5 groups with 15 animals each and treated with phosphate buffered saline (PBS), group 1; BCG, group 2; BCG + acetylic salicylic acid (ASA), group 3; BCG + pentoxifylline (POF), group 4; autoclaved BCG (aBCG), group 5. Intravesical instillation of 1.35 mg. BCG was initiated one day after tumor inoculation and repeated in weekly intervals for 4 instillations altogether. ASA and POF in doses of 200 mg./kg. and 150 mg./kg., respectively, were given continuously with the drinking water starting at the first instillation. Autoclaved BCG served as control for the importance of viability and was given at the same dose as viable BCG. Mice were monitored for survival, gross hematuria and body weight and after 28 days evaluated for bladder weight and tumor occurrence. Autoclaved BCG and PBS had no effect on tumor growth, whereas animals treated with viable BCG alone and in combination with POF and ASA, respectively, showed a significant reduction in bladder weight: PBS, 248 mg.; BCG, 140 mg. (p = 0.0009); BCG + ASA, 123 mg. (p = 0.0001); BCG + POF, 145 mg. (p = 0.0004); autoclaved BCG, 283 mg. (p = 0.21). Mice treated with BCG, BCG + ASA and BCG + POF showed a significantly higher proportion of survival until day 28 as compared to PBS alone. Autoclaved BCG had no therapeutic efficacy (Kaplan-Meier method/log rank test: BCG, p = 0.0053; BCG + ASA, p = 0.0044; BCG + POF, p = 0.0027; aBCG, p = 0.33). No significant differences among the 3 groups treated with viable BCG, with or without anti-inflammatory drugs, regarding bladder weight and survival were detectable. The efficacy of BCG therapy in murine orthotopic bladder cancer is dependent on BCG viability and is not compromised by ASA or POF. Clinical trials to evaluate the efficacy of routine ASA or POF to reduce BCG side effects in patients, using self-assessment criteria, should be initiated.

Recommendations for the Diagnosis and Management of Bladder Pain Syndrome. Spanish Urological Association Consensus Document.

PubMed

Esteban, M; Adot, J M; Arlandis, S; Peri, L; Prieto, L; Salinas, J; Cozar, J M

2015-10-01

Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) and other bladder pathologies share common manifestations, such as the presence of mictional symptoms and a negative impact on the patient's quality of life. To be properly diagnosed and clinically managed, it is important to distinguish between its clinical modalities and diagnostic criteria for adequate exclusion. The purpose of this study was to standardize criteria for making decisions in BPS management, for its diagnosis, initial treatment and follow-up. A nominal group methodology was employed, using scientific evidence on BPS taken from a systematic (non-exhaustive) literature review for developing recommendations along with specialist expert opinions. The diagnosis of BPS should be made based on the patient's clinical history, with emphasis on pain and mictional symptoms as well as excluding other pathologies with similar symptomatology. BPS treatment should be directed towards restoring normal bladder function, preventing symptom relapse and improving patients' quality of life. It is therefore advisable to start with conservative treatment and to adopt less conservative treatments as the level of clinical severity increases. It is also recommended to abandon ineffective treatments and reconsider other therapeutic options. Quickly identifying the pathology is important when trying to positively influence morbidity and care quality for these patients. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Structural and vascular response of normal and obstructed rabbit whole bladders to distension.

PubMed

Matsumoto, Seiji; Chichester, Paul; Kogan, Barry A; Levin, Robert M

2003-12-01

To investigate the structural and morphologic effect of distension after partial outlet obstruction in rabbits. Thirty male New Zealand white rabbits were separated into two groups: control (sham) and partial outlet obstruction (3 weeks). Three rabbits from each group were distended to 5%, 25%, 50%, 100%, and 125% of capacity. Each bladder was fixed at the volume in buffered formalin for 6 to 8 hours. Sections of dorsal and ventral bladder were blocked, and cross sections were evaluated. Quantitative morphometry was performed, and CD31 immunohistochemistry was used to characterize the vascularity. Partial outlet obstruction resulted in increased bladder weight and capacity and increased thickness of the mucosa, submucosa, detrusor, and serosa. In the control bladder, the greatest thinning was seen between 5% and 25% capacity, and in the obstructed group, the greatest thinning occurred between 25% and 50%. The level of vascular collapse was significantly greater for the control bladders than for the obstructed bladders at all levels of distension. Finally, the obstructed bladders showed a significantly greater level of vascularity in the submucosa than the control bladders. Normal bladder distension resulted in significant morphologic changes when the bladder was distended to 25% of capacity but changed relatively little between 25% and 125%. However, distension of the obstructed bladder resulted in significant morphologic changes when the bladder was distended from 25% to 50% of capacity but changed relatively little between 50% and 125%.

The current status and clinical value of circulating tumor cells and circulating cell-free tumor DNA in bladder cancer

PubMed Central

Soave, Armin; Rink, Michael

2017-01-01

Urothelial carcinoma of the bladder (UCB) is a complex disease, which is associated with highly aggressive tumor biologic behavior, especially in patients with muscle-invasive and advanced tumors. Despite multimodal therapy options including surgery, radiotherapy and chemotherapy, UCB patients frequently suffer from poor clinical outcome. Indeed, the potential of diverse opportunities for modern targeted therapies is not sufficiently elucidated in UCB yet. To improve the suboptimal treatment situation in UCB, biomarkers are urgently needed that help detecting minimal residual disease (MRD), predicting therapy response and subsequently prognosis as well as enabling patient stratification for further therapies and therapy monitoring, respectively. To date, decision making regarding treatment planning is mainly based on histopathologic evaluation of biopsies predominantly derived from the primary tumors and on clinical staging. However, both methods are imperfect for sufficient outcome prediction. During disease progression, individual disseminated tumor cells and consecutively metastases can acquire characteristics that do not match those of the corresponding primary tumors, and often are only hardly assessable for further evaluation. Therefore, during recent years, strong efforts were directed to establish non-invasive biomarkers from liquid biopsies. Urine cytology and serum tumor markers have been established for diagnostic purposes, but are still insufficient as universal biomarkers for decision-making and treatment of UCB patients. To date, the clinical relevance of various newly established blood-based biomarkers comprising circulating tumor cells (CTCs), circulating cell-free nucleic acids or tumor-educated platelets is being tested in cancer patients. In this review we summarize the current state and clinical application of CTCs and circulating cell-free tumor DNA originating from blood as biomarkers in patients with different UCB stages. PMID:29354496

Analysis of nocturia with 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration: concept for effective treatment modality.

PubMed

Udo, Yukihiro; Nakao, Masahiro; Honjo, Hisashi; Ukimura, Osamu; Kawauchi, Akihiro; Kitakoji, Hiroshi; Miki, Tsuneharu

2011-03-01

• To determine the relationship between the number of nocturia and 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration as well as to assess the significance of these factors with respect to eliminating nocturnal voidings in individual patients with nocturia. • Among 532 participants who completed a 3-day bladder diary between April 2005 and December 2006, the diaries of 450 participants without 24-h polyuria were analyzed. • Clinical variables such as the number of daytime and night-time voids, 24-h urine volume, nocturnal polyuria index, daytime and night-time maximum voided volumes (MVV), night/day MVV ratio, sleep duration and proportion of night/day urine production rates were obtained from each diary. • Participants were classified into eight groups according to values of three factors: nocturnal MVV, proportion of night/day urine production rates and length of sleep duration. • Each group was divided into three subgroups: non-nocturics (number of nocturnal voidings is zero), mild nocturics (number of nocturnal voidings is one) and severe nocturics (number of nocturnal voidings is two or more). • The data from non-nocturics with three normal factors were regarded as the normal control and compared with the variables of the other subgroups using Dunnett's method. • Variables that form the basis of classifying participants into eight groups and corresponding to abnormal factors of each group were statistically significant in all the subgroups of each group. • Furthermore, a significantly increased 24-h urine volume was found in severe nocturics of the group with three normal factors. • A significantly decreased 24-h urine volume was found in non-nocturics of groups with nocturnal polyuria, decreased bladder capacity and both long sleep duration and nocturnal polyuria. • A significantly increased nocturnal MVV and night/day MVV ratio were shown in non-nocturics and mild nocturics of the groups with nocturnal polyuria and both long sleep duration and nocturnal polyuria. • Because nocturia is a multifactorial disorder and closely related to four factors (i.e. 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration), the evaluation of all these factors appears to be clinically useful for determining the main contributing factor in patients with nocturia as well as the suitable treatment modality on an individual basis. • Physicians should take all these factors into consideration in the evaluation and treatment of nocturia. © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

SU-G-JeP3-05: Geometry Based Transperineal Ultrasound Probe Positioning for Image Guided Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Camps, S; With, P de; Verhaegen, F

2016-06-15

Purpose: The use of ultrasound (US) imaging in radiotherapy is not widespread, primarily due to the need for skilled operators performing the scans. Automation of probe positioning has the potential to remove this need and minimize operator dependence. We introduce an algorithm for obtaining a US probe position that allows good anatomical structure visualization based on clinical requirements. The first application is on 4D transperineal US images of prostate cancer patients. Methods: The algorithm calculates the probe position and orientation using anatomical information provided by a reference CT scan, always available in radiotherapy workflows. As initial test, we apply themore » algorithm on a CIRS pelvic US phantom to obtain a set of possible probe positions. Subsequently, five of these positions are randomly chosen and used to acquire actual US volumes of the phantom. Visual inspection of these volumes reveal if the whole prostate, and adjacent edges of bladder and rectum are fully visualized, as clinically required. In addition, structure positions on the acquired US volumes are compared to predictions of the algorithm. Results: All acquired volumes fulfill the clinical requirements as specified in the previous section. Preliminary quantitative evaluation was performed on thirty consecutive slices of two volumes, on which the structures are easily recognizable. The mean absolute distances (MAD) between actual anatomical structure positions and positions predicted by the algorithm were calculated. This resulted in MAD of 2.4±0.4 mm for prostate, 3.2±0.9 mm for bladder and 3.3±1.3 mm for rectum. Conclusion: Visual inspection and quantitative evaluation show that the algorithm is able to propose probe positions that fulfill all clinical requirements. The obtained MAD is on average 2.9 mm. However, during evaluation we assumed no errors in structure segmentation and probe positioning. In future steps, accurate estimation of these errors will allow for better evaluation of the achieved accuracy.« less

Radiation-induced cystitis following intracavitary irradiation for superficial bladder cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maatman, T.J.; Novick, A.C.; Montague, D.K.

Intracavitary irradiation is effective in the treatment of noninvasive papillary transitional cell carcinoma and carcinoma in situ of the bladder. Mortality has not been associated with this form of therapy. The morbidity associated with intracavitary irradiation consists of mild to severe radiation cystitis and we report 2 such cases. One patient is from a series of 65 patients with noninvasive bladder tumors treated with intracavitary irradiation at this clinic since 1965. The second patient had noninvasive bladder tumors and was treated with intracavitary irradiation elsewhere. In both patients severe radiation cystitis subsequently developed, requiring simple cystectomy and urinary diversion. Themore » potential for this serious side effect must be considered when choosing a form of therapy for patients with noninvasive papillary transitional cell carcinoma and carcinoma in situ of the bladder.« less

Hematuria and clot retention after transvaginal oocyte aspiration: a case report.

PubMed

Modder, Joshua; Kettel, L Michael; Sakamoto, Kyoko

2006-09-01

To report a case of bladder injury with hematuria and urinary retention after transvaginal oocyte aspiration. Case report. Emergency room in a university medical center. A 28-year-old woman presented with urinary retention and suprapubic pain 8 hours after oocyte aspiration. Foley catheter, intravenous fluid bolus, bladder irrigation, and computed tomography with postvoid films that showed a blood clot in the bladder. Patient was discharged home with antibiotics and catheter in place. Clinical follow-up. Patient passed voiding trial 4 days later and was artificially inseminated. No further hematuria or voiding problems were reported, and she had a successful pregnancy. Patients who elect to undergo oocyte aspiration should be warned about the possibility of bladder injury because of the close proximity of the ovaries to the bladder, and physicians should have an appropriate treatment plan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schooneveldt, G.; Kok, H.P.; Bakker, A.

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 CTmore » 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.« less

Transient neuropathic bladder following herpes simplex genitalis.

PubMed

Riehle, R A; Williams, J J

1979-08-01

A case of transient bladder dysfunction and urinary retention concomitant with herpes genitalis is presented. The protean manifestations of the herpes simplex virus, the similar neurotropic behavior of simplex and zoster, and the neurologic sequelae of the cutaneous simplex eruption are discussed. The possibility of sacral radiculopathy after herpes genitalis must be considered when evaluating acute or episodic neurogenic bladders.

Embryonal Rhabdomyosarcoma of the Adult Urinary Bladder: A Rare Case Report of Misclassification as Inflammatory Myofibroblastic Tumor

PubMed Central

Chen, Kelven Weijing; Wu, Fiona Mei Wen; Lee, Victor Kwan Min; Esuvaranathan, Kesavan

2015-01-01

Embryonal rhabdomyosarcoma (ERMS) of the adult urinary bladder is a rare malignant tumour. Inflammatory myofibroblastic tumour (IMT) of the bladder is a benign genitourinary tumour that may appear variable histologically but usually lacks unequivocal malignant traits. Techniques like flow cytometry and immunohistochemistry may be used to differentiate these two tumours. Our patient, a 46-year-old male, had rapidly recurring lower urinary tract symptoms after two transurethral resections of the prostate. He subsequently underwent a transvesical prostatectomy which showed IMT on histology. However, his symptoms did not resolve and an open resection done at our institution revealed a 6 cm tumour arising from the right bladder neck. This time, histology was ERMS with diffuse anaplasia of the bladder. Rapid recurrence of urinary symptoms with prostate regrowth after surgery is unusual. Differential diagnoses of uncommon bladder malignancies should be considered if there is an inconsistent clinical course as treatment approaches are different. PMID:25737794

Fibrosarcoma of the urinary bladder in a cat

PubMed Central

Capasso, Angelo; Raiano, Vera; Sontuoso, Antonio; Olivero, Daniela

2015-01-01

Case summary A 5-year-old female spayed domestic shorthair cat was presented with haematuria, pollakiuria and stranguria of 2 months’ duration, and a firm non-painful mass in the urinary bladder was palpated. Abdominal radiographs showed thickening and irregular cranial margins of the urinary bladder wall. Abdominal ultrasound showed a vascularised mass of mixed echogenicity almost entirely occupying the urinary bladder lumen. During explorative laparotomy, the mass appeared pedunculated and was totally excised. Histopathology was characterised by infiltration of the mucosal, submucosal and muscular layers by proliferated atypical mesenchymal cells; immunochemistry confirmed the diagnosis of fibrosarcoma. The cat was discharged with normal urination 5 days after surgery. The owner declined any imaging follow-up but reported the cat to be free of any clinical signs at 16 months after surgery. Relevance and novel information To the best of our knowledge, this is the first case of primary fibrosarcoma of the urinary bladder in the cat. Fibrosarcoma should be included in the differential diagnosis of urinary bladder neoplasia. PMID:28491352

Fibrosarcoma of the urinary bladder in a cat.

PubMed

Capasso, Angelo; Raiano, Vera; Sontuoso, Antonio; Olivero, Daniela; Greci, Valentina

2015-01-01

A 5-year-old female spayed domestic shorthair cat was presented with haematuria, pollakiuria and stranguria of 2 months' duration, and a firm non-painful mass in the urinary bladder was palpated. Abdominal radiographs showed thickening and irregular cranial margins of the urinary bladder wall. Abdominal ultrasound showed a vascularised mass of mixed echogenicity almost entirely occupying the urinary bladder lumen. During explorative laparotomy, the mass appeared pedunculated and was totally excised. Histopathology was characterised by infiltration of the mucosal, submucosal and muscular layers by proliferated atypical mesenchymal cells; immunochemistry confirmed the diagnosis of fibrosarcoma. The cat was discharged with normal urination 5 days after surgery. The owner declined any imaging follow-up but reported the cat to be free of any clinical signs at 16 months after surgery. To the best of our knowledge, this is the first case of primary fibrosarcoma of the urinary bladder in the cat. Fibrosarcoma should be included in the differential diagnosis of urinary bladder neoplasia.

Minimally invasive percutaneous cystostomy with ureteroscopic pneumatic lithotripsy for calculus in bladder diverticula

PubMed Central

GU, SI-PING; YOU, ZHI-YUAN; HUANG, YUNTENG; LU, YI-JIN; HE, CAOHUI; CAI, XIAO-DONG; ZHOU, XIAO-MING

2013-01-01

The aim of this study was to investigate the effectiveness of minimally invasive percutaneous cystostomy with ureteroscopic pneumatic lithotripsy for treating calculus in bladder diverticula. Percutaneous cystostomy with ureteroscopic pneumatic lithotripsy was performed on six elderly male patients with calculi in bladder diverticula, who could not be treated with transurethral ureteroscopic lithotripsy. The stones were successfully removed from all patients, with no complications such as bladder perforation, rupture, urethritis or cystitis. The surgery time was 15–60 min, with an average time of 32 min. Postoperative ultrasound or X-ray examination showed no stone residues and the bladder stoma healed well. No recurrent stones were detected in the follow-up of 3–24 months (average, 16 months). Minimally invasive percutaneous cystostomy with ureteroscopic pneumatic lithotripsy is a safe, efficient and easy treatment for calculus in bladder diverticula. This method provides a new clinical approach for lithotripsy and we suggest that it is worthy of wider use. PMID:23837044

Dysregulation of miRNAs in bladder cancer: altered expression with aberrant biogenesis procedure

PubMed Central

Dong, Fan; Xu, Tianyuan; Shen, Yifan; Zhong, Shan; Chen, Shanwen; Ding, Qiang; Shen, Zhoujun

2017-01-01

Aberrant expression profiles of miRNAs are widely observed in the clinical tissue specimens and urine samples as well as the blood samples of bladder cancer patients. These profiles are closely related to the pathological features of bladder cancer, such as the tumour stage/grade, metastasis, recurrence and chemo-sensitivity. MiRNA biogenesis forms the basis of miRNA expression and function, and its dysregulation has been shown to be essential for variations in miRNA expression profiles as well as tumourigenesis and cancer progression. In this review, we summarize the up-to-date and widely reported miRNAs in bladder cancer that display significantly altered expression. We then compare the miRNA expression profiles among three different sample types (tissue, urine and blood) from patients with bladder cancer. Moreover, for the first time, we outline the dysregulated miRNA biogenesis network in bladder cancer from different levels and analyse its possible relationship with aberrant miRNA expression and the pathological characteristics of the disease. PMID:28187437

Bovine papillomavirus type 2 infects the urinary bladder of water buffalo (Bubalus bubalis) and plays a crucial role in bubaline urothelial carcinogenesis.

PubMed

Roperto, Sante; Russo, Valeria; Ozkul, Ayhan; Sepici-Dincel, Aylin; Maiolino, Paola; Borzacchiello, Giuseppe; Marcus, Ioan; Esposito, Iolanda; Riccardi, Marita Georgia; Roperto, Franco

2013-02-01

Bovine papillomavirus type 2 (BPV-2) has been shown to infect and play a role in urinary bladder carcinogenesis of buffaloes grazed on pastures with ferns from the Marmara and Black Sea Regions of Turkey. BPV-2 DNA has been found in both neoplastic and non-neoplastic lesions of the urinary bladder. Furthermore, this virus may be a normal inhabitant of the urinary bladder since BPV-2 DNA has also been detected in clinically normal buffaloes. The viral activation by fern immunosuppressant or carcinogen may trigger the urothelial cell transformation. The E5 oncoprotein was solely detected in urothelial tumours and appeared to be co-localized with the overexpressed and phosphorylated platelet derived growth factor (PDGF) β receptor in a double-colour immunofluorescence assay. Our results indicate that the E5-PDGF β receptor interaction also occurs in spontaneous tumours of the bubaline urinary bladder, revealing an additional role of BPV-2 in bladder carcinogenesis of buffaloes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Brian C.; Bosch, Walter R.; Bahl, Amit

Purpose: To develop multi-institutional consensus clinical target volumes (CTVs) and organs at risk (OARs) for male and female bladder cancer patients undergoing adjuvant radiation therapy (RT) in clinical trials. Methods and Materials: We convened a multidisciplinary group of bladder cancer specialists from 15 centers and 5 countries. Six radiation oncologists and 7 urologists participated in the development of the initial contours. The group proposed initial language for the CTVs and OARs, and each radiation oncologist contoured them on computed tomography scans of a male and female cystectomy patient with input from ≥1 urologist. On the basis of the initial contouring, themore » group updated its CTV and OAR descriptions. The cystectomy bed, the area of greatest controversy, was contoured by another 6 radiation oncologists, and the cystectomy bed contouring language was again updated. To determine whether the revised language produced consistent contours, CTVs and OARs were redrawn by 6 additional radiation oncologists. We evaluated their contours for level of agreement using the Landis-Koch interpretation of the κ statistic. Results: The group proposed that patients at elevated risk for local-regional failure with negative margins should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac, obturator, and presacral), whereas patients with positive margins should be treated to the pelvic nodes and cystectomy bed. Proposed OARs included the rectum, bowel space, bone marrow, and urinary diversion. Consensus language describing the CTVs and OARs was developed and externally validated. The revised instructions were found to produce consistent contours. Conclusions: Consensus descriptions of CTVs and OARs were successfully developed and can be used in clinical trials of adjuvant radiation therapy for bladder cancer.« less

Paraganglioma of the Urinary Bladder: A Rare Cause of Hypertension and Urinary Tract Infections.

PubMed

Chaaya, Gerard; Morales, Jorge; Castiglioni, Analia; Subhani, Noman; Asmar, Abdo

2018-02-01

Pheochromocytoma is a neoplasm, which develops from cells of the chromaffin tissues that are derived from the ectodermic neural system and mostly situated within the adrenal medulla. Approximately 15% of pheochromocytoma cases arise from extra-adrenal chromaffin tissue. Pheochromocytoma of the bladder is rare and accounts for less than 0.06% of all bladder neoplasms and less than 1% of all pheochromocytomas. We report a case of a young woman who presented with uncontrolled hypertension, recurrent urinary tract infections and micturition attacks and was found to have a metastatic bladder paraganglioma. In addition, we provide a summary table of the clinical manifestations of paragangliomas based on anatomic locations. Published by Elsevier Inc.

Use of a laparoscopic specimen retrieval pouch to facilitate removal of intact or fragmented cystic calculi from standing sedated horses: 8 cases (2012-2015).

PubMed

Katzman, Scott A; Vaughan, Betsy; Nieto, Jorge E; Galuppo, Larry D

2016-08-01

OBJECTIVE To evaluate the use of a laparoscopic specimen retrieval pouch for removal of intact or fragmented cystic calculi from standing horses. DESIGN Retrospective case series. ANIMALS 8 horses (5 geldings and 3 mares) with cystic calculi. PROCEDURES Physical examination and cystoscopic, ultrasonographic, and hematologic evaluations of urinary tract function were performed for each horse. A diagnosis of cystic calculus was made on the basis of results of cystoscopy and ultrasonography. Concurrent urolithiasis or other urinary tract abnormalities identified during preoperative evaluation were recorded. Horses were sedated and placed in standing stocks, and the perineum was aseptically prepared. Direct access to the urinary bladder was gained in geldings via perineal urethrotomy or in mares by a transurethral approach. Calculi were visualized endoscopically, manipulated into the retrieval pouch, and removed intact or fragmented (for larger calculi). RESULTS For 4 geldings and 1 mare, fragmentation was necessary to facilitate calculus removal. Mean duration of surgery was 125 minutes, and trauma to the urinary bladder and urethra was limited to areas of hyperemia and submucosal petechiation. No postoperative complications were encountered for any horse. When lithotripsy was required, the retrieval pouch provided an effective means of stabilizing calculi and containing the fragments for removal. CONCLUSIONS AND CLINICAL RELEVANCE Use of the laparoscopic specimen retrieval pouch was an effective, minimally traumatic method for retrieving cystic calculi from standing horses. The pouch protected the urinary bladder and urethra from trauma during calculus removal and allowed for stabilization, containment, and fragmentation of calculi when necessary.

Dosimetric evaluation of a novel high dose rate (HDR) intraluminal / interstitial brachytherapy applicator for gastrointestinal and bladder cancers

PubMed Central

Aghamiri, Seyyed Mahmoud Reza; Najarian, Siamak; Jaberi, Ramin

2010-01-01

High dose rate (HDR) brachytherapy is one of the accepted treatment modalities in gastro‐intestinal tract and bladder carcinomas. Considering the shortcoming of contact brachytherapy routinely used in gastrointestinal tract in treatment of big tumors or invasive method of bladder treatment, an intraluminal applicator with the capability of insertion into the tumor depth seems to be useful. This study presents some dosimetric evaluations to introduce this applicator to the clinical use. The radiation attenuation characteristics of the applicator were evaluated by means of two dosimetric methods including well‐type chamber and radiochromic film. The proposed 110 cm long applicator has a flexible structure made of stainless steel for easy passage through lumens and a needle tip to drill into big tumors. The 2 mm diameter of the applicator is thick enough for source transition, while easy passage through any narrow lumen such as endoscope or cystoscope working channel is ensured. Well‐chamber results showed an acceptably low attenuation of this steel springy applicator. Performing absolute dosimetry resulted in a correlation coefficient of R=0.9916(p‐value≈10−7) between standard interstitial applicator and the one proposed in this article. This study not only introduces a novel applicator with acceptable attenuation but also proves the response independency of the GAFCHROMIC EBT films to energy. By applying the dose response of the applicator in the treatment planning software, it can be used as a new intraluminal / interstitial applicator. PACS number: 87.53.Bn, 87.53.Jw, 29.40.Cs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, JY; Hong, DL

Purpose: To investigate the impact of bladder filling status of the organs at risk (OARs) on dose distribution during intensity modulated radiotherapy (IMRT) for cervical cancer patients. Methods: Twelve cervical cancer patients treated with IMRT were selected for this study. The prescription dose was 45Gy/25 fractions with the 6 MV photon beam. All patients performed two CT scans, one with an empty bladder, the other one with bladder filled. For the registration of two CT scans, the fusion was automatically carried out upon the bony anatomy. The OARs (bladder, rectum, pelvic bone and small intestine) were delineated to planning CTmore » to evaluate the dose distributions. These dose distributions were compared between empty bladder and bladder filling. Results: The bladder volume with empty bladder and bladder filling was 403.2±124.13cc and 101.4±87.5cc, respectively. There were no statistical differences between empty bladder and bladder filling in the mean value of pelvic bone V10Gy, V20Gy, V40Gy; rectum V40Gy and V45Gy. The bladder V40Gy and V45Gy were lower in the bladder filling group than in the empty bladder group (63.7%±5.8% vs 87.5%±7.8%, 45.1%±9.5% vs 62.4%±11.8%, respectively). The V45Gy for small intestine in the bladder filling group was significantly less than the empty bladder group (146.7cc±95.3cc vs 245.7cc±101.8cc). Conclusion: Our study finds that the bladder filling status did not have a significant impact on dose distribution in the rectum and pelvic bone. However, the changes of bladder filling have a large impact on bladder and small intestine doses. A full bladder is strongly recommended during treatment for cervical cancer patients.« less

Robotic Y-V Plasty for Recalcitrant Bladder Neck Contracture.

PubMed

Granieri, Michael A; Weinberg, Aaron C; Sun, Jeffrey Y; Stifleman, Michael; Zhao, Lee

2018-07-01

To demonstrate the technique and the outcomes of robot assisted Y-V plasty bladder neck reconstruction (RYVBNR). We present our technique for treatment of recalcitrant bladder neck contracture (BNC) in 7 patients who underwent RYVBNR at our institution between March 2016 and September 2017. Indication for the procedure was incomplete emptying, recurrent urinary tract infections, and dysuria. On follow-up, patients were assessed for clinical success by absence of infections, symptoms, and cystoscopic evaluation. Robotic assisted dissection is performed to open the space of Retzius and mobilize the bladder. The cystoscope is passed to the level of the BNC, and Firefly technology is used to localize the BNC. The BNC is incised anteriorly, and a V-shaped bladder flap is advanced into the BNC in a Y-V plasty fashion. We place a perioperative closed suction drain, which is removed before discharge, and a 22 Fr catheter, which that will be removed in the office at approximately 2 weeks. Six men developed recalcitrant BNCs and 1 developed a recalcitrant vesicourethral anastomotic stenosis. All patients had previously undergone an endoscopic procedure. Median time for last attempt at endoscopic management to robot-assisted bladder neck repair was 4.7 months. The average number of prior attempts at endoscopic management was 2. All patients underwent RYVBNR without conversion to open surgery. The median operative time was 240 minutes, estimated blood loss was 67 mL, and length of stay was 1 day. There were no intraoperative complications. Catheters were removed in the office at a median time of 15 days. At a median follow-up of 8 months, all cases were successful with no evidence of recurrence. Only 2 patients had persistent urinary incontinence at 1 pad per day. RYVBNR with a Y-V plasty is a feasible and effective technique for managing a difficult reconstructive problem. Copyright © 2018 Elsevier Inc. All rights reserved.

Hyposensitivity of C-fiber Afferents at the Distal Extremities as an Indicator of Early Stages Diabetic Bladder Dysfunction in Type 2 Diabetic Women

PubMed Central

Lee, Wei-Chia; Wu, Han-Ching; Huang, Kuo-How; Wu, Huey-Peir; Yu, Hong-Jeng; Wu, Chia-Ching

2014-01-01

Purpose To investigate the relationship between distal symmetric peripheral neuropathy and early stages of autonomic bladder dysfunction in type 2 diabetic women. Materials and Methods A total of 137 diabetic women with minimal coexisting confounders of voiding dysfunction followed at a diabetes clinic were subject to the following evaluations: current perception threshold (CPT) tests on myelinated and unmyelinated nerves at the big toe for peroneal nerve and middle finger for median nerve, uroflowmetry, post-void residual urine volume, and overactive bladder (OAB) symptom score questionnaire. Patients presenting with voiding difficulty also underwent urodynamic studies and intravesical CPT tests. Results Based on the OAB symptom score and urodynamic studies, 19% of diabetic women had the OAB syndrome while 24.8% had unrecognized urodynamic bladder dysfunction (UBD). The OAB group had a significantly greater mean 5 Hz CPT test value at the big toe by comparison to those without OAB. When compared to diabetic women without UBD, those with UBD showed greater mean 5 Hz CPT test values at the middle finger and big toe. The diabetic women categorized as C-fiber hyposensitivity at the middle finger or big toe by using CPT test also had higher odds ratios of UBD. Among diabetic women with UBD, the 5 Hz CPT test values at the big toe and middle finger were significantly associated with intravesical 5 Hz CPT test values. Conclusions Using electrophysiological evidence, our study revealed that hyposensitivity of unmyelinated C fiber afferents at the distal extremities is an indicator of early stages diabetic bladder dysfunction in type 2 diabetic women. The C fiber dysfunction at the distal extremities seems concurrent with vesical C-fiber neuropathy and may be a sentinel for developing early diabetic bladder dysfunction among female patients. PMID:24466107

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

PubMed Central

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. PMID:27563352

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

PubMed

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.

