Trimodality therapy in bladder cancer: Who, what and when?

PubMed Central

Premo, Christopher; Apolo, Andrea B.; Agarwal, Piyush K.

2015-01-01

Summary Radical cystectomy is a standard treatment for non-metastatic, muscle-invasive bladder cancer. Treatment with trimodality therapy consisting of maximal transurethral resection of the bladder tumor (TURBT) followed by concurrent chemotherapy and radiation has emerged as a method to preserve the native bladder in highly motivated patients. A number of factors can impact the likelihood of long term bladder preservation after trimodality therapy, and therefore should be taken into account when selecting patients. New radiation techniques such as intensity modulated radiation therapy and image guided radiation therapy may decrease the toxicity of radiotherapy in this setting, but remain an area of active study. Novel chemotherapy regimens may improve response rates and minimize toxicity. PMID:25882559

Caudal clonidine-bupivicaine block with bladder hydrodistension: a novel combined treatment for the painful bladder

PubMed Central

Tempest, Heidi; Stoneham, Mark; Frampton, Claire; Noble, Jeremy

2011-01-01

The authors describe a new combination procedure consisting of bladder hydrodistension with clonidine-bupivicaine caudal block for the symptomatic relief of bladder pain. They report this new technique whereby patients who had tried multiple forms of therapy with little response, including bladder hydrodistension under general anaesthesia for their chronic pelvic bladder pain, responded to this novel combination therapy. PMID:22696635

Caudal clonidine-bupivicaine block with bladder hydrodistension: a novel combined treatment for the painful bladder.

PubMed

Tempest, Heidi; Stoneham, Mark; Frampton, Claire; Noble, Jeremy

2011-04-19

The authors describe a new combination procedure consisting of bladder hydrodistension with clonidine-bupivicaine caudal block for the symptomatic relief of bladder pain. They report this new technique whereby patients who had tried multiple forms of therapy with little response, including bladder hydrodistension under general anaesthesia for their chronic pelvic bladder pain, responded to this novel combination therapy.

Comparison of Bladder Directed and Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain Syndrome

DTIC Science & Technology

2017-09-01

PROJECT NUMBER Kenneth M. Peters 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT...AWARD NUMBER: W81XWH-16-1-0307 TITLE: Comparison of Bladder-Directed and Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain...Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain Syndrome 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

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

Researchers studying alternative to bladder removal for bladder cancer patients | Center for Cancer Research

Cancer.gov

A new phase I clinical trial conducted by researchers at the Center for Cancer Research (CCR) is evaluating the safety and tolerability, or the degree to which any side effects can be tolerated by patients, of a two-drug combination as a potential alternative to bladder removal for bladder cancer patients. The trial targets patients with non-muscle invasive bladder cancer

Complementary and alternative medical therapies for interstitial cystitis: an update from the United States

PubMed Central

Atchley, Megan Danielle; Shah, Nima M.

2015-01-01

The diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) has shifted from organ-specific to a multifactorial, multidisciplinary and individualized approach. Patients with refractory and debilitating symptoms may respond to complementary and alternative medical treatments (CAM). Through CAM therapies, practitioners assist the patient to be at the center of their care, empowering them to be emotionally and physically involved. Multi-disciplinary care, including urology, gynecology, gastroenterology, neurology, psychology, physiotherapy and pain medicine, is also identified to be the crux of adequate management of patients with chronic pelvic pain because of its variable etiology. The purpose of this review is to emphasize these changes and discuss management strategies. PMID:26816868

Complementary and alternative medical therapies for interstitial cystitis: an update from the United States.

PubMed

Atchley, Megan Danielle; Shah, Nima M; Whitmore, Kristene E

2015-12-01

The diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) has shifted from organ-specific to a multifactorial, multidisciplinary and individualized approach. Patients with refractory and debilitating symptoms may respond to complementary and alternative medical treatments (CAM). Through CAM therapies, practitioners assist the patient to be at the center of their care, empowering them to be emotionally and physically involved. Multi-disciplinary care, including urology, gynecology, gastroenterology, neurology, psychology, physiotherapy and pain medicine, is also identified to be the crux of adequate management of patients with chronic pelvic pain because of its variable etiology. The purpose of this review is to emphasize these changes and discuss management strategies.

[Methods of traditional chinese medicine in the treatment of patients with interstitial cystitis/bladder pain syndrome].

PubMed

Ignashov, A Yu; Deng, B; Kuzmin, I V; Slesarevskaya, M N

2018-03-01

In recent years, there has been an increasing interest in alternative (complementary) treatments of interstitial cystitis/bladder pain syndrome (IC/BPS). This is due both to the high incidence of IC/BPS and to a lack of effectiveness of conventional treatments. One of the directions of alternative therapies is a traditional Chinese medicine using a special diet, various animal and plant-derived medicines, breathing exercises and acupuncture. This review analyzes the accumulated experience in using traditional Chinese medicine in the treatment of patients with IC/BPS. The presented data indicate that these methods appear to be promising, since they are effective in a significant number of patients, lead to an improvement in their quality of life, are non-invasive and well tolerated. However, due to the lack of clinical studies, the efficacy of this treatment modalities needs to be confirmed.

Fatal hemorrhagic cystitis induced by pelvic irradiation and cyclophosphamide therapy. Case reports and review

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

Price, W.E.; Keldahl, L.R.

The potent cytotoxic drug cyclophosphamide has been used extensively for neoplastic and non-neoplastic diseases. Patients taking this drug may have received or may be receiving pelvic irradiation concurrently. This report describes two patients who developed fatal hemorrhagic cystitis induced by pelvic irradiation and cyclophosphamide therapy. Etiology, incidence, pathologic descriptions, and diagnostic and therapeutic aspects of this entity are described. The incidence and risk of serious, life-threatening bladder hemorrhage from cyclophosphamide therapy is increased by prior or concurrent pelvic irradiation. Alternative cytotoxic, non-urotoxic chemotherapy should be used in these high-risk patients.

The role of acupuncture in managing overactive bladder; a review of the literature.

PubMed

Forde, James C; Jaffe, Edward; Stone, Benjamin V; Te, Alexis E; Espinosa, Geo; Chughtai, Bilal

2016-11-01

Overactive bladder (OAB) affects a considerable proportion of men and women in the United States and is associated with significant costs and quality of life (QoL) reduction. While medication remains a mainstay of treatment, there is increasing interest in the use of alternative medicine in the form of acupuncture. We reviewed the literature on the role of acupuncture in managing OAB. A narrative review was compiled after searching electronic databases (PubMed, MEDLINE, Scopus, and EMBASE) for clinical studies involving acupuncture in treating OAB. Databases were searched from the time of inception through September 2015 by a clinician for articles reporting the results related to the use of acupuncture in OAB. Key search terms were acupuncture, overactive bladder, bladder instability, urgency, urinary incontinence. Articles in English or translated into English were included. Initial animal studies suggest several biochemical mechanisms of action underlying the effect of acupuncture on OAB suppression. The experience in humans includes two case series and six comparative trials. All studies demonstrated subjective improvement in OAB symptoms, and some reported objective improvement in urodynamic studies. Notably, some comparative trials showed the benefit of acupuncture to be comparable with antimuscarinic treatment. Despite their limitations, existing studies serve as a promising foundation for suggesting a role for acupuncture as an alternative therapy for OAB. Further well-designed studies are required to investigate optimal technique and their outcomes.

Bladder biopsy

MedlinePlus

... than usual ( oliguria ). You cannot urinate despite a strong urge to do so. Alternative Names Biopsy - bladder Images Bladder catheterization, female Bladder catheterization, male Female urinary tract Male urinary tract Bladder biopsy ...

Photoselective Vaporisation of the Bladder for the Management of Radiation Cystitis - Technique and Initial Outcomes.

PubMed

Pascoe, Claire; Christidis, Daniel; Manning, Todd; Lamb, Benjamin W; Murphy, Declan G; Lawrentschuk, Nathan

2018-05-16

Objective To describe our technique utilising photoselective vaporisation of the bladder (PVB) for the management of haemorrhagic cystitis and initial results of 12 patients. Materials and Method An audit of theatre records of a single surgeon was performed to identify patients who had undergone PVB for management of radiation-cystitis. Rigid cystoscopy was performed. Ureteric catheters were placed and active bleeding sites targeted to optimise vision. Ablation was commenced using the vaporize function. When lasering around delicate structures the coagulation function was used. Ureteric catheters remained in situ for 24h. An 18Fr Foley catheter was placed. When urine output was clear continuous bladder irrigation was ceased. Both uretetric catheters and Foley catheter were removed prior to the 24hour mark. Results 12 patients were identified. 8 had previously required blood transfusion secondary to bladder haemorrhage. 9 were successfully treated and 2 saw improvement in haematuria but required a repeat procedure at 3 weeks post operatively. 4 went on to receive hyperbaric oxygenation as consolidative therapy. 1 patient was unsuccessfully treated and went on to cystectomy. There were no mortalities. No patients sustained bladder perforation or damage to surrounding structures. Conclusion Radiation cystitis can be life threatening and remains a challenge for the urologist with traditional intra-vescical treatments such as aluminium or formalin having variable results. We present an alternate technique using PVB to ablate the bladder mucosa, with good results. Consolidation with hyperbaric oxygen therapy may be considered. Our study is limited by small sample size and the presence of bilateral ureteric catheters leaving the bladder free from urine may impact immediate post operative outcomes. These initial results are promising however further prospective evaluation with a larger cohort and pre and post operative cystograms would enable better evaluation of this technique as a definitive management option for haemorrhagic cystitis. Copyright © 2018. Published by Elsevier Inc.

Long-Term Outcomes Among Patients Who Achieve Complete or Near-Complete Responses After the Induction Phase of Bladder-Preserving Combined-Modality Therapy for Muscle-Invasive Bladder Cancer: A Pooled Analysis of NRG Oncology/RTOG 9906 and 0233

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

Mitin, Timur, E-mail: mitin@ohsu.edu; George, Asha; Zietman, Anthony L.

Purpose: To investigate the differences in outcomes among patients with muscle-invasive bladder cancer on NRG Oncology Radiation Therapy Oncology Group protocols 9906 and 0233 who achieved complete response and near-complete response after induction chemoradiation and then completed bladder-preserving therapy with chemoradiation therapy (chemo-RT) to full dose (60-64 Gy). Patients and Methods: A pooled analysis was performed on 119 eligible patients with muscle-invasive bladder cancer enrolled on NRG Oncology Radiation Therapy Oncology Group trials 9906 and 0233, who were classified as having a complete (T0) or near-complete (Ta or Tis) response after induction chemo-RT and completed consolidation with a total RT dose ofmore » at least 60 Gy. Bladder recurrence, salvage cystectomy rates, and disease-specific survival were estimated by the cumulative incidence method and bladder-intact and overall survivals by the Kaplan-Meier method. Results: Among the 119 eligible patients, 101 (85%) achieved T0, and 18 (15%) achieved Ta or Tis after induction chemo-RT and proceeded to consolidation. After a median follow-up of 5.9 years, 36 of 101 T0 patients (36%) versus 5 of 18 Ta or Tis patients (28%) experienced bladder recurrence (P=.52). Thirteen patients among complete responders eventually required late salvage cystectomy for tumor recurrence, compared with 1 patient among near-complete responders (P=.63). Disease-specific, bladder-intact, and overall survivals were not significantly different between T0 and Ta/Tis cases. Conclusions: The bladder recurrence and salvage cystectomy rates of the complete and the near-complete responders were similar. Therefore it is reasonable to recommend that patients with Ta or Tis after induction chemo-RT continue with bladder-sparing therapy with consolidation chemo-RT to full dose (60-64 Gy).« less

Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

PubMed Central

Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

2016-01-01

Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

Introduction to regenerative medicine and tissue engineering.

PubMed

Stoltz, J-F; Decot, V; Huseltein, C; He, X; Zhang, L; Magdalou, J; Li, Y P; Menu, P; Li, N; Wang, Y Y; de Isla, N; Bensoussan, D

2012-01-01

Human tissues don't regenerate spontaneously, explaining why regenerative medicine and cell therapy represent a promising alternative treatment (autologous cells or stem cells of different origins). The principle is simple: cells are collected, expanded and introduced with or without modification into injured tissues or organs. Among middle-term therapeutic applications, cartilage defects, bone repair, cardiac insufficiency, burns, liver or bladder, neurodegenerative disorders could be considered.

Intravesical antineoplastic therapy following transurethral resection of bladder tumors: nursing implications from the operating room to discharge.

PubMed

Washburn, Donna J

2007-08-01

An aging population and latent effects from exposure to carcinogens will likely augment the current trend of increased incidence of urinary bladder cancer. Intravesical antineoplastic therapy is a common treatment for urinary bladder cancer. Transurethral resection of bladder tumors often is followed immediately by the instillation of an antineoplastic agent in the operating room or postanesthesia care unit. Oncology nurses, who have a unique knowledge of safe handling and patient care, can improve staff safety and patient outcomes in several areas of healthcare organizations, as well as reduce the mortality and morbidity of urinary bladder cancer by learning more about the disease and intravesical antineoplastic therapy.

The Patient Burden of Bladder Outlet Obstruction after Prostate Cancer Treatment.

PubMed

Liberman, Daniel; Jarosek, Stephanie; Virnig, Beth A; Chu, Haitao; Elliott, Sean P

2016-05-01

Bladder outlet obstruction after prostate cancer therapy imposes a significant burden on health and quality of life in men. Our objective was to describe the burden of bladder outlet obstruction after prostate cancer therapy by detailing the type of procedures performed and how often those procedures were repeated in men with recurrent bladder outlet obstruction. Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data from 1992 to 2007 with followup through 2009 we identified 12,676 men who underwent at least 1 bladder outlet obstruction procedure after prostate cancer therapy, including external beam radiotherapy in 3,994, brachytherapy in 1,485, brachytherapy plus external beam radiotherapy in 1,847, radical prostatectomy in 4,736, radical prostatectomy plus external beam radiotherapy in 369 and cryotherapy in 245. Histogram, incidence rates and Cox proportional hazards models with repeat events analysis were done to describe the burden of repeat bladder outlet obstruction treatments stratified by prostate cancer therapy type. We describe the type of bladder outlet obstruction surgery grouped by level of invasiveness. At a median followup of 8.8 years 44.6% of men underwent 2 or more bladder outlet obstruction procedures. Compared to men who underwent radical prostatectomy those treated with brachytherapy and brachytherapy plus external beam radiotherapy were at increased adjusted risk for repeat bladder outlet obstruction treatment (HR 1.2 and 1.32, respectively, each p <0.05). After stricture incision the men treated with radical prostatectomy or radical prostatectomy plus external beam radiotherapy were most likely to undergo dilation at a rate of 34.7% to 35.0%. Stricture resection/ablation was more common after brachytherapy, external beam radiotherapy or brachytherapy plus external beam radiotherapy at a rate of 28.9% to 41.2%. Almost half of the men with bladder outlet obstruction after prostate cancer therapy undergo more than 1 procedure. Furthermore men with bladder outlet obstruction after radiotherapy undergo more invasive endoscopic therapies and are at higher risk for multiple treatments than men with bladder outlet obstruction after radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

Uses of Complementary and Alternative Medicine in Multiple Sclerosis

PubMed Central

Namjooyan, Foroogh; Ghanavati, Rahil; Majdinasab, Nastaran; Jokari, Shiva; Janbozorgi, Mohammad

2014-01-01

Multiple sclerosis (MS) is a chronic, disabling, recurrent demyelination of the central nervous system (CNS). It could affect different regions in the brain and spinal cord, and according to the domain which is affected, it could cause different symptoms such as motor, sensory, or visual impairment; fatigue; bowel, bladder, and sexual dysfunction; cognitive impairment; and depression. MS patients also face reduced quality of life. Drugs that are used in MS are not fully efficient and patients suffer from many symptoms and adverse effects. Today there is an increasing trend of using complementary and alternative medicine (CAM). People are more likely to use this type of treatment. Using appropriate lifestyle and CAM therapy can subside some of the symptoms and could improve the quality of life in these patients. Many people with MS explore CAM therapies for their symptoms. This review is aimed to introduce CAM therapies that could be used in MS patients. PMID:25161918

Retrospective study of efficacy of intravesical BCG alone in treatment of superficial bladder cancer.

PubMed

Mydlo, J H; Usher, S M; Camacho, F; Freed, S

1986-09-01

This is a review of 100 patients at our institution who were treated for superficial bladder cancer. In those patients with carcinoma in situ of the bladder who were treated with conventional therapy (resection and/or fulguration) and intravesical bacillus Calmette-Guerin (BCG) without intradermal BCG, and those patients who were treated with conventional therapy alone, we found a response rate of 60 per cent versus 40 per cent at the end of three months. In comparing those patients with superficial papillary cancer, we found a response of 39 per cent after conventional therapy and 63 per cent after conventional therapy and intravesical BCG. This suggests that intravesical BCG without intradermal BCG can be an important adjunct to the conventional therapy of bladder tumors.

Androgen receptor activation: a prospective therapeutic target for bladder cancer?

PubMed

Mizushima, Taichi; Tirador, Kathleen A; Miyamoto, Hiroshi

2017-03-01

Patients with non-muscle-invasive or muscle-invasive bladder cancer undergoing surgery and currently available conventional therapy remain having a high risk of tumor recurrence or progression, respectively. Novel targeted molecular therapy is therefore expected to improve patient outcomes. Meanwhile, substantially higher incidence of bladder cancer in men has prompted research on androgen-mediated androgen receptor (AR) signaling in this malignancy. Indeed, preclinical evidence has suggested that AR signaling plays an important role in urothelial carcinogenesis and tumor outgrowth as well as resistance to some of the currently available conventional non-surgical therapies. Areas covered: We summarize and discuss available data suggesting the involvement of AR and its potential downstream targets in the development and progression of bladder cancer. Associations between AR signaling and sensitivity to cisplatin/doxorubicin or bacillus Calmette-Guérin treatment are also reviewed. Expert opinion: AR activation is likely to correlate with the promotion of urothelial carcinogenesis and cancer outgrowth as well as resistance to conventional therapies. Molecular therapy targeting the AR may thus provide effective chemopreventive and therapeutic approaches for urothelial cancer. Accordingly, bladder cancer can now be considered as an endocrine-related neoplasm. Clinical application of various anti-AR therapies available for AR-dependent prostate cancer to bladder cancer patients is anticipated.

Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004)

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

Huddart, Robert A., E-mail: robert.huddart@icr.ac.uk; Hall, Emma; Hussain, Syed A.

2013-10-01

Purpose: To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. Methods and Materials: In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. Themore » primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Results: Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population. Conclusions: In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.« less

Photodynamic therapy of bladder cancer - a phase I study using hexaminolevulinate (HAL).

PubMed

Bader, M J; Stepp, Herbert; Beyer, Wolfgang; Pongratz, Thomas; Sroka, Ronald; Kriegmair, Martin; Zaak, Dirk; Welschof, Mona; Tilki, Derya; Stief, Christian G; Waidelich, Raphaela

2013-10-01

To assess the safety and feasibility of hexaminolevulinate (HAL) based photodynamic therapy (PDT) as adjuvant treatment after transurethral resection of the bladder (TURB) in patients with intermediate or high-risk urothelial cell carcinoma (UCC) of the bladder. Seventeen patients received 50 ml of either a 16 mM (4 patients) or 8 mM HAL (13 patients) solution instilled intravesically. Bladder wall irradiation was performed using an incoherent white light source coupled via a quartz fiber assembled into a flexible transurethral irrigation catheter. Each patient received 3 treatments with HAL-PDT 6 weeks apart. After PDT, patients were followed by regular cystoscopy for up to 21 months to assess time to recurrence. Reported adverse events (AEs) were coded according the World Health Organization Adverse Reaction Terminology (WHO-ART). Efficacy was assessed by cystoscopy, cytology, and histology, and was defined as the number of patients who were tumor-free at 6 or 21 months after initial PDT treatment. Transient bladder irritability was reported by 15 of the 17 patients and resolved completely in all patients. No evidence of a cumulative effect of treatment on the incidence of AEs could be detected. PDT treatment was performed without any technical complications. Furthermore preliminary assessment of efficacy showed that of the 17 patients included, 9 (52.9%; 95% CI: 27.8-77.0) were tumor-free at 6 months, 4 (23.5%; 95% CI: 6.8-49.9) were tumor-free at 9 months, and 2 (11.8%, 95% CI: 1.5-36.4) were tumor-free after 21 months. PDT using hexaminolevulinate and an incoherent white light system with the special flexible irradiation catheter system is technically feasible and safe and may offer an alternative in the treatment of non-muscle-invasive intermediate and high-risk bladder cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Interstitial cystitis intravesical therapy

PubMed Central

2017-01-01

Interstitial cystitis (IC) is a progressive bladder disorder that presents with symptoms of bladder urgency, frequency and pain. The aetiology of the disease remains uncertain, but it is postulated that there is an initial infective insult which damages the glycosaminoglycan (GAG) layer of the bladder urothelium. This defect allows an influx of ions, particularly potassium, which initiates an inflammatory reaction in the bladder wall, which incites the symptoms described above. Treatment initially involves behavioural and oral medication, with second line being intravesical instillation therapy. Treatment strategies focus on restoring lower urinary tract epithelial function, inhibiting neural activation, controlling allergies and relieving symptoms. In this review, current intravesical therapy will be discussed, as well as what lies on the horizon for intravesical therapy in IC. PMID:28791236

Microcirculation and structural reorganization of the bladder mucosa in chronic cystitis under conditions of ozone therapy.

PubMed

Neimark, A I; Nepomnyashchikh, L M; Lushnikova, E L; Bakarev, M A; Abdullaev, N A; Sizov, K A

2014-01-01

Structural reorganization of the bladder mucosa in chronic cystitis and its correction by ozone therapy were studied. A relationship between the epithelial layer restructuring of different kinds (dystrophy, metaplasia, and degeneration), level of cell proliferation, and ultrastructural organization of urotheliocytes was detected. This complex of structural reactions was combined with dysregulation of tissue bloodflow in the bladder mucosa, shown by laser Doppler flowmetry. Positive structural changes were most marked in intravesical and less so in parenteral ozone therapy added to the therapeutic complex and manifested in reduction of inflammation and alteration in parallel with more intense reparative reactions. A special feature of parenteral ozone therapy was a significant improvement of microcirculation in the bladder mucosa.

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.

[Effective dimethyl sulfoxide (DMSO) occlusive dressing technique for amyloidosis of the urinary bladder].

PubMed

Hasegawa, Yoshihiro; Kanda, Hideki; Miki, Manabu; Masui, Satoru; Yoshio, Yuko; Yamada, Yasushi; Soga, Norihito; Arima, Kiminobu; Sugimura, Yoshiki

2013-10-01

A 48-year-old married woman complaining of macroscopic hematuria and cystitis symptom was admitted to our institute. Flexible cystoscopy revealed many yellowish, nodular masses at the paries posterior of the urinary bladder, and cold-punch biopsy proved it to be amyloidosis. Serum amyloid protein A (SAA) was high, and suggested systemic amyloidosis. Renal biopsy and colon fiberscopy did not reveal any abnormalities. We therefore diagnosed a primary localized amyloidosis of the urinary bladder. Transurethral resection and dimethyl sulfoxide (DMSO) infusion therapy are used to treat amyloidosis of the urinary bladder. However there is no definite cure for amyloidosis of the urinary bladder. Therefore we selected DMSO occlusive dressing technique therapy. After 5 years of therapy, there was no evidence of a recurrence of amyloidosis.

Immune Response Following Photodynamic Therapy For Bladder Cancer

NASA Astrophysics Data System (ADS)

Raymond K.

1989-06-01

This study was undertaken to determine if photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2 and tumor necrosis factor-alpha were assayed in the urine of four patients treated with photodynamic therapy for bladder cancer, in seven patients undergoing transurethral procedures, and in five healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients treated with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy or in the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer. Such an immunologic response activated by PDT may be an additional mechanism involved in bladder tumor destruction.

Refractory overactive bladder: Beyond oral anticholinergic therapy

PubMed Central

Glinski, Ronald W.; Siegel, Steven

2007-01-01

Objectives: In this review, we discuss the treatment of refractory overactive bladder (OAB) that has not adequately responded to medication therapy and we propose an appropriate care pathway to the treatment of OAB. We also attempt to address the cost of OAB treatments. Materials and Methods: A selective expert review of the current literature on the subject of refractory OAB using MEDLINE was performed and the data is summarized. We also review our experience in treating refractory OAB. The role and outcomes of various treatment options for refractory OAB are discussed and combined therapy with oral anticholinergics is explored. Emerging remedies including intravesical botulinum toxin injection and pudendal neuromodulation are also reviewed, along with conventional surgical options. Results: In general behavioral therapy, pelvic floor electrical stimulation, magnetic therapy and posterior tibial nerve stimulation (PTNS), have shown symptom decreases in 50-80% of patients with OAB. Depending on the study, combination therapy with oral anticholinergics seems to improve efficacy of behavioral therapy and PTNS in approximately 10-30%. In multicenter, long-term randomized controlled trials, sacral neuromodulation has been shown to improve symptoms of OAB and OAB incontinence in up to 80% of the patients treated. Studies involving emerging therapies such as pudendal serve stimulation suggest that there may be a 15-20% increase in efficacy over sacral neuromodulation, but long-term studies are not yet available. Another emerging therapy, botulinum toxin, is also showing similar success in reducing OAB symptoms in 80-90% of patients. Surgical approaches, such as bladder augmentation, are a last resort in the treatment of OAB and are rarely used at this point unless upper tract damage is a concern and all other treatment options have been exhausted. Conclusion: The vast majority of OAB patients can be managed successfully by behavioral options with or without anticholinergic medications. When those fail, neuromodulation or intravesical botulinum toxin therapies are successful alternatives for most of the remaining group. We encourage practitioners responsible for the care of OAB patients to gain experience with these options. More research is needed to assess the cost-effectiveness of various OAB treatments PMID:19675795

Quantification of effectiveness of bilateral and unilateral neuromodulation in the rat bladder rhythmic contraction model

PubMed Central

2013-01-01

Background Using the isovolumetric bladder rhythmic contraction (BRC) model in anesthetized rats, we have quantified the responsiveness to unilateral and bilateral stimulation of the L6 spinal nerve (SN) and characterized the relationship between stimulus intensity and inhibition of the bladder micturition reflex. Methods A wire electrode was placed under either one or both of the L6 SN roots. A cannula was placed into the bladder via the urethra and the urethra was ligated. Saline infusion induced BRC. Results At motor threshold (Tmot) intensity, SN stimulation of both roots (10 Hz) for 10 min reduced bladder contraction frequency from 0.63 ± 0.04 to 0.17 ± 0.09 contractions per min (26 ± 14% of baseline control; n = 10, p < 0.05). However, the same intensity of unilateral stimulation (n = 15) or sequential stimulation of both SNs (e.g. 5 min per side alternatively for a total of 10 min or 20 min) was less efficacious. The greater sensitivity to bilateral stimulation is not dependent upon precise bilateral timing of the stimulation pulses. Bilateral stimulation also produced both acute and prolonged- inhibition on bladder contractions in a stimulation intensity dependent fashion. Conclusions Using the bladder rhythmic contraction model, bilateral stimulation was more effective than unilateral stimulation of the SN. Clinical testing should be conducted to further compare efficacies of unilateral and bilateral stimulation. Bilateral stimulation may allow the use of lower stimulation intensities to achieve higher efficacy for neurostimulation therapies on urinary tract control. PMID:23866931

Functional and molecular characterization of kinin B1 and B 2 receptors in human bladder cancer: implication of the PI3Kγ pathway.

PubMed

Sgnaolin, V; Pereira, T C B; Bogo, M R; Zanin, R; Battastini, A M O; Morrone, F B; Campos, M M

2013-08-01

Kinins and their receptors have been recently implicated in cancer. Using functional and molecular approaches, we investigated the relevance of kinin B1 and B2 receptors in bladder cancer. Functional studies were conducted using bladder cancer cell lines, and human biopsies were employed for molecular studies. Both B1 des-Arg(9)-BK and B2 BK receptor agonists stimulated the proliferation of grade 3-derived T24 bladder cancer cells. Furthermore, treatment with B1 and B2 receptor antagonists (SSR240612 and HOE140) markedly inhibited the proliferation of T24 cells. Only higher concentrations of BK increased the proliferation of the grade 1 bladder cancer cell line RT4, while des-Arg(9)-BK completely failed to induce its proliferation. Real-time PCR revealed that the mRNA expression of kinin receptors, particularly B1 receptors, was increased in T24 cells relative to RT4 cells. Data from bladder cancer human biopsies revealed that B1 receptor expression was increased in all tumor samples and under conditions of chronic inflammation. We also show novel evidence demonstrating that the pharmacological inhibition of PI3Kγ (phosphatidylinositol 3-kinase) with AS252424, concentration-dependently reduced T24 cell proliferation induced by BK or des-Arg(9)-BK. Finally, the incubation of T24 cells with kinin agonists led to a marked activation of the PI3K/AKT and ERK 1/2 signaling pathways, whereas p38 MAP kinase remained unaffected. Kinin receptors, especially B1 receptors, appear to be implicated in bladder cancer progression. It is tempting to suggest that selective kinin antagonists might represent potential alternative therapies for bladder cancer.

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.

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

Potential of Endocannabinoids to Control Bladder Pain.

PubMed

Bjorling, Dale E; Wang, Zun-Yi

2018-01-01

Bladder-related pain is one of the most common forms of visceral pain, and visceral pain is among the most common complaints for which patients seek physician consultation. Despite extensive studies of visceral innervation and treatment of visceral pain, opioids remain a mainstay for management of bladder pain. Side effects associated with opioid therapy can profoundly diminish quality of life, and improved options for treatment of bladder pain remain a high priority. Endocannabinoids, primarily anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are endogenously-produced fatty acid ethanolamides with that induce analgesia. Animal experiments have demonstrated that inhibition of enzymes that degrade AEA or 2-AG have the potential to prevent development of visceral and somatic pain. Although experimental results in animal models have been promising, clinical application of this approach has proven difficult. In addition to fatty acid amide hydrolase (FAAH; degrades AEA) and monacylglycerol lipase (MAGL; degrades 2-AG), cyclooxygenase (COX) acts to metabolize endocannabinoids. Another potential limitation of this strategy is that AEA activates pro-nociceptive transient receptor potential vanilloid 1 (TRPV1) channels. Dual inhibitors of FAAH and TRPV1 or FAAH and COX have been synthesized and are currently undergoing preclinical testing for efficacy in providing analgesia. Local inhibition of FAAH or MAGL within the bladder may be viable options to reduce pain associated with cystitis with fewer systemic side effects, but this has not been explored. Further investigation is required before manipulation of the endocannabinoid system can be proven as an efficacious alternative for management of bladder pain.

Bladder Function Preservation With Brachytherapy, External Beam Radiation Therapy, and Limited Surger in Bladder Cancer Patients: Long-Term Results

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

Aluwini, Shafak, E-mail: s.aluwini@erasmusmc.nl; Rooij, Peter H.E. van; Kirkels, Wim J.

2014-03-01

Purpose: To report long-term results of a bladder preservation strategy for muscle-invasive bladder cancer (MIBC) using external beam radiation therapy and brachytherapy/interstitial radiation therapy (IRT). Methods and Materials: Between May 1989 and October 2011, 192 selected patients with MIBC were treated with a combined regimen of preoperative external beam radiation therapy and subsequent surgical exploration with or without partial cystectomy and insertion of source carrier tubes for afterloading IRT using low dose rate and pulsed dose rate. Data for oncologic and functional outcomes were prospectively collected. The primary endpoints were local recurrence-free survival (LRFS), bladder function preservation survival, and salvage cystectomy-freemore » survival. The endpoints were constructed according to the Kaplan-Meier method. Results: The mean follow-up period was 105.5 months. The LRFS rate was 80% and 73% at 5 and 10 years, respectively. Salvage cystectomy-free survival at 5 and 10 years was 93% and 85%. The 5- and 10-year overall survival rates were 65% and 46%, whereas cancer-specific survival at 5 and 10 years was 75% and 67%. The distant metastases-free survival rate was 76% and 69% at 5 and 10 years. Multivariate analysis revealed no independent predictors of LRFS. Radiation Therapy Oncology Group grade ≥3 late bladder and rectum toxicity were recorded in 11 patients (5.7%) and 2 patients (1%), respectively. Conclusions: A multimodality bladder-sparing regimen using IRT offers excellent long-term oncologic outcome in selected patients with MIBC. The late toxicity rate is low, and the majority of patients preserve their functional bladder.« less

Innovation in Bladder Cancer Immunotherapy.

PubMed

Grossman, H Barton; Lamm, Donald L; Kamat, Ashish M; Keefe, Stephen; Taylor, John A; Ingersoll, Molly A

2016-10-01

Bladder cancer is understudied despite its high prevalence and its remarkable response to immunotherapy. Indeed, funding for studies to explore mechanisms of tumor immunity and novel new therapeutics is disproportionately lower for bladder cancer in comparison with malignancies of the breast, prostate, or lung. However, the recent successes of checkpoint blockade therapy suggest that new therapeutic strategies are on the horizon for bladder cancer. Here, we give a perspective into the evolution of bladder cancer therapy, focusing on strategies to treat high-risk nonmuscle invasive disease, followed by a discussion of recent advances in the treatment of muscle invasive bladder cancer and their potential applicability to lower stage disease. Finally, we explore immunotherapeutic strategies, which have been demonstrated to be successful in the treatment of other malignancies, for their potential to treat and cure patients with nonmuscle and muscle invasive bladder cancer.

Medicinal Leech Therapy for Glans Penis Congestion After Primary Bladder Exstrophy-Epispadias Repair in an Infant: A Case Report.

PubMed

Wagenheim, Gavin N; Au, Jason; Gargollo, Patricio C

2016-01-01

Many postoperative complications have been reported after repair of classic bladder exstrophy. We present a case of medicinal leech therapy for glans penis congestion following exstrophy repair in an infant. A 2-week-old male with classic bladder exstrophy underwent complete primary repair. On postoperative day 1, he developed rapidly worsening glans penis venous congestion. Medicinal leech therapy was instituted with antibiotics and blood transfusions to maintain a hematocrit >30%. After 24 hours, venous congestion improved and therapy was discontinued. The patient's remaining hospital course was uncomplicated. Medicinal leeches are an effective therapy to relieve glans penis venous congestion. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Local anaesthetic 5-aminolaeuvulinic acid photodynamic therapy in the treatment of superficial bladder cancer

NASA Astrophysics Data System (ADS)

Shackley, David C.

The aim of this thesis was to study aspects of the treatment of superficial bladder carcinoma using photodynamic therapy by combining the delivery of laser light energy with the photosensitiser 5-aminolaeuvulinic acid (ALA). ALA is a novel pro-drug, which can be absorbed intravesically where it is converted in diseased urothelium and tumour to the active photosensitiser, PpK. Following whole bladder light irradiation there is release of toxic radicals, which are scavenged by oxygen causing selective necrosis (PDT). Preliminary studies on animals suggest that ALA is superior to earlier bladder PDT sensitisers in that generalised photosensitivity and bladder contracture are avoided. These problems in conjunction with the complexity of PDT whereby a general anaesthetic with rigid cystoscopy under continuous irrigation are required, have previously limited the development of this modality as a practical therapy. (Abstract shortened by ProQuest.).

Updated results of bladder-sparing trimodality approach for invasive bladder cancer.

PubMed

Zapatero, Almudena; Martin de Vidales, Carmen; Arellano, Ramón; Bocardo, Gloria; Pérez, Mar; Ríos, Patricia

2010-01-01

To update long-term results with selective organ preservation in invasive bladder cancer using aggressive transurethral resection of bladder tumor (TURBT) and radiochemotherapy (RCT) and to identify treatment factors that may predict overall survival (OS). Between 1990 and 2007, a total of 74 patients with T2-T4 bladder cancer were enrolled in 2 sequential bladder-sparing protocols including aggressive TURB and RCT. From 1990 to 1999, 41 patients were included in protocol no. 1 (P1) that consisted of three cycles of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy prior to re-evaluation and followed by radiotherapy (RT) 60 Gy in complete responders. Between 2000 and 2007, 33 patients were entered in protocol no. 2 (P2) that consisted of concurrent RCT 64, 8 Gy with weekly cisplatin. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. Primary endpoints were OS, overall survival with bladder preservation (OSB), and late toxicity. The mean follow-up for the whole series was 54 months (range 9-156), 69 months for patients in P1 and 36 months for patients in P2. The actuarial 5-year OS and OSB for all series were 72% and 60%, respectively. Distant metastases were diagnosed in 11 (15%) patients. Grade 3 late genitourinary (GU) and intestinal (GI) complications were 5% and 1.3%, respectively. There were no significant differences in the incidence of superficial recurrences (P = 0.080), muscle-invasive relapses (P = 0.722), distant metastasis (P = 0.744), grade >/=2 late complications (P = 0.217 for GU and P = 0.400 for GI), and death among the 2 protocols (P value for OS = 0.643; P value for OSB = 0.532). These data confirm that trimodality therapy with bladder preservation represents a real alternative to radical cystectomy in selected patients, resulting in an acceptable rate of the long-term survivors retaining functional bladders. Copyright 2010 Elsevier Inc. All rights reserved.

COMBINED USE OF α-ADRENERGIC AND MUSCARINIC ANTAGONISTS FOR THE TREATMENT OF VOIDING DYSFUNCTION

PubMed Central

RUGGIERI, MICHAEL R.; BRAVERMAN, ALAN S.; PONTARI, MICHEL A.

2012-01-01

Purpose We provide an overview of the medical literature supporting the combined use of muscarinic and α-adrenergic antagonist therapy for the treatment of voiding dysfunction. Materials and Methods The MEDLINE database (1966 to 2004) of the United States National Library of Medicine was searched for pertinent studies. Results Although the mechanism of action of α-adrenergic antagonist therapy for voiding dysfunction has traditionally been assumed to be relaxation of the periurethral, prostatic and bladder neck smooth muscle, substantial evidence supports action at extraprostatic sites involved in micturition, including the bladder dome smooth muscle, peripheral ganglia, spinal cord and brain. Likewise the mechanism of action of anticholinergic therapy has been traditionally assumed to be inhibition of the M3 muscarinic receptor subtypes that mediate normal bladder contractions. However, M2 receptor mediates hypertrophied bladder contractions and there is evidence for an M2 component to the suprasacral control of voiding. Conclusions Based on the physiology of α-adrenergic and muscarinic receptors the inhibition of each one would be expected to be more beneficial than that of either alone because they would work on 2 components of detrusor function. Patients who would likely benefit from this combination therapy are men with lower urinary tract symptoms, women with urgency/frequency syndrome (overactive bladder), patients with uninhibited bladder contractions due to neurogenic bladder, and patients with pelvic pain and voiding symptoms, ie interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome. PMID:16217275

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.

Chronic Bladder Infection: Is There a Cure?

MedlinePlus

... to get recurrent bladder infections, a type of urinary tract infection (UTI). These factors include: Kidney or bladder stones Bacteria ... your doctor at the first sign of a UTI Vaginal estrogen therapy — if you don't already ...

An alternative treatment modality in closing bladder exstrophy: use of rectus abdominus muscle flap--preliminary results in a rat model.

PubMed

Büyükünal, S N; Kaner, G; Celayir, S

1989-06-01

The aim of this study was to find a new alternate method for bladder exstrophies with small capacity and inelasticity, and to resolve complications of other bladder augmentation techniques. In 50 Wistar albino rats, a large bladder defect was created excising at least one half of their original bladder, keeping the peritrigonal zone intact. In each rat, a 2.5 x 1-cm inferiorly based rectus abdominus muscle flap was prepared from the lower abdominal quadrant. This flap was then rotated to cover the bladder defect. The inner layer formed by the peritoneum was sutured to the edges of the bladder defect by 6-0 separate sutures. The post-operative radiologic and scintigraphic examination of the urinary system done at different intervals showed no difference from that of normal rats. The only observed disadvantage of this technique was the formation of calculi in the bladder in 8/50 rats in the late post-operative period. Post-mortem histopathologic investigations performed at different intervals showed the inner layer of the flap to be completely covered by the transitional urinary epithelium of the bladder. We think this technique is easy to perform, non-time-consuming, and has a low complication rate. It may be useful in infants with small, noncompliant, inelastic bladder exstrophies.

Disseminated Mycobacterium bovis infection post-kidney transplant following remote intravesical BCG therapy for bladder cancer.

PubMed

Ziegler, Jennifer; Ho, Julie; Gibson, Ian W; Nayak, Jasmir G; Stein, Markus; Walkty, Andrew; Orr, Pamela

2018-05-29

Intravesical Bacillus Camlette-Guérin (BCG) is the treatment of choice for non-muscle invasive bladder cancer, and has been used successfully for over 40 years. A rare and potentially fatal complication of intravesical BCG therapy is BCG-induced sepsis. We report a rare case in which a patient with end-stage renal disease secondary to chronic granulomatous interstitial nephritis underwent remote, pre-transplant intravesical BCG treatment for high-grade non-invasive papillary bladder carcinoma. The patient subsequently received a deceased donor kidney transplant 5 years after BCG therapy, with thymoglobulin induction therapy and standard triple maintenance immunosuppression. Two years post-transplant, he developed BCG-induced sepsis confirmed by cultures from urine, blood and left native kidney biopsy. He died from disseminated BCG-induced sepsis and failure of his renal allograft. This case highlights the potential adverse reactions associated with intravesical BCG therapy that may occur years after bladder cancer therapy is completed, and should heighten physician awareness for BCG-related infections during pre-transplant assessment and post-transplant care of solid organ transplants recipients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Alterations in ubiquitin ligase Siah-2 and its corepressor N-CoR after P-MAPA immunotherapy and anti-androgen therapy: new therapeutic opportunities for non-muscle invasive bladder cancer

PubMed Central

Garcia, Patrick Vianna; Apolinário, Letícia Montanholi; Böckelmann, Petra Karla; Nunes, Iseu da Silva; Duran, Nelson; Fávaro, Wagner José

2015-01-01

The present study describes the role of the ubiquitin ligase Siah-2 and corepressor N-CoR in controlling androgen receptor (AR) and estrogen receptors (ERα and ERβ) signaling in an appropriate animal model (Fischer 344 female rats) of non-muscle invasive bladder cancer (NMIBC), especially under conditions of anti-androgen therapy with flutamide. Furthermore, this study describes the mechanisms of a promising therapeutic alternative for NMIBC based on Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) intravesical immunotherapy combined with flutamide, involving the interaction among steroid hormone receptors, their regulators and Toll-like receptors (TLRs). Our results demonstrated that increased Siah-2 and AR protein levels and decreased N-CoR, cytochrome P450 (CYP450) and estrogen receptors levels played a critical role in the urothelial carcinogenesis, probably leading to escape of urothelial cancer cells from immune system attack. P-MAPA immunotherapy led to distinct activation of innate immune system TLRs 2 and 4-mediated, resulting in increase of interferon signaling pathway, which was more effective in recovering the immunosuppressive tumor immune microenvironment and in recovering the bladder histology features than BCG (Bacillus Calmette-Guerin) treatments. The AR blockade therapy was important in the modulating of downstream molecules of TLR2 and TLR4 signaling pathway, decreasing the inflammatory cytokines signaling and enhancing the interferon signaling pathway when associated with P-MAPA. Taken together, the data obtained suggest that interferon signaling pathway activation and targeting AR and Siah-2 signals by P-MAPA intravesical immunotherapy alone and/ or in combination with AR blockade may provide novel therapeutic approaches for NMIBC. PMID:26191134

Alterations in ubiquitin ligase Siah-2 and its corepressor N-CoR after P-MAPA immunotherapy and anti-androgen therapy: new therapeutic opportunities for non-muscle invasive bladder cancer.

PubMed

Garcia, Patrick Vianna; Apolinário, Letícia Montanholi; Böckelmann, Petra Karla; da Silva Nunes, Iseu; Duran, Nelson; Fávaro, Wagner José

2015-01-01

The present study describes the role of the ubiquitin ligase Siah-2 and corepressor N-CoR in controlling androgen receptor (AR) and estrogen receptors (ERα and ERβ) signaling in an appropriate animal model (Fischer 344 female rats) of non-muscle invasive bladder cancer (NMIBC), especially under conditions of anti-androgen therapy with flutamide. Furthermore, this study describes the mechanisms of a promising therapeutic alternative for NMIBC based on Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) intravesical immunotherapy combined with flutamide, involving the interaction among steroid hormone receptors, their regulators and Toll-like receptors (TLRs). Our results demonstrated that increased Siah-2 and AR protein levels and decreased N-CoR, cytochrome P450 (CYP450) and estrogen receptors levels played a critical role in the urothelial carcinogenesis, probably leading to escape of urothelial cancer cells from immune system attack. P-MAPA immunotherapy led to distinct activation of innate immune system TLRs 2 and 4-mediated, resulting in increase of interferon signaling pathway, which was more effective in recovering the immunosuppressive tumor immune microenvironment and in recovering the bladder histology features than BCG (Bacillus Calmette-Guerin) treatments. The AR blockade therapy was important in the modulating of downstream molecules of TLR2 and TLR4 signaling pathway, decreasing the inflammatory cytokines signaling and enhancing the interferon signaling pathway when associated with P-MAPA. Taken together, the data obtained suggest that interferon signaling pathway activation and targeting AR and Siah-2 signals by P-MAPA intravesical immunotherapy alone and/ or in combination with AR blockade may provide novel therapeutic approaches for NMIBC.

Current state of immunotherapy for bladder cancer.

PubMed

Kassouf, Wassim; Kamat, Ashish M

2004-12-01

Bacillus Calmette-Guerin (BCG) has been shown to be the most effective agent for the treatment of superficial bladder cancer since its approval by the US Food and Drug Administration for the treatment of carcinoma in situ of the bladder in 1990. Recently, augmentation of BCG immunotherapy with interferon-alpha2b and other agents is emerging as salvage therapy for those patients who fail initial treatment. This review summarizes the role of various immunotherapeutic agents in the treatment of bladder cancer, with special emphasis on the appropriate administration and schedule of BCG therapy as well as salvage with the combination of BCG with interferon-alpha2b.

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises.

PubMed

Aragon-Ching, Jeanny B; Trump, Donald L

2016-09-01

Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.

Bladder Cancer Treatment (PDQ®)—Patient Version

Cancer.gov

Treatment of bladder cancer depends on the stage of the cancer. Treatment options include different types of surgery (transurethral resection, radical and partial cystectomy, and urinary diversion), radiation therapy, chemotherapy, and immunotherapy. Learn more about how bladder cancer is treated.

Atezolizumab in urothelial bladder carcinoma.

PubMed

Hamilou, Zineb; Lavaud, Pernelle; Loriot, Yohann

2018-02-01

Metastatic bladder cancer is an aggressive malignancy with a poor prognosis when presenting with advanced stage. Cisplatin-based therapy has been the mainstay of first-line treatment but therapy in second-line setting has been an unmet medical need for decades. Moreover, many patients are unable to receive cisplatin-based therapy. Recently, immune-checkpoint inhibitors transformed the management and prognosis of many malignancies and will certainly redefine the standard of care for bladder cancer. Atezolizumab, an anti-PD-L1 antibody, was the first immune-checkpoint inhibitor to be approved by the US FDA in May 2016 for patients with urothelial carcinoma. In this review, we discuss the evidence behind this promising drug.

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

Canyilmaz, Emine, E-mail: dremocan@yahoo.com; Yavuz, Melek Nur; Serdar, Lasif

Purpose: The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. Methods and Materials: Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) weremore » at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. Results: The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. Conclusions: The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy.« less

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

Preclinical assessment of potential interactions between botulinum toxin and neuromodulation for bladder micturition reflex.