Monitoring of lower urinary tract function in patients with spinal cord injury using near infrared spectroscopy

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Macnab, Andrew; Nigro, Mark; Stothers, Lynn

2012-02-01

Background: One of the most important conditions where there is loss of normal bladder function is spinal cord injury (SCI). Currently, evaluation of bladder function is limited to periodic invasive urodynamic testing (UDS). The purpose of this study was to assess the feasibility and usefulness of near-infrared spectroscopy (NIRS) in monitoring bladder function in patients with SCI during bladder filling and emptying and to investigate the correlations of NIRS measures with simultaneous UDS parameters. NIRS is a non-invasive optical method to study tissue oxygenation, hemodynamics and function by monitoring changes in the chromophore concentrations of oxygenated (O2Hb), deoxygenated (HHb) and total hemoglobin (tHb). Methods: 10 adult paraplegic patients with neurogenic bladder dysfunction who were referred for regular urodynamic evaluation were recruited. Changes in O2Hb, HHb and tHb, and tissue saturation index (TSI%) in the detrusor were monitored and recorded by a wireless NIRS system during the urodynamic evaluation. Time points of urgency and urinary leakage were marked and patterns of change in NIRS parameters were compared to standard urodynamic pressure tracings. Results: Strong consistency between changes in NIRS-derived tHb and changes in intravesical pressure were observed during filling across the subjects. During bladder filling a gradual increase in O2Hb and tHb with minimal changes in HHb was observed. Interestingly, a drop in TSI% was detected seconds before strong urgency and urinary leakage. Conclusions: Our preliminary data suggest a relationship between noninvasive NIRS measures and UDS parameters during bladder filling in SCI patients.

Sonographic evaluation of the bladder neck in continent and stress-incontinent women.

PubMed

Schaer, G N; Perucchini, D; Munz, E; Peschers, U; Koechli, O R; Delancey, J O

1999-03-01

To evaluate a new sonographic method to measure depth and width of proximal urethral dilation during coughing and Valsalva maneuver and to report its use in a group of stress-incontinent and continent women. Fifty-eight women were evaluated, 30 with and 28 without stress incontinence proven urodynamically, with a bladder volume of 300 mL and the subjects upright. Urethral pressure profiles at rest were performed with a 10 French microtip pressure catheter. Bladder neck dilation and descent were assessed by perineal ultrasound (5 MHz curved linear array transducer) with the help of ultrasound contrast medium (galactose suspension-Echovist-300), whereas abdominal pressure was assessed with an intrarectal balloon catheter. Statistical analysis used the nonparametric Mann-Whitney test. The depth and diameter of urethral dilation could be measured in all women. During Valsalva, all 30 incontinent women exhibited urethral dilation. One incontinent woman showed dilation only while performing a Valsalva maneuver, not during coughing. In the continent group, 12 women presented dilation during Valsalva and six during coughing. In continent women, dilation was visible only in those who were parous. Nulliparous women did not have dilation during Valsalva or coughing. Bladder neck descent was visible in continent and incontinent women. This method permits quantification of depth and diameter of bladder neck dilation, showing that both incontinent and continent women might have bladder neck dilation and that urinary continence can be established at different locations along the urethra in different women. Parity seems to be a main prerequisite for a proximal urethral defect with bladder neck dilation.

[The role of telomerase activity in non-invasive diagnostics of bladder cancer].

PubMed

Glybochko, P V; Alyaev, J G; Potoldykova, N V; Polyakovsky, K A; Vinarov, A Z; Glukhov, A I; Gordeev, S A

2016-08-01

To evaluate the potentials of determining the telomerase activity (TA) in the cellular material of the urine for noninvasive diagnosis of bladder cancer (BC). Evaluation of TA was performed in the urine of 48 patients with bladder cancer (study group) before and after transurethral resection of the bladder wall (n=38), an open resection of the bladder (n=4), and cystectomy (n=6). TA was also evaluated in 48 tumor tissue samples obtained from these patients during removal of the bladder tumor. Each sample of the tumor tissue was separated into two parts, one of which was subjected to histological examination, and the latter was used to determine the telomerase activity. In all cases, the diagnosis of bladder cancer was confirmed morphologically. Determination of TA in the samples was performed by the modified TRAP-method (telomerase repeat amplification protocol), RT-PCR, PCR, and electrophoresis. As a control, cell material of the urine and tissue in 12 patients with chronic cystitis was investigated. TA before surgery was found in 45 (93.75%) of 48 samples of cellular material of the urine from patients with suspected bladder cancer. BC was histologically verified in all patients in this group. In the postoperative period, TA was not observed in the 48 samples of cellular material of the urine from patients with BC. In the control group of patients with histologically verified cystitis, weak TA was determined only in one sample of cellular material of the urine. The analysis indicates statistically significant predominance of patients with bladder cancer in case of TA in the urine (P=0.001). TA was detected in all samples of tumor tissue. We also analyzed the dependence of TA levels in urine and tissue on the degree of BC differentiation. In patients with highly differentiated BC, mean AT in the cellular materials of the urine was 0,61% (n=15), in patients with moderately differentiated BC - 0.95% (n=23), in patients with low-grade bladder cancer - 1.33% (n=10); in other words, increase in the TA levels with decreasing the degree of differentiation was observed. This finding can be used in the prognosis of the course of disease based on determining the TA level in these patients. Preliminary data indicate the possibility of use of determining the TA in cellular material of the urine for the diagnosis and monitoring of bladder cancer recurrence.

Effects of increased Kindlin-2 expression in bladder cancer stromal fibroblasts.

PubMed

Wu, Jitao; Yu, Cuicui; Cai, Li; Lu, Youyi; Jiang, Lei; Liu, Chu; Li, Yongwei; Feng, Fan; Gao, Zhenli; Zhu, Zhe; Yu, Shengqiang; Yuan, Hejia; Cui, Yuanshan

2017-08-01

Kindlin-2 is a focal adhesion protein highly expressed in bladder cancer stromal fibroblasts. We investigated the prognostic significance of Kindlin-2 in bladder cancer stromal fibroblasts and evaluated the effects of Kindlin-2 on the malignant behaviors of tumor cells. Immunohistochemical staining of 203 paraffin-embedded bladder cancer tissues showed that Kindlin-2 expression correlated with advanced stage, high grade, and relapse of bladder cancer. Kaplan-Meier survival analysis demonstrated that patients exhibiting high Kindlin-2 expression had shorter survival times than those with low Kindlin-2 expression ( p < 0.01). Multivariate analysis revealed that high Kindlin-2 expression leads to poor prognosis in bladder cancer. Using cancer-associated fibroblasts (CAFs) isolated from human bladder cancer tissue, we observed that Kindlin-2 knockdown decreased CAFs activation, resulting in decreased expression of α-smooth muscle actin (α-SMA) and the extracellular matrix protein fibronectin. Kindlin-2 suppression also reduced CAF-induced bladder cancer cell migration and invasion. Moreover, we found that Kindlin-2 activates CAFs and promotes the invasiveness of bladder cancer cells by stimulating TGF-β-induced epithelial-mesenchymal transition. These results support targeting Kindlin-2 and the corresponding activated CAFs in bladder cancer therapy.

SU-F-BRF-09: A Non-Rigid Point Matching Method for Accurate Bladder Dose Summation in Cervical Cancer HDR Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, H; Zhen, X; Zhou, L

2014-06-15

Purpose: To propose and validate a deformable point matching scheme for surface deformation to facilitate accurate bladder dose summation for fractionated HDR cervical cancer treatment. Method: A deformable point matching scheme based on the thin plate spline robust point matching (TPSRPM) algorithm is proposed for bladder surface registration. The surface of bladders segmented from fractional CT images is extracted and discretized with triangular surface mesh. Deformation between the two bladder surfaces are obtained by matching the two meshes' vertices via the TPS-RPM algorithm, and the deformation vector fields (DVFs) characteristic of this deformation is estimated by B-spline approximation. Numerically, themore » algorithm is quantitatively compared with the Demons algorithm using five clinical cervical cancer cases by several metrics: vertex-to-vertex distance (VVD), Hausdorff distance (HD), percent error (PE), and conformity index (CI). Experimentally, the algorithm is validated on a balloon phantom with 12 surface fiducial markers. The balloon is inflated with different amount of water, and the displacement of fiducial markers is benchmarked as ground truth to study TPS-RPM calculated DVFs' accuracy. Results: In numerical evaluation, the mean VVD is 3.7(±2.0) mm after Demons, and 1.3(±0.9) mm after TPS-RPM. The mean HD is 14.4 mm after Demons, and 5.3mm after TPS-RPM. The mean PE is 101.7% after Demons and decreases to 18.7% after TPS-RPM. The mean CI is 0.63 after Demons, and increases to 0.90 after TPS-RPM. In the phantom study, the mean Euclidean distance of the fiducials is 7.4±3.0mm and 4.2±1.8mm after Demons and TPS-RPM, respectively. Conclusions: The bladder wall deformation is more accurate using the feature-based TPS-RPM algorithm than the intensity-based Demons algorithm, indicating that TPS-RPM has the potential for accurate bladder dose deformation and dose summation for multi-fractional cervical HDR brachytherapy. This work is supported in part by the National Natural ScienceFoundation of China (no 30970866 and no 81301940)« less

The use of a gas chromatography-sensor system combined with advanced statistical methods, towards the diagnosis of urological malignancies

PubMed Central

Aggio, Raphael B. M.; de Lacy Costello, Ben; White, Paul; Khalid, Tanzeela; Ratcliffe, Norman M.; Persad, Raj; Probert, Chris S. J.

2016-01-01

Prostate cancer is one of the most common cancers. Serum prostate-specific antigen (PSA) is used to aid the selection of men undergoing biopsies. Its use remains controversial. We propose a GC-sensor algorithm system for classifying urine samples from patients with urological symptoms. This pilot study includes 155 men presenting to urology clinics, 58 were diagnosed with prostate cancer, 24 with bladder cancer and 73 with haematuria and or poor stream, without cancer. Principal component analysis (PCA) was applied to assess the discrimination achieved, while linear discriminant analysis (LDA) and support vector machine (SVM) were used as statistical models for sample classification. Leave-one-out cross-validation (LOOCV), repeated 10-fold cross-validation (10FoldCV), repeated double cross-validation (DoubleCV) and Monte Carlo permutations were applied to assess performance. Significant separation was found between prostate cancer and control samples, bladder cancer and controls and between bladder and prostate cancer samples. For prostate cancer diagnosis, the GC/SVM system classified samples with 95% sensitivity and 96% specificity after LOOCV. For bladder cancer diagnosis, the SVM reported 96% sensitivity and 100% specificity after LOOCV, while the DoubleCV reported 87% sensitivity and 99% specificity, with SVM showing 78% and 98% sensitivity between prostate and bladder cancer samples. Evaluation of the results of the Monte Carlo permutation of class labels obtained chance-like accuracy values around 50% suggesting the observed results for bladder cancer and prostate cancer detection are not due to over fitting. The results of the pilot study presented here indicate that the GC system is able to successfully identify patterns that allow classification of urine samples from patients with urological cancers. An accurate diagnosis based on urine samples would reduce the number of negative prostate biopsies performed, and the frequency of surveillance cystoscopy for bladder cancer patients. Larger cohort studies are planned to investigate the potential of this system. Future work may lead to non-invasive breath analyses for diagnosing urological conditions. PMID:26865331

Replacing cystoscopy by urine markers in the follow-up of patients with low-risk non-muscle-invasive bladder cancer?-An International Bladder Cancer Network project.

PubMed

Schmitz-Dräger, Claudia; Bonberg, Nadine; Pesch, Beate; Todenhöfer, Tilman; Sahin, Sevim; Behrens, Thomas; Brüning, Thomas; Schmitz-Dräger, Bernd J

2016-10-01

Numerous molecular urine markers for the diagnosis of bladder cancer have been developed and evaluated mostly in case-control settings through the past decades. However, despite all efforts none of them has been included into clinical decision-making and guideline recommendations until today. The aim of this retrospective longitudinal analysis was to investigate if a molecular marker might be able to replace cystoscopy as a primary examination in diagnosis and follow-up of patients with pTa grade 1-2 bladder cancer. Totally 36 patients (32 men) with pTa grade 1-2 bladder cancer underwent 232 follow-up examinations including urine analysis, cytology, immunocytology (uCyt+), and urethrocystoscopy (UC). Mean age at study entry was 63 years. Patients were observed through a median follow-up interval of 3.8 years. In summary, 47 Transurethral Resection of Bladder Tumors (TURB) procedures were indicated based upon a positive UC (44) or as re-TURB (3) and 33 tumors (plus 1 case of pTa G0) were histopathologically confirmed. Although uCyt+was positive in 12/13 primary tumors (92.3%), sensitivity dropped to 13/20 (65%) in tumor recurrence presumably because of their smaller size. Urine cytology had a sensitivity and a specificity of 30.3% and 94.9%, respectively, but did not improve the sensitivity of uCyt+alone. If UC was based upon a positive uCyt+test, 8/33 tumors (24.2%) would have been overlooked or diagnosed late. In contrast, 173 UCs (74%) would have been saved and 5 presumably unnecessary TURB procedures would not have been indicated. This longitudinal study suggests a potential of molecular urine tests in replacing cystoscopy in the follow-up of patients with pTa G1-2 bladder cancer. The use of additional markers might further improve sensitivity of urine testing. A prospective randomized study has been initiated to prospectively investigate the performance of a marker panel against UC. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic and Prediction Tools in Bladder Cancer: A Comprehensive Review of the Literature.

PubMed

Kluth, Luis A; Black, Peter C; Bochner, Bernard H; Catto, James; Lerner, Seth P; Stenzl, Arnulf; Sylvester, Richard; Vickers, Andrew J; Xylinas, Evanguelos; Shariat, Shahrokh F

2015-08-01

This review focuses on risk assessment and prediction tools for bladder cancer (BCa). To review the current knowledge on risk assessment and prediction tools to enhance clinical decision making and counseling of patients with BCa. A literature search in English was performed using PubMed in July 2013. Relevant risk assessment and prediction tools for BCa were selected. More than 1600 publications were retrieved. Special attention was given to studies that investigated the clinical benefit of a prediction tool. Most prediction tools for BCa focus on the prediction of disease recurrence and progression in non-muscle-invasive bladder cancer or disease recurrence and survival after radical cystectomy. Although these tools are helpful, recent prediction tools aim to address a specific clinical problem, such as the prediction of organ-confined disease and lymph node metastasis to help identify patients who might benefit from neoadjuvant chemotherapy. Although a large number of prediction tools have been reported in recent years, many of them lack external validation. Few studies have investigated the clinical utility of any given model as measured by its ability to improve clinical decision making. There is a need for novel biomarkers to improve the accuracy and utility of prediction tools for BCa. Decision tools hold the promise of facilitating the shared decision process, potentially improving clinical outcomes for BCa patients. Prediction models need external validation and assessment of clinical utility before they can be incorporated into routine clinical care. We looked at models that aim to predict outcomes for patients with bladder cancer (BCa). We found a large number of prediction models that hold the promise of facilitating treatment decisions for patients with BCa. However, many models are missing confirmation in a different patient cohort, and only a few studies have tested the clinical utility of any given model as measured by its ability to improve clinical decision making. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Preconditioning methods influence tumor property in an orthotopic bladder urothelial carcinoma rat model

PubMed Central

MIYAZAKI, KOZO; MORIMOTO, YUJI; NISHIYAMA, NOBUHIRO; SATOH, HIROYUKI; TANAKA, MASAMITSU; SHINOMIYA, NARIYOSHI; ITO, KEIICHI

2014-01-01

Urothelial carcinoma (UC) is an extremely common type of cancer that occurs in the bladder. It has a particularly high rate of recurrence. Therefore, preclinical studies using animal models are essential to determine effective forms of treatment. In the present study, in order to establish an orthotopic bladder UC animal model with clinical relevance, the effects of preconditioning methods on properties of the developed tumor were evaluated. The bladder cavity was pretreated with phosphate-buffered saline (PBS), acid-base, trypsin (TRY) or poly (L-lysine) (PLL) and then rat UC cells (AY-27) (4×106 cells) were inoculated. The results demonstrated that, two weeks later, the tumorigenic rate (88%) and tumor count (2.3 per rat) were not significantly different among the preconditioning methods, whereas tumor volume and invasion depth into bladder tissue were significantly different. Average tumor volumes were >50 mm3 in the PBS and acid-base-treated groups and <10 mm3 in the TRY- and PLL-treated groups. The percentage of invasive tumors (T2 or more advanced stage) was ∼75% of total tumors in the PBS- and acid-base-treated groups, whereas the percentages were reduced in the TRY- and PLL-treated groups (58 and 32%, respectively). Non-invasive tumors (Ta or T1) accounted for 54% of tumors in the PLL-treated group, which was 2-5-fold higher than the percentages in the remaining groups. Properties of the developed tumor in the rat orthotopic UC model were different depending on preconditioning methods. Therefore, different animal models suitable for a discrete preclinical examination may be established by using the appropriate preconditioning condition. PMID:24649309

Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: a pilot study.

PubMed

Autenrieth, Michael E; Seidl, Christof; Bruchertseifer, Frank; Horn, Thomas; Kurtz, Florian; Feuerecker, Benedikt; D'Alessandria, Calogero; Pfob, Christian; Nekolla, Stephan; Apostolidis, Christos; Mirzadeh, Saed; Gschwend, Jürgen E; Schwaiger, Markus; Scheidhauer, Klemens; Morgenstern, Alfred

2018-07-01

Patients with carcinoma in situ (CIS) of the bladder refractory to bacillus Calmette-Guérin (BCG) treatment are usually treated with cystectomy. Therefore, new treatment options with preservation of the urinary bladder are needed. The objective of the study was to investigate the feasibility, safety and efficacy of a novel targeted alpha-emitter immunotherapy for CIS after BCG treatment failure. A pilot study was conducted in 12 patients (age range 64-86 years, ten men, two women) with biopsy-proven CIS of the bladder refractory to BCG treatment. The patients were treated intravesically with a single instillation (one patient was treated twice) of the alpha-emitter 213 Bi coupled to an anti-EGFR antibody (366-821 MBq). The primary aims of the study were to determine the feasibility of treatment with the 213 Bi-immunoconjugate and evaluation of adverse effects. Therapeutic efficacy was monitored by histological mapping of the urinary bladder 8 weeks after treatment and at different time points thereafter. The study proved that intravesical instillation of the 213 Bi-immunoconjugate targeting EGFR is feasible. No adverse effects were observed and all blood and urine parameters determined remained in their normal ranges. Therapeutic efficacy was considered satisfactory, in that three of the 12 patients showed no signs of CIS 44, 30 and 3 months after treatment. Intravesical instillation of 213 Bi-anti-EGFR monoclonal antibody was well tolerated and showed therapeutic efficacy. Repeated instillation and/or instillation of higher activities of the 213 Bi-immunoconjugate might lead to better therapeutic outcomes. A phase I clinical trial is planned.

Spectrophotometric photodynamic detection involving extracorporeal treatment with hexaminolevulinate for bladder cancer cells in voided urine.

PubMed

Nakai, Yasushi; Ozawa, Toshiyuki; Mizuno, Fumiko; Onishi, Sayuri; Owari, Takuya; Hori, Syunta; Morizawa, Yosuke; Tatsumi, Yosihiro; Miyake, Makito; Tanaka, Nobumichi; Tsuruta, Daisuke; Fujimoto, Kiyohide

2017-11-01

To evaluate the feasibility of hexaminolevulinate (HAL) for the photodynamic detection of cancer cells in voided urine. This study included 50 patients with bladder cancer that was confirmed histologically after transurethral resection (bladder cancer group) and 50 outpatients without a history of urothelial carcinoma or cancer-related findings (no malignancy group). One third of the voided urine samples were incubated with aminolevulinic acid (ALA-treated samples), one third were incubated with HAL (HAL-treated samples), and the remaining samples were incubated without treatment (untreated samples). For detecting cellular protoporphyrin IX levels, the intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated or HAL-treated samples and the untreated samples at 635 nm was calculated. HAL-induced fluorescence cytology (HFC) showed that the difference was significantly higher in patients with high-grade tumors than in those with low-grade tumors (p = 0.0003) and the difference was significantly higher in patients with low-grade tumors than in those without a history of urothelial carcinoma or cancer-related findings (p = 0.021). The areas under the receiver operating characteristic curves of ALA-induced fluorescence cytology (AFC) and HFC were 0.77 and 0.81, respectively. The AUC of HFC was significantly higher than that of AFC (p < 0.0001). The overall sensitivity values for conventional cytology, AFC, and HFC were 49, 74, and 74%, respectively. The overall specificity values for AFC and HFC were 70 and 94%, respectively. Spectrophotometric photodynamic detection involving extracorporeal treatment with HAL for bladder cancer cells in voided urine showed high accuracy. This bladder cancer detection method is easy and cost-effective, and has the potential for clinical use.

Use of a hand-held bladder ultrasound scanner in the assessment of dehydration and monitoring response to treatment in a paediatric emergency department.

PubMed

Enright, Kevin; Beattie, Tom; Taheri, Sepideh

2010-10-01

Dehydration is a common concern in paediatric emergency care. Limited tools are available to assess reduced urine production, which is commonly cited as a reliable marker of dehydration. To evaluate the utility of a hand-held bladder ultrasound scanner in monitoring urine production in children attending the emergency department with suspected dehydration. A prospective pilot study was undertaken on a convenience sample of patients presenting with suspected dehydration. Serial bladder ultrasound scanning was performed to monitor urine output. Dehydration was assessed clinically using the WHO guide to dehydration assessment. Decisions about treatment and admission were made independently of the urine output measurements obtained using the bladder scanner. 45 children were studied. Using the WHO guide, 33 (73%) had mild dehydration, 8 (18%) had moderate dehydration and 4 (9%) had severe dehydration. There was a significant difference in estimated urine production between those admitted and those discharged (0.9±1.2 ml/kg/h vs 1.8±1.5 ml/kg/h, p=0.01) and between those with mild dehydration versus moderate/severe dehydration (2.3±1.5 ml/kg/h vs 0.6±0.7 ml/kg/h, p=0.0011). Urine output had been significantly reduced in those who had received an intravenous fluid bolus compared with those who had not (0.4±0.46 ml/kg/h vs 1.9±1.6 ml/kg/h, p=0.001). The hand-held bladder scanner is a convenient, non-invasive and objective adjunct in the assessment and management of children attending the emergency department with suspected dehydration.

Activation of RAS family genes in urothelial carcinoma.

PubMed

Boulalas, I; Zaravinos, A; Karyotis, I; Delakas, D; Spandidos, D A

2009-05-01

Bladder cancer is the fifth most common malignancy in men in Western society. We determined RAS codon 12 and 13 point mutations and evaluated mRNA expression levels in transitional cell carcinoma cases. Samples from 30 human bladder cancers and 30 normal tissues were analyzed by polymerase chain reaction/restriction fragment length polymorphism and direct sequencing to determine the occurrence of mutations in codons 12 and 13 of RAS family genes. Moreover, we used real-time reverse transcriptase-polymerase chain reaction to evaluate the expression profile of RAS genes in bladder cancer specimens compared to that in adjacent normal tissues. Overall H-RAS mutations in codon 12 were observed in 9 tumor samples (30%). Two of the 9 patients (22%) had invasive bladder cancer and 7 (77%) had noninvasive bladder cancer. One H-RAS mutation (11%) was homozygous and the remaining 89% were heterozygous. All samples were WT for K and N-RAS oncogenes. Moreover, 23 of 30 samples (77%) showed over expression in at least 1 RAS family gene compared to adjacent normal tissue. K and N-RAS had the highest levels of over expression in bladder cancer specimens (50%), whereas 27% of transitional cell carcinomas demonstrated H-RAS over expression relative to paired normal tissues. Our results underline the importance of H-RAS activation in human bladder cancer by codon 12 mutations. Moreover, they provide evidence that increased expression of all 3 RAS genes is a common event in bladder cancer that is associated with disease development.

Medical student responses to clinical procedure teaching in the anatomy lab.

PubMed

Wilson, Donald R; Nava, Pedro B

2010-03-01

the teaching of gross anatomy to first-year medical students has progressed from a 'stand-alone' discipline to one with much clinical emphasis. The curriculum at Loma Linda University School of Medicine has had increasing clinical correlates in recent years. We decided to supplement this with procedure demonstrations early in the course, and measure the student response. clinical procedures were performed on cadavers in the anatomy lab. For example, pleural and pericardial effusions were simulated by placing bags of intravenous fluid in the pleural and pericardial cavities; pneumothorax and tension pneumothorax were simulated using an inflatable rubber bladder. Videos were made and then presented in sequence with gross anatomy lectures. The student response was evaluated with a survey sheet. the Student response was overwhelmingly positive, with all students stating that the presentations made anatomy more relevant, and most indicating that anatomy also became easier to learn. Feedback confirmed that first-year medical students have a strong clinical orientation, which can facilitate both the teaching and learning of gross anatomy. advantages of having clinicians present simulated procedures in the anatomy lab include: heightened student interest; mentoring and modelling for students; introduction to clinical concepts now encountered in basic science examinations; supplementation of the thinning ranks of qualified gross anatomy teachers. The use of intravenous fluid bags and distensible bladders to simulate abnormal collections of fluid and air in body cavities is simple, inexpensive, and can be replicated in any anatomy lab. Blackwell Publishing Ltd 2010.

Implication of androgen receptor in urinary bladder cancer: a critical mini review.

PubMed

Rahmani, Arshad H; Alzohairy, Mohammad; Babiker, Ali Yousif Y; Khan, Amjad A; Aly, Salah M; Rizvi, Moshahid A

2013-01-01

Cancer is probably the most dreaded disease of mankind and the bladder cancer is the fifth most common type of cancer worldwide. It is a major cause of cancer morbidity and mortality. From amongst the bladder cancer, the Transitional Cell Carcinoma (TCC) is the most prevalent cancer of the bladder and accounts for 90% of all bladder cancer cases. Despite such a high prevalence, the molecular mechanism involved in the induction of bladder carcinoma and its progression are poorly understood. Tumorigenesis and tumor progression of bladder carcinomas are thought to result from the accumulation of multiple genetic alterations. The Androgen Receptor (AR) gene is located on the q arm of X chromosome (q11-12) and considered as a ligand-inducible transcription factor that regulates target gene expression. The Androgen plays a vital role in the development and maintenance of the normal urinary bladder. The AR is also involved in the development and progression of urinary bladder carcinoma, which is the most common type of carcinoma. Mutation in AR alters the ligand binding ability that may cause the progression and development of bladder cancer. Tumorigenesis and tumor progression are thought to result from changes in the function of hormonal receptor gene. The accumulation of the changes in AR expressions, determines the tumor's phenotype and ultimately the patient's clinical outcome. The early detection of which may help in management and prediction, how will it behave and respond to the therapeutic regimen. The present review aimed to study the mechanism and alteration of AR gene that play a vital role in the tumorIgenesis of bladder carcinoma.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coen, John J., E-mail: jcoen@harthosp.org; Paly, Jonathan J.; Niemierko, Andrzej

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. Patientsmore » 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.« less

Acute and Chronic Deficits in the Urinary Bladder after Spinal Contusion Injury in the Adult Rat

PubMed Central

Herrera, Juan J.; Haywood-Watson, Ricky J.L.

2010-01-01

Abstract Traumatic spinal cord injury (SCI) permanently alters bladder function in humans. Hematuria and cystitis occur in both human SCI as well as in rodent models of SCI. Others have reported early SCI-dependent disruption to bladder uroepithelial integrity that results in increased permeability to urine and urine-borne substances. This can result in cystitis, or inflammation of the bladder, an ongoing pathological condition present throughout the chronic phase of SCI in humans. The goals of our study were twofold: (1) to begin to examine the inflammatory and molecular changes that occur within the bladder uroepithelium using a clinically-relevant spinal contusion model of injury, and (2) to assess whether these alterations continue into the chronic phase of SCI. Rats received either moderate SCI or sham surgery. Urine was collected from SCI and sham subjects over 7 days or at 7 months to assess levels of excreted proteins. Inflammation in the bladder wall was assessed via biochemical and immunohistochemical methods. Bladder tight junction proteins, mediators of uroepithelial integrity, were also measured in both the acute and chronic phases of SCI. Urine protein and hemoglobin levels rapidly increase following SCI. An SCI-dependent elevation in numbers of neutrophils within the bladder wall peaked at 48 h. Bladder tight junction proteins demonstrate a rapid but transient decrease as early as 2 h post-SCI. Surprisingly, elevated levels of urine proteins and significant deficits in bladder tight junction proteins could be detected in chronic SCI, suggesting that early pathological changes to the bladder may continue throughout the chronic phase of injury. PMID:19891526

Treating acute cystitis with biodegradable micelle-encapsulated quercetin

PubMed Central

Wang, Bi Lan; Gao, Xiang; Men, Ke; Qiu, Jinfeng; Yang, Bowen; Gou, Ma Ling; Huang, Mei Juan; Huang, Ning; Qian, Zhi Yong; Zhao, Xia; Wei, Yu Quan

2012-01-01

Intravesical application of an anti-inflammatory drug is an efficient strategy for acute cystitis therapy. Quercetin (QU) is a potent anti-inflammatory agent; however, its poor water solubility restricts its clinical application. In an attempt to improve water solubility of QU, biodegradable monomethoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) micelles were used to encapsulate QU by self-assembly methods, creating QU/MPEG-PCL micelles. These QU/MPEG-PCL micelles with DL of 7% had a mean particle size of <34 nm, and could release QU for an extended period in vitro. The in vivo study indicated that intravesical application of MPEG-PCL micelles did not induce any toxicity to the bladder, and could efficiently deliver cargo to the bladder. Moreover, the therapeutic efficiency of intravesical administration of QU/MPEG-PCL micelles on acute cystitis was evaluated in vivo. Results indicated that QU/MPEG-PCL micelle treatment efficiently reduced the edema and inflammatory cell infiltration of the bladder in an Escherichia coli-induced acute cystitis model. These data suggested that MPEG-PCL micelle was a candidate intravesical drug carrier, and QU/MPEG-PCL micelles may have potential application in acute cystitis therapy. PMID:22661886

Relationship of PCNA, C-erbB2 and CD44s expression with tumor grade and stage in urothelial carcinomas of the bladder

PubMed Central

Yıldırım, Ayhan; Kösem, Mustafa; Sayar, İlyas; Gelincik, İbrahim; Yavuz, Alparslan; Bozkurt, Aliseydi; Erkorkmaz, Ünal; Bayram, İrfan

2014-01-01

In the present study, the intention was to reveal the relationship of histological grade and stage with c-erbB2, CD44s, and PCNA immunoreactivity in bladder urothelial carcinomas (UC). In our study, we evaluated 46 items of transurethral resection material of patients submitted by YYU Faculty of Medicine, Main Department of Pathology, with a mass revealed in their bladder after clinical and radiological studies at our laboratories and who were diagnosed with urothelial carcinomas. PCNA, c-erbB2, and CD44s were applied in an immunohistochemical manner comprised from nine low-malignant potential papillary urothelial neoplasia, 23 low-grade papillary urothelial carcinoma, and 14 high-grade papillary urothelial carcinoma. Immunostaining was scored according to the percentage of positive cells. The immunohistochemical study demonstrated that the c-erbB2 and PCNA staining ratio increased when an increase occurred in stage and grade. The CD44s staining ratio decreased. C-erbB2, PCNA, and CD44s appear to be a useful marker in the assessment of the prognosis and treatment options in urothelial carcinomas. PMID:25035774

Identification of Methylated Genes Associated with Aggressive Bladder Cancer

PubMed Central

Marsit, Carmen J.; Houseman, E. Andres; Christensen, Brock C.; Gagne, Luc; Wrensch, Margaret R.; Nelson, Heather H.; Wiemels, Joseph; Zheng, Shichun; Wiencke, John K.; Andrew, Angeline S.; Schned, Alan R.; Karagas, Margaret R.; Kelsey, Karl T.