PubMed

Su, Xin; Nickles, Angela; Nelson, Dwight E

2015-06-09

While botulinum toxin A (BoNT-A) has become a more commonly used second-line treatment for patients with detrusor overactivity, it remains unknown whether the impacts of this therapy may persist to influence other therapies such as sacral neuromodulation. In this preclinical study we have evaluated urodynamic functions to intradetrusor injection of BoNT-A and the bladder inhibitory effects of spinal nerve stimulation (SNS) following BoNT-A treatment. Female rats were anesthetized with 3 % isoflurane. BoNT-A (2 units, 0.2 ml) or saline were injected into the detrusor. Rats then were housed for 2 days to 1 month before neuromodulation study. Monopolar electrodes were placed under each of the L6 spinal nerve bilaterally under urethane anesthesia. A bladder cannula was inserted via the urethra for saline infusion and intravesical pressure recording. Intradetrusor injection of BoNT-A for 1-2 weeks or 1 month significantly increased bladder capacity compared with saline injection (p < 0.05, two-way ANOVA). Following BoNT-A, SNS attenuated the frequency of bladder contractions, either eliminating bladder contractions or reducing the contraction frequency during electrical stimulation. Inhibition of the contraction frequency by SNS following BoNT-A treated rats was not different from that measured following saline injection. BoNT-A increased the bladder capacity, but compensating for additional saline infusion to the enlarged urinary bladder in BoNT-A pretreated rats, the bladder contractions induced by bladder filling were attenuated by SNS. BoNT-A did not alter the ability of SNS to inhibit bladder contraction following intradetrusor injection of BoNT-A for 2 days, 1-2 weeks or 1 month. These results support further pre-clinical and clinical studies to evaluate potential interactions or combination therapy with neuromodulation and intradetrusor BoNT-A therapeutic approaches.

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

Bladder Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Bladder cancer treatment options depend on if it is nonmuscle or muscle invasive and may include surgery, BCG, chemotherapy, and targeted therapy. Get detailed information about the diagnosis and treatment of newly diagnosed and recurrent bladder cancer in this summary for clinicians.

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

Surgical technique for en bloc transurethral resection of bladder tumour with a Hybrid Knife(®).

PubMed

Islas-García, J J O; Campos-Salcedo, J G; López-Benjume, B I; Torres-Gómez, J J; Aguilar-Colmenero, J; Martínez-Alonso, I A; Gil-Villa, S A

2016-05-01

Bladder cancer is the second most common malignancy of the urinary tract and the 9th worldwide. Latin American has an incidence of 5.6 per 100,000 inhabitants per year. Seventy-five percent of newly diagnosed cases are nonmuscle invasive bladder cancer, and 25% of cases present as muscle invasive. The mainstay of treatment for nonmuscle invasive bladder cancer is loop transurethral resection. In 2013, the group led by Dr Mundhenk of the University Hospital of Tübingen, Germany, was the first to describe the Hybrid Knife(®) equipment for performing en bloc bladder tumour resection, with favourable functional and oncological results. To describe the surgical technique of en bloc bladder tumour resection with a Hybrid Knife(®) as an alternative treatment for nonmuscle invasive bladder tumours. A male patient was diagnosed by urotomography and urethrocystoscopy with a bladder tumour measuring 2×1cm on the floor. En bloc transurethral resection of the bladder tumour was performed with a Hybrid Knife(®). Surgery was performed for 35min, with 70 watts for cutting and 50 watts for coagulation, resecting and evacuating en bloc the bladder tumour, which macroscopically included the muscle layer of the bladder. There were no complications. The technique of en bloc bladder tumour resection with Hybrid Knife(®) is an effective alternative to bipolar loop transurethral resection. Resection with a Hybrid Knife(®) is a procedure with little bleeding and good surgical vision and minimises the risk of bladder perforation and tumour implants. The procedure facilitates determining the positivity of the neoplastic process, vascular infiltration and bladder muscle invasion in the histopathology study. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Intravesical dosimetry applied to laser positioning in photodynamic therapy

NASA Astrophysics Data System (ADS)

Beslon, Guillaume; Ambroise, Philippe; Heit, Bernard; Bremont, Jacques; Guillemin, Francois H.

1996-12-01

Superficial bladder tumor is a challenging indication for photodynamic therapy. Due to lack of specificity of the sensitizers, the light has to be precisely monitored over the bladder surface, illuminated by an isotropic source, to restrict the cytotoxic effect to the tumor without affecting the normal epithelium. In order to assist the surgeon while processing the therapy, an urothelium illumination model is proposed. It is computed through a spline interpolation, on the basis of 12 intravesical sensors. This paper presents the overall system architecture and details the modelization and visualization processes. With this model, the surgeon is able to master the source displacement inside the bladder and to homogenize the tissue exposure.

Nonantimuscarinic treatment for overactive bladder: a systematic review.

PubMed

Olivera, Cedric K; Meriwether, Kate; El-Nashar, Sherif; Grimes, Cara L; Chen, Chi Chiung Grace; Orejuela, Francisco; Antosh, Danielle; Gleason, Jon; Kim-Fine, Shunaha; Wheeler, Thomas; McFadden, Brook; Balk, Ethan M; Murphy, Miles

2016-07-01

The purpose of the study was to determine the efficacy and safety of nonantimuscarinic treatments for overactive bladder. Medline, Cochrane, and other databases (inception to April 2, 2014) were used. We included any study design in which there were 2 arms and an n > 100, if at least 1 of the arms was a nonantimuscarinic therapy or any comparative trial, regardless of number, if at least 2 arms were nonantimuscarinic therapies for overactive bladder. Eleven reviewers double-screened citations and extracted eligible studies for study: population, intervention, outcome, effects on outcome categories, and quality. The body of evidence for categories of interventions were summarized and assessed for strength. Ninety-nine comparative studies met inclusion criteria. Interventions effective to improve subjective overactive bladder symptoms include exercise with heat and steam generating sheets (1 study), diaphragmatic (1 study), deep abdominal (1 study), and pelvic floor muscle training exercises (2 studies). Pelvic floor exercises are more effective in subjective and objective outcomes with biofeedback or verbal feedback. Weight loss with diet and exercise, caffeine reduction, 25-50% reduction in fluid intake, and pelvic floor muscle exercises with verbal instruction and or biofeedback were all efficacious. Botulinum toxin A improves urge incontinence episodes, urgency, frequency, quality of life, nocturia, and urodynamic testing parameters. Acupuncture improves quality of life and urodynamic testing parameters. Extracorporeal magnetic stimulation improves urodynamic parameters. Mirabegron improves daily incontinence episodes, nocturia, number of daily voids, and urine volume per void, whereas solabegron improves daily incontinence episodes. Short-term posterior tibial nerve stimulation is more efficacious than pelvic floor muscle training exercises and behavioral therapy for improving: urgency, urinary incontinence episodes, daily voids, volume per void, and overall quality of life. Sacral neuromodulation is more efficacious than antimuscarinic treatment for subjective improvement of overactive bladder and quality of life. Transvaginal electrical stimulation demonstrates subjective improvement in overactive bladder symptoms and urodynamic parameters. Multiple therapies, including physical therapy, behavioral therapy, botulinum toxin A, acupuncture, magnetic stimulation, mirabegron, posterior tibial nerve stimulation, sacral neuromodulation, and transvaginal electrical stimulation, are efficacious in the treatment of overactive bladder. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Recombinant Mycobacterium bovis BCG for immunotherapy in nonmuscle invasive bladder cancer.

PubMed

Begnini, K R; Buss, J H; Collares, T; Seixas, F K

2015-05-01

In the past three decades, intravesical instillation of Mycobacterium bovis bacille Calmette-Guérin (BCG) has been used for treating bladder cancer and it still remains at the forefront of immunotherapy for cancer patients. Although BCG-based therapy is the most effective intravesical therapy for this kind of tumor and represents the only agent known to reduce progression into muscle invasive bladder cancer, BCG is ineffective in approximately 30-40 % of cases and disease recurs in up to 50 % of patients. Since that BCG is considered an effective vehicle for delivery of antigens due to its unique characteristics, the genetic manipulation of these mycobacteria has been appealing in the search for less toxic and more potent therapeutic agents for bladder cancer immunotherapy. Herein, we discuss current advances in recombinant BCG construction, research, concerns, and future directions to promote the development of this promising immunotherapeutic approach for bladder cancer.

Intravesical treatments of bladder pain syndrome/interstitial cystitis.

PubMed

Neuhaus, Jochen; Schwalenberg, Thilo

2012-12-01

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a disabling chronic condition that affects up to 7% of women in the USA. In men, BPS/IC seems to be less common, but might be underestimated because it can be confused with chronic prostatitis. The aetiology and pathophysiology of BPS/IC are not well understood. Consequently, diagnosis and treatment is challenging and most therapies used to date are off-label. These therapies include bladder instillation with dimethyl sulfoxide (DMSO) and BCG, as well as hyperbaric oxygen therapy. Overall, botulinum neurotoxin A injection, intravesical sodium hyaluronate instillation and DMSO instillation seem to be the best-performing treatments, with response rates of 79%, 76% and 75%, respectively, and can be used effectively as second-line or third-line therapies for BPS/IC. However, additional high-quality randomized controlled trials are necessary to improve the available data.

Myasthenia Gravis After Nivolumab Therapy for Squamous Cell Carcinoma of the Bladder.

PubMed

Chang, Elaine; Sabichi, Anita L; Sada, Yvonne H

2017-04-01

Checkpoint inhibitors have become standard therapy for multiple cancers, and their use will increase in the next year as regulatory approvals for additional indications are expected. It is essential for clinicians to be aware of the potential for rare immune-related adverse effects. Here, we report the case of a new diagnosis of myasthenia gravis (MG) after the use of nivolumab for squamous cell carcinoma of the bladder. A review the literature identified 10 cases of MG diagnosed after programmed cell death protein 1 inhibitor therapy. This is the first case, to our knowledge, reported in association with bladder cancer. The precise diagnosis of MG has important implications on management, as treatment with steroids can transiently worsen myasthenia in nearly 50% of cases.

A randomized, multicenter, controlled study, comparing efficacy and safety of a new complementary and alternative medicine (CAM) versus Solifenacin Succinate in women with overactive bladder syndrome.

PubMed

Vecchioli-Scaldazza, Carlo; Morosetti, Carolina; Maruccia, Serena; Casellato, Stefano; Rociola, Wilma; Illiano, Ester; Garofalo, Francesco

2017-12-31

To assess efficacy and tolerability of a new complementary and alternative medicine (CAM) consisting of vitamins (C and D), herbal products (cucurbita maxima, capsicum annum, polygonum capsicatum) and amino acid L-Glutammina, in the treatment of female Overactive Bladder syndrome (OAB). 90 consecutive women with OAB symptoms were enrolled in this prospective, randomized, controlled study. Women were divided randomly into two groups of 45 patients each. In group A, women received Solifenacin Succinate (SS), 5 mg. once a day for 12 weeks. In group B, women received CAM, 930 mg, twice daily for 12 weeks. Women were assessed with 3-day micturition diary, Patient Perception of Intensity of Urgency Scale (PPIUS), Overactive Bladder questionnaire Short Form (OAB-q SF) and Patient Global Impression of Improvement questionnaire (PGI-I). 8 patients in group A and 1 patient in group B dropped out from therapy because of side effects. A reduction in the number of daily micturitions, nocturia and episodes of urge incontinence was present with both SS and CAM with statistically highly significant differences, but CAM was significantly more effective than SS. PPIUS and OAB-q SF showed improvements with both SS and CAM with a more significant efficacy of CAM. PGI-I, demonstrated improvements in the two groups of patients with a greater satisfaction expressed by patients treated with CAM. the small number of patients does not permit definitive conclusions; however, the results of the research showed the greater effectiveness and tolerability of CAM.

Frequent or urgent urination

MedlinePlus

Urgent urination; Urinary frequency or urgency; Urgency-frequency syndrome; Overactive bladder (OAB) syndrome; Urge syndrome ... Medicines such as water pills (diuretics) Overactive bladder syndrome Radiation therapy to the pelvis, which is used ...

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

Combined Chemoradiation Therapy With Twice-Weekly Gemcitabine and Cisplatin for Organ Preservation in Muscle-Invasive Bladder Cancer: Long-Term Results of a Phase 1 Trial

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

Azria, David, E-mail: david.azria@icm.unicancer.fr; INSERM, U896, IRCM, Montpellier; Riou, Olivier

2014-03-15

Purpose: Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting. Methods and Materials: Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabinemore » twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control. Results: Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months. Conclusions: This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing.« less

Long-term outcomes of intravesical dimethyl sulfoxide/heparin/hydrocortisone therapy for interstitial cystitis/bladder pain syndrome.

PubMed

Lim, Yik N; Dwyer, Peter; Murray, Christine; Karmakar, Debjyoti; Rosamilia, Anna; Thomas, Elizabeth

2017-07-01

For decades, intravesical dimethyl sulfoxide (DMSO) cocktail therapy has been used for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS), but little is known about its long-term efficacy. We aimed to assess the long-term efficacy of intravesical DMSO/heparin/hydrocortisone/bupivacaine therapy in patients with IC/BPS. Patients with IC/BPS from our institutions who underwent this therapy with >2 years follow-up were surveyed with O'Leary-Sant interstitial cystitis symptom and problem index questionnaires before and after therapy. Chart reviews and telephone surveys were then conducted to determine their posttherapy course. Of 68 eligible women, 55 (80.0%) with a median follow-up of 60 months (range 24-142) were surveyed. Their mean age at therapy onset was 44.8 years and their mean body mass index was 26.2 kg/m 2 . There were statistically significant improvements in O'Leary-Sant and pain scores of 23-47% at both 6 weeks and the end of the follow-up period. At the end of the follow-up period, 19 of the 55 women (34.5%) were cured (requiring no further treatment) and 12 (21.8%) were significantly improved (requiring only ongoing oral medication). Univariate and multivariate analyses showed that DMSO treatment failure was more likely in patients with pretreatment day-time urinary frequency more than 15 episodes per day (OR 1.41), nocturia more than two episodes per night (OR 2.47), maximum bladder diary voided volume <200 ml (OR 1.39) and bladder capacity under anaesthesia <500 ml (OR 1.6). At a median follow-up of 60 months, intravesical DMSO cocktail therapy appeared moderately effective for the treatment of IC/BPS. Treatment failure was more frequent in patients with pretreatment symptoms of reduced bladder capacity.

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.

Bladder Smooth Muscle Cells Differentiation from Dental Pulp Stem Cells: Future Potential for Bladder Tissue Engineering

PubMed Central

Song, Bing; Jiang, Wenkai; Alraies, Amr; Liu, Qian; Gudla, Vijay; Oni, Julia; Wei, Xiaoqing; Sloan, Alastair; Ni, Longxing; Agarwal, Meena

2016-01-01

Dental pulp stem cells (DPSCs) are multipotent cells capable of differentiating into multiple cell lines, thus providing an alternative source of cell for tissue engineering. Smooth muscle cell (SMC) regeneration is a crucial step in tissue engineering of the urinary bladder. It is known that DPSCs have the potential to differentiate into a smooth muscle phenotype in vitro with differentiation agents. However, most of these studies are focused on the vascular SMCs. The optimal approaches to induce human DPSCs to differentiate into bladder SMCs are still under investigation. We demonstrate in this study the ability of human DPSCs to differentiate into bladder SMCs in a growth environment containing bladder SMCs-conditioned medium with the addition of the transforming growth factor beta 1 (TGF-β1). After 14 days of exposure to this medium, the gene and protein expression of SMC-specific marker (α-SMA, desmin, and calponin) increased over time. In particular, myosin was present in differentiated cells after 11 days of induction, which indicated that the cells differentiated into the mature SMCs. These data suggested that human DPSCs could be used as an alternative and less invasive source of stem cells for smooth muscle regeneration, a technology that has applications for bladder tissue engineering. PMID:26880982

Vaginal motion and bladder and rectal volumes during pelvic intensity-modulated radiation therapy after hysterectomy.

PubMed

Jhingran, Anuja; Salehpour, Mohammad; Sam, Marianne; Levy, Larry; Eifel, Patricia J

2012-01-01

To evaluate variations in bladder and rectal volume and the position of the vaginal vault during a 5-week course of pelvic intensity-modulated radiation therapy (IMRT) after hysterectomy. Twenty-four patients were instructed how to fill their bladders before simulation and treatment. These patients underwent computed tomography simulations with full and empty bladders and then underwent rescanning twice weekly during IMRT; patients were asked to have full bladder for treatment. Bladder and rectal volumes and the positions of vaginal fiducial markers were determined, and changes in volume and position were calculated. The mean full and empty bladder volumes at simulation were 480 cc (range, 122-1,052) and 155 cc (range, 49-371), respectively. Bladder volumes varied widely during IMRT: the median difference between the maximum and minimum volumes was 247 cc (range, 96-585). Variations in rectal volume during IMRT were less pronounced. For the 16 patients with vaginal fiducial markers in place throughout IMRT, the median maximum movement of the markers during IMRT was 0.59 cm in the right-left direction (range, 0-0.9), 1.46 cm in the anterior-posterior direction (range, 0.8-2.79), and 1.2 cm in the superior-inferior direction (range, 0.6-2.1). Large variations in rectal or bladder volume frequently correlated with significant displacement of the vaginal apex. Although treatment with a full bladder is usually preferred because of greater sparing of small bowel, our data demonstrate that even with detailed instruction, patients are unable to maintain consistent bladder filling. Variations in organ position during IMRT can result in marked changes in the position of the target volume and the volume of small bowel exposed to high doses of radiation. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical Outcomes of Image Guided Adaptive Hypofractionated Weekly Radiation Therapy for Bladder Cancer in Patients Unsuitable for Radical Treatment

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

Hafeez, Shaista, E-mail: shaista.hafeez@icr.ac.uk; The Royal Marsden NHS Foundation Trust, Sutton, Surrey; McDonald, Fiona

Purpose and Objectives: We report on the clinical outcomes of a phase 2 study assessing image guided hypofractionated weekly radiation therapy in bladder cancer patients unsuitable for radical treatment. Methods and Materials: Fifty-five patients with T2-T4aNx-2M0-1 bladder cancer not suitable for cystectomy or daily radiation therapy treatment were recruited. A “plan of the day” radiation therapy approach was used, treating the whole (empty) bladder to 36 Gy in 6 weekly fractions. Acute toxicity was assessed weekly during radiation therapy, at 6 and 12 weeks using the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was assessed at 6 months and 12 monthsmore » using Radiation Therapy Oncology Group grading. Cystoscopy was used to assess local control at 3 months. Cumulative incidence function was used to determine local progression at 1 at 2 years. Death without local progression was treated as a competing risk. Overall survival was estimated using the Kaplan-Meier method. Results: Median age was 86 years (range, 68-97 years). Eighty-seven percent of patients completed their prescribed course of radiation therapy. Genitourinary and gastrointestinal grade 3 acute toxicity was seen in 18% (10/55) and 4% (2/55) of patients, respectively. No grade 4 genitourinary or gastrointestinal toxicity was seen. Grade ≥3 late toxicity (any) at 6 and 12 months was seen in 6.5% (2/31) and 4.3% (1/23) of patients, respectively. Local control after radiation therapy was 92% of assessed patients (60% total population). Cumulative incidence of local progression at 1 year and 2 years for all patients was 7% (95% confidence interval [CI] 2%-17%) and 17% (95% CI 8%-29%), respectively. Overall survival at 1 year was 63% (95% CI 48%-74%). Conclusion: Hypofractionated radiation therapy delivered weekly with a plan of the day approach offers good local control with acceptable toxicity in a patient population not suitable for radical bladder treatment.« less

Prevention of recurrent urinary tract infections by intravesical administration of heparin: a pilot study.

PubMed

Ablove, Tova; Patankar, Manish; Seo, Songwon

2013-12-01

To assess the effect of bladder instillations using heparin on the rate of urinary tract infections in women resistant to standard therapy. The medical records of all women who received bladder instillations between May 2009 and January of 2010 at the University of Wisconsin urogynecology clinic were reviewed. Eighteen women (mean age 67 years) with a history of recurrent urinary tract infections received intravesical instillations (heparin 40,000 U, 2% lidocaine 8 ml, sodium bicarbonate 4 ml) once weekly for 6 weeks. Patients were considered resistant to standard therapy if their condition failed to respond to chronic suppression antibiotic therapy; they had chronic infections and for this reason could not be placed on chronic suppression; or they were not candidates for chronic suppression due to drug allergies. The number of urinary tract infections was monitored during treatment and for 6 months after therapy. The urinary tract infection rates were compared with the rates of urinary tract infection in the 6 months before treatment. Seventy-eight percent of patients responded to therapy. Subjects were thought to have responded to therapy if there was a greater than 50% reduction in the rate of urinary tract infection. Other variables reviewed included evidence of chronic infection, hormonal status, glomerular filtration rate, age, body mass index, antibiotic allergies, diabetes, hypertension, and chronic antibiotic therapy during bladder instillations. None of these variables were found to be statistically significant. Bladder instillations decreased the rate of urinary tract infection in this pilot study; this effect persisted into the post-treatment period. More research is needed to confirm these preliminary findings.

Early penile metastasis from primary bladder cancer as the first systemic manifestation: a case report.

PubMed

Sönmez, Nurettin Cem; Coşkun, Burhan; Arisan, Serdar; Güney, Soner; Dalkiliç, Ayhan

2009-08-14

Metastatic involement of penis is an exceptionally rare condition. 77% of the metastases are originated from the pelvic region; prostate and bladder are the most frequent primary locations. Retrograde venous route, retrograde lymphatic route, arterial spread, direct extension, implantation and secondary to instrumentation are the mechanisms of metastasis. Approximately two thirds of all penile metastasis are detected at a mean time of 18 months after the detection of the primary tumor and the remaining one third is presented at the same time with primary tumor. Diagnosis is usually made by biopsy and also non invasive methods as MRI or colour-coded duplex ultrasonography. Treatment options in these patients are local excision, partial or complete penectomy, external beam radiation therapy and chemotheraphy. Despite these alternatives prognosis is usually poor.We present a case of urethelial carcinoma of the bladder and coincidental prostate adenocarcinoma with penile metastasis which is presented with priapism 6 months after radical cystectomy as the first systemic manifestation. We performed biopsy initially for staging and the patient underwent MRI showing the extension of the disease. The patient underwent radiotherapy of 56 gy and priapism partially resolved after the treatment. Chemotheraphy was also planned but the patient died 3 months following radiotheraphy.

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.

Collaborating to Move Research Forward: Proceedings of the 10th Annual Bladder Cancer Think Tank.

PubMed

Kamat, Ashish M; Agarwal, Piyush; Bivalacqua, Trinity; Chisolm, Stephanie; Daneshmand, Sia; Doroshow, James H; Efstathiou, Jason A; Galsky, Matthew; Iyer, Gopa; Kassouf, Wassim; Shah, Jay; Taylor, John; Williams, Stephen B; Quale, Diane Zipursky; Rosenberg, Jonathan E

2016-04-27

The 10th Annual Bladder Cancer Think Tank was hosted by the Bladder Cancer Advocacy Network and brought together a multidisciplinary group of clinicians, researchers, representatives and Industry to advance bladder cancer research efforts. Think Tank expert panels, group discussions, and networking opportunities helped generate ideas and strengthen collaborations between researchers and physicians across disciplines and between institutions. Interactive panel discussions addressed a variety of timely issues: 1) data sharing, privacy and social media; 2) improving patient navigation through therapy; 3) promising developments in immunotherapy; 4) and moving bladder cancer research from bench to bedside. Lastly, early career researchers presented their bladder cancer studies and had opportunities to network with leading experts.

[Systematic review on conservative treatment options in non-muscle-invasive bladder cancer patients refractory to Bacillus Calmette-Guérin instillation therapy].

PubMed

Martini, Thomas; Wezel, Felix; Löbig, Niklas; Mitterberger, Michael J; Colleselli, Daniela

2017-08-01

Background Adjuvant Bacillus Calmette-Guérin (BCG) intravesical instillation is the recommended standard treatment in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). However, a significant proportion of patients fail treatment, and radical cystectomy (RC) is the subsequent gold standard. On the other hand, there is an unmet need for conservative alternatives for patients who are unfit or unwilling to undergo surgery. This study aimed to identify conservative treatment options in NMIBC patients after BCG failure. Material and Methods We performed a systematic search in the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, including all randomised controlled trials (RCTs), quasi-RCTs and single-arm studies, in which patients with NMIBC were treated with second-line intravesical or systemic therapy after BCG failure. A minimum of eight patients were included in each treatment arm. Full papers were restricted to English language. Literature research and data analysis were assessed independently by two reviewers. Data on treatment response, recurrence, time to recurrence, progression and rate of cystectomy were collected and analysed. Results  This systematic review included 42 publications with a total of 3521 patients (2371 BCG failures). Valrubicin, taxanes, gemcitabine, combination chemotherapy, thermochemotherapy, photodynamic therapy, combination of BCG and interferon and immunotherapies or targeted therapies were identified as conservative treatment options. For taxanes, gemcitabine and thermochemotherapy there is the highest evidence for a clinical meaningful response with minor toxicities. Conclusions Despite some promising response rates for taxanes, gemcitabine or thermochemotherapy, an evidence-based recommendation for treatment options superior to RC in patients failing BCG therapy cannot be made. The definition of BCG failure is still inconsistent and heterogeneous outcomes in patients with BCG failure have been reported. In order to identify effective conservative therapy options in patients failing BCG therapy, prospective trials with a standardised trial design are needed. © Georg Thieme Verlag KG Stuttgart · New York.

Update on extracorporeal magnetic innervation (EXMI) therapy for stress urinary incontinence.

PubMed

Galloway, N T; El-Galley, R E; Sand, P K; Appell, R A; Russell, H W; Carlin, S J

2000-12-04

Pulsed magnetic technology has been developed for pelvic floor muscle strengthening for the treatment of urinary incontinence. This report includes an update of the prospective multicenter study of extracorporeal magnetic innervation (ExMI) therapy for stress incontinence and a discussion of the possible mechanisms of action. Issues of patient selection for ExMI therapy will also be discussed. One hundred and eleven women with demonstrable stress urinary incontinence were studied. The mean age was 55 +/- 13 years, and the mean duration of symptoms was 11 years. Ninety-seven completed ExMI therapy and analysis. Evaluation before treatment included bladder diaries, dynamic pad weight test, urodynamics, and a quality-of-life survey. For treatment the patients were seated fully clothed in a Neocontrol chair with a magnetic field therapy head in the seat. Treatment sessions were for 20 minutes, twice a week, for 6 weeks. After ExMI therapy, all of the measures were repeated at 8 weeks, including the dynamic pad weight testing and quality-of-life survey. At 6 months, further data were added, including repeat bladder diary, pad use, and quality-of-life survey. Forty-seven women completed 6 months of follow-up; of the 47, 13 patients were completely dry (28%) and 25 used no pad or less than 1 pad per day (53%). Pad use was reduced in 33 patients (70%). The median number of pads was reduced from 2.16 to 1 per day (Wilcoxon signed rank test, P <0.005). The frequency of leak episodes was reduced from 3.0 to 1.7 at 6 months (Wilcoxon signed rank test, P = 0.004). Detrusor instability was demonstrated in 10 before and 6 after ExMI (P <0.05). ExMI offers an alternative approach for the treatment of urinary incontinence. ExMI therapy is effective for both stress and urge incontinence. The best results are achieved in those patients who use no more than 3 pads a day and have had no prior continence surgery.

Nod for Atezolizumab in Advanced Bladder Cancer.

PubMed

2017-06-01

The FDA approved atezolizumab to treat advanced bladder cancer when cisplatin chemotherapy is contraindicated. The approval offers a potentially more effective alternative to carboplatin-based chemotherapy for frail, elderly patients. ©2017 American Association for Cancer Research.

Vaginal Motion and Bladder and Rectal Volumes During Pelvic Intensity-Modulated Radiation Therapy After Hysterectomy

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

Jhingran, Anuja, E-mail: ajhingra@mdanderson.org; Salehpour, Mohammad; Sam, Marianne

2012-01-01

Purpose: To evaluate variations in bladder and rectal volume and the position of the vaginal vault during a 5-week course of pelvic intensity-modulated radiation therapy (IMRT) after hysterectomy. Methods and Materials: Twenty-four patients were instructed how to fill their bladders before simulation and treatment. These patients underwent computed tomography simulations with full and empty bladders and then underwent rescanning twice weekly during IMRT; patients were asked to have full bladder for treatment. Bladder and rectal volumes and the positions of vaginal fiducial markers were determined, and changes in volume and position were calculated. Results: The mean full and empty bladdermore » volumes at simulation were 480 cc (range, 122-1,052) and 155 cc (range, 49-371), respectively. Bladder volumes varied widely during IMRT: the median difference between the maximum and minimum volumes was 247 cc (range, 96-585). Variations in rectal volume during IMRT were less pronounced. For the 16 patients with vaginal fiducial markers in place throughout IMRT, the median maximum movement of the markers during IMRT was 0.59 cm in the right-left direction (range, 0-0.9), 1.46 cm in the anterior-posterior direction (range, 0.8-2.79), and 1.2 cm in the superior-inferior direction (range, 0.6-2.1). Large variations in rectal or bladder volume frequently correlated with significant displacement of the vaginal apex. Conclusion: Although treatment with a full bladder is usually preferred because of greater sparing of small bowel, our data demonstrate that even with detailed instruction, patients are unable to maintain consistent bladder filling. Variations in organ position during IMRT can result in marked changes in the position of the target volume and the volume of small bowel exposed to high doses of radiation.« less

Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer.

PubMed

Blute, Michael L; Rushmer, Timothy J; Shi, Fangfang; Fuller, Benjamin J; Abel, E Jason; Jarrard, David F; Downs, Tracy M

2015-11-01

Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer. Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival. Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in 52 in whom it was combined with angiotensin converting enzyme inhibitor/angiotensin receptor blocker. Multivariate analysis revealed that patients treated with bacillus Calmette-Guérin alone (HR 2.19, 95% CI 1.01-4.77, p = 0.04) showed worse recurrence-free survival compared to patients treated with bacillus Calmette-Guérin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (stage Ta HR 0.45, 95% CI 0.21-0.98, p = 0.04). Pharmacological inhibition of the renin-angiotensin system is associated with improved outcomes in patients with bladder cancer. Renin-angiotensin system inhibitor administration in nonmuscle invasive bladder cancer cases should be studied in a prospective randomized trial. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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.

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.

Fibronectin Attachment Protein (FAP) From Bacillus Calmette-Guerin As Targeting Agent For Bladder Tumor Cells

PubMed Central

Coon, Brian G.; Crist, Scott; González-Bonet, Andrés M.; Kim, Hee-Kwon; Sowa, Jennifer; Thompson, David H.; Ratliff, Timothy L.; Aguilar, R. Claudio

2011-01-01

The adjuvant therapy of choice for superficial bladder cancer is the intravesical instillation of live Mycobacterium bovis Bacillus Calmette-Guerin (BCG). In spite of the fact that this therapy is the most effective treatment for superficial bladder cancer, intravesical administration of BCG is associated with high local morbidity and the potential for systemic infection. Therefore, there is a need for the development of safer, less toxic approaches to fight this disease. Since fibronectin attachment protein (FAP) is a key element in BCG retention and targeting to cells, we hypothesize that this protein can be used as targeting agent to deliver cytotoxic cargo for the treatment of bladder tumors. Here we evaluated the ability of bladder tumor cells to bind and endocytose FAP via fibronectin-integrin complexes. We found that microaggregation induced by an anti-FAP polyclonal antibody accelerated FAP uptake by T24 bladder tumor cells. FAP was determined to be internalized via a clathrin-independent, caveolae-dependent mechanism. Further, once within the endosomal compartment, FAP was targeted to the lysosomal compartment with negligible recycling to the plasma membrane. Importantly, we demonstrated that FAP microaggregation and internalization could also be triggered by multivalent Ni2+NTA-bearing liposomes. Overall, our studies validate the use of FAP as a targeting vector and provide the foundation for the design of more effective, less toxic bladder cancer therapeutics. PMID:21901746

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.

Risk factors for bladder calculi in patients with benign prostatic hyperplasia.

PubMed

Huang, Wei; Cao, Jun-Jie; Cao, Min; Wu, Hong-Shen; Yang, Yong-Yi; Xu, Zi-Meng; Jin, Xiao-Dong

2017-08-01

We aim to find the risk factors that influence the formation of bladder calculi in patients with benign prostate hyperplasia (BPH) and to reduce the surgical intervention related to bladder calculi.Between January 2015 and October 2016, 332 patients with BPH underwent surgical therapy were retrospectively evaluated. Patients with BPH were categorized into 2 groups: 94 patients with bladder calculi in group 1 and 238 patients without bladder calculi in group 2. Medical history, age, body mass index (BMI), total prostate specific antigen, total prostate volume (TPV), International Prostate Symptom Score (IPSS), intravesical prostatic protrusion (IPP), urodynamic parameters, and urine culture were compared between groups.There was no significant difference in the age, BMI, peak flow rate, and total IPSS between groups. TPV, total prostate specific antigen, and duration of BPH were significantly lower in group 1 than those in group 2. In addition, IPP was significantly higher in group 1 than group 2 (P < .001). Besides, after exclusion of patients with urinary retention and indwelling catheter, group 1 associated with a significantly higher preoperative positive rate of urine culture than that of group 2 (P = .046). Multivariate analysis indicated that IPP was a significant independent risk factor for the presence of bladder calculi.The incidence of bladder calculi in patients with BPH was proved to be closely associated with preoperative positive urine culture and longer IPP in our study. Furthermore, the IPP was presented to be an independent risk factor for the formation of bladder calculi. And early antibacterial therapy of urinary tract infection (UTI) may help to prevent the presence of bladder calculi in patients with BPH.

Genetic variant as a marker for bladder cancer therapy

Cancer.gov

Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research a

Chemoradiation May Help Some Patients with Bladder Cancer Avoid Radical Surgery

Cancer.gov

Researchers in the United Kingdom have found that adding chemotherapy to radiation therapy as a treatment for bladder cancer may reduce the risk of a recurrence more than radiation alone, without causing a substantial increase in side effects.

Understanding the Role of Non-Coding RNAs in Bladder Cancer: From Dark Matter to Valuable Therapeutic Targets

PubMed Central

Pop-Bica, Cecilia; Gulei, Diana; Cojocneanu-Petric, Roxana; Braicu, Cornelia; Petrut, Bogdan; Berindan-Neagoe, Ioana

2017-01-01

The mortality and morbidity that characterize bladder cancer compel this malignancy into the category of hot topics in terms of biomolecular research. Therefore, a better knowledge of the specific molecular mechanisms that underlie the development and progression of bladder cancer is demanded. Tumor heterogeneity among patients with similar diagnosis, as well as intratumor heterogeneity, generates difficulties in terms of targeted therapy. Furthermore, late diagnosis represents an ongoing issue, significantly reducing the response to therapy and, inevitably, the overall survival. The role of non-coding RNAs in bladder cancer emerged in the last decade, revealing that microRNAs (miRNAs) may act as tumor suppressor genes, respectively oncogenes, but also as biomarkers for early diagnosis. Regarding other types of non-coding RNAs, especially long non-coding RNAs (lncRNAs) which are extensively reviewed in this article, their exact roles in tumorigenesis are—for the time being—not as evident as in the case of miRNAs, but, still, clearly suggested. Therefore, this review covers the non-coding RNA expression profile of bladder cancer patients and their validated target genes in bladder cancer cell lines, with repercussions on processes such as proliferation, invasiveness, apoptosis, cell cycle arrest, and other molecular pathways which are specific for the malignant transformation of cells. PMID:28703782

Understanding the Role of Non-Coding RNAs in Bladder Cancer: From Dark Matter to Valuable Therapeutic Targets.

PubMed

Pop-Bica, Cecilia; Gulei, Diana; Cojocneanu-Petric, Roxana; Braicu, Cornelia; Petrut, Bogdan; Berindan-Neagoe, Ioana

2017-07-13

The mortality and morbidity that characterize bladder cancer compel this malignancy into the category of hot topics in terms of biomolecular research. Therefore, a better knowledge of the specific molecular mechanisms that underlie the development and progression of bladder cancer is demanded. Tumor heterogeneity among patients with similar diagnosis, as well as intratumor heterogeneity, generates difficulties in terms of targeted therapy. Furthermore, late diagnosis represents an ongoing issue, significantly reducing the response to therapy and, inevitably, the overall survival. The role of non-coding RNAs in bladder cancer emerged in the last decade, revealing that microRNAs (miRNAs) may act as tumor suppressor genes, respectively oncogenes, but also as biomarkers for early diagnosis. Regarding other types of non-coding RNAs, especially long non-coding RNAs (lncRNAs) which are extensively reviewed in this article, their exact roles in tumorigenesis are-for the time being-not as evident as in the case of miRNAs, but, still, clearly suggested. Therefore, this review covers the non-coding RNA expression profile of bladder cancer patients and their validated target genes in bladder cancer cell lines, with repercussions on processes such as proliferation, invasiveness, apoptosis, cell cycle arrest, and other molecular pathways which are specific for the malignant transformation of cells.

[Photodynamic therapy of urinary bladder cancer using a chlorin based photosensitizer].

PubMed

Iagudaev, D M; Martov, A G; Sorokatyĭ, A E; Geĭnits, A V

2006-01-01

Photodynamic therapy (PDT) is a modem, low-invasive method of urinary bladder (UB) cancer treatment. PDT can induce complete or partial destruction of the tumor, reduce recurrence rate, provide assistance to elderly patients with compromised somatic status who are not radically operable. A combined technique improves the results of photodynamic therapy in patients with surface and invasive UB cancer of stage T2 because photodynamic impact affects not only the tumor but also all UB mucosa by light fiber with cylindric diffusor introduced in a silicon balloon with water. This leads to tumor destruction and a recurrence rate decrease.

Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response

PubMed Central

Bhuvaneswari, Ramaswamy; Gan, Yik Yuen; Soo, Khee Chee; Olivo, Malini

2009-01-01

Background Photodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. Treatment induced hypoxia is one of the main side effects of PDT and efforts are underway to optimize PDT protocols for improved efficacy. The aim of this study was to investigate the anti-tumor effects of PDT plus Erbitux, an angiogenesis inhibitor that targets epidermal growth factor receptor (EGFR), on human bladder cancer model. Tumor-bearing nude mice were assigned to four groups that included control, PDT, Erbitux and PDT plus Erbitux and tumor volume was charted over 90-day period. Results Our results demonstrate that combination of Erbitux with PDT strongly inhibits tumor growth in the bladder tumor xenograft model when compared to the other groups. Downregulation of EGFR was detected using immunohistochemistry, immunofluorescence and western blotting. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In addition, we identified the dephosphorylation of ErbB4 at tyrosine 1284 site to play a major role in tumor inhibition. Also, at the RNA level downregulation of EGFR target genes cyclin D1 and c-myc was observed in tumors treated with PDT plus Erbitux. Conclusion The combination therapy of PDT and Erbitux effectively inhibits tumor growth and is a promising therapeutic approach in the treatment of bladder tumors. PMID:19878607

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

Advances in urothelial bladder cancer immunotherapy, dawn of a new age of treatment.

PubMed

Aoun, Fouad; Rassy, Elie El; Assi, Tarek; Albisinni, Simone; Katan, Joseph

2017-03-01

Urothelial bladder cancer displays a high number of somatic mutations that render these tumors more responsive to immunotherapy. Several immunotherapeutic agents were examined in patients with advanced stage urothelial bladder cancer and recently atezolizumab - an (PDL-1) immune checkpoint inhibitor antibody - was approved for the treatment of patients with metastatic disease progressing after platinum combination therapy. Despite the great success, there are still some unanswered questions and ongoing trials that are in progress to define the role of combination therapy and sequencing strategies. The objective of our manuscript is to summarize the most recent data on immunotherapy in advanced urothelial cancer. Current challenges and future perspectives of immunotherapy as a monotherapy or in combination strategies will also be analyzed.

Combining Adult Learning Theory with Occupational Therapy Intervention for Bladder and Bowel Management after Spinal Cord Injury: A Case Report.

PubMed

Gallagher, Gina; Bell, Alison

2016-01-01

Bladder and bowel management is an important goal of rehabilitation for clients with spinal cord injury. Dependence is these areas have been linked to a variety of secondary complications, including decreased quality of life, urinary tract infections and pressure ulcers (Hammell, 2010; Hicken et al, 2001). Occupational therapists have been identified as important members of the health care team in spinal cord injury rehabilitation; however, specific roles and interventions have not been clearly described. This case report will describe occupational therapy interventions embedded with principles of adult learning theory to address bladder and bowel management with an adult client who sustained an incomplete thoracic level spinal cord injury.

Modulation of urinary bladder innervation: TRPV1 and botulinum toxin A.

PubMed

Charrua, Ana; Avelino, António; Cruz, Francisco

2011-01-01

The persisting interest around neurotoxins such as vanilloids and botulinum toxin (BoNT) derives from their marked effect on detrusor overactivity refractory to conventional antimuscarinic treatments. In addition, both are administered by intravesical route. This offers three potential advantages. First, intravesical therapy is an easy way to provide high concentrations of pharmacological agents in the bladder tissue without causing unsuitable levels in other organs. Second, drugs effective on the bladder, but inappropriate for systemic administration, can be safely used as it is the case of vanilloids and BoNT. Third, the effects of one single treatment might be extremely longlasting, contributing to render these therapies highly attractive to patients despite the fact that the reasons to the prolonged effect are still incompletely understood. Attractive as it may be, intravesical pharmacological therapy should still be considered as a second-line treatment in patients refractory to conventional oral antimuscarinic therapy or who do not tolerate its systemic side effects. However, the increasing off-label use of these neurotoxins justifies a reappraisal of their pharmacological properties.

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.

Auxotrophic recombinant Mycobacterium bovis BCG overexpressing Ag85B enhances cytotoxicity on superficial bladder cancer cells in vitro.

PubMed

Begnini, Karine Rech; Rizzi, Caroline; Campos, Vinicius Farias; Borsuk, Sibele; Schultze, Eduarda; Yurgel, Virginia Campello; Nedel, Fernanda; Dellagostin, Odir Antônio; Collares, Tiago; Seixas, Fabiana Kömmling

2013-02-01

BCG therapy remains at the forefront of immunotherapy for treating patients with superficial bladder cancer. The high incidence of local side effects and the presence of non-responder diseases have led to efforts to improve the therapy. Hence, we proposed that an auxotrophic recombinant BCG strain overexpressing Ag85B (BCG ∆leuD/Ag85B), could enhance the cytotoxicity to the human bladder carcinoma cell line 5637. The rBCG was generated using an expression plasmid encoding the mycobacterial antigen Ag85B to transform a BCG ∆leuD strain. The inhibitory effect of BCG ∆leuD/Ag85B on 5637 cells was determined by the MTT method, morphology observation and a LIVE/DEAD assay. Gene expression profiles for apoptotic, cell cycle-related and oxidative stress-related genes were investigated by qRT-PCR. Bax, bcl-2 and p53 induction by BCG ∆leuD/Ag85B treatment was evaluated by Western blotting. BCG ∆leuD/Ag85B revealed a superior cytotoxicity effect compared to the control strains used in this study. The results showed that the expression level of pro-apoptotic and cell cycle-related genes increased after BCG ∆leuD/Ag85B treatment, whereas the mRNA levels of anti-apoptotic genes decreased. Interestingly, BCG ∆leuD/Ag85B also increased the mRNA level of antioxidant enzymes in the bladder cancer cell line. Bax and p53 proteins levels increased following treatment. In conclusion, these results suggest that treatment with BCG ∆leuD/Ag85B enhances cytotoxicity for superficial bladder cancer cells in vitro. Therefore, rBCG therapy may have potential benefits in the treatment of bladder cancer.

Intravesical Bacillus Calmette-Guérin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of Bacillus Calmette-Guérin.

PubMed

Ratliff, T L; Palmer, J O; McGarr, J A; Brown, E J

1987-04-01

Intravesical Bacillus Calmette-Guérin (BCG) is considered to be one of the most effective treatments for superficial bladder cancer. Although the mechanisms by which BCG inhibits tumor growth are not known, previous studies have shown that systemic immunization to BCG and the local expression of the immune response in the bladder are associated with a favorable response to BCG therapy. We have investigated the conditions required for the initiation of an immunological response after the intravesical instillation of BCG. Initial histological studies showed that BCG attached to the bladder wall only in areas where the urothelium was damaged by electrocautery and suggested that attachment was associated with the fibrin clot. Quantitative studies verified the histological observations. Minimal BCG attachment (mean less than 10(2) colony forming units) was observed in normal bladders in contrast with a mean of 1.42 X 10(4) colony forming units/bladder in bladders damaged by electrocautery (10 separate experiments). BCG attachment to the bladder wall was durable since organisms were observed in bladders 48 h after instillation. To investigate the proteins to which BCG attached, we tested the binding of BCG to extracellular matrix and inflammatory proteins which comprise a significant portion of the fibrin clot. BCG bound in vitro to coverslips coated in vivo with extracellular matrix proteins but did not bind to control albumin-coated coverslips. BCG also bound to coverslips coated with purified plasma fibronectin but not to coverslips coated with other purified extracellular matrix proteins including laminin, fibrinogen, and type IV collagen. BCG attachment to coverslips coated with either extracellular matrix proteins or purified fibronectin was inhibited by antibodies specific for fibronectin. Moreover, BCG attachment to cauterized bladders in vivo was inhibited by antifibronectin antibodies. These results demonstrate that fibronectin mediates the attachment of BCG to surfaces and suggest that it is the primary component mediating attachment within the bladder. Moreover, the data suggest that the BCG-fibronectin interaction may be a requisite first step for the initiation of the antitumor activity in intravesical BCG for bladder cancer.

[Carcinosarcoma of the bladder: a case report].

PubMed

Khabir, A; Boudawara, T; Jemel, S; Mhiri, M N; Jlidi, R

2000-02-01

Carcinosarcoma of the urinary bladder is a uncommon tumor with characteristic histopathologic and immunohistochemical findings; his histogenesis have still not been clear; the prognosis seems to be improved by radical cystectomy and adjuvants therapies. We report a case of 47 years old women suffering from suprapubic pains, dysuria and hematuria of five months duration and had a 10 cm suprapubic mass that was found on physical examination. Radiographically, the tumor invaded the dome of the urinary bladder and causes bilateral hydronephrosis. Microscopically it was an urinary bladder carcinosarcoma. Our objective is to discuss the histogenesis, the anatomoclinical and prognosis of these rare tumors.

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.

Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer.

PubMed

Buss, Julieti Huch; Begnini, Karine Rech; Bender, Camila Bonemann; Pohlmann, Adriana R; Guterres, Silvia S; Collares, Tiago; Seixas, Fabiana Kömmling

2017-01-01

Mycobacterium bovis bacillus Calmette-Guerin (BCG) remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1) controlling drug release for extended time frames, (2) combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3) reducing systemic side effects, (4) increasing bioavailability, (5) and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.

Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer

PubMed Central

Buss, Julieti Huch; Begnini, Karine Rech; Bender, Camila Bonemann; Pohlmann, Adriana R.; Guterres, Silvia S.; Collares, Tiago; Seixas, Fabiana Kömmling

2018-01-01

Mycobacterium bovis bacillus Calmette–Guerin (BCG) remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1) controlling drug release for extended time frames, (2) combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3) reducing systemic side effects, (4) increasing bioavailability, (5) and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer. PMID:29379438

Smooth muscle membrane organization in the normal and dysfunctional human urinary bladder: a structural analysis.

PubMed

Burkhard, Fiona C; Monastyrskaya, Katia; Studer, Urs E; Draeger, Annette

2005-01-01

The decline in contractile properties is a characteristic feature of the dysfunctional bladder as a result of infravesical outlet obstruction. During clinical progression of the disease, smooth muscle cells undergo structural modifications. Since adaptations to constant changes in length require a high degree of structural organization within the sarcolemma, we have investigated the expression of several proteins, which are involved in smooth muscle membrane organization, in specimens derived from normal and dysfunctional organs. Specimen from patients with urodynamically normal/equivocal (n = 4), obstructed (n = 2), and acontractile (n = 2) bladders were analyzed relative to their structural features and sarcolemmal protein profile. Smooth muscle cells within the normal urinary bladder display a distinct sarcolemmal domain structure, characterized by firm actin-attachment sites, alternating with flexible "hinge" regions. In obstructed bladders, foci of cells displaying degenerative sarcolemmal changes alternate with areas of hypertrophic cells in which the membrane appears unaffected. In acontractile organs, the overall membrane structure remains intact, however annexin 6, a protein belonging to a family of Ca2+-dependent, "membrane-organizers," is downregulated. Degenerative changes in smooth muscle cells, which are chronically working against high resistance, are preferentially located within the actin-attachment sites. In acontractile bladders, the downregulation of annexin 6 might have a bearing on the fine-tuning of the plasma membrane during contraction/relaxation cycles. Copyright 2005 Wiley-Liss, Inc.