2010-01-01

Approximately 500,000 individuals diagnosed with bladder cancer in the U.S. require routine cystoscopic follow-up to monitor for disease recurrences or progression, resulting in over $2 billion in annual expenditures. Identification of new diagnostic and monitoring strategies are clearly needed, and markers related to DNA methylation alterations hold great promise due to their stability, objective measurement, and known associations with the disease and with its clinical features. To identify novel epigenetic markers of aggressive bladder cancer, we utilized a high-throughput DNA methylation bead-array in two distinct population-based series of incident bladder cancer (n = 73 and n = 264, respectively). We then validated the association between methylation of these candidate loci with tumor grade in a third population (n = 245) through bisulfite pyrosequencing of candidate loci. Array based analyses identified 5 loci for further confirmation with bisulfite pyrosequencing. We identified and confirmed that increased promoter methylation of HOXB2 is significantly and independently associated with invasive bladder cancer and methylation of HOXB2, KRT13 and FRZB together significantly predict high-grade non-invasive disease. Methylation of these genes may be useful as clinical markers of the disease and may point to genes and pathways worthy of additional examination as novel targets for therapeutic treatment. PMID:20808801

Identification of methylated genes associated with aggressive bladder cancer.

PubMed

Marsit, Carmen J; Houseman, E Andres; Christensen, Brock C; Gagne, Luc; Wrensch, Margaret R; Nelson, Heather H; Wiemels, Joseph; Zheng, Shichun; Wiencke, John K; Andrew, Angeline S; Schned, Alan R; Karagas, Margaret R; Kelsey, Karl T

2010-08-23

Approximately 500,000 individuals diagnosed with bladder cancer in the U.S. require routine cystoscopic follow-up to monitor for disease recurrences or progression, resulting in over $2 billion in annual expenditures. Identification of new diagnostic and monitoring strategies are clearly needed, and markers related to DNA methylation alterations hold great promise due to their stability, objective measurement, and known associations with the disease and with its clinical features. To identify novel epigenetic markers of aggressive bladder cancer, we utilized a high-throughput DNA methylation bead-array in two distinct population-based series of incident bladder cancer (n = 73 and n = 264, respectively). We then validated the association between methylation of these candidate loci with tumor grade in a third population (n = 245) through bisulfite pyrosequencing of candidate loci. Array based analyses identified 5 loci for further confirmation with bisulfite pyrosequencing. We identified and confirmed that increased promoter methylation of HOXB2 is significantly and independently associated with invasive bladder cancer and methylation of HOXB2, KRT13 and FRZB together significantly predict high-grade non-invasive disease. Methylation of these genes may be useful as clinical markers of the disease and may point to genes and pathways worthy of additional examination as novel targets for therapeutic treatment.

Urinary tract infections in children.

PubMed

Sedberry-Ross, Sherry; Pohl, Hans G

2008-03-01

Urinary tract infections can be a significant source of morbidity in the pediatric population. The mainstay of evaluating urinary tract infections in children has been physical examination, urinalysis and culture, and renal and bladder sonography and contrast cystography. However, novel clinical paradigms now consider the importance of various risk factors, such as bacterial virulence and antibiotic-resistance patterns, elimination disorders, and the role of innate immunity and inflammation in determining the likelihood of renal cortical scarring.

Overactive bladder is a negative predictor of achieving continence after robot-assisted radical prostatectomy.

PubMed

Yamada, Yuta; Fujimura, Tetsuya; Fukuhara, Hiroshi; Sugihara, Toru; Miyazaki, Hideyo; Nakagawa, Tohru; Kume, Haruki; Igawa, Yasuhiko; Homma, Yukio

2017-10-01

To investigate predictors of continence outcomes after robot-assisted radical prostatectomy. Clinical records of 272 patients who underwent robot-assisted radical prostatectomy were investigated. Preoperative Overactive Bladder Symptom Score, International Prostate Symptom Score and clinicopathological factors were investigated, and relationships between factors and recovery of continence after robot-assisted radical prostatectomy were assessed. The presence of overactive bladder was defined as having urgency for more than once a week and having ≥3 points according to the Overactive Bladder Symptom Score. Age (≤66 years) was significantly associated with continence within 6 months after robot-assisted radical prostatectomy (P = 0.033). The absence of overactive bladder and lower Overactive Bladder Symptom Score (<3) were significantly associated with recovery of continence within 12 months after surgery (both variables P = 0.009). In terms of achieving recovery of continence after robot-assisted radical prostatectomy, Kaplan-Meier curves showed earlier recovery in "age ≤66 years," "prostate weight ≤40 g" and "overactive bladder symptom score <3" (P = 0.0072, 0.0172 and 0.0140, respectively). Multivariate analysis showed that the presence of overactive bladder was an independent negative predictor for recovery of continence within 12 months after surgery (P = 0.019). The presence of baseline overactive bladder seems to represent an independent negative predictor for recovery of continence at 12 months after robot-assisted radical prostatectomy. © 2017 The Japanese Urological Association.

Peristeen anal irrigation as a substitute for the MACE procedure in children who are in need of reconstructive bladder surgery

PubMed Central

Alenezi, Husain; Alhazmi, Hamdan; Trbay, Mahmoud; Khattab, Amna; Neel, Khalid Fouda

2014-01-01

Introduction: We evaluate the efficacy of the Peristeen (Coloplast A/S, Kokkedal, Denmark) transanal irrigation (TAI) system, as a stool cleansing mechanism, to gain stool continence in children who need reconstructive bladder surgery and have fecal incontinence. Methods: We prospectively evaluated children with neuropathic bladder and bowel dysfunction who were intended for reconstructive bladder surgery and the Malone antegrade continence enema (MACE) procedure. All patients were started on the Peristeen TAI system at least 3 months before surgery to assess their response. Each patient’s bowel function, frequency of using the system, satisfaction (and that of their parents) and diaper independency were evaluated before and after reconstructive surgery. Results: We included 18 patients (11 female, 7 male) who were evaluated from April 2006 to the present. The mean age of the group was 7.6 years (range: 4–15). Fifteen patients (83.3%) showed complete dryness from stools. Of the 15 patients, 8 (53.3%) were able to be diaper-free, while 6 continued wearing diapers due to fear of soiling and 1 due to urinary incontinence. The patients underwent reconstructive bladder surgery and continued to use the Peristeen TAI system with the same results postoperatively. The main limitation of this study is the small number of patients included, although this is a very specific patient group. Conclusion: Our initial results suggest that the Peristeen TAI system is a successful conservative substitute for the MACE procedure in children who require reconstructive bladder surgery. PMID:24454594

Quantitative elasticity measurement of urinary bladder wall using laser-induced surface acoustic waves.

PubMed

Li, Chunhui; Guan, Guangying; Zhang, Fan; Song, Shaozhen; Wang, Ruikang K; Huang, Zhihong; Nabi, Ghulam

2014-12-01

The maintenance of urinary bladder elasticity is essential to its functions, including the storage and voiding phases of the micturition cycle. The bladder stiffness can be changed by various pathophysiological conditions. Quantitative measurement of bladder elasticity is an essential step toward understanding various urinary bladder disease processes and improving patient care. As a nondestructive, and noncontact method, laser-induced surface acoustic waves (SAWs) can accurately characterize the elastic properties of different layers of organs such as the urinary bladder. This initial investigation evaluates the feasibility of a noncontact, all-optical method of generating and measuring the elasticity of the urinary bladder. Quantitative elasticity measurements of ex vivo porcine urinary bladder were made using the laser-induced SAW technique. A pulsed laser was used to excite SAWs that propagated on the bladder wall surface. A dedicated phase-sensitive optical coherence tomography (PhS-OCT) system remotely recorded the SAWs, from which the elasticity properties of different layers of the bladder were estimated. During the experiments, series of measurements were performed under five precisely controlled bladder volumes using water to estimate changes in the elasticity in relation to various urinary bladder contents. The results, validated by optical coherence elastography, show that the laser-induced SAW technique combined with PhS-OCT can be a feasible method of quantitative estimation of biomechanical properties.

Secondary bladder amyloidosis with familial Mediterranean fever in a living donor kidney transplant recipient: a case report.

PubMed

Imamura, Sentaro; Narita, Shintaro; Nishikomori, Ryuta; Tsuruta, Hiroshi; Numakura, Kazuyuki; Maeno, Atsushi; Saito, Mitsuru; Inoue, Takamitsu; Tsuchiya, Norihiko; Nanjo, Hiroshi; Heike, Toshio; Satoh, Shigeru; Habuchi, Tomonori

2016-10-19

Secondary bladder amyloidosis is an extremely rare disease, resulting from a chronic systematic inflammatory disorder associated with amyloid deposits. Although uncommon in Japan, familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent episodes of fever of short duration and serositis and is frequently associated with systemic amyloidosis. Here, we present a case of a Japanese patient complaining of fever and macroscopic hematuria after a living donor renal transplantation. Consequently, he was diagnosed with secondary bladder amyloidosis with FMF. A 64-year-old Japanese male received a living ABO-incompatible kidney transplant from his wife. The postoperative clinical course was normal, and the patient was discharged 21 days after the transplantation with a serum creatinine level of 0.78 mg/dl. The patient frequently complained of general fatigue and fever of unknown origin. Six months later, the patient presented with continuous general fatigue, macroscopic hematuria, and fever. Cystoscopic examination of the bladder showed an edematous region with bleeding, and a transurethral biopsy revealed amyloid deposits. His wife stated that the patient had a recurrent high fever since the age of 40 years and that his younger brother was suspected to have a familial autoinflammatory syndrome; thus, the patient was also suspected to have a familial autoinflammatory syndrome. Based on his brother's medical history and the genetic tests, which showed a homozygous mutation (M694V/M694V) for the Mediterranean fever protein, he was diagnosed with FMF. Although colchicine treatment for FMF was planned, the patient had an untimely death due to heart failure. We re-evaluated the pathological findings of the various tissue biopsies obtained during the treatment after the renal transplantation. Immunohistochemistry revealed amyloid deposits in the bladder region, renal allograft, and myocardium and the condition was diagnosed as AA amyloidosis associated with FMF. We presented a case of systemic amyloidosis with FMF, involving the bladder region, myocardium, and renal allograft, diagnosed after renal transplantation. Bladder amyloidosis should be considered in patients with macroscopic hematuria, particularly in the kidney transplant recipients with idiopathic chronic renal disease. Diagnosis of secondary bladder amyloidosis may result in the early detection of underlying diseases, which may contribute to patient prognosis.

Pathogenesis of Bladder Calculi in the Presence of Urinary Stasis

PubMed Central

Childs, M. Adam; Mynderse, Lance A.; Rangel, Laureano J.; Wilson, Torrence M.; Lingeman, James E.; Krambeck, Amy E.

2013-01-01

Purpose Although minimal evidence exists, bladder calculi in men with benign prostatic hyperplasia are thought to be secondary to bladder outlet obstruction induced urinary stasis. We performed a prospective, multi-institutional clinical trial to determine whether metabolic differences were present in men with and without bladder calculi undergoing surgical intervention for benign prostatic hyperplasia induced bladder outlet obstruction. Materials and Methods Men who elected surgery for bladder outlet obstruction secondary to benign prostatic hyperplasia with and without bladder calculi were assessed prospectively and compared. Men without bladder calculi retained more than 150 ml urine post-void residual urine. Medical history, serum electrolytes and 24-hour urinary metabolic studies were compared. Results Of the men 27 had bladder calculi and 30 did not. Bladder calculi were associated with previous renal stone disease in 36.7% of patients (11 of 30) vs 4% (2 of 27) and gout was associated in 13.3% (4 of 30) vs 0% (0 of 27) (p <0.01 and 0.05, respectively). There was no observed difference in the history of other medical conditions or in serum electrolytes. Bladder calculi were associated with lower 24-hour urinary pH (median 5.9 vs 6.4, p = 0.02), lower 24-hour urinary magnesium (median 106 vs 167 mmol, p = 0.01) and increased 24-hour urinary uric acid supersaturation (median 2.2 vs 0.6, p <0.01). Conclusions In this comparative prospective analysis patients with bladder outlet obstruction and benign prostatic hyperplasia with bladder calculi were more likely to have a renal stone disease history, low urinary pH, low urinary magnesium and increased urinary uric acid supersaturation. These findings suggest that, like the pathogenesis of nephrolithiasis, the pathogenesis of bladder calculi is likely complex with multiple contributing lithogenic factors, including metabolic abnormalities and not just urinary stasis. PMID:23159588

The morphological regeneration and functional restoration of bladder defects by a novel scaffold and adipose-derived stem cells in a rat augmentation model.

PubMed

Wang, Qiong; Xiao, Dong-Dong; Yan, Hao; Zhao, Yang; Fu, Shi; Zhou, Juan; Wang, Zhong; Zhou, Zhe; Zhang, Ming; Lu, Mu-Jun

2017-06-24

Due to the multilineage differentiation ability and paracrine role of adipose-derived stem cells (ASCs) for bladder defect repair, various scaffolds have been applied in combination with ASCs to promote bladder regeneration and restore bladder function. However, the low survival rate of ASCs and the difficulty of promoting bladder functional recovery are still unsolved. To explore these problems, we investigated the feasibility of a novel scaffold seeded with ASCs in a rat model of bladder augmentation. A novel autologous myofibroblast (AM)-silk fibroin (SF) scaffold was harvested after subcutaneously prefabricating the bladder acellular matrix grafts (BAMG) and SF by removing the BAMG. The AM-SF scaffolds were then seeded with ASCs (AM-SF-ASCs). Fifty percent supratrigonal cystectomies were performed followed by augmenting the cystectomized defects with AM-SF scaffolds or AM-SF-ASCs. The histological and functional assessments of bladders were performed 2, 4, and 12 weeks after surgery while the ASCs were tracked in vivo. For bladder tissue regeneration, immunofluorescence analysis revealed that AM-SF-ASCs (the experimental group) promoted better morphological regeneration of the urothelium, vessels, bladder smooth muscle, and nerve than AM-SF scaffolds (the control group). Regarding functional restoration, the AM-SF-ASC group exhibited higher bladder compliance and relatively normal micturition pattern compared to the AM-SF group. In addition, a certain number of surviving ASCs could be found in vivo 12 weeks after implantation, and some of them had differentiated into smooth muscle cells. The AM-SF scaffolds with ASCs could rapidly promote bladder morphological regeneration and improved bladder urinary function. In addition, the bag-shaped structure of the AM-SF scaffold can improve the survival of ASCs for at least 12 weeks. This strategy of AM-SF-ASCs has a potential to repair large-scale bladder defects in the clinic in the future.

Systematic reviews of bladder training and voiding programmes in adults: a synopsis of findings from data analysis and outcomes using metastudy techniques.

PubMed

Roe, Brenda; Ostaszkiewicz, Joan; Milne, Jill; Wallace, Sheila

2007-01-01

This paper reports a comparison of the data analysis and outcomes from four Cochrane systematic reviews on bladder training and voiding programmes for the management of urinary incontinence using metastudy descriptive techniques to inform clinical practice, generate new ideas and identify future research directions. Bladder training is used for cognitively and physically able adults to regain continence by increasing the time interval between voids. Prompted voiding, habit retraining and timed voiding, collectively known as voiding programmes, are generally used for people with cognitive and physical impairments in institutional settings. Bladder training and voiding programmes feature as common clinical practice for the management of urinary incontinence. A synopsis of four Cochrane systematic reviews that included randomized controlled trials on bladder training, prompted voiding, habit retraining and timed voiding was undertaken using metastudy techniques for the synthesis of qualitative research, and has provided a discursive comparison and contrast of the meta-data analysis and outcomes of these reviews. Frequency of incontinence was the most common and constant outcome measure of effectiveness in the reviews. Limited data were available on other health outcomes, change in dependency status, quality of life and cost-effectiveness. The systematic review on bladder training included different types of urinary incontinence, whereas those on voiding programmes did not differentiate the type of incontinence. There is evidence on the effectiveness of bladder training but long-term follow up studies are needed. Evidence on the effectiveness of voiding programmes is limited and not available for many outcomes. Future research needs to consider the theory underpinning interventions for bladder training and voiding programmes for urinary incontinence and should incorporate recognized 'quality' research designs, established outcomes and long-term follow up. It is unclear whether health outcomes for people with comorbidities, cognitive and physical impairments will improve if extensive diagnostic and assessment investigations are undertaken.

Recommendations for future development of contractility and obstruction nomograms for women. ICI-RS 2014.

PubMed

Rademakers, Kevin; Apostolidis, Apostolos; Constantinou, Christos; Fry, Christopher; Kirschner-Hermanns, Ruth; Oelke, Matthias; Parsons, Brian; Nelson, Pierre; Valentini, Françoise; Gammie, Andrew

2016-02-01

At present, existing bladder outlet obstruction (BOO) nomograms for women are still not universally accepted. Moreover, only limited information is available regarding bladder contractility in women. The aim is to present the discussions and recommendations from the think tank session "Can we construct and validate contractility and obstruction nomograms for women?" held at the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK. An overview of clinical significance, bladder mechanics and modelling, lack of existing nomograms for women, and development of new nomograms were presented and discussed in a multidisciplinary think tank session. This think tank session was based on a collaboration between physicians, engineers, and researchers and consensus was achieved on future research initiatives. Based on the think tank discussion, the ICI-RS panel put forward the following recommendations: the need to acquire normative age-matched data in women to define "normal" and "pathological" values of urodynamic parameters; the inclusion of additional clinical data in new nomograms and the use of this extra dimension to develop clinically applicable nomograms for female BOO and contractility; and finally, the need to take into account the variability of BOO in women when developing female bladder contractility nomograms. © 2016 Wiley Periodicals, Inc.

[Tissue engineering of urinary bladder using acellular matrix].

PubMed

Glybochko, P V; Olefir, Yu V; Alyaev, Yu G; Butnaru, D V; Bezrukov, E A; Chaplenko, A A; Zharikova, T M

2017-04-01

Tissue engineering has become a new promising strategy for repairing damaged organs of the urinary system, including the bladder. The basic idea of tissue engineering is to integrate cellular technology and advanced bio-compatible materials to replace or repair tissues and organs. of the study is the objective reflection of the current trends and advances in tissue engineering of the bladder using acellular matrix through a systematic search of preclinical and clinical studies of interest. Relevant studies, including those on methods of tissue engineering of urinary bladder, was retrieved from multiple databases, including Scopus, Web of Science, PubMed, Embase. The reference lists of the retrieved review articles were analyzed for the presence of the missing relevant publications. In addition, a manual search for registered clinical trials was conducted in clinicaltrials.gov. Following the above search strategy, a total of 77 eligible studies were selected for further analysis. Studies differed in the types of animal models, supporting structures, cells and growth factors. Among those, studies using cell-free matrix were selected for a more detailed analysis. Partial restoration of urothelium layer was observed in most studies where acellular grafts were used for cystoplasty, but no the growth of the muscle layer was observed. This is the main reason why cellular structures are more commonly used in clinical practice.

α-Information Based Registration of Dynamic Scans for Magnetic Resonance Cystography

PubMed Central

Han, Hao; Lin, Qin; Li, Lihong; Duan, Chaijie; Lu, Hongbing; Li, Haifang; Yan, Zengmin; Fitzgerald, John

2015-01-01

To continue our effort on developing magnetic resonance (MR) cystography, we introduce a novel non–rigid 3D registration method to compensate for bladder wall motion and deformation in dynamic MR scans, which are impaired by relatively low signal–to–noise ratio in each time frame. The registration method is developed on the similarity measure of α–information, which has the potential of achieving higher registration accuracy than the commonly-used mutual information (MI) measure for either mono-modality or multi-modality image registration. The α–information metric was also demonstrated to be superior to both the mean squares and the cross-correlation metrics in multi-modality scenarios. The proposed α–registration method was applied for bladder motion compensation via real patient studies, and its effect to the automatic and accurate segmentation of bladder wall was also evaluated. Compared with the prevailing MI-based image registration approach, the presented α–information based registration was more effective to capture the bladder wall motion and deformation, which ensured the success of the following bladder wall segmentation to achieve the goal of evaluating the entire bladder wall for detection and diagnosis of abnormality. PMID:26087506

Health-Related Quality of Life after Cystectomy and Urinary Diversion for Bladder Cancer

PubMed Central

Shih, Cheryl; Porter, Michael P.

2011-01-01

With multiple options for urinary diversion after radical cystectomy for bladder cancer that have comparable cancer control and complication rates, health-related quality of life (HRQOL) has become an important consideration. This article reviews the methods for defining HRQOL, the challenges in measuring HRQOL in bladder cancer, and the literature comparing HRQOL after various methods of urinary diversion. Recent contributions include the validation of HRQOL instruments specific to bladder cancer and the publication of several prospective studies measuring HRQOL outcomes after cystectomy and urinary diversion. There is no convincing evidence from existing literature that any particular method of urinary diversion offers superior HRQOL outcomes. Rather, there is growing evidence that good HRQOL can be achieved with patient education and consideration of each patient's clinical and psychosocial situation. Future research should utilize the validated bladder cancer specific HRQOL instruments and perhaps explore the impact of preoperative counseling on postoperative HRQOL. PMID:21826139

The Epigenetics of Kidney Cancer and Bladder Cancer

PubMed Central

Hoffman, Amanda M.; Cairns, Paul

2012-01-01

Summary This review focuses on the epigenetic alterations of aberrant promoter hypermethylation of genes, histone modifications or RNA interference in cancer cells. The current knowledge of hypermethylation of allele(s) in classical tumor suppressor genes in inherited and sporadic cancer, candidate tumor suppressor and other cancer genes is summarized gene by gene. Global and array-based studies of tumor cell hypermethylation are discussed. The importance of standardization of scoring of the methylation status of a gene is highlighted. The histone marks associated with hypermethylated genes, and the microRNAs with dysregulated expression, in kidney or bladder tumor cells are also discussed. Kidney cancer has the highest mortality rate of the genitourinary cancers. There are management issues with the high recurrence rate of superficial bladder cancer while muscle invasive bladder cancer has a poor prognosis. These clinical problems are the basis for translational application of gene hypermethylation to the diagnosis and prognosis of kidney and bladder cancer. PMID:22126150

Impact of dosimetric and clinical parameters on clinical side effects in cervix cancer patients treated with 3D pulse-dose-rate intracavitary brachytherapy.

PubMed

Levitchi, Mihai; Charra-Brunaud, Claire; Quetin, Philippe; Haie-Meder, Christine; Kerr, Christine; Castelain, Bernard; Delannes, Martine; Thomas, Laurence; Desandes, Emmanuel; Peiffert, Didier

2012-06-01

To assess the association between dosimetric/clinical parameters and gastrointestinal/urinary grade 2-4 side effects in cervix cancer patients treated with 3D pulse dose rate brachytherapy. Three hundred and fifty-two patients received brachytherapy associated with external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent surgery. The doses for the most exposed 2, and 0.1 cm(3) (D(2cc) and D(0.1cc)) volumes of the rectum and bladder as well as bladder ICRU point dose (D(ICRU)) were converted into isoeffective doses in 2-Gy fractions. The clinical parameters analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery, FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were defined separately for patients treated with EBRT and brachytherapy (Group 1) and with preoperative brachytherapy (Group 2). The median follow-up was 23.4months. In Group 1 a significant predictive value of rectum D(0.1cc) and D(2cc), bladder D(0.1cc) and D(ICRU) for gastrointestinal and urinary toxicity was found using as cutoff 83, 68, 109 and 68Gy(α)(/)(β)(3). In Group 2 a significant predictive value of bladder D(0.1cc), D(2cc) and D(ICRU) for urinary toxicity was found using as cutoff 141, 91 and 67Gy(α)(/)(β)(3), but not for the rectum D(0.1cc) and D(2cc); smoking had a significant predictive value on urinary toxicity. For patients treated with brachytherapy and EBRT, rectum D(0.1cc) and D(2cc) and bladder D(0.1cc) and D(ICRU) had a predictive value for toxicity. For patients treated with preoperative brachytherapy, bladder D(0.1cc), D(2cc) and D(ICRU) and smoking had a predictive value for urinary toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Biodistribution and Safety Assessment of Bladder Cancer Specific Recombinant Oncolytic Adenovirus in Subcutaneous Xenografts Tumor Model in Nude Mice

PubMed Central

Wang, Fang; Wang, Zhiping; Tian, Hongwei; Qi, Meijiao; Zhai, Zhenxing; Li, Shuwen; Li, Renju; Zhang, Hongjuan; Wang, Wenyun; Fu, Shenjun; Lu, Jianzhong; Rodriguez, Ronald; Guo, Yinglu; Zhou, Liqun

2012-01-01

Background The previous works about safety evaluation for constructed bladder tissue specific adenovirus are poorly documented. Thus, we investigated the biodistribution and body toxicity of bladder specific oncolytic adenovirus Ad-PSCAE-UPII-E1A (APU-E1A) and Ad-PSCAE-UPII-E1A-AR (APU-E1A-AR), providing meaningful information prior to embarking on human clinical trials. Materials and Method Conditionally replicate recombinant adenovirus (CRADs) APU-E1A, APU-EIA-AR were constructed with bladder tissue specific Uroplakin II (UP II) promoter to induce the expression of Ad5E1A gene and E1A-AR fusing gene, and PSCAE was inserted at upstream of promoter to enhance the function of promoter. Based on the cytopathic and anti-tumor effect of bladder cancer, these CRADs were intratumorally injected into subcutaneous xenografts tumor in nude mice. We then determined the toxicity through general health and behavioral assessment, hepatic and hematological toxicity evaluation, macroscopic and microscopic postmortem analyses. The spread of the transgene E1A of adenovirus was detected with RT-PCR and Western blot. Virus replication and distribution were examined with APU-LUC administration and Luciferase Assay. Results General assessment and body weight of the animals did not reveal any alteration in general behavior. The hematological alterations of groups which were injected with 5×108 pfu or higher dose (5×109 pfu) of APU-E1A and APU-E1A-AR showed no difference in comparison with PBS group, and only slight increased transaminases in contrast to PBS group at 5×109 pfu of APU-E1A and APU-E1A-AR were observed. E1A transgene did not disseminate to organs outside of xenograft tumor. Virus replication was not detected in other organs beside tumor according to Luciferase Assay. Conclusions Our study showed that recombinant adenovirus APU-E1A-AR and APU-E1A appear safe with 5×107 pfu and 5×108 pfu intratumorally injection in mice, without any discernable effects on general health and behavior. PMID:22384806

Biodistribution and safety assessment of bladder cancer specific recombinant oncolytic adenovirus in subcutaneous xenografts tumor model in nude mice.

PubMed

Wang, Fang; Wang, Zhiping; Tian, Hongwei; Qi, Meijiao; Zhai, Zhenxing; Li, Shuwen; Li, Renju; Zhang, Hongjuan; Wang, Wenyun; Fu, Shenjun; Lu, Jianzhong; Rodriguez, Ronald; Guo, Yinglu; Zhou, Liqun

2012-04-01

The previous works about safety evaluation for constructed bladder tissue specific adenovirus are poorly documented. Thus, we investigated the biodistribution and body toxicity of bladder specific oncolytic adenovirus Ad-PSCAE-UPII-E1A (APU-E1A) and Ad-PSCAE-UPII-E1A-AR (APU-E1A-AR), providing meaningful information prior to embarking on human clinical trials. Conditionally replicate recombinant adenovirus (CRADs) APU-E1A, APU-EIA-AR were constructed with bladder tissue specific UroplakinII(UPII) promoter to induce the expression of Ad5E1A gene and E1A-AR fusing gene, and PSCAE was inserted at upstream of promoter to enhance the function of promoter. Based on the cytopathic and anti-tumor effect of bladder cancer, these CRADs were intratumorally injected into subcutaneous xenografts tumor in nude mice. We then determined the toxicity through general health and behavioral assessment, hepatic and hematological toxicity evaluation, macroscopic and microscopic postmortem analyses. The spread of the transgene E1A of adenovirus was detected with RT-PCR and Western blot. Virus replication and distribution were examined with APU-LUC administration and Luciferase Assay. General assessment and body weight of the animals did not reveal any alteration in general behavior. The hematological alterations of groups which were injected with 5x10(8) pfu or higher dose (5x10(9) pfu) of APU-E1A and APU-E1A-AR showed no difference in comparison with PBS group, and only slight increased transaminases in contrast to PBS group at 5x10(9) pfu of APU-E1A and APU-E1A-AR were observed. E1A transgene did not disseminate to organs outside of xenograft tumor. Virus replication was not detected in other organs beside tumor according to Luciferase Assay. Our study showed that recombinant adenovirus APU-E1A-AR and APU-E1A appear safe with 5x10(7) pfu and 5x10(8) pfu intratumorally injection in mice, without any discernable effects on general health and behavior.

Metal artifact reduction software used with abdominopelvic dual-energy CT of patients with metal hip prostheses: assessment of image quality and clinical feasibility.

PubMed

Han, Seung Chol; Chung, Yong Eun; Lee, Young Han; Park, Kwan Kyu; Kim, Myeong Jin; Kim, Ki Whang

2014-10-01

The objective of our study was to determine the feasibility of using Metal Artifact Reduction (MAR) software for abdominopelvic dual-energy CT in patients with metal hip prostheses. This retrospective study included 33 patients (male-female ratio, 19:14; mean age, 63.7 years) who received total hip replacements and 20 patients who did not have metal prostheses as the control group. All of the patients underwent dual-energy CT. The quality of the images reconstructed using the MAR algorithm and of those reconstructed using the standard reconstruction was evaluated in terms of the visibility of the bladder wall, pelvic sidewall, rectal shelf, and bone-prosthesis interface and the overall diagnostic image quality with a 4-point scale. The mean and SD attenuation values in Hounsfield units were measured in the bladder, pelvic sidewall, and rectal shelf. For validation of the MAR interpolation algorithm, pelvis phantoms with small bladder "lesions" and metal hip prostheses were made, and images of the phantoms both with and without MAR reconstruction were evaluated. Image quality was significantly better with MAR reconstruction than without at all sites except the rectal shelf, where the image quality either had not changed or had worsened after MAR reconstruction. The mean attenuation value was changed after MAR reconstruction to its original expected value at the pelvic sidewall (p < 0.001) and inside the bladder (p < 0.001). The SD attenuation value was significantly decreased after MAR reconstruction at the pelvic sidewall (p = 0.019) but did not show significant differences at the bladder (p = 0.173) or rectal shelf (p = 0.478). In the phantom study, all lesions obscured by metal artifacts on the standard reconstruction images were visualized after MAR reconstruction; however, new artifacts had developed in other parts of the MAR reconstruction images. The use of MAR software with dual-energy CT decreases metal artifacts and increases diagnostic confidence in the assessment of the pelvic cavity but also introduces new artifacts that can obscure pelvic structures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyasaka, Y; Kadoya, N; Ito, K

Purpose: Accurate deformable image registration (DIR) between external beam radiotherapy (EBRT) and HDR brachytherapy (BT) CT images in cervical cancer is challenging. DSC has been evaluated only on the basis of the consistency of the structure, and its use does not guarantee an anatomically reasonable deformation. We evaluate the DIR accuracy for cervical cancer with DSC and anatomical landmarks using a 3D-printed pelvis phantom. Methods: A 3D-printed, deformable female pelvis phantom was created on the basis of the patient’s CT image. Urethane and silicon were used as materials for creating the uterus and bladder, respectively, in the phantom. We performedmore » DIR in two cases: case-A with a full bladder (170 ml) in both the EBRT and BT images and case-B with a full bladder in the BT image and a half bladder (100 ml) in the EBRT image. DIR was evaluated using DSCs and 70 uterus and bladder landmarks. A Hybrid intensity and structure DIR algorithm with two settings (RayStation) was used. Results: In the case-A, DSCs of the intensity-based DIR were 0.93 and 0.85 for the bladder and uterus, respectively, whereas those of hybrid-DIR were 0.98 and 0.96, respectively. The mean landmark error values of intensity-based DIR were 0.73±0.29 and 1.70±0.19 cm for the bladder and uterus, respectively, whereas those of Hybrid-DIR were 0.43±0.33 and 1.23±0.25 cm, respectively. In both cases, the Hybrid-DIR accuracy was better than the intensity-based DIR accuracy for both evaluation methods. However, for several bladder landmarks, the Hybrid-DIR landmark errors were larger than the corresponding intensity-based DIR errors (e.g., 2.26 vs 1.25 cm). Conclusion: Our results demonstrate that Hybrid-DIR can perform with a better accuracy than the intensity-based DIR for both DSC and landmark errors; however, Hybrid-DIR shows a larger landmark error for some landmarks because the technique focuses on both the structure and intensity.« less

[Post-traumatic complication of trans-appendiceal cystostomy: urinary peritonitis].