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.

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.

[Sacral nerve stimulation in the treatment of the lower urinary tract function disorders].

PubMed

Miotła, Paweł; Kulik-Rechberger, Beata; Skorupski, Paweł; Rechberger, Tomasz

2011-11-01

Functional disorders of the female lower urinary tract like urge incontinence, idiopathic urinary retention and symptoms of urgency-frequency occasionally do not respond properly to classical behavioral and pharmacological therapy Therefore, additional alternative therapies are needed to alleviate these bothersome symptoms. Sacral neuromodulation (SNS) utilize mild electrical pulses which activate or suppress neural reflexes responsible for voiding by stimulating the sacral nerves that innervate the bladder, external urethral sphincter and pelvic floor muscles. The exact mechanism of SNS action is not yet fully understood but it is assumed that it influences the neuroaxis at different levels of the central nervous system and restores the balance between inhibitory and activatory control over the voiding reflex. There is numerous evidence on the success of SNS not only in the treatment of refractory urge incontinence in adult and children but also in idiopathic urinary retention and symptoms of urgency-frequency

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

PubMed

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

2014-03-01

To assess the effectiveness of conservative therapeutic approaches in a multiple sclerosis population. Review was performed in PubMed, PEDro, Scopus and Cochrane Library using combinations of the following keywords: multiple sclerosis; bladder dysfunction; overactive bladder; detrusor hyperreflexia; urge incontinence; urgency; stress incontinence; pelvic floor muscle; biofeedback; PTNS; tibial nerve; bladder training; physical therapy; physiotherapy; conservative treatment and behavioral therapy. Six randomized articles including 289 patients were selected. Four papers exhibited strong scores for the methodological quality assessment. The parameters always significantly improved concerned: number of incontinence episodes (decreased from 64% to 86% after treatment versus before treatment), quality of life (P≤0.001), severity of irritative symptoms (decreased by more than 50% after treatment versus before treatment), and nocturia (P=0.035 to P<0.001). Activities and participation, maximum flow rate, mean voided volume and daytime frequency were not significantly improved in all trials. The physical therapy techniques could be effective for the treatment of urinary disorders in multiple sclerosis populations with mild disability. However, the analyses are based on six studies within only four showed good methodological quality. No strong conclusions regarding treatment approaches can be drawn from this review. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Immunotherapy for bladder cancer

PubMed Central

Fuge, Oliver; Vasdev, Nikhil; Allchorne, Paula; Green, James SA

2015-01-01

It is nearly 40 years since Bacillus Calmette–Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear. PMID:26000263

Management of OAB in those over age 65.

PubMed

Natalin, Ricardo; Lorenzetti, Fabio; Dambros, Miriam

2013-10-01

The International Continence Society (ICS) defines overactive bladder (OAB) as an association of symptoms including "urgency, with or without urge incontinence, usually with increased frequency and nocturia". This conditon has been associated with a decrease in quality of life and a higher related risk of overall health condition decrease, and is rising since its prevalence increases with age and the forecast for the world population estimates an increase of those over 65 years old. Aging alone can be considered a major risk factor for developing OAB symptoms that are considered multifactorial and due to body tissue and anatomic changes, lifestyle-associated factors, comorbidities and personal characteristics. The high prevalence of this condition and multiple etiology factors makes of its treatment a challenge-especially in the older population. A major concern over OAB treatment of elderly patients is the risk of cognitive side effects due to the pharmacologic treatment with anticholinergic drugs. First-line treatment for OAB symptoms are the use of pharmacologic therapy with antimuscarinic drugs, which has been proved to be effective in controlling urgency, urge incontinence episodes, incontinence episodes, and nocturia. The impact caused by this condition is significant regarding the economic and human costs associated bringing into attention the need of studying and reviewing this specific population. Conservative Management and Lifestyle Modifications: Behavioral therapy's aims are to reduce urinary frequency and urgency to an accepted level and to increase bladder outlet volume. It consists of actions to teach patients to improve and learn bladder control. Lifestyle modifications are a conjunct of daily activities that can be managed to have the lowest interference on the functioning of the urinary tract. Pharmacologic Therapy: There are various medications with antimuscarinic properties available for the treatment of OAB symptoms. The most commonly used are oxybutinin, tolterodine, solifenacin, darifenacin, fesosterodine and trospium. Second-line Therapy: OAB treatment accounts for some refractory to conventional treatment patients who will require alternative therapies to achieve improvement of symptoms as the use of intradetrusor injection of botulinum A toxin by binding to receptors on the membrane of cholinergic nerves causing temporary chemodenervation and consequent muscle relaxation. Neuromodulation is also an effective therapy that aims to achieve inhibition of detrusor activity by continuous neural stimulation through peripheral nerves as the use of the tibial nerve or central as it is performed by direct spine stimulation on sacral roots through the implantation of an automated generator. In conclusion, evidence from the literature has shown that antimuscarinic treatment of OAB in the elderly population is safe and effective in improving symptoms and patient's quality of life. Managing OAB symptoms in this population is a great challenge. An optimal therapeutic approach to treat should involve medical treatment with drug and behavioral therapy in addition to lifestyle advice.

Understanding bladder management on a palliative care unit: a grounded theory study.

PubMed

Gutmanis, Iris; Hay, Melissa; Shadd, Joshua; Byrne, Janette; McCallum, Sarah; Bishop, Kristen; Whitfield, Patricia; Faulds, Cathy

2017-03-16

Research regarding factors associated with nursing-initiated changes to bladder management at end-of-life is sparse. To explore the process of Palliative Care Unit (PCU) nurses' approach to bladder management changes. Nursing staff from one PCU in London, Canada were interviewed regarding bladder management care practices. A constructivist grounded theory was generated. Four interconnected themes emerged: humanity (compassionate support of patients); journey (making the most of a finite timeline); health condition (illness, functional decline); and context (orders, policies, supplies). These overlapping themes must be considered in light of ongoing changes which prompt recycling through the framework. While bladder management necessitates shared decision-making and individualised care, nurses' phronetic experience may serve to detect the presence of change and the need to consider other alternatives. End-of-life bladder management requires nurses to continually reconsider the significance of humanity, journey, health condition and context in light of ongoing changes.

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.

Adjuvant photodynamic therapy (PDT) with photosensitizer photosens for superficial bladder cancer: experimental investigations to treat prostate cancer by PDT with photosens

NASA Astrophysics Data System (ADS)

Apolikhin, Oleg I.; Chernishov, Igor V.; Sivkov, Andrey V.; Altunin, Denis V.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

2007-07-01

14 patients with transional-cell bladder cancer in stage T1N0M0G2 after transurethral bladder resection were offered adjuvant treatment with PDT. Adjuvant PDT was performed 1-1.5 months after transurethral bladder resection for superficial bladder cancer. Prior to PDT conventional and fluorescent cystoscopy were performed. In the absence of inflammation and after full epitalisation of postoperative wound a session of therapy was performed. 24 hours prior to PDT-session photosensitizer Photosens was injected intravenously in the dose of 0.8 mg per kg of body weight. Prior to PDT local anesthesia of urethra with lidocain-gel was performed. Cystoscopy was carried out. PDT was performed with diode laser "Biospec" (675 nm). During the session the place of standing diffuser and the volume of a bladder were controlled. After 7 months of observation no tumor recidivists were observed. Registered side effects were not life-threatened. 5 patients had pain or discomfort in suprapubic area, ceasing spontaneously or requiring administration of analgetics. No systemic side-effects or allergic reactions were observed. The method can be used in out-patient practice. Absence of early recidivists shows efficiency of PDT in the treatment of superficial bladder cancer. Further study is necessary to estimate optimal regimen of PDT. The further controlling of condition on the patients in this group is required. At the laboratory animals' experiment, we conducted the explorations devoted to the influence of the photodynamic effect at the prostate's tissues.

Phosphatidylserine targeted single-walled carbon nanotubes for photothermal ablation of bladder cancer

NASA Astrophysics Data System (ADS)

Virani, Needa A.; Davis, Carole; McKernan, Patrick; Hauser, Paul; Hurst, Robert E.; Slaton, Joel; Silvy, Ricardo P.; Resasco, Daniel E.; Harrison, Roger G.

2018-01-01

Bladder cancer has a 60%-70% recurrence rate most likely due to any residual tumour left behind after a transurethral resection (TUR). Failure to completely resect the cancer can lead to recurrence and progression into higher grade tumours with metastatic potential. We present here a novel therapy to treat superficial tumours with the potential to decrease recurrence. The therapy is a heat-based approach in which bladder tumour specific single-walled carbon nanotubes (SWCNTs) are delivered intravesically at a very low dose (0.1 mg SWCNT per kg body weight) followed 24 h later by a short 30 s treatment with a 360° near-infrared light that heats only the bound nanotubes. The energy density of the treatment was 50 J cm-2, and the power density that this treatment corresponds to is 1.7 W cm-2, which is relatively low. Nanotubes are specifically targeted to the tumour via the interaction of annexin V (AV) and phosphatidylserine, which is normally internalised on healthy tissue but externalised on tumours and the tumour vasculature. SWCNTs are conjugated to AV, which binds specifically to bladder cancer cells as confirmed in vitro and in vivo. Due to this specific localisation, NIR light can be used to heat the tumour while conserving the healthy bladder wall. In a short-term efficacy study in mice with orthotopic MB49 murine bladder tumours treated with the SWCNT-AV conjugate and NIR light, no tumours were visible on the bladder wall 24 h after NIR light treatment, and there was no damage to the bladder. In a separate survival study in mice with the same type of orthotopic tumours, there was a 50% cure rate at 116 days when the study was ended. At 116 days, no treatment toxicity was observed, and no nanotubes were detected in the clearance organs or bladder.

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.

Attenuated XPC Expression Is Not Associated with Impaired DNA Repair in Bladder Cancer

PubMed Central

Naipal, Kishan A. T.; Raams, Anja; Bruens, Serena T.; Brandsma, Inger; Verkaik, Nicole S.; Jaspers, Nicolaas G. J.; Hoeijmakers, Jan H. J.; van Leenders, Geert J. L. H.; Pothof, Joris; Kanaar, Roland; Boormans, Joost; van Gent, Dik C.

2015-01-01

Bladder cancer has a high incidence with significant morbidity and mortality. Attenuated expression of the DNA damage response protein Xeroderma Pigmentosum complementation group C (XPC) has been described in bladder cancer. XPC plays an essential role as the main initiator and damage-detector in global genome nucleotide excision repair (NER) of UV-induced lesions, bulky DNA adducts and intrastrand crosslinks, such as those made by the chemotherapeutic agent Cisplatin. Hence, XPC protein might be an informative biomarker to guide personalized therapy strategies in a subset of bladder cancer cases. Therefore, we measured the XPC protein expression level and functional NER activity of 36 bladder tumors in a standardized manner. We optimized conditions for dissociation and in vitro culture of primary bladder cancer cells and confirmed attenuated XPC expression in approximately 40% of the tumors. However, NER activity was similar to co-cultured wild type cells in all but one of 36 bladder tumors. We conclude, that (i) functional NER deficiency is a relatively rare phenomenon in bladder cancer and (ii) XPC protein levels are not useful as biomarker for NER activity in these tumors. PMID:25927440

[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.

Current trends in the management of bladder cancer.

PubMed

Patel, Amit R; Campbell, Steven C

2009-01-01

This article provides a review of bladder cancer etiology, diagnosis, and management for WOC nurses. Bladder cancer incidence continues to rise yearly in the United States, and patients with bladder cancer comprise some of the most challenging cases in urologic oncology. Nurses are involved with all aspects of the processes of care for the patient with bladder cancer, from initial diagnosis and treatment to postsurgical care and follow-up. For nonmuscle invasive bladder cancer, treatment includes transurethral resection followed by intravesical chemotherapy or immunotherapy to prevent recurrence or progression. Radical cystectomy along with chemotherapy protocols provides a survival advantage for muscle invasive bladder cancer, although the timing of chemotherapy remains controversial. Numerous factors are considered when determining the type of urinary diversion used at the time of radical cystectomy, but patient, family, surgeon, and nursing input are essential for preserving an optimal health-related quality of life and reducing morbidity. Patients with metastatic bladder cancer are generally treated with a cisplatin-based chemotherapy but continue to have a poor prognosis. Newer therapies involving novel molecular-targeted agents provide hope for the future for patients with metastatic disease.

Studies of a novel photosensitizer Pd-bacteriopheophorbide (Tookad) for the prostate cancer PDT in canine model

NASA Astrophysics Data System (ADS)

Huang, Zheng; Chen, Qun; Brun, Pierre-Herve; Wilson, Brian C.; Scherz, Avigdor; Salomon, Yoram; Luck, David L.; Beckers, Jill; Hetzel, Fred W.

2003-12-01

Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad), is investigated as an alternative modality for the total ablation of prostate cancer. In vivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the i.v. infused photosensitizer drug. The effects of two-session PDT were evaluated. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week, post second-session PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. Two-session PDT or one single session PDT induced a similar extent of damage. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Maximum lesion size of over 3 cm in dimension could be achieved with a single 1-cm interstitial treatment, suggesting the therapy is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat prostate cancer.

Tibial nerve stimulation for overactive bladder syndrome unresponsive to medical therapy.

PubMed

Ridout, A E; Yoong, W

2010-02-01

Overactive bladder syndrome is defined as a symptom syndrome which includes urinary urgency, with or without urge incontinence, usually accompanied by frequency (>8 micturitions/24 h) and nocturia. Conservative treatment usually comprises behavioural techniques, bladder retraining, pelvic floor re-education and pharmacotherapy but up to 30% of patients will remain refractory to treatment. Although second-line treatment options such as sacral nerve stimulation and intravesical botulinum A injections are valuable additions to the therapeutic arsenal, they are relatively invasive and can have serious side-effects. Inhibition of detrusor activity by peripheral neuromodulation of the posterior tibial nerve was first described in 1983, with recent authors further confirming a 60-80% positive response rate. This review was undertaken to examine published literature on percutaneous tibial nerve stimulation and to discuss outcome measures, maintenance therapy and prognostic factors of this technique.

Solitary extramedullary plasmacytoma of the bladder: a case report and literature.

PubMed

Khaliq, Waseem; Uzoaru, Ikechukwu; Konchanin, Ronald P; Sapiente, Ronald A; Egner, James R

2010-08-01

Plasmacytoma is a rare B-lymphocyte neoplastic disorder that usually presents as the generalized disease multiple myeloma. Less than 5% of the cases present as a solitary mass of monoclonal plasma cells in the bone or soft tissue. Although solitary extramedullary plasmacytoma (SEP) may arise in any organ, it rarely involves the urinary bladder. A 67-year-old male without a history of multiple myeloma presented with urinary frequency and nocturia; he was later diagnosed with SEP of the bladder. The patient was initially treated with a course of radiation therapy without symptomatic improvement; therefore a chemotherapy regimen consisting of lenalidomide and dexamethasone was subsequently given for six cycles. SEP usually carries a better prognosis and higher cure rate than solitary plasmacytoma of bone, as SEP is radiation sensitive. The role of adjuvant chemotherapy in the treatment of SEP that is resistant to radiation therapy is not clear, since most of the recommendations have been derived from the experience of head and neck SEP. The literature also lacks recommendations for choice of a chemotherapy regimen and surveillance of isolated bladder plasmacytoma. Here we present the first case of a radiation-resistant solitary plasmacytoma of the bladder that was successfully treated with lenalidomide and dexamethasone with successful clinical remission.

The Other Bladder Syndrome: Underactive Bladder

PubMed Central

Miyazato, Minoru; Yoshimura, Naoki; Chancellor, Michael B

2013-01-01

Detrusor underactivity, or underactive bladder (UAB), is defined as a contraction of reduced strength and/or duration resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span. UAB can be observed in many neurologic conditions and myogenic failure. Diabetic cystopathy is the most important and inevitable disease developing from UAB, and can occur silently and early in the disease course. Careful neurologic and urodynamic examinations are necessary for the diagnosis of UAB. Proper management is focused on prevention of upper tract damage, avoidance of overdistension, and reduction of residual urine. Scheduled voiding, double voiding, al-blockers, and intermittent self-catheterization are the typical conservative treatment options. Sacral nerve stimulation may be an effective treatment option for UAB. New concepts such as stem cell therapy and neurotrophic gene therapy are being explored. Other new agents for UAB that act on prostaglandin E2 and EP2 receptors are currently under development. The pharmaceutical and biotechnology industries that have a pipeline in urology and women’s health may want to consider UAB as a potential target condition. Scientific counsel and review of the current pharmaceutical portfolio may uncover agents, including those in other therapeutic fields, that may benefit the management of UAB. PMID:23671401

SU-F-J-97: A Joint Registration and Segmentation Approach for Large Bladder Deformations in Adaptive Radiotherapy

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

Derksen, A; Koenig, L; Heldmann, S

Purpose: To improve results of deformable image registration (DIR) in adaptive radiotherapy for large bladder deformations in CT/CBCT pelvis imaging. Methods: A variational multi-modal DIR algorithm is incorporated in a joint iterative scheme, alternating between segmentation based bladder matching and registration. Using an initial DIR to propagate the bladder contour to the CBCT, in a segmentation step the contour is improved by discrete image gradient sampling along all surface normals and adapting the delineation to match the location of each maximum (with a search range of +−5/2mm at the superior/inferior bladder side and step size of 0.5mm). An additional graph-cutmore » based constraint limits the maximum difference between neighboring points. This improved contour is utilized in a subsequent DIR with a surface matching constraint. By calculating an euclidean distance map of the improved contour surface, the new constraint enforces the DIR to map each point of the original contour onto the improved contour. The resulting deformation is then used as a starting guess to compute a deformation update, which can again be used for the next segmentation step. The result is a dense deformation, able to capture much larger bladder deformations. The new method is evaluated on ten CT/CBCT male pelvis datasets, calculating Dice similarity coefficients (DSC) between the final propagated bladder contour and a manually delineated gold standard on the CBCT image. Results: Over all ten cases, an average DSC of 0.93±0.03 is achieved on the bladder. Compared with the initial DIR (0.88±0.05), the DSC is equal (2 cases) or improved (8 cases). Additionally, DSC accuracy of femoral bones (0.94±0.02) was not affected. Conclusion: The new approach shows that using the presented alternating segmentation/registration approach, the results of bladder DIR in the pelvis region can be greatly improved, especially for cases with large variations in bladder volume. Fraunhofer MEVIS received funding from a research grant by Varian Medical Systems.« less

Bioimpedance Harmonic Analysis as a Diagnostic Tool to Assess Regional Circulation and Neural Activity

NASA Astrophysics Data System (ADS)

Mudraya, I. S.; Revenko, S. V.; Khodyreva, L. A.; Markosyan, T. G.; Dudareva, A. A.; Ibragimov, A. R.; Romich, V. V.; Kirpatovsky, V. I.

2013-04-01

The novel technique based on harmonic analysis of bioimpedance microvariations with original hard- and software complex incorporating a high-resolution impedance converter was used to assess the neural activity and circulation in human urinary bladder and penis in patients with pelvic pain, erectile dysfunction, and overactive bladder. The therapeutic effects of shock wave therapy and Botulinum toxin detrusor injections were evaluated quantitatively according to the spectral peaks at low 0.1 Hz frequency (M for Mayer wave), respiratory (R) and cardiac (C) rhythms with their harmonics. Enhanced baseline regional neural activity identified according to M and R peaks was found to be presumably sympathetic in pelvic pain patients, and parasympathetic - in patients with overactive bladder. Total pulsatile activity and pulsatile resonances found in the bladder as well as in the penile spectrum characterised regional circulation and vascular tone. The abnormal spectral parameters characteristic of the patients with genitourinary diseases shifted to the norm in the cases of efficient therapy. Bioimpedance harmonic analysis seems to be a potent tool to assess regional peculiarities of circulatory and autonomic nervous activity in the course of patient treatment.

New treatments for incontinence.

PubMed

MacLachlan, Lara S; Rovner, Eric S

2015-07-01

Urinary incontinence (UI) is a common, yet underdetected and under-reported, health problem that can significantly affect quality of life. UI may also have serious medical and economic ramifications for untreated or undertreated patients, including perineal dermatitis, worsening of pressure ulcers, urinary tract infections, and falls. To prevent incontinence, the urethral sphincter must maintain adequate closure to resist the flow of urine from the bladder at all times until voluntary voiding is initiated and the bladder must accommodate increasing volumes of urine at a low pressure. UI can be categorized as a result of urethral underactivity (stress UI), bladder overactivity (urge UI), a combination of the 2 (mixed incontinence), or urethral overactivity/bladder underactivity (overflow incontinence). The main goal of therapy for the management of UI is to reduce the number of UI episodes, prevent complications, and, if possible, restore continence. This review highlights the existing treatment of stress, urge, mixed, and overflow UI in adult men and women and discusses many of the novel treatments including potential future or emerging therapies. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

[BCG infection of the glans penis after intravesical BCG therapy].

PubMed

Michelet, N; Spenatto, N; Viraben, R; Cuny, J-F; Mazet, J; Trechot, P; Barbaud, A; Schmutz, J-L

2008-01-01

BCG therapy is an effective adjuvant treatment for superficial bladder tumors. Therapy involves intravesical instillation of live attenuated Calmette-Guérin bacilli. BCG infection of the glans is a rare local complication associated with this treatment, two cases of which are reported below. Case 1: A 77-year-old man presented relapsing urothelial bladder carcinoma treated by endoscopic resection and BCG therapy. One week after the seventh instillation, severe balanitis developed. Three months later, examination revealed massive painful perimeatal ulceration with yellowish papules in the peripheral regions. Histology revealed epithelioid giant-cell granulomas. Ziehl-Neelsen staining was positive. Slow cure of the lesions was achieved within 12months using double antitubercular antibiotic therapy. Case 2: In a 61-year-old man receiving BCG therapy for relapsing bladder carcinoma in situ, the sixth instillation was considered traumatic since it was highly painful. One week later, papular nodules appeared on the glans with a sclerosing lesion of the balanopreputial sac, dark purple perimeatal papules and a mass beneath the mucosa of the glans. Antibiotic treatment comprising ofloxacin followed by rifampicin for two months proved ineffective. Histology revealed granulomatous dermal lesions with eosinophilic necrosis. Triple antitubercular antibiotic therapy was initiated. The first reported case of BCG infection of the glans in patients undergoing intravesical BCG therapy was published in 1992. Since then, there have been nine other reports. There is no stereotypical clinical presentation. In most cases, an infiltrated erythematosus plaque is seen together with yellowish papules in certain patients. Diagnosis is based upon history and histological examination.

Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

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

Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E.

2014-02-01

Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analysesmore » were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone seems to be associated with a reduction in late GU toxicity.« less

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.

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.

Tookad-mediated photodynamic effects on the prostate and its adjacent tissues: in vivo study in canine models

NASA Astrophysics Data System (ADS)

Huang, Zheng; Chen, Qun; Luck, David; Beckers, Jill; Blanc, Dominique; Hetzel, Fred W.

2005-04-01

Photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (pd-bacteriopheophorbide), was investigated as an alternative treatment modality for prostate cancer. Tookad photodynamic effects on the prostate and its adjacent tissues were evaluated in canine models. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (763 nm) and 1-cm cylindrical diffuser fibers at various light doses to activate the IV administered photosensitizer Tookad (1 - 2 mg/kg). The sensitivity of the adjacent tissues to Tookad-PDT was determined by superficially irradiating the surfaces of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. PDT effect on the prostatic urethra was evaluated by transurethral irradiation. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathologic examination. At one-week post interstitial prostate PDT, the animals recovered well with little or no urethral complications. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus, appeared to also be sensitive to Tookad-PDT at light dose levels greater than 40 Jcm2. Urethral mucosa appeared less sensitive to Tookad-PDT. In conclusion, Tookad-mediated PDT demonstrates very strong vascular effects and can provide an effective alternative for the treatment of localized prostate cancer. Protection of the adjacent tissues should be taken into consideration in the total prostate ablation process due to their sensitivity to the Tookad-mediated PDT.

[Urodynamic changes in patients with obstructive sleep apnea-hypopnea syndrome and nocturnal polyuria].

PubMed

Hu, Ke; Tu, Zuo-sheng; Lü, Sheng-qi; Li, Qing-quan; Chen, Xue-qin

2011-03-01

To investigate the urodynamic changes in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and nocturnal polyuria. From Sept. 2002 to Jun. 2008, 23 patients with nocturnal polyuria were diagnosed as having OSAHS by polysomnography (PSG). The number and output of nocturia, the osmotic pressure and the excretion of Na(+) were recorded during both the PSG night and CPAP titrating night. Plasma levels of brain natriuretic peptide (BNP) and atrial natriuretic peptides (ANP) were also measured at 11PM in the 2 nights and 7AM in the next mornings. Urodynamic studies including urine flow, bladder pressure during filling, pressure-flow study during voiding and urethral pressure were carried out in these patients. Urodynamic studies were performed again after treatment with CPAP for 3 months. PSG showed that the patients with nocturnal polyuria had moderate to severe OSAHS, in which the apnea-hypopnea index (AHI) being 48 ± 15 events per hour. The number of nocturnal voiding during the PSG night was more than that during the CPAP titrating night. During the PSG night, the output of nocturia, the nocturia excretion of Na(+), ANP levels (at 7am in the next morning after PSG night) increased and the osmotic pressure of nocturia decreased. CPAP therapy could reverse these abnormalities. The main characteristics of urodynamics in these patients included weak detrusor contraction, hypoesthesia in filling cystometry, and decreased bladder compliance, and detrusor external sphincter dyssynergia. After 3 months of CPAP treatment, both the motility of the detrusor of bladder and the bladder compliance improved. CPAP therapy can effectively reverse the nocturnal polyuria in OSAHS patients. In OSAHS patients, the features of nocturia, including the changes of output, osmotic pressure and the excretion of Na(+), may be related to the secretion of high-level of ANP. During the course of chronic progressively OSAHS pathophysiology, detrusor function of bladder may be damaged. CPAP therapy could decrease the nocturnal excretion of ANP, and improve the motility of the detrusor of bladder.

Novel Neoadjuvant Therapy Paradigms for Bladder Cancer: Results from the National Cancer Center Institute Forum

PubMed Central

Dinney, Colin P.N.; Hansel, Donna; McConkey, David; Shipley, William; Hagan, Michael; Dreicer, Robert; Lerner, Seth; Czerniak, Bogdan; Waldman, Fred; Groshen, Susan; True, Lawrence D.; Petricoin, Emanuel; Theodorescu, Dan; Hruszkewycz, Andrew; Bajorin, Dean

2014-01-01

Although bladder cancer (BC) is a significant health threat to the US population, integrated clinical and laboratory investigations of this disease lag behind those of other types of cancer. Advances in BC are especially challenged due in part to a general decreased level of funding over the past 5 years. It is ironic that despite the awareness that BC is the 5th most commonly diagnosed solid malignancy in the United States, and one of the most costly to treat, funding for this organ site lags far behind that of other less common malignancies. Moreover, BC offers several unique opportunities for translational research that make it an ideal candidate for investigation. One distinct advantage over other solid tumor sites is that urine and tissue are readily available for translational studies that can direct the development of novel therapy for this disease. The NCI sponsored “Novel Neoadjuvant Therapy for Bladder Cancer” forum held in brought leading clinical and laboratory-based scientists together with the advocacy community to lay the groundwork for collaborative discovery and translation. The goal of the meeting was to bridge the gaps in translational science and develop the concepts for two novel biomarker-driven clinical trials, one in the neoadjuvant presurgical setting and the other in the setting of bladder preservation with chemoradiation. The meeting provided a unique opportunity to launch a collective effort to establish molecular-based therapy for UC. Herein, we summarize the proceedings of this meeting, and the future plans resulting from this forum. PMID:25443274

Characterization of dynamic physiology of the bladder by optical coherence tomography

NASA Astrophysics Data System (ADS)

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

2012-03-01

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

Androgen Receptor Signaling in Bladder Cancer

PubMed Central

Li, Peng; Chen, Jinbo; Miyamoto, Hiroshi

2017-01-01

Emerging preclinical findings have indicated that steroid hormone receptor signaling plays an important role in bladder cancer outgrowth. In particular, androgen-mediated androgen receptor signals have been shown to correlate with the promotion of tumor development and progression, which may clearly explain some sex-specific differences in bladder cancer. This review summarizes and discusses the available data, suggesting the involvement of androgens and/or the androgen receptor pathways in urothelial carcinogenesis as well as tumor growth. While the precise mechanisms of the functions of the androgen receptor in urothelial cells remain far from being fully understood, current evidence may offer chemopreventive or therapeutic options, using androgen deprivation therapy, in patients with bladder cancer. PMID:28241422

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.

Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain

PubMed Central

Goins, WF; Goss, JR; Chancellor, MB; de Groat, WC; Glorioso, JC; Yoshimura, N

2009-01-01

Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a painful debilitating chronic visceral pain disorder of unknown etiology that affects an estimated 1 million people in the, United States alone. It is characterized by inflammation of the bladder that results in chronic pelvic pain associated with bladder symptoms of urinary frequency and urgency. Regardless of the etiology, IC/PBS involves either increased and/or abnormal activity in afferent nociceptive sensory neurons. Pain-related symptoms in patients with IC/PBS are often very difficult to treat. Both medical and surgical therapies have had limited clinical utility in this debilitating disease and numerous drug treatments, such as heparin, dimethylsulfoxide and amitriptyline, have proven to be palliative at best, and in some IC/PBS patients provide no relief whatsoever. Although opiate narcotics have been employed to help alleviate IC/PBS pain, this strategy is fraught with problems as systemic narcotic administration causes multiple unwanted side effects including mental status change and constipation. Moreover, chronic systemic narcotic use leads to dependency and need for dose escalation due to tolerance: therefore, new therapies are desperately needed to treat refractory IC/PBS. This has led our group to develop a gene therapy strategy that could potentially alleviate chronic pelvic pain using the herpes simplex virus-directed delivery of analgesic proteins to the bladder. PMID:19242523

Hyperbaric Oxygen Therapy in Treating Long-Term Gastrointestinal Adverse Effects Caused by Radiation Therapy in Patients With Pelvic Cancer

ClinicalTrials.gov

2011-07-14

Bladder Cancer; Cervical Cancer; Colorectal Cancer; Endometrial Cancer; Gastrointestinal Complications; Long-term Effects Secondary to Cancer Therapy in Adults; Ovarian Cancer; Prostate Cancer; Radiation Toxicity; Sarcoma; Testicular Germ Cell Tumor; Vaginal Cancer

A cone beam CT-Based Study for Clinical Target Definition Using Pelvic Anatomy During Postprostatectomy Radiotherapy.

PubMed

Showalter, Timothy N; Nawaz, A Omer; Xiao, Ying; Galvin, James M; Valicenti, Richard K

2008-02-01

There are no accepted guidelines for target volume definition for online image-guided radiation therapy (IGRT) after radical prostatectomy (RP). This study used cone beam CT (CBCT) imaging to generate information for use in post-RP IGRT. The pelvic anatomy of 10 prostate cancer patients undergoing post-RP radiation therapy (RT) to 68.4 Gy was studied using CBCT images obtained immediately before treatment. Contoured bladder and rectal volumes on CBCT images were compared with planning CT (CT(ref)) volumes from seminal vesicle stump (SVS) to bladder-urethral junction. This region was chosen to approximate the prostatic fossa (PF) during a course of post-RP RT. Anterior and posterior planning target volume margins were calculated using ICRU report 71 guidelines, accounting for systematic and random error based on bladder and rectal motion, respectively. A total of 176 CBCT study sets obtained 2 to 5 times weekly were analyzed. The rectal and bladder borders were reliably identified in 166 of 176 (94%) of CBCT images. Relative to CT(ref), mean posterior bladder wall position was anterior by 0.1 to 1.5 mm, and mean anterior rectum wall position was posterior by 1.6 to 2.7 mm. Calculated anterior margin as derived from bladder motion ranged from 5.9 to 7.1 mm. Calculated posterior margin as derived from rectal motion ranged from 8.6 to 10.2 mm. Normal tissue anatomy was definable by CBCT imaging throughout the course of post-RP RT, and the interfraction anteroposterior motion of the bladder and rectum was studied. This information should be considered in devising post-RP RT techniques using image guidance.

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

PubMed

Yates, D R; Rouprêt, M

2011-08-01

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

Cystitis glandularis in a cat.

PubMed

Agut, Amalia; Carrillo, Juana D; Soler, Marta; García, Juan D; Belda, Eliseo; Gómez, Miguel A; Bernabe, Antonio

2014-04-01

An 8-year-old intact male Persian cat was presented for investigation of chronic haematuria. The cat had episodes of haematuria on several occasions that were non-responsive to antimicrobial therapy. Abdominal ultrasound examination revealed dilation of the renal pelvis and ureters of both kidneys. The urinary bladder wall was thickened, a mass of heterogeneous echogenicity filled the lumen of the bladder, and two parallel thin hyperechoic lines were identified within the lumen, which suggested a urethral catheter. Differential diagnoses for the urinary bladder mass included cystitis and neoplasia. The mass was surgically removed from the urinary bladder, and a urethral catheter was found embedded in the mass. Histopathological findings were consistent with cystitis glandularis of a typical type. Periodic bladder ultrasonographic studies were performed; at the time of writing, over 2 years later, recurrence had not been detected.

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.

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.

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

Common theme for drugs effective in overactive bladder treatment: Inhibition of afferent signaling from the bladder

PubMed Central

Hood, Brandy; Andersson, Karl-Erik

2013-01-01

The overactive bladder syndrome and detrusor overactivity are conditions that can have major effects on quality of life and social functioning. Antimuscarinic drugs are still first-line treatment. These drugs often have good initial response rates, but adverse effects and decreasing efficacy cause long-term compliance problems, and alternatives are needed. The recognition of the functional contribution of the urothelium/suburothelium, the autonomous detrusor muscle activity during bladder filling and the diversity of nerve transmitters involved has sparked interest in both peripheral and central modulation of overactive bladder syndrome/detrusor overactivity pathophysiology. Three drugs recently approved for treatment of overactive bladder syndrome/detrusor overactivity (mirabegron, tadalafil and onabotulinum toxin A), representing different pharmacological mechanisms; that is, β-adrenoceptor agonism, phosphodiesterase type 5 inhibition, and inhibition of nerve release of efferent and afferent transmitters, all seem to have one effect in common: inhibition of the afferent nervous activity generated by the bladder during filling. In the present review, the different mechanisms forming the pharmacological basis for the use of these drugs are discussed. PMID:23072271

Spectroscopic analysis of bladder cancer tissues using Fourier transform infrared spectroscopy

NASA Astrophysics Data System (ADS)

Al-Muslet, Nafie A.; Ali, Essam E.

2012-03-01

Bladder cancer is one of the most common cancers in Africa. It takes several days to reach a diagnosis using histological examinations of specimens obtained by endoscope, which increases the medical expense. Recently, spectroscopic analysis of bladder cancer tissues has received considerable attention as a diagnosis technique due to its sensitivity to biochemical variations in the samples. This study investigated the use of Fourier transform infrared (FTIR) spectroscopy to analyze a number of bladder cancer tissues. Twenty-two samples were collected from 11 patients diagnosed with bladder cancer from different hospitals without any pretreatment. From each patient two samples were collected, one normal and another cancerous. FTIR spectrometer was used to differentiate between normal and cancerous bladder tissues via changes in spectra of these samples. The investigations detected obvious changes in the bands of proteins (1650, 1550 cm-1), lipids (2925, 2850 cm-1), and nucleic acid (1080, 1236 cm-1). The results show that FTIR spectroscopy is promising as a rapid, accurate, nondestructive, and easy to use alternative method for identification and diagnosis of bladder cancer tissues.

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

Prospective evaluation of antibiotic treatment for urological procedure in patients presenting with neurogenic bladder.

PubMed

Weglinski, L; Rouzaud, C; Even, A; Bouchand, F; Davido, B; Duran, C; Salomon, J; Perronne, C; Denys, P; Chartier-Kastler, E; Dinh, A

2016-09-01

Patients presenting with neurogenic bladder often require urological procedures (urodynamic testing and botulinum toxin injections) and a preventive antibiotic therapy. We aimed to assess the efficacy of this little known strategy in a cohort of patients. All patients presenting with neurogenic bladder who underwent urological procedure were included in the study. They received an antibiotic therapy in accordance with the urine cytobacteriological examination results. The antibiotic therapy was initiated two days before the procedure and prolonged up until two days after the procedure if the culture was positive. Patients were treated with a single dose of fosfomycin-trometamol in case of a negative culture. The main study outcome was the occurrence of urinary tract infection (UTI), defined by a positive urine culture and symptoms, up until 14 days after the procedure. A total of 80 urological procedures were performed. Mean patient age was 47±13.1 years (sex ratio 1.22); 59 (73.8%) presented with asymptomatic bacteriuria before the procedure. Nine (11.1%) UTIs were recorded on Day 14, of which one (1.2%) was febrile. Two patients required an additional curative antibiotic therapy. No patient was hospitalized. Overall, 77.8% of UTIs were cured without antibiotic therapy. Screening and treating asymptomatic bacteriuria before urological procedures seems unnecessary and vainly exposes this population at high risk of infectious diseases to antibiotic therapies. This data should be confirmed by a randomized clinical trial. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Physiotherapy in Women with Overactive Bladder].

PubMed

Henscher, U; Tholen, R; Kirschner-Hermanns, R

2016-08-01

As regards treatment for overactive bladder, physiotherapeutic interventions can be seen as an alternative to drug treatment. Targeted pelvic floor and bladder training is used to decrease the number of voids and the incontinence episodes or to increase the average voided volume in women with overactive bladder (3 systematic reviews with evidence level 1/1a).An additional option to treat women with overactive bladder is to use functional electrical stimulation and magnetic stimulation.2 systematic reviews 1 2 and 2 RCTs 3 4 reveal a low level of evidence (2 studies with level 2/2b) for the use of electrical stimulation (transcutaneous, vaginal or transanal) to reduce incontinence episodes and the number of voids and to increase the average voided volume. The trial from Yamanishi et al. (2014) shows that magnetic stimulation has a positive effect 5. Further studies are needed to evaluate the benefit of conservative treatment procedures for overactive bladder. © Georg Thieme Verlag KG Stuttgart · New York.

Stromal Mesenchyme Cell Genes in Prostate Cancer Development: Epigenetic Markers for Cancer and Potential Targets for Therapy

DTIC Science & Technology

2006-12-01

magnetic beads (MACS) Our CD phenotyping result showed a layer of stromal cells beneath the bladder urothelium that was positive for CD13 whereas the...bladder, CD13 stains a subpopulation of stromal cells (black arrow) in the lamina propria as shown on the right. The partially denuded urothelium is

Stromal Mesenchyme Cell Genes in Prostate Cancer Development: Epigenetic Markers for Cancer and Potential Targets for Therapy

DTIC Science & Technology

2007-12-01

bladder urothelium that was positive for CD13 whereas the stromal cells next to the prostatic epithelium were not (Fig. 1). This comparative analysis was...denuded urothelium is indicated by the red arrow. Magnification is 40x. Figure 2. Distribution of differentially expressed stromal genes in bladder

Spontaneous regression of tumour and the role of microbial infection – possibilities for cancer treatment

PubMed Central

Cervinkova, Monika

2016-01-01

This review deals with the role of microorganisms in spontaneous regression of a tumour. Spontaneous cancer regression is a phenomenon that has been described for many centuries. One of the most well known methods of inducing spontaneous regression of cancer is the application of Coley’s toxin (heat-killed Streptococcus pyogenes and Serratia marcescens), which has been used for the successful treatment of sarcomas, carcinomas, lymphomas, myelomas and melanomas. In clinical practice, the use of Bacillus Calmette-Guérin vaccine for the treatment of superficial urinary bladder cancer is the most common instance of the application of microorganisms for the treatment of cancer. This review provides further information on other tested bacteria – Clostridium spp., Bifidobacterium spp., Lactobacillus spp. and Salmonella spp. – in this field of study. Among new age methods, bactofection, alternative gene therapy, combination bacteriolytic therapy and bacteria-directed enzyme prodrug therapy are some of the potential cancer treatment modalities that use microorganisms. We have also provided information about the interconnection among microorganisms, immune system response, and the possible mechanisms involved in the spontaneous regression of tumours. PMID:26813865

Spontaneous regression of tumour and the role of microbial infection--possibilities for cancer treatment.

PubMed

Kucerova, Petra; Cervinkova, Monika

2016-04-01

This review deals with the role of microorganisms in spontaneous regression of a tumour. Spontaneous cancer regression is a phenomenon that has been described for many centuries. One of the most well known methods of inducing spontaneous regression of cancer is the application of Coley's toxin (heat-killed Streptococcus pyogenes and Serratia marcescens), which has been used for the successful treatment of sarcomas, carcinomas, lymphomas, myelomas and melanomas. In clinical practice, the use of Bacillus Calmette-Guérin vaccine for the treatment of superficial urinary bladder cancer is the most common instance of the application of microorganisms for the treatment of cancer. This review provides further information on other tested bacteria--Clostridium spp., Bifidobacterium spp., Lactobacillus spp. and Salmonella spp.--in this field of study. Among new age methods, bactofection, alternative gene therapy, combination bacteriolytic therapy and bacteria-directed enzyme prodrug therapy are some of the potential cancer treatment modalities that use microorganisms. We have also provided information about the interconnection among microorganisms, immune system response, and the possible mechanisms involved in the spontaneous regression of tumours.

Expression of Epidermal Growth Factor Receptor and Transforming Growth Factor Alpha in Cancer Bladder: Schistosomal and Non-Schistosomal

PubMed Central

Badawy, Afkar A.; El-Hindawi, Ali; Hammam, Olfat; Moussa, Mona; Helal, Noha S.; Kamel, Amira

2017-01-01

Introduction Overexpression of epidermal growth factor receptor (EGFR) has been described in several solid tumors including bladder cancer. Transforming growth factor alpha (TGFα) is frequently deregulated in neoplastic cells and plays a role in the development of bladder cancer. TGFα-EGFR ligand-receptor combination constitutes an important event in multistep tumorigenesis. Methods This study was done on 30 bladder biopsies from patients with urothelial carcinoma, 15 with squamous cell carcinoma, 10 with cystitis and 5 normal control bladder specimens. All were immuohistochemically stained with EGFR and TGFα antibodies. Results EGFR and TGFα were over-expressed in higher grades and late stages of bladder cancer. Moreover, they show higher expression in squamous cell carcinoma compared to urothelial carcinoma and in schistosomal associated lesions than in non-schistosomal associated lesions. Conclusion EGFR and TGFα could be used as prognostic predictors in early stage and grade of bladder cancer cases, especially those with schistosomal association. In addition they can help in selecting patients who can get benefit from anti-EGFR molecular targeted therapy. PMID:28413380

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.

Hypofractionated Intensity Modulated Radiation Therapy in Combined Modality Treatment for Bladder Preservation in Elderly Patients With Invasive Bladder Cancer

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

Turgeon, Guy-Anne; Souhami, Luis, E-mail: luis.souhami@muhc.mcgill.ca; Cury, Fabio L.

2014-02-01

Purpose/Objective(s): To review our experience with bladder-preserving trimodality treatment (TMT) using hypofractionated intensity modulated radiation therapy (IMRT) for the treatment of elderly patients with muscle-invasive bladder cancer. Methods and Materials: Retrospective study of elderly patients treated with TMT using hypofractionated IMRT (50 Gy in 20 fractions) with concomitant weekly radiosensitizing chemotherapy. Eligibility criteria were as follows: age ≥70 years, a proven diagnosis of muscle-invasive transitional cell bladder carcinoma, stage T2-T3N0M0 disease, and receipt of TMT with curative intent. Response rate was assessed by cystoscopic evaluation and bladder biopsy. Results: 24 patients with a median age of 79 years were eligible.more » A complete response was confirmed in 83% of the patients. Of the remaining patients, 1 of them underwent salvage cystectomy, and no disease was found in the bladder on histopathologic assessment. After a median follow-up time of 28 months, of the patients with a complete response, 2 patients had muscle-invasive recurrence, 1 experienced locoregional failure, and 3 experienced distant metastasis. The overall and cancer-specific survival rates at 3 years were 61% and 71%, respectively. Of the surviving patients, 75% have a disease-free and functioning bladder. All patients completed hypofractionated IMRT, and 19 patients tolerated all 4 cycles of chemotherapy. Acute grade 3 gastrointestinal or genitourinary toxicities occurred in only 4% of the patients, and acute grade 3 or 4 hematologic toxicities, liver toxicities, or both were experienced by 17% of the cohort. No patient experienced grade 4 gastrointestinal or genitourinary toxicity. Conclusions: Hypofractionated IMRT with concurrent radiosensitizing chemotherapy appears to be an effective and well-tolerated curative treatment strategy in the elderly population and should be considered for patients who are not candidates for cystectomy or who wish to avoid cystectomy.« less

The Role(s) of Cytokines/Chemokines in Urinary Bladder Inflammation and Dysfunction

PubMed Central

Gonzalez, Eric J.; Arms, Lauren; Vizzard, Margaret A.

2014-01-01

Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder related and with at least one urinary symptom. It was recently concluded that 3.3–7.9 million women (>18 years old) in the United States exhibit BPS/IC symptoms. The impact of BPS/IC on quality of life is enormous and the economic burden is significant. Although the etiology and pathogenesis of BPS/IC are unknown, numerous theories including infection, inflammation, autoimmune disorder, toxic urinary agents, urothelial dysfunction, and neurogenic causes have been proposed. Altered visceral sensations from the urinary bladder (i.e., pain at low or moderate bladder filling) that accompany BPS/IC may be mediated by many factors including changes in the properties of peripheral bladder afferent pathways such that bladder afferent neurons respond in an exaggerated manner to normally innocuous stimuli (allodynia). The goals for this review are to describe chemokine/receptor (CXCL12/CXCR4; CCL2/CCR2) signaling and cytokine/receptor (transforming growth factor (TGF-β)/TGF-β type 1 receptor) signaling that may be valuable LUT targets for pharmacologic therapy to improve urinary bladder function and reduce somatic sensitivity associated with urinary bladder inflammation. PMID:24738044

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

Identification and characterization of DNAzymes targeting DNA methyltransferase I for suppressing bladder cancer proliferation

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

Wang, Xiangbo; Zhang, Lu; Ding, Nianhua

2015-05-29

Epigenetic inactivation of genes plays a critical role in many important human diseases, especially in cancer. A core mechanism for epigenetic inactivation of the genes is methylation of CpG islands in genome DNA, which is catalyzed by DNA methyltransferases (DNMTs). The inhibition of DNMTs may lead to demethylation and expression of the silenced tumor suppressor genes. Although DNMT inhibitors are currently being developed as potential anticancer agents, only limited success is achieved due to substantial toxicity. Here, we utilized a multiplex selection system to generate efficient RNA-cleaving DNAzymes targeting DNMT1. The lead molecule from the selection was shown to possessmore » efficient kinetic profiles and high efficiency in inhibiting the enzyme activity. Transfection of the DNAzyme caused significant down-regulation of DNMT1 expression and reactivation of p16 gene, resulting in reduced cell proliferation of bladder cancers. This study provides an alternative for targeting DNMTs for potential cancer therapy. - Highlights: • Identified DNMT1-targeted DNAzymes by multiplex selection system. • Biochemically characterized a lead DNAzyme with high kinetic efficiency. • Validated DNMT1-targeted DNAzyme in its enzymatic and cellular activities.« less

Expert consensus document: Consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer.

PubMed

Kamat, Ashish M; Flaig, Thomas W; Grossman, H Barton; Konety, Badrinath; Lamm, Donald; O'Donnell, Michael A; Uchio, Edward; Efstathiou, Jason A; Taylor, John A

2015-04-01

Multiple clinical trials have demonstrated that intravesical Bacillus Calmette-Guérin (BCG) treatment reduces recurrences and progression in patients with non-muscle-invasive bladder cancer (NMIBC). However, although BCG has been in use for almost 40 years, this agent is often underutilized and practice patterns of administration vary. This neglect is most likely caused by uncertainties about the optimal use of BCG, including unawareness of optimal treatment schedules and about patient populations that most benefit from BCG treatment. To address this deficit, a focus group of specialized urologic oncologists (urologists, medical oncologists and radiation oncologists) reviewed the current guidelines and clinical evidence, discussed their experiences and formed a consensus regarding the optimal use of BCG in the management of patients with NIMBC. The experts concluded that continuing therapy with 3-week BCG maintenance is superior to induction treatment only and is the single most important factor in improving outcomes in patients with NMIBC. They also concluded that a reliable alternative to radical cystectomy in truly BCG-refractory disease remains the subject of clinical trials. In addition, definitions for common terms of BCG failure, such as BCG-refractory and BCG-intolerant, have been formulated.

Management of vesicoureteral reflux in neurogenic bladder.

PubMed

Wu, Charlotte Q; Franco, Israel

2017-06-01

Vesicoureteral reflux (VUR) is a significant risk factor for pyelonephritis and renal scarring. VUR can occur through a defective ureterovesical junction (UVJ) or an overwhelmed normal UVJ mechanism such as in bladder dysfunction of congenital, acquired, or behavioral etiology. There are numerous causes for the development of a neurogenic bladder from spinal dysraphisms to spinal cord trauma and even centrally based abnormalities in children with apparently normal motor function (inappropriately termed nonneurogenic neurogenic bladder). The foundation of managing reflux in these neurogenic bladders is to maintain low bladder pressures which will commonly mean that compliance will be normal as well. There have been several publications that have shown that if bladder pressures are lowered simply with clean intermittent catheterization and medications that the reflux can resolve spontaneously. Alternatively, the patients that are in need of bladder augmentation can have spontaneous resolution of their reflux with the resulting increase in capacity. Surgical intervention is called for when bladder capacity is adequate and the reflux persists or if it is part of a larger operation to increase capacity and to manage outlet resistance. In some instances, reimplantation is necessary because the ureters interfere with the bladder neck procedure. Aside from open and robotic surgical intervention the use of endoscopic injectable agents is beginning to become more popular especially when combined with intravesical botulinum toxin A injections. Great strides are being made in the management of patients with neurogenic bladders and we are seeing more choices for the urologist to be able to manage these patients.

Mucinous adenocarcinoma of the bladder associated with long term suprapubic tube: a case report.

PubMed

Bauman, Tyler M; Potretzke, Theodora A; Potretzke, Aaron M; Siegel, Cary L; Brandes, Steven B

2015-12-03

Chronic indwelling catheters may induce histologic changes within the bladder, and these changes are sometimes pre-malignant. There are many documented cases of squamous cell carcinoma associated with indwelling catheters, but only three cases of catheter-associated adenocarcinoma have been reported. In this case report, we present radiographic findings of a case of mucinous adenocarcinoma of the bladder and suprapubic (SP) tract in a quadriplegic patient. A 71-year-old male with a history of spinal cord injury presented with hematuria and SP discharge after SP catheterization for 51 years. CT urography was performed and revealed an irregular, infiltrative, and heterogeneous mass arising from the anterior bladder at the level of the suprapubic catheter and extending along the SP tube tract. Cystoscopy and biopsy revealed an adenocarcinoma of the anterior bladder and stoma with extensive associated mucin production and a background of acute and chronic inflammation. Surgical therapy included cystoprostatectomy, abdominal wall resection, ileal conduit creation, and abdominal wall reconstruction. The final diagnosis was a high-grade, T2a/N0/M0 (Stage II) mucinous adenocarcinoma of the bladder. There has been no evidence of tumor recurrence over the previous 5 years. Few cases of adenocarcinoma associated with long term indwelling catheter have been reported in the literature, and due to the rarity of this disease process, the prognosis with surgical therapy is not well known. The patient described herein has been free of recurrence for the previous five years, suggesting that surgery is a viable management option for these patients.

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.

Pelvic Nodal Dosing With Registration to the Prostate: Implications for High-Risk Prostate Cancer Patients Receiving Stereotactic Body Radiation Therapy

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

Kishan, Amar U., E-mail: aukishan@mednet.ucla.edu; Lamb, James M.; Jani, Shyam S.

2015-03-15

Purpose: To determine whether image guidance with rigid registration (RR) to intraprostatic markers (IPMs) yields acceptable coverage of the pelvic lymph nodes in the context of a stereotactic body radiation therapy (SBRT) regimen. Methods and Materials: Four to seven kilovoltage cone-beam CTs (CBCTs) from 12 patients with high-risk prostate cancer were analyzed, allowing approximation of an SBRT regimen. The nodal clinical target volume (CTV{sub N}) and bladder were contoured on all kilovoltage CBCTs. The V{sub 100} CTV{sub N}, expressed as a ratio to the same parameter on the initial plan, and the magnitude of translational shift between RR to themore » IPMs versus RR to the pelvic bones, were computed. The ability of a multimodality bladder filling protocol to minimize bladder height variation was assessed in a separate cohort of 4 patients. Results: Sixty-five CBCTs were assessed. The average V{sub 100} CTV{sub N} was 92.6%, but for a subset of 3 patients the average was 80.0%, compared with 97.8% for the others (P<.0001). The average overall and superior–inferior axis magnitudes of the bony-to-fiducial translations were significantly larger in the subgroup with suboptimal nodal coverage (8.1 vs 3.9 mm and 5.8 vs 2.4 mm, respectively; P<.0001). Relative bladder height changes were also significantly larger in the subgroup with suboptimal nodal coverage (42.9% vs 18.5%; P<.05). Use of a multimodality bladder-filling protocol minimized bladder height variation (P<.001). Conclusion: A majority of patients had acceptable nodal coverage after RR to IPMs, even when approximating SBRT. However, a subset of patients had suboptimal nodal coverage. These patients had large bony-to-fiducial translations and large variations in bladder height. Nodal coverage should be excellent if the superior–inferior axis bony-to-fiducial translation and the relative bladder height change (both easily measured on CBCT) are kept to a minimum. Implementation of a strict bladder filling protocol may achieve this goal.« less

Cerebral control of the bladder in normal and urge-incontinent women

PubMed Central

Griffiths, Derek; Tadic, Stasa D.; Schaefer, Werner; Resnick, Neil M.

2007-01-01

Aim: To identify age-related changes in the normal brain/bladder control system, and differences between urge incontinence in younger and older women, as shown by brain responses to bladder filling; and to use age, bladder volume, urge incontinence and detrusor overactivity (DO) as probes to reveal control-system function. Functional MRI was used to examine regional brain responses to bladder infusion in 21 females (26 – 85 years): 11 “cases” with urge incontinence and DO (proven previously) and 10 normal “controls”. Responses and their age dependence were determined at small and large bladder volumes, in whole brain and in regions of interest representing right insula and anterior cingulate (ACG). In “controls”, increasing bladder volume/sensation led to increasing insular responses; with increasing age, insular responses became weaker. In younger “cases”, ACG responded abnormally strongly at large bladder volumes/strong sensation. Elderly “cases” showed strong ACG responses even at small bladder volume, but more moderate responses at larger volumes; if DO occurred, pontine micturition center (PMC) activation did not increase. Conclusion: Among normal “controls”, increasing age leads to decreased responses in brain regions involved in bladder control, including right insula, consistent with its role in mapping normal bladder sensations. Strong ACG activation occurs in urge-incontinent “cases” and may be a sign of urgency, indicating recruitment of alternative pathways when loss of bladder control is feared. Easier ACG provocation in older “cases” reflects lack of physiological reserve or different etiology. ACG responses seem associated with PMC inhibition: reduced ACG activity accompanies failure of inhibition (DO). PMID:17574871

Urothelial carcinoma of the bladder and the upper tract: disparate twins.

PubMed

Green, David A; Rink, Michael; Xylinas, Evanguelos; Matin, Surena F; Stenzl, Arnulf; Roupret, Morgan; Karakiewicz, Pierre I; Scherr, Douglas S; Shariat, Shahrokh F

2013-04-01

Urothelial carcinoma of the bladder is the 4th most common malignancy in men and the 8th most common cause of male cancer death in the United States. Conversely, upper tract urothelial carcinoma accounts for only 5% to 10% of all urothelial carcinoma. Due to the relative preponderance of urothelial carcinoma of the bladder, much of the clinical decision making regarding upper tract urothelial carcinoma is extrapolated from evidence that is based on urothelial carcinoma of the bladder cohorts. In fact, only 1 major urological organization has treatment guidelines specific for upper tract urothelial carcinoma. While significant similarities exist between these 2 diseases, ignoring the important differences may be preventing us from optimizing therapy in patients with upper tract urothelial carcinoma. Therefore, we explored these dissimilarities, including the differential importance of gender, anatomy, staging, intracavitary therapy, surgical lymphadenectomy and perioperative systemic chemotherapy on the behavior of urothelial carcinoma of the bladder and upper tract urothelial carcinoma. A nonsystematic literature search using the MEDLINE/PubMed® database was conducted to identify original articles, review articles and editorials. Searches were limited to the English language and studies in humans and in adults, and used the key words urothelial carcinoma, upper tract urothelial carcinoma or transitional cell carcinoma combined with several different sets of key words to identify appropriate publications for each section of the manuscript. The key words, broken down by section, were 1) epidemiology, sex, gender; 2) location, tumor location; 3) staging, stage; 4) intracavitary, intravesical, topical therapy; 5) lymphadenectomy, lymph node, lymph node dissection and 6) adjuvant, neoadjuvant, chemotherapy. Women who present with urothelial carcinoma of the bladder do so with less favorable tumor characteristics and have worse survival than men. However, gender does not appear to be associated with survival outcomes in upper tract urothelial carcinoma. The prognostic effect that urothelial carcinoma tumor location has on outcomes prediction is a matter of debate, and the influence of tumor location may reflect our technical ability to accurately stage and treat the disease more than the actual tumor biology. Moreover, technical limitations of upper tract urothelial carcinoma sampling compared to transurethral resection for urothelial carcinoma of the bladder are the most important source of staging differences between the 2 diseases. Intravesical chemotherapy and immunotherapy are essential components of standard of care for most nonmuscle invasive bladder cancer, while adjuvant intracavitary therapy for patients with upper tract urothelial carcinoma treated endoscopically or percutaneously has been sparsely used and without any clear guidelines. The widespread adoption of the use of intracavitary therapy in the upper tract will likely not only require additional data to support its efficacy, but will also require a less cumbersome means of administration. Lymphadenectomy at the time of radical cystectomy is widely accepted while lymphadenectomy at the time of radical nephroureterectomy is performed largely at the discretion of the surgeon. Among other reasons, this may be due in part to the variable lymphatic drainage along the course of the ureter compared to the relatively confined lymphatic landing sites for the bladder. Level I evidence has demonstrated a clear survival benefit for systemic chemotherapy before radical surgery or radiation in patients with clinical T2-4N0M0 urothelial carcinoma of the bladder. Such data are not available in the population with upper tract urothelial carcinoma. However, the use of neoadjuvant chemotherapy may be even more important in upper tract urothelial carcinoma than in urothelial carcinoma of the bladder because of the obligatory kidney function loss that occurs at radical nephroureterectomy. While urothelial carcinoma of the bladder and upper tract urothelial carcinoma share many characteristics, they represent 2 distinct diseases. There are practical, anatomical, biological and molecular differences that warrant consideration when risk stratifying and treating patients with these disparate twin diseases. To overcome the challenges that impede progress toward evidence-based medicine in upper tract urothelial carcinoma, we believe that focused collaborative efforts will best augment our understanding of this rare disease and ultimately improve the care we deliver to our patients. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Urinary fibronectin levels in patients treated with intravesical bacillus Calmette-Guérin for superficial bladder cancer.

PubMed

Danişman, A; Bulut, K; Kukul, E; Ozen, I; Sevük, M

2000-01-01

Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma (TCC) of the bladder, but the precise mechanism of action of BCG remains poorly understood. Fibronectin (FN), an important component of the extracellular matrix, has been found to play a role in BCG therapy. Some studies have shown that the soluble form of FN can compete efficiently with the matrix form of binding to the specific receptors on the bacteria and could consequently diminish the effect of BCG treatment. To evaluate a possible correlation between the urinary levels of FN and the efficacy of BCG therapy, we determined prospectively the urinary FN levels in 38 patients with TCC of the bladder and in 25 control subjects without malignancy matched for age and sex. All TCC patients were treated with transurethral tumor resection plus 6 weekly intravesical BCG instillations. After an average follow-up of 30 months, 8 patients (21.1%) had recurrent tumors, while 30 (78.9%) were free of tumor after intravesical BCG therapy. Urinary levels of FN in cancer patients have been shown to be significantly higher than controls (p < 0.001). These elevated levels were not decreased significantly after the operation (p > 0. 05). It was also found that the mean urinary FN levels were not statistically significant between patients with recurrence and complete remission. The data suggest that BCG-bladder tumor cell binding is not influenced by soluble fibronectin and urinary FN may not be a ideal marker for selecting patients to BCG therapy. Copyright 2000 S. Karger AG, Basel

Characterization of a human anti-tumoral NK cell population expanded after BCG treatment of leukocytes

PubMed Central

García-Cuesta, Eva M.; Esteso, Gloria; Ashiru, Omodele; López-Cobo, Sheila; Álvarez-Maestro, Mario; Linares, Ana; Ho, Mei M.; Martínez-Piñeiro, Luis; T. Reyburn, Hugh; Valés-Gómez, Mar

2017-01-01

ABSTRACT Immunotherapy, via intra-vesical instillations of BCG, is the therapy of choice for patients with high-risk non-muscle invasive bladder cancer. The subsequent recruitment of lymphocytes and myeloid cells, as well as the release of cytokines and chemokines, is believed to induce a local immune response that eliminates these tumors, but the detailed mechanisms of action of this therapy are not well understood. Here, we have studied the phenotype and function of the responding lymphocyte populations as well as the spectrum of cytokines and chemokines produced in an in vitro model of human peripheral blood mononuclear cells (PBMCs) co-cultured with BCG. Natural killer (NK) cell activation was a prominent feature of this immune response and we have studied the expansion of this lymphocyte population in detail. We show that, after BCG stimulation, CD56dim NK cells proliferate, upregulate CD56, but maintain the expression of CD16 and the ability to mediate ADCC. CD56bright NK cells also contribute to this expansion by increasing CD16 and KIR expression. These unconventional CD56bright cells efficiently degranulated against bladder cancer cells and the expansion of this population required the release of soluble factors by other immune cells in the context of BCG. Consistent with these in vitro data, a small, but significant increase in the intensity of CD16 expression was noted in peripheral blood CD56bright cells from bladder cancer patients undergoing BCG therapy, that was not observed in patients treated with mitomycin-C instillations. These observations suggest that activation of NK cells may be an important component of the anti-tumoral immune response triggered by BCG therapy in bladder cancer. PMID:28507799

First-Line Atezolizumab Effective in Bladder Cancer.

PubMed

2016-08-01

Results from a phase II study indicate that the PD-L1 inhibitor atezolizumab, recently approved for advanced bladder cancer that's refractory to standard platinum chemotherapy, is effective as first-line therapy for this disease. Durable responses to atezolizumab were seen in nearly a quarter of the study patients, who were all ineligible to receive cisplatin. ©2016 American Association for Cancer Research.

New clinical trial will test COXEN’s ability to choose best therapy for patients with advanced bladder cancer | Center for Cancer Research

Cancer.gov

The Genitourinary Malignancies Branch is now enrolling participants for a clinical trial that will evaluate whether analyzing a tumor’s genetic profile can identify which approved anticancer drugs are most likely to benefit individual patients whose bladder cancer has stopped responding to standard treatments. Learn more...

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.

The long-term effects of radiation therapy on patients with ovarian dysgerminoma

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

Mitchell, M.F.; Gershenson, D.M.; Soeters, R.P.

A retrospective chart review and questionnaire study was undertaken to look at the long-term effects of radiation therapy in ovarian dysgerminoma patients. Forty-three patients and 55 controls responded to a questionnaire that detailed bowel, bladder, thyroid, menstrual, reproductive, sexual, and growth function. Statistically significant differences in the number of bowel movements were noticed when comparing patients with controls. The authors noticed no significant differences between cases and controls in bladder function. No thyroid disorders were attributable to mediastinal radiation therapy. Most patients with intact uteri bleed monthly on hormonal replacement. Three patients with a remaining ovary and uterus resumed menstrualmore » function after substantial doses of abdominopelvic radiation therapy. No patients have conceived. The authors noticed a slight increase in dyspareunia in the treated group, but most patients were satisfied with their sexual function. One premenarchal patient exhibited a growth disorder.« less

Enhancement of antitumor activity of gammaretrovirus carrying IL-12 gene through genetic modification of envelope targeting HER2 receptor: a promising strategy for bladder cancer therapy.

PubMed

Tsai, Y-S; Shiau, A-L; Chen, Y-F; Tsai, H-T; Tzai, T-S; Wu, C-L

2010-01-01

The objective of this study was to develop an HER2-targeted, envelope-modified Moloney murine leukemia virus (MoMLV)-based gammaretroviral vector carrying interleukin (IL)-12 gene for bladder cancer therapy. It displayed a chimeric envelope protein containing a single-chain variable fragment (scFv) antibody to the HER2 receptor and carried the mouse IL-12 gene. The fragment of anti-erbB2scFv was constructed into the proline-rich region of the viral envelope of the packaging vector lacking a transmembrane subunit of the carboxyl terminal region of surface subunit. As compared with envelope-unmodified gammaretroviruses, envelope-modified ones had extended viral tropism to human HER2-expressing bladder cancer cell lines, induced apoptosis, and affected cell cycle progression despite lower viral titers. Moreover, animal studies showed that envelope-modified gammaretroviruses carrying IL-12 gene exerted higher antitumor activity in terms of retarding tumor growth and prolonging the survival of tumor-bearing mice than unmodified ones, which were associated with enhanced tumor cell apoptosis as well as increased intratumoral levels of IL-12, interferon-gamma, IL-1beta, and tumor necrosis factor-alpha proteins. Therefore, the antitumor activity of gammaretroviruses carrying the IL-12 gene was enhanced through genetic modification of the envelope targeting HER2 receptor, which may be a promising strategy for bladder cancer therapy.

Advances in stem cell therapy for the lower urinary tract.

PubMed

Lin, Ching-Shwun

2010-02-26

Lower urinary tract diseases are emotionally and financially burdensome to the individual and society. Current treatments are ineffective or symptomatic. Conversely, stem cells (SCs) are regenerative and may offer long-term solutions. Among the different types of SCs, bone marrow SCs (BMSCs) and skeletal muscle-derived SCs (SkMSCs) have received the most attention in pre-clinical and clinical trial studies concerning the lower urinary tract. In particular, clinical trials with SkMSCs for stress urinary incontinence have demonstrated impressive efficacy. However, both SkMSCs and BMSCs are difficult to obtain in quantity and therefore neither is optimal for the eventual implementation of SC therapy. On the other hand, adipose tissue-derived SCs (ADSCs) can be easily and abundantly obtained from "discarded" adipose tissue. Moreover, in several head-on comparison studies, ADSCs have demonstrated equal or superior therapeutic potential compared to BMSCs. Therefore, across several different medical disciplines, including urology, ADSC research is gaining wide attention. For the regeneration of bladder tissues, possible differentiation of ADSCs into bladder smooth muscle and epithelial cells has been demonstrated. For the treatment of bladder diseases, specifically hyperlipidemia and associated overactive bladder, ADSCs have also demonstrated efficacy. For the treatment of urethral sphincter dysfunction associated with birth trauma and hormonal deficiency, ADSC therapy was also beneficial. Finally, ADSCs were able to restore erectile function in various types of erectile dysfunction (ED), including those associated with diabetes, hyperlipidemia, and nerve injuries. Thus, ADSCs have demonstrated remarkable therapeutic potentials for the lower urinary tract.

Marked hydronephrosis and hydroureter after distigmine therapy in an adult male patient with paraplegia due to spinal cord injury: a case report

PubMed Central

Mansour, Paul; Soni, Bakul M; Hughes, Peter L; Singh, Gurpreet; Oo, Tun

2009-01-01

Introduction Distigmine, a long-acting anti-cholinesterase, is associated with side effects such as Parkinsonism, cholinergic crisis, and rhabdomyolysis. We report a spinal cord injury patient, who developed marked hydronephrosis and hydroureter after distigmine therapy, which led to a series of complications over subsequent years. Case presentation A 38-year-old male developed T-9 paraplegia in 1989. Intravenous urography, performed in 1989, showed normal kidneys, ureters and bladder. He was prescribed distigmine bromide orally and was allowed to pass urine spontaneously. In 1992, intravenous urography showed bilateral marked hydronephrosis and hydroureter. Distigmine was discontinued. He continued to pass urine spontaneously. In 2006, intravenous urography showed moderate dilatation of both pelvicalyceal systems and ureters down to the level of urinary bladder. This patient was performing self-catheterisation only once a day. He was advised to do catheterisations at least three times a day. In December 2008, this patient developed haematuriawhich lasted for nearly four months.. He received trimethoprim, then cephalexin, followed by Macrodantin, amoxicillin and ciprofloxacin. In February 2009, intravenous urography showed calculus at the lower pole of left kidney. Both kidneys were moderately hydronephrotic. Ureters were dilated down to the bladder. Dilute contrast was seen in the bladder due to residual urine. This patient was advised to perform six catheterisations a day, and take propiverine hydrochloride 15 mg, three times a day. Microbiology of urine showed Klebsiella oxytoca, Pseudomonas aeruginosa, and Enterococcus faecalis. Cystoscopy revealed papillary lesions in bladder neck and trigone. Transurethral resection was performed. Histology showed marked chronic cystitis including follicular cystitis and papillary/polypoid cystitis. There was no evidence of malignancy. Conclusion Distigmine therapy resulted in marked bilateral hydronephrosis and hydroureter. Persistence of hydronephrosis after omitting distigmine, and presence of residual urine in bladder over many years probably predisposed to formation of polypoid cystitis and follicular cystitis, and contributed to prolonged haematuria, which occurred after an episode of urine infection. This case illustrates the dangers of prescribing distigmine to promote spontaneous voiding in spinal cord injury patients. Instead of using distigmine, spinal cord injury patients should be advised to consider intermittent catheterisation together with oxybutynin or propiverine to achieve complete, low-pressure emptying of urinary bladder. PMID:19918519

Receptors, channels, and signalling in the urothelial sensory system in the bladder

PubMed Central

Merrill, Liana; Gonzalez, Eric J.; Girard, Beatrice M.; Vizzard, Margaret A.

2017-01-01

The storage and periodic elimination of urine, termed micturition, requires a complex neural control system to coordinate the activities of the urinary bladder, urethra, and urethral sphincters. At the level of the lumbosacral spinal cord, lower urinary tract reflex mechanisms are modulated by supraspinal controls with mechanosensory input from the urothelium, resulting in regulation of bladder contractile activity. The specific identity of the mechanical sensor is not yet known, but considerable interest exists in the contribution of transient receptor potential (TRP) channels to the mechanosensory functions of the urothelium. The sensory, transduction, and signalling properties of the urothelium can influence adjacent urinary bladder tissues including the suburothelial nerve plexus, interstitial cells of Cajal, and detrusor smooth muscle cells. Diverse stimuli, including those that activate TRP channels expressed by the urothelium, can influence urothelial release of chemical mediators (such as ATP). Changes to the urothelium are associated with a number of bladder pathologies that underlie urinary bladder dysfunction. Urothelial receptor and/or ion channel expression and the release of signalling molecules (such as ATP and nitric oxide) can be altered with bladder disease, neural injury, target organ inflammation, or psychogenic stress. Urothelial receptors and channels represent novel targets for potential therapies that are intended to modulate micturition function or bladder sensation. PMID:26926246

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

PubMed

Anderson, Beverley

2018-05-10

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

Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand

NASA Astrophysics Data System (ADS)

Doherty, Rachel E.; Sazanovich, Igor V.; McKenzie, Luke K.; Stasheuski, Alexander S.; Coyle, Rachel; Baggaley, Elizabeth; Bottomley, Sarah; Weinstein, Julia A.; Bryant, Helen E.

2016-03-01

Photodynamic therapy that uses photosensitizers which only become toxic upon light-irradiation provides a strong alternative to conventional cancer treatment due to its ability to selectively target tumour material without affecting healthy tissue. Transition metal complexes are highly promising PDT agents due to intense visible light absorption, yet the majority are toxic even without light. This study introduces a small, photostable, charge-neutral platinum-based compound, Pt(II) 2,6-dipyrido-4-methyl-benzenechloride, complex 1, as a photosensitizer, which works under visible light. Activation of the new photosensitizer at low concentrations (0.1-1 μM) by comparatively low dose of 405 nm light (3.6 J cm-2) causes significant cell death of cervical, colorectal and bladder cancer cell lines, and, importantly, a cisplatin resistant cell line EJ-R. The photo-index of the complex is 8. We demonstrate that complex 1 induces irreversible DNA single strand breaks following irradiation, and that oxygen is essential for the photoinduced action. Neither light, nor compound alone led to cell death. The key advantages of the new drug include a remarkably fast accumulation time (diffusion-controlled, minutes), and photostability. This study demonstrates a highly promising new agent for photodynamic therapy, and attracts attention to photostable metal complexes as viable alternatives to conventional chemotherapeutics, such as cisplatin.

The photokilling of bladder carcinoma cells in vitro by phenothiazine dyes.

PubMed

Fowler, G J; Rees, R C; Devonshire, R

1990-09-01

The potential photodynamic therapy photosensitizers Methylene Blue, Azure C, Methylene Violet, Thionine, Methylene Green, Haematoporphyrin, Nile Blue A, chloroaluminium phthalocyanine and bis-aluminium phthalocyanine were examined for their photoeffects and dark toxicity against a human superficial bladder carcinoma cell-line. By examination of [3H]thymidine uptake into dye-treated cells after irradiation with a copper-vapour pumped dye laser, it was found that Methylene Blue was the most phototoxic and dark toxic of all the dyes tested, suggesting that the dye might be of some use as a topically applied photodrug for use in photodynamic therapy of superficial or early-recurring carcinomas.

Urolume stent placement for the treatment of postbrachytherapy bladder outlet obstruction.

PubMed

Konety, B R; Phelan, M W; O'Donnell, W F; Antiles, L; Chancellor, M B

2000-05-01

Transurethral resection (TURP) or incision of the prostate is generally not effective for treating bladder outlet obstruction after transperineal brachytherapy for prostate cancer. Furthermore, TURP could compromise full-dose effective radiation delivery to the prostate. We analyzed the efficacy of the UroLume stent in treating the urinary outflow obstruction in such patients. Five patients who had undergone brachytherapy (3 with (192)Ir high-dose radiation and 2 with (125)I) subsequently developed one or more episodes of urinary retention 2 weeks to 4 years after treatment. The patients failed or could not tolerate alpha-blockers or clean intermittent catheterization. Three patients subsequently underwent urethral dilation/optical internal urethrotomy for strictures, and 1 patient underwent suprapubic tube placement. Following the failure of these interventions, each of these patients had a UroLume stent placement. A single UroLume stent (2 cm in 3 patients and 2.5 cm in 2 patients) was placed under local/spinal anesthesia. All patients were able to void spontaneously immediately after stent placement. Of the patients with previous urethral strictures, 1 remained continent and 1 had persistent incontinence. Neither of the patients with early postbrachytherapy retention developed incontinence after stent placement. The main complaints following stent placement were referred pain to the head of the penis and dysuria. Stent-related symptoms necessitated stent removal in 2 of 5 patients, 4 to 6 weeks after placement. The UroLume stent can be used as an alternative form of therapy for managing postbrachytherapy bladder outlet obstruction. The treatment is easily reversible by removing the stent when obstruction resolves.

Ultrasound-guided urinary bladder biopsy through a urinary catheter in a bitch.

PubMed

Lopez, Julio; Norman, Brian C

2014-01-01

A 34.4 kg 5 yr old spayed female mixed-breed dog was presented for evaluation of a urinary bladder mass. The dog had a recent onset of hematuria and stranguria but otherwise appeared to be healthy. Abdominal ultrasound revealed a mass in the urinary bladder. The dog was sedated and a 10-French rubber catheter that had the blunt end removed was passed from the urethra to the urinary bladder. Using ultrasound guidance, ellipsoid cup biopsy forceps were advanced through the rubber catheter to the urinary bladder mass and biopsies were successfully obtained. The dog was discharged from the hospital a few hours after the procedure. Histopathology of the mass was consistent with polypoid cystitis. Follow-up surgical removal of the polyp was uneventful, and histopathology confirmed the presurgical biopsy diagnosis. Procurement of urinary bladder biopsies through a urinary catheter with ultrasound guidance was used as a minimally invasive alternative to either cystoscopy or surgery in a bitch. Use of this technique achieved a diagnosis without the need for specialized endoscopic equipment, anesthesia, or surgery.

Comparison of the efficacy and feasibility of laser enucleation of bladder tumor versus transurethral resection of bladder tumor: a meta-analysis.

PubMed

Yang, Huan; Wang, Ning; Han, Shanfu; Male, Musa; Zhao, Chenming; Yao, Daqiang; Chen, Zhiqiang

2017-12-01

The transurethral resection of bladder tumor (TURBT) remains the most widely used method in the surgical treatment of the non-muscle invasive bladder tumor (NMIBT). Despite its popularity, the laser technique has been widely used in urology as an alternative, via the application of transurethral laser enucleation of bladder tumor. The aim of the present study was to compare the efficacy and feasibility between transurethral laser enucleation and transurethral resection of bladder tumor. A systematic search of the following databases was conducted: PubMed, Wed of Science, Cochrane Library, EMBASE, Google scholar, and Medline. The search included studies up to the 1st of January 2017. The outcomes of interest that were used in order to assess the two techniques included operation time, catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, 24-month-recurrence rate, and the postoperative adjuvant intravesical chemotherapy. A total of 13 trials with 2012 participants were included, of which 975 and 1037 underwent transurethral laser enucleation and transurethral resection of bladder tumor, respectively. No significant difference was noted in the operation time between the two groups, although significant differences were reported for the variables catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, and 24-month-recurrence rate. In the mitomycin and epirubicin subgroups, no significant differences were observed in the laser enucleation and TURBT methods with regard to the 24-month-recurrence rate. The laser enucleation was superior to TURBT with regard to the parameters obturator nerve reflex, bladder perforation, catheterization time, hospitalization time, and 24-month-recurrence rate. Moreover, laser enucleation can offer a more accurate result of the tumor's pathological stage and grade.

The Antineoplastic Activity of Photothermal Ablative Therapy with Targeted Gold Nanorods in an Orthotopic Urinary Bladder Cancer Model.

PubMed

Yang, Xiaoping; Su, Lih-Jen; La Rosa, Francisco G; Smith, Elizabeth Erin; Schlaepfer, Isabel R; Cho, Suehyun K; Kavanagh, Brian; Park, Wounjhang; Flaig, Thomas W

2017-07-27

Gold nanoparticles treated with near infrared (NIR) light can be heated preferentially, allowing for thermal ablation of targeted cells. The use of novel intravesical nanoparticle-directed therapy in conjunction with laser irradiation via a fiber optic cystoscope, represents a potential ablative treatment approach in patients with superficial bladder cancer. To examine the thermal ablative effect of epidermal growth factor receptor (EGFR)-directed gold nanorods irradiated with NIR light in an orthotopic urinary bladder cancer model. Gold nanorods linked to an anti-EGFR antibody (Conjugated gold NanoRods - CNR) were instilled into the bladder cavity of an orthotopic murine xenograft model with T24 bladder cancer cells expressing luciferase. NIR light was externally administered via an 808 nm diode laser. This treatment was repeated weekly for 4 weeks. The anti-cancer effect was monitored by an in vivo imaging system in a non-invasive manner, which was the primary outcome of our study. The optimal approach for an individual treatment was 2.1 W/cm 2 laser power for 30 seconds. Using this in vivo model, NIR light combined with CNR demonstrated a statistically significant reduction in tumor-associated bioluminescent activity ( n  = 16) compared to mice treated with laser alone ( n  = 14) at the end of the study ( p  = 0.035). Furthermore, the CNR+NIR light treatment significantly abrogated bioluminescence signals over a 6-week observation period, compared to pre-treatment levels ( p  = 0.045). Photothermal tumor ablation with EGFR-directed gold nanorods and NIR light proved effective and well tolerated in a murine in vivo model of urinary bladder cancer.

A short review of drug-food interactions of medicines treating overactive bladder syndrome.

PubMed

Paśko, Paweł; Rodacki, Tomasz; Domagała-Rodacka, Renata; Owczarek, Danuta

2016-12-01

Background Overactive bladder syndrome is a condition where one or more of the symptoms such as pollakiuria, urgent need to urinate, nocturia and urinary incontinence is observed. Its prevalence ranges between 7 and 27 % in men and 9-43 % in women. The role of a pharmacist is to educate the patient on medications administration scheme, and drug interactions with particular food or food components. Aim of the review To assess a potential impact of food and fruit juice on the pharmacokinetic and therapeutic effects of medications used in treating overactive bladder syndrome. This information will enhance pharmaceutical care and is vital and helpful for pharmacists counseling their patients. Method In order to gather information on interactions of medications employed in bladder dysfunctions, the English language reports published in the PubMed, Embase, Cochrane and CINAHL database over the years 1996-2015 were studied. Additionally, other resources, namely drugs.com, Medscape, UpToDate, Micromedex, Medical Letter, as well as Stockley Drugs Interaction electronic publication were included in the study. The analysis also covered product data sheets for particular medicinal products. Results Meals and the consumption of grapefruit juice were found to exert a diversified effect on the pharmacokinetics of drugs employed in overactive bladder syndrome therapy. Neither tolterodine, nor mirabegron interact with food and citrus fruit juice, whereas darifenacin, fesoterodine, oxybutynin and solifenacin do interact with grapefruit and others citrus fruit juice. The effects of such interactions may potentially be negative to patients. Trospium absorption is significantly decreased by food. Conclusion For selected medicines used in treating bladder dysfunctions food and grapefruit juice consumption may significantly affect efficacy and safety of the therapy. All information on the topic is likely to enhance the quality of pharmaceutical care.

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.

[Epithelial intestine cells transdifferentiate into bladder urothelium in experiments in vivo].

PubMed

Popov, B K; Zaĭchik, A M; Bud'ko, M B; Zlobina, O V; Tolkunova, E N; Zhidkova, O V; Petrov, N S

2011-01-01

The autoplastic surgery by intestine tissue has been used for reconstructive therapy of the urinary tract since the middle of the last century; however, cell mechanisms of the urothelium engraftment are still obscure. Intestine stem cells possess plasticity and presumably enable after the autoplastic surgery to transdifferentiate into mature cells of urinary tract. Using the preliminary developed in vivo model for evaluation of somatic cells transdifferentiation into urothelium, we have found that the epithelial intestine cells producing Gfp transdifferentiate into the cryoinjured bladder urothelium of the syngenetic C57BL mice. Gfp was detected in the bladder tissue of mice-recipients using reverted polymerase chain reaction, primary fluorescence and immunofluorescence, while colocalization of the Gfp and Her-4 revealing similar to urothelium staining pattern was demonstrated in a few urothelium cells by double immunohistochemical staining of the bladder tissue with specific antibodies. The results obtained suggest that epithelial intestine cells enable to transdifferentiate into bladder urothelium, however the transdifferentiation level is low and presumably can not provide full functional urothelium engraftment in the case of autoplastic bladder surgery by intestine tissue.

Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis.

PubMed

Chen, Jun-Feng; Yu, Bi-Xia; Yu, Rui; Ma, Liang; Lv, Xiu-Yi; Cheng, Yue; Ma, Qi

2017-02-01

Epirubicin (EPI) is one of the most used intravesical chemotherapy agents after transurethral resection to non-muscle invasive bladder tumors (NMIBC) to prevent cancer recurrence and progression. However, even after resection of bladder tumors and intravesical chemotherapy, half of them will recur and progress. RON is a membrane tyrosine kinase receptor usually overexpressed in bladder cancer cells and associated with poor pathological features. This study aims to investigate the effects of anti-RON monoclonal antibody Zt/g4 on the chemosensitivity of bladder cells to EPI. After Zt/g4 treatment, cell cytotoxicity was significantly increased and cell invasion was markedly suppressed in EPI-treated bladder cancer cells. Further investigation indicated that combing Zt/g4 with EPI promoted cell G1/S-phase arrest and apoptosis, which are the potential mechanisms that RON signaling inhibition enhances chemosensitivity of EPI. Thus, combing antibody-based RON targeted therapy enhances the therapeutic effects of intravesical chemotherapy, which provides new strategy for further improvement of NMIBC patient outcomes.

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

Expression of EphA2 and Ephrin A-1 in carcinoma of the urinary bladder.

PubMed

Abraham, Shaji; Knapp, Deborah W; Cheng, Liang; Snyder, Paul W; Mittal, Suresh K; Bangari, Dinesh S; Kinch, Michael; Wu, Lan; Dhariwal, Jay; Mohammed, Sulma I

2006-01-15

The EphA2 receptor tyrosine kinase is believed to play a role in tumor growth and metastasis. The clinical significance of the expression of EphA2 was observed in breast, prostate, colon, skin, cervical, ovarian, and lung cancers. The purpose of this work was to determine the expression of EphA2 and its ligand, Ephrin A-1, and E-cadherin in carcinoma of the urinary bladder, and determine EphA2 as a new target for therapy in bladder cancer. EphA2 mRNA and protein expression was investigated by reverse transcription-PCR and Western blot, respectively, in bladder cancer cell lines. In addition, the expression of EphA2, Ephrin A-1, and E-cadherin in tissues from patients with different stages of urinary bladder cancer was determined by immunohistochemistry. Furthermore, the ability of Ephrin A-1 to inhibit growth of bladder cancer cells was also investigated using an adenoviral delivery system. Western blot analysis showed high EphA2 expression in TCCSUP, T24, and UMUC-3 cell lines. In tissues, the staining intensity of EphA2 was less in normal urothelium but increased greatly in advancing stages of urothelial carcinoma (P < 0.05). Similarly, the staining intensity of Ephrin A-1 was low in normal tissues and high in cancerous tissues, but it was similar across the various stages of urothelial carcinoma (T(a)-T(4)). E-cadherin immunoreactivity decreased in urothelial cancer. Association of EphA2 and Ephrin A-1 expression was found to be significant between T(a) stage and T(1)-T(2) (P < 0.04) and T(a) and T(3)-T(4) stages (P < 0.0001). Adenovirus delivery of Ephrin A-1 inhibited proliferation of TCCSUP cells. EphA2 may serve as a novel target for bladder cancer therapy.

Chronic hematuria and localized bladder damage following combined cyclophosphamide and local radiotherapy

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

Kende, G.; Wajsman, Z.; Thomas, P.R.M.

1979-01-01

A 13-year-old white male had Ewing sarcoma of the right pubic and ischial bones. Initial therapy consisted of 5400 rads in seven weeks to the right side of the pelvis and 14 intravenous injections of cyclophosphamide (Cytoxan, CTX) at 500 mg/m/sup 2/; BCNU and Adriamycin maintenance therapy continued for a total of two years. He has now been disease-free for five years. Three months following the completion of the right pelvic radiotherapy (RT), while on intravenous CTX, severe hematuria appeared, which subsided, but at present he has continuous microscopic hematuria, as well as periodic episodes of gross hematuria. Serial cystocopiesmore » initially revealed thickening and hemorrhagic and edematous changes on the right (irradiated) side of the bladder, and recent multiple telangiectatic patches have been demonstrated as a late healing phase. This case demonstrates the additive toxicity to the bladder of CTX and RT, illustrating that the hemorrhagic cystitis can be extremely protracted lasting five years.« less

Botulinum toxin A for the Treatment of Overactive Bladder.

PubMed

Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung

2016-02-29

The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.

Advances in Therapeutic Development for Radiation Cystitis.

PubMed

Rajaganapathy, Bharathi Raja; Jayabalan, Nirmal; Tyagi, Pradeep; Kaufman, Jonathan; Chancellor, Michael B

2014-01-01

Radiation treatment for pelvic malignancies is typically associated with radiation injury to urinary bladder that can ultimately lead to radiation cystitis (RC). The late sequelae of radiation therapy may take many years to develop and include bothersome storage symptoms such as hematuria, which may be life-threatening in severe cases of hemorrhagic cystitis. Although no definitive treatment is currently available, various interventions are used for radiation and hemorrhagic cystitis including blood transfusion, bladder irrigation, intravesical instillation of substances such as alum, silver nitrate, prostaglandins or formalin, and fulguration of intravesical bleeding sites and surgery options such as supravesical urinary diversions and cystectomy. Effects of non-surgical treatments for radiation and hemorrhagic cystitis are of modest success and studies are lacking to control the effects caused by RC. When such measures have proven ineffective, use of bladder botulinum toxin injection has been reported. New therapy, such as intravesical immunosuppression with local tacrolimus formulation is being developed for the treatment of radiation hemorrhagic cystitis. © 2013 Wiley Publishing Asia Pty Ltd.

[Using autonomous electrostimulation device Erektron in treating female overactive bladder].

PubMed

Yarin, G Yu; Shelyakina, O V; Fedorenko, V N; Alekseeva, A V; Vilgelmi, I A

2016-11-01

Overactive bladder (OAB) is one of the most common syndromes of lower urinary tract dysfunction. Besides standard therapy using anticholinergic medications, comprehensive management of overactive bladder includes physiotherapy. To test the clinical effectiveness and safety of autonomous electrostimulation device "Erektron" in treating OAB in women. The study was conducted at the Urology and Gynecology Clinic of the Innovative Medical Technology Center between 25.04.2014 and 30.01.2015. It included 20 women with newly diagnosed OAB both with and without urinary urgency incontinence or urinary stress incontinence. The patients were divided into 2 groups. All patients were treated with the first line anticholinergic agent solifenacin 5 mg daily. In patients of group 1, anticholinergic therapy was administered concurrently with intravaginal electrostimulation using "Erektron" device. In both groups, the treatment resulted in positive results, but a more pronounced improvement was found in group 1 patients with mixed incontinence. Autonomous electrostimulation device MT-RV "Erektron" can be used in comprehensive management of patients with OAB, including those with stress urinary incontinence.

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)

Lin, Paul-Yann; Lin, Yung-Lun; Huang, Chin-Chin

Epidemiological studies have revealed that exposure to an arsenic-contaminated environment correlates with the incidence of bladder cancer. Bladder cancer is highly recurrent after intravesical therapy, and most of the deaths from this disease are due to invasive metastasis. In our present study, the role of inorganic arsenic in bladder carcinogenesis is characterized in a mouse model. This work provides the first evidence that inorganic arsenic in drinking water promotes N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder tissue damage, including the urothelium and submucosal layer. This damage to the bladder epithelium induced by BBN includes thickening of the submucosal layer, the loss of the glycosaminoglycanmore » layer and an increase in both the deoxyguanosine oxidation and cytosine methylation levels in the DNA. Further, when 10 ppm inorganic arsenic is combined with BBN, the number of bladder submucosal capillaries is increased. In addition, inorganic arsenic also increases the deoxyguanosine oxidation level, alters the cytosine methylation state, decreases the activities of glutathione reductase and glucose-6-phosphate dehydrogenase, decreases the protein expression of NAD(P)H quinone oxidoreductase-1 (NQO-1) and increases the protein expression of specific protein 1 (Sp1) in bladder tissues. In summary, our data reveal that inorganic arsenic in drinking water promotes the BBN-induced pre-neoplastic damage of bladder tissue in mice, and that the 8-hydroxy-2′-deoxyguanosine, 5-methylcytosine, NQO-1 protein and Sp1 protein levels may be pre-neoplastic markers of bladder tumors. -- Highlights: ► The role of inorganic arsenic in bladder carcinogenesis is characterized in mice. ► We examine the changes in the histology and biochemistry of bladder tissues. ► Inorganic arsenic enhances BBN-induced DNA oxidation while decreases BBN-induced DNA methylation in the mouse bladder. ► Inorganic arsenic alters the activities of the anti-oxidant enzymes in the mouse bladder. ► Inorganic arsenic increases Sp1 while decreases NQO-1 protein expression in the mouse whole bladder.« less

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.

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

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.

Comparative Toxicity and Dosimetric Profile of Whole-Pelvis Versus Prostate Bed-Only Intensity-Modulated Radiation Therapy After Prostatectomy

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

Deville, Curtiland, E-mail: deville@uphs.upenn.edu; Vapiwala, Neha; Hwang, Wei-Ting

2012-03-15

Purpose: To assess whether whole-pelvis (WP) intensity modulated radiation therapy (IMRT) for prostate cancer (PCa) after prostatectomy is associated with increased toxicity compared to prostate-bed only (PB) IMRT. Methods and Materials: All patients (n = 67) undergoing postprostatectomy IMRT to 70.2 Gy at our institution from January 2006 to January 2009 with minimum 12-month follow-up were divided into WP (n = 36) and PB (n = 31) comparison groups. WP patients received initial pelvic nodal IMRT to 45 Gy. Pretreatment demographics, bladder and rectal dose-volume histograms, and maximum genitourinary (GU) and gastrointestinal (GI) toxicities were compared. Logistic regression models evaluatedmore » uni- and multivariate associations between pretreatment demographics and toxicities. Results: Pretreatment demographics including age and comorbidities were similar between groups. WP patients had higher Gleason scores, T stages, and preoperative prostate-specific antigen (PSA) levels, and more WP patients underwent androgen deprivation therapy (ADT). WP minimum (Dmin) and mean bladder doses, bladder volumes receiving more than 5 Gy (V5) and V20, rectal Dmin, and PB bladder and rectal V65 were significantly increased. Maximum acute GI toxicity was Grade 2 and was increased for WP (61%) vs. PB (29%) patients (p = 0.001); there was no significant difference in acute Grade {>=}2 GU toxicity (22% WP vs. 10% PB; p = 0.193), late Grade {>=}2 GI toxicity (3% WP vs. 0% PB; p = 0.678), or late Grade {>=}2 GU toxicity (28% WP vs. 19% PB; p = 0.274) with 25-month median follow-up (range, 12-44 months). On multivariate analysis, long-term ADT use was associated with Grade {>=}2 late GU toxicity (p = 0.02). Conclusion: Despite dosimetric differences in irradiated bowel, bladder, and rectum, WP IMRT resulted only in clinically significant increased acute GI toxicity in comparison to that with PB IMRT, with no differences in GU or late GI toxicity.« less

mTORC2 activation is regulated by the urokinase receptor (uPAR) in bladder cancer.