PubMed

Landry, J L; Dubois, R; Chaffange, P; Pelizzo, G; Dodat, H

2001-04-01

Two children who had undergone a transappendicular urinary diversion (type Mitrofanoff) developed bladder rupture, one following abdominal trauma, 4 months after the operation and the other following traumatic self-catheterization at 4 years. The clinical history and standard radiological examinations (ultrasonography, cystography) confirmed the diagnosis of urinary peritonitis. Emergency surgical repair was possible in both cases with an uneventful postoperative course. This serious and rare complication requires emergency surgery and justifies rigorous selection of children suitable for this type of diversion giving preference to increased bladder neck resistance over bladder neck closure.

Update on tolterodine extended-release for treatment of overactive bladder

PubMed Central

Omotosho, Tola; Chen, Chi Chiung Grace

2010-01-01

Overactive bladder is a prevalent condition which negatively impacts quality of life and puts a significant economical burden on society. First-line therapy often includes pharmacotherapy with antimuscarinic medications, and numerous research studies have demonstrated that tolterodine extended-release (ER) is an efficacious and tolerable formulation of this class of medication. This review provides an update on the clinical use of tolterodine ER, detailing the current literature on its efficacy, tolerability, adverse effects, and comparability with other commonly prescribed medications for the treatment of overactive bladder. PMID:24198627

Cigarette Smoking and the Risk of Bladder Cancer in Men and Women

PubMed Central

Quirk, Jeffrey T; Li, Qiang; Natarajan, Nachimuthu; Mettlin, Curtis J; Cummings, K Michael

2004-01-01

Although cigarette smoking is a principal risk factor for bladder cancer in both men and women, few studies have statistically evaluated whether gender modifies the effect of smoking on bladder cancer risk. We initiated the present case-control study at Roswell Park Cancer Institute in Buffalo, New York, U.S., to provide further data on this important issue. We observed similar risk estimates for men and women with comparable smoking exposures, but did not observe a statistically significant interaction between gender and lifetime smoking exposure. We conclude that cigarette smoking is a major risk factor for bladder cancer in both sexes, but that gender does not modify the effect of smoking on bladder cancer risk.

Clinicopathological characteristics of incidental prostate cancer discovered from radical cystoprostatectomy specimen: a multicenter French study.

PubMed

Pignot, Géraldine; Salomon, Laurent; Neuzillet, Yann; Masson-Lecomte, Alexandra; Lebacle, Cédric; Patard, Jean-Jacques; Lunardi, Pierre; Rischmann, Pascal; Pasticier, Gilles; Bernhard, Jean-Christophe; Cohen, Jérémy; Timsit, Marc-Olivier; Verkarre, Virginie; Peyronnet, Benoit; Verhoest, Gregory; Le Goux, Constance; Zerbib, Marc; Brecheteau, François; Bigot, Pierre; Larre, Stéphane; Murez, Thibault; Thuret, Rodolphe; Lacarriere, Emeric; Champy, Cécile; Roupret, Morgan; Comperat, Eva; Berger, Julien; Descazeaud, Aurélien; Toledano, Harry; Bastide, Cyrille; Lavilledieu, Sébastien; Avances, Christophe; Delage, Francky; Valeri, Antoine; Molimard, Benoit; Houlgatte, Alain; Gres, Pascal; Donnaint, Alain; Kleinclauss, François; Legal, Sophie; Doerfler, Arnaud; Koutlidis, Nicolas; Cormier, Luc; Hetet, Jean-François; Colls, Philippe; Arvin-Berod, Alexis; Rambeaud, Jean-Jacques; Quintens, Hervé; Soulie, Michel; Pfister, Christian

2014-02-01

The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated. We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa. Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7%). Most tumors (90.1%) were organ-confined (pT2), whereas 9.9% of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9%), 6 in 575 cases (61.7%), 7 (3 + 4) in 149 cases (16.0%), 7 (4 + 3) in 38 cases (4.1%), and >7 in 40 cases (4.3%). After a median follow-up of 25.5 months (interquartile range 14.2-47.4), 35.4% of patients had bladder cancer recurrence and 23.8% died of bladder cancer. Only 16 patients (1.9%) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa. The rate of incidentally diagnosed PCa in RCP specimens was 21.7%. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9% of cases during follow-up.

A Pilot Study Combining a GC-Sensor Device with a Statistical Model for the Identification of Bladder Cancer from Urine Headspace

PubMed Central

Khalid, Tanzeela; White, Paul; De Lacy Costello, Ben; Persad, Raj; Ewen, Richard; Johnson, Emmanuel; Probert, Chris S.; Ratcliffe, Norman

2013-01-01

There is a need to reduce the number of cystoscopies on patients with haematuria. Presently there are no reliable biomarkers to screen for bladder cancer. In this paper, we evaluate a new simple in–house fabricated, GC-sensor device in the diagnosis of bladder cancer based on volatiles. Sensor outputs from 98 urine samples were used to build and test diagnostic models. Samples were taken from 24 patients with transitional (urothelial) cell carcinoma (age 27-91 years, median 71 years) and 74 controls presenting with urological symptoms, but without a urological malignancy (age 29-86 years, median 64 years); results were analysed using two statistical approaches to assess the robustness of the methodology. A two-group linear discriminant analysis method using a total of 9 time points (which equates to 9 biomarkers) correctly assigned 24/24 (100%) of cancer cases and 70/74 (94.6%) controls. Under leave-one-out cross-validation 23/24 (95.8%) of cancer cases were correctly predicted with 69/74 (93.2%) of controls. For partial least squares discriminant analysis, the correct leave-one-out cross-validation prediction values were 95.8% (cancer cases) and 94.6% (controls). These data are an improvement on those reported by other groups studying headspace gases and also superior to current clinical techniques. This new device shows potential for the diagnosis of bladder cancer, but the data must be reproduced in a larger study. PMID:23861976

Evaluation of contemporary prostate and urothelial lineage biomarkers in a consecutive cohort of poorly differentiated bladder neck carcinomas.

PubMed

Mohanty, Sambit K; Smith, Steven C; Chang, Elena; Luthringer, Daniel J; Gown, Allen M; Aron, Manju; Amin, Mahul B

2014-08-01

New immunohistochemical (IHC) markers of urothelial carcinoma (UCa) and prostatic adenocarcinoma (PCa) have emerged in recent years, yet comparative studies to establish markers remain lacking. We aimed to identify an effective but parsimonious approach for poorly differentiated bladder neck lesions, to establish a best practice panel approach in a setting simulating prospective use. We tested the performance of a panel of IHC markers on whole sections of a consecutive cohort of transurethral resection specimens of poorly differentiated, challenging bladder neck resections (n=36). In the setting of poorly differentiated bladder neck carcinomas, biomarker sensitivities for UCa were as follows: GATA3, 100%; S100P, 88%; p63, 75%; and cytokeratin (CK) 5/6, 56%; specificities of each were 100%. CK7 and CK20 showed sensitivities of 75% and 63%, though these were only 85% and 80% specific. For PCa markers, NKX3.1, p501S, prostate-specific membrane antigen, and androgen receptor (AR) each showed 100% sensitivity, outperforming ERG (35%) and prostate-specific antigen (PSA; 25%). All the prostate histogenesis markers were 100% specific, except for AR, which was positive in 13% of the UCa cases. Novel IHC markers show improved diagnostic performance that enables positive and negative support for identifying histogenesis with the use of as few as two markers for this critical therapeutic distinction. PSA underperforms newer markers. Copyright© by the American Society for Clinical Pathology.

Mutational patterns in chemotherapy resistant muscle-invasive bladder cancer.

PubMed

Liu, David; Abbosh, Philip; Keliher, Daniel; Reardon, Brendan; Miao, Diana; Mouw, Kent; Weiner-Taylor, Amaro; Wankowicz, Stephanie; Han, Garam; Teo, Min Yuen; Cipolla, Catharine; Kim, Jaegil; Iyer, Gopa; Al-Ahmadie, Hikmat; Dulaimi, Essel; Chen, David Y T; Alpaugh, R Katherine; Hoffman-Censits, Jean; Garraway, Levi A; Getz, Gad; Carter, Scott L; Bellmunt, Joaquim; Plimack, Elizabeth R; Rosenberg, Jonathan E; Van Allen, Eliezer M

2017-12-19

Despite continued widespread use, the genomic effects of cisplatin-based chemotherapy and implications for subsequent treatment are incompletely characterized. Here, we analyze whole exome sequencing of matched pre- and post-neoadjuvant cisplatin-based chemotherapy primary bladder tumor samples from 30 muscle-invasive bladder cancer patients. We observe no overall increase in tumor mutational burden post-chemotherapy, though a significant proportion of subclonal mutations are unique to the matched pre- or post-treatment tumor, suggesting chemotherapy-induced and/or spatial heterogeneity. We subsequently identify and validate a novel mutational signature in post-treatment tumors consistent with known characteristics of cisplatin damage and repair. We find that post-treatment tumor heterogeneity predicts worse overall survival, and further observe alterations in cell-cycle and immune checkpoint regulation genes in post-treatment tumors. These results provide insight into the clinical and genomic dynamics of tumor evolution with cisplatin-based chemotherapy, suggest mechanisms of clinical resistance, and inform development of clinically relevant biomarkers and trials of combination therapies.

[DAB2IP expression in bladder transitional cell carcinoma and its correlation with clinical outcome].

PubMed

Zhu, Jian-Ning; Wu, Kai-Jie; Guan, Zhen-Feng; Liu, Li-Xia; Ning, Zhong-Yun; Zhou, Jian-Cheng; Wang, Xin-Yang; Fan, Jin-Hai

2014-07-01

To investigate the expression of DAB2IP in bladder transitional cell carcinoma (BTCC) and its correlation with clinical characteristics and prognosis of BTCC patients. Immunohistochemical staining was applied to detect DAB2IP protein level in 79 cases of TCCB tissues and 11 cases of normal bladder tissues, and the relationships of the staining results with pathological grade, stage, lymph node metastasis, gender, age and the 3-year survival rate of the patients were analyzed. The expression of DAB2IP in BTCC tissues was significantly lower than that in normal bladder epithelium, and the expression score and rate of DAB2IP in the high-grade, invasive and metastatic BTCC were significantly lower than those in low-grade, superficial and non-metastatic BTCC (P < 0.05). The 3-year survival rate of the patients with high DAB2IP expression was significantly higher than that of the patients with low DAB2IP expression. DAB2IP may be one of the important inhibitory factors during the occurrence and progression of BTCC.

A clinical audit of postoperative urinary retention in the postanesthesia care unit.

PubMed

McLeod, Laura; Southerland, Kerry; Bond, Jade

2013-08-01

Postoperative urinary retention (PUR) is a common postsurgical complication. Early detection and management of PUR is of particular concern to nurses working in the postanesthesia care unit (PACU) because a single episode of bladder distention may result in permanent bladder damage. A clinical audit (CA) was conducted that examined the risk factors that may contribute to the development of PUR in the PACU. The CA was conducted over a 1-week time period and used a data collection tool that was developed from the current literature. A total of 34 patients met the inclusion criteria for the CA, and a prevalence rate of 20.6% was reported, which was consistent with prevalence rates reported by larger research studies. Despite the small sample size of this CA, results suggested that PUR should be of concern to nurses in the PACU. Recommendations included the development and implementation of a guideline relating to bladder scanning in the PACU and modification of existing PACU discharge criteria to include bladder management. Copyright © 2013 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Neuroprostheses to treat neurogenic bladder dysfunction: current status and future perspectives.

PubMed

Rijkhoff, Nico J M

2004-02-01

Neural prostheses are a technology that uses electrical activation of the nervous system to restore function to individuals with neurological or sensory impairment. This article provides an introduction to neural prostheses and lists the most successful neural prostheses (in terms of implanted devices). The article then focuses on neurogenic bladder dysfunction and describes two clinically available implantable neural prostheses for treatment of neurogenic bladder dysfunction. Special attention is given to the usage of these neural prostheses in children. Finally, three new developments that may lead to a new generation of implantable neural prostheses for bladder control are described. They may improve the neural prostheses currently available and expand further the population of patients who can benefit from a neural prosthesis.

Bladder tissue engineering using biocompatible nanofibrous electrospun constructs: feasibility and safety investigation.

PubMed

Shakhssalim, Nasser; Dehghan, Mohammad Mehdi; Moghadasali, Reza; Soltani, Mohammad Hossein; Shabani, Iman; Soleimani, Masoud

2012-01-01

To investigate the feasibility and safety of using biocompatible, nanofibrous electrospun polycaprolactone (PCL) and combination of polylactic acid (PLLA) and PCL mats in a canine model. Plasma-treated electrospun unseeded mats were implanted in three dogs. The first dog was sacrificed after 3 months and the second and third ones after 4 months, and then, the graft was examined macroscopically with subsequent morphological and histochemical evaluation. Both films showed high levels of cell infiltration and tissue formation, but body response to PLLA/PCL mat in comparison to PCL mat was very low. All three implantation models showed the same light microscopic morphology, immunohistochemistry, and scanning electron microscopy results; nevertheless, only the PCL/PLLA model showed favorable clinical results. Based on these data, nanofibrous PLLA/PCL scaffolding could be a suitable material for the bladder tissue engineering; however, it deserves further investigations.

Clinical utility of three-dimensional contrast-enhanced ultrasound in the differentiation between noninvasive and invasive neoplasms of urinary bladder.

PubMed

Li, Qiu-yang; Tang, Jie; He, En-hui; Li, Yan-mi; Zhou, Yun; Zhang, Xu; Chen, Guangfu

2012-11-01

The purpose of this study was to evaluate the effectiveness of three-dimensional contrast-enhanced ultrasound in differentiating invasive and noninvasive neoplasms of urinary bladder. A total of 60 lesions in 60 consecutive patients with bladder tumors received three dimensional ultrasonography, low acoustic power contrast enhanced ultrasonography and low acoustic power three-dimensional contrast-enhanced ultrasound examination. The IU22 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The contrast-specific sonographic imaging modes were PI (pulse inversion) and PM (power modulation). The three dimensional ultrasonography, contrast enhanced ultrasonography, and three-dimensional contrast-enhanced ultrasound images were independently reviewed by two readers who were not in the images acquisition. Images were analyzed off-site. A level of confidence in the diagnosis of tumor invasion of the muscle layer was assigned on a 5° scale. Receiver operating characteristic analysis was used to assess overall confidence in the diagnosis of muscle invasion by tumor. Kappa values were used to assess inter-readers agreement. Histologic diagnosis was obtained for all patients. Final pathologic staging revealed 44 noninvasive tumors and 16 invasive tumors. Three-dimensional contrast-enhanced ultrasound depicted all 16 muscle-invasive tumors. The diagnostic performance of three-dimensional contrast-enhanced ultrasound was better than those of three dimensional ultrasonography and contrast enhanced ultrasonography. The receiver operating characteristic curves were 0.976 and 0.967 for three-dimensional contrast-enhanced ultrasound, those for three dimensional ultrasonography were 0.881 and 0.869, those for contrast enhanced ultrasonography were 0.927 and 0.929. The kappa values in the three dimensional ultrasonography, contrast enhanced ultrasonography and three-dimensional contrast-enhanced ultrasound for inter-reader agreements were 0.717, 0.794 and 0.914. Three-dimensional contrast-enhanced ultrasound imaging, with contrast-enhanced spatial visualization is clinical useful for differentiating invasive and noninvasive neoplasms of urinary bladder objectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Childhood bladder and bowel dysfunction predicts irritable bowel syndrome phenotype in adult interstitial cystitis/bladder pain syndrome patients.

PubMed

Doiron, R Christopher; Kogan, Barry A; Tolls, Victoria; Irvine-Bird, Karen; Nickel, J Curtis

2017-08-01

Many clinicians have suggested that a history of bladder and bowel dysfunction (BBD) in childhood predisposes to the development of interstitial cystitis/bladder pain syndrome (IC/BPS) or irritable bowel syndrome (IBS) in adulthood. We hypothesized that BBD symptoms in childhood would predict the IBS-associated phenotype in adult IC/BPS patients. Consecutive female patients (n=190) with a diagnosis of IC/BPS were administered a modified form of a clinical BBD questionnaire (BBDQ) to capture childhood BBD-like symptoms, as well as Interstitial Cystitis Symptoms Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Pelvic Pain and Urgency/Frequency (PUF) questionnaires and UPOINT categorization. Patients were stratified to IBS-positive or IBS-negative according to clinical assessment of IBS-like symptoms. The 127 patients (67%) identified with IBS-like symptoms recalled significantly higher BBDQ scores than the 63 patients (33%) who were IBS-negative (2.8 vs. 2.3; p=0.05). The IBS-positive patients also reported a higher number of UPOINT domains than their non-IBS counterparts (3.8 vs. 2.9; p=0.0001), while their PUF total scores were significantly higher (13.6 vs. 12.3; p=0.04). IBS-positive patients more often recalled that in childhood they did not have a daily bowel movement (BM) (p=0.04) and had "to push for a BM" (p=0.009). In childhood, they "urinated only once or twice per day" (p=0.03) and recalled "painful urination" more than those without IBS (p=0.03). There were no significant differences between the groups in answers to the other five questions of the BBDQ. Our symptom recollection survey was able to predict the IBS phenotype of IC/BPS based on a childhood BBDQ. Further prospective studies are needed to further evaluate these novel findings.

Purification, characterization and anticancer activity of a polysaccharide from Panax ginseng.

PubMed

Li, Cong; Cai, Jianping; Geng, Jingshu; Li, Yinghong; Wang, Zhenyu; Li, Rui

2012-12-01

In this study, we purified a homogeneous polysaccharide (PGPW1) from the root of Panax ginseng. Its molecular weight was estimated to be 3.5×10(5) Da by high performance liquid chromatography (HPLC) and Gas chromatography (GC) analysis identified that PGPW1 contained Glc, Gal, Man and Ara in the molar ratio of 3.3:1.2:0.5:1.1. Furthermore the antitumor potential of PGPW1 on human bladder T24 cells was evaluated in vitro by MTT, lactate dehydrogenase (LDH), wound scratch and transwell motility assays. PGPW1 dose-dependently displayed potent anti-proliferation and anti-metastatic activities. Moreover the modulating effect of PGPW1 on the binding of (3)H-NMS to M3 muscarinic receptors on the surface of T24 cells was evaluated. In muscarinic receptor binding assay, the attenuated expression of M3 muscarinic receptor on the surface of T24 cells by PGPW1 would contribute to its antitumor functions. All the data indicated the potential of its clinical application for the prevention and treatment of bladder cancer metastasis. Copyright © 2012 Elsevier B.V. All rights reserved.

Targeting DNA Methyltranferases in Urological Tumors

PubMed Central

Marques-Magalhães, Ângela; Graça, Inês; Henrique, Rui; Jerónimo, Carmen

2018-01-01

Urological cancers are a heterogeneous group of malignancies accounting for a considerable proportion of cancer-related morbidity and mortality worldwide. Aberrant epigenetic traits, especially altered DNA methylation patterns constitute a hallmark of these tumors. Nonetheless, these alterations are reversible, and several efforts have been carried out to design and test several epigenetic compounds that might reprogram tumor cell phenotype back to a normal state. Indeed, several DNMT inhibitors are currently under evaluation for therapeutic efficacy in clinical trials. This review highlights the critical role of DNA methylation in urological cancers and summarizes the available data on pre-clinical assays and clinical trials with DNMT inhibitors in bladder, kidney, prostate, and testicular germ cell cancers. PMID:29706891

NOTCH pathway inactivation promotes bladder cancer progression

PubMed Central

Maraver, Antonio; Fernandez-Marcos, Pablo J.; Cash, Timothy P.; Mendez-Pertuz, Marinela; Dueñas, Marta; Maietta, Paolo; Martinelli, Paola; Muñoz-Martin, Maribel; Martínez-Fernández, Mónica; Cañamero, Marta; Roncador, Giovanna; Martinez-Torrecuadrada, Jorge L.; Grivas, Dimitrios; de la Pompa, Jose Luis; Valencia, Alfonso; Paramio, Jesús M.; Real, Francisco X.; Serrano, Manuel

2015-01-01

NOTCH signaling suppresses tumor growth and proliferation in several types of stratified epithelia. Here, we show that missense mutations in NOTCH1 and NOTCH2 found in human bladder cancers result in loss of function. In murine models, genetic ablation of the NOTCH pathway accelerated bladder tumorigenesis and promoted the formation of squamous cell carcinomas, with areas of mesenchymal features. Using bladder cancer cells, we determined that the NOTCH pathway stabilizes the epithelial phenotype through its effector HES1 and, consequently, loss of NOTCH activity favors the process of epithelial-mesenchymal transition. Evaluation of human bladder cancer samples revealed that tumors with low levels of HES1 present mesenchymal features and are more aggressive. Together, our results indicate that NOTCH serves as a tumor suppressor in the bladder and that loss of this pathway promotes mesenchymal and invasive features. PMID:25574842

Survey of spinal cord injury-induced neurogenic bladder studies using the Web of Science.

PubMed

Zou, Benjing; Zhang, Yongli; Li, Yucheng; Wang, Zantao; Zhang, Ping; Zhang, Xiyin; Wang, Bingdong; Long, Zhixin; Wang, Feng; Song, Guo; Wang, Yan

2012-08-15

To identify global trends in research on spinal cord injury-induced neurogenic bladder, through a bibliometric analysis using the Web of Science. We performed a bibliometric analysis of studies on spinal cord injury-induced neurogenic bladder using the Web of Science. Data retrieval was performed using key words "spinal cord injury", "spinal injury", "neurogenic bladder", "neuropathic bladder", "neurogenic lower urinary tract dysfunction", "neurogenic voiding dysfunction", "neurogenic urination disorder" and "neurogenic vesicourethral dysfunction". (a) published peer-reviewed articles on spinal cord injury-induced neurogenic bladder indexed in the Web of Science; (b) type of articles: original research articles and reviews; (c) year of publication: no limitation. (a) articles that required manual searching or telephone access; (b) Corrected papers and book chapters. (1) Annual publication output; (2) distribution according to journals; (3) distribution according to subject areas; (4) distribution according to country; (5) distribution according to institution; and (6) top cited publications. There were 646 research articles addressing spinal cord injury-induced neurogenic bladder in the Web of Science. Research on spinal cord injury-induced neurogenic bladder was found in the Science Citation Index-Expanded as of 1946. The United States, Ireland and Switzerland were the three major countries contributing to studies in spinal cord injury-induced neurogenic bladder in the 1970s. However, in the 1990s, the United States, the United Kingdom, the Netherlands, Germany and Japan published more papers on spinal cord injury-induced neurogenic bladder than Switzerland, and Ireland fell off the top ten countries list. In this century, the United States ranks first in spinal cord injury-induced neurogenic bladder studies, followed by France, the United Kingdom, Germany, Switzerland and Japan. Subject categories including urology, nephrology and clinical neurology, as well as rehabilitation, are represented in spinal cord injury-induced neurogenic bladder studies. From our analysis of the literature and research trends, we conclude that spinal cord injury-induced neurogenic bladder is a hot topic that will continue to generate considerable research interest in the future.

Bladder cancer treatment response assessment with radiomic, clinical, and radiologist semantic features

NASA Astrophysics Data System (ADS)

Gordon, Marshall N.; Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Cohan, Richard H.; Caoili, Elaine M.; Paramagul, Chintana; Alva, Ajjai; Weizer, Alon Z.

2018-02-01

We are developing a decision support system for assisting clinicians in assessment of response to neoadjuvant chemotherapy for bladder cancer. Accurate treatment response assessment is crucial for identifying responders and improving quality of life for non-responders. An objective machine learning decision support system may help reduce variability and inaccuracy in treatment response assessment. We developed a predictive model to assess the likelihood that a patient will respond based on image and clinical features. With IRB approval, we retrospectively collected a data set of pre- and post- treatment CT scans along with clinical information from surgical pathology from 98 patients. A linear discriminant analysis (LDA) classifier was used to predict the likelihood that a patient would respond to treatment based on radiomic features extracted from CT urography (CTU), a radiologist's semantic feature, and a clinical feature extracted from surgical and pathology reports. The classification accuracy was evaluated using the area under the ROC curve (AUC) with a leave-one-case-out cross validation. The classification accuracy was compared for the systems based on radiomic features, clinical feature, and radiologist's semantic feature. For the system based on only radiomic features the AUC was 0.75. With the addition of clinical information from examination under anesthesia (EUA) the AUC was improved to 0.78. Our study demonstrated the potential of designing a decision support system to assist in treatment response assessment. The combination of clinical features, radiologist semantic features and CTU radiomic features improved the performance of the classifier and the accuracy of treatment response assessment.

Urothelial Dysfunction and Chronic Inflammation are Associated With Increased Bladder Sensation in Patients With Chronic Renal Insufficiency.

PubMed

Cheng, Sheng-Fu; Jiang, Yuan-Hong; Kuo, Hann-Chorng

2018-01-01

Chronic kidney disease (CKD) or end-stage renal disease (ESRD) patients usually have lower urinary tract symptoms, such as frequency and urgency. Additionally, they frequently suffer from urinary tract infections. This study investigated dysfunction and chronic inflammation of the bladder urothelium in ESRD/CKD patients. This study enrolled 27 patients with CKD (n=13) or ESRD (n=14) for urodynamic studies and bladder biopsies. Patients presented with detrusor underactivity (DU; n=8) or bladder oversensitivity (BO; n=19). Bladder biopsies were performed in these patients and in 20 controls. The bladder mucosa was examined for E-cadherin and zonula occludens-1 (ZO-1) expression, activated mast cell count (through tryptase staining), and urothelial apoptosis (through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling [TUNEL]). The urodynamic parameters were also compared with variables regarding urothelial dysfunction. The bladder mucosa samples of ESRD and CKD patients revealed significantly higher mast cell counts, more urothelial apoptosis, and lower levels of ZO-1 expression than the control samples. E-cadherin expression was significantly reduced in ESRD/CKD patients with DU, but not in ESRD/CKD patients with BO. Increased mast cell and apoptotic cell counts were also associated with ESRD/CKD with BO. Less expression of ZO-1 and E-cadherin was significantly associated with increased bladder sensation and a small bladder capacity. Bladder urothelial dysfunction and chronic inflammation were present to a noteworthy extent in patients with ESRD or CKD. Increased inflammation and defective barrier function were more notable in ESRD/CKD bladders with BO than in those with DU. The clinical characteristics of these patients may involve urothelial pathophysiology.

HAMLET treatment delays bladder cancer development.

PubMed

Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

2010-04-01

HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Design and evaluation of potentiometric principles for bladder volume monitoring: a preliminary study.

PubMed

Chen, Shih-Ching; Hsieh, Tsung-Hsun; Fan, Wen-Jia; Lai, Chien-Hung; Chen, Chun-Lung; Wei, Wei-Feng; Peng, Chih-Wei

2015-06-01

Recent advances in microelectronics and wireless transmission technology have led to the development of various implantable sensors for real-time monitoring of bladder conditions. Although various sensing approaches for monitoring bladder conditions were reported, most such sensors have remained at the laboratory stage due to the existence of vital drawbacks. In the present study, we explored a new concept for monitoring the bladder capacity on the basis of potentiometric principles. A prototype of a potentiometer module was designed and fabricated and integrated with a commercial wireless transmission module and power unit. A series of in vitro pig bladder experiments was conducted to determine the best design parameters for implementing the prototype potentiometric device and to prove its feasibility. We successfully implemented the potentiometric module in a pig bladder model in vitro, and the error of the accuracy of bladder volume detection was <±3%. Although the proposed potentiometric device was built using a commercial wireless module, the design principles and animal experience gathered from this research can serve as a basis for developing new implantable bladder sensors in the future.