PubMed

Hau, Andrew M; Leivo, Mariah Z; Gilder, Andrew S; Hu, Jing-Jing; Gonias, Steven L; Hansel, Donna E

2017-01-01

Mammalian target of rapamycin complex 2 (mTORC2) has been identified as a major regulator of bladder cancer cell migration and invasion. Upstream pathways that mediate mTORC2 activation remain poorly defined. Urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored membrane protein and known activator of cell-signaling. We identified increased uPAR expression in 94% of invasive human bladder cancers and in 54-71% of non-invasive bladder cancers, depending on grade. Normal urothelium was uPAR-immunonegative. Analysis of publicly available datasets identified uPAR gene amplification or mRNA upregulation in a subset of bladder cancer patients with reduced overall survival. Using biochemical approaches, we showed that uPAR activates mTORC2 in bladder cancer cells. Highly invasive bladder cancer cell lines, including T24, J82 and UM-UC-3 cells, showed increased uPAR mRNA expression and protein levels compared with the less aggressive cell lines, UROtsa and RT4. uPAR gene-silencing significantly reduced phosphorylation of Serine-473 in Akt, an mTORC2 target. uPAR gene-silencing also reduced bladder cancer cell migration and Matrigel invasion. S473 phosphorylation was observed by immunohistochemistry in human bladder cancers only when the tumors expressed high levels of uPAR. S473 phosphorylation was not controlled by uPAR in bladder cancer cell lines that are PTEN-negative; however, this result probably did not reflect altered mTORC2 regulation. Instead, PTEN deficiency de-repressed alternative kinases that phosphorylate S473. Our results suggest that uPAR and mTORC2 are components of a single cell-signaling pathway. Targeting uPAR or mTORC2 may be beneficial in patients with bladder cancer. Copyright © 2016. Published by Elsevier Inc.

Treatment of radiation-induced cystitis with hyperbaric oxygen

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

Weiss, J.P.; Boland, F.P.; Mori, H.

The effects of hyperbaric oxygen on radiation cystitis have been documented in 3 patients with radiation-induced hemorrhagic cystitis refractory to conventional therapy. Cessation of gross hematuria and reversal of cystoscopic bladder changes were seen in response to a series of hyperbaric oxygen treatments of 2 atmosphere absolute pressure for 2 hours. To our knowledge this is the first report of cystoscopically documented healing of radiation-induced bladder injury.

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy.

PubMed

Wei, Yi; Gao, Li; Wang, Lu; Shi, Lin; Wei, Erdong; Zhou, Baotong; Zhou, Li; Ge, Bo

2017-11-01

We reported a simple polydopamine (PDA)-based surface modification method to prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in terms of size, size distribution, zeta potential, transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) surface area and drug loading content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA-PEP had similar release kinetic profiles of DOX. The PDA coating well controlled DOX release and was highly sensitive to pH value. Confocal laser scanning microscopy (CLSM) showed that drug-loaded MSNs could be internalized by human bladder cancer cell line HT-1376, and DOX-loaded MSNs@PDA-PEP had the highest cellular uptake efficiency due to ligand-receptor recognition. The antitumor effects of DOX-loaded nanoparticles were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted nanocarriers DOX-loaded MSNs@PDA-PEP were significantly superior to free DOX and DOX-loaded MSNs@PDA. The novel DOX-loaded MSNs@PDA-PEP, which specifically recognized HT-1376 cells, can be used as a potential targeted drug delivery system for bladder cancer therapy.

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.

Diffusion and localization of hematoporphyrin derivative in the normal bladder wall of pig and rat after local administration

NASA Astrophysics Data System (ADS)

Bisson, Jean F.; Notter, Dominique; Labrude, P.; Vigneron, C.; Guillemin, Francois H.

1996-01-01

Photodynamic therapy (PDT) consists in the administration of a photosensitizer and subsequent irradiation of the tumor with visible light. Routinely, the photosensitizer is given intravenously (i.v.), but the major drawback of this procedure is the resulting skin photosensitivity. The goal of our study was to examine whether intravesical (i.b.) instillation of the photosensitizer for PDT of bladder cancer might be feasible in order to target the tumors and to avoid the photosensitization phenomenon. After studying the normal bladder histology of pig and rat, not much described so far, we studied the diffusion and localization of hematoporphyrin derivative (HpD) in vitro on the pig bladder and the biodistribution of HpD in vivo in the rat bladder, two and four hours after intravesical administration, by spectrofluorimetry and fluorescence microscopy. We have the following results: (1) no diffusion through the pig bladder wall was detected; (2) the penetration depth of HpD into the pig bladder wall was 450 plus or minus 44 micrometers (n equals 8), including urothelium and chorion in totality and a small part of the muscles; (3) the penetration depth of HpD into the rat bladder wall was 55 plus or minus 9 micrometer (n equals 9) after two hours and 960 plus or minus 118 micrometer (n equals 9) after four hours, corresponding respectively to the totality of the urothelium and a small part of the chorion or almost completely in the bladder wall, a small part of the adventicia being excluded. In conclusion, intravesical instillation is feasible and, as superficial bladder cancer, especially carcinoma in situ particularly occur in the urothelium or in the chorion, a bladder instillation of two hours should be advantageous.

CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation and migration

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

Zheng, Jiajia; Zhu, Xi; Zhang, Jie, E-mail: zhangjiebjmu@163.com

2014-03-28

Highlights: • We first demonstrated CXCL5 is highly expressed in human bladder tumor tissues and cells. • CXCL5 knockdown inhibits proliferation, migration and promotes apoptosis in T24 cells. • CXCL5 knockdown inhibits Snail, PI3K-AKT and ERK1/2 signaling pathways in T24 cells. • CXCL5 is critical for bladder tumor growth and progression. - Abstract: CXCL5 (epithelial neutrophil activating peptide-78) which acts as a potent chemoattractant and activator of neutrophil function was reported to play a multifaceted role in tumorigenesis. To investigate the role of CXCL5 in bladder cancer progression, we examined the CXCL5 expression in bladder cancer tissues by real-time PCRmore » and Western blot, additionally, we used shRNA-mediated silencing to generate stable CXCL5 silenced bladder cancer T24 cells and defined its biological functions. Our results demonstrated that mRNA and protein of CXCL5 is increased in human bladder tumor tissues and cell lines, down-regulation of CXCL5 in T24 cells resulted in significantly decreased cell proliferation, migration and increased cell apoptosis in vitro through Snail, PI3K-AKT and ERK1/2 signaling pathways. These data suggest that CXCL5 is critical for bladder tumor growth and progression, it may represent a potential application in cancer diagnosis and therapy.« less

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

Li, Kuiqing; Chen, Xu; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120

Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinasemore » p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway.« less

[Hemocyanins as immunostimulants].

PubMed

Del Campo, Miguel; Arancibia, Sergio; Nova, Esteban; Salazar, Fabián; González, Andrea; Moltedo, Bruno; De Ioannes, Pablo; Ferreira, Jorge; Manubens, Augusto; Becker, María Inés

2011-02-01

Hemocyanins, the giant oxygen transporter glycoproteins of diverse mollusks, are xenogenic to the mammalian immune system and they display a remarkable immuno-genicity. Therefore they are ideal non-specific immunostimulants to treat some types of cancer. They are used as an alternative therapy for superficial urinary bladder cancer (SBC), that has been traditionally treated with Bacillus Calmette-Guerin (BCG). In contrast to BCG, hemocyanins do not cause side-effects, making them ideal for long-term repetitive treatments. Hemocyanins have also been exploited as carriers to develop antibodies against hapten molecules and peptides, as carrier-adjuvants for cutting-edge vaccines against cancer, drug addiction, and infectious diseases and in the diagnosis of parasitic diseases, such as Schistosomiasis. The hemocyanin from Megathura crenulata, also known as keyhole limpet hemocyanin (KLH), has been used for over thirty years for the purposes described above. More recently, hemoc yanin from the Chilean mollusk Concholepas concholepas (CCH) has proved to be a reliable alternative to KLH, either as carrier protein, and as a likely alternative for the immunotherapy of SBC. Despite KLH and CCH differ significantly in their origin and structure, we have demonstrated that both hemocyanins stimulate the immune system of mammals in a similar way by inducing a potent Thl-polarized cellular and humoral response.

Outcomes of different protocols of pelvic floor physical therapy and anti-cholinergics in women with wet over-active bladder: A 4-year follow-up.

PubMed

Azuri, Joseph; Kafri, Rachel; Ziv-Baran, Tomer; Stav, Kobi

2017-03-01

We investigated the 4-year outcomes of three protocols of pelvic floor physical therapy and anticholinergic drug in women with wet over-active bladder (OAB). One hundred and sixty-four women were randomly allocated to one of four interventions: drug therapy (DT), bladder training (BT), pelvic floor muscle training (PFMT), or combined pelvic floor rehabilitation (CPFR) that includes BT, PFMT, and behavioral advice. The active treatment in each group lasted 3 months. Of the 132 women who completed a 1-year follow-up, 120 women (90%) responded to our questionnaires and therefore were included in this study. Outcome measures were the number of voids per day, number of urgency urinary incontinence (UUI) episodes per week, completely dry rate and Incontinence Quality of Life questionnaire (I-QOL) at 4 years. After 4 years of follow-up, the outcome measures improved significantly and equally in all four groups. The median number of UUI episodes/week dropped by 3, 1, 2, and 2 in the DT, BT, PFMT, and CPFR groups, respectively (P = ns). The dry rates were 25%, 31%, 44%, 34% in the DT, BT, PFMT, and CPFR groups, respectively (P = ns). I-QOL scores improved significantly in all four groups. Women who suffer from wet-OAB may experience the same degree of long-term improvement following various pelvic floor physical therapy protocols as they would from drug therapy. Neurourol. Urodynam. 36:755-758, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

G-protein-coupled receptor 137 accelerates proliferation of urinary bladder cancer cells in vitro.

PubMed

Du, Yiheng; Bi, Wenhuan; Zhang, Fei; Wu, Wenbo; Xia, Shujie; Liu, Haitao

2015-01-01

Urinary bladder cancer is a worldwide concern because of its level of incidence and recurrence. To search an effective therapeutic strategy for urinary bladder cancer, it is important to identify proteins involved in tumorigenesis that could serve as potential targets for diagnosis and treatment. G-protein-coupled receptors (GPRs) constitute a large protein family of receptors that sense molecules outside the cell and activate signal transduction pathways and cellular responses inside the cell. GPR137 is a newly discovered human gene encoding orphan GPRs. In this study, we aimed to investigate the physiological role of GPR137 in urinary bladder cancer. The effect of GPR137 on cell growth was examined via an RNA interference (RNAi) lentivirus system in two human urinary bladder cancer cell lines BT5637 and T24. Lentivirus-mediated RNAi could specifically suppressed GPR137 expression in vitro, resulting in alleviated cell viability and impaired colony formation, as well as blocks G0/G1 and S phases of the cell cycle. These results suggested GPR137 as an essential player in urinary bladder cancer cell growth, and it may serve as a potential target for gene therapy in the treatment of urinary bladder cancer. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

Tissue responses to hexyl 5-aminolevulinate-induced photodynamic treatment in syngeneic orthotopic rat bladder cancer model: possible pathways of action

NASA Astrophysics Data System (ADS)

Arum, Carl-Jørgen; Gederaas, Odrun A.; Larsen, Eivind L. P.; Randeberg, Lise L.; Hjelde, Astrid; Krokan, Hans E.; Svaasand, Lars O.; Chen, Duan; Zhao, Chun-Mei

2011-02-01

Orthotopic bladder cancer model in rats mimics human bladder cancer with respect to urothelial tumorigenesis and progression. Utilizing this model at pT1 (superficial stage), we analyze the tissue responses to hexyl 5-aminolevulinate-induced photodynamic therapy (HAL-PDT). In comparison to untreated rats, HAL-PDT causes little change in tumor-free rat bladder but induces inflammatory changes with increased lymphocytes and mononuclear cell infiltration in rat bladders with tumor. Immunohistochemistry reveals that HAL-PDT is without effect on proliferating cell nuclear antigen expression within the tumor and increases caspase-3 expression in both normal urothelium and the tumor. Transmission electron microscopy reveals severe mitochondrial damage, formations of apoptotic bodies, vacuoles, and lipofuscin bodies, but no microvillus-formed niches in HAL-PDT-treated bladder cancer rats. Bioinformatics analysis of the gene expression profile indicates an activation of T-cell receptor signaling pathway in bladder cancer rats without PDT. HAL-PDT increases the expression of CD3 and CD45RA in the tumor (determined by immunohistochemistry). We suggest that pathways of action of HAL-PDT may include, at least, activations of mitochondrial apoptosis and autophagy, breakdown of cancer stem cell niches, and importantly, enhancement of T-cell activation.

Contact laser prostatectomy in a patient on chronic anticoagulation

NASA Astrophysics Data System (ADS)

Mueller, Edward J.

1995-05-01

The `gold standard' therapy for patients with symptomatic bladder outlet obstruction secondary to benign prostatic hyperplasia has always been electrocautery TURP. However, in patients with medical problems requiring chronic anticoagulation, this procedure is contraindicated due to the extreme risk of hemorrhage, both during the procedure and the immediate post operative period. With the recent development of contact laser prostatectomy the patient on chronic anticoagulation can safely undergo the procedure. Herein, I present a case of a 60 year old with significant bladder outlet obstruction yielding an AUA symptom score of 18. The patient had a history of multiple episodes of deep venous thrombosis of the left leg with three prior pulmonary emboli. He was maintained on chronic anticoagulation with alternating days of 3.5 mg. and 5.0 mg. of warfarin sodium (coumadin). Preoperative cystoscopy showed a 4 cm prostatic fossa obstructed by tri-lobar hypertrophy, with large kissing lateral lobes and visual obstruction from the verumontanum. The patient underwent a contact laser prostatectomy with the SLT Nd:YAG laser at 50 watts. There was minimal bleeding both during the procedure and in the immediate postoperative period. At three months post-op the AUA symptom score had decreased to 2. This case demonstrated that contact laser prostatectomy can be safely and effectively performed in patients on chronic anticoagulation.

Additional low-dose antimuscarinics can improve overactive bladder symptoms in patients with suboptimal response to beta 3 agonist monotherapy

PubMed Central

Shin, Jung Hyun; Kim, Aram

2017-01-01

Purpose We aimed to assess the patient-reported outcome (PRO) and efficacy of add-on low-dose antimuscarinic therapy in over-active bladder (OAB) patients with suboptimal response to 4-week treatment with beta 3 agonist monotherapy (mirabegron, 50 mg). Materials and Methods We enrolled OAB patients with 4-week mirabegron (50 mg) treatment if the patients' symptoms improved, but not to a satisfactory extent (patient perception of bladder condition [PPBC] ≥4). Enrolled patients had 8-week low-dose antimuscarinics add-on therapy (propiverine HCl, 10 mg). Patients recorded 3-day voiding diary at screening, enrollment (after 4 weeks of mirabegron monotherapy) and after 8 weeks of add-on therapy. We assessed the change of PRO (PPBC) as a primary end point and the efficacy of add-on therapy (change of frequency, urgency, urinary urgency incontinence [UUI] based on voiding diary) as a secondary end point. Results Thirty patients (mean age, 62.3±12.8 years; mean symptom duration, 16.0±12.3 months) were finally enrolled in the study. The mean PPBC value was 4.3±0.4 after mirabegron monotherapy, and decreased to 3.2±1.0 after 8-week add-on therapy. The mean urinary frequency decreased from 10.1±3.1 to 8.8±3, the mean number of urgency episodes decreased from 3.6±1.6 to 1.8±1.2 and the number of urgency incontinence episodes decreased from 0.7±1.0 to 0.2±0.5 after add-on therapy. No patients had event of acute urinary retention and three patients complained of mild dry mouth after add-on therapy. Conclusions Add-on therapy of low-dose antimuscarinics exhibits good efficacy and safety in patients with suboptimal response after 4-week of mirabegron (50 mg) monotherapy. PMID:28681036

Additional low-dose antimuscarinics can improve overactive bladder symptoms in patients with suboptimal response to beta 3 agonist monotherapy.

PubMed

Shin, Jung Hyun; Kim, Aram; Choo, Myung-Soo

2017-07-01

We aimed to assess the patient-reported outcome (PRO) and efficacy of add-on low-dose antimuscarinic therapy in over-active bladder (OAB) patients with suboptimal response to 4-week treatment with beta 3 agonist monotherapy (mirabegron, 50 mg). We enrolled OAB patients with 4-week mirabegron (50 mg) treatment if the patients' symptoms improved, but not to a satisfactory extent (patient perception of bladder condition [PPBC] ≥4). Enrolled patients had 8-week low-dose antimuscarinics add-on therapy (propiverine HCl, 10 mg). Patients recorded 3-day voiding diary at screening, enrollment (after 4 weeks of mirabegron monotherapy) and after 8 weeks of add-on therapy. We assessed the change of PRO (PPBC) as a primary end point and the efficacy of add-on therapy (change of frequency, urgency, urinary urgency incontinence [UUI] based on voiding diary) as a secondary end point. Thirty patients (mean age, 62.3±12.8 years; mean symptom duration, 16.0±12.3 months) were finally enrolled in the study. The mean PPBC value was 4.3±0.4 after mirabegron monotherapy, and decreased to 3.2±1.0 after 8-week add-on therapy. The mean urinary frequency decreased from 10.1±3.1 to 8.8±3, the mean number of urgency episodes decreased from 3.6±1.6 to 1.8±1.2 and the number of urgency incontinence episodes decreased from 0.7±1.0 to 0.2±0.5 after add-on therapy. No patients had event of acute urinary retention and three patients complained of mild dry mouth after add-on therapy. Add-on therapy of low-dose antimuscarinics exhibits good efficacy and safety in patients with suboptimal response after 4-week of mirabegron (50 mg) monotherapy.

Experience with 100 consecutive simultaneous kidney-pancreas transplants with bladder drainage.

PubMed Central

Sollinger, H W; Knechtle, S J; Reed, A; D'Alessandro, A M; Kalayoglu, M; Belzer, F O; Pirsch, J

1991-01-01

From December 1985 to December 1989, 100 consecutive simultaneous pancreas-kidney (SPK) transplants were performed at the University of Wisconsin Hospital and Clinics. Bladder drainage technique was used for all grafts. One- and three-year patient survival was 93% and 90%; kidney survival, 90% and 85%; and pancreas survival, 86% and 84%. Quadruple immunosuppressive therapy was used in all patients and consisted of either MALG or OKT3 induction, and cyclosporine, prednisone, and azathioprine maintenance therapy. OKT3 induction therapy was used in 42 patients and Minnesota antilymphocyte globule in 58 patients, with equivalent results except for more opportunistic infection with OKT3. The duodenal button technique was used in the first 17 patients with systemic anticoagulation and was associated with significantly more postoperative bleeding and infection compared with the duodenal segment technique. The most common surgical complication of the duodenal segment technique was urine leak (13%), which usually occurred from the distal duodenal segment. The most common urologic complication of bladder drainage was hematuria (13%), which was usually self-limited. Within 6 months of transplantation, 84% of patients developed urinary tract infections, and 25% of patients had opportunistic infections. The surgical techniques and immunosuppressive methods used in this series are reviewed, and strategies for preventing medical and surgical complications are outlined. PMID:1741650

Do we have biomarkers to predict response to neoadjuvant and adjuvant chemotherapy and immunotherapy in bladder cancer?

PubMed Central

Wezel, Felix; Vallo, Stefan

2017-01-01

Radical cystectomy (RC) is the standard of care treatment of localized muscle-invasive bladder cancer (BC). However, about 50% of patients develop metastases within 2 years after cystectomy. Neoadjuvant cisplatin-based chemotherapy before cystectomy improves the overall survival (OS) in patients with muscle-invasive BC. Pathological response to neoadjuvant treatment is a strong predictor of better disease-specific survival. Nevertheless, some patients do not benefit from chemotherapy. The identification of reliable biomarkers enabling clinicians to identify patients who might benefit from chemotherapy is a very important clinical task. An identification tool could lead to individualized therapy, optimizing response rates. In addition, unnecessary treatment with chemotherapy which potentially leads to a loss of quality of life and which might also might cause a delay of cystectomy in a neoadjuvant setting could be avoided. The present review aims to summarize and discuss the current literature on biomarkers for the prediction of response to systemic therapy in muscle-invasive BC. Tremendous efforts in genetic and molecular characterization have led to the identification of predictive candidate biomarkers in urothelial carcinoma (UC), although prospective validation is pending. Ongoing clinical trials examining the benefit of individual therapies in UC of the bladder (UCB) by molecular patient selection hold promise to shed light on this question. PMID:29354494

Anti-NGF Local Therapy for Autonomic Dysreflexia in Spinal Cord Injury

DTIC Science & Technology

2013-10-01

growth factor in the urothelium of sham treated rats, which was decreased 5 by antisense treatment (Fig. 4A) and (5) increased nerve growth...sensitization. B Figure 4. A: Antisense OND mediated suppression of acetic acid (AA) induced NGF protein expression in urothelium . AA exposure...upregulation in the bladder urothelium of SCI rats  Detection of hyperexcitability of bladder afferent neurons due to the reduction of A-type K+ channel

Biomarkers in patients treated with BCG: an update.

PubMed

Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

2014-08-01

Bacillus Calmette-Guerin (BCG) instillations are the recommended treatment for non-muscle invasive bladder cancer but high recurrence and progression rates remain after treatment. Despite patients risk stratification, BCG effectiveness remains unpredictable. A close, invasive and expensive follow up is mandatory. To improve or even replace this heavy surveillance in this high risk population, validated biomarkers were developed. To identify the useful tools for the urologist in monitoring bladder cancer patients, we reviewed the literature focusing on plasma and urinary biomarkers of BCG-therapy outcome. Articles dated from 1988 to 2013 including specific keywords (urinary bladder neoplasm, biological markers, intravesical administration, recurrence) were examined and relevant papers were selected. Before treatment initiation, genetic polymorphisms of multiple agents (cytokines, matrix-metalloproteinases) were found to become very useful to tailor therapy and monitoring. Those biomarkers belong to personalized medicine which is a topic of great interest today, but still need to be validated in cohorts from different ethnicities. During instillations, cytokines (IL-2, IL-8, IL-6/IL-10) were reported to be reliable to determine treatment response and efficacy. Further studies are needed to confirm results and standardize thresholds. After treatment, UroVysion, the FDA-approved fluorescence in situ hybridization (FISH), appeared to be the most robust marker of all the clinical parameters reviewed; but is not yet validated for BCG-treated patients. No recommendations for everyday practice can be established today, but a combination of several markers and clinicopathological characteristics may be the future. As bladder cancer diagnosis and management are evolving, practicing urologists should be aware of and utilize bladder cancer markers in clinical practice.

Artificial intelligence for predicting recurrence-free probability of non-invasive high-grade urothelial bladder cell carcinoma.

PubMed

Cai, Tommaso; Conti, Gloria; Nesi, Gabriella; Lorenzini, Matteo; Mondaini, Nicola; Bartoletti, Riccardo

2007-10-01

The objective of our study was to define a neural network for predicting recurrence and progression-free probability in patients affected by recurrent pTaG3 urothelial bladder cancer to use in everyday clinical practice. Among all patients who had undergone transurethral resection for bladder tumors, 143 were finally selected and enrolled. Four follow-ups for recurrence, progression or survival were performed at 6, 9, 12 and 108 months. The data were analyzed by using the commercially available software program NeuralWorks Predict. These data were compared with univariate and multivariate analysis results. The use of Artificial Neural Networks (ANN) in recurrent pTaG3 patients showed a sensitivity of 81.67% and specificity of 95.87% in predicting recurrence-free status after transurethral resection of bladder tumor at 12 months follow-up. Statistical and ANN analyses allowed selection of the number of lesions (multiple, HR=3.31, p=0.008) and the previous recurrence rate (>or=2/year, HR=3.14, p=0.003) as the most influential variables affecting the output decision in predicting the natural history of recurrent pTaG3 urothelial bladder cancer. ANN applications also included selection of the previous adjuvant therapy. We demonstrated the feasibility and reliability of ANN applications in everyday clinical practice, reporting a good recurrence predicting performance. The study identified a single subgroup of pTaG3 patients with multiple lesions, >or=2/year recurrence rate and without any response to previous Bacille Calmette-Guérin adjuvant therapy, that seem to be at high risk of recurrence.

Biodistribution and photodynamic effect of protoporphyrin IX in rat urinary bladders after intravesical instillation of 5-aminolaevulinic acid

NASA Astrophysics Data System (ADS)

Chang, Shi-Chung; MacRobert, Alexander J.; Bown, Stephen G.

1995-03-01

Photodynamic therapy (PDT) has considerable potential for the treatment of superficial bladder neoplasia. Complications such as scarring of the detrusor muscle and prolonged cutaneous photosensitivity may be reduced by using the new photosensitizer precursor, 5- aminolaevulinic acid (ALA). After instillation of ALA, the concentration, pH, and time of bladder retention of ALA solution were found to be the key factors to a satisfactory PpIX buildup in the mucosa. The optimum PpIX fluorescence intensity ratio between mucosa and muscle layer is 10 to 1 with a pH 5.5, 1% ALA solution retained for 5 hours. Higher concentration resulted in more mucosal PpIX formation, but less selectivity. Unbuffered ALA was unsuitable for bladder instillation. Two days after laser treatment with 25 J/cm2 at 630 nm with optimal sensitization, typical histological findings were urothelial sloughing and lamina propria edema without obvious muscle damage. After 7 days, recovery of the urothelium was almost complete and fibroblast infiltration was minimal. ALA induced PpIX after bladder instillation may be an appropriate photosensitizer for future management of superficial bladder cancer.

Keratin expression profiling of transitional epithelium in the painful bladder syndrome/interstitial cystitis.

PubMed

Laguna, Pilar; Smedts, Frank; Nordling, Jörgen; Horn, Thomas; Bouchelouche, Kirsten; Hopman, Anton; de la Rosette, Jean

2006-01-01

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a severely debilitating condition. Its cause is poorly understood; therapy is symptomatic and often unsuccessful. To study urothelial involvement, we characterized the keratin phenotype of bladder urothelium in 18 patients with PBS/IC using a panel of 11 keratin antibodies recognizing simple keratins found in columnar epithelia (keratins 7, 8, 18, and 20) and keratins associated with basal cell compartments of squamous epithelia (keratins 5, 13, 14, and 17). We also tested 2 antibodies recognizing more than 1 keratin also directed against basal cell compartments of squamous epithelia (D5/16 B4 and 34betaE12). Bladder urothelium in PBS/IC showed distinct differences in the profiles of keratins 7, 8, 14, 17, 18, and 20 compared with literature reports for normal bladder urothelium. These were characterized by a shift from the normal bladder urothelial keratin phenotype to a more squamous keratin profile, despite the lack of morphologic evidence of squamous epithelial differentiation and a loss of compartmentalization of keratin expression. The severity of these changes varied between biopsy specimens. Whether these changes are primary or secondary to another underlying condition remains to be determined.

[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.

Lymphocytic infiltration of bladder after local cellular immunotherapy.

PubMed

Ingram, M; Bishai, M B; Techy, G B; Narayan, K S; Saroufeem, R; Yazan, O; Marshall, C E

2000-01-01

This is a case report of a patient who received cellular immunotherapy, in the form of local injections of autologous stimulated lymphocytes (ASL) into individual tumors in the urinary bladder. A major consideration in cellular immunotherapy being the ability of immune cells to reach all target areas, we hypothesized that direct delivery of effector cells into individual bladder tumors might assure such access. ASL were generated by exposing the patient's PBL to phytohemagglutinin and culturing them in the presence of IL-2 to expand the population. ASL were injected into the base of individual bladder tumors three times at intervals of 3 weeks. The patient died of a myocardial infarct, unrelated to cell therapy, 20 days after the third injection. An autopsy was performed. Histological sections of the bladder showed extensive lymphocytic infiltration of virtually the entire organ. No conclusions about the therapeutic efficacy of local immunotherapy using ASL are possible. Nevertheless, the observations reported, taken together with reports of therapeutic efficacy of other immunotherapy regimens in the management of bladder cancer, suggest that ready access of stimulated lymphocytes to all regions of the organ may account, in part, for the relatively high rate of therapeutic success reported for various immunotherapy regimens for this malignancy.

Image-Guided Transvesicular Drainage of Pelvic Fluid Collections: A Safe and Effective Alternative Approach.

PubMed

Ayyagari, Raj R; Yeh, Cliff; Arici, Melih; Mojibian, Hamid; Reiner, Eric; Pollak, Jeffrey S

2016-05-01

To evaluate the safety and efficacy of percutaneous transvesicular drainage of pathologic pelvic fluid collections, a series of 15 patients who underwent 16 transvesicular drainage catheter placements was retrospectively reviewed. All patients had collections suspicious for infection that were posterior to the bladder or superior to the bladder behind loops of bowel, and were otherwise inaccessible. All 15 collections were percutaneously accessed via the bladder with standard drainage catheters. All collections resolved completely with no complications. Percutaneous transvesicular drainage was a safe and effective technique in this series, and can be considered when no direct percutaneous access routes are available. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

KTP laser selective vaporization of the prostate in the management of urinary retention due to BPH

NASA Astrophysics Data System (ADS)

Kleeman, M. W.; Nseyo, Unyime O.

2003-06-01

High-powered photoselective vaporization of the prostate (PVP) is a relatively new addition in the armamentarium against bladder outlet obstruction due to BPH. With BPH, the prostate undergoes stromal and epithelial hyperplasia, particularly in the transitional zone, mediated by dihydrotestosterone (DHT). This periurethral enlargement can compress the prostatic urethra leading to bladder outlet obstruction and eventually urinary retention. Treatment of uncomplicated symptomatic BPH has evolved from the standard transurethral resection of the prostate (TURP) to multiple medical therapies and the putative minimally invasive surgical procedures. These include microwave ablation, needle ablation, balloon dilation, stents, as well as fluid based thermo-therapy, ultrasound therapy and cryotherapy. Different forms of lasers have been applied to treat BPH with variable short and long term benefits of urinary symptoms. However, the controversy remains about each laser regarding its technical applicability and efficacy.

Effects of intravesical dexpanthenol use on lipid peroxidation and bladder histology in a chemical cystitis animal model.

PubMed

Bayrak, Omer; Seckiner, Ilker; Solakhan, Mehmet; Karakok, Metin; Erturhan, Sakip M; Yagci, Faruk

2012-05-01

To demonstrate the effects of intravesical dexpanthenol use on bladder histology and lipid peroxidation in a chemical cystitis animal model. Thirty-five New Zealand rabbits were divided into 3 groups. Cystitis was conducted with transurethral intravesical hydrochloric acid instillation on the subjects in groups I and II. Then, Group I subjects were transurethrally administered intravesical dexpanthenol therapy twice a week, Group II subjects were given only intravesical isotonic NaCl instillation, and Group III subjects were administered intravesical isotonic NaCl instillation without conducting chemical cystitis to create the same stress. Treatment schemes of all groups were arranged in the same manner. After 6-week therapy, the rabbits were sacrificed and histopathologic investigations were carried out to demonstrate changes in the urinary bladder. Serum and tissue malondialdehyde (MDA) values were examined to investigate the effect of dexpanthenol on lipid peroxidation. We observed that the basal membrane and mucosal integrity were maintained, inflammatory cells were suppressed, and MDA levels decreased in group I, which received dexpanthenol therapy. However, it was also observed that mucosal integrity was spoiled, numerous inflammatory cells were accumulated, and MDA levels were significantly increased in group II, which was administered isotonic NaCl. In light of our findings, intravesical dexpanthenol therapy could be a new therapeutic approach in the treatment of interstitial cystitis because of its low cost and acceptable side effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Novel [corrected] medical management of primary bladder endometriosis with dienogest: a case report.

PubMed

Takagi, H; Matsunami, K; Ichigo, S; Imai, A

2011-01-01

Because of its low incidence, medical treatment of has not yet been well established although surgical excision is generally considered effective. We report the first case of primary bladder endometriosis successfully managed with a novel progestin dienogest. A 39-year-old woman, nulligravida, presented with lower urinary tract symptoms, especially during menstruation. Cystoscopy, with subsequent cold cup biopsy, revealed a solitary submucosal mass (2 x 2 cm) in the bladder on the posterior wall; histopathology revealed the diagnosis of extraperitoneal endometriosis. MRI and laparoscopy confirmed no peritoneal endometriosis implants or adenomyosis. She was treated with oral 2 mg/day dienogest for six months. The measurable lesion exhibited a remarkable reduction in its size, accompanied with immediate relief of the lesion-related symptoms. At one year after medication cessation, she is well and symptom-free. Dienogest may be a novel conservative alternative for bladder endometriosis, in particular for women who wish to avoid surgical intervention.

Physiotherapy and behavior therapy for the treatment of overactive bladder syndrome: a prospective cohort study.

PubMed

Wolz-Beck, Martina; Reisenauer, Christl; Kolenic, Giselle E; Hahn, Sabine; Brucker, Sara Y; Huebner, Markus

2017-05-01

To determine the efficacy of physiotherapy and behavior therapy and to find specific subgroups of women with overactive bladder syndrome that might gain increased benefit from this therapy. Women with ≥10 micturitions per 24-h period were included. Six to nine therapy sessions were held within a 14-day interval. Efficacy end point was a reduction in micturitions and in episodes of nocturia. Secondary outcomes included ICIQ-OAB, ICIQ-OABqol and visual analog scales. Follow-up was 6 months. Levene test, Student's t test, Pearson´s and Spearman's correlations were utilized as well as the Friedman test and a multivariable-multilevel model. 32 women were included. Mean age was 51 ± 15.9 (years ± standard deviation, sd). Mean body mass index (BMI) was 24.4 ± 4.8 (kg/m 2  ± sd). There was a 22.9% reduction in the number of micturitions per 24 h (11.7 ± 1.6 vs. 9.0 ± 1.3 p < 0.001), a 21.3% reduction during the day (10.3 ± 1.4 vs. 8.1 ± 1.1 p < 0.001) and a 34.7% reduction in episodes of nocturia (1.5 ± 1.0 vs. 1.0 ± 0.8 p = 0.026). Both ICIQ-OAB (8.7 ± 2.3 vs. 5.8 ± 2.7 vs. 6.3 ± 3.3 p < 0.001) and ICIQ-OABqol (73.4 ± 25.9 vs. 47.5 ± 14.5 vs. 47.7 ± 18.6 p < 0.001) questionnaires as well as VAS (7.5 ± 1.4 vs. 4.1 ± 2.4 vs. 4.2 ± 2.7 p < 0.001) showed significant improvement persisting in the 6-month follow-up. In addition, in a multivariable model controlling for age, women who were overactive bladder syndrome therapy naïve responded significantly better than those who had already been under therapy (p < 0.001). This study shows the efficacy of physiotherapy and behavior therapy in women with overactive bladder syndrome with a post-therapy effect especially for women with no prior treatment.

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

Effects of low energy shock wave therapy on inflammatory moleculars, bladder pain, and bladder function in a rat cystitis model.

PubMed

Wang, Hung-Jen; Lee, Wei-Chia; Tyagi, Pradeep; Huang, Chao-Cheng; Chuang, Yao-Chi

2017-08-01

Low energy shock wave (LESW) is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. We examined the effects of LESW on the expression of inflammatory molecules, pain behavior, and bladder function in a rat cystitis model. Control and experimental animals were injected with saline or cyclophosphamide (CYP; 75 mg/kg intraperitoneally) on day 1 and 4. After lower midline incision, the bladders were exposed to LESW (300 pulses, 0.12 mJ/mm 2 ) or sham operation on day 2. In study 1 (N = 12, 4 for each group), the nociceptive effects of CYP were evaluated for 30 min by behavioral assessment on day 4 one hour after CYP injection. In study 2 (N = 21, 7 for each group), continuous cystometry (CMG) was performed on day 8. The bladder was harvested after behavioral assessment or CMG for histology and Western blotting. CYP-induced upregulation of COX2 and IL6 expression, caused pain behavior (eye closing and hypolocomotion), and bladder inflammation was noted on days 4 and 8 along with bladder hyperactivity. LESW treatment reduced pain behavior and downregulated the NGF expression (33.3%, P < 0.05) on day 4 and IL6 (40.9%, P < 0.05). LESW treatment suppressed bladder overactivity (intercontraction interval 77.8% increase, P < 0.05) by decreasing inflammation and COX2 (38.6%, P < 0.05) expression and NGF expression (25.2%, P = 0.0812). CYP-induced bladder pain, inflammation, and overactivity involves activation of IL6, NGF, and COX2 expression. These changes are suppressed by LESW, indicating it as a potential candidate for relieving bladder inflammatory conditions and overactivity. © 2016 Wiley Periodicals, Inc.

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.

SU-E-J-44: Design a Platform and Phantom Model for Photoacoustic Imaging in Combination with CT

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

Sick, J; Alsanea, F; Rancilio, N

2014-06-01

Purpose: Our (long-term) objective is to develop a US manipulator that will provide in situ radiation response and image-guided therapy for bladder cancer based on photoacoustic molecular imaging. Methods: A platform was devised to provide a reproducible positional frame of reference for targeting anatomic structure between MDCT and US scans, in lieu of CBCT, and to fuse photoacoustic molecular imaging. US and photoacoustic scans are taken of a patient while in the CT scanner and IRMT. Through co-registration, based on anatomical positions, we identified a common coordinate system to be used in Eclipse. A bladder phantom was constructed to validatemore » anatomical tracking via US and photoacoustic imaging. We tested the platform using phantom model to demonstrate validity once moved from the CT couch to the linear accelerator couch. Results: This platform interlocks with Varian exact couch index points for reproducibility of positioning. Construction from low Z material and sized appropriately to fit in CT/IMRT gantry. Error in conversion from cylindrical coordinates of the manipulator to X, Y, Z coordinates of the treatment couch was less than 1mm. We measured the bladder size in 3 different directions in both Eclipse from the CT and Acuson from US. The error was less than 2mm in all directions. CT and US images were co-registered in MATLAB. Co-registration of photoacoustic images is still being developed. Conclusion: For Linear Accelerators without on board imaging, MV portal images are not a viable option for the localization of soft tissue anatomy. We believe our manipulator provides an alternative using US imaging, which will be examined in an upcoming clinical trial. We plan to examine the value of hypoxia guided treatment through photoacoustic imaging during this trial.« less

Basic mechanisms of urgency: roles and benefits of pharmacotherapy.

PubMed

Michel, Martin Christian; Chapple, Christopher R

2009-12-01

Since urgency is key to the overactive bladder syndrome, we have reviewed the mechanisms underlying how bladder filling and urgency are sensed, what causes urgency and how this relates to medical therapy. Review of published literature. As urgency can only be assessed in cognitively intact humans, mechanistic studies of urgency often rely on proxy or surrogate parameters, such as detrusor overactivity, but these may not necessarily be reliable. There is an increasing evidence base to suggest that the sensation of ‘urgency’ differs from the normal physiological urge to void upon bladder filling. While the relative roles of alterations in afferent processes, central nervous processing, efferent mechanisms and in intrinsic bladder smooth muscle function remain unclear, and not necessarily mutually exclusive, several lines of evidence support an important role for the latter. A better understanding of urgency and its causes may help to develop more effective treatments for voiding dysfunction.

Synchrotron X-Ray Fluorescence Microscopy of Gallium in Bladder Tissue following Gallium Maltolate Administration during Urinary Tract Infection

PubMed Central

Sampieri, Francesca; Chirino, Manuel; Hamilton, Don L.; Blyth, Robert I. R.; Sham, Tsun-Kong; Dowling, Patricia M.; Thompson, Julie

2013-01-01

A mouse model of cystitis caused by uropathogenic Escherichia coli was used to study the distribution of gallium in bladder tissue following oral administration of gallium maltolate during urinary tract infection. The median concentration of gallium in homogenized bladder tissue from infected mice was 1.93 μg/g after daily administration of gallium maltolate for 5 days. Synchrotron X-ray fluorescence imaging and X-ray absorption spectroscopy of bladder sections confirmed that gallium arrived at the transitional epithelium, a potential site of uropathogenic E. coli infection. Gallium and iron were similarly but not identically distributed in the tissues, suggesting that at least some distribution mechanisms are not common between the two elements. The results of this study indicate that gallium maltolate may be a suitable candidate for further development as a novel antimicrobial therapy for urinary tract infections caused by uropathogenic E. coli. PMID:23877680

Dual Use of Bladder Anticholinergics and Cholinesterase Inhibitors: Long-Term Functional and Cognitive Outcomes

PubMed Central

Sink, Kaycee M.; Thomas, Joseph; Xu, Huiping; Craig, Bruce; Kritchevsky, Steven; Sands, Laura P.

2015-01-01

OBJECTIVES To determine the cognitive and functional consequences of dual use of cholinesterase inhibitors (ChIs) and the bladder anticholinergics oxybutynin or tolterodine. DESIGN Prospective cohort study. SETTING Nursing homes (NHs) in the state of Indiana. PARTICIPANTS Three thousand five hundred thirty-six Medicaid-eligible NH residents aged 65 and older taking a ChI between January 1, 2003, and December 31, 2004. Residents were excluded if they were taking an anticholinergic other than oxybutynin or tolterodine. MEASUREMENTS Indiana Medicaid claims data were merged with data from the Minimum Data Set (MDS). Repeated-measures analyses were performed to assess the effects of dual therapy on change in cognitive function measured using the MDS Cognition Scale (MDS-COGS; scored 0–10) and change in activity of daily living (ADL) function using the seven ADL items in the MDS (scored 0–28). Potential covariates included age, sex, race, number of medications, and Charlson Comorbidity Index score. RESULTS Three hundred seventy-six (10.6%) residents were prescribed oxybutynin or tolterodine concomitantly with a ChI. In residents in the top quartile of ADL function, ADL function declined an average of 1.08 points per quarter when not taking bladder anticholinergics (ChI alone), compared with 1.62 points per quarter when taking dual therapy, a 50% greater rate in quarterly decline in ADL function (P =.01). There was no excess decline attributable to dual therapy in MDS-COGS scores or in ADL function for residents who started out with lower functioning. CONCLUSION In higher-functioning NH residents, dual use of ChIs and bladder anticholinergics may result in greater rates of functional decline than use of ChIs alone. The MDS-COGS may not be sensitive enough to detect differences in cognition due to dual use. PMID:18384584

The health economics of bladder cancer: an updated review of the published literature.

PubMed

Yeung, Christina; Dinh, Tuan; Lee, Joseph

2014-11-01

The purpose of this paper is to provide a current view of the economic burden of bladder cancer, with a focus on the cost effectiveness of available interventions. This review updates a previous systematic review and includes 72 new papers published between 2000 and 2013. Bladder cancer continues to be one of the most common and expensive malignancies. The annual cost of bladder cancer in the USA during 2010 was $US4 billion and is expected to rise to $US5 billion by 2020. Ten years ago, urinary markers held the potential to lower treatment costs of bladder cancer. However, subsequent real-world experiments have demonstrated that further work is necessary to identify situations in which these technologies can be applied in a cost-effective manner. Adjunct cytology remains a part of diagnostic standard of care, but recent research suggests that it is not cost effective due to its low diagnostic yield. Analysis of intravesical chemotherapy after transurethral resection of bladder tumor (TURBT), neo-adjuvant therapy for cystectomy, and robot-assisted laparoscopic cystectomy suggests that these technologies are cost effective and should be implemented more widely for appropriate patients. The existing literature on the cost effectiveness of bladder cancer treatments has improved substantially since 2000. The body of work now includes many new models, registry analyses, and real-world studies. However, there is still a need for new implementation guidelines, new risk modeling tools, and a better understanding of the empirical burden of bladder cancer.

Pharmacotherapy for benign prostatic hyperplasia.

PubMed Central

Narayan, P; Indudhara, R

1994-01-01

Benign prostatic hyperplasia is a benign neoplasm of the prostate seen in men of advancing age. Microscopic evidence of the disorder is seen in about 70% of men by 70 years of age, whereas symptoms requiring some form of surgical intervention occur in 30% of men during their lifetime. Although the exact cause of benign prostatic hyperplasia is not clear, it is well recognized that high levels of intraprostatic androgens are required for the maintenance of prostatic growth. In recent years, extensive surveys of patients undergoing transurethral resection of the prostate reveal an 18% incidence of morbidity that has essentially not changed in the past 30 years. This procedure is also the second highest reimbursed surgical therapy under Medicare. These findings have resulted in an intensive search for alternative therapies for prostatic hyperplasia. An alternative that has now been well defined is the use of alpha-adrenergic blockers to relax the prostatic urethra. This is based on findings that a major component of benign prostatic hyperplasia symptoms is spasm of the prostatic urethra and bladder neck, which is mediated by the alpha-adrenergic nerves. A second approach is to block androgens involved in maintaining prostate growth. Several such drugs are now available for clinical use, and we discuss their side effects and use. We also include the newer recommendations on evaluating benign prostatic hyperplasia that are cost-effective yet comprehensive. Images PMID:7528957

Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder? ICI-RS 2014.

PubMed

Apostolidis, Apostolos; Rahnama'i, Mohammad S; Fry, Christopher; Dmochowski, Roger; Sahai, Arun

2016-02-01

The use of botulinum toxin A (BoNT/A) is commonplace now in the management of refractory overactive bladder and neurogenic detrusor overactivity (NDO). Despite one formulation now having a license, the full mechanism of action is not fully understood. Furthermore practice varies worldwide in the way the toxin is delivered to the bladder. At the ICI-RS 2014 Meeting in Bristol, UK a Think Tank session was conducted on the topic of "Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder?" This manuscript reflects the Think Tank's summary and opinion. An overview of the existing evidence and consensus regarding mechanism of action and practical aspects of BoNT/A administration was presented. Further avenues of potential research were suggested. BoNT/A effect in the bladder is complex with likely effects on both efferent and afferent nerves. The site of action is controversial with the relative contribution of the detrusor as opposed to the suburothelial effects remaining unclear and open to further studying. The classical concept of prevention of acetylcholine release in the bladder is not supported by a wealth of evidence on neurotransmitters although co-localization studies have suggested cholinergic nerves are the most affected by BoNT/A. There is more robust evidence for effects on the purinergic system and afferent desensitization and emerging evidence for central effects. A variety of technique studies were presented. OnabotlinumtoxinA has recently been studied in large phase III trials and with this there is a standardized injection technique which is trigone-sparing. The evidence for altering location of injection is mixed with some studies suggesting less voiding dysfunction in bladder base injections alone but others suggesting location of injection does not affect outcomes. Early pilot data and evidence of instillation either with electromotive drug administration (EMDA) or in liposomes were also presented as an alternative to injections. The mechanism of action of BoNT/A in the bladder is complex and not fully understood. There is emerging support for its role on afferent mechanisms. The technical aspects of the injection procedure have been standardized to a certain extent but further study is required in larger scale studies to assess minimizing voiding dysfunction, improving tolerability, and assessing alternatives to injections. © 2016 Wiley Periodicals, Inc.

Application of 1,2-diethyl-3-hydroxypyridin-4-one to enhance tissue selectivity for photodynamic therapy of the bladder

NASA Astrophysics Data System (ADS)

Chang, Shi-Chung; MacRobert, Alexander J.; Porter, John B.; Bown, Stephen G.

1995-03-01

Five-aminolaevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven to be a useful photosensitizer for photodynamic therapy (PDT). In living cells, the conversion of PpIX to photoinactive haem is catalyzed by ferrochelatase in the presence of tissue iron and inhibition of this final committed step results in increased accumulation of PpIX. The in vivo effect of a new iron chelator, 1,2-diethyl-3-hydroxypyridin-4-one (CP94), on the buildup of PpIX in different bladder layers was evaluated. In CP94 treated rats, 5 - 7 hours after intravesical instillation of ALA solution, the fluorescence intensity of PpIX in the urothelium was doubled whilst in the muscle layer it remained low at a similar level to those seen without the iron chelator. With CP94, further reduction of skin photosensitization is possible as a similar photodynamic effect on the bladder could be achieved at lower ALA concentration. The addition of CP94 seems an effective and convenient way to potentiate ALA induced PpIX tissue selectivity.

Chloroquine and hydroxychloroquine inhibit bladder cancer cell growth by targeting basal autophagy and enhancing apoptosis.

PubMed

Lin, Yi-Chia; Lin, Ji-Fan; Wen, Sheng-I; Yang, Shan-Che; Tsai, Te-Fu; Chen, Hung-En; Chou, Kuang-Yu; Hwang, Thomas I-Sheng

2017-05-01

Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7). We found that 24-hour treatment of CQ or HCQ significantly decreased the clonogenic formation in 5637 and T24 cells compared to SV-Huc-1. As human bladder cancer tumor exhibits high basal level of autophagic activities, we detected the autophagic flux in cells treated with CQ and HCQ, showing an alternation in LC3 flux in CQ- or HCQ-treated cells. Moreover, bladder cancer cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase 3/7 activities, increased level of cleaved poly(ADP-ribose) polymerase (PARP), caspase 3, and DNA fragmentation. Given these results, targeting autophagy with CQ and HCQ represents an effective cancer therapeutic strategy against human bladder cancer. Copyright © 2017. Published by Elsevier Taiwan.

Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury

DTIC Science & Technology

2013-10-01

TERMS Lower urinary tract symptoms (LUTS), spinal cord injury (SCI), Botulinum Toxin Type A and β3 adrenoceptor agonists 16. SECURITY...focused on the therapeutic benefits of β3 adrenoceptor agonists, botulinum neurotoxin type A (BTX-A) intradetrusor injections and their combination...compromised by the toxin . Thus, β3 adrenoceptor agonists in combination with BTX-A are beneficial in improving bladder function in SCI patients. 15. SUBJECT

[REASONS OF DELAYED DIAGNOSIS OF BLADDER TUBERCULOSIS].

PubMed

Kul'chavenja, E V; Holtobin, D P

2015-01-01

The fourth, terminal, stage of bladder tuberculosis (BT) manifests itself in irreversible changes and requires surgical treatment. To identify the reasons for delayed diagnosis of this urogenital tuberculosis complication. Medical history of 26 urogenital tuberculosis patients with a complicated form of stage 4 BT, referred to the Novosibirsk TB Research Institute for reconstructive surgery were analysed. In 22 patients, bladder volume ranged from 55 to 100 ml, 4 patients previously underwent cystostomy due to extremely small bladder volume. Average duration of BT hidden in the guise of "urogenital infection" was 6.2 years. Patients were treated with norfloxacin (a total of 104 courses), ciprofloxacin (86 courses), amikacin (43 courses), nitroxoline (27 courses), third generation cephalosporins (32 courses), lomefloxacin (17 courses), levofloxacin (11 courses), Amoxicillin clavulanate (4 courses), ampicillin (2 courses). It was demonstrated that all cases of BT stage 4 were iatrogenic. Irreversible debilitating complications occurred due to suboptimal therapy, primarily due to administration of amikacin and fluoroquinolones for urogenital infections, which was tuberculosis in disguise. Absence of M. tuberculosis growth does not exclude tuberculosis; pathological specimens must be further examined at least by PCR. Interventional material must be mandatory examined histologically and stained by Ziehl-Neelsen method to identify M. tuberculosis. Effective and not masking tuberculosis, optimal therapy for urogenital infections includes fosfomycin, furazidin (nitrofurantoin), gentamicin, III generation cephalosporins (in outpatient settings dispersible form of efixime should be preferable).

[Chemical peritonitis after a bladder lesion during a cesarean section. A case report and literature review].

PubMed

Castro-Cuenca, Alejandro; Ángel-Muller, Edith; González-Carrillo, Viviana Andrea

2015-02-01

This paper reviews the case of a patient who underwent a cesarean surgery and re-entered with an oral way intolerance, postprandial emesis, abdominal pain and clear-fluid exit from surgical wound. After possible bladder injury and secondary chemistry peritonitis, the patient was taken to surgery where the diagnosis was confirmed, and the correction of bladder injury as well as peritoneal lavage were performed, it antibiotic therapy for three days and the patient had satisfactory evolution. Bladder injury is a rare complication of cesarean section with an estimated incidence between 0.0016 and 0.94%; but if it is not diagnosed intraoperative it can trigger a clinical setting of secondary chemical peritonitis, due to secondary irritation of the peritoneum. Chemical peritonitis is among the classification of secondary peritonitis. Within the pathophysiology, the mechanical, chemical or bacterial stimulus generates an inflammatory reaction, with progressive generation of exudate, leukocytes and fibrin deposit, which injure mesothelial cells, disrupt the defense and maintenance of peritoneal homeostasis, triggering serious complications, which can lead to multiple organ failure and death. The chemical peritonitis should be suspected with the clinical setting and the risk factors of recent surgical history and timely management should be instituted properly with correction of the cause, antimicrobial treatment, blood volume therapy and nutritional support, which leads to a favorable outcome for the patient and improves survival with fewer complications.

Propensity Score Analysis of Radical Cystectomy Versus Bladder-Sparing Trimodal Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic.

PubMed

Kulkarni, Girish S; Hermanns, Thomas; Wei, Yanliang; Bhindi, Bimal; Satkunasivam, Raj; Athanasopoulos, Paul; Bostrom, Peter J; Kuk, Cynthia; Li, Kathy; Templeton, Arnoud J; Sridhar, Srikala S; van der Kwast, Theodorus H; Chung, Peter; Bristow, Robert G; Milosevic, Michael; Warde, Padraig; Fleshner, Neil E; Jewett, Michael A S; Bashir, Shaheena; Zlotta, Alexandre R

2017-07-10

Purpose Multidisciplinary management improves complex treatment decision making in cancer care, but its impact for bladder cancer (BC) has not been documented. Although radical cystectomy (RC) currently is viewed as the standard of care for muscle-invasive bladder cancer (MIBC), radiotherapy-based, bladder-sparing trimodal therapy (TMT) that combines transurethral resection of bladder tumor, chemotherapy for radiation sensitization, and external beam radiotherapy has emerged as a valid treatment option. In the absence of randomized studies, this study compared the oncologic outcomes between patients treated with RC or TMT by using a propensity score matched-cohort analysis. Methods Data from patients treated in a multidisciplinary bladder cancer clinic (MDBCC) from 2008 to 2013 were reviewed retrospectively. Those who received TMT for MIBC were identified and matched (for sex, cT and cN stage, Eastern Cooperative Oncology Group status, Charlson comorbidity score, treatment date, age, carcinoma in situ status, and hydronephrosis) with propensity scores to patients who underwent RC. Overall survival and disease-specific survival (DSS) were assessed with Cox proportional hazards modeling and a competing risk analysis, respectively. Results A total of 112 patients with MIBC were included after matching (56 who had been treated with TMT, and 56 who underwent RC). The median age was 68.0 years, and 29.5% had stage cT3/cT4 disease. At a median follow-up of 4.51 years, there were 20 deaths (35.7%) in the RC group (13 as a result of BC) and 22 deaths (39.3%) in the TMT group (13 as a result of BC). The 5-year DSS rate was 73.2% and 76.6% in the RC and TMT groups, respectively ( P = .49). Salvage cystectomy was performed in 6 (10.7%) of 56 patients who received TMT. Conclusion In the setting of a MDBCC, TMT yielded survival outcomes similar to those of matched patients who underwent RC. Appropriately selected patients with MIBC should be offered the opportunity to discuss various treatment options, including organ-sparing TMT.

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.

A case of large cell neuroendocrine carcinoma of the bladder with prolonged spontaneous remission

PubMed Central

Chong, Vincent; Zwi, Jonathan; Hanning, Fritha; Lim, Remy; Cadwallader, Jon

2017-01-01

Abstract Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder are rare. We present a case of a 72-year-old man who presented with back pain and acute renal failure. Ultrasound showed a soft tissue mass in the base of the bladder causing bilateral ureteric obstruction. Subsequent biopsy of this mass demonstrated neuroendocrine carcinoma. He was commenced on neoadjuvant chemotherapy (carboplatin/etoposide) and proceeded to a radical cysto-prostatectomy. Histology revealed a LCNEC involving the bladder, T4a with invasion through to adipose tissue and posteriorly at perivesical resection margins. In addition, there was a Gleason score 9 prostatic adenocarcinoma, distinct from the neuroendocrine carcinoma. Following surgery, the patient developed gross local-regional recurrence and refused further systemic therapy. However, 1 year following referral to palliative care, a further CT-PET showed complete spontaneous remission of his disease. There are only few case reports of LCNEC of the urinary bladder therefore the pathogenesis and treatment protocol are still unclear. This case report highlights the unpredictable nature of this disease. PMID:28560016

A case of large cell neuroendocrine carcinoma of the bladder with prolonged spontaneous remission.

PubMed

Chong, Vincent; Zwi, Jonathan; Hanning, Fritha; Lim, Remy; Williams, Andrew; Cadwallader, Jon

2017-05-01

Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder are rare. We present a case of a 72-year-old man who presented with back pain and acute renal failure. Ultrasound showed a soft tissue mass in the base of the bladder causing bilateral ureteric obstruction. Subsequent biopsy of this mass demonstrated neuroendocrine carcinoma. He was commenced on neoadjuvant chemotherapy (carboplatin/etoposide) and proceeded to a radical cysto-prostatectomy. Histology revealed a LCNEC involving the bladder, T4a with invasion through to adipose tissue and posteriorly at perivesical resection margins. In addition, there was a Gleason score 9 prostatic adenocarcinoma, distinct from the neuroendocrine carcinoma. Following surgery, the patient developed gross local-regional recurrence and refused further systemic therapy. However, 1 year following referral to palliative care, a further CT-PET showed complete spontaneous remission of his disease. There are only few case reports of LCNEC of the urinary bladder therefore the pathogenesis and treatment protocol are still unclear. This case report highlights the unpredictable nature of this disease.

[Neuroendocrine carcinoma of the urinary bladder. A case report].

PubMed

Aragón-Tovar, Anel Rogelio; Pineda-Rodríguez, Marco Elí; Puente-Gallegos, Francisco Edgardo; Zavala-Pompa, Angel

2014-01-01

Small cell carcinoma of the urinary bladder is an infrequent lesion. We present the case of a 68-year-old male who arrived at the emergency room with a history of 24-h gross hematuria. Imaging studies show a urinary bladder tumor with a 218 cc volume that during a 20-day period increased to 426 cc. Histopathological images with hematoxylin-eosin show an infiltrating solid mass with uneven borders. It is composed of neoplastic cells with evident nuclei predominance and scant cytoplasm (small cells). Chromogranin immunohistochemical staining shows a diffusely positive cytoplasmic granular pattern on neoplastic cells. High molecular weight cytokeratin staining shows a negative pattern on neoplastic cells along with a positive pattern on reporsurrounding normal urothelium. Tumoral mass is positive for synaptophysin and CD-56 and negative for CK-7 and CK-20. Patient therapy was based on radiation plus chemotherapy. Small cell carcinoma of the urinary bladder represents 0.35-0.70% of urinary bladder tumors. Histological and immunohistochemical identification are key elements in the diagnosis. Treatment approach is based on cisplatin-based chemotherapy plus radical cystectomy, except when metastatic disease is present.

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

PubMed

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

2013-03-01

Study Type - Therapy (cost effectiveness analysis) Level of Evidence 2a What's known on the subject? and What does the study add? Bladder cancer is one of the costliest malignancies to treat throughout the life of a patient. The most cost-effective management for low-risk non-muscle-invasive bladder cancer is not known. The current study shows that employing cystoscopic office fulguration for low-risk appearing bladder cancer recurrences can materially impact the cost-effectiveness of therapy. In a follow-up protocol where office fulguration is routinely employed for low-risk bladder cancers, peri-operative intravesical chemotherapy may not provide any additional cost-effectiveness benefit. To examine the cost-effectiveness of fulguration vs transurethral resection of bladder tumour (TURBT) with and without perioperative intravesical chemotherapy (PIC) for managing low-risk carcinoma not invading bladder muscle (NMIBC). Low-risk NMIBC carries a low progression rate, lending support to the use of office-based fulguration for small recurrences rather than traditional TURBT. A Markov state transition model was created to simulate treatment of NMIBC with vs without PIC, with recurrence treated by formal TURBT vs treatment with fulguration. Costing data were obtained from the Medicare Resource Based Relative Value Scale. Data regarding the success of PIC were obtained from the peer-reviewed literature, as were corresponding utilities for bladder cancer-related procedures. Sensitivity analyses were performed. At 5-year follow-up, a strategy of fulguration without PIC was the most cost-effective (mean cost-effectiveness = US $654.8/quality-adjusted life year), despite a lower recurrence rate with PIC. Both fulguration strategies dominated each TURBT strategy. Sensitivity analysis showed that fulguration without PIC dominated all other strategies when the recurrence rate after PIC was increased to ≥14.2% per year. Similarly, the cost-effectiveness of TURBT becomes more competitive with fulguration when the total cost of TURBT declines < US $1175. The present study shows that fulguration without PIC was the most cost-effective strategy for treating low-risk NMIBC. The effectiveness of PIC and the cost of TURBT can materially impact the cost-effectiveness of the different management strategies. These results should be considered in treatment decisions in the context of preserving oncological control. © 2012 BJU INTERNATIONAL.

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

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.

[Laparoscopic radical cystectomy with enteric urinary diversion. Alternative to open cystectomy?].

PubMed

Lucan, M; Iacob, G; Lucan, V; Măgurean, O; Elec, F; Burghelea, C; Bărbos, A

2005-01-01

Radical cystectomy is the standard therapy for invasive bladder cancer, with best oncological results compared to any other therapeutic alternative. Even if laparoscopic radical cystectomy (LRC) is a well established surgical procedure, performing the urinary diversion completely intracorporeal, is still a challenge due to technical difficulties and associated complications. The aim of our study is to present the first series of LRC with ureterosigmoidostomy. Since May 2004 were performed 7 LRC (5 males and 2 females) (Gr. A). All cases were T2N0 clinical stage. These patients were compared with a retrospective group of 50 patients who underwent open procedure (Gr. B) in term of: operative time, blood loss, analgesic requirements, and hospital stay. LRC has a longer operative time but with statistically significant lower blood loss, less analgesia, and shorter hospital stay. The resection margins of the surgical specimens were tumor free at pathologic examination. Long-term follow-up is pending. On short-term, the results of laparoscopic radical cystectomy are encouraging. When significant experience in laparoscopic surgery is lacking, surgeons should exercise caution with completely intracorporeal urinary diversion.

Using individual patient anatomy to predict protocol compliance for prostate intensity-modulated radiotherapy

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

Caine, Hannah; Whalley, Deborah; Kneebone, Andrew

If a prostate intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) plan has protocol violations, it is often a challenge knowing whether this is due to unfavorable anatomy or suboptimal planning. This study aimed to create a model to predict protocol violations based on patient anatomical variables and their potential relationship to target and organ at risk (OAR) end points in the setting of definitive, dose-escalated IMRT/VMAT prostate planning. Radiotherapy plans from 200 consecutive patients treated with definitive radiation for prostate cancer using IMRT or VMAT were analyzed. The first 100 patient plans (hypothesis-generating cohort) were examined to identifymore » anatomical variables that predict for dosimetric outcome, in particular OAR end points. Variables that scored significance were further assessed for their ability to predict protocol violations using a Classification and Regression Tree (CART) analysis. These results were then validated in a second group of 100 patients (validation cohort). In the initial analysis of the hypothesis-generating cohort, percentage of rectum overlap in the planning target volume (PTV) (%OR) and percentage of bladder overlap in the PTV (%OB) were highlighted as significant predictors of rectal and bladder dosimetry. Lymph node treatment was also significant for bladder outcomes. For the validation cohort, CART analysis showed that %OR of < 6%, 6% to 9% and > 9% predicted a 13%, 63%, and 100% rate of rectal protocol violations respectively. For the bladder, %OB of < 9% vs > 9% is associated with 13% vs 88% rate of bladder constraint violations when lymph nodes were not treated. If nodal irradiation was delivered, plans with a %OB of < 9% had a 59% risk of violations. Percentage of rectum and bladder within the PTV can be used to identify individual plan potential to achieve dose-volume histogram (DVH) constraints. A model based on these factors could be used to reduce planning time, improve work flow, and strengthen plan quality and consistency.« less

Comparison of 3 Different Teaching Methods for a Behavioral Therapy Program for Female Overactive Bladder: A Randomized Controlled Trial.

PubMed

Gezginci, Elif; Iyigun, Emine; Yilmaz, Sercan

The purpose of this study was to compare the effect of 3 instructional methods for behavioral therapy on lower urinary tract symptom (LUTS) severity and health-related quality of life (HRQOL) in women with overactive bladder. Single-center, parallel-group, randomized, clinical trial. The sample comprised 60 women diagnosed with overactive bladder. The study setting was a university-based female urology clinic in Ankara, Turkey; data were collected from November 2012 to May 2013. Eligible participants were ambulatory women 18 years or older with predominant overactive bladder and urge urinary incontinence (UI) symptoms, with or without stress UI symptoms. Subjects were randomized into 4 groups based on educational intervention; group 1 received structured verbal instruction plus a leaflet, group 2 received structured verbal instruction, group 3 received a leaflet alone, and group 4 received usual care that included unstructured verbal counseling about continence care. The primary outcome measures were Incontinence Impact Questionnaire-7 (IIQ-7) and Urinary Distress Inventory-6 (UDI-6) scores. We also measured changes in UI-specific HRQOL scores via the Urinary Incontinence Quality of Life Instrument (I-QOL). All outcomes were measured before and 6 to 8 weeks after the interventions. The Wilcoxon test was used to identify differences in LUTS severity and HRQOL before and after the educational intervention. The Kruskall-Wallis test was used to compare differences among the groups. The severity of LUTS and UI-specific quality of life assessed by the IIQ-7, UDI-6, and I-QOL scores significantly improved after training in all 4 groups (P < .05). The group that received structured verbal instruction plus an educational leaflet achieved significantly lower LUTS scores and significantly higher UI-specific HRQOL when compared to the other groups (P < .05). Findings suggest that structured verbal instruction plus educational leaflet is the most effective method of bladder training in women with overactive bladder and urge UI.

Adenoviral mediated interferon-alpha 2b gene therapy suppresses the pro-angiogenic effect of vascular endothelial growth factor in superficial bladder cancer.

PubMed

Adam, Liana; Black, Peter C; Kassouf, Wassim; Eve, Beryl; McConkey, David; Munsell, Mark F; Benedict, William F; Dinney, Colin P N

2007-05-01

Intravesical adenovirus mediated interferon-alpha gene transfer has a potent therapeutic effect against superficial human bladder carcinoma xenografts growing in the bladder of athymic nude mice. We determined whether the inhibition of angiogenesis might contribute to the antitumor effect. We treated several human urothelial carcinoma cells with adenovirus mediated interferon-alpha 2b and monitored its effects on the production of angiogenic factors using real-time reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemical analysis and a gel shift based transcription factor array. To assess the role of adenovirus mediated interferon 2b in angiogenic activity we used in vitro invasion assays and evaluated the anti-angiogenic effects of adenovirus mediated interferon gene therapy in an orthotopic murine model of human superficial bladder cancer. In adenovirus mediated interferon-alpha infected 253J B-V cells vascular endothelial growth factor was decreased and anti-angiogenic interferon-gamma inducible protein 10 was up-regulated. In contrast, the addition of as much as 100,000 IU recombinant interferon had no apparent effect on vascular endothelial growth factor production. Conditioned medium derived from adenovirus mediated interferon 2b infected 253J B-V cells greatly decreased the invasive potential of human endothelial cells and down-regulated their matrix metalloproteinase 2 expression compared to controls. Furthermore, adenovirus mediated interferon 2b blocked pro-angiogenic nuclear signals, such as the transcription factors activating protein-1 and 2, stimulating protein-1, nuclear factor kappaB and c-myb. In vivo experiments revealed significant vascular endothelial growth factor down-regulation and decreased tumor vessel density in the adenovirus mediated interferon 2b treated group compared to controls. Treatment with adenovirus mediated interferon 2b increases the angiostatic activity of the bladder cancer microenvironment. This inhibition may prove beneficial for treating superficial bladder cancer with adenovirus mediated interferon-alpha and hopefully contribute to a decreased recurrence rate of this neoplasm.

Utilization of cone-beam CT for offline evaluation of target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment.

PubMed

Paluska, Petr; Hanus, Josef; Sefrova, Jana; Rouskova, Lucie; Grepl, Jakub; Jansa, Jan; Kasaova, Linda; Hodek, Miroslav; Zouhar, Milan; Vosmik, Milan; Petera, Jiri

2012-01-01

To assess target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment and to assess possibility of safety margin reduction. Implementation of IGRT should influence safety margins. Utilization of cone-beam CT provides current 3D anatomic information directly in irradiation position. Such information enables reconstruction of the actual dose distribution. Seventeen prostate patients were treated with daily bony anatomy image-guidance. Cone-beam CT (CBCT) scans were acquired once a week immediately after bony anatomy alignment. After the prostate, seminal vesicles, rectum and bladder were contoured, the delivered dose distribution was reconstructed. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed a 1 cm safety margin. Alternative plans assuming a smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with the initial ones. Rectal and bladder volumes irradiated with doses higher than 75 Gy, 70 Gy, 60 Gy, 50 Gy and 40 Gy were analyzed. In 12% of reconstructed plans the prostate coverage was not sufficient. The prostate underdosage was observed in 5 patients. Coverage of seminal vesicles was not satisfactory in 3% of plans. Most of the target underdosage corresponded to excessive rectal or bladder filling. Evaluation of alternative plans assuming a smaller 7 mm margin revealed 22% and 11% of plans where prostate and seminal vesicles coverage, respectively, was compromised. These were distributed over 8 and 7 patients, respectively. Sufficient dose coverage of target volumes was not achieved for all patients. Reducing of safety margin is not acceptable. Initial rectal and bladder volumes cannot be considered representative for subsequent treatment.

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.

An AOP-based alternative testing strategy to predict the impact of thyroid hormone disruption on swim bladder inflation in zebrafish

EPA Science Inventory

Within the field of chemical safety assessment, there is a desire to replace costly whole organism testing with more efficient and cost-effective alternatives based on in vitro test systems. Disruption of thyroid hormone signaling via inhibition of enzymes called deiodinases is o...

Management of bladder dysfunction in Wolfram syndrome with Mitrofanoff appendicovesicostomy: long-term follow-up.

PubMed

Mozafarpour, Sarah; Kajbafzadeh, Abdol-Mohammad; Mojtahed, Ali; Mojtahed, Mohammad; Mahboubi, Hossein; Shalileh, Keivan

2015-07-01

To present the long-term outcomes of appendicovesicostomy using the Mitrofanoff principle for end-stage Wolfram bladder dysfunction as an alternative to clean intermittent self-catheterization (CIC) per urethra mainly following blindness. Twelve Wolfram patients presenting with bilateral hydroureteronephrosis and advanced bladder dysfunction were included in this study. All patients were managed initially by CIC per urethra. All of these patients became blind during follow-up and were unable to perform urethral CIC independently. Out of these patients, six patients agreed to proceed to appendicovesicostomy. Appendicovesicostomy urinary diversion using the Mitrofanoff principle was performed in these six blind patients. The rest of the patients stopped CIC or performed CIC irregularly. Severe hydroureteronephrosis and large bladders were found in all patients prior to intervention. All patients were able to conduct CIC independently through the stoma and maintained overnight bladder free drainage. In all patients with urinary diversion and CIC, the hydroureteronephrosis was reduced and renal function returned to normal. However, the non-intervention group ended with different degrees of progressive renal failure with three mortalities during the follow-up. We suggest appendicovesicostomy as a safe and lifesaving procedure for long-term management of bladder dysfunction in Wolfram syndrome particularly after progression to blindness. Copyright © 2015 Elsevier Inc. All rights reserved.

Prospective Study Delivering Simultaneous Integrated High-dose Tumor Boost (≤70 Gy) With Image Guided Adaptive Radiation Therapy for Radical Treatment of Localized Muscle-Invasive Bladder Cancer

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

Hafeez, Shaista, E-mail: Shaista.Hafeez@icr.ac.uk; The Royal Marsden National Health Service Foundation Trust, London; Warren-Oseni, Karole

Purpose: Image guided adaptive radiation therapy offers individualized solutions to improve target coverage and reduce normal tissue irradiation, allowing the opportunity to increase the radiation tumor dose and spare normal bladder tissue. Methods and Materials: A library of 3 intensity modulated radiation therapy plans were created (small, medium, and large) from planning computed tomography (CT) scans performed at 30 and 60 minutes; treating the whole bladder to 52 Gy and the tumor to 70 Gy in 32 fractions. A “plan of the day” approach was used for treatment delivery. A post-treatment cone beam CT (CBCT) scan was acquired weekly to assess intrafraction fillingmore » and coverage. Results: A total of 18 patients completed treatment to 70 Gy. The plan and treatment for 1 patient was to 68 Gy. Also, 1 patient's plan was to 70 Gy but the patient was treated to a total dose of 65.6 Gy because dose-limiting toxicity occurred before dose escalation. A total of 734 CBCT scans were evaluated. Small, medium, and large plans were used in 36%, 48%, and 16% of cases, respectively. The mean ± standard deviation rate of intrafraction filling at the start of treatment (ie, week 1) was 4.0 ± 4.8 mL/min (range 0.1-19.4) and at end of radiation therapy (ie, week 5 or 6) was 1.1 ± 1.6 mL/min (range 0.01-7.5; P=.002). The mean D{sub 98} (dose received by 98% volume) of the tumor boost and bladder as assessed on the post-treatment CBCT scan was 97.07% ± 2.10% (range 89.0%-104%) and 99.97% ± 2.62% (range 96.4%-112.0%). At a median follow-up period of 19 months (range 4-33), no muscle-invasive recurrences had developed. Two patients experienced late toxicity (both grade 3 cystitis) at 5.3 months (now resolved) and 18 months after radiation therapy. Conclusions: Image guided adaptive radiation therapy using intensity modulated radiation therapy to deliver a simultaneous integrated tumor boost to 70 Gy is feasible, with acceptable toxicity, and will be evaluated in a randomized trial.« less

History of Non-Muscle-Invasive Bladder Cancer May Have a Worse Prognostic Impact in cT2-4aN0M0 Bladder Cancer Patients Treated With Radical Cystectomy.

PubMed

Kayama, Emina; Kikuchi, Eiji; Fukumoto, Keishiro; Shirotake, Suguru; Miyazaki, Yasumasa; Hakozaki, Kyohei; Kaneko, Gou; Yoshimine, Shunsuke; Tanaka, Nobuyuki; Takahiro, Maeda; Kanai, Kunimitsu; Oyama, Masafumi; Nakajima, Yosuke; Hara, Satoshi; Monma, Tetsuo; Oya, Mototsugu

2018-04-28

To investigate whether a history of non-muscle-invasive bladder cancer (NMIBC) plays a prognostic role in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy in the era when neoadjuvant chemotherapy was established as standard therapy for MIBC. A total of 282 patients who were diagnosed with cT2-T4aN0M0 bladder cancer treated with open radical cystectomy at our institutions were included. Initially diagnosed MIBC without a history of NMIBC was defined as primary MIBC group (n = 231), and MIBC that progressed from NMIBC was defined as progressive MIBC (n = 51). The rate of cT3/4a tumors was significantly higher in the primary MIBC group than in the progressive MIBC group (P = .004). Five-year recurrence-free survival and cancer-specific survival (CSS) rates for the primary MIBC group versus progressive MIBC group were 68.2% versus 55.9% (P = .039) and 76.1% versus 61.6% (P = .005), respectively. Progressive MIBC (hazard ratio, 2.170; P = .008) was independently associated with cancer death. In the primary MIBC group, the 5-year CSS rate in patients treated with neoadjuvant chemotherapy was 85.4%, which was significantly higher than that in patients without (71.5%, P = .023). In the progressive MIBC group, no significant differences were observed in CSS between patients treated with and without neoadjuvant chemotherapy. MIBC that progressed from NMIBC had a significantly worse clinical outcome than MIBC without a history of NMIBC and may not respond as well to neoadjuvant chemotherapy. These results are informative, even for NMIBC patients treated with conservative intravesical therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Tissue engineering of bladder using vascular endothelial growth factor gene-modified endothelial progenitor cells.

PubMed

Chen, Bai-Song; Xie, Hua; Zhang, Sheng-Li; Geng, Hong-Quan; Zhou, Jun-Mei; Pan, Jun; Chen, Fang

2011-12-01

This study assessed the use of vascular endothelial growth factor (VEGF) gene-modified endothelial progenitor cells (EPCs) seeded onto bladder acellular matrix grafts (BAMGs), to enhance the blood supply in tissue-engineered bladders in a porcine model. Autologous porcine peripheral EPCs were isolated, cultured, expanded, characterized, and modified with the VEGF gene using an adenovirus vector. The expression of VEGF was examined using reverse transcriptase polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). VEGF gene modified EPCs were seeded onto BAMG and cultured for 3 days before implantation into pigs for bladder tissue engineering. A partial bladder cystectomy was performed in 12 pigs. The experimental group (6 pigs) received VEGF gene-modified EPC-seeded BAMG. The control group (6 pigs) received BAMG without seeded EPCs. The resulting tissue-engineered bladders were subject to a general and histological analysis. Microvessel density (MVD) was assessed using immunohistochemistry. The ex vivo transfection efficiency of EPCs was greater than 60%-70% when concentrated adenovirus was used. The genetically modified cells expressed both VEGF and green fluorescent protein (GFP). Scanning electron microscopy (SEM) and Masson's trichrome staining of cross sections of the cultured cells seeded to BAMG showed cell attachment and proliferation on the surface of the BAMG. Histological examination revealed bladder regeneration in a time-dependent fashion. Significant increases in MVD were observed in the experimental group, in comparison with the control group. VEGF-modified EPCs significantly enhanced neovascularization, compared with BAMG alone. These results indicate that EPCs, combined with VEGF gene therapy, may be a suitable approach for increasing blood supply in the tissue engineering of bladders. Thus, a useful strategy to achieve a tissue-engineered bladder is indicated.

The dosimetric effects of photon energy on the quality of prostate volumetric modulated arc therapy.

PubMed

Mattes, Malcolm D; Tai, Cyril; Lee, Alvin; Ashamalla, Hani; Ikoro, N C

2014-01-01

Studies comparing the dosimetric effects of high- and low-energy photons to treat prostate cancer using 3-dimensional conformal and intensity modulated radiation therapy have yielded mixed results. With the advent of newer radiation delivery systems like volumetric modulated arc therapy (VMAT), the impact of changing photon energy is readdressed. Sixty-five patients treated for prostate cancer at our institution from 2011 to 2012 underwent CT simulation. A target volume encompassing the prostate and entire seminal vesicles was treated to 50.4 Gy, followed by a boost to the prostate and proximal seminal vesicles to a total dose of 81 Gy. The VMAT plans were generated for 6-MV and 10-MV photons under identical optimization conditions using the Eclipse system version 8.6 (Varian Medical Systems, Palo Alto, CA). The analytical anisotropic algorithm was used for all dose calculations. Plans were normalized such that 98% of the planning target volume (PTV) received 100% of the prescribed dose. Dose-volumetric data from the treatment planning system was recorded for both 6-MV and 10-MV plans, which were compared for both the entire cohort and subsets of patients stratified according to the anterior-posterior separation. Plans using 10-MV photons had statistically significantly lower relative integral dose (4.1%), gradient measure (4.1%), skin Dmax (16.9%), monitor units (13.0%), and bladder V(30) (3.1%) than plans using 6-MV photons (P < .05). There was no difference in rectal dose, high-dose-region bladder dose, PTV coverage, or conformity index. The benefit of 10-MV photons was more pronounced for thicker patients (anterior-posterior separation >21 cm) for most parameters, with statistically significant differences in bladder V(30), bladder V(65), integral dose, conformity index, and monitor units. The main dosimetric benefits of 10-MV as compared with 6-MV photons are seen in thicker patients, though for the entire cohort 10-MV plans resulted in a lower integral dose, gradient measure, skin Dmax, monitor units, and bladder V(30), possibly at the expense of higher rectum V(81). Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Bacillus Calmette-Guérin enhances production and secretion of type IV collagenases in peripheral blood mononuclear cells.

PubMed

Kageyama, Y; Kawakami, S; Fujii, Y; Kihara, K; Oshima, H

1997-03-01

Intravesical administration of bacillus Calmette-Guérin (BCG) is an effective and widely accepted treatment for superficial bladder cancer. Rapid progression of the disease after BCG therapy, however, has been reported in some cases refractory to the treatment. We examined whether BCG treatment and coexistence of peripheral blood mononuclear cells (PBMCs) alter the invasive potential of bladder cancer cells. Production and secretion of two type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP 9, by PBMCs from five healthy donors or bladder cancer cells (T24, JTC 30, and JTC 32) were evaluated by gelatin zymography, western blot analysis, and northern blot analysis. Invasion of bladder cancer cells was also examined using reconstituted basement membrane (Matrigel). BCG (5, 50, and 500 micrograms/ml) had no effect on secretion of MMP 2 and MMP 9 by bladder cancer cells, but increased the production and secretion of MMP 9 by PBMCs in a dose-dependent manner. The coexistence of PBMCs increased invasion of T24 cells and BCG further enhanced the invasion. Thus, BCG promotes invasion of bladder cancer cells under certain conditions. An increase in the secretion of MMP 9 by PBMCs may account in part for the effect.

An analysis of suppressing migratory effect on human urinary bladder cancer cell line by silencing of snail-1.

PubMed

Salehi, Shima; Mansoori, Behzad; Mohammadi, Ali; Davoudian, Sadaf; Musavi Shenas, Seyed Mohammad Hossein; Shajari, Neda; Majidi, Jafar; Baradaran, Behzad

2017-12-01

Snail-1 actively participates in tumor progression, invasion, and migration. Targeting snail-1 expression can suppress the EMT process in cancer. The aim of this study was to investigate the effect of snail1 silencing on urinary bladder cancer. Quantitative RT-PCR was used to detect snail-1 and other related metastatic genes expression following siRNA knockdown in urinary bladder cancer EJ-138 cells. The protein level of snail1 was assessed by Western blot. MTT and TUNEL assays were assessed to understand if snail-1 had survival effects on EJ-138 cells. Scratch wound healing assay measured cell motility effects after snail1 suppression. The significant silencing of snail-1 reached 60pmol siRNA in a 48-h post-transfection. The result of scratch assay showed that snail-1 silencing significantly decreased Vimentin, MMPs, and CXCR4 expression; however, expression of E-cadherin was induced. The cell death assay indicated that snail-1 played the crucial role in bladder cancer survival rate. These results propose that snail-1 plays a major role in the progression and migration of urinary bladder cancer, and can be a potential therapeutic target for target therapy of invasive urinary bladder cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Carcinosarcoma of the urinary bladder and renal metastasis].

PubMed

Jlidi, R; Remadi, S; Gloor, J; Chatelanat, F

1991-01-01

A 74 year-old woman developed a polypoid tumor of the bladder which was discovered by hematuria. Upon histological examination, the tumor was shown to be a carcinosarcoma with a weak epithelial composition confirmed by immunolabelling with keratin and was composed essentially of chondrosarcomatous material. Six months later, the patient developed metastases in the kidney, in the paravertebral muscles, and in the right para-ureteral lymph nodes. There are 55 cases of carcinosarcoma of the bladder described in the literature [3, 20, 22]. It is a tumor found more frequently in men than in women, between the ages of 33 to 83. The prognosis is very gloomy .70% death rate within 2 years), but it seems to be improved by radical cystectomy and adjuvant therapy.

Bacteriophage therapy for refractory Pseudomonas aeruginosa urinary tract infection.

PubMed

Khawaldeh, A; Morales, S; Dillon, B; Alavidze, Z; Ginn, A N; Thomas, L; Chapman, S J; Dublanchet, A; Smithyman, A; Iredell, J R

2011-11-01

We describe the success of adjunctive bacteriophage therapy for refractory Pseudomonas aeruginosa urinary tract infection in the context of bilateral ureteric stents and bladder ulceration, after repeated failure of antibiotics alone. No bacteriophage-resistant bacteria arose, and the kinetics of bacteriophage and bacteria in urine suggest self-sustaining and self-limiting infection.

Neuromodulation for the Treatment of Lower Urinary Tract Symptoms.

PubMed

Yamanishi, Tomonori; Kaga, Kanya; Fuse, Miki; Shibata, Chiharu; Uchiyama, Tomoyuki

2015-09-01

Neuromodulation therapy incorporates electrical stimulation to target specific nerves that control lower urinary tract symptoms (LUTS). The objectives of this article are to review the mechanism of action, the type of neuromodulation, and the efficacy of neuromodulation mainly according to the results of randomized controlled trials. Neuromodulation includes pelvic floor electrical stimulation (ES) using vaginal, anal and surface electrodes, interferential therapy (IF), magnetic stimulation (MS), percutaneous tibial nerve stimulation, and sacral nerve stimulation (SNS). The former four stimulations are used for external periodic (short-term) stimulation, and SNS are used for internal, chronic (long-term) stimulation. All of these therapies have been reported to be effective for overactive bladder or urgency urinary incontinence. Pelvic floor ES, IF, and MS have also been reported to be effective for stress urinary incontinence. The mechanism of neuromodulation for overactive bladder has been reported to be the reflex inhibition of detrusor contraction by the activation of afferent fibers by three actions, i.e., the activation of hypogastric nerve, the direct inhibition of the pelvic nerve within the sacral cord and the supraspinal inhibition of the detrusor reflex. The mechanism of neuromodulation for stress incontinence is contraction of the pelvic floor muscles through an effect on the muscle fibers as well as through the stimulation of pudendal nerves. Overall, cure and improvement rates of these therapies for urinary incontinence are 30-50, and 60-90% respectively. MS has been considered to be a technique for stimulating nervous system noninvasively. SNS is indicated for patients with refractory overactive bladder and urinary retention. © 2015 Wiley Publishing Asia Pty Ltd.

Near infrared imaging to identify sentinel lymph nodes in invasive urinary bladder cancer

NASA Astrophysics Data System (ADS)

Knapp, Deborah W.; Adams, Larry G.; Niles, Jacqueline D.; Lucroy, Michael D.; Ramos-Vara, Jose; Bonney, Patty L.; deGortari, Amalia E.; Frangioni, John V.

2006-02-01

Approximately 12,000 people are diagnosed with invasive transitional cell carcinoma of the urinary bladder (InvTCC) each year in the United States. Surgical removal of the bladder (cystectomy) and regional lymph node dissection are considered frontline therapy. Cystectomy causes extensive acute morbidity, and 50% of patients with InvTCC have occult metastases at the time of diagnosis. Better staging procedures for InvTCC are greatly needed. This study was performed to evaluate an intra-operative near infrared fluorescence imaging (NIRF) system (Frangioni laboratory) for identifying sentinel lymph nodes draining InvTCC. NIRF imaging was used to map lymph node drainage from specific quadrants of the urinary bladder in normal dogs and pigs, and to map lymph node drainage from naturally-occurring InvTCC in pet dogs where the disease closely mimics the human condition. Briefly, during surgery NIR fluorophores (human serum albumen-fluorophore complex, or quantum dots) were injected directly into the bladder wall, and fluorescence observed in lymphatics and regional nodes. Conditions studied to optimize the procedure including: type of fluorophore, depth of injection, volume of fluorophore injected, and degree of bladder distention at the time of injection. Optimal imaging occurred with very superficial injection of the fluorophore in the serosal surface of the moderately distended bladder. Considerable variability was noted from dog to dog in the pattern of lymph node drainage. NIR fluorescence was noted in lymph nodes with metastases in dogs with InvTCC. In conclusion, intra-operative NIRF imaging is a promising approach to improve sentinel lymph node mapping in invasive urinary bladder cancer.

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

NASA Astrophysics Data System (ADS)

Nseyo, Unyime O.; Barnes, C. R.; Martin, Jessicca I.; Lamm, Donald L.; Carpenter, Cindy

2003-06-01

While 55 - 60% of newly diagnosed bladder cancers are superficial, a significant number recur as higher grade and/or stage tumors. WBPDT has been used to treat some of these recurrent superficial tumors, although its use has been associated with dose-dependent side effects. Preclinical investigation of three sequential WBPDT treatments using lower PDT dose in normal canine bladder resulted in a lack of permanent bladder contracture. Lower dose single PDT treatment has shown less durable tumor response; however, sequential WBPDT treatments with lower dose may result in durable tumor response. Five patients (4 male, 1 female), average age 65.6 (62-72 years), with recurrent or resistant superficial TCC of the bladder received two WBPDT treatments. First treatment occurred at baseline and the second treatment at 6 months. Photofrin (1.5 mg/kg) was given intravenously 48 hours prior to each cystoscopic treatment with laser light (630 nm, Coherent Lambda-Plus laser). Total light treatment doses were 1500 - 2500 Joules at baseline and 1000- 1500 Joules at 6 months. Moderate irritative bladder symptoms occurred in all patients the first week post PDT. No cases of bladder contracture have occurred. 4 of 5 patients showed no evidence of disease during the follow-up period (12 - 18 months post second treatment). One patient had a recurrence at 18 months post second treatment. Mean disease-free interval is 16.2 months. The safety of two sequential WBPDT treatments is suggested by this preliminary data. Assessment of efficacy will be possible wit a large number of patients and a longer follow-up period.

The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

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

Conde, Vanessa R.; Oliveira, Pedro F.; Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto – UMIB/ICBAS/UP

Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similarmore » in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression.« less

Simplifying the diagnosis of 4 common voiding conditions using uroflow/electromyography, electromyography lag time and voiding history.

PubMed

Van Batavia, Jason P; Combs, Andrew J; Hyun, Grace; Bayer, Agnes; Medina-Kreppein, Daisy; Schlussel, Richard N; Glassberg, Kenneth I

2011-10-01

Noninvasive uroflowmetry with simultaneous electromyography is useful to triage cases of lower urinary tract symptoms into 4 urodynamically defined conditions, especially when incorporating short and long electromyography lag times in the analysis. We determined the prevalence of these 4 conditions at a single referral institution and the usefulness of uroflowmetry with simultaneous electromyography and electromyography lag time to confirm the diagnosis, guide treatment and monitor response. We retrospectively reviewed the records of 100 consecutive normal children who presented with persistent lower urinary tract symptoms, underwent uroflowmetry with electromyography as part of the initial evaluation and were diagnosed with 1 of 4 conditions based on certain uroflowmetry/electromyography features. The conditions included 1) dysfunctional voiding--active pelvic floor electromyography during voiding with or without staccato flow, 2a) idiopathic detrusor overactivity disorder-A--a quiet pelvic floor during voiding and shortened lag time (less than 2 seconds), 2b) idiopathic detrusor overactivity disorder-B--a quiet pelvic floor with a normal lag time, 3) detrusor underutilization disorder--volitionally deferred voiding with expanded bladder capacity but a quiet pelvic floor, and 4) primary bladder neck dysfunction--prolonged lag time (greater than 6 seconds) and a depressed, right shifted uroflowmetry curve with a quiet pelvic floor during voiding. Treatment was tailored to the underlying condition in each patient. The group consisted of 50 males and 50 females with a mean age of 8 years (range 3 to 18). Dysfunctional voiding was more common in females (p <0.05) while idiopathic detrusor overactivity disorder-B and primary bladder neck dysfunction were more common in males (p <0.01). With treatment uroflowmetry parameters normalized for all types. Electromyography lag time increased in idiopathic detrusor overactivity disorder-A cases and decreased in primary bladder neck dysfunction cases. Noninvasive uroflowmetry with simultaneous electromyography offers an excellent alternative to invasive urodynamics to diagnose 4 urodynamically defined conditions. It identifies the most appropriate therapy for the specific condition and objectively monitors the treatment response. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[A case of vesicovaginal fistula repair with rectus abdominus myofascial interposition flap after radical hysterectomy and radiation therapy].

PubMed

Endo, Yuki; Iigaya, Shigeki; Nishimura, Taiji; Ishii, Naohiro; Kitaoka, Yoshihisa; Kawashima, Toshifumi; Ohara, Chiharu; Hamasaki, Tsutomu; Kondo, Yukihiro

2014-10-01

Vesicovaginal fistulas (VVFs) caused after radiation are difficult to repair and require interposition of non-irradiated, well-vascularized tissue between urinary bladder and vagina. A 48-year-old female suffered cervical cancer and underwent radical hysterectomy followed by radiation therapy which caused VVF. The initial surgical repair performed 3 months after development of VVF, was unsuccessful because of the absence of peritoneum or omentum to interpose between urinary bladder and vagina probably due to history of cesarean section and radical hysterectomy. The second surgical repair was performed 15 months after the first surgery utilizing a rectus abdominus myofascial (RAM) interposition flap. Fifteen months after the second operation, she remains free from incontinence. This case suggests that RAM is useful even for postradiation VVF.

Novel Neurostimulation of Autonomic Pelvic Nerves Overcomes Bladder-Sphincter Dyssynergia

PubMed Central

Peh, Wendy Yen Xian; Mogan, Roshini; Thow, Xin Yuan; Chua, Soo Min; Rusly, Astrid; Thakor, Nitish V.; Yen, Shih-Cheng

2018-01-01

The disruption of coordination between smooth muscle contraction in the bladder and the relaxation of the external urethral sphincter (EUS) striated muscle is a common issue in dysfunctional bladders. It is a significant challenge to overcome for neuromodulation approaches to restore bladder control. Bladder-sphincter dyssynergia leads to undesirably high bladder pressures, and poor voiding outcomes, which can pose life-threatening secondary complications. Mixed pelvic nerves are potential peripheral targets for stimulation to treat dysfunctional bladders, but typical electrical stimulation of pelvic nerves activates both the parasympathetic efferent pathway to excite the bladder, as well as the sensory afferent pathway that causes unwanted sphincter contractions. Thus, a novel pelvic nerve stimulation paradigm is required. In anesthetized female rats, we combined a low frequency (10 Hz) stimulation to evoke bladder contraction, and a more proximal 20 kHz stimulation of the pelvic nerve to block afferent activation, in order to produce micturition with reduced bladder-sphincter dyssynergia. Increasing the phase width of low frequency stimulation from 150 to 300 μs alone was able to improve voiding outcome significantly. However, low frequency stimulation of pelvic nerves alone evoked short latency (19.9–20.5 ms) dyssynergic EUS responses, which were abolished with a non-reversible proximal central pelvic nerve cut. We demonstrated that a proximal 20 kHz stimulation of pelvic nerves generated brief onset effects at lower current amplitudes, and was able to either partially or fully block the short latency EUS responses depending on the ratio of the blocking to stimulation current. Our results indicate that ratios >10 increased the efficacy of blocking EUS contractions. Importantly, we also demonstrated for the first time that this combined low and high frequency stimulation approach produced graded control of the bladder, while reversibly blocking afferent signals that elicited dyssynergic EUS contractions, thus improving voiding by 40.5 ± 12.3%. Our findings support advancing pelvic nerves as a suitable neuromodulation target for treating bladder dysfunction, and demonstrate the feasibility of an alternative method to non-reversible nerve transection and sub-optimal intermittent stimulation methods to reduce dyssynergia. PMID:29618971

Therapeutic options for intractable hematuria in advanced bladder cancer.

PubMed

Abt, Dominik; Bywater, Mirjam; Engeler, Daniel Stephan; Schmid, Hans-Peter

2013-07-01

Intractable hematuria is a common and severe complication in patients with inoperable bladder carcinoma. The aim was to provide an overview of therapeutic options for such cases, and analyze their effectiveness and risk profile, so a systematic literature search of peer-reviewed papers published up to September 2012 was carried out. Various options are available to treat hematuria in patients with inoperable bladder cancer; these include orally administered epsilon-aminocaproic acid, intravesical formalin, alum or prostaglandin irrigation, hydrostatic pressure, urinary diversion, radiotherapy, embolization and intraarterial mitoxantrone perfusion. These treatment options are associated with different prospects of success, risks and side-effects. Well-designed and large studies comparing options are completely lacking. Despite various treatment options, management of intractable hematuria in patients with inoperable bladder cancer remains a challenge, and most of the reported methods should be seen as experimental. Interventional radiology and alum instillation seem to be suitable alternative options for patients who, after critical consideration, cannot be treated by irrigation, transurethral resection or palliative cystectomy. © 2013 The Japanese Urological Association.

'Cutting for the stone': the ancient art of lithotomy.