Exposure to polycyclic aromatic hydrocarbons (PAHs) and bladder cancer: evaluation from a gene-environment perspective in a hospital-based case-control study in the Canary Islands (Spain)

PubMed Central

Boada, Luis D; Henríquez-Hernández, Luis A; Navarro, Patricio; Zumbado, Manuel; Almeida-González, Maira; Camacho, María; Álvarez-León, Eva E; Valencia-Santana, Jorge A; Luzardo, Octavio P

2015-01-01

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to bladder cancer. Objective: To evaluate the role of PAHs in bladder cancer, PAHs serum levels were measured in patients and controls from a case-control study. Methods: A total of 140 bladder cancer patients and 206 healthy controls were included in the study. Sixteen PAHs were analyzed from the serum of subjects by gas chromatography–mass spectrometry. Results: Serum PAHs did not appear to be related to bladder cancer risk, although the profile of contamination by PAHs was different between patients and controls: pyrene (Pyr) was solely detected in controls and chrysene (Chry) was exclusively detected in the cases. Phenanthrene (Phe) serum levels were inversely associated with bladder cancer (OR = 0·79, 95%CI = 0·64–0·99, P = 0·030), although this effect disappeared when the allelic distribution of glutathione-S-transferase polymorphisms of the population was introduced into the model (multinomial logistic regression test, P = 0·933). Smoking (OR = 3·62, 95%CI = 1·93–6·79, P<0·0001) and coffee consumption (OR = 1·73, 95%CI = 1·04–2·86, P = 0·033) were relevant risk factors for bladder cancer. Conclusions: Specific PAH mixtures may play a relevant role in bladder cancer, although such effect seems to be highly modulated by polymorphisms in genes encoding xenobiotic-metabolizing enzymes. PMID:25291984

Outcome Measures in Spinal Cord Injury

PubMed Central

Alexander, Marcalee S.; Anderson, Kim; Biering-Sorensen, Fin; Blight, Andrew R.; Brannon, Ruth; Bryce, Thomas; Creasey, Graham; Catz, Amiram; Curt, Armin; Donovan, William; Ditunno, John; Ellaway, Peter; Finnerup, Nanna B.; Graves, Daniel E.; Haynes, Beth Ann; Heinemann, Allen W.; Jackson, Amie B.; Johnston, Mark; Kalpakjian, Claire Z.; Kleitman, Naomi; Krassioukov, Andrei; Krogh, Klaus; Lammertse, Daniel; Magasi, Susan; Mulcahey, MJ; Schurch, Brigitte; Sherwood, Arthur; Steeves, John D.; Stiens, Steven; Tulsky, David S.; van Hedel, Hubertus J.A.; Whiteneck, Gale

2009-01-01

Study Design review by the Spinal Cord Outcomes Partnership Endeavor (SCOPE), which is a broad-based international consortium of scientists and clinical researchers representing academic institutions, industry, government agencies, not-for-profit organizations and foundations. Objectives assessment of current and evolving tools for evaluating human spinal cord injury (SCI) outcomes for both clinical diagnosis and clinical research studies. Methods a framework for the appraisal of evidence of metric properties was used to examine outcome tools or tests for accuracy, sensitivity, reliability and validity for human SCI. Results imaging, neurological, functional, autonomic, sexual health, bladder/bowel, pain, and psycho-social tools were evaluated. Several specific tools for human SCI studies have or are being developed to allow the more accurate determination for a clinically meaningful benefit (improvement in functional outcome or quality of life) being achieved as a result of a therapeutic intervention. Conclusion significant progress has been made, but further validation studies are required to identify the most appropriate tools for specific targets in a human SCI study or clinical trial. PMID:19381157

Discovery and Validation of Novel Expression Signature for Postcystectomy Recurrence in High-Risk Bladder Cancer

PubMed Central

Lam, Lucia L.; Ghadessi, Mercedeh; Erho, Nicholas; Vergara, Ismael A.; Alshalalfa, Mohammed; Buerki, Christine; Haddad, Zaid; Sierocinski, Thomas; Triche, Timothy J.; Skinner, Eila C.; Davicioni, Elai; Daneshmand, Siamak; Black, Peter C.

2014-01-01

Background Nearly half of muscle-invasive bladder cancer patients succumb to their disease following cystectomy. Selecting candidates for adjuvant therapy is currently based on clinical parameters with limited predictive power. This study aimed to develop and validate genomic-based signatures that can better identify patients at risk for recurrence than clinical models alone. Methods Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. Genomic (GC) and clinical (CC) classifiers for predicting recurrence were developed on a discovery set (n = 133). Performances of GC, CC, an independent clinical nomogram (IBCNC), and genomic-clinicopathologic classifiers (G-CC, G-IBCNC) were assessed in the discovery and independent validation (n = 66) sets. GC was further validated on four external datasets (n = 341). Discrimination and prognostic abilities of classifiers were compared using area under receiver-operating characteristic curves (AUCs). All statistical tests were two-sided. Results A 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set. This was higher than individual clinical variables, IBCNC (AUC = 0.73), and comparable to CC (AUC = 0.78). Performance was improved upon combining GC with clinical nomograms (G-IBCNC, AUC = 0.82; G-CC, AUC = 0.86). G-CC high-risk patients had elevated recurrence probabilities (P < .001), with GC being the best predictor by multivariable analysis (P = .005). Genomic-clinicopathologic classifiers outperformed clinical nomograms by decision curve and reclassification analyses. GC performed the best in validation compared with seven prior signatures. GC markers remained prognostic across four independent datasets. Conclusions The validated genomic-based classifiers outperform clinical models for predicting postcystectomy bladder cancer recurrence. This may be used to better identify patients who need more aggressive management. PMID:25344601

Safe percutaneous suprapubic catheterisation.

PubMed

Goyal, N K; Goel, A; Sankhwar, S N

2012-11-01

We describe our technique of percutaneous suprapubic catheter insertion with special reference to steps that help to avoid common complications of haematuria and catheter misplacement. The procedure is performed using a stainless steel reusable trocar under local infiltrative anaesthesia, usually at the bedside. After clinical confirmation of a full bladder, the trocar is advanced into the bladder through a skin incision. Once the bladder is entered, the obturator is removed and the assistant inserts a Foley catheter followed by rapid balloon inflation. Slight traction is applied to the catheter for about five minutes. Patients with previous lower abdominal surgery, an inadequately distended bladder or acute pelvic trauma do not undergo suprapubic catheterisation using this method. The procedure was performed in 72 men (mean age: 42.4 years, range: 18-78 years) with urinary retention with a palpable bladder. The average duration of the procedure was less than five minutes. No complications were noted in any of the patients. Trocar suprapubic catheter insertion is a safe and effective bedside procedure for emergency bladder drainage and can be performed by resident surgeons. The common complications associated with the procedure can be avoided with a few careful steps.

OnabotulinumtoxinA significantly attenuates bladder afferent nerve firing and inhibits ATP release from the urothelium.

PubMed

Collins, Valerie M; Daly, Donna M; Liaskos, Marina; McKay, Neil G; Sellers, Donna; Chapple, Christopher; Grundy, David

2013-11-01

To investigate the direct effect of onabotulinumtoxinA (OnaBotA) on bladder afferent nerve activity and release of ATP and acetylcholine (ACh) from the urothelium. Bladder afferent nerve activity was recorded using an in vitro mouse preparation enabling simultaneous recordings of afferent nerve firing and intravesical pressure during bladder distension. Intraluminal and extraluminal ATP, ACh, and nitric oxide (NO) release were measured using the luciferin-luciferase and Amplex(®) Red assays (Molecular Probes, Carlsbad, CA, USA), and fluorometric assay kit, respectively. OnaBotA (2U), was applied intraluminally, during bladder distension, and its effect was monitored for 2 h after application. Whole-nerve activity was analysed to classify the single afferent units responding to physiological (low-threshold [LT] afferent <15 mmHg) and supra-physiological (high-threshold [HT] afferent >15 mmHg) distension pressures. Bladder distension evoked reproducible pressure-dependent increases in afferent nerve firing. After exposure to OnaBotA, both LT and HT afferent units were significantly attenuated. OnaBotA also significantly inhibited ATP release from the urothelium and increased NO release. These data indicate that OnaBotA attenuates the bladder afferent nerves involved in micturition and bladder sensation, suggesting that OnaBotA may exert its clinical effects on urinary urgency and the other symptoms of overactive bladder syndrome through its marked effect on afferent nerves. © 2013 The Authors. BJU International © 2013 BJU International.

Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

PubMed

Gad, Parag N; Roy, Roland R; Zhong, Hui; Lu, Daniel C; Gerasimenko, Yury P; Edgerton, V Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Lu, Daniel C.; Gerasimenko, Yury P.; Edgerton, V. Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury. PMID:25264607

Bladder sensory physiology: neuroactive compounds and receptors, sensory transducers, and target-derived growth factors as targets to improve function

PubMed Central

Gonzalez, Eric J.; Merrill, Liana

2014-01-01

Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered. PMID:24760999

Cigarette Smoking and the Risk of Bladder Cancer in Men and Women

PubMed Central

Quirk, Jeffrey T; Li, Qiang; Natarajan, Nachimuthu; Mettlin, Curtis J; Cummings, K Michael

2004-01-01

Although cigarette smoking is a principal risk factor for bladder cancer in both men and women, few studies have statistically evaluated whether gender modifies the effect of smoking on bladder cancer risk. We initiated the present case-control study at Roswell Park Cancer Institute in Buffalo, New York, U.S., to provide further data on this important issue. We observed similar risk estimates for men and women with comparable smoking exposures, but did not observe a statistically significant interaction between gender and lifetime smoking exposure. We conclude that cigarette smoking is a major risk factor for bladder cancer in both sexes, but that gender does not modify the effect of smoking on bladder cancer risk. PMID:19570280

Intravesical foreign body–induced bladder calculi resulting in obstructive renal failure

PubMed Central

Kamal, Fadi; Clark, Aaron T.D.; Lavallée, Luke Thomas; Roberts, Matthew; Watterson, James

2008-01-01

We report the case of a 30-year-old man who presented with obstructive renal failure and urosepsis due to bladder outlet–obstructing bladder calculi that formed around 3 copper wires that were self-inserted into his urinary bladder 15 years previously. We present the evaluation, imaging and management of the unique complications resulting from the self-insertion of an intra-vesical foreign body. Our patient’s case was unique for 2 reasons. First, the length of time (15 yr) from foreign body insertion to presentation is the longest interval reported in the literature. Second, this is the first report of bladder calculi induced by the insertion of a foreign body that resulted in obstructive renal failure. PMID:18953457

MicroRNA-137 Upregulation Increases Bladder Cancer Cell Proliferation and Invasion by Targeting PAQR3

PubMed Central

Xia, Shunyao; Jin, Chengjun; Yin, Huaifu; Zhao, Weiming; Wu, Qiong

2014-01-01

There is increasing evidence suggesting that dysregulation of some microRNAs (miRNAs) may contribute to tumor progression and metastasis and have been proposed to be key regulators of diverse biological processes such as transcriptional regulation, cell growth and tumorigenesis. Previous studies have shown that miR-137 is dysregulated in some malignancies, but its role in bladder cancer is still unknown. In our study, we find that miR-137 is up-regulated in human bladder cancer tissues and cell lines. Moreover, the higher level of miR-137 was associated with pM or pTNM stage in clinical bladder cancer patients. Enforced expression of miR-137 in bladder cancer cells significantly enhanced their proliferation, migration and invasion. Bioinformatics analysis identified the tumor suppressor gene PAQR3 as a potential miR-137 target gene. Further studies indicated that miR-137 suppressed the expression of PAQR3 by binding to its 3′-untranslated region. Silencing of PAQR3 by small interfering RNAs phenocopied the effects of miR-137 overexpression, whereas restoration of PAQR3 in bladder cancer cells bladder cancer cells overexpressing miR-137, partially reversed the suppressive effects of miR-137. These findings indicate that miR-137 could be a potential oncogene in bladder cancer. PMID:25330156

Bladder and bowel dysfunctions in 1748 children referred to pelvic physiotherapy: clinical characteristics and locomotor problems in primary, secondary, and tertiary healthcare settings.

PubMed

van Engelenburg-van Lonkhuyzen, Marieke L; Bols, Esther M J; Benninga, Marc A; Verwijs, Wim A; de Bie, Rob A

2017-02-01

The aims of this study are to evaluate in a pragmatic cross-sectional study, the clinical characteristics of childhood bladder and/or bowel dysfunctions (CBBD) and locomotor problems in the primary through tertiary health care setting. It was hypothesized that problems would increase, going from primary to tertiary healthcare. Data were retrieved from patient-records of children (1-16 years) presenting with CBBD and visiting pelvic physiotherapists. Prevalence's of dysfunctions were compared between healthcare settings and gender using ANOVA and chi-square test. Agreement between physicians' diagnoses and parent-reported symptoms was evaluated (Cohen's Kappa). One thousand seventy hundred forty-eight children (mean age 7.7 years [SD 2.9], 48.9% boys) were included. Daytime urinary incontinence (P = 0.039) and enuresis (P < 0.001) were more diagnosed in primary healthcare, whereas constipation (P < 0.001) and abdominal pain (P = 0.009) increased from primary to tertiary healthcare. All parent-reported symptoms occurred more frequently than indicated by the physicians. Poor agreement between physicians' diagnoses and parent-reported symptoms was found (k = 0.16). Locomotor problems prevailed in all healthcare settings, motor skills (P = 0.041) and core stability (P = 0.015) significantly more in tertiary healthcare. Constipation and abdominal pain (physicians' diagnoses) and the parent-reported symptoms hard stools and bloating increased from primary to tertiary healthcare. Discrepancies exist between the prevalence's of physicians' diagnoses and parent-reported symptoms. Locomotor problems predominate in all healthcare settings. What is Known: • Childhood bladder and/or bowel dysfunctions (CCBD) are common. • Particularly tertiary healthcare characteristics of CBBD are available What is New: • Characteristics of CBBD referred to pelvic physiotherapy are comparable in primary, secondary, and tertiary healthcare settings. • Concomitant CBBD appeared to be more prevalent than earlier reported. • Discrepancies exist between referring physicians' diagnoses and parent-reported symptoms.

Evaluation of educational content of YouTube videos relating to neurogenic bladder and intermittent catheterization

PubMed Central

Ho, Matthew; Stothers, Lynn; Lazare, Darren; Tsang, Brian; Macnab, Andrew

2015-01-01

Introduction: Many patients conduct internet searches to manage their own health problems, to decide if they need professional help, and to corroborate information given in a clinical encounter. Good information can improve patients’ understanding of their condition and their self-efficacy. Patients with spinal cord injury (SCI) featuring neurogenic bladder (NB) require knowledge and skills related to their condition and need for intermittent catheterization (IC). Methods: Information quality was evaluated in videos accessed via YouTube relating to NB and IC using search terms “neurogenic bladder intermittent catheter” and “spinal cord injury intermittent catheter.” Video content was independently rated by 3 investigators using criteria based on European Urological Association (EAU) guidelines and established clinical practice. Results: In total, 71 videos met the inclusion criteria. Of these, 12 (17%) addressed IC and 50 (70%) contained information on NB. The remaining videos met inclusion criteria, but did not contain information relevant to either IC or NB. Analysis indicated poor overall quality of information, with some videos with information contradictory to EAU guidelines for IC. High-quality videos were randomly distributed by YouTube. IC videos featuring a healthcare narrator scored significantly higher than patient-narrated videos, but not higher than videos with a merchant narrator. About half of the videos contained commercial content. Conclusions: Some good-quality educational videos about NB and IC are available on YouTube, but most are poor. The videos deemed good quality were not prominently ranked by the YouTube search algorithm, consequently user access is less likely. Study limitations include the limit of 50 videos per category and the use of a de novo rating tool. Information quality in videos with healthcare narrators was not higher than in those featuring merchant narrators. Better material is required to improve patients’ understanding of their condition. PMID:26644803

Mirabegron improves quality-of-life, treatment satisfaction, and persistence in patients with overactive bladder: a multi-center, non-interventional, real-world, 12-month study.

PubMed

Freeman, Robert; Foley, Steve; Rosa Arias, José; Vicente, Eduardo; Grill, Robert; Kachlirova, Zuzana; Stari, Anny; Huang, Moses; Choudhury, Nurul

2018-05-01

Observational studies can provide evidence about patient outcomes in routine clinical practice. This prospective, non-interventional study (BELIEVE) is the largest real-world European study to date to assess quality-of-life, treatment satisfaction, resource utilization, and persistence in patients with overactive bladder (OAB) who were prescribed mirabegron as part of routine clinical practice. The primary objective was to evaluate change from baseline in quality-of-life based on overactive bladder questionnaire (OAB-q) sub-scales. Secondary objectives included evaluation of treatment persistence, patient satisfaction, healthcare resource utilization and adverse events (AEs). Follow-up was for 12 months with visit windows at 2-4 and 10-12 months. Median change from baseline in total OAB-q and its sub-scales (Health-related quality-of-life [HRQoL] and symptom bother scale) were assessed. Overall, 862 patients were enrolled from eight European countries. In the Full Analysis Set (FAS), 73.7% were female, mean age was 61.2 years; 47.7% ≥65 years. At baseline, 41.3% had switched from other OAB treatments, 42.2% were treatment naïve, 10.1% were lapsed, and 6.4% were on combination treatment. Symptom bother and HRQoL total scores improved from baseline to 2-4 and 10-12 months. There was a notable improvement in dry rate, increasing from 34.9% at baseline to 43.7% at 10-12 months in the FAS, and a reduction in pad use. Persistence was high, with 53.8% of FAS patients remaining on mirabegron at 10-12 months. Overall, no unexpected safety issues were observed and AEs were consistent with the known safety profile of mirabegron. Patients receiving mirabegron in a real-world setting reported meaningful improvements in QoL and health status, with a persistence rate of 53.8% at 12 months for the FAS. No unexpected safety issues were observed, and AEs were consistent with the known safety profile of mirabegron.

Clinical Evaluation of 68Ga-PSMA-II and 68Ga-RM2 PET Images Reconstructed With an Improved Scatter Correction Algorithm.

PubMed

Wangerin, Kristen A; Baratto, Lucia; Khalighi, Mohammad Mehdi; Hope, Thomas A; Gulaka, Praveen K; Deller, Timothy W; Iagaru, Andrei H

2018-06-06

Gallium-68-labeled radiopharmaceuticals pose a challenge for scatter estimation because their targeted nature can produce high contrast in these regions of the kidneys and bladder. Even small errors in the scatter estimate can result in washout artifacts. Administration of diuretics can reduce these artifacts, but they may result in adverse events. Here, we investigated the ability of algorithmic modifications to mitigate washout artifacts and eliminate the need for diuretics or other interventions. The model-based scatter algorithm was modified to account for PET/MRI scanner geometry and challenges of non-FDG tracers. Fifty-three clinical 68 Ga-RM2 and 68 Ga-PSMA-11 whole-body images were reconstructed using the baseline scatter algorithm. For comparison, reconstruction was also processed with modified sampling in the single-scatter estimation and with an offset in the scatter tail-scaling process. None of the patients received furosemide to attempt to decrease the accumulation of radiopharmaceuticals in the bladder. The images were scored independently by three blinded reviewers using the 5-point Likert scale. The scatter algorithm improvements significantly decreased or completely eliminated the washout artifacts. When comparing the baseline and most improved algorithm, the image quality increased and image artifacts were reduced for both 68 Ga-RM2 and for 68 Ga-PSMA-11 in the kidneys and bladder regions. Image reconstruction with the improved scatter correction algorithm mitigated washout artifacts and recovered diagnostic image quality in 68 Ga PET, indicating that the use of diuretics may be avoided.

Current preclinical models for the advancement of translational bladder cancer research.

PubMed

DeGraff, David J; Robinson, Victoria L; Shah, Jay B; Brandt, William D; Sonpavde, Guru; Kang, Yibin; Liebert, Monica; Wu, Xue-Ru; Taylor, John A

2013-02-01

Bladder cancer is a common disease representing the fifth most diagnosed solid tumor in the United States. Despite this, advances in our understanding of the molecular etiology and treatment of bladder cancer have been relatively lacking. This is especially apparent when recent advances in other cancers, such as breast and prostate, are taken into consideration. The field of bladder cancer research is ready and poised for a series of paradigm-shifting discoveries that will greatly impact the way this disease is clinically managed. Future preclinical discoveries with translational potential will require investigators to take full advantage of recent advances in molecular and animal modeling methodologies. We present an overview of current preclinical models and their potential roles in advancing our understanding of this deadly disease and for advancing care. ©2012 AACR.

Intravesical application of rebamipide promotes urothelial healing in a rat cystitis model.

PubMed

Funahashi, Yasuhito; Yoshida, Masaki; Yamamoto, Tokunori; Majima, Tsuyoshi; Takai, Shun; Gotoh, Momokazu

2014-12-01

Rebamipide is used as a topical therapeutic agent for various organs. We examined the healing effects of intravesical rebamipide on damaged urothelium in a rat model of chemically induced cystitis. Hydrochloride was injected in the bladder of female Sprague Dawley® rats to induce cystitis. On days 1 and 4 rebamipide (1 or 10 mM) or vehicle was administered in the bladder and maintained for 1 hour. Histopathology, urothelial permeability, cystometrogram and nociceptive behaviors were evaluated on day 7. Also, tissue rebamipide concentrations after the 1-hour bladder instillation were quantified using high performance liquid chromatography. Intravesically administered rebamipide permeated the bladder, particularly in hydrochloride treated rats, and the pharmacologically effective tissue dose remained for greater than 6 hours. Bladder histological evaluation revealed polymorphological inflammatory cell infiltration and decreased positive staining for uroplakin 3A in hydrochloride treated rats. Scanning electron microscopy showed damaged tight junctions in the hydrochloride group. Evans blue absorption in the bladder wall was increased in hydrochloride treated rats. These findings, which were associated with urothelial injury and increased permeability, were dependently suppressed by the rebamipide treatment dose. Cystometrogram demonstrated that the intercontraction interval was shorter in hydrochloride treated rats but prolonged by rebamipide. The increased nociceptive behaviors observed after intravesical resiniferatoxin administration were also suppressed by rebamipide. Intravesical rebamipide accelerated the repair of damaged urothelium, protected urothelial barrier function and suppressed bladder overactivity and nociception. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Hemangiopericytoma arising from the wall of the urinary bladder.

PubMed

Kibar, Y; Uzar, A I; Erdemir, F; Ozcan, A; Coban, H; Seckin, B

2006-01-01

Hemangiopericytoma (HPC) arising from within the urinary bladder is exceptionally rare. A 45-year-old man having the symptoms of left groin pain, vague suprapubic discomfort and frequency was admitted to our clinic. Pelvic tomography revealed a tumor in the bladder wall measuring 4 x 3 cm and was not clearly distinct from the lower abdominal wall. Partial cystectomy was performed and the histopathological examination confirmed the hemangiopericytoma. Three thousand rad exterior beam irradiation was performed after operation. Partial cystectomy and adjuvant radiotherapy may be a simple and effective alternative operation for the patient with HPC.

Objective measurement of bladder sensation: use of a new patient-activated device and response to neuromodulation.

PubMed

Craggs, Michael D

2005-09-01

Detrusor overactivity is the primary objective focus of most investigations into the diagnosis and management of patients with urgency incontinence. Patients with an overactive bladder are characteristically troubled by subjective sensations of bladder fullness and urinary urgency, and frequently void at low bladder volumes attained before noticeable detrusor overactivity occurs. Bladder sensations are therefore crucial to understanding voiding patterns and symptoms, but little progress has been made in objectively describing the range of these sensations, and adequate information is lacking about their response to neuromodulation. Towards this end, a keypad 'urge score' device was designed to measure sensations during bladder filling. This patient-activated device gathers information about patient perceptions of bladder filling and the successive stages of increasing bladder sensation, without prompting or intervention by the investigator. The accuracy of the 'urge keypad' during filling cystometrography was validated in patients with urgency incontinence, and compared with data abstracted from patient voiding diaries. The device provides reliable and repeatable measures of different bladder sensations, with excellent, statistically significant consistency between bladder volumes and corresponding levels of sensation. Subsequently, it was shown that the sensation of urgency can be suppressed by neuromodulation in most patients tested; this suppression occurs with improvements in bladder capacity and voided volumes. It is therefore suggested that urodynamics with concurrent sensory evaluation may offer a more useful assessment tool for selecting those patients for therapies such as neuromodulation who present predominantly with the symptom of urgency.

Computer-aided detection of bladder wall thickening in CT urography (CTU)

NASA Astrophysics Data System (ADS)

Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon Z.; Gordon, Marshall N.; Samala, Ravi K.

2018-02-01

We are developing a computer-aided detection system for bladder cancer in CT urography (CTU). Bladder wall thickening is a manifestation of bladder cancer and its detection is more challenging than the detection of bladder masses. We first segmented the inner and outer bladder walls using our method that combined deep-learning convolutional neural network with level sets. The non-contrast-enhanced region was separated from the contrast-enhanced region with a maximum-intensity-projection-based method. The non-contrast region was smoothed and gray level threshold was applied to the contrast and non-contrast regions separately to extract the bladder wall and potential lesions. The bladder wall was transformed into a straightened thickness profile, which was analyzed to identify regions of wall thickening candidates. Volume-based features of the wall thickening candidates were analyzed with linear discriminant analysis (LDA) to differentiate bladder wall thickenings from false positives. A data set of 112 patients, 87 with wall thickening and 25 with normal bladders, was collected retrospectively with IRB approval, and split into independent training and test sets. Of the 57 training cases, 44 had bladder wall thickening and 13 were normal. Of the 55 test cases, 43 had wall thickening and 12 were normal. The LDA classifier was trained with the training set and evaluated with the test set. FROC analysis showed that the system achieved sensitivities of 93.2% and 88.4% for the training and test sets, respectively, at 0.5 FPs/case.

Decreased expression of zonula occludens-1 and occludin in the bladder urothelium of patients with interstitial cystitis/painful bladder syndrome.

PubMed

Lee, Jane-Dar; Lee, Ming-Huei

2014-01-01

Unique barrier properties of the urothelial surface membrane permit urine storage without contents leak into the bloodstream. Previous reports suggested that the bladder urothelial barrier might be compromised in interstitial cystitis/painful bladder syndrome (IC/PBS). We examined the changes of tight junction proteins (zonula occludens-1 (ZO-1) and occludin) in IC/PBS patients. Bladder samples were derived from of 32 patients with IC/PBS and eight controls. We detected the tight junction proteins of ZO-1 and occludin expression by immunoblotting, immunohistochemical (IHC) staining and double immunofluorescent (IF) staining with confocal microscopy. Data were analyzed using the Mann-Whitney U-test. Expression of ZO-1 and occludin in the IC/PBS group was reduced compared to the control group by immunoblotting and IHC staining. Also, the thinning and denudation of urothelium were demonstrated in the IC/PBS group by histological study. IF staining showed the interruption of bladder urothelium in IC/PBS patients under confocal microscopy. Our data showed that decreased expression of tight junction proteins (ZO-1 and occludin) and interruption of bladder urothelium in IC/PBS patients. Treatment to repair the discontinuous urothelium may be useful to relieve some clinical symptoms of patients with IC/PBS. Copyright © 2012. Published by Elsevier B.V.

Genome-wide association studies in bladder cancer: first results and potential relevance.

PubMed

Kiemeney, Lambertus A; Grotenhuis, Anne J; Vermeulen, Sita H; Wu, Xifeng

2009-09-01

The role of genetic susceptibility in the development of urinary bladder cancer is unclear, as it is in many other types of cancer. Since 2007, however, an innovative research approach (i.e. genome-wide association studies or GWASs) has led to the identification of numerous genomic loci that harbor susceptibility factors for one or more cancer sites. All GWASs have been published in high-impact journals and the strengths of the design are acknowledged by all experts, but there is criticism about the relevance of the results. Late 2008, the first GWAS in bladder cancer was published. In this review, the principles of GWASs are explained, as well as their strengths and limitations. The study in bladder cancer among 4000 cases and 38,000 controls identified three new susceptibility loci at 8q24, 3q28, and 5p15 that increase the risk of bladder cancer by 22, 19, and 16%, respectively. The results of two other GWASs in bladder cancer are expected to appear this year. Joint analysis of the three studies will probably identify additional susceptibility loci. The results of bladder cancer GWASs may point the way to yet unknown disease mechanisms. So far, the findings are not sufficiently discriminative for risk predictions to be used in clinical care or public health.

A novel automatic regulatory device for continuous bladder irrigation based on wireless sensor in patients after transurethral resection of the prostate: A prospective investigation.

PubMed

Ding, Aimin; Cao, Huling; Wang, Lihua; Chen, Jiangang; Wang, Jian; He, Bosheng

2016-12-01

Benign prostatic hyperplasia is a common progressive disease in aging men, which leads to a significant impact on daily lives of patients. Continuous bladder irrigation (CBI) is a supplementary option for preventing the adverse events following transurethral resection of the prostate (TURP). Regulation of the flow rate based on the color of drainage bag is significant to prevent the clot formation and retention, which is controlled manually at present. To achieve a better control of flow rate and reduce inappropriate flow rate-related adverse effects, we designed an automatic flow rate controller for CBI applied with wireless sensor and evaluated its clinical efficacy. The therapeutic efficacy was evaluated in patients receiving the novel automatic bladder irrigation post-TURP in the experimental group compared with controls receiving traditional bladder irrigation in the control group. A total of 146 patients were randomly divided into 2 groups-the experimental group (n = 76) and the control group (n = 70). The mean irrigation volume of the experimental group (24.2 ± 3.8 L) was significantly lower than that of the controls (54.6 ± 5.4 L) (P < 0.05). Patients treated with automatic irrigation device had significantly decreased incidence of clot retention (8/76) and cystospasm (12/76) compared to controls (21/70; 39/70, P < 0.05). There was no significant difference between the 2 groups with regard to irrigation time (28.6 ± 2.7 vs 29.5 ± 3.4 hours, P = 0.077). The study suggests that the automatic regulating device applied with wireless sensor for CBI is safe and effective for patients after TURP. However, studies with a large population of patients and a long-term follow-up should be conducted to validate our findings.

A novel automatic regulatory device for continuous bladder irrigation based on wireless sensor in patients after transurethral resection of the prostate

PubMed Central

Ding, Aimin; Cao, Huling; Wang, Lihua; Chen, Jiangang; Wang, Jian; He, Bosheng

2016-01-01

Abstract Background: Benign prostatic hyperplasia is a common progressive disease in aging men, which leads to a significant impact on daily lives of patients. Continuous bladder irrigation (CBI) is a supplementary option for preventing the adverse events following transurethral resection of the prostate (TURP). Regulation of the flow rate based on the color of drainage bag is significant to prevent the clot formation and retention, which is controlled manually at present. To achieve a better control of flow rate and reduce inappropriate flow rate–related adverse effects, we designed an automatic flow rate controller for CBI applied with wireless sensor and evaluated its clinical efficacy. Methods: The therapeutic efficacy was evaluated in patients receiving the novel automatic bladder irrigation post-TURP in the experimental group compared with controls receiving traditional bladder irrigation in the control group. Results: A total of 146 patients were randomly divided into 2 groups—the experimental group (n = 76) and the control group (n = 70). The mean irrigation volume of the experimental group (24.2 ± 3.8 L) was significantly lower than that of the controls (54.6 ± 5.4 L) (P < 0.05). Patients treated with automatic irrigation device had significantly decreased incidence of clot retention (8/76) and cystospasm (12/76) compared to controls (21/70; 39/70, P < 0.05). There was no significant difference between the 2 groups with regard to irrigation time (28.6 ± 2.7 vs 29.5 ± 3.4 hours, P = 0.077). Conclusion: The study suggests that the automatic regulating device applied with wireless sensor for CBI is safe and effective for patients after TURP. However, studies with a large population of patients and a long-term follow-up should be conducted to validate our findings. PMID:28033276

Comparison of dose volume parameters evaluated using three forward planning – optimization techniques in cervical cancer brachytherapy involving two applicators

PubMed Central

Basu-Roy, Somapriya; Kar, Sanjay Kumar; Das, Sounik; Lahiri, Annesha

2017-01-01

Purpose This study is intended to compare dose-volume parameters evaluated using different forward planning- optimization techniques, involving two applicator systems in intracavitary brachytherapy for cervical cancer. It looks for the best applicator-optimization combination to fulfill recommended dose-volume objectives in different high-dose-rate (HDR) fractionation schedules. Material and methods We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients in two fractions of brachytherapy. Six plans were generated for each patient utilizing 3 forward optimization techniques for each applicator used: equal dwell weight/times (‘no optimization’), ‘manual dwell weight/times’, and ‘graphical’. Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose volume and dose point parameters were compared. Results Without graphical optimization, maximum width and thickness of volume enclosed by 100% isodose line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum, median, and average dose to both rectum and bladder are significantly higher with Fletcher applicator. Even if it is done, dose to both points B, minimum dose to CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc, minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder remain significantly higher with this applicator. Dose to bladder point is similar (p > 0.05) between two applicators, after all optimization techniques. Conclusions Fletcher applicator generates higher dose to both CTV and organs at risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum is possible using graphical optimization only during selected HDR fractionation schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid colon always gets permissible dose. Contrarily, graphical optimization with ring applicators fulfills all dose volume objectives in all HDR fractionations practiced. PMID:29204164

Effectiveness of urine fibronectin as a non-invasive diagnostic biomarker in bladder cancer patients: a systematic review and meta-analysis.