PubMed

Herr, Harry W

2008-05-01

Bladder stone was a common ailment plaguing mankind from antiquity to the 20th century. Largely forgotten today, lithotomy relieved the anguish of bladder stones and identified urology as a medical specialty nearly 2500 years ago. The historical literature pertaining to lithotomy was reviewed. Translated and original documents describing operative techniques and developments pertaining to the history of lithotomy were obtained through the internet and library sources. The ancient art of lithotomy was first recorded by the Greeks and evolved through five phases: the Celsian method, or 'lesser operation'; the Marian, or 'greater operation'; the lateral operation; suprapubic cystotomy, or 'high operation', and proctocystotomy. The practice of open lithotomy ceased to exist owing to better minimally invasive alternative methods and most notably by the virtual disappearance of bladder stones in modern man. The history of lithotomy is a fascinating story of how early surgeons forced by the culture and customs of the time dealt with common but devastating bladder stones. Out of their efforts, urology was born.

Identification of Carbonic Anhydrase IX as a Novel Target for Endoscopic Molecular Imaging of Human Bladder Cancer.

PubMed

Wang, Jiaqi; Fang, Ruizhe; Wang, Lu; Chen, Guang; Wang, Hongzhi; Wang, Zhichao; Zhao, Danfeng; Pavlov, Valentin N; Kabirov, Ildar; Wang, Ziqi; Guo, Pengyu; Peng, Li; Xu, Wanhai

2018-06-27

Emerging novel optical imaging techniques with cancer-specific molecular imaging agents offer a powerful and promising platform for cancer detection and resection. White-light cystoscopy and random bladder biopsies remain the most appropriate but nonetheless suboptimal diagnostic technique for bladder cancer, which is associated with high morbidity and recurrence. However, white-light cystoscopy has intrinsic shortcomings. Although current optical imaging technologies hold great potential for improved diagnostic accuracy, there are few imaging agents for specific molecular targeting. Carbonic anhydrase IX (CAIX) plays a pivotal role in tumorigenesis and tumor progression with potential value as an imaging target. Here, we investigated the feasibility of CAIX as a target and validated the diagnostic performance and significance of CAIX as an imaging agent. We first analyzed the data from The Cancer Genome Atlas (TCGA). Pairs of samples comprising bladder cancer and adjacent normal tissue were collected. All tissue samples were used for real-time PCR and immunohistochemistry to compare CAIX expression in normal and cancer tissue. Using blue-light cystoscopy, we observed the optical distribution of fluorescently labeled CAIX antibody in freshly excised human bladders and obtained random bladder biopsies to assess sensitivity and specificity. The TCGA data revealed that CAIX expression was significantly higher in bladder cancer specimens than in normal tissue. The outcome was similar in quantitative real-time PCR analysis. In immunohistochemical analysis, bladder cancer specimens classified in four pathological subtypes presented a variety of positive staining intensities, whereas no benign specimens showed CAIX staining. Using blue-light cystoscopy, we distinguished bladder cancers that were mainly papillary, some variants of urothelial carcinoma, and less carcinoma in situ, from benign tissue, despite the presence of suspicious-appearing mucosa. The sensitivity and specificity for CAIX-targeted imaging were 88.00% and 93.75%, respectively. CAIX-targeted molecular imaging could be a feasible and adaptive alternative approach for the accurate diagnosis and complete resection of bladder cancer. © 2018 The Author(s). Published by S. Karger AG, Basel.

[Bladder injury during sling operation in the treatment of SUI--review of literature and case report].

PubMed

Gałczyński, Krzysztof; Futyma, Konrad; Bar, Krzysztof; Rechberger, Tomasz

2012-10-01

Sling operations have been performed for over 15 years. In recent years these operations have become the gold standard in the treatment of stress urinary incontinence (SUI) due to their efficacy safety and low invasiveness. Approximately 4% of women will undergo a surgery for SUI in the course of their life. As with any surgical intervention, there may be some technical problems, as well as intra- and postoperative complications, the most common of which is bladder injury Other complications encountered during mid-urethral slings procedures include bleeding (retropubic or vaginal hematomas), urethral perforation, urinary tract infections, postoperative vaginal or urethral erosions, bowel perforation, chronic pelvic pain, wound infection, nerve injury transient and persistent voiding dysfunction such as de novo urgency incomplete bladder emptying or urinary retention. Below we present a case of a patient with diagnosed vesicovaginal fistula after sling operation (TVT-tension-free vaginal tape). Upon admission the patient reported dysuria, persistent urinary leakage and abnormal, abundant vaginal discharge. Case report and review of literature concerning surgical treatment of stress urinary incontinence and its complications. Analysis of medical documentation of the patient treated at the Second Department of Gynecology Medical University of Lublin. Review of abstracts or papers in the Medline database related to surgical treatment of urinary incontinence and its complications. Bladder perforation is one of the most common complications of the retropubic approach for MUS placement. The presence of mesh within the bladder may arise from direct bladder perforation or from subsequent erosion of the sling. Such lesions do not cause any serious health consequences for patients on condition they are detected intraoperatively and appropriately repaired, but when unrecognized, they results in the development of considerable symptoms and negatively influence the quality of patient life. Improperly treated, it can lead to development of an abnormal communication between the urinary bladder and the anterior wall of the vagina -vesicovaginal fistula. We should suspect unrecognized bladder injury in case of patients with any persistent voiding symptoms after a sling procedure such as long lasting dysuria, persistent urinary leakage, hematuria, recurrent infections, chronic pain and voiding difficulties. Diagnosis and treatment of vesicovaginal fistula is long lasting and difficult for the patient and the surgeon. Füth-Mayo operation is an effective treatment method for the majority of vesicovaginal fistulas. During this operation we suture all layers of fistula separately (bladder perivesical fascia and vaginal wall). Although with this operation we solve one problem, the patient still might suffer from recurrent SUI. Alternative methods of treatment which can be offered to patients after unsuccessful SUI operation are periurethral injections with bulking agents or electrical stimulation of the pelvic floor muscles. Both methods are effective in the therapy of recurrent SUI. In our case periurtehral injection of Bulkamid did not provide a total cure. Therefore, we completed the treatment with electrical stimulation of the pelvic floor muscles using patient-controlled electrodes placed in the vagina to stimulate muscles with current frequency of 50 Hz, amperage between 0-60 mA and duration of 250 micros. This procedure produced a series of changes in the stimulated area and enabled to cure the incontinence.

An AOP-based alternative testing strategy to predict the impact of thyroid hormone disruption on swim bladder inflation in zebrafish (poster)

EPA Science Inventory

Within the field of chemical safety assessment, there is a desire to replace costly whole organism testing with more efficient and cost-effective alternatives based on in vitro test systems. Disruption of thyroid hormone signaling via inhibition of enzymes called deiodinases is o...

Silibinin inhibits β-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial-mesenchymal transition and stemness.

PubMed

Wu, Kaijie; Ning, Zhongyun; Zeng, Jin; Fan, Jinhai; Zhou, Jiancheng; Zhang, Tingting; Zhang, Linlin; Chen, Yule; Gao, Yang; Wang, Bin; Guo, Peng; Li, Lei; Wang, Xinyang; He, Dalin

2013-12-01

Muscle-invasive bladder cancer is associated with a high frequency of metastasis, and fewer therapies substantially prolong survival. Silibinin, a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including bladder cancer. Our and other previous studies have demonstrated that silibinin induced apoptosis and inhibited proliferation of bladder cancer cells, whether silibinin could suppress bladder cancer metastasis has not been elucidated. In the present study, we utilized a novel highly metastatic T24-L cell model, and found that silibinin treatment not only resulted in the suppression of cell migration and invasion in vitro, but also decreased bladder cancer lung metastasis and prolonged animal survival in vivo. Mechanistically, silibinin could inhibit glycogen synthase kinase-3β (GSK3β) phosphorylation, β-catenin nuclear translocation and transactivation, and ZEB1 gene transcription that subsequently regulated the expression of cytokeratins, vimentin and matrix metalloproteinase-2 (MMP2) to reverse epithelial-mesenchymal transition (EMT). On the other hand, silibinin inhibited ZEB1 expression and then suppressed the properties of cancer stem cells (CSCs), which were evidenced as decreased spheroid colony formation, side population, and the expression of stem cell factor CD44. Overall, this study reveals a novel mechanism for silibinin targeting bladder cancer metastasis, in which inactivation of β-catenin/ZEB1 signaling by silibinin leads to dual-block of EMT and stemness. © 2013.

PLK-1 Silencing in Bladder Cancer by siRNA Delivered With Exosomes.

PubMed

Greco, Kristin A; Franzen, Carrie A; Foreman, Kimberly E; Flanigan, Robert C; Kuo, Paul C; Gupta, Gopal N

2016-05-01

To use exosomes as a vector to deliver small interfering ribonucleic acid (siRNA) to silence the polo-like kinase 1 (PLK-1) gene in bladder cancer cells. Exosomes were isolated from both human embryonic kidney 293 (HEK293) cell and mesenchymal stem cell (MSC) conditioned media. Fluorescently labeled exosomes were co-cultured with bladder cancer and normal epithelial cells and uptake was quantified by image cytometry. PLK-1 siRNA and negative control siRNA were loaded into HEK293 and MSC exosomes using electroporation. An invasive bladder cancer cell line (UMUC3) was co-cultured with the electroporated exosomes. Quantitative reverse transcriptase polymerase chain reaction was performed. Protein analysis was performed by Western blot. Annexin V staining and MTT assays were used to investigate effects on apoptosis and viability. Bladder cancer cell lines internalize an increased percentage of HEK293 exosomes when compared to normal bladder epithelial cells. Treatment of UMUC3 cells with exosomes electroporated with PLK-1 siRNA achieved successful knockdown of PLK-1 mRNA and protein when compared to cells treated with negative control exosomes. HEK293 and MSC exosomes were effectively used as a delivery vector to transport PLK-1 siRNA to bladder cancer cells in vitro, resulting in selective gene silencing of PLK-1. The use of exosomes as a delivery vector for potential intravesical therapy is attractive. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Larval fathead minnow swim bladder inflation following exposure to 2-mercaptobenzothiazole

EPA Pesticide Factsheets

In this study, a hypothesized adverse outcome pathway (AOP) linking inhibition of thyroid peroxidase (TPO) activity to impaired swim bladder inflation was investigated in experiments in which fathead minnows were exposed to the TPO inhibitor 2-mercaptobenzothiazole (MBT). Results show that anterior, but not posterior, swim bladder inflation was impacted by exposure to MBT supporting the development of an AOP linking a specific thyroid-disrupting molecular initiating event to a significant phenotypic outcome. Results also suggest an alternative short-term in vivo test with larval fathead minnows that could be used to screen chemicals for thyroid disrupting activity and possibly distinguish thyroid disrupting modes of action. The dataset contains information on TPO expression, thyroid hormone concentrations, and swim bladder inflation measurements in larval fathead minnows.This dataset is associated with the following publication:Nelson, K., A. Schroeder , G. Ankley , B. Blackwell, C. Blanksma, S. Degitz , K. Jensen , R. Johnson , M. Kahl , D. Knapen, P. Kosian , R. Milsk, E. Randolph, T. Saari, E. Stinckens, L. Vergauwen, and D. Villeneuve. Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-Mercaptobenzothiazole Part I: Fathead minnow. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 173: 192-203, (2016).

Discordance Between Preoperative and Postoperative Bladder Cancer Location: Implications for Partial-Bladder Radiation

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

Goldsmith, Benjamin; Tucker, Kai; Conway, Robert Greg

2013-03-01

Purpose: There is strong interest in partial-bladder radiation whether as a boost or definitive therapy to limit long-term toxicity. It is unclear that a standard preoperative examination can accurately identify all sites of disease within the bladder. The purpose of this study was to determine the correlation between preoperative localization of bladder tumors with postoperative findings to facilitate partial-bladder radiation techniques when appropriate. Methods and Materials: We examined patients with clinically staged T1-T4 invasive transitional cell carcinoma (TCC) or TCC with variant histology with no history of radiation or partial cystectomy undergoing radical cystectomy. Patients were scored as “under-detected” ifmore » a bladder site was involved with invasive disease (≥T1) at the time of cystectomy, but not identified preoperatively. Patients were additionally scored as “widely under-detected” if they had postoperative lesions that were not identified preoperatively in a given site, nor in any adjacent site. Rates of under-detected and widely under-detected lesions, as well as univariate and multivariate association between clinical variables and under-detection, were evaluated using logistic regression. Results: Among 222 patients, 96% (213/222) had at least 1 area of discordance. Fifty-eight percent of patients were under-detected in at least 1 location, whereas 12% were widely under-detected. Among 24 patients with a single site of disease on preoperative evaluation, 21/24 (88%) had at least 1 under-detected lesion and 14/24 (58%) were widely under-detected. On multivariate analysis, only solitary site of preoperative disease was associated with increased levels of under-detection of invasive disease (OR = 4.161, 95% CI, 1.368-12.657). Conclusion: Our study shows a stark discordance between preoperative and postoperative localization of bladder tumors. From a clinical perspective, incomplete localization of all sites of disease within the bladder may lead to marginal misses when a partial-bladder technique is used.« less

Screening biomarkers of bladder cancer using combined miRNA and mRNA microarray analysis.

PubMed

Jin, Ning; Jin, Xuefei; Gu, Xinquan; Na, Wanli; Zhang, Muchun; Zhao, Rui

2015-08-01

Biomarkers, such as microRNAs (miRNAs) may be useful for the diagnosis of bladder cancer. In order to understand the molecular mechanisms underlying bladder cancer, differentially expressed miRNAs (DE-miRNAs) and their target genes in bladder cancer were analyzed. In the present study, miRNA and mRNA expression profiles (GSE40355) were obtained from the Gene Expression Omnibus. These consisted of healthy bladder samples (n=8) and urothelial carcinoma samples (low-grade, n=8 and high-grade, n=8). DE-miRNAs and differentially expressed genes (DEGs) were identified using the limma package and the Benjamin and Hochberg method from the multtest package in R. Target genes of DE-miRNAs were screened. Associations between DEGs were investigated using STRING, and an interaction network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed for DEGs from the interaction network. 87 DE-miRNAs and 2058 DEGs were screened from low-grade bladder cancer samples, and 40 DE-miRNAs and 2477 DEGs were screened from high-grade bladder cancer samples. DE-target genes were significantly associated with the regulation of cell apoptosis. Bladder cancer, non-small cell lung cancer and pancreatic cancer biological pathways were found to be enriched. The results of the present study demonstrated that E2F transcription factor 1, which is targeted by miR-106b, and cyclin-dependent kinase inhibitor 2A (CDKN2A) and V-Erb-B2 avian erythroblastic leukemia viral oncogene homolog-2, which are targeted by miR-125b, participate in the bladder cancer pathway. In conclusion, DE-miRNAs in bladder cancer tissue samples and DE-targeted genes, such as miR-106b and CDKN2A, which were identified in the present study, may provide the basis for targeted therapy for breast cancer and enhance understanding of its pathogenesis.

Sacral root neuromodulation in the treatment of various voiding and storage problems.

PubMed

Shaker, H; Hassouna, M M

1999-01-01

This paper reviews the use of sacral neuromodulation as a treatment modality for patients with bladder dysfunction. The dual functions of the urinary bladder are to act as a reservoir and to evacuate under voluntary control. Bladder dysfunction is a descriptive term describing the loss or the impairment of one or both of these functions. In the first part of the manuscript we describe the different components of sacral neuromodulation: the screening test known as percutaneous nerve evaluation (PNE), which involves screening patients who could potentially benefit from the therapy. Those who show a satisfactory response will have a permanent neuroprosthesis implanted. The technical aspects of both components of neuromodulation are described in detail, as well as the technical difficulties encountered. In the second part we present our long-term results in patients with sacral neuromodulation. Sacral neuromodulation is a safe and efficient therapeutic modality that helps patients with refractory voiding dysfunction restore their bladder function.

Detrusor underactivity and the underactive bladder: Symptoms, function, cause-what do we mean? ICI-RS think tank 2014.

PubMed

Smith, Phillip P; Birder, Lori A; Abrams, Paul; Wein, Alan J; Chapple, Chris R

2016-02-01

Impaired bladder emptying is a well-recognized cause of lower urinary tract symptoms. However, the symptoms produced do not always relate to voiding, and may include frequency, urgency and incontinence. Conversely, the etiology of symptoms of disturbed voiding is not necessarily dependent upon objectively impaired voiding. Terms including underactive bladder, detrusor underactivity, and impaired contractility describe aspects of these problems, and have been used somewhat interchangeably. It is possible that the present lack of effective therapy in many cases relates to both etiologic and diagnostic uncertainty stemming from terminologic imprecision. Detrusor underactivity has a standardized definition, unlike underactive bladder and impaired contractility. The relationships of symptoms, function, and cause were the focus of a 2014 ICI-RS Think Tank entitled Does Detrusor Underactivity Exist, and if so it is neurogenic, myogenic, or both? This review presents a summary of the problem and the Think Tank conclusions. A terminologic hierarchy and specific research goals are presented. © 2016 Wiley Periodicals, Inc.

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

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

PubMed

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

2015-01-01

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

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.

The use of intravesicular alteplase for thrombolysis in a dog with urinary bladder thrombi.

PubMed

Hooi, Kimberly S; Lemetayer, Julie D

2017-09-01

To describe the use of alteplase for intravesicular thrombolysis in a dog after development of urinary tract obstruction from a blood clot in the urinary bladder. A 5.8 kg, 6.5-year-old female neutered Bichon Frise was presented for signs of acute hematuria. A complete blood count (CBC) revealed marked thrombocytopenia and leukopenia, and nonregenerative anemia. Bone marrow aspirate cytology revealed mild hypercellularity, mild megakaryocytic hyperplasia, mildly left-shifted erythroid maturation, and moderately left-shifted myeloid maturation, suggesting ongoing recovery from an acute bone marrow insult. Thrombocytopenia and hematuria resolved concurrently; however, stranguria and oliguria developed acutely. Ultrasonography identified two large presumed thrombi within the urinary bladder. A urinary catheter was placed and 4 doses of 0.5 mg of alteplase diluted in 10 mL of 0.9% sodium chloride were instilled into the bladder with a 4-hour dwell time at 12-hour intervals. Prothombin and activated partial thromboplastin times were monitored during therapy and remained within normal limits. One thrombus was successfully dissolved after 48 hours of therapy and the remaining thrombus was reduced in size and was voided upon removal of the urinary catheter. This report describes the use of alteplase in a dog for thrombolysis of intravesicular thrombi. In patients that develop intravesicular thrombi, intravesical instillation of alteplase can be considered as a method for dissolution of these thrombi. © Veterinary Emergency and Critical Care Society 2017.

Gene therapy strategies for urological dysfunction.

PubMed

Chancellor, M B; Yoshimura, N; Pruchnic, R; Huard, J

2001-07-01

Novel molecular techniques such as conventional and ex vivo gene therapy, and tissue engineering have only recently been introduced to the field of urology. The lower urinary tract is ideally suited for minimally invasive therapy, and also ex vivo approaches would limit the risk of systemic side effects. Muscle-derived stem cells have been used successfully to treat stress incontinence, and rats with diabetic bladder dysfunction benefited from nerve growth factor (NGF)-based gene therapy. Nitric oxide synthase and capase-7 might provide suitable gene therapy targets for erectile dysfunction and benign prostatic hyperplasia, respectively.

Abdominal and Pelvic CT

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[Retroviral-mediated transfer of a hygromycin phosphotransferase-thymidine kinase fusion gene into human bladder carcinoma cell].

PubMed

Ye, C; Chen, S; Pei, X; Li, L; Feng, K

1999-08-01

To evaluate the therapeutic efficacy of retroviral-mediated hygromycin phosphotransferase-thymidine kinase fusion gene (HyTK)/GCV on human bladder carcinoma cell. A retroviral expression vector pL (HyTK) SN was constructed. By using FuGENE 6-mediated transfection and "ping-pong effect" technique, high-titer of retroviral supernatant was obtained and HyTK gene was transferred into EJ cells. A retroviral vector encoding, enhanced green fluorescent protein, EGFP was used to rapidly detect the transduction efficiency. Antitumor effects were observed after GCV treatment. In vitro experiments demonstrated the EJ cells transferred by HyTK gene were killed in the GCV treatment. Non-transduced parental cells were not sensitive to GCV, but they were dead by the bystander killing of neighboring cells when mixed with EJ/HyTK cells at various ratios. In addition, this not only affect wild-type EJ cells but also cells from different bladder carcinoma cell lines. Retroviral-mediated HyTK/GCV systems were a promising suicide gene therapy for bladder carcinoma. EGFP may act as a convenient and rapid reporter to monitor retroviral-mediated gene transfer and expression in bladder carcinoma cells.

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

Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy

ClinicalTrials.gov

2018-06-01

Adult Solid Neoplasm; Bladder Carcinoma; Colon Carcinoma; Estrogen Receptor Negative; Head and Neck Squamous Cell Carcinoma; Hepatocellular Carcinoma; HER2/Neu Negative; Melanoma; Non-Small Cell Lung Carcinoma; Pancreatic Carcinoma; Progesterone Receptor Negative; Rectal Carcinoma; Renal Cell Carcinoma; Soft Tissue Sarcoma; Triple-Negative Breast Carcinoma; TP53 Gene Mutation; Unresectable Solid Neoplasm

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.

Molecular networks discriminating mouse bladder responses to intravesical bacillus Calmette-Guerin (BCG), LPS, and TNF-α

PubMed Central

Saban, Marcia R; O'Donnell, Michael A; Hurst, Robert E; Wu, Xue-Ru; Simpson, Cindy; Dozmorov, Igor; Davis, Carole; Saban, Ricardo

2008-01-01

Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG) remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression in the bladder target organ beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following chronic intravesical BCG therapy and to compare the results to non-specific pro inflammatory stimuli (LPS and TNF-α). For this purpose, C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-α. Seven days after the last instillation, the urothelium along with the submucosa was removed from detrusor muscle and the RNA was extracted from both layers for cDNA array experiments. Microarray results were normalized by a robust regression analysis and only genes with an expression above a conditional threshold of 0.001 (3SD above background) were selected for analysis. Next, genes presenting a 3-fold ratio in regard to the control group were entered in Ingenuity Pathway Analysis (IPA) for a comparative analysis in order to determine genes specifically regulated by BCG, TNF-α, and LPS. In addition, the transcriptome was precipitated with an antibody against RNA polymerase II and real-time polymerase chain reaction assay (Q-PCR) was used to confirm some of the BCG-specific transcripts. Results Molecular networks of treatment-specific genes generated several hypotheses regarding the mode of action of BCG. BCG-specific genes involved small GTPases and BCG-specific networks overlapped with the following canonical signaling pathways: axonal guidance, B cell receptor, aryl hydrocarbon receptor, IL-6, PPAR, Wnt/β-catenin, and cAMP. In addition, a specific detrusor network expressed a high degree of overlap with the development of the lymphatic system. Interestingly, TNF-α-specific networks overlapped with the following canonical signaling pathways: PPAR, death receptor, and apoptosis. Finally, LPS-specific networks overlapped with the LPS/IL-1 mediated inhibition of RXR. Because NF-kappaB occupied a central position in several networks, we further determined whether this transcription factor was part of the responses to BCG. Electrophoretic mobility shift assays confirmed the participation of NF-kappaB in the mouse bladder responses to BCG. In addition, BCG treatment of a human urothelial cancer cell line (J82) also increased the binding activity of NF-kappaB, as determined by precipitation of the chromatin by a NF-kappaB-p65 antibody and Q-PCR of genes bearing a NF-kappaB consensus sequence. Next, we tested the hypothesis of whether small GTPases such as LRG-47 are involved in the uptake of BCG by the bladder urothelium. Conclusion As expected, BCG treatment induces the transcription of genes belonging to common pro-inflammatory networks. However, BCG also induces unique genes belonging to molecular networks involved in axonal guidance and lymphatic system development within the bladder target organ. In addition, NF-kappaB seems to play a predominant role in the bladder responses to BCG therapy. Finally, in intact urothelium, BCG-GFP internalizes in LRG-47-positive vesicles. These results provide a molecular framework for the further study of the involvement of immune and nervous systems in the bladder responses to BCG therapy. PMID:18267009

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

Therapeutic efficacy of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome.

PubMed

Kajiwara, Mitsuru; Inoue, Shougo; Kobayashi, Kanao; Ohara, Shinya; Teishima, Jun; Matsubara, Akio

2014-04-01

Narrow band imaging cystoscopy can increase the visualization and detection of Hunner's lesions. A single-center, prospective clinical trial was carried out aiming to show the effectiveness of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome. A total of 23 patients (19 women and 4 men) diagnosed as having ulcer-type interstitial cystitis/painful bladder syndrome were included. All typical Hunner's lesions and suspected areas identified by narrow band imaging were electrocoagulated endoscopically after the biopsy of those lesions. Therapeutic efficacy was assessed prospectively by using visual analog scale score of pain, O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score. The mean follow-up period was 22 months. All patients (100%) experienced a substantial improvement in pain. The average visual analog scale pain scores significantly decreased from 7.3 preoperatively to 1.2 1 month postoperatively. A total of 21 patients (91.3%) who reported improvement had at least a 50% reduction in bladder pain, and five reported complete resolution. Daytime frequency was significantly decreased postoperatively. O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score were significantly decreased postoperatively. However, during the follow-up period, a total of six patients had recurrence, and repeat narrow band imaging-assisted transurethral electrocoagulation of the recurrent lesions was carried out for five of the six patients, with good response in relieving bladder pain. Our results showed that narrow band imaging-assisted transurethral electrocoagulation could be a valuable therapeutic alternative in patients with ulcer-type interstitial cystitis/painful bladder syndrome, with good efficacy and reduction of recurrence rate. © 2014 The Japanese Urological Association.

Stages of Rectal Cancer

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

Stages of Colon Cancer

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

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.

[The diagnostic value of microsatellite LOH analysis and the prognostic relevance of angiogenic gene expression in urinary bladder cancer].

PubMed

Szarvas, Tibor

2009-12-01

Bladder cancer is the second most common malignancy affecting the urinary system. Currently, histology is the only tool that determines therapy and patients' prognosis. As the treatment of non-invasive (Ta/T1) and muscle invasive (T2-T4) bladder tumors are completely different, correct staging is important, although it is often hampered by disturbing factors. Molecular methods offer new prospects for early disease detection, confirmation of unclear histological findings and prognostication. Applying molecular biological methods, the present study is searching for answers to current diagnostic and prognostic problems in bladder carcinoma. We analyzed tumor, blood and/or urine samples of 334 bladder cancer patients and 117 control individuals. Genetic alterations were analyzed in urine samples of patients and controls, both by PCR-based microsatellite loss of heterozigosity (LOH) analysis using 12 fluorescently labeled primers and by DNA hybridization based UroVysion FISH technique using 4 probes, to assess the diagnostic values of these methods. Whole genome microsatellite analysis (with 400 markers) was performed in tumor and blood specimens of bladder cancer patients to find chromosomal regions, the loss of which may be associated with tumor stage. Furthermore, we assessed the prognostic value of Tie2, VEGF, Angiopoietin-1 and -2. We concluded that DNA analysis of voided urine samples by microsatellite analysis and FISH are sensitive and non-invasive methods to detect bladder cancer. Furthermore, we established a panel of microsatellite markers that could differentiate between non-invasive and invasive bladder cancer. However, further analyses in a larger cohort of patients are needed to assess their specificity and sensitivity. Finally, we identified high Ang-2 and low Tie2 gene expression as significant and independent risk factors of tumor recurrence and cancer related survival.

The mechanism of the growth-inhibitory effect of coxsackie and adenovirus receptor (CAR) on human bladder cancer: a functional analysis of car protein structure.

PubMed

Okegawa, T; Pong, R C; Li, Y; Bergelson, J M; Sagalowsky, A I; Hsieh, J T

2001-09-01

The coxsackie and adenovirus receptor (CAR) is identified as a high-affinity receptor for adenovirus type 5. We observed that invasive bladder cancer specimens had significantly reduced CAR mRNA levels compared with superficial bladder cancer specimens, which suggests that CAR may play a role in the progression of bladder cancer. Elevated CAR expression in the T24 cell line (CAR-negative cells) increased its sensitivity to adenovirus infection and significantly inhibited its in vitro growth, accompanied by p21 and hypophosphorylated retinoblastoma accumulation. Conversely, decreased CAR levels in both RT4 and 253J cell lines (CAR-positive cells) promoted their in vitro growth. To unveil the mechanism of action of CAR, we showed that the extracellular domain of CAR facilitated intercellular adhesion. Furthermore, interrupting intercellular adhesion of CAR by a specific antibody alleviates the growth-inhibitory effect of CAR. We also demonstrated that both the transmembrane and intracellular domains of CAR were critical for its growth-inhibitory activity. These data indicate that the cell-cell contact initiated by membrane-bound CAR can elicit a negative signal cascade to modulate cell cycle regulators inside the nucleus of bladder cancer cells. Therefore, the presence of CAR cannot only facilitate viral uptake of adenovirus but also inhibit cell growth. These results can be integrated to formulate a new strategy for bladder cancer therapy.

The Ethanol Extract of the Inner Bark of Caesalpinia pyramidalis (Tul.) Reduces Urinary Bladder Damage during Cyclophosphamide-Induced Cystitis in Rats

PubMed Central

Moraes, Janaína P.; Pereira, Denyson S.; Matos, Alexandre S.; Santana, Danielle G.; Santos, Cliomar A.; Estevam, Charles S.; Fakhouri, Ricardo; de Lucca Junior, Waldecy; Camargo, Enilton A.

2013-01-01

Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy, which deserves new therapeutic strategies, such as those based on natural products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) (EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities as previously showed by our group. We have investigated the effect of EECp on the cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the injection of cyclophosphamide. These animals were pretreated with EECp (100–400 mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation were measured in urinary bladder and other tissues. Bladder edema and histopathological alterations and serum nitric oxide metabolites concentration NOx − were also evaluated. Treatment with EECp (100–400 mg/kg) or mesna impaired the increase of myeloperoxidase activity in urinary bladder and the serum NOx − induced by cyclophosphamide but did not reduce edema in this tissue, as did mesna. Total histological score was reduced by EECp (100 mg/kg). Lung myeloperoxidase activity, which was increased by cyclophosphamide, was decreased significantly by EECp (400 mg/kg). EECp also diminished the malondialdehyde formation in bladder, lung, and spleen, although these parameters were not affected by cyclophosphamide. These results indicate that EECp reduced urinary bladder damage during cyclophosphamide-induced HC in rats. PMID:24348180

Ifosfamide Injection

MedlinePlus

... Also tell your doctor if you have a urinary tract infection or if you have or have ever had radiation (x-ray) therapy to the bladder. Tell your doctor and pharmacist if you are taking or have ever received ...

Treatment Option Overview (Colon Cancer)

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

Treatment Options by Stage (Rectal Cancer)

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

Stages of Thymoma and Thymic Carcinoma

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs, surgery, or radiation therapy is used to ...

Treatment Option Overview (Rectal Cancer)

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

Recurrent urinary tract infections in women: How promising is the use of probiotics?

PubMed

Gupta, Varsha; Nag, Deepika; Garg, Pratibha

2017-01-01

Urinary tract infections (UTIs) currently rank amongst the most prevalent bacterial infections, representing a major health hazard. UTIs in females usually start as vaginal infections and ascend to the urethra and bladder. Recurrent UTIs (rUTIs) can be defined as at least three episodes of UTI in 1 year or two episodes in 6 months. Various antibiotics have been the mainstay of therapy in ameliorating the incidence of UTIs, but recurrent infections continue to afflict many women. It necessitates the exploitation of alternative antimicrobial therapy. Probiotics have been shown to be effective in varied clinical trials for long-term preventions of rUTI. Because Escherichia coli is the primary pathogen involved in UTIs which spreads from the rectum to vagina and then ascends up the sterile urinary tract, improving the gut or vaginal flora will thus impact the urinary tract. Since a healthy vaginal microbiota is mainly dominated by Lactobacillus species, in this context, exogenously administered probiotics containing Lactobacilli play a pivotal role in reducing the risk of rUTI. The concept of artificially boosting the Lactobacilli numbers through probiotic administration has long been conceived but has been recently shown to be possible. Lactobacilli may especially be useful for women with a history of recurrent, complicated UTIs or on prolonged antibiotic use. Probiotics do not cause antibiotic resistance and may offer other health benefits due to vaginal re-colonisation with Lactobacilli. However, more comprehensive research is still needed, to recommend for probiotics as an alternative to antibiotics.

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

PubMed

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

2017-11-10

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

OnabotulinumtoxinA injection therapy in men with LUTS due to primary bladder-neck dysfunction: objective and patient-reported outcomes.

PubMed

Sacco, Emilio; Tienforti, Daniele; Bientinesi, Riccardo; D'Addessi, Alessandro; Racioppi, Marco; Pinto, Francesco; Totaro, Angelo; Vittori, Matteo; D'Agostino, Daniele; Bassi, Pierfrancesco

2014-01-01

To determine efficacy and safety of OnabotulinumtoxinA (BoNT-A) injection therapy in medically refractory patients with lower urinary tract symptoms (LUTS) due to primary bladder-neck dysfunction (PBND). Thirty-five consecutive ambulatory males diagnosed with PBND and refractory to medical therapy, with IPSS > 15, Qmax < 15 ml/sec, and total prostate volume < 30 cm(3), were screened from January 2010 to December 2011. Eligible patients underwent transurethral bladder-neck injection of BoNT-A (200 U, 50 U/ml × 4 sites) and were assessed at baseline, 2-, 6-, 9-, and 12-month postprocedure and until duration of clinical response. The primary outcome was the change from baseline in total IPSS, and secondary outcome were storage- and voiding-IPSS, QoL score, Qmax, and postvoiding residual volume (PVR), patient-reported outcomes. Adverse effects were also recorded, including ejaculatory dysfunctions. Of 30 enrolled patients (mean age 33.8 years), 29 (96.7%) completed the study. A statistically significant improvement of total IPSS was observed from 21.9 at baseline, to 7.8, 10.3, and 16.6 at 2, 6, and 9 months, respectively (P < 0.000). Statistically significant improvements from baseline of storage- and voiding-IPSS, QoL score, Qmax, and PVR were also observed until 9-month postprocedure. The proportion of patients with overall satisfaction was favorable although decreasing from 80% at 2 months, to 44.8% at 12 months. No significant adverse effects or ejaculatory dysfunctions were noted. BoNT-A injection therapy appears effective and safe in medically refractory men with PBND, although repeated procedures are required for long-term sustained benefit. Randomized controlled trials are warranted in order to corroborate these results. © 2013 Wiley Periodicals, Inc.

A Phase II Safety and Efficacy Study of the Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor Pazopanib in Patients With Metastatic Urothelial Cancer

PubMed Central

Pili, Roberto; Qin, Rui; Flynn, P.J.; Picus, Joel; Millward, Michael; Ho, Wing Ming; Pitot, Henry; Tan, Winston; Miles, Kiersten M.; Erlichman, Charles; Vaishampayan, Ulka

2013-01-01

Vascular endothelial growth factor (VEGF) is expressed in human bladder tumors. A phase II study was conducted to assess the VEGF inhibitor pazopanib in patients with metastatic, urothelial carcinoma. Nineteen patients with one prior systemic therapy were enrolled. No objective responses were observed and median progression-free survival was 1.9 months. The role of anti-VEGF therapies in urothelial carcinoma remains to be determined. Background Vascular endothelial growth factor (VEGF) is produced by bladder cancer cell lines in vitro and expressed in human bladder tumor tissues. Pazopanib is a vascular endothelial receptor tyrosine kinase inhibitor with anti-angiogenesis and anti-tumor activity in several preclinical models. A 2-stage phase II study was conducted to assess the activity and toxicity profile of pazopanib in patients with metastatic, urothelial carcinoma. Methods Patients with one prior systemic therapy for metastatic urothelial carcinoma were eligible. Patients received pazopanib at a dose of 800 mg orally for a 4-week cycle. Results Nineteen patients were enrolled. No grade 4 or 5 events were experienced. Nine patients experienced 11 grade 3 adverse events. Most common toxicities were anemia, thrombocytopenia, leucopenia, and fatigue. For stage I, none of the first 16 evaluable patients were deemed a success (complete response or partial response) by the Response Evaluation Criteria In Solid Tumors criteria during the first four 4-week cycles of treatment. Median progression-free survival was 1.9 months. This met the futility stopping rule of interim analysis, and therefore the trial was recommended to be permanently closed. Conclusions Pazopanib did not show significant activity in patients with urothelial carcinoma. The role of anti-VEGF therapies in urothelial carcinoma may need further evaluation in rational combination strategies. PMID:23891158

Multimodal vaginal toning for bladder symptoms and quality of life in stress urinary incontinence.

PubMed

de la Torre, Sarah; Miller, Larry E

2017-08-01

Treatment options for women with stress urinary incontinence (SUI) have limitations. We hypothesized that multimodal vaginal toning therapy would improve bladder symptoms and quality of life in women with postpartum SUI and sexual function complaints. Patients self-administered 24 sessions of multimodal vaginal toning therapy lasting 10 min each over 50 days. Outcomes included 1-h pad weight test, Urogenital Distress Inventory Short Form (UDI-6), Incontinence Impact Questionnaire-Short Form (IIQ-7), Female Sexual Distress Scale-Revised 2005 (FSDS-R), Female Sexual Function Index (FSFI), pelvic floor muscle strength, patient satisfaction, and adverse events. Of the 55 patients enrolled (safety population), 48 completed the study per-protocol (PP population). A total of 38 (79%) patients had a positive 1-h pad weight test at baseline. In this group, urine leakage was moderate or severe in 82% of patients at baseline, but in only 18% after treatment. Treatment success was 84%, defined as >50% improvement in pad weight relative to baseline. In the PP population, mean UDI-6 score improved by 50% (p < 0.001) and IIQ-7 score improved by 69% (p < 0.001). Sexual function quality of life improved by 54% for FSDS-R and 15% for FSFI (both p < 0.001). Pelvic floor muscle strength significantly improved (p < 0.001). Patient satisfaction with therapy was reported in 83% of patients. In the safety population, 2 (3.6%) adverse events were reported-1 urinary tract infection and 1 report of discomfort due to excessive warmth. Multimodal vaginal toning therapy yields clinically meaningful improvements in bladder symptoms, pelvic floor muscle strength, and quality of life in women with SUI.

SU-E-J-214: Comparative Assessment On IGRT On Partial Bladder Cancer Treatment Between CT-On-Rails (CTOR) and KV Cone Beam CT (CBCT)

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

Lin, T; Ma, C

2014-06-01

Purpose: Image-Guided radiation therapy(IGRT) depends on reliable online patient-specific anatomy information to address random and progressive anatomy changes. Large margins have been suggested to bladder cancer treatment due to large daily bladder anatomy variation. KV Cone beam CT(CBCT) has been used in IGRT localization prevalently; however, its lack of soft tissue contrast makes clinicians hesitate to perform daily soft tissue alignment with CBCT for partial bladder cancer treatment. This study compares the localization uncertainties of bladder cancer IGRT using CTon- Rails(CTOR) and CBCT. Methods: Three T2N0M0 bladder cancer patients (total of 66 Gy to partial bladder alone) were localized dailymore » with either CTOR or CBCT for their entire treatment course. A total of 71 sets of CTOR and 22 sets of CBCT images were acquired and registered with original planning CT scans by radiation therapists and approved by radiation oncologists for the daily treatment. CTOR scanning entailed 2mm slice thickness, 0.98mm axial voxel size, 120kVp and 240mAs. CBCT used a half fan pelvis protocol from Varian OBI system with 2mm slice thickness, 0.98axial voxel size, 125kVp, and 680mAs. Daily localization distribution was compared. Accuracy of CTOR and CBCT on partial bladder alignment was also evaluated by comparing bladder PTV coverage. Results: 1cm all around PTV margins were used in every patient except target superior limit margin to 0mm due to bowel constraint. Daily shifts on CTOR averaged to 0.48, 0.24, 0.19 mms(SI,Lat,AP directions); CBCT averaged to 0.43, 0.09, 0.19 mms(SI,Lat,AP directions). The CTOR daily localization showed superior results of V100% of PTV(102% CTOR vs. 89% CBCT) and bowel(Dmax 69.5Gy vs. 78Gy CBCT). CTOR images showed much higher contrast on bladder PTV alignment. Conclusion: CTOR daily localization for IGRT is more dosimetrically beneficial for partial bladder cancer treatment than kV CBCT localization and provided better soft tissue PTV identification.« less

Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury

DTIC Science & Technology

2014-12-01

and the dome connected to tension transducers. Preparations were stretched to optimal resting tension ( Lo ) and allowed to equilibrate for 30 min...B SCT (200x) Uro LumenA Red: P2Y6 Green: vimentin Blue: DAPI Figure 11 13 This suggests there are different populations of IC within the bladder...Lumen Uro Control (200x) SCT (600x) Green: CD34 Blue: DAPI Red: P2Y6 Green: CD34 Blue: DAPI Figure 12 14 It was the first animal model

NCCN Guidelines® Insights Bladder Cancer, Version 2.2016 Featured Updates to the NCCN Guidelines

PubMed Central

Clark, Peter E.; Spiess, Philippe E.; Agarwal, Neeraj; Bangs, Rick; Boorjian, Stephen A.; Buyyounouski, Mark K.; Efstathiou, Jason A.; Flaig, Thomas W.; Friedlander, Terence; Greenberg, Richard E.; Guru, Khurshid A.; Hahn, Noah; Herr, Harry W.; Hoimes, Christopher; Inman, Brant A.; Kader, A. Karim; Kibel, Adam S.; Kuzel, Timothy M.; Lele, Subodh M.; Meeks, Joshua J.; Michalski, Jeff; Montgomery, Jeffrey S.; Pagliaro, Lance C.; Pal, Sumanta K.; Patterson, Anthony; Petrylak, Daniel; Plimack, Elizabeth R.; Pohar, Kamal S.; Porter, Michael P.; Sexton, Wade J.; Siefker-Radtke, Arlene O.; Sonpavde, Guru; Tward, Jonathan; Wile, Geoffrey; Dwyer, Mary A.; Smith, Courtney

2017-01-01

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice. PMID:27697976

NCCN Guidelines Insights: Bladder Cancer, Version 2.2016.

PubMed

Clark, Peter E; Spiess, Philippe E; Agarwal, Neeraj; Bangs, Rick; Boorjian, Stephen A; Buyyounouski, Mark K; Efstathiou, Jason A; Flaig, Thomas W; Friedlander, Terence; Greenberg, Richard E; Guru, Khurshid A; Hahn, Noah; Herr, Harry W; Hoimes, Christopher; Inman, Brant A; Kader, A Karim; Kibel, Adam S; Kuzel, Timothy M; Lele, Subodh M; Meeks, Joshua J; Michalski, Jeff; Montgomery, Jeffrey S; Pagliaro, Lance C; Pal, Sumanta K; Patterson, Anthony; Petrylak, Daniel; Plimack, Elizabeth R; Pohar, Kamal S; Porter, Michael P; Sexton, Wade J; Siefker-Radtke, Arlene O; Sonpavde, Guru; Tward, Jonathan; Wile, Geoffrey; Dwyer, Mary A; Smith, Courtney

2016-10-01

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice. Copyright © 2016 by the National Comprehensive Cancer Network.

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.

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

On the nature of bladder sensation: the concept of sensory modulation.

PubMed

De Wachter, S G; Heeringa, R; van Koeveringe, G A; Gillespie, J I

2011-09-01

Going to the toilet is an essential everyday event. Normally, we do not give much thought to the sensations and factors that trigger voiding behavior: we just go. For many people, this apparently simple task is complicated and dominates their life. They have strong sensations and sudden desires to void, often resulting in incontinence. It is therefore important that we understand the origins for this functional change and identify means to alleviate it. Literature survey. A considerable body of work has focused on this problem and ideas and concepts on the nature of bladder sensations are embedded in the literature. In this paper we argue the necessity to return to first principles and a re-examination of the problem. We explore the use of focus groups to identify relevant bladder sensation and what triggers 'bladder' behavior. We argue that there are differences in what can be described as 'introspective bladder sensations' and the sensations reported immediately before a void, 'void sensations'. Finally, we propose an alternative model describing how peripheral information generating 'introspective sensations' and 'void sensations' might be different but interrelated sensations. By exploring such ideas and identifying such complexity it is our intention to stimulate debate and generate further research in the field in order to understand better the physiology of bladder sensation and the pathology of increased urge, frequency and incontinence. Review of the literature on bladder sensation and the established ideas suggests that we might be missing something and the problem of normal and increased sensation and of urgency may be much more complex. Copyright © 2011 Wiley-Liss, Inc.

Microwave radiometry for non-invasive detection of vesicoureteral reflux (VUR) following bladder warming

NASA Astrophysics Data System (ADS)

Stauffer, Paul R.; Maccarini, Paolo F.; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K.; Bardati, Fernando; Tognolotti, Piero; Snow, Brent

2011-03-01

Background: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. Methods: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. Results: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. Conclusion: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects >=2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.

Microwave Radiometry for Non-Invasive Detection of Vesicoureteral Reflux (VUR) Following Bladder Warming.

PubMed

Stauffer, Paul R; Maccarini, Paolo F; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K; Bardati, Fernando; Tognolatti, Piero; Snow, Brent

2011-01-01

BACKGROUND: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. METHODS: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. RESULTS: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. CONCLUSION: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects ≥2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.

Minimally invasive percutaneous management of large bladder stones with a laparoscopic entrapment bag.

PubMed

Tan, Yung K; Gupta, Dilan M; Weinberg, Aaron; Matteis, August J; Kotwal, Sunny; Gupta, Mantu

2014-01-01

The treatment of large volume bladder stones is a management conundrum. Transurethral methods are plagued by long operative times, trauma to the bladder mucosa, and the need for a postoperative urethral catheter. Open cystolithotomy has higher morbidity. We present the percutaneous management of bladder stones with the novel use of a laparoscopic entrapment bag. Twenty-five patients (mean age 65.7), including 22 men and 3 women, 4 with a neurogenic bladder and 21 with a prior diagnosis of benign prostatic hyperplasia, underwent our novel technique. The mean number of stones was 6.8±8.0 (range, 1 to 30) and total stone burden 10.4±10.5 cm (range, 3.0 to 50.0 cm). Using regional or general anesthesia and flexible cystoscopic guidance, percutaneous bladder access was achieved. The tract was balloon dilated to 30F and stones captured in a laparoscopic entrapment bag. The bag's opening was exteriorized and stone fragmentation and comminution were achieved using a nephroscope and pneumatic or ultrasonic lithotripters. The bag was extracted and a 22F suprapubic catheter was inserted into the bladder; the patient was discharged the next day after a voiding trial. The procedure was done without fluoroscopy. No foley catheter was necessary. All patients were rendered stone free. The mean estimated blood loss was 11.1±3.93 mL (range, 10 to 25 mL). The mean operative time was 102.3 minutes. There was minimal trauma to the bladder mucosa and no complications of fluid extravasation, hematuria, or urethral trauma were noted. All patients were discharged within 24 hours of the operation. Percutaneous cystolithotomy with the use of an entrapment bag is an efficient, safe technique for treating large volume bladder calculi. We recommend this technique as an alternative to open surgery for patients with too large a stone burden to remove transurethrally.

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.

Discrimination of healthy and cancer cells of the bladder by metabolic state, based on autofluorescence

NASA Astrophysics Data System (ADS)

Palmer, S.; Litvinova, Karina; Rafailov, E. U.; Nabi, G.

2015-02-01

Bladder cancer is among the most common cancers worldwide (4th in men). It is responsible for high patient morbidity and displays rapid recurrence and progression. Lack of sensitivity of gold standard techniques (white light cystoscopy, voided urine cytology) means many early treatable cases are missed. The result is a large number of advanced cases of bladder cancer which require extensive treatment and monitoring. For this reason, bladder cancer is the single most expensive cancer to treat on a per patient basis. In recent years, autofluorescence spectroscopy has begun to shed light into disease research. Of particular interest in cancer research are the fluorescent metabolic cofactors NADH and FAD. Early in tumour development, cancer cells often undergo a metabolic shift (the Warburg effect) resulting in increased NADH. The ratio of NADH to FAD ("redox ratio") can therefore be used as an indicator of the metabolic status of cells. Redox ratio measurements have been used to differentiate between healthy and cancer breast cells and to monitor cellular responses to therapies. Here, we have demonstrated, using healthy and bladder cancer cell lines, a statistically significant difference in the redox ratio of bladder cancer cells, indicative of a metabolic shift. To do this we customised a standard flow cytometer to excite and record fluorescence specifically from NADH and FAD, along with a method for automatically calculating the redox ratio of individual cells within large populations. These results could inform the design of novel probes and screening systems for the early detection of bladder cancer.