PubMed

Dong, Fan; Shen, Yifan; Xu, Tianyuan; Wang, Xianjin; Gao, Fengbin; Zhong, Shan; Chen, Shanwen; Shen, Zhoujun

2018-03-21

Previous researches pointed out that the measurement of urine fibronectin (Fn) could be a potential diagnostic test for bladder cancer (BCa). We conducted this meta-analysis to fully assess the diagnostic value of urine Fn for BCa detection. A systematic literature search in PubMed, ISI Web of Science, EMBASE, Cochrane library, and CBM was carried out to identify eligible studies evaluating the urine Fn in diagnosing BCa. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with their 95% confidence intervals (CIs) were calculated, and summary receiver operating characteristic (SROC) curves were established. We applied the STATA 13.0, Meta-Disc 1.4, and RevMan 5.3 software to the meta-analysis. Eight separate studies with 744 bladder cancer patients were enrolled in this meta-analysis. The pooled sensitivity, specificity, and DOR were 0.80 (95%CI = 0.77-0.83), 0.79 (95%CI = 0.73-0.84), and 15.18 (95%CI = 10.07-22.87), respectively, and the area under the curve (AUC) of SROC was 0.83 (95%CI = 0.79-0.86). The diagnostic power of a combined method (urine Fn combined with urine cytology) was also evaluated, and its sensitivity and AUC were significantly higher (0.86 (95%CI = 0.82-0.90) and 0.89 (95%CI = 0.86-0.92), respectively). Meta-regression along with subgroup analysis based on various covariates revealed the potential sources of the heterogeneity and the detailed diagnostic value of each subgroup. Sensitivity analysis supported that the result was robust. No threshold effect and publication bias were found in this meta-analysis. Urine Fn may become a promising non-invasive biomarker for bladder cancer with a relatively satisfactory diagnostic power. And the combination of urine Fn with cytology could be an alternative option for detecting BCa in clinical practice. The potential value of urine Fn still needs to be validated in large, multi-center, and prospective studies.

Sorafenib induces cathepsin B-mediated apoptosis of bladder cancer cells by regulating the Akt/PTEN pathway. The Akt inhibitor, perifosine, enhances the sorafenib-induced cytotoxicity against bladder cancer cells

PubMed Central

Amantini, Consuelo; Morelli, Maria Beatrice; Santoni, Matteo; Soriani, Alessandra; Cardinali, Claudio; Farfariello, Valerio; Eleuteri, Anna Maria; Bonfili, Laura; Mozzicafreddo, Matteo; Nabissi, Massimo; Cascinu, Stefano; Santoni, Giorgio

2015-01-01

Sorafenib, a tyrosine kinase inhibitor, has been demonstrated to exert anti-tumor effects. However, the molecular mechanisms underlying its effects on bladder cancer remain unknown. Here, we evaluated the mechanisms responsible for the sorafenib-induced anti-tumor effects on 5637 and T24 bladder cancer cells. We demonstrated that sorafenib reduces cell viability, stimulates lysosome permeabilization and induces apoptosis of bladder cancer cells. These effects are dependent by the activation of cathepsin B released from lysosomes. The sorafenib-increased cathepsin B activity induced the proteolysis of Bid into tBid that stimulates the intrinsic pathway of apoptosis characterized by mitochondrial membrane depolarization, oxygen radical generation and cytochrome c release. Moreover, we found that cathepsin B enzymatic activity, induced by sorafenib, is dependent on its dephosphorylation via PTEN activation and Akt inactivation. Pretreatment with orthovanadate rescued bladder cancer cells from apoptosis. In addition, the Akt inhibitor perifosine increased the sensitivity of bladder cancer cells to sorafenib-induced cytotoxicity. Overall, our results show that apoptotic cell death induced by sorafenib in bladder cancer cells is dependent on cathepsin B activity and involved PTEN and Akt signaling pathways. The Akt inhibitor perifosine increased the cytotoxic effects of sorafenib in bladder cancer cells. PMID:26097873

Psychosocial screening at paediatric BEEC clinics: a pilot evaluation study.

PubMed

Hurrell, Ruth A; Fullwood, Catherine; Keys, Joni; Dickson, Alan P; Fishwick, Janet; Whitnall, Beverley; Cervellione, Raimondo M

2015-04-01

Bladder Exstrophy and Epispadias Complex (BEEC) is associated with an increased risk of impaired mental health, quality of life, and psychosocial functioning. Therefore, screening patients to help identify and evaluate potential psychosocial difficulty is arguably an important consideration for BEEC Services. To screen paediatric BEEC patients for a range of general psychosocial difficulties in a multi-disciplinary out-patient clinic setting. This cross-sectional evaluation was conducted between April 2012 and July 2013. Families attending BEEC multi-disciplinary out-patient clinics were asked to complete a range of standardised psychosocial questionnaires, including the Paediatric Quality of Life Inventory (PedsQL 4.0 Generic Core and Family Impact Module), the Strengths and Difficulties Questionnaire (SDQ), the Paediatric Index of Emotional Distress (PI-ED), and the Hospital Anxiety and Depression Scale (HADS). 108 children attended clinic of which 80 (74.1%) patients and their parents/carers completed some or all of the questionnaires. The mean patient age was 8.41 years (SD = 4.46, range = 1-18 years). There were more boys (N = 50, 62.5%) and the majority had a diagnosis of classic bladder exstrophy (N = 51, 63.8%), followed by primary epispadias (N = 22, 27.5%) and cloacal exstrophy (N = 7, 8.7%). Mean total scores fell within the average/normal range on all questionnaires used (See table below). However, variation around these means was high. Age, gender and diagnosis were found to significantly influence certain questionnaire responses with older-age groups, males, and those with classic bladder exstrophy particularly at risk across some domains. The children/adolescents self-reported better health related quality of life (HRQoL) scores than published results for a range of paediatric chronic health conditions. Differences between parent and child responses on both the PedsQL and SDQ favoured a more positive response on the child self-report questionnaire but were not statistically significant. Mean scores on the measures used suggest a relatively optimistic picture of general psychosocial well-being, especially for HRQoL, in the BEEC population studied. Positive HRQoL outcomes have recently been reported for BEEC paediatric populations. Our results reflect this trend with better mean HRQoL scores than paediatric patients with a range of other chronic health conditions. However, this optimism is cautious given the limitations of this evaluation study and the high variation around the means. Limitations included the small sample size (especially for patients with cloacal exstrophy), the lack of a control group, the limited sensitivity of generic questionnaires in respect of BEEC-specific issues, and the low mean age of patients in the study. Future screening programmes may wish to consider measuring BEEC-specific variables (e.g. satisfaction with genital appearance/function); collecting information on medical aspects, such as continence, pubertal stage and frequency/timing of medical intervention; and asking both parents/carers (where possible) to complete the questionnaires. Screening questionnaire responses were used in conjunction with clinical psychology consultations to evaluate a range of psychosocial aspects in BEEC paediatric patients. Whilst mean scores on the measures used suggest a relatively optimistic picture, certain individual scores did fall within the clinical ranges, highlighting the potential need for further assessment. Developmentally tailored consultations with a clinical psychologist can provide detailed information around questionnaire responses and further assess BEEC specific aspects. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

A randomized clinical trial of how to best position retropubic slings for stress urinary incontinence: Development of a study protocol for the mid-urethral sling tensioning (MUST) trial.

PubMed

Brennand, Erin A; Kim-Fine, Shunaha

2016-08-15

The goal of this trial is to compare two techniques for tensioning retropubic midurethral slings: a Mayo scissor between the tape and urethra vs. a Babcock clamp creating a measured loop underneath the urethra. The primary outcome is a composite of abnormal bladder function at 12 months post surgery. Abnormal bladder function is defined as bothersome stress incontinence or worsening over active bladder symptoms, a positive cough stress test, re-treatment of stress urinary incontinence, post-operative urinary retention requiring either catheterization beyond 6 weeks or surgical intervention. Secondary outcomes include the duration of post operative urinary retention, quality of life scores, and physical examination. This article describes the rationale and design of this clinical trial, which will be of interest to those who care for patient with pelvic floor disorders such as stress urinary incontinence.

The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation.

PubMed

Matos, Rita; Serrão, Paula; Rodriguez, Larissa; Birder, Lori Ann; Cruz, Francisco; Charrua, Ana

2017-08-01

Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.

New Amniotic Membrane Based Biocomposite for Future Application in Reconstructive Urology

PubMed Central

Tworkiewicz, Jakub; Kowalczyk, Tomasz; van Breda, Shane V.; Tyloch, Dominik; Kloskowski, Tomasz; Bodnar, Magda; Skopinska-Wisniewska, Joanna; Marszałek, Andrzej; Frontczak-Baniewicz, Malgorzata; Kowalewski, Tomasz A.; Drewa, Tomasz

2016-01-01

Objective Due to the capacity of the amniotic membrane (Am) to support re-epithelisation and inhibit scar formation, Am has a potential to become a considerable asset for reconstructive urology i.e., reconstruction of ureters and urethrae. The application of Am in reconstructive urology is limited due to a poor mechanical characteristic. Am reinforcement with electrospun nanofibers offers a new strategy to improve Am mechanical resistance, without affecting its unique bioactivity profile. This study evaluated biocomposite material composed of Am and nanofibers as a graft for urinary bladder augmentation in a rat model. Material and Methods Sandwich-structured biocomposite material was constructed from frozen Am and covered on both sides with two-layered membranes prepared from electrospun poly-(L-lactide-co-E-caprolactone) (PLCL). Wistar rats underwent hemicystectomy and bladder augmentation with the biocomposite material. Results Immunohistohemical analysis (hematoxylin and eosin [H&E], anti-smoothelin and Masson’s trichrome staining [TRI]) revealed effective regeneration of the urothelial and smooth muscle layers. Anti-smoothelin staining confirmed the presence of contractile smooth muscle within a new bladder wall. Sandwich-structured biocomposite graft material was designed to regenerate the urinary bladder wall, fulfilling the requirements for normal bladder tension, contraction, elasticity and compliance. Mechanical evaluation of regenerated bladder wall conducted based on Young’s elastic modulus reflected changes in the histological remodeling of the augmented part of the bladder. The structure of the biocomposite material made it possible to deliver an intact Am to the area for regeneration. An unmodified Am surface supported regeneration of the urinary bladder wall and the PLCL membranes did not disturb the regeneration process. Conclusions Am reinforcement with electrospun nanofibers offers a new strategy to improve Am mechanical resistance without affecting its unique bioactivity profile. PMID:26766636

Genome-wide interaction study of smoking and bladder cancer risk

PubMed Central

Figueroa, Jonine D.; Han, Summer S.; Garcia-Closas, Montserrat; Baris, Dalsu; Jacobs, Eric J.; Kogevinas, Manolis; Schwenn, Molly; Malats, Nuria; Johnson, Alison; Purdue, Mark P.; Caporaso, Neil; Landi, Maria Teresa; Prokunina-Olsson, Ludmila; Wang, Zhaoming; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Vineis, Paolo; Siddiq, Afshan; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Bueno-de-Mesquita, H.Bas; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Karagas, Margaret R.; Schned, Alan; Armenti, Karla R.; Hosain, G.M.Monawar; Haiman, Chris A.; Fraumeni, Joseph F.; Chanock, Stephen J.; Chatterjee, Nilanjan; Rothman, Nathaniel; Silverman, Debra T.

2014-01-01

Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 × 10− 5 were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20–1.50, P value = 5.18 × 10− 7]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67–0.84, P value = 6.35 × 10− 7). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers—including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene–environment interactions for tobacco and bladder cancer. PMID:24662972

Detection of bladder metabolic artifacts in (18)F-FDG PET imaging.

PubMed

Roman-Jimenez, Geoffrey; Crevoisier, Renaud De; Leseur, Julie; Devillers, Anne; Ospina, Juan David; Simon, Antoine; Terve, Pierre; Acosta, Oscar

2016-04-01

Positron emission tomography using (18)F-fluorodeoxyglucose ((18)F-FDG-PET) is a widely used imaging modality in oncology. It enables significant functional information to be included in analyses of anatomical data provided by other image modalities. Although PET offers high sensitivity in detecting suspected malignant metabolism, (18)F-FDG uptake is not tumor-specific and can also be fixed in surrounding healthy tissue, which may consequently be mistaken as cancerous. PET analyses may be particularly hampered in pelvic-located cancers by the bladder׳s physiological uptake potentially obliterating the tumor uptake. In this paper, we propose a novel method for detecting (18)F-FDG bladder artifacts based on a multi-feature double-step classification approach. Using two manually defined seeds (tumor and bladder), the method consists of a semi-automated double-step clustering strategy that simultaneously takes into consideration standard uptake values (SUV) on PET, Hounsfield values on computed tomography (CT), and the distance to the seeds. This method was performed on 52 PET/CT images from patients treated for locally advanced cervical cancer. Manual delineations of the bladder on CT images were used in order to evaluate bladder uptake detection capability. Tumor preservation was evaluated using a manual segmentation of the tumor, with a threshold of 42% of the maximal uptake within the tumor. Robustness was assessed by randomly selecting different initial seeds. The classification averages were 0.94±0.09 for sensitivity, 0.98±0.01 specificity, and 0.98±0.01 accuracy. These results suggest that this method is able to detect most (18)F-FDG bladder metabolism artifacts while preserving tumor uptake, and could thus be used as a pre-processing step for further non-parasitized PET analyses. Copyright © 2016. Published by Elsevier Ltd.

Effects of streptozotocin-induced diabetes on bladder and erectile (dys)function in the same rat in vivo.

PubMed

Christ, George J; Hsieh, Yi; Zhao, Weixin; Schenk, Gregory; Venkateswarlu, Karicheti; Wang, Hong-Zhan; Tar, Moses T; Melman, Arnold

2006-05-01

To establish the methods, feasibility and utility of evaluating the impact of diabetes on bladder and erectile function in the same rat, as more than half of diabetic patients have bladder dysfunction, and half of diabetic men have erectile dysfunction, but the severity of coincident disease has not been rigorously assessed. In all, 16 F-344 rats had diabetes induced by streptozotocin (STZ), and were divided into insulin-treated (five) and untreated (11), and compared with age-matched controls (10), all assessed in parallel. All STZ rats were diabetic for 8-11 weeks. Cystometric studies were conducted on all rats, with cavernosometric studies conducted on a subset of rats. There were insulin-reversible increases in the following cystometric variables; bladder weight, bladder capacity, micturition volume, residual volume, micturition pressure and spontaneous activity (P < 0.05, in all, one-way analysis of variance, anova). Cavernosometry showed a diabetes-related, insulin-reversible decline in the cavernosal nerve-stimulated intracavernosal pressure (ICP) response at all levels of current stimulation (P < 0.05, in all one-way anova). Plotting erectile capacity (i.e. ICP) against bladder capacity showed no correlation between the extent of the decline in erectile capacity and the magnitude of the increase in bladder capacity. These studies extend previous work to indicate that the extent of diabetes-related bladder and erectile dysfunction can vary in the same rat. As such, these findings highlight the importance of evaluating the impact of diabetes on multiple organ systems in the lower urinary tract. Future studies using this model system should lead to a better understanding of the initiation, development, progression and coincidence of these common diabetic complications.

A Review of ERCC1 Gene in Bladder Cancer: Implications for Carcinogenesis and Resistance to Chemoradiotherapy.

PubMed

Kawashima, Atsunari; Takayama, Hitoshi; Tsujimura, Akira

2012-01-01

The excision repair cross-complementing group 1 (ERCC1) gene performs a critical incision step in DNA repair and is reported to be correlated with carcinogenesis and resistance to drug or ionizing radiation therapy. We reviewed the correlation between ERCC1 and bladder cancer. In carcinogenesis, several reports discussed the relation between ERCC1 single nucleotide polymorphisms and carcinogenesis in bladder cancer only in case-control studies. Regarding the relation between ERCC1 and resistance to chemoradiotherapy, in vitro and clinical studies indicate that ERCC1 might be related to resistance to radiation therapy rather than cisplatin therapy. It is controversial whether ERCC1 predicts prognosis of bladder cancer treated with cisplatin-based chemotherapy. Tyrosine kinase receptors or endothelial-mesenchymal transition are reported to regulate the expression of ERCC1, and further study is needed to clarify the mechanism of ERCC1 expression and resistance to chemoradiotherapy in vitro and to discover novel therapies for advanced and metastatic bladder cancer.

Gall bladder rupture associated with cholecystitis in a domestic ferret (Mustela putorius).

PubMed

Huynh, M; Guillaumot, P; Hernandez, J; Ragetly, G

2014-09-01

A six-year-old neutered female albino ferret was presented with an acute episode of lethargy and anorexia. Clinical examination revealed marked cranial abdominal pain. A severe neutrophilic leukocytosis was present. Abdominal ultrasound was consistent with a diffuse peritonitis and severe bile duct inflammation. Cytology of the abdominal effusion revealed bile peritonitis. An exploratory laparotomy was performed and the gall bladder appeared inflamed with multiple perforations. A cholecystectomy was performed. The ferret recovered without complication. Bacteriological culture of the bile and gall bladder yielded a pure growth of Pseudomonas aeruginosa. Histopathological analysis of the gall bladder and liver was consistent with a marked cholecystitis and cholangiohepatitis. On the basis of sensitivity testing, the ferret was treated with marbofloxacin for one month. No complications or reoccurrence were seen up to 1 year after the diagnosis. To the author's knowledge, this is the first report of bile peritonitis secondary to gall bladder rupture in a ferret. © 2014 British Small Animal Veterinary Association.

[A patient with high creatinine levels but no renal failure: reversed autodialysis in a patient with a ruptured bladder].

PubMed

Raeymaeckers, Steven; Tosi, Maurizio; Van Bael, Kobe; Brussaard, Carola; De Mey, Johan

2016-01-01

In case of a ruptured bladder with urine leakage into the peritoneal cavity 'reversed autodialysis' can occur, in which urea and creatinine diffuse back into the bloodstream via the peritoneum. This causes clinical signs of pseudorenal failure, with raised concentrations of creatinine and urea. The urea/creatinine ratio does not change. A 34-year-old female patient experienced increasing abdominal pain 3 days after laparoscopic myomectomy. Acute renal failure was suspected because of increased serum concentrations of creatinine and urea, but no cause could be found. There was a build-up of fluid in the abdominal cavity, which proved to be urine originating from an iatrogenic rupture of the bladder. Serum levels normalised following repair of the rupture. If serum creatinine levels rise rapidly following abdominal surgery or blunt abdominal trauma the bladder should be examined for possible perforation, particularly if the abdominal dimension increases. A ruptured bladder leading to pseudorenal failure is an indication for rapid surgical intervention.

[Association of serum decoy receptor 3 protein level with the clinicopathologic features of bladder transitional cell carcinoma].

PubMed

Wang, Dong; Wang, Jian; Chen, Guojun

2013-12-01

To investigate the association of serum levels of decoy receptor 3(DcR3) protein and the clinicopathologic features of bladder transitional cell carcinoma. Enzyme-linked immunosorbent assay was used to examine the serum levels of DcR3 in patients with bladder transitional cell carcinoma for analysis of its association with the patients' age, gender, clinical stages and pathological classification. The patients with bladder transitional cell carcinoma showed a significantly elevated serum level of DcR3 (183.43 ∓78.45 pg/m1) compared with the normal level (116.65∓97.43 pg/m1, P<0.05). The serum level of DcR3 in the patients showed close correlations with the TNM stage and pathological classification of the tumor (P<0.05) but not with the patients' age or gender (P>0.05). In patients with bladder transitional cell carcinoma, a high serum level of DcR3 suggests a higher malignancy of the tumor.

Cell-Based Therapies in Lower Urinary Tract Disorders.

PubMed

Gopinath, Chaitanya; Ponsaerts, Peter; Wyndaele, Jean Jacques

2015-01-01

Cell-based therapy for the bladder has its beginnings in the 1990s with the successful isolation and culture of bladder smooth muscle cells. Since then, several attempts have been made to artificially implant native cell types and stem cell-derived cells into damaged bladders in the form of single-cell injectables or as grafts seeded onto artificial extracellular matrix. We critically examined in the literature the types of cells and their probable role as an alternative to non-drug-based, non-bowel-based graft replacement therapy in disorders of the urinary bladder. The limitations and plausible improvements to these novel therapies have also been discussed, keeping in mind an ideal therapy that could suit most bladder abnormalities arising out of varied number of disorders. In conclusion, muscle-derived cell types have consistently proven to be a promising therapy to emerge in the coming decade. However, tissue-engineered constructs have yet to prove their success in preclinical and long-term clinical setting.

Validation of non-rigid point-set registration methods using a porcine bladder pelvic phantom

NASA Astrophysics Data System (ADS)

Zakariaee, Roja; Hamarneh, Ghassan; Brown, Colin J.; Spadinger, Ingrid

2016-01-01

The problem of accurate dose accumulation in fractionated radiotherapy treatment for highly deformable organs, such as bladder, has garnered increasing interest over the past few years. However, more research is required in order to find a robust and efficient solution and to increase the accuracy over the current methods. The purpose of this study was to evaluate the feasibility and accuracy of utilizing non-rigid (affine or deformable) point-set registration in accumulating dose in bladder of different sizes and shapes. A pelvic phantom was built to house an ex vivo porcine bladder with fiducial landmarks adhered onto its surface. Four different volume fillings of the bladder were used (90, 180, 360 and 480 cc). The performance of MATLAB implementations of five different methods were compared, in aligning the bladder contour point-sets. The approaches evaluated were coherent point drift (CPD), gaussian mixture model, shape context, thin-plate spline robust point matching (TPS-RPM) and finite iterative closest point (ICP-finite). The evaluation metrics included registration runtime, target registration error (TRE), root-mean-square error (RMS) and Hausdorff distance (HD). The reference (source) dataset was alternated through all four points-sets, in order to study the effect of reference volume on the registration outcomes. While all deformable algorithms provided reasonable registration results, CPD provided the best TRE values (6.4 mm), and TPS-RPM yielded the best mean RMS and HD values (1.4 and 6.8 mm, respectively). ICP-finite was the fastest technique and TPS-RPM, the slowest.

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

PubMed

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.

Morphological examination of the effects of defibrotide on experimentally induced bladder injury and its relation to interstitial cystitis.

PubMed

Aydin, H; Ercan, F; Cetinel, S; San, T

2001-08-01

This morphological study aims to investigate the effects of defibrotide, a deoxyribonucleic acid derivative drug with cytoprotective, immunosuppressive and vasorelaxant effects, on protamine sulfate induced bladder injury. Wistar albino female rats were catheterized and intravesically infused with phosphate buffered solution (control group) or, either protamine sulfate (bladder injury group) or protamine sulfate+defibrotide (bladder injury+defibrotide group) dissolved in phosphate buffered solution. The morphology of the urinary bladder was investigated using light and electron microscopy. The number of mast cells in the mucosa, mucosal alterations, intercellular junctions, surface topography and the glycosaminoglycan (GAG) layer as well as microvillus formation on the luminal surface were evaluated. In the bladder injury group, ulcerated areas, irregularity of the GAG layer, increased number of mast cells, vacuole formation, dilated perinuclear cistern, formation of pleomorphic and uniform microvilli and dilatations in the intercellular spaces in the urothelium were observed. In the bladder injury+defibrotide group a relatively normal urothelial topography, GAG layer and a few mast cells in the mucosa, some dilatations between the intercellular areas, less uniform microvilli, regular perinuclear cistern and tight junctions were observed. These results show that defibrotide can inhibit PS induced bladder damage.

Pheochromocytoma of urinary bladder - a case report.

PubMed

Sharma, Shaleen; Gokhro, Sunil; Sharma, K K; Sadasukhi, T C

2007-08-01

Pheochromocytomas are catecholamine producing neuroendocrine tumours. Bladder involvement with pheochromocytoma is rare that usually presents with hypertension, hematuria and syncope often related to voiding. Clinical manifestation may be inconsistent and high index of suspicion is required for accurate diagnosis. We report a case, who presented with gross intermittent hematuria and mild elevation of pulserate and bloodpressure. Patient was adequately treated with partial cystectomy.

Predicting the failure of retrograde ureteral stent insertion for managing malignant ureteral obstruction in outpatients

PubMed Central

WANG, JIN-YOU; ZHANG, HAI-LIANG; ZHU, YAO; QIN, XIAO-JIAN; DAI, BO; YE, DING-WEI

2016-01-01

Malignant ureteral obstruction (MUO) is an unpropitious sign that is commonly observed in patients with advanced incurable cancer. The present study aimed to evaluate predictive factors for the failure of retrograde ureteral stent insertion in the management of MUO in outpatients. A total of 164 patients with MUO were retrospectively assessed in this study. Clinical factors, including age, gender, type of malignancy, level of obstruction, cause of obstruction, pre-operative creatinine level, degree of hydronephrosis, condition of the contralateral ureter, prior radiotherapy, Eastern Cooperative Oncology Group performance status (ECOG PS), bladder wall invasion and technical failure, were recorded for each case. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for predicting the failure of retrograde ureteral stent insertion. In total, 38 out of 164 patients experienced bilateral obstruction, therefore, a total of 202 ureteral units were available for data analysis. The rate of insertion failure in MUO was 34.65%. Multivariate analyses identified ECOG PS, degree of hydronephrosis and bladder wall invasion as independent predictors for insertion failure. Overall, the present study found that rate of retrograde ureteral stent insertion failure is high in outpatients with MUO, and that ECOG PS, degree of hydronephrosis and bladder invasion are potential independent predictors of insertion failure. PMID:26870299

The analysis of incontinence episodes and other count data in patients with overactive bladder by Poisson and negative binomial regression.

PubMed

Martina, R; Kay, R; van Maanen, R; Ridder, A

2015-01-01

Clinical studies in overactive bladder have traditionally used analysis of covariance or nonparametric methods to analyse the number of incontinence episodes and other count data. It is known that if the underlying distributional assumptions of a particular parametric method do not hold, an alternative parametric method may be more efficient than a nonparametric one, which makes no assumptions regarding the underlying distribution of the data. Therefore, there are advantages in using methods based on the Poisson distribution or extensions of that method, which incorporate specific features that provide a modelling framework for count data. One challenge with count data is overdispersion, but methods are available that can account for this through the introduction of random effect terms in the modelling, and it is this modelling framework that leads to the negative binomial distribution. These models can also provide clinicians with a clearer and more appropriate interpretation of treatment effects in terms of rate ratios. In this paper, the previously used parametric and non-parametric approaches are contrasted with those based on Poisson regression and various extensions in trials evaluating solifenacin and mirabegron in patients with overactive bladder. In these applications, negative binomial models are seen to fit the data well. Copyright © 2014 John Wiley & Sons, Ltd.

Complete treatment with partial cystectomy in giant xanthogranulomatous cystitis case imitating bladder tumor.

PubMed

Balasar, Mehmet; Sönmez, Mehmet Giray; Oltulu, Pembe; Kandemir, Abdülkadir; Kılıç, Mehmet; Gürbüz, Recai

2017-01-01

Xanthogranulomatous cystitis (XC) is a very rare chronic benign inflammatory disease of the bladder. It may cause local invasion although it is not a malign lesion and may occur together with malign lesions. It has a clinical importance as the distinction from malign lesions is difficult clinically and pathologically. Sharing a 37-year-old female case with giant XC imitating bladder tumor referring to the hospital with hematuria and stomach ache, together with current literature, we wanted to present that the disease can be treated with bladder-preserving approaches instead of radical approaches even though the mass is big in these cases. Application of basic excision and partial resection for small masses and radical cystectomy for large masses was reported in literature. We think that our case may provide a contribution to literature in treatment approach since we provided surgical cure with partial resection in a big mass with dimensions of 9 cm × 8 cm which is different from the present literature. Even though XC is a rare disease, it should be considered in prediagnosis for especially big dimensioned masses, and treatment should be planned according to the pathology result after together with cystoscopy in suitable patients.

Systematic literature review of clinical trials evaluating pharmacotherapy for overactive bladder in elderly patients: An assessment of trial quality.

PubMed

Kistler, Kristin D; Xu, Yingxin; Zou, Kelly H; Ntanios, Fady; Chapman, Douglass S; Luo, Xuemei

2018-01-01

Overactive bladder (OAB) disproportionately affects older-aged adults, yet most randomized controlled trials (RCTs) underrepresent patients ≥65. This systematic literature review (SLR) identified RCTs evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly patients with OAB, and compared study quality across trials. MEDLINE ® , Embase ® , and Cochrane Collaboration Central Register of Clinical Trials databases were searched from inception through April 28, 2015 to identify published, peer-reviewed RCT reports evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly OAB patients (either ≥65 years or study-described as "elderly"). To assess study quality of RCT reports, we focused on internal/external validity, assessed via two scales: the validated Effective Public Health Practice Project [EPHPP]): Quality Assessment Tool for Quantitative Studies, and a tool commissioned by the Agency for Healthcare Research and Quality (AHRQ). Database searches yielded 1380 records that were then screened according to predefined inclusion/exclusion criteria. We included eight papers meeting study criteria. Despite scientific community efforts to improve RCT reporting standards, published reports still include incomplete and inconsistent reporting-of subject attrition, baseline patient characteristics, inclusion/exclusion criteria, and other important details. Only three of the eight OAB RCTs in this review received quality ratings of Strong (EPHPP) or Fair (AHRQ) and were multicenter with large samples. Despite the prevalence of OAB among older age individuals, relatively few RCTs evaluate OAB treatments explicitly among elderly subjects. The findings from this quality assessment suggest some areas for improvement in both conduct and reporting of future RCTs assessing OAB treatment in elderly. © 2017 Wiley Periodicals, Inc.

Bladder outlet obstruction triggers neural plasticity in sensory pathways and contributes to impaired sensitivity in erectile dysfunction.

PubMed

Malykhina, Anna P; Lei, Qi; Chang, Shaohua; Pan, Xiao-Qing; Villamor, Antonio N; Smith, Ariana L; Seftel, Allen D

2013-05-15

Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are common problems in aging males worldwide. The objective of this work was to evaluate the effects of bladder neck nerve damage induced by partial bladder outlet obstruction (PBOO) on sensory innervation of the corpus cavernosum (CC) and CC smooth muscle (CCSM) using a rat model of PBOO induced by a partial ligation of the bladder neck. Retrograde labeling technique was used to label dorsal root ganglion (DRG) neurons that innervate the urinary bladder and CC. Contractility and relaxation of the CCSM was studied in vitro, and expression of nitric oxide synthase (NOS) was evaluated by Western blotting. Concentration of the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide was measured by ELISA. Partial obstruction of the bladder neck caused a significant hypertrophy of the urinary bladders (2.5-fold increase at 2 wk). Analysis of L6-S2 DRG sections determined that sensory ganglia received input from both the urinary bladder and CC with 5-7% of all neurons double labeled from both organs. The contractile responses of CC muscle strips to KCl and phenylephrine were decreased after PBOO, followed by a reduced relaxation response to nitroprusside. A significant decrease in neuronal NOS expression, but not in endothelial NOS or protein kinase G (PKG-1), was detected in the CCSM of the obstructed animals. Additionally, PBOO caused some impairment to sensory nerves as evidenced by a fivefold downregulation of SP in the CC (P ≤ 0.001). Our results provide evidence that PBOO leads to the impairment of bladder neck afferent innervation followed by a decrease in CCSM relaxation, downregulation of nNOS expression, and reduced content of sensory neuropeptides in the CC smooth muscle. These results suggest that nerve damage in PBOO may contribute to LUTS-ED comorbidity and trigger secondary changes in the contraction/relaxation mechanisms of CCSM.

Bladder sensory desensitization decreases urinary urgency.

PubMed

Silva, Carlos; Silva, João; Castro, Helder; Reis, Frederico; Dinis, Paulo; Avelino, António; Cruz, Francisco

2007-06-11

Bladder desensitization has been investigated as an alternative treatment for refractory detrusor overactivity. Most open and controlled clinical trials conducted with intravesical RTX showed that desensitization delays the appearance of involuntary detrusor contractions during bladder filling and decreases the number of episodes of urgency incontinence. Urgency is being recognised as the fundamental symptom of overactive bladder (OAB), a symptomatic complex which recent epidemiological studies have shown to affect more than 10% of the Western population. As anti-muscarinic drugs, the first line treatment for OAB, are far from being able to fully control urgency, the opportunity to test other therapeutic approaches is created. The present work was, therefore, designed as an exploratory investigation to evaluate the effect of bladder desensitization on urinary urgency. Twenty-three OAB patients with refractory urgency entered, after given informed consent, a 30 days run-in period in which medications influencing the bladder function were interrupted. At the end of this period patients filled a seven-day voiding chart where they scored, using a 0-4 scale, the bladder sensations felt before each voiding. Then, patients were instilled with 100 ml of 10% ethanol in saline (vehicle solution) and 30 days later a second seven-day voiding chart was collected. Finally, patients were instilled with 100 ml of 50 nM RTX in 10% ethanol in saline. At 1 and 3 months additional voiding charts were collected. At the end of the vehicle and 3 months period patients were asked to give their subjective impression about the outcome of the treatment and about the willingness to repeat the previous instillation. At the end of the run-in period the mean number of episodes of urgency per week was 71 +/- 12 (mean +/- SEM). After vehicle instillation, the mean number of episodes of urgency was 56 +/- 11, but only 4 patients (17%) considered that their urinary condition had improved enough to repeat the treatment. At 1 and 3 months after RTX the number of episodes of urgency decreased to 39 +/- 9 (p = 0.002) and 37 +/- 6 (p = 0.02), respectively (p indicates statistical differences against vehicle). The percentage of patients with subjective improvement after RTX and willing to repeat the instillation at a later occasion was 69%. In OAB patients with refractory urgency bladder desensitization should be further investigated as an alternative to the standard management. Additionally, the specific effect of RTX on TRPV1 receptors suggests that urothelium and sub-urothelial C-fibers play an important role to the generation of urgency sensation.

Urinary tract infection pattern in adult women followed from childhood.

PubMed

Gebäck, Carin; Hansson, Sverker; Martinell, Jeanette; Sandberg, Torsten; Jodal, Ulf

2016-07-01

The aim of this study was to describe the pattern of urinary tract infection (UTI) and bladder function in women who had experienced recurrent UTI in childhood, with and without consequent renal damage, and followed for three to four decades. A population-based cohort of women who had been followed from the first UTI in childhood and previously studied at a median age of 27 years was studied at a median age of 41 years. Renal damage was evaluated by (99m)Tc-dimercaptosuccinic acid scan. Clinical data were collected on the pattern of recurrent UTIs and bladder function. A total of 86 women were investigated, of whom 58 had suffered renal damage and 28 were without. Febrile UTI in adulthood had occurred in 22 patients, once in 15 women and twice or more in seven women. There was a change in the infection pattern over time, evident already in childhood, that was characterized by a decrease in UTI frequency and a shift from febrile to non-febrile infections. A significant association was found between renal damage and febrile UTI (p = 0.046), and between abnormal bladder function and recurrent non-febrile UTI (p = 0.002). There was no relationship between persisting vesicoureteral reflux (VUR) and proneness to either symptomatic UTI (p = 0.99) or febrile UTI in adulthood (p = 0.14). Among this study cohort there was a continuously decreasing rate of febrile UTI in adulthood. Persisting VUR was not related to UTI in adulthood. Abnormal bladder function was related to non-febrile UTI but not to febrile UTI.

Detrusor after-contraction: a new insight.

PubMed

Valentini, Francoise A; Marti, Brigitte G; Robain, Gilberte; Nelson, Pierre P

2015-01-01

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. 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 <30mL and increase of detrusor pressure >10cmH(2)O. VBN model was used for analysis of both pressure and flow curves, and simulations of pathophysiological conditions. 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). 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.

The International Bladder Cancer Bank: proposal for a new study concept.

PubMed

Goebell, Peter J; Groshen, Susan; Schmitz-Dräger, Bernd J; Sylvester, Richard; Kogevinas, Manolis; Malats, Núria; Sauter, Guido; Barton Grossman, H; Waldman, Fred; Cote, Richard J

2004-01-01

At present, results of marker studies are often inconsistent and sometimes contradictory. Recognized problems include multiple different methods of performing the assays, different subsets of patients and different endpoints, leading to incompatible datasets. Although there has been discussion of establishing general methodological principles and guidelines (analogous to those for clinical trials) for design, conduct, analysis, and reporting of marker studies, these have not been widely implemented. There are no well-recognized prototypes or examples that the urologic researcher can use to model future marker studies. We will discuss our plans to establish a multi-institutional bladder cancer data base and virtual tumor bank as a resource for participating institutions to evaluate the biological and prognostic significance of potential markers for bladder cancer. Samples will be identified and stored at each participating institution and will be available for analysis. A standard, minimal set of patient and pathologic information will be collected. The use of common software, as part of this proposal will facilitate the data transfer of updated patient information to a central database. All contributing centers will have access to summarized information, also to simplify the process of finding collaborating partners. Prospectively collected, consistent datasets with available long-term follow-up, should provide information sooner than with a conventional prospective study. Furthermore, the quality of these data and samples may be superior to that of retrospectively collected data and samples. The proposed International Bladder Cancer Bank of specimens and data will be an effective tool during all phases of marker development. Copyright 2004 Elsevier Inc.

Management of non-neuropathic underactive bladder in children with voiding dysfunction by animated biofeedback: a randomized clinical trial.

PubMed

Ladi-Seyedian, Sanam; Kajbafzadeh, Abdol-Mohammad; Sharifi-Rad, Lida; Shadgan, Babak; Fan, Eileen

2015-01-01

To assess the efficacy of animated biofeedback and pelvic floor muscle (PFM) exercise in managing children with non-neuropathic underactive bladder (UB). A total of 50 children with UB without underlying neuropathic disease, aged 5-16 years, were included in this study. They were randomly divided into 2 equal treatment groups comprising standard urotherapy (hydration, scheduled voiding, toilet training, and diet) with (group A) or without (group B) animated biofeedback and PFM exercise. The follow-up period for each participant was 1 year. A complete voiding and bowel habit diary was recorded by participants' parents before and after 2 evaluations. In addition, uroflowmetry with electromyography and bladder ultrasound were performed before, 6 months, and 1 year after treatment. Results were compared between the 2 cohorts. Mean number of voiding episodes was significantly increased in group A after biofeedback therapy compared with group B with only standard urotherapy (6.6 ± 1.6 vs 4.5 ± 1 times a day; P <.000). Urinary tract infection did not relapse in 9 of 11 (81%) and 8 of 15 (38%) patients in groups A and B, respectively (P <.02). Postvoid residual volume and voiding time decreased considerably, whereas maximum urine flow increased significantly in group A compared with group B (17.2 ± 4.7 vs 12.9 ± 4.6 mL/s; P <.01). Combination of animated biofeedback and PFM exercise effectively improves sensation of bladder fullness and contractility in children with UB due to voiding dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Pharmacodynamic evaluation of Lys5, MeLeu9, Nle10-NKA(4–10) prokinetic effects on bladder and colon activity in acute spinal cord transected and spinally intact rats

PubMed Central

Kullmann, F. Aura; Katofiasc, M.; Thor, K.B.; Marson, L.

2017-01-01

Purpose To determine feasibility of a novel therapeutic approach to drug-induced voiding after spinal cord injury (SCI) using a well-characterized, peptide, neurokinin 2 receptor (NK2 receptor) agonist, Lys5, MeLeu9, Nle10-NKA(4–10) (LMN-NKA). Methods Cystometry and colorectal pressure measurements were performed in urethane anesthetized, intact and acutely spinalized, female rats. Bladder pressure and voiding were monitored in response to intravenous LMN-NKA given with the bladder filled to 70% capacity. Results LMN-NKA (0.1–300 µg/kg) produced dose dependent, rapid (< 60 s), short duration (< 15 min) increases in bladder pressure. In intact rats, doses above 0.3–1 µg/kg induced urine release (voiding efficiency of ~ 70% at ≥ 1 µg/kg). In spinalized rats, urine release required higher doses (≥ 10 µg/kg) and was less efficient (30–50%). LMN-NKA (0.1–100 µg/kg) also produced dose dependent increases in colorectal pressure. No tachyphylaxis was observed, and the responses were blocked by an NK2 receptor antagonist (GR159897, 1 mg/kg i.v.). No obvious cardiorespiratory effects were noted. Conclusions These results suggest that rapid-onset, short duration, drug-induced voiding is possible in acute spinal and intact rats with intravenous administration of an NK2 receptor agonist. Future challenges remain in regards to finding alternative routes of administration that produce clinically significant voiding, multiple times per day, in animal models of chronic SCI. PMID:27889808

Multielectrode array recordings of bladder and perineal primary afferent activity from the sacral dorsal root ganglia

NASA Astrophysics Data System (ADS)

Bruns, Tim M.; Gaunt, Robert A.; Weber, Douglas J.

2011-10-01

The development of bladder and bowel neuroprostheses may benefit from the use of sensory feedback. We evaluated the use of high-density penetrating microelectrode arrays in sacral dorsal root ganglia (DRG) for recording bladder and perineal afferent activity. Arrays were inserted in S1 and S2 DRG in three anesthetized cats. Neural signals were recorded while the bladder volume was modulated and mechanical stimuli were applied to the perineal region. In two experiments, 48 units were observed that tracked bladder pressure with their firing rates (79% from S2). At least 50 additional units in each of the three experiments (274 total; 60% from S2) had a significant change in their firing rates during one or more perineal stimulation trials. This study shows the feasibility of obtaining bladder-state information and other feedback signals from the pelvic region with a sacral DRG electrode interface located in a single level. This natural source of feedback would be valuable for providing closed-loop control of bladder or other pelvic neuroprostheses.

Intrafraction Bladder Motion in Radiation Therapy Estimated From Pretreatment and Posttreatment Volumetric Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foroudi, Farshad, E-mail: farshad.foroudi@petermac.org; Pham, Daniel; Bressel, Mathias

2013-05-01

Purpose: The use of image guidance protocols using soft tissue anatomy identification before treatment can reduce interfractional variation. This makes intrafraction clinical target volume (CTV) to planning target volume (PTV) changes more important, including those resulting from intrafraction bladder filling and motion. The purpose of this study was to investigate the required intrafraction margins for soft tissue image guidance from pretreatment and posttreatment volumetric imaging. Methods and Materials: Fifty patients with muscle-invasive bladder cancer (T2-T4) underwent an adaptive radiation therapy protocol using daily pretreatment cone beam computed tomography (CBCT) with weekly posttreatment CBCT. A total of 235 pairs of pretreatmentmore » and posttreatment CBCT images were retrospectively contoured by a single radiation oncologist (CBCT-CTV). The maximum bladder displacement was measured according to the patient's bony pelvis movement during treatment, intrafraction bladder filling, and bladder centroid motion. Results: The mean time between pretreatment and posttreatment CBCT was 13 minutes, 52 seconds (range, 7 min 52 sec to 30 min 56 sec). Taking into account patient motion, bladder centroid motion, and bladder filling, the required margins to cover intrafraction changes from pretreatment to posttreatment in the superior, inferior, right, left, anterior, and posterior were 1.25 cm (range, 1.19-1.50 cm), 0.67 cm (range, 0.58-1.12 cm), 0.74 cm (range, 0.59-0.94 cm), 0.73 cm (range, 0.51-1.00 cm), 1.20 cm (range, 0.85-1.32 cm), and 0.86 cm (range, 0.73-0.99), respectively. Small bladders on pretreatment imaging had relatively the largest increase in pretreatment to posttreatment volume. Conclusion: Intrafraction motion of the bladder based on pretreatment and posttreatment bladder imaging can be significant particularly in the anterior and superior directions. Patient motion, bladder centroid motion, and bladder filling all contribute to changes between pretreatment and posttreatment imaging. Asymmetric expansion of CTV to PTV should be considered. Care is required in using image-guided radiation therapy protocols that reduce CTV to PTV margins based only on daily pretreatment soft tissue position.« less

Modulation of gene expression and cell-cycle signaling pathways by the EGFR inhibitor gefitinib (Iressa) in rat urinary bladder cancer.

PubMed

Lu, Yan; Liu, Pengyuan; Van den Bergh, Francoise; Zellmer, Victoria; James, Michael; Wen, Weidong; Grubbs, Clinton J; Lubet, Ronald A; You, Ming

2012-02-01

The epidermal growth factor receptor inhibitor Iressa has shown strong preventive efficacy in the N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) model of bladder cancer in the rat. To explore its antitumor mechanism, we implemented a systems biology approach to characterize gene expression and signaling pathways in rat urinary bladder cancers treated with Iressa. Eleven bladder tumors from control rats, seven tumors from rats treated with Iressa, and seven normal bladder epithelia were profiled by the Affymetrix Rat Exon 1.0 ST Arrays. We identified 713 downregulated and 641 upregulated genes in comparing bladder tumors versus normal bladder epithelia. In addition, 178 genes were downregulated and 96 genes were upregulated when comparing control tumors versus Iressa-treated tumors. Two coexpression modules that were significantly correlated with tumor status and treatment status were identified [r = 0.70, P = 2.80 × 10(-15) (bladder tumor vs. normal bladder epithelium) and r = 0.63, P = 2.00 × 10(-42) (Iressa-treated tumor vs. control tumor), respectively]. Both tumor module and treatment module were enriched for genes involved in cell-cycle processes. Twenty-four and twenty-one highly connected hub genes likely to be key drivers in cell cycle were identified in the tumor module and treatment module, respectively. Analysis of microRNA genes on the array chips showed that tumor module and treatment module were significantly associated with expression levels of let-7c (r = 0.54, P = 3.70 × 10(-8) and r = 0.73, P = 1.50 × 10(-65), respectively). These results suggest that let-7c downregulation and its regulated cell-cycle pathway may play an integral role in governing bladder tumor suppression or collaborative oncogenesis and that Iressa exhibits its preventive efficacy on bladder tumorigenesis by upregulating let-7 and inhibiting the cell cycle. Cell culture study confirmed that the increased expression of let-7c decreases Iressa-treated bladder tumor cell growth. The identified hub genes may also serve as pharmacodynamic or efficacy biomarkers in clinical trials of chemoprevention in human bladder cancer. ©2011 AACR.

Ultrasound assessment of bladder wall thickness as a screening test for detrusor instability.

PubMed

Abou-Gamrah, Amgad; Fawzy, Mounir; Sammour, Hazem; Tadros, Sherif

2014-05-01

The aim of the current study was to evaluate the diagnostic accuracy of transvaginal ultrasound measurement of bladder wall thickness (BWT) in diagnosis of over active bladder (OAB). The current prospective study was conducted at Ain Shams University Maternity Hospital over 2 years. Patients presented to the urogynecology outpatient clinic with symptoms of urinary frequency, urgency, nocturia and/or urge incontinence were included in this study. The allocated patients were divided into two groups; Group 1(study group): fifty (50) patients with urodynamic diagnosis of detrusor instability (OAB) were included. Group 2 (control): fifty (50) patients with urodynamic diagnosis of stress incontinence were included. Using a transvaginal probe, BWT was measured in three sites at the thickest part of (a) the dome of the bladder (b) the trigone, and (c) the anterior wall of the bladder. An average of the three measurements was considered as the mean bladder thickness. A total of 100 patients with lower urinary symptoms were finally analyzed. There were no statistical significant differences between both groups regarding age, parity and body mass index, while there was statistically longer disease duration in group 2. Excluding urgency, there was statistical significant difference (P < 0.001) regarding lower urinary tract symptoms namely frequency, urgency incontinence, coital incontinence and nocturia. Patients in group 1 were more positive to symptoms of frequency, urgency incontinence, and nocturia, while patients in group 2 were more positive regarding coital incontinence. The thickness of trigon, dome, anterior wall and mean BWT was significantly higher in group 1 when compared to group 2. Receiver operator characteristics curve was constructed for estimating the association between mean BWT and prediction of OAB in patients with lower urinary tract symptoms. Mean BWT at 4.78 mm was considered as best cut-off value for prediction of OAB with sensitivity of 90 % and specificity of 78 %. Mean BWT was significantly associated with OAB > 4.78 mm as denoted by the significantly large area under the curve [AUC], AUC was 0.905. In women with lower urinary tract symptom, transvaginal ultrasounds measured mean BWT seems to be an effective non invasive diagnostic tool for prediction of OAB.

[Intra-detrusor injection of botulinumtoxin in patients with refractory overactive bladder].

PubMed

Krhut, J; Kopecký, J

2007-12-01

Symptoms of overactive bladder affect the quality of patients' life significantly. There is a standard treatment consisting in application of anticholinergics or possibly other conservative methods. This treatment fails at a certain part of patients however. While radical surgical therapy used to be offered to such patients in the past, the botulinumtoxin injection is available at present. The aim of the paper is to assess the efficacy and safety of this treatment method in own set of female patients with refractory overractive bladder. The set totals of 16 female patients with refractory overactive bladder. The average age in the set is 52.7 (38-69) years. Patients were treated by the application of botulinumtoxin in the period 6/2004-12/2006; the follow-up is 21.6 (6-36) months. In all cases the Dysport preparation in the dose 1000 UI was used for application. Botulinumtoxin has been applied during a short endoscopic procedure using a flexible needle into 40 points in the detrusor. Subjective satisfaction, data from voiding diaries, urodynamic parameters and the duration of effect persistence were evaluated. Subjective satisfaction with the treatment result was reached in 13 (81.3%) patients. In 12 (75.0%) patients the full continence was obtained. Average urinary bladder evacuation frequency decreased from 15.8/24 h to 5.5/24 h after the treatment, the number of urgency episodes decreased from 7.7/24 h to 0.8/24 h while average evacuated volume increased from 107.9 to 329.0 ml. The maximum cystometric capacity increased from 151.9 ml to 311.2 ml while maximum detrusor pressure decreased from 31.0 to 143 cm H2O at urodynamic assesment. The changes in all monitored parameters were statistically significant. The effect duration was 10.3 (6-13) months. No side effects of the application were registered during the treatment. The application of botulinumtoxin into detrusor is an effective and safe treatment method for refractory overactive bladder. Final standardization of the treatment by botulinumtoxin additional studies focused especially to the research of the relation among the dose, solution and clinical effect are necessary.

The effect of intravesical chemotherapy in the prevention of intravesical recurrence after nephroureterectomy for upper tract urothelial carcinoma: a meta-analysis.

PubMed

Yuan, Haichao; Mao, Xiangming; Bai, Yunjin; Li, Hengping; Liu, Liangren; Pu, Chunxiao; Li, Jinhong; Tang, Yin; Wei, Qiang; Han, Ping

2015-08-01

The standard management of upper urinary tract urothelial carcinoma (UUT-UC) is nephroureterectomy with bladder cuff excision, but after surgery, approximately 22-47% of patients with UUT-UC develop subsequent bladder tumour recurrence, potentially because of the implantation of cancer cells from the primary tumour. To conduct a meta-analysis to evaluate the effect of prophylactic intravesical chemotherapy in the prevention of bladder recurrence after nephroureterectomy for UUT-UC. An electronic database search of Medline, Embase, the Cochrane Library, CancerLit and ClinicalTrials.gov was performed to identify appropriate studies prior to March 2013.All studies comparing nephroureterectomy alone with prophylactic intravesical chemotherapy after nephroureterectomy were included. The main outcome measure for this meta-analysis was the rate of bladder recurrence after nephroureterectomy. The search was not limited by language. The review process followed the guidelines of the Cochrane Collaboration. The analysis was conducted using the Review Manager Version RevMan 5.0 software (The Nordic Cochrane Centre, The Cochrane Collaboration). A total of 592 patients were included in this study, of whom 257 underwent intravesical instillation after nephroureterectomy and 335 underwent nephroureterectomy alone. Our meta-analysis demonstrated that the rate of recurrence after 12 months was significantly lower in the intravesical instillation after nephroureterectomy group than in the nephroureterectomy-alone group [odds ratio (OR): 0.48; 95% confidence interval (CI): 0.28-0.81; P = 0.006]. A significant decrease in bladder recurrence after at least 24  months was also observed in the intravesical instillation after nephroureterectomy group (OR: 0.40; 95% CI: 0.24-0.67; P = 0.0004). A subgroup analysis demonstrated that the pattern of differences was similar to those from the total group analysis. Prophylactic intravesical chemotherapy was effective for the prevention of bladder recurrence after nephroureterectomy. Therefore, we suggest that prophylactic intravesical chemotherapy should be performed in patients with UUT-UC after nephroureterectomy, but the optimal chemotherapy regimen and the initial time of instillation should be explored in future studies.

[Bladder rupture caused by spontaneous perforation of an infected urachal cyst].

PubMed

Maruschke, M; Kreutzer, H J; Seiter, H

2003-06-01

Anomalies of the fetal urachus are rare. Normally, the postnatal urachus presents as a fibrous band extending from the bladder to the umbilicus. Urachal cysts may occur in postnatal life. Spontaneous perforation of urachal cysts is a very rare condition, which clinically may not be distinguishable from other acute abdominal conditions. We report a case of a 63-year-old male with a history of recurrent urinary tract infections and a bladder rupture caused by a spontaneous perforation of an infected urachal cyst. The symptomatology showed abdominal rigidity and pain, a palpable mass in the lower abdomen, and hematuria. Laboratory findings showed leukocytosis and an increased CRP level. The bladder rupture was confirmed by cystography. Bacteriologic examination identified Proteus vulgaris, Corynebacterium species, and Klebsiella pneumoniae. Most of the published cases in the literature report about intraperitoneal perforation of infected urachal cysts. In the present case, we found a spontaneous perforation of an infected urachal cyst leading to an extraperitoneal bladder rupture with an extraperitoneal limitation of the infection. The definitive therapy was complete surgical excision including a cuff of the bladder, drainage, and systemic broad-spectrum and local application of antibiotics. The further course was uneventful.

Overactive bladder – 18 years – part I

PubMed Central

Truzzi, Jose Carlos; Gomes, Cristiano Mendes; Bezerra, Carlos A.; Plata, Ivan Mauricio; Campos, Jose; Garrido, Gustavo Luis; Almeida, Fernando G.; Averbeck, Marcio Augusto; Fornari, Alexandre; Salazar, Anibal; Dell'Oro, Arturo; Cintra, Caio; Sacomani, Carlos Alberto Ricetto; Tapia, Juan Pablo; Brambila, Eduardo; Longo, Emilio Miguel; Rocha, Flavio Trigo; Coutinho, Francisco; Favre, Gabriel; Garcia, José Antonio; Castaño, Juan; Reyes, Miguel; Leyton, Rodrigo Eugenio; Ferreira, Ruiter Silva; Duran, Sergio; López, Vanda; Reges, Ricardo

2016-01-01

ABSTRACT Abstract: Overactive bladder syndrome is one of the lower urinary tract dysfunctions with the highest number of scientific publications over the past two decades. This shows the growing interest in better understanding this syndrome, which gathers symptoms of urinary urgency and increased daytime and nighttime voiding frequency, with or without urinary incontinence and results in a negative impact on the quality of life of approximately one out of six individuals – including both genders and almost all age groups. The possibility of establishing the diagnosis just from clinical data made patients' access to specialized care easier. Physiotherapy resources have been incorporated into the urological daily practice. A number of more selective antimuscarinic drugs with consequent lower adverse event rates were released. Recently, a new class of oral drugs, beta-adrenergic agonists has become part of the armamentarium for Overactive Bladder. Botulinum toxin injections in the bladder and sacral neuromodulation are routine modalities of treatment for refractory cases. During the 1st Latin-American Consultation on Overactive Bladder, a comprehensive review of the literature related to the evolution of the concept, epidemiology, diagnosis, and management was conducted. This text corresponds to the first part of the review Overactive Bladder 18-years. PMID:27176184

Safe percutaneous suprapubic catheterisation

PubMed Central

Goyal, NK; Goel, A; Sankhwar, SN

2012-01-01

INTRODUCTION We describe our technique of percutaneous suprapubic catheter insertion with special reference to steps that help to avoid common complications of haematuria and catheter misplacement. METHODS The procedure is performed using a stainless steel reusable trocar under local infiltrative anaesthesia, usually at the bedside. After clinical confirmation of a full bladder, the trocar is advanced into the bladder through a skin incision. Once the bladder is entered, the obturator is removed and the assistant inserts a Foley catheter followed by rapid balloon inflation. Slight traction is applied to the catheter for about five minutes. Patients with previous lower abdominal surgery, an inadequately distended bladder or acute pelvic trauma do not undergo suprapubic catheterisation using this method. RESULTS The procedure was performed in 72 men (mean age: 42.4 years, range: 18–78 years) with urinary retention with a palpable bladder. The average duration of the procedure was less than five minutes. No complications were noted in any of the patients. CONCLUSIONS Trocar suprapubic catheter insertion is a safe and effective bedside procedure for emergency bladder drainage and can be performed by resident surgeons. The common complications associated with the procedure can be avoided with a few careful steps. PMID:23131233

Intraperitoneal Urinary Bladder Perforation with Pneumoperitoneum in Association with Indwelling Foley Catheter Diagnosed in Emergency Department.

PubMed

Zhan, Chenyang; Maria, Pedro P; Dym, R Joshua

2017-11-01

Indwelling Foley catheter is a rare cause of urinary bladder perforation, a serious injury with high mortality that demands accurate and prompt diagnosis. While the gold standard for diagnosis of bladder injury is computed tomography (CT) cystography, few bladder ruptures associated with Foley catheter have been reported to be diagnosed in the emergency department (ED). An 83-year-old man with indwelling Foley catheter presented to the ED for hematuria and altered mental status. He was diagnosed to have intraperitoneal rupture of the urinary bladder in the ED using abdominal and pelvic CT without contrast, which demonstrated bladder wall discontinuity, intraperitoneal free fluid, and pneumoperitoneum. The patient was treated successfully with medical management and bladder drainage. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: To our knowledge, this is the first report of intraperitoneal urinary bladder perforation associated with Foley catheter diagnosed in the ED by CT without contrast. Pneumoperitoneum found in this case was a clue to the diagnosis and is a benign finding that does not necessitate urgent surgical intervention. The early and accurate diagnosis in this case allowed for effective management with good clinical outcome. The use of indwelling Foley catheter has a high prevalence, especially in long-term care facility residents, who are frequent visitors in the ED. Therefore, emergency physicians and radiologists should be familiar with the presentation and imaging findings of this potential injury associated with Foley catheters. Copyright © 2017 Elsevier Inc. All rights reserved.

Empty-bladder (hysterographic) view on US for evaluation of intrauterine devices. Work in progress.

PubMed

Carroll, R; Gombergh, R

1987-06-01

Ultrasound scanning of the pelvis with an empty bladder permits a true frontal view of the uterus to be easily obtained. This view is comparable to the en face view seen at hysterography performed with contrast material. Good definition both of the endometrium and the uterine wall makes this the optimal method for the evaluation of an intrauterine contraceptive device.

Overexpression of HER-2 via immunohistochemistry in canine urinary bladder transitional cell carcinoma - A marker of malignancy and possible therapeutic target.

PubMed

Millanta, F; Impellizeri, J; McSherry, L; Rocchigiani, G; Aurisicchio, L; Lubas, G

2018-06-01

Transitional cell carcinoma (TCC) is the most commonly diagnosed neoplasm in the urinary bladder. Distant metastases to the regional lymph nodes, lungs, abdominal organs or bones are noted in up to 50% of dogs at time of death. Surgical excision is often not practical as TCC typically involve the trigone of the bladder and/or occurs multifocally throughout the bladder with field cancerization. Therapeutic approaches are very challenging and the requirement to evaluate alternative therapeutic protocols that may prolong survival times in dogs bearing these tumours is compelling. We assessed the immunohistochemical expression of HER-2 in 23 cases of canine TCCs of the urinary bladder and compare it with non-neoplastic urothelium in order to evaluate a rationale for targeted therapies and gene-based vaccines. HER-2 positivity was recorded in 13/23 (56%) neoplastic lesions. The receptor was significantly overexpressed in neoplastic than in non-neoplastic samples (P = .015). According to our preliminary results, it would be of interest to further evaluate the role of HER-2 in canine TCCs as a marker of malignancy and a therapeutic target for cancer vaccine and antibodies. Moreover, the significantly different overexpression of HER-2 in TCCs than in non-neoplastic urothelium further supports to investigate its role in the progression toward malignancy of non-neoplastic lesions. © 2017 John Wiley & Sons Ltd.

Bladder Tumor in Women with Microscopic Hematuria: An Iranian Experience and a Review of the Literature

PubMed Central

Abbaszadeh, Shahin; Taheri, Saeed; Nourbala, Mohammad Hossein

2009-01-01

Aim. In this study we report our experience with microhematuria and its relation with bladder tumors in Iranian women. Materials and Methods. Overall 249 women were evaluated. Microscopic hematuria was defined as three or more red blood cells per high-power field on at least two different occasions. Patients with a history of gross hematuria or coagulation disorders, having organic diseases, urinary stones, urinary tract infections, nephrological diseases, and local lesions such as urethral caruncle were excluded from the study population. Final diagnosis of malignant tumors was done with cystoscopy and biopsy specimen pathological assessment in all cases. Results. Age for the study population was 49.7 ± 11.8 years. 95 (38%) of patients were identified during routine check up and presenting symptoms in other patients were frequency, dysuria, stress urge incontinence, urge incontinence, feeling of incomplete urine emptying, and flunk pain, respectively. Finally, 7 (2.8%) of study subjects were confirmed as having bladder tumors. One of tumor cases was diagnosed 24 months after initial assessments. Patients with bladder tumor were significantly older; more frequently had diverticulum in their bladder wall (P < .05). Conclusion. Female microscopic hematuria is relevant and deserves evaluations, especially in elderly patients. Patients whose reason for microhematuria would not be diagnosed at the initial evaluations should be followed. PMID:19639044

The economics of bladder cancer: costs and considerations of caring for this disease.

PubMed

Svatek, Robert S; Hollenbeck, Brent K; Holmäng, Sten; Lee, Richard; Kim, Simon P; Stenzl, Arnulf; Lotan, Yair

2014-08-01

Due to high recurrence rates, intensive surveillance strategies, and expensive treatment costs, the management of bladder cancer contributes significantly to medical costs. To provide a concise evaluation of contemporary cost-related challenges in the care of patients with bladder cancer. An emphasis is placed on the initial diagnosis of bladder cancer and therapy considerations for both non-muscle-invasive bladder cancer (NMIBC) and more advanced disease. A systematic review of the literature was performed using Medline (1966 to February 2011). Medical Subject Headings (MeSH) terms for search criteria included "bladder cancer, neoplasms" OR "carcinoma, transitional cell" AND all cost-related MeSH search terms. Studies evaluating the costs associated with of various diagnostic or treatment approaches were reviewed. Routine use of perioperative chemotherapy following complete transurethral resection of bladder tumor has been estimated to provide a cost savings. Routine office-based fulguration of small low-grade recurrences could decrease costs. Another potential important target for decreasing variation and cost lies in risk-modified surveillance strategies after initial bladder tumor removal to reduce the cost associated with frequent cystoscopic and radiographic procedures. Optimizing postoperative care after radical cystectomy has the potential to decrease length of stay and perioperative morbidity with substantial decreases in perioperative care expenses. The gemcitabine-cisplatin regimen has been estimated to result in a modest increase in cost effectiveness over methotrexate, vinblastine, doxorubicin, and cisplatin. Additional costs of therapies need to be balanced with effectiveness, and there are significant gaps in knowledge regarding optimal surveillance and treatment of both early and advanced bladder cancer. Regardless of disease severity, improvements in the efficiency of bladder cancer care to limit unnecessary interventions and optimize effective cancer treatment can reduce overall health care costs. Two scenarios where economic and comparative-effectiveness research is limited but would be most beneficial are (1) the management of NMIBC patients where excessive costs are due to vigilant surveillance strategies and (2) in patients with metastatic disease due to the enormous cost associated with late-stage and end-of-life care. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Tissue engineering of urinary bladder - current state of art and future perspectives.

PubMed

Adamowicz, Jan; Kowalczyk, Tomasz; Drewa, Tomasz

2013-01-01

Tissue engineering and biomaterials science currently offer the technology needed to replace the urinary tract wall. This review addresses current achievements and barriers for the regeneration of the urinary blad- der based on tissue engineering methods. Medline was search for urinary bladder tissue engineering regenerative medicine and stem cells. Numerous studies to develop a substitute for the native urinary bladder wall us- ing the tissue engineering approach are ongoing. Stem cells combined with biomaterials open new treatment methods, including even de novo urinary bladder construction. However, there are still many issues before advances in tissue engineering can be introduced for clinical application. Before tissue engineering techniques could be recognize as effective and safe for patients, more research stud- ies performed on large animal models and with long follow-up are needed to carry on in the future.

Street ketamine-associated bladder dysfunction: an emerging health problem.

PubMed

Lee, Py; Ong, Ta; Chua, Cb; Lei, Ccm; Teh, Gc

2009-01-01

Ketamine is frequently abused nowadays as a recreational drug. Case reports are emerging since 2007 to describe a new clinical entity of severe bladder dysfunction associated with chronic abuse of street ketamine. Severe lower urinary tract symptoms of urinary frequency and urgency which are refractory to conventional treatment. Quality of life is adversely affected as a consequence. Chronic kidney disease will develop in advanced cases. Investigation findings: The urine is sterile on culture. Ultrasound will show reduced bladder capacity with thickened bladder wall. In advanced stage, hydronephrosis and renal impairment will develop. Patients should be advised to stop street ketamine use immediately. Anticholinergic medication could be tried to alleviate the symptoms. Refractory cases with dilatation of the upper urinary tract might need urinary diversion. Awareness of this new condition is essential in diagnosis. Early intervention offers better treatment outcome.

Interfractional variation in bladder volume and its impact on cervical cancer radiotherapy: Clinical significance of portable bladder scanner

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Huanli; Jin, Fu; Yang, Dingyi

Purpose: A constant bladder volume (BV) is essential to direct the radiotherapy (RT) of pelvic tumors with precision. The purpose of this study was to investigate changes in BV and their impact on cervical cancer RT and to assess the clinical significance of a portable bladder scanner (BS) in achieving a constant BV. Methods: A standard bladder phantom (133 ml) and measurements of actual urine volume were both used as benchmarks to evaluate the accuracy of the BS. Comparisons of BS with computed tomography (CT), cone-beam CT (CBCT), and an ultrasound diagnostic device (iU22) were made. Twenty-two consecutive patients withmore » cervical cancer treated with external beam radical RT were divided into an experimental group (13 patients) and a control group (9 patients). In the experimental group, the BV was measured multiple times by BS pre-RT until it was consistent with that found by planning CT. Then a CBCT was performed. The BV was measured again immediately post-RT, after which the patient’s urine was collected and recorded. In the control group, CBCT only was performed pre-RT. Interfractional changes in BV and their impact on cervical cancer RT were investigated in both groups. The time of bladder filling was also recorded and analyzed. Results: In measuring the volume of the standard bladder phantom, the BS deviated by 1.4% in accuracy. The difference between the measurements of the BS and the iU22 had no statistical significance (linear correlation coefficient 0.96, P < 0.05). The BV measured by the BS was strongly correlated with the actual urine volume (R = 0.95, P < 0.05), planning CT (R = 0.95, P < 0.05), or CBCT (R = 0.91, P < 0.05). Compared with the BV at the time of CT, its value changed by −36.1% [1 SD (standard deviation) 42.3%; range, −79.1%–29.4%] in the control group, and 5.2% (1 SD 21.5%; range, −13.3%–22.1%) in the experimental group during treatment. The change in BV affected the target position in the superior–inferior (SI) direction but had little or no effect in the anterior–posterior and right–left directions. Based on the collected data, the target displacement in the SI direction was reduced from 2.0 to 0.4 mm, while the CTV-to-PTV (CTV: clinical target volume; PTV: planning target volume) margin in the SI direction was reduced from 11.1 to 6.4 mm. The BV increased by 3.7 ± 1.0 ml/min (range, 1.7–4.7 ml/min), which depended on the amount of water ingested by the patient (R = 0.96, P < 0.05). No correlation was found between the rate of urinary inflow and the patient’s body mass. The authors were able to reduce the workload of measuring by using individual patient information including the patient’s age, the water-drinking amount, time at which water-drinking began, and patient’s diet. Conclusions: Changes in the BV have an influence on the RT of cervical cancer. A consistent and reproducible BV is acquired by using a portable BS, whereby the target displacement and CTV-to-PTV margin can be both reduced in the SI direction.« less

Bladder Retraining

MedlinePlus

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Bladder Outlet Obstruction: Causes in Men?

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A pilot study on bladder wall thickness at different filling stages

NASA Astrophysics Data System (ADS)

Zhang, Xi; Liu, Yang; Li, Baojuan; Zhang, Guopeng; Liang, Zhengrong; Lu, Hongbing

2015-03-01

The ever-growing death rate and the high recurrence of bladder cancer make the early detection and appropriate followup procedure of bladder cancer attract more attention. Compare to optical cystoscopy, image-based studies have revealed its potentials in non-invasive observations of the abnormities of bladder recently, in which MR imaging turns out to be a better choice for bladder evaluation due to its non-ionizing and high contrast between urine and wall tissue. Recent studies indicate that bladder wall thickness tends to be a good indicator for detecting bladder wall abnormalities. However, it is difficult to quantitatively compare wall thickness of the same subject at different filling stages or among different subjects. In order to explore thickness variations at different bladder filling stages, in this study, we preliminarily investigate the relationship between bladder wall thickness and bladder volume based on a MRI database composed of 40 datasets acquired from 10 subjects at different filling stages, using a pipeline for thickness measurement and analysis proposed in our previous work. The Student's t-test indicated that there was no significant different on wall thickness between the male group and the female group. The Pearson correlation analysis result indicated that negative correlation with a correlation coefficient of -0.8517 existed between the wall thickness and bladder volume, and the correlation was significant(p <0.01). The corresponding linear regression equation was then estimated by the unary linear regression. Compared to the absolute value of wall thickness, the z-score of wall thickness would be more appropriate to reflect the thickness variations. For possible abnormality detection of a bladder based on wall thickness, the intra-subject and inter-subject thickness variation should be considered.

Whole-Pelvis or Bladder-Only Chemoradiation for Lymph Node-Negative Invasive Bladder Cancer: Single-Institution Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tunio, Mutahir A., E-mail: drmutahirtonio@hotmail.com; Hashmi, Altaf; Qayyum, Abdul

2012-03-01

Purpose: Whole-pelvis (WP) concurrent chemoradiation (CCRT) is the standard bladder preserving option for patients with invasive bladder cancer. The standard practice is to treat elective pelvic lymph nodes, so our aim was to evaluate whether bladder-only (BO) CCRT leads to results similar to those obtained by standard WP-CCRT. Methods and Materials: Patient eligibility included histopathologically proven muscle-invasive bladder cancer, lymph nodes negative (T2-T4, N-) by radiology, and maximal transurethral resection of bladder tumor with normal hematologic, renal, and liver functions. Between March 2005 and May 2006, 230 patients were accrued. Patients were randomly assigned to WP-CCRT (120 patients) and BO-CCRTmore » (110 patients). Data regarding the toxicity profile, compliance, initial complete response rates at 3 months, and occurrence of locoregional or distant failure were recorded. Results: With a median follow-up time of 5 years (range, 3-6), WP-CCRT was associated with a 5-year disease-free survival of 47.1% compared with 46.9% in patients treated with BO-CCRT (p = 0.5). The bladder preservation rates were 58.9% and 57.1% in WP-CCRT and BO-CCRT, respectively (p = 0.8), and the 5-year overall survival rates were 52.9% for WP-CCRT and 51% for BO-CCRT (p = 0.8). Conclusion: BO-CCRT showed similar rates of bladder preservation, disease-free survival, and overall survival rates as those of WP-CCRT. Smaller field sizes including bladder with 2-cm margins can be used as bladder preservation protocol for patients with muscle-invasive lymph node-negative bladder cancer to minimize the side effects of CCRT.« less

Diagnosis and Management of Lower Urinary Tract Dysfunction.

PubMed

McDonough, Robert C; Ryan, Stephen T

2016-06-01

Lower urinary tract dysfunction is an umbrella diagnosis that covers difficulty evacuating urine from the bladder. In its most simple form, it is either an inability to store urine or an inability to empty the bladder of urine appropriately. The normal and the abnormal bladder, the role of urodynamics in evaluation of lower urinary tract dysfunction, and the medical and behavioral management of some of these disorders are reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Transitional cell carcinoma of the bladder in children and adolescents: six-case series and review of the literature.

PubMed

Lerena, Javier; Krauel, Lucas; García-Aparicio, Luis; Vallasciani, Santiago; Suñol, Mariona; Rodó, Joan

2010-10-01

Lower urinary tract tumours are uncommon in paediatrics. Transitional cell carcinoma of the bladder (TCCB) is rarely found in the first two decades of life and is exceptional under 10 years of age. The present series aimed to expand the number of reported cases in the literature. In 1984-2007, six patients (four male, two female), aged 6, 9, 12, 13, 14 and 17 years, were treated at our centre. Clinical presentation was macroscopic haematuria in five and pyelonephritis in one. Physical examination, laboratory analysis, ultrasound and cystoscopy were performed before surgical treatment in all patients. Follow up was by clinical and ultrasound assessment. Neither physical examination nor laboratory analysis revealed any significant abnormalities, but ultrasound showed exophytic intravesical lesions. Surgical resection was performed endoscopically. Histological studies showed grade I TCCB in all cases. The immediate postoperative period was uneventful and long-term follow up did not reveal recurrence. Despite its low incidence in children, TCCB must be suspected in the event of macroscopic haematuria. Ultrasound followed by cystoscopy are the ideal diagnostic tools for visualization of these tumours. Endoscopic resection proved effective in all the present cases. Follow up must be clinical with periodic ultrasound evaluation. Urine cytologic examination is ineffective. Periodic cystoscopy is indicated only in cases of clinical or ultrasonographic suspicion of recurrence. Copyright © 2009 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Stem cell bioprocessing: fundamentals and principles

PubMed Central

Placzek, Mark R.; Chung, I-Ming; Macedo, Hugo M.; Ismail, Siti; Mortera Blanco, Teresa; Lim, Mayasari; Min Cha, Jae; Fauzi, Iliana; Kang, Yunyi; Yeo, David C.L.; Yip Joan Ma, Chi; Polak, Julia M.; Panoskaltsis, Nicki; Mantalaris, Athanasios

2008-01-01

In recent years, the potential of stem cell research for tissue engineering-based therapies and regenerative medicine clinical applications has become well established. In 2006, Chung pioneered the first entire organ transplant using adult stem cells and a scaffold for clinical evaluation. With this a new milestone was achieved, with seven patients with myelomeningocele receiving stem cell-derived bladder transplants resulting in substantial improvements in their quality of life. While a bladder is a relatively simple organ, the breakthrough highlights the incredible benefits that can be gained from the cross-disciplinary nature of tissue engineering and regenerative medicine (TERM) that encompasses stem cell research and stem cell bioprocessing. Unquestionably, the development of bioprocess technologies for the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation and safety of the process and the product. The successful translation will require contributions from fundamental research (from developmental biology to the ‘omics’ technologies and advances in immunology) and from existing industrial practice (biologics), especially on automation, quality assurance and regulation. The timely development, integration and execution of various components will be critical—failures of the past (such as in the commercialization of skin equivalents) on marketing, pricing, production and advertising should not be repeated. This review aims to address the principles required for successful stem cell bioprocessing so that they can be applied deftly to clinical applications. PMID:19033137

Stem cell bioprocessing: fundamentals and principles.

PubMed

Placzek, Mark R; Chung, I-Ming; Macedo, Hugo M; Ismail, Siti; Mortera Blanco, Teresa; Lim, Mayasari; Cha, Jae Min; Fauzi, Iliana; Kang, Yunyi; Yeo, David C L; Ma, Chi Yip Joan; Polak, Julia M; Panoskaltsis, Nicki; Mantalaris, Athanasios

2009-03-06

In recent years, the potential of stem cell research for tissue engineering-based therapies and regenerative medicine clinical applications has become well established. In 2006, Chung pioneered the first entire organ transplant using adult stem cells and a scaffold for clinical evaluation. With this a new milestone was achieved, with seven patients with myelomeningocele receiving stem cell-derived bladder transplants resulting in substantial improvements in their quality of life. While a bladder is a relatively simple organ, the breakthrough highlights the incredible benefits that can be gained from the cross-disciplinary nature of tissue engineering and regenerative medicine (TERM) that encompasses stem cell research and stem cell bioprocessing. Unquestionably, the development of bioprocess technologies for the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation and safety of the process and the product. The successful translation will require contributions from fundamental research (from developmental biology to the 'omics' technologies and advances in immunology) and from existing industrial practice (biologics), especially on automation, quality assurance and regulation. The timely development, integration and execution of various components will be critical-failures of the past (such as in the commercialization of skin equivalents) on marketing, pricing, production and advertising should not be repeated. This review aims to address the principles required for successful stem cell bioprocessing so that they can be applied deftly to clinical applications.

Evaluation of transforming growth factor-β1 suppress Pokemon/epithelial-mesenchymal transition expression in human bladder cancer cells.

PubMed

Li, Wei; Kidiyoor, Amritha; Hu, Yangyang; Guo, Changcheng; Liu, Min; Yao, Xudong; Zhang, Yuanyuan; Peng, Bo; Zheng, Junhua

2015-02-01

Transforming growth factor-β1 (TGF-β1) plays a dual role in apoptosis and in proapoptotic responses in the support of survival in a variety of cells. The aim of this study was to determine the function of TGF-β1 in bladder cancer cells and the relationship with POK erythroid myeloid ontogenic factor (Pokemon). TGF-β1 and its receptors mediate several tumorigenic cascades that regulate cell proliferation, migration, and survival of bladder cancer cells. Bladder cancer cells T24 were treated with different levels of TGF-β1. Levels of Pokemon, E-cadherin, Snail, MMP2, MMP9, Twist, VEGF, and β-catenin messenger RNA (mRNA) and protein were examined by real-time quantitative fluorescent PCR and Western blot analysis, respectively. The effects of TGF-β1 on epithelial-mesenchymal transition of T24 cells were evaluated with wound-healing assay, proliferation of T24 was evaluated with reference to growth curves with MTT assay, and cell invasive ability was investigated by Transwell assay. Data show that Pokemon was inhibited by TGF-β1 treatment; the gene and protein of E-cadherin and β-catenin expression level showed decreased markedly after TGF-β1 treatment (P < 0.05). While the bladder cancer cell after TGF-β1 treatment showed a significantly reduced wound-closing efficiency at 6, 12, and 24 h, mechanistic analyses demonstrated that different levels of TGF-β1 promotes tumor cell growth, migration, and invasion in bladder cancer cells (P < 0.01, P < 0.05, respectively). In summary, our findings suggest that TGF-β1 may inhibit the expression of Pokemon, β-catenin, and E-cadherin. The high expression of TGF-β1 leads to an increase in the phenotype and apical-base polarity of epithelial cells. These changes of cells may result in the recurrence and progression of bladder cancer at last. Related mechanism is worthy of further investigation.

Quantitative Evaluation of Heavy Metals and Trace Elements in the Urinary Bladder: Comparison Between Cancerous, Adjacent Non-cancerous and Normal Cadaveric Tissue.

PubMed

Abdel-Gawad, Mahmoud; Elsobky, Emad; Shalaby, Mahmoud M; Abd-Elhameed, Mohamed; Abdel-Rahim, Mona; Ali-El-Dein, Bedeir

2016-12-01

The role of heavy metals and trace elements (HMTE) in the development of some cancers has been previously reported. Bladder carcinoma is a frequent malignancy of the urinary tract. The most common risk factors for bladder cancer are exposure to industrial carcinogens, cigarette smoking, gender, and possibly diet. The aim of this study was to evaluate HTME concentrations in the cancerous and adjacent non-cancerous tissues and compare them with those of normal cadaveric bladder. This prospective study included 102 paired samples of full-thickness cancer and adjacent non-cancerous bladder tissues of radical cystectomy (RC) specimens that were histologically proven as invasive bladder cancer (MIBC). We used 17 matched controls of non-malignant bladder tissue samples from cadavers. All samples were processed and evaluated for the concentration of 22 HMTE by using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Outcome analysis was made by the Mann-Whitney U, chi-square, Kruskal-Wallis, and Wilcoxon signed ranks tests. When compared with cadaveric control or cancerous, the adjacent non-cancerous tissue had higher levels of six elements (arsenic, lead, selenium, strontium, zinc, and aluminum), and when compared with the control alone, it had a higher concentration of calcium, cadmium, chromium, potassium, magnesium, and nickel. The cancerous tissue had a higher concentration of cadmium, lead, chromium, calcium, potassium, phosphorous, magnesium, nickel, selenium, strontium, and zinc than cadaveric control. Boron level was higher in cadaveric control than cancerous and adjacent non-cancerous tissue. Cadmium level was higher in cancerous tissue with node-positive than node-negative cases. The high concentrations of cadmium, lead, chromium, nickel, and zinc, in the cancerous together with arsenic in the adjacent non-cancerous tissues of RC specimens suggest a pathogenic role of these elements in BC. However, further work-up is needed to support this conclusion by the application of these HMTE on BC cell lines.

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

PubMed

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.

Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy.

PubMed

Mavroidis, Panayiotis; Pearlstein, Kevin A; Dooley, John; Sun, Jasmine; Saripalli, Srinivas; Das, Shiva K; Wang, Andrew Z; Chen, Ronald C

2018-02-02

To estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms. Ninety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods. For the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D 50  = 64.2Gy, m = 0.50, n = 1.0; 2) D 50  = 95.0Gy, m = 0.45, n = 0.50; 3) D 50  = 83.1Gy, m = 0.56, n = 1.00; and 4) D 50  = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3. Different dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes.

[Giant prostatic calculus with neurogenic bladder disease and prostate diverticulum: a case report and review of the literature].

PubMed

Li, Xiao-Shi; Quan, Chang-Yi; Li, Gang; Cai, Qi-Liang; Hu, Bin; Wang, Jiu-Wei; Niu, Yuan-Jie

2013-02-01

To study the etiology, clinical manifestation, diagnosis and treatment of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum. We retrospectively analyzed the clinical data of a case of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum and reviewed the relevant literature. The patient was a 37-year-old man, with urinary incontinence for 22 years and intermittent dysuria with frequent micturition for 9 years, aggravated in the past 3 months. He had received surgery for spina bifida and giant vesico-prostatic calculus. The results of preoperative routine urinary examination were as follows: WBC 17 -20/HPF, RBC 12 - 15/HPF. KUB, IVU and pelvic CT revealed spina bifida occulta, neurogenic bladder and giant prostatic calculus. The patient underwent TURP and transurethral lithotripsy with holmium-YAG laser. The prostatic calculus was carbonate apatite in composition. Urinary dynamic images at 2 weeks after surgery exhibited significant improvement in the highest urine flow rate and residual urine volume. Seventeen months of postoperative follow-up showed dramatically improved urinary incontinence and thicker urine stream. Prostate diverticulum with prostatic giant calculus is very rare, and neurogenic bladder may play a role in its etiology. Cystoscopy is an accurate screening method for its diagnosis. For the young patients and those who wish to retain sexual function, TURP combined with holmium laser lithotripsy can be employed, and intraoperative rectal examination should be taken to ensure complete removal of calculi.

Transient microbiota exposures activate dormant Escherichia coli infection in the bladder and drive severe outcomes of recurrent disease

PubMed Central

2017-01-01

Pathogens often inhabit the body asymptomatically, emerging to cause disease in response to unknown triggers. In the bladder, latent intracellular Escherichia coli reservoirs are regarded as likely origins of recurrent urinary tract infection (rUTI), a problem affecting millions of women worldwide. However, clinically plausible triggers that activate these reservoirs are unknown. Clinical studies suggest that the composition of a woman’s vaginal microbiota influences her susceptibility to rUTI, but the mechanisms behind these associations are unclear. Several lines of evidence suggest that the urinary tract is routinely exposed to vaginal bacteria, including Gardnerella vaginalis, a dominant member of the vaginal microbiota in some women. Using a mouse model, we show that bladder exposure to G. vaginalis triggers E. coli egress from latent bladder reservoirs and enhances the potential for life-threatening outcomes of the resulting E. coli rUTI. Transient G. vaginalis exposures were sufficient to cause bladder epithelial apoptosis and exfoliation and interleukin-1-receptor-mediated kidney injury, which persisted after G. vaginalis clearance from the urinary tract. These results support a broader view of UTI pathogenesis in which disease can be driven by short-lived but powerful urinary tract exposures to vaginal bacteria that are themselves not “uropathogenic” in the classic sense. This “covert pathogenesis” paradigm may apply to other latent infections, (e.g., tuberculosis), or for diseases currently defined as noninfectious because routine culture fails to detect microbes of recognized significance. PMID:28358889

Urea transporter UT-B deletion induces DNA damage and apoptosis in mouse bladder urothelium.

PubMed

Dong, Zixun; Ran, Jianhua; Zhou, Hong; Chen, Jihui; Lei, Tianluo; Wang, Weiling; Sun, Yi; Lin, Guiting; Bankir, Lise; Yang, Baoxue

2013-01-01

Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line. Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis. UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders.

Urea Transporter UT-B Deletion Induces DNA Damage and Apoptosis in Mouse Bladder Urothelium

PubMed Central

Zhou, Hong; Chen, Jihui; Lei, Tianluo; Wang, Weiling; Sun, Yi; Lin, Guiting; Bankir, Lise; Yang, Baoxue

2013-01-01

Background Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line. Methodology/Principal Findings Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis. Conclusions/Significance UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders. PMID:24204711

Relook TURBT in superficial bladder cancer: its importance and its correlation with the tumor ploidy.

PubMed

Dwivedi, Udai S; Kumar, Abhay; Das, Suren K; Trivedi, Sameer; Kumar, Mohan; Sunder, Shyam; Singh, Pratap B

2009-01-01

To evaluate various prognostic factor predictors of residual growth in Relook transurethral resection of bladder tumor (TURBT) in superficial bladder cancer. Also, to evaluate the role of Relook TURBT along with the ploidy for prediction of recurrence and stage progression in these patients. Fifty patients with superficial bladder cancer underwent TURBT after complete evaluation. Ploidy of the tumor specimen was evaluated by flow cytometry. After 4 to 6 weeks of initial TURBT, these patients underwent Relook TURBT. Final treatment was given after the results of the histological evaluation of these specimens. Patients who underwent bladder sparing treatment were followed-up. Of the patients, 28.5% had residual tumor in Relook TURBT. Growth was found to be at the same site in 66.7% and at a different site 33.3%; 75% had single while 25% had multiple residual growth. Residual malignant tissue had a statistically significant correlation with size of the tumor (>3 cm), appearance (solid tumor), number (>3), grade (high), and multiple previous resections. Overall, the up-migration of stage and grade leads to change in treatment in 41.6%; 5 underwent radical cystectomy and 1 opted for radiotherapy; in 2 patients, intravesical BCG was given. In follow-up of mean 11.5 months, 16.6% had recurrence. Presence of residual growth in Relook TURBT along with number, size, morphology, and multiple previous resections were found to have significant correlation with the recurrence in these patients. Ploidy and grade of the tumor were not found to have correlation. Multiple, more than 3 cm, solid high grade tumor with > 3 previous resections were predictors of presence of residual tumor in Relook TURBT. Presence of residual growth is a significant risk factor for recurrence. Ploidy was not found to be significantly correlated with recurrence.

Bladder cancer and occupation: a case-control study in northern Italy.

PubMed Central

Porru, S; Aulenti, V; Donato, F; Boffetta, P; Fazioli, R; Cosciani Cunico, S; Alessio, L

1996-01-01

OBJECTIVES--A hospital based case-control study was conducted between 1992 and 1993 in the province of Brescia, a highly industrialised area in northern Italy, to evaluate occupational risk factors of bladder cancer. METHODS--The study evaluated 355 histologically confirmed cases of bladder cancer (275 men, 80 women) and 579 controls affected by urological non-neoplastic diseases (397 men, 182 women). Lifetime occupational history, smoking and drinking habits, and sociodemographic characteristics were recorded by means of a structured questionnaire. Odds ratios (ORs) were computed with adjustment for age, smoking, alcohol and coffee consumption, education, and place of residence. RESULTS--A significant (P < 0.05) increase of risk of bladder cancer were found in men for labourers in the construction industry (OR 2.1, 95% confidence interval (95% CI) 1.1-3.9) and for recreational and cultural services (OR 5.0, 95% CI 1.3-18.9). Increased risks, although not significant, were found for various other occupations and industries such as machinery mechanics, metal processers and polishers, blacksmiths, gunsmiths, painters; for transport workers, an increased risk with increasing duration of employment was found. CONCLUSIONS--Occupational exposures seem to contribute to bladder cancer risk in the area under study. PMID:8563860

[Glandular squamous cell carcinoma of the urinary bladder].

PubMed

Kovylina, M V; Pushkar', D Iu; Zaĭrat'iants, O V; Rasner, P I

2006-01-01

The paper gives a clinical observation of a 52 year-old male with a rare histological urinary bladder tumor primary grandular-squamous-cell carcinoma (pT3N IM0). The tumor is represented by two components large acinic-cell adenocarcinoma and squamous-cell carcinoma with keratinization, which smoothly pass one into another; the tumor has grown through all layers of the urinary bladder wall but it has failed to grow into the peritoneum. A microscopic study has indicated that the urachus is intact. Metastases were found in 3 of 8 lymph nodes: one showed high-grade adenocarcinoma and two others displayed average-grade squamous-cell carcinoma.

Recurring priapism may be a symptom of voiding dysfunction – case report and literature review

PubMed Central

de Jesus, Lisieux Eyer; Teixeira, Leonardo; Bertelli, André

2016-01-01

ABSTRACT Recurring priapism is rare in pre-pubertal children and may be attributed to multiple causes. We propose that voiding dysfunction (VD) may also justify this symptom and detail a clinical case of recurring stuttering priapism associated to overactive bladder that completely resolved after usage of anticholinergics and urotherapy. Sacral parasympathetic activity is responsible for detrusor contraction and for spontaneous erections and a relationship between erections and bladder status has been proved in healthy subjects (morning erections) and models of medullar trauma. High bladder pressures and/or volumes, voiding incoordination and posterior urethritis can potentially trigger reflex erections. PMID:27256196

Fibroblast growth factor receptor (FGFR) alterations in squamous differentiated bladder cancer: a putative therapeutic target for a small subgroup.

PubMed

Baldia, Philipp H; Maurer, Angela; Heide, Timon; Rose, Michael; Stoehr, Robert; Hartmann, Arndt; Williams, Sarah V; Knowles, Margaret A; Knuechel, Ruth; Gaisa, Nadine T

2016-11-01

Although drugable fibroblast growth factor receptor (FGFR) alterations in squamous cell carcinomas (SCC) of various entities are well known, little is known about FGFR modifications in squamous differentiated bladder cancer. Therefore, our study evaluated FGFR1-3 alterations as a putative therapeutic target in this subgroup. We analyzed 73 squamous differentiated bladder cancers (n = 10 pT2, n = 55 pT3, n = 8 pT4) for FGFR1-3 protein expression, FGFR1-3 copy number variations, FGFR3 chromosomal rearrangements (fluorescence in situ hybridization (FISH)) and FGFR3 mutations (SNapShot analysis). Only single cases displayed enhanced protein expression, most frequently FGFR3 overexpression (9.4% (6/64)). FISH showed no amplifications of FGFR1, 2 or 3. Break apart events were only slightly above the cut off in 12.1% (8/66) of cases and no FGFR3-TACC3 rearrangements could be proven by qPCR. FGFR3 mutations (p.S249C) were found in 8.5% (6/71) of tumors and were significantly associated with FGFR3 protein overexpression (p < 0.001), and unfavourable clinical outcome (p = 0.001). Our findings are consistent with the results of the TCGA data set for the "squamous-like" subtype of bladder cancer (n = 85), which revealed reduced overall expression of FGFR1 and FGFR2 in tumors compared to normal tissue, while expression of FGFR3 remained high. In the TCGA "squamous-like" subtype FGFR3 mutations were found in 4.9% and correlated with high FGFR3 RNA expression. Mutations of FGFR1 and FGFR2 were less frequent (2.4% and 1.2%). Hence, our comprehensive study provides novel insights into a subgroup of squamous differentiated bladder tumors that hold clues for novel therapeutic regimens and may benefit from FGFR3-targeted therapies.

Interesting Layering of Excreted 18F-FDG in the Urinary Bladder in Patients with Urinary Tract Infection and Distended Bladder.

PubMed

Shen, Guohua; Zhang, Wenjie; Jia, Zhiyun; Deng, Houfu

2015-09-01

Settling of (18)F-FDG in the bladder is often noted on whole-body PET/CT images, but this phenomenon has never received any careful attention and the mechanism has been unclear. The 2 patients described in this report, one with a T1 pathologic fracture and another with widespread bone and lymph node metastases from an unknown primary tumor, underwent PET/CT. Both had urinary tract infection and a distended bladder during scanning. The interesting layering of (18)F-FDG in the urinary bladder was observed in both patients. The presence of this phenomenon demands careful evaluation of the urine by the clinician, and the mechanism is hypothesized to be slow (18)F-FDG excretion in patients with a distended urinary bladder, resulting in delayed mixing with urine. In addition, urinary tract infection may be a potential cause. Images showing this interesting layering should be interpreted with care. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.