The Role of Brain-Derived Neurotrophic Factor (BDNF) in the Development of Neurogenic Detrusor Overactivity (NDO)

PubMed Central

Frias, Bárbara; Santos, João; Morgado, Marlene; Sousa, Mónica Mendes; Gray, Susannah M.Y.; McCloskey, Karen D.; Allen, Shelley; Cruz, Francisco

2015-01-01

Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients. PMID:25653370

Antitumor potential of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles in human bladder cancer cells.

PubMed

Tessmann, Josiane Weber; Buss, Julieti; Begnini, Karine Rech; Berneira, Lucas Moraes; Paula, Favero Reisdorfer; de Pereira, Claudio Martin Pereira; Collares, Tiago; Seixas, Fabiana Kömmling

2017-10-01

Bladder cancer is a genitourinary malignant disease common worldwide. Current chemotherapy is often limited mainly due to toxicity and drug resistance. Thus, there is a continued need to discover new therapies. Recently evidences shows that pyrazoline derivatives are promising antitumor agents in many types of cancers, but there are no studies with bladder cancer. In order to find potent and novel chemotherapy drugs for bladder cancer, a series of pyrazoline derivatives 2a-2d were tested for their antitumor activity in two human bladder cancer cell lines 5647 and T24. The MTT assay showed that the compounds 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole (2a) and 1-thiocarbamoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (2c) decrease the cell viability of 5637 cells. Molecular modeling indicated that these compounds had a good oral bioavailability and low toxicities. Clonogenic assay and flow cytometric analysis were used to assess colony formation, apoptosis induction and cell cycle distribution. Overall, our results suggest that pyrazoline 2a and 2c, with the substituents hydrogen and chlorine respectively, may decrease cell viability and colony formation of bladder cancer 5637 cell line by inhibition of cell cycle progression, and for pyrazoline 2a, by induction of apoptosis. As indicated by the physicochemical properties of these compounds, the steric factor influences the activity. Therefore, these pyrazoline derivatives can be considered promising anticancer agents for the treatment of bladder cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall.

PubMed

Lepiarczyk, E; Bossowska, A; Kaleczyc, J; Majewski, M

2011-01-01

Botulinum toxin (BTX) belongs to a family of neurotoxins which strongly influence the function of autonomic neurons supplying the urinary bladder. Accordingly, BTX has been used as an effective drug in experimental therapies of a range of neurogenic bladder disorders. However, there is no detailed information dealing with the influence of BTX on the morphological and chemical properties of nerve fibres supplying the urinary bladder wall. Therefore, the present study investigated, using double-labeling immunohistochemistry, the distribution, relative frequency and chemical coding of cholinergic and noradrenergic nerve fibers supplying the wall of the urinary bladder in normal female pigs (n = 6) and in the pigs (n = 6) after intravesical BTX injections. In the pigs injected with BTX, the number of adrenergic (DbetaH-positive) nerve fibers distributed in the bladder wall (urothelium, submucosa and muscle coat) was distinctly higher while the number of cholinergic (VAChT-positive) nerve terminals was lower than that found in the control animals. Moreover, the injections of BTX resulted in some changes dealing with the chemical coding of the adrenergic nerve fibers. In contrast to the normal pigs, in BTX injected animals the number of DbetaH/NPY- or DbetaH/CGRP-positive axons was higher in the muscle coat, and some fibres distributed in the urothelium and submucosa expressed immunoreactivity to CGRP. The results obtained suggest that the therapeutic effects of BTX on the urinary bladder might be dependent on changes in the distribution and chemical coding of nerve fibers supplying this organ.

Current status of photodynamic therapy for human cancer

NASA Astrophysics Data System (ADS)

Marcus, Stuart L.

1991-06-01

Although clinical trials in photodynamic therapy (PDT) have been ongoing for over a decade, attempts to apply for approval of the therapy from boards of health for general use began only in 1989. The steps which are being taken to approve PDT for the treatment of endobronchial lung cancer, superficial bladder cancer and esophageal cancer are described. Technological innovations which have been suggested as increasing the ease of use of PDT as a therapeutic modality are briefly discussed.

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.

Treatment Option Overview (Carcinoma of Unknown Primary)

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs, surgery, or radiation therapy are used to ...

Treatment Options (by Stage) for Colon Cancer

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... VEGF inhibitors and angiogenesis inhibitors . Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on ...

Treatment Options for Thymoma and Thymic Carcinoma

MedlinePlus

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs, surgery, or radiation therapy is used to ...

Characterization of Asymptomatic Bacteriuria Escherichia coli Isolates in Search of Alternative Strains for Efficient Bacterial Interference against Uropathogens

PubMed Central

Stork, Christoph; Kovács, Beáta; Rózsai, Barnabás; Putze, Johannes; Kiel, Matthias; Dorn, Ágnes; Kovács, Judit; Melegh, Szilvia; Leimbach, Andreas; Kovács, Tamás; Schneider, György; Kerényi, Monika; Emödy, Levente; Dobrindt, Ulrich

2018-01-01

Asymptomatic bacterial colonization of the urinary bladder (asymptomatic bacteriuria, ABU) can prevent bladder colonization by uropathogens and thus symptomatic urinary tract infection (UTI). Deliberate bladder colonization with Escherichia coli ABU isolate 83972 has been shown to outcompete uropathogens and prevent symptomatic UTI by bacterial interference. Many ABU isolates evolved from uropathogenic ancestors and, although attenuated, may still be able to express virulence-associated factors. Our aim was to screen for efficient and safe candidate strains that could be used as alternatives to E. coli 83972 for preventive and therapeutic bladder colonization. To identify ABU E. coli strains with minimal virulence potential but maximal interference efficiency, we compared nine ABU isolates from diabetic patients regarding their virulence- and fitness-associated phenotypes in vitro, their virulence in a murine model of sepsis and their genome content. We identified strains in competitive growth experiments, which successfully interfere with colonization of ABU isolate 83972 or uropathogenic E. coli strain 536. Six isolates were able to outcompete E. coli 83972 and two of them also outcompeted UPEC 536 during growth in urine. Superior competitiveness was not simply a result of better growth abilities in urine, but seems also to involve expression of antagonistic factors. Competitiveness in urine did not correlate with the prevalence of determinants coding for adhesins, iron uptake, toxins, and antagonistic factors. Three ABU strains (isolates 61, 106, and 123) with superior competitiveness relative to ABU model strain 83972 display low in vivo virulence in a murine sepsis model, and susceptibility to antibiotics. They belong to different phylogroups and differ in the presence of ExPEC virulence- and fitness-associated genes. Importantly, they all lack marked cytotoxic activity and exhibit a high LD50 value in the sepsis model. These strains represent promising candidates for a more detailed assessment of relevant fitness traits in urine and their suitability for therapeutic bladder colonization. PMID:29491858

An overview of targeted alpha therapy with 225Actinium and 213Bismuth.

PubMed

Morgenstern, Alfred; Apostolidis, Christos; Kratochwil, Clemens; Sathekge, Mike; Krolicki, Leszek; Bruchertseifer, Frank

2018-05-01

Recent reports of the remarkable therapeutic efficacy of 225Ac-labeled PSMA-617 for therapy of metastatic castration-resistant prostate cancer have underlined the clinical potential of targeted alpha therapy. This review describes methods for the production of 225Ac and its daughter nuclide 213Bi and summarizes the current clinical experience with both alpha emitters with particular focus on recent studies of targeted alpha therapy of bladder cancer, brain tumors, neuroendocrine tumors and prostate cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Perivascular epithelioid cell tumor (PEComa) of the urinary bladder associated with Xp11 translocation.

PubMed

Russell, Christopher M; Buethe, David D; Dickinson, Shohreh; Sexton, Wade J

2014-01-01

Perivascular epithelioid cell-containing tumors (PEComas) represent a rare family of neoplasms. Their dichotomous phenotypic features, including both myogenic and mylanocytic features, can make a definitive diagnosis difficult. Such tumors have been associated with the overexpression of transcription factor E3 (TFE3). An Xp11 translocation could account for the aberrant activity of TFE3 but has never before been described in affiliation with a PEComa of the urinary bladder. While PEComas of the bladder have exhibited benign clinical courses to date, here we present an intravesical PEComa shown to have an Xp11 translocation and resultant overexpression of TFE3, indicating an aggressive, metastatic nature. No consistent tumor characteristics have proven accurate at identifying aggressive tumors. However, mTOR inhibitors offer a mechanistic management strategy when systemic therapy is warranted.

Spotlight on atezolizumab and its potential in the treatment of advanced urothelial bladder cancer.

PubMed

Aydin, Ahmet Murat; Woldu, Solomon L; Hutchinson, Ryan C; Boegemann, Martin; Bagrodia, Aditya; Lotan, Yair; Margulis, Vitaly; Krabbe, Laura-Maria

2017-01-01

Metastatic urothelial carcinoma of the bladder is an aggressive malignancy with poor prognosis, reflecting a lack of effective systemic therapies. The current standard of care includes multiagent platinum-based chemotherapy; however a majority of patients do not respond to treatment and most eventually succumb to disease. Recently, renewed interest in immunotherapy in the form of immune-checkpoint inhibition has gained widespread attention for a number of malignancies. Atezolizumab, an anti-PDL1 antibody, has been shown to be effective in a subset of patients previously treated with or unfit for platinum-based chemotherapy, and has shown durable responses with a good tolerability profile. We review the mechanism of action and clinical evidence of atezolizumab for metastatic urothelial bladder cancer, and discuss this drug within the context of ongoing developments in this dynamic field of immunooncology.

Spotlight on atezolizumab and its potential in the treatment of advanced urothelial bladder cancer

PubMed Central

Aydin, Ahmet Murat; Woldu, Solomon L; Hutchinson, Ryan C; Boegemann, Martin; Bagrodia, Aditya; Lotan, Yair; Margulis, Vitaly; Krabbe, Laura-Maria

2017-01-01

Metastatic urothelial carcinoma of the bladder is an aggressive malignancy with poor prognosis, reflecting a lack of effective systemic therapies. The current standard of care includes multiagent platinum-based chemotherapy; however a majority of patients do not respond to treatment and most eventually succumb to disease. Recently, renewed interest in immunotherapy in the form of immune-checkpoint inhibition has gained widespread attention for a number of malignancies. Atezolizumab, an anti-PDL1 antibody, has been shown to be effective in a subset of patients previously treated with or unfit for platinum-based chemotherapy, and has shown durable responses with a good tolerability profile. We review the mechanism of action and clinical evidence of atezolizumab for metastatic urothelial bladder cancer, and discuss this drug within the context of ongoing developments in this dynamic field of immunooncology. PMID:28331342

Spatial and temporal clonal evolution during development of metastatic urothelial carcinoma.

PubMed

Thomsen, Mathilde B H; Nordentoft, Iver; Lamy, Philippe; Høyer, Søren; Vang, Søren; Hedegaard, Jakob; Borre, Michael; Jensen, Jørgen B; Ørntoft, Torben F; Dyrskjøt, Lars

2016-11-01

Patients with metastatic bladder cancer have a median survival of only 13-14 months. Precision medicine using targeted therapy may improve survival. Here we investigated spatial and temporal tumour evolution and tumour heterogeneity in order to evaluate the potential use of targeted treatment of metastatic bladder cancer. We performed a proof-of-concept study by whole exome sequencing of multiple tumour regions (n = 22) from three patients with metastatic bladder cancer. DNA from primary and metastatic tumour biopsies was analysed for mutations using Mutect and potential therapeutic targets were identified. We identified 256, 265 and 378 somatic mutations per patient, encompassing mutations with an estimated functional impact in 6-12 known disease driver genes per patient. Disease driver mutations present in all tumour regions could be identified in all cases, however, over time metastasis specific driver mutations emerged. For each patient we identified 6-10 potentially therapeutic targets, however very few targets were present in all regions. Low mutational allele frequencies were observed in most regions suggesting a complex mixture of different cancer cells with no spatial demarcation of subclones. In conclusion, primary bladder tumours and metastatic lesions showed heterogeneity at the molecular level, but within the primary tumour the heterogeneity appeared low. The observed lack of potential therapeutic targets common to all cancer cells in primary tumours and metastases emphasizes the challenges in designing rational targeted therapy solely based on analysis of the primary tumours. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Volumetric-modulated arc therapy in postprostatectomy radiotherapy patients: A planning comparison study

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

Forde, Elizabeth, E-mail: eforde@tcd.ie; Kneebone, Andrew; Northern Clinical School, University of Sydney, New South Wales

2013-10-01

The purpose of this study was to compare postprostatectomy planning for volumetric-modulated arc therapy (VMAT) with both single arc (SA) and double arcs (DA) against dynamic sliding window intensity-modulated radiotherapy (IMRT). Ten cases were planned with IMRT, SA VMAT, and DA VMAT. All cases were planned to achieve a minimum dose of 68 Gy to 95% of the planning target volume (PTV) and goals to limit rectal volume >40 Gy to 35% and >65 Gy to 17%, and bladder volumes >40 Gy to 50% and >65 Gy to 25%. Plans were averaged across the 10 patients and compared for meanmore » dose, conformity, homogeneity, rectal and bladder doses, and monitor units. The mean dose to the clinical target volume and PTV was significantly higher (p<0.05) for SA compared with DA or IMRT. The homogeneity index was not significantly different: SA = 0.09; DA = 0.08; and IMRT = 0.07. The rectal V40 was lowest for the DA plan. The rectal V20 was significantly lower (p<0.05) for both the VMAT plans compared with IMRT. There were no significant differences for bladder V40 or rectal and bladder V65. The IMRT plans required 1400 MU compared with 745 for DA and 708 for SA. This study shows that for equivalent dose coverage, SA and DA VMAT plans result in higher mean doses to the clinical target volume and PTV. This greater dose heterogeneity is balanced by improved low-range rectal doses and halving of the monitor units.« less

[Therapeutic effect of mitomycin C in the immediate postoperative period in patients with intermediate-risk non-muscle-invasive bladder tumors].

PubMed

Jalón Monzón, A; Fernández Gómez, J M; Escaf Barmadah, S; Alvarez Múgica, M; Martín Benito, J L; Regadera Sejas, F J

2008-10-01

Approximately 70-85% of transitional bladder cell carcinomas are non-muscle-invasive. After an initial surgery, around 60-90% will have a recurrence, being the highest risk period the first two years. Urothelium instability could be the main reason for recurrence in mid grade tumours, reason why a single dose of a chemotherapy after transurethral resection of the bladder (TURB) might be insufficient. That is why a deferred therapy in occasions associated with maintenance is recommended. A prospective, controlled and randomized study was performed. We included non-muscle-invasive mid risk bladder tumours. All patients had initially a TURB performed and were randomized to receive a single dose of mitomycin C (MMC), in the immediate postoperative period. A total of 105 patients were included. Mean follow-up was 22, 70 +/- 8, 15 months. MMC was administered to 53 patients. Of these 66, 0% had no recurrence and 34.0% had a non-muscle-invasive recurrence. Of the 52 patients in the non MMC group, 53.8% had no recurrence and 44.2% had a non-muscle-invasive recurrence and only 1 patient had a muscle-invasive progression. We did not find significantly differences in time to recurrence in mid risk tumours when using immediate postoperative single dose of MMC or deferred therapy. There was only one case of myelosuppression. In mid risk non-muscle-invasive tumors, some studies suggest that early intravesical instillation of chemotherapy reduces the risk of recurrence after TURB. We could not show significantly differences when comparing postoperatorive MMC versus traditional deferred instillations.

Management of transitional cell carcinoma of the urinary bladder in dogs: a review.

PubMed

Fulkerson, Christopher M; Knapp, Deborah W

2015-08-01

Transitional cell carcinoma (TCC), also referred to as urothelial carcinoma, is the most common form of urinary bladder cancer in dogs, affecting tens of thousands of dogs worldwide each year. Canine TCC is usually a high grade invasive cancer. Problems associated with TCC include urinary tract obstruction, distant metastases in >50% of affected dogs, and clinical signs that are troubling both to the dogs and to their owners. Risk factors for TCC include exposure to older types of flea control products and lawn chemicals, obesity, female sex, and a very strong breed-associated risk. This knowledge is allowing pet owners to take steps to reduce the risk of TCC in their dog. The diagnosis of TCC is made by histopathology of tissue biopsies obtained by cystoscopy, surgery, or catheter. Percutaneous aspirates and biopsies should be avoided due to the risk of tumor seeding. TCC is most commonly located in the trigone region of the bladder precluding complete surgical resection. Medical treatment is the mainstay for TCC therapy in dogs. Although TCC is not usually curable in dogs, multiple drugs have activity against it. Approximately 75% of dogs respond favorably to TCC treatment and can enjoy several months to a year or more of good quality life. Many promising new therapies for TCC are emerging and with the close similarity between TCC in dogs and high grade invasive bladder cancer in humans, new treatment strategies found to be successful in canine studies are expected to help dogs and to be subsequently translated to humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

[En bloc resection and vaporization techniques for the treatment of bladder cancer].

PubMed

Struck, J P; Karl, A; Schwentner, C; Herrmann, T R W; Kramer, M W

2018-04-12

Modifications in resection techniques may overcome obvious limitations of conventionally performed transurethral resection (e. g., tumor fragmentation) of bladder tumors or provide an easier patient treatment algorithm (e. g., tumor vaporization). The present review article summarizes the current literature in terms of en bloc resection techniques, histopathological quality, complication rates, and oncological outcomes. A separate data search was performed for en bloc resection (ERBT, n = 27) and vaporization (n = 15) of bladder tumors. In most cases, ERBT is performed in a circumferential fashion. Alternatively, ERBT may be performed by undermining the tumor base via antegrade application of short energy impulses. Based on high rates of detrusor in specimens of ERBT (90-100%), a better histopathological quality is assumed. Significant differences in perioperative complication rates have not been observed, although obturator-nerve-based bladder perforations are not seen when laser energy is used. There is a nonstatistically significant trend towards lower recurrence rates in ERBT groups. Tumor vaporization may provide a less invasive technique for older patients with recurrences of low-risk bladder cancer. It can be performed in an outpatient setting. ERBT may provide better histopathological quality. Tumor vaporization is performed in health care systems where reimbursement is adequate.

Robotic-assisted versus open radical cystectomy in bladder cancer: A meta-analysis of four randomized controlled trails.

PubMed

Tang, Jin-Qiu; Zhao, Zhihong; Liang, Yiwen; Liao, Guixiang

2018-02-01

Robot-assisted radical cystectomy (RARC) is increasing annually for treatment of bladder cancer. The objective of this meta-analysis was to compare the safety and efficacy of RARC and open radical cystectomy (ORC) for bladder cancer. Our meta-analysis searches were conducted using PubMed, Web of Science, and Cochrane Library databases to identify randomized controlled trials (RCT) assessing the two techniques. Four RCT studies were identified, including 239 cases. Our studies indicated that RARC was associated with longer operative time (WMD: 69.69, 95% CI:17.25 to122.12; P= 0.009), lower estimated blood loss (WMD: -299.83, 95% CI:-414.66to -184.99; P<0.00001). The two groups had no significant difference in overall perioperative complications, length of hospital stay, lymph node yield and positive surgical margins. RARC is mini-invasive alternative to ORC for bladder cancer. The advantage of RARC was reduced estimated blood loss. More studies are needed to compare the two techniques. Copyright © 2017 John Wiley & Sons, Ltd.

Lower Urinary Tract Symptoms: What's New in Medical Treatment?

PubMed

Peyronnet, Benoit; Brucker, Benjamin M; Michel, Martin C

2018-04-14

Pharmacological treatment is a cornerstone in the management of patients with lower urinary tract symptoms (LUTS). To review emerging evidence in the medical treatment of LUTS. An Embase/Pubmed-based literature search was conducted in December 2017, screening for randomized controlled trials (RCTs), prospective and retrospective series, animal model studies, and reviews on medical treatment of LUTS. The main medical innovation in recent years in overactive bladder (OAB) has been the approval of the first β 3 -adrenoceptor agonists (mirabegron) and intradetrusor onabotulinum toxin A, while several other drugs such as antiepileptics, phosphodiesterase inhibitors, or other β 3 -agonists have brought promising results in phase 3 trials. Intraprostatic injections of various drugs for LUTS/benign prostatic hyperplasia have been investigated, but results of phase 3 trials are still pending, while combination therapies of phosphodiesterase type 5 inhibitors+α-blockers or finasteride have been proved as superior to single therapies in RCTs conducted in these patients. Two new formulations of desmopressin have been approved for nocturia in the USA (desmopressin nasal spray) and Europe/Canada/Australia (desmopressin orally disintegrated tablet). Fedovapagon, a vasopressin V 2 receptor agonist, has recently completed a large phase 3 trial in male patients with nocturia. Other phase 3 trials are ongoing in bladder pain syndrome (AQX 11-25, a SHIP-1 activator) and in neurogenic detrusor overactivity (mirabegron and abobotulinum toxin A). Medical treatment of LUTS is a very active research field with recently approved drugs for nocturia (desmopressin acetate nasal spray/orally disintegrated tablet) and numerous emerging drugs currently investigated in OAB, LUTS/benign prostatic hyperplasia, nocturia, bladder pain syndrome, and neurogenic detrusor overactivity. Medical treatment of lower urinary tract symptoms is a very active research field with recently approved drugs for nocturia (desmopressin acetate nasal spray/orally disintegrated tablet) and numerous emerging drugs in overactive bladder, nocturia, neurogenic detrusor overactivity, bladder pain syndrome, or benign prostatic hyperplasia. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Differences of response of human bladder cancer cells to photodynamic therapy (PDT) with Hypericum perforantum L extract and Photofrin

NASA Astrophysics Data System (ADS)

Nseyo, Unyime; Kim, Albert; Stavropoulos, Nikos E.; Skalkos, Dimitris; Nseyo, Unwana U.; Chung, Theodore D.

2005-04-01

Refractory carcinoma in situ and resistant multifocal transitional cell carcinoma (TCC) of the human urinary bladder respond modestly to PHOTOFRIN (PII) PDT. Hypericum perforatum L., (St. John"s wort /Epirus" Vasalmo, Greece), a medicinal plant used for many human ailments, is under investigation as a new photosensitizer. We have reported on the antiproliferative activity of the lipophilic extract of the Hypericum perforatum L. (HP) against cultured T-24, and NBT-11 bladder cancer cells. We investigated response of the polar methanolic fraction (PMF) of the HP extract versus PHOTOFRIN in photodynamic therapy (PDT) of human bladder cancer cells, RT-4 and T-24.The PMF was extracted from the dry herb with methanol, followed by liquid extraction with petroleum ether. RT-4/T-24, were plated (105 cells/well) and placed in the incubator (370 C, 5%CO) for 24 hours prior to addition of drugs. PII 2ug/ml, or PMF 60ug /ml was added and incubation continued. After 24 hours, the cells were treated with laser light (630nm) with 0,1,2,4 and 8 Joules. The cells were then washed and reincubated for another 24 hours. After this incubation cell survival was assessed by the MTT assay. PMF-PDT induced percent cell kill of 0%, 0%, 0%, 29% and 75%, in RT-4 cells (primary noninvasive urinary bladder TCC) versus 5%, 9%, 13%, 69% and 86%, in T-24 cells(metastatic TTC) at 0,1,2,4 and 8 Joules respectively. PII-PDT induced cell kill of 0 %, 0% ,0%,0% and 9 %, in RT-4 cells versus 0%,10%,0%,21% and 77%, in T-24 cells at 0,1,2,4 and 8 Joules respectively.RT-24 cells were relatively more resistant than T-24 cells to PMF and PII-PDT. Understanding mechanisms of such differential responses might prove useful

Lower urinary tract development and disease

PubMed Central

Rasouly, Hila Milo; Lu, Weining

2013-01-01

Congenital Anomalies of the Lower Urinary Tract (CALUT) are a family of birth defects of the ureter, the bladder and the urethra. CALUT includes ureteral anomalies such as congenital abnormalities of the ureteropelvic junction (UPJ) and ureterovesical junction (UVJ), and birth defects of the bladder and the urethra such as bladder-exstrophy-epispadias complex (BEEC), prune belly syndrome (PBS), and posterior urethral valves (PUV). CALUT is one of the most common birth defects and is often associated with antenatal hydronephrosis, vesicoureteral reflux (VUR), urinary tract obstruction, urinary tract infections (UTI), chronic kidney disease and renal failure in children. Here, we discuss the current genetic and molecular knowledge about lower urinary tract development and genetic basis of CALUT in both human and mouse models. We provide an overview of the developmental processes leading to the formation of the ureter, bladder, and urethra, and different genes and signaling pathways controlling these developmental processes. Human genetic disorders that affect the ureter, bladder and urethra and associated gene mutations are also presented. As we are entering the post-genomic era of personalized medicine, information in this article may provide useful interpretation for the genetic and genomic test results collected from patients with lower urinary tract birth defects. With evidence-based interpretations, clinicians may provide more effective personalized therapies to patients and genetic counseling for their families. PMID:23408557

[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.

Tissue Engineering of Urinary Bladder and Urethra: Advances from Bench to Patients

PubMed Central

Bouhout, Sara; Chabaud, Stéphane; Bolduc, Stéphane

2013-01-01

Urinary tract is subjected to many varieties of pathologies since birth including congenital anomalies, trauma, inflammatory lesions, and malignancy. These diseases necessitate the replacement of involved organs and tissues. Shortage of organ donation, problems of immunosuppression, and complications associated with the use of nonnative tissues have urged clinicians and scientists to investigate new therapies, namely, tissue engineering. Tissue engineering follows principles of cell transplantation, materials science, and engineering. Epithelial and muscle cells can be harvested and used for reconstruction of the engineered grafts. These cells must be delivered in a well-organized and differentiated condition because water-seal epithelium and well-oriented muscle layer are needed for proper function of the substitute tissues. Synthetic or natural scaffolds have been used for engineering lower urinary tract. Harnessing autologous cells to produce their own matrix and form scaffolds is a new strategy for engineering bladder and urethra. This self-assembly technique avoids the biosafety and immunological reactions related to the use of biodegradable scaffolds. Autologous equivalents have already been produced for pigs (bladder) and human (urethra and bladder). The purpose of this paper is to present a review for the existing methods of engineering bladder and urethra and to point toward perspectives for their replacement. PMID:24453796

A novel single compartment in vitro model for electrophysiological research using the perfluorocarbon FC-770.

PubMed

Choudhary, M; Clavica, F; van Mastrigt, R; van Asselt, E

2016-06-20

Electrophysiological studies of whole organ systems in vitro often require measurement of nerve activity and/or stimulation of the organ via the associated nerves. Currently two-compartment setups are used for such studies. These setups are complicated and require two fluids in two separate compartments and stretching the nerve across one chamber to the other, which may damage the nerves. We aimed at developing a simple single compartment setup by testing the electrophysiological properties of FC-770 (a perfluorocarbon) for in vitro recording of bladder afferent nerve activity and electrical stimulation of the bladder. Perflurocarbons are especially suitable for such a setup because of their high oxygen carrying capacity and insulating properties. In male Wistar rats, afferent nerve activity was recorded from postganglionic branches of the pelvic nerve in vitro, in situ and in vivo. The bladder was stimulated electrically via the efferent nerves. Organ viability was monitored by recording spontaneous contractions of the bladder. Additionally, histological examinations were done to test the effect of FC-770 on the bladder tissue. Afferent nerve activity was successfully recorded in a total of 11 rats. The bladders were stimulated electrically and high amplitude contractions were evoked. Histological examinations and monitoring of spontaneous contractions showed that FC-770 maintained organ viability and did not cause damage to the tissue. We have shown that FC-770 enables a simple, one compartment in vitro alternative for the generally used two compartment setups for whole organ electrophysiological studies.

Urinary catheters: history, current status, adverse events and research agenda

PubMed Central

Feneley, Roger C. L.; Hopley, Ian B.; Wells, Peter N. T.

2015-01-01

Abstract For more than 3500 years, urinary catheters have been used to drain the bladder when it fails to empty. For people with impaired bladder function and for whom the method is feasible, clean intermittent self-catheterization is the optimal procedure. For those who require an indwelling catheter, whether short- or long-term, the self-retaining Foley catheter is invariably used, as it has been since its introduction nearly 80 years ago, despite the fact that this catheter can cause bacterial colonization, recurrent and chronic infections, bladder stones and septicaemia, damage to the kidneys, the bladder and the urethra, and contribute to the development of antibiotic resistance. In terms of medical, social and economic resources, the burden of urinary retention and incontinence, aggravated by the use of the Foley catheter, is huge. In the UK, the harm resulting from the use of the Foley catheter costs the National Health Service between £1.0–2.5 billion and accounts for ∼2100 deaths per year. Therefore, there is an urgent need for the development of an alternative indwelling catheter system. The research agenda is for the new catheter to be easy and safe to insert, either urethrally or suprapubically, to be retained reliably in the bladder and to be withdrawn easily and safely when necessary, to mimic natural physiology by filling at low pressure and emptying completely without damage to the bladder, and to have control mechanisms appropriate for all users. PMID:26383168

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

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.

Effect of extracorporeal magnetic energy stimulation on bothersome lower urinary tract symptoms and quality of life in female patients with stress urinary incontinence and overactive bladder.

PubMed

Lo, Tsia-Shu; Tseng, Ling-Hong; Lin, Yi-Hao; Liang, Ching-Chung; Lu, Ching-Yi; Pue, Leng Boi

2013-11-01

The aim of this study was to investigate the efficacy of extracorporeal magnetic stimulation (EMS) for the treatment of bothersome and severe symptoms of stress urinary incontinence (SUI) and overactive bladder syndrome (OAB) in female patients. A retrospective review was conducted on patients with SUI and OAB who were referred to EMS therapy. Successful treatment for the bothersome symptoms of OAB and SUI was defined as score ≤1 for questions 2 and 3 on the Urodynamic Distress Inventory-6. The objective cure of SUI and OAB was defined as no urinary leakage during the cough stress test and any urgency, urge incontinence and voiding frequency of less than eight times per 24 h based on the 3-day bladder diary, after the 9 weeks of treatment, respectively. Ninety-three patients with SUI or OAB underwent a 9-week course of EMS at 20 min twice weekly. Seventy-two (77%) patients completed EMS treatment. Geographical factor and poor economic status were two main factors for dropout. A total of 94.1% (32 of 34) and 86.8% (33 of 38) of subjects had successful treatment for the bothersome symptoms of OAB and SUI, respectively. In contrast, the cure rate for OAB and SUI was only 61.7% and 42.1%, respectively. There was also a significant improvement in both Urogenital Distress Inventory Short Form (bothersome on lower urinary tract symptoms) and the Incontinence Impact Questionnaire Short Form (quality of life) total score in both groups after EMS. EMS is a safe and effective alternative method for treating SUI and OAB. Further studies are needed to evaluate the long-term efficacy. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

[Drug therapy of female urinary incontinence].

PubMed

Hampel, C; Gillitzer, R; Pahernik, S; Melchior, S W; Thüroff, J W

2005-03-01

Drug treatment for female urinary incontinence requires a thorough knowledge of the differential diagnosis and pathophysiology of incontinence as well as of the pharmacological agents employed. Pharmacotherapy has to be tailored to suit the incontinence subtype and should be carefully balanced according to efficacy and side effects of the drug. Women with urge incontinence require treatment that relaxes or desensitizes the bladder (antimuscarinics, estrogens, alpha-blockers, beta-mimetics, botulinum toxin A, resiniferatoxin, vinpocetine), whereas patients with stress incontinence need stimulation and strengthening of the pelvic floor and external sphincter (alpha-mimetics, estrogens, duloxetine). Females with overflow incontinence need reduction of outflow resistance (baclofen, alpha-blockers, intrasphincteric botulinum toxin A) and/or improvement of bladder contractility (parasympathomimetics). If nocturia or nocturnal incontinence are the major complaints, control of diuresis is obtained by administration of the ADH analogue desmopressin. Future developments will help to further optimize the pharmacological therapy for female urinary incontinence.

Practical application of color Doppler ultrasonography in patients with ejaculatory dysfunction.

PubMed

Hara, Ryoei; Nagai, Atsushi; Fujii, Tomohiro; Fukumoto, Kazuhiko; Ohira, Shin; Jo, Yoshimasa; Yokoyama, Teruhiko; Miyaji, Yoshiyuki

2015-06-01

We describe two cases in which dynamic analysis of ejaculation using color Doppler ultrasonography was useful in diagnosis of ejaculatory dysfunction and planning of therapy. The first patient was a 32-year-old man with a diagnosis of retrograde ejaculation. A bladder neck collagen injection was carried out, as the main cause was thought to be the bladder neck remaining open during ejaculation. The patient had antegrade ejaculation 1 week later. The second patient was a 48-year-old man with a diagnosis of anorgasmia accompanied by decreased seminal emission and insufficient function of the rhythmic pelvic striated muscles. The patient was prescribed etilefrine hydrochloride 15 mg/day. The symptom improved 2 weeks after starting this drug. These cases suggest that the use of color Doppler ultrasonography during ejaculation can improve the understanding of ejaculatory dysfunction and therapy for this condition. © 2015 The Japanese Urological Association.

Pharmacology of the lower urinary tract

PubMed Central

Hennenberg, Martin; Stief, Christian G.; Gratzke, Christian

2014-01-01

Pharmacology of the lower urinary tract provides the basis for medical treatment of lower urinary tract symptoms (LUTS). Therapy of LUTS addresses obstructive symptoms (frequently explained by increased prostate smooth muscle tone and prostate enlargement) in patients with benign prostate hyperplasia (BPH) and storage symptoms in patients with overactive bladder (OAB). Targets for medical treatment include G protein-coupled receptors (α1-adrenoceptors, muscarinic acetylcholine receptors, β3-adrenoceptors) or intracellular enzymes (5α-reductase; phosphodiesterase-5, PDE5). Established therapies of obstructive symptoms aim to induce prostate smooth muscle relaxation by α1-blockers or PDE5 inhibitors, or to reduce prostate growth and volume with 5α-reductase inhibitors. Available options for treatment of OAB comprise anitmuscarinics, β3-adrenoceptor agonists, and botulinum toxin A, which improve storage symptoms by inhibition of bladder smooth muscle contraction. With the recent approval of β3-antagonists, PDE inhibitors, and silodosin for therapy of LUTS, progress from basic research of lower urinary tract pharmacology was translated into new clinical applications. Further targets are in preclinical stages of examination, including modulators of the endocannabinoid system and transient receptor potential (TRP) channels. PMID:24744518

[A case of eosinophilic cystitis mimicking an invasive bladder cancer].

PubMed

Okazaki, Satoshi; Hori, Jun-Ichi; Kita, Masafumi; Yamaguchi, Satoshi; Kawakami, Norihiro; Kakizaki, Hidehiro

2014-12-01

A 60-year-old woman was referred to our hospital because of gross hematuria, right lumbar pain and lower abdominal pain. Computed tomography (CT) scan revealed hydronephrosis of the right kidney, irregular bladder wall thickening at the right lateral and posterior portion and external iliac lymph node swelling of the right side. Laboratory data revealed disseminated intravascular coagulation syndrome (DIC) and eosinophilia. Because she developed a high fever that was caused by acute obstructive pyelonephritis of the right kidney, percutaneous nephrostomy was placed and the therapy for DIC was initiated. Pathological examination of transurethral resection of bladder tumor performed twice showed no malignancy but inflammatory infiltration of many eosinocytes, leading to the diagnosis of eosinophilic cystitis (EC). We considered the possibility of allergic reaction to the drugs she was taking as the etiology of EC and discontinued all drugs. Although eosinophilia was resolved afterward, she then developed brain infarction, followed by cerebral hemorrhage. She was transferred to a rehabilitation hospital for long-term care. CT scan that was performed 4 months after the initial presentation showed the resolution of hydronephrosis of the right kidney and external iliac lymph node swelling and the improvement of bladder wall thickness. Hydronephrosis of the right kidney has not recurred after removing the nephrostomy catheter. EC is a rare condition that could mimic an invasive bladder cancer. EC should be considered if bladder tumor is associated with eosinophilia. Therapeutic consideration for thromboembolic events should be made in patients with EC.

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.

Smac mimetic enables the anticancer action of BCG-stimulated neutrophils through TNF-α but not through TRAIL and FasL.

PubMed

Jinesh G, Goodwin; Chunduru, Srinivas; Kamat, Ashish M

2012-07-01

BCG, the current gold standard immunotherapy for bladder cancer, exerts its activity via recruitment of neutrophils to the tumor microenvironment. Many patients do not respond to BCG therapy, indicating the need to understand the mechanism of action of BCG-stimulated neutrophils and to identify ways to overcome resistance to BCG therapy. Using isolated human neutrophils stimulated with BCG, we found that TNF-α is the key mediator secreted by BCG-stimulated neutrophils. RT4v6 human bladder cancer cells, which express TNFR1, CD95/Fas, CD95 ligand/FasL, DR4, and DR5, were resistant to BCG-stimulated neutrophil conditioned medium but effectively killed by the combination of conditioned medium and Smac mimetic. rhTNF-α and rhFasL, but not rhTRAIL, in combination with Smac mimetic, generated signature molecular events similar to those produced by BCG-stimulated neutrophils in combination with Smac mimetic. However, experiments using neutralizing antibodies to these death ligands showed that TNF-α secreted from BCG-stimulated neutrophils was the key mediator of anticancer action. These findings explain the mechanism of action of BCG and identified Smac mimetics as potential combination therapeutic agents for bladder cancer.

Bladder augmentation without integration of intact bowel segments: critical review and future perspectives.

PubMed

Gurocak, Serhat; De Gier, Robert P E; Feitz, Wouter

2007-03-01

We evaluated the long-term results of autoaugmentation in the pediatric age group and summarized technical adaptations, experimental options and future perspectives for treating these patients. A directed MEDLINE literature review was performed to assess different techniques and alternative options in autoaugmentation procedures. Of 150 studies 49 in the subgroup with the longest duration of followup to show the long-term outcome of the autoaugmentation procedures were chosen for this review. Information gained from these data was reviewed and new perspectives were summarized. Enterocystoplasy is an effective mode of therapy with acceptable morbidity and satisfactory clinical results, although it is major intraperitoneal surgery with various complications and patients need prolonged convalescence to adapt to these surgical procedures. On the other hand, patient selection seems to be the most crucial step for the success of autoaugmentation procedures because the clinical outcome does not appear to be durable. Achievement of better compliance after autoaugmentation procedures seems to be less pronounced and of shorter duration than that of conventional enterocystoplasty. On the other hand, the low morbidity and lack of side effects of bowel integration into the urinary tract are the definite advantages of this technique. It is the responsibility of the physician to determine the balance between the limited efficacy of the procedures vs the definite advantages. Although functionally improved parameters are obtained in tissue engineered autologous bladders, there is an absolute need for additional studies before this challenging technique could be applied widely.

Clostridium butyricum MIYAIRI 588 shows antitumor effects by enhancing the release of TRAIL from neutrophils through MMP-8.

PubMed

Shinnoh, Masahide; Horinaka, Mano; Yasuda, Takashi; Yoshikawa, Sae; Morita, Mie; Yamada, Takeshi; Miki, Tsuneharu; Sakai, Toshiyuki

2013-03-01

Bacillus Calmette-Guérin (BCG) intravesical therapy against superficial bladder cancer is one of the most successful immunotherapies in cancer, though the precise mechanism has not been clarified. Recent studies have demonstrated urinary tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels to be higher in BCG-responsive patients than non-responders and shown that polymorphonuclear neutrophils (PMNs) migrating to the bladder after BCG instillation release large amounts of TRAIL. To establish a safer and more effective intravesical therapy than BCG, we examined whether other bacteria induced similar effects. We stimulated PMNs or peripheral blood mononuclear cells (PBMCs) with BCG or other bacteria, and then aliquots of the culture supernatants or cell lysates were assayed for TRAIL. We examined the signaling pathway regulating the release of TRAIL from PMNs and evaluated the antitumor effects of BCG or other bacteria in vitro and in vivo. We have found that Clostridium butyricum MIYAIRI 588 (CBM588) induces the release of endogenous TRAIL from PMNs as well as BCG. In addition, we have shown that matrix metalloproteinase 8 (MMP-8) is one of the key factors responsible for the release. Interestingly, TLR2/4 signaling pathway has been suggested to be important for the release of TRAIL by MMP-8. CBM588 has been proven to be as effective as BCG against cancer cells by inducing apoptosis in vivo as well as in vitro. Taken together, these results strongly suggest that CBM588 is promising for a safer and more effective therapy against bladder cancer.

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

PubMed

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

2017-09-01

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

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

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

Plataniotis, George A., E-mail: george.plataniotis@nhs.net; Dale, Roger G.

2014-03-15

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

The use of urinary bladder matrix in the treatment of complicated open wounds.

PubMed

Lanteri Parcells, Alexis; Abernathie, Brenon; Datiashvili, Ramazi

2014-07-01

Management of complicated open wounds represents a challenge when reconstructive options are not applicable. Urinary bladder matrix (UBM) provides a biocompatible material that allows inductivetissue remodeling. The use of urinary bladder matrix inthe treatment of 5 patients with complicated open wounds that failed toheal with conventional therapy is presented. A 3-year old male sustained a second-degree oil burn measuring 8 cm x 4 cm to his dorsal forearm; UBM was applied weekly and the wound epithelialized in 3 weeks. A 52-year old male sustained massive second and third degree burns to his leg after a fire; UBM was applied weekly and the wound epithelialized in 28 weeks. A 61-year old female sustained a severe crushing injury to her right knee. A gastrocnemius muscle transfer and rectus abdominus muscle free flap transfer both failed, then UBM and vacuum-assisted closure therapy were applied and the wound epithelialized in 24 weeks. A 54-year old female underwent a breast mastectomy and immediate reconstruction with pedicled transverse rectus abdominus flap. The patient developed partial necrosis and the wound was managed with UBM and vacuum-assisted closure therapy. The wound epithelialized in 12 weeks. A 36-year old female sustained severe degloving injuries to both hands with exposed metacarpals. Weekly application of UBM provided tissue remodeling over the bones, which allowed successful skin grafting and closure. These experiences show UBM to be an effective method in management of complicated open wounds in select cases. Further studies need to be implemented to confirm this conclusion.

Effects of Cyclooxygenase on the Urothelium of the Urinary Bladder of Mice Exposed to Pelvic Radiation.

PubMed

Ozbilgin, M Kemal; Onal, Tuna; Ozcan, Cemil; Temel, Merve; Aktas, Caner; Gareveran, Manuchehr Salehi; Uluer, Elgin Turkoz; Inan, Sevinc; Kurtman, Cengiz

2016-04-01

To determine the role of cyclooxygenase (COX) expression in the urothelium of the urinary bladder during radiation injury caused by pelvic radiotherapy for cancer therapy. Twenty-four male Swiss Albino mice were separated into 4 groups. The first group was the control group (Group 1) and the second, third, and fourth groups were euthanized after 24 hours (Group 2), 48 hours (Group 3), and 7 days (Group 4), respectively. A single-fractioned 10 Gy of ionizing radiation was applied to all mice's pelvic zone with Co-60. Bladders were removed completely from the pelvic region. Histochemical analysis using hematoxylin and eosin and immunohistochemical analysis using anti-COX-1 and COX-2 antibodies were performed on tissue samples. The immunoreactivities of the urinary bladder were quantified using H-score measurement, and statistical comparison was performed. In the immunohistochemical examination the COX-1 immunoreactivities were found to be higher in the urothelium of the bladder in the radiation exposed groups than in the normal control group (group 1) (p < 0.005). Additionally, high immunoreactivity of COX-2 molecule was established in groups 2, 3, and 4 of radiation groups as compared to group 1 (p < 0.005) in examination of the urothelium. COX-1 and COX-2 immunoreactivities in the submucosa were detected higher in group 4 than in the other groups (p < 0.005). COX-1 and COX-2 expressions in the urothelium and subepithelium of the urinary bladder were investigated in mice during the acute radiation response. The expression of COX-1 and COX-2 in the urothelium seems to prevent bladder damage from radiation, supplying differentiation and restoration of the urothelium.

Deformable structure registration of bladder through surface mapping.

PubMed

Xiong, Li; Viswanathan, Akila; Stewart, Alexandra J; Haker, Steven; Tempany, Clare M; Chin, Lee M; Cormack, Robert A

2006-06-01

Cumulative dose distributions in fractionated radiation therapy depict the dose to normal tissues and therefore may permit an estimation of the risk of normal tissue complications. However, calculation of these distributions is highly challenging because of interfractional changes in the geometry of patient anatomy. This work presents an algorithm for deformable structure registration of the bladder and the verification of the accuracy of the algorithm using phantom and patient data. In this algorithm, the registration process involves conformal mapping of genus zero surfaces using finite element analysis, and guided by three control landmarks. The registration produces a correspondence between fractions of the triangular meshes used to describe the bladder surface. For validation of the algorithm, two types of balloons were inflated gradually to three times their original size, and several computerized tomography (CT) scans were taken during the process. The registration algorithm yielded a local accuracy of 4 mm along the balloon surface. The algorithm was then applied to CT data of patients receiving fractionated high-dose-rate brachytherapy to the vaginal cuff, with the vaginal cylinder in situ. The patients' bladder filling status was intentionally different for each fraction. The three required control landmark points were identified for the bladder based on anatomy. Out of an Institutional Review Board (IRB) approved study of 20 patients, 3 had radiographically identifiable points near the bladder surface that were used for verification of the accuracy of the registration. The verification point as seen in each fraction was compared with its predicted location based on affine as well as deformable registration. Despite the variation in bladder shape and volume, the deformable registration was accurate to 5 mm, consistently outperforming the affine registration. We conclude that the structure registration algorithm presented works with reasonable accuracy and provides a means of calculating cumulative dose distributions.

Treatment Trends and Outcomes of Small-Cell Carcinoma of the Bladder

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

Koay, Eugene J.; MD Anderson Cancer Center, Houston, Texas; Teh, Bin S., E-mail: bteh@tmh.org

2012-05-01

Purpose: Treatment for small-cell carcinoma of the bladder is largely guided by case reports, retrospective reviews, and small prospective trials. This study aimed to study outcomes using a large population-based database. Methods: The Surveillance, Epidemiology, and End Results-Medicare database (1991-2005) was used to analyze how different treatment combinations of specific bladder surgeries, chemotherapy, and radiation affected patient outcomes. Trends in the use of these combinations over time were also analyzed. Results: A total of 533 patients were retrieved from the database. A bladder-sparing approach involving transurethral resection of the bladder tumor (TURBT) combined with chemotherapy and radiation yielded no significantmore » difference in overall survival compared with patients undergoing at least a cystectomy (of whom over 90% received radical cystectomy) with chemotherapy (p > 0.05). The analysis of treatment trends indicated that these two general strategies for cure combined to account for fewer than 20% of patients. A majority of patients (54%) received TURBT as their only surgical treatment, and a subset analysis of these patients indicated that chemotherapy played a role in all stages of disease (p < 0.05) whereas radiation improved overall survival in regional-stage disease (p < 0.05). Conclusion: Relatively few patients with small-cell carcinoma of the bladder receive potentially curative therapies. Chemotherapy should be a major component of treatment. Cystectomy and bladder-sparing approaches represent two viable strategies and deserve further investigation to identify the patients who may benefit from organ preservation or not. In addition, the role of radiation in regional-stage disease should be investigated further, because it positively affects survival after TURBT.« less

Diagnosis of cystocele--the correlation between clinical and radiological evaluation.

PubMed

Altman, Daniel; Mellgren, Anders; Kierkegaard, Jonas; Zetterström, Jan; Falconer, Christian; López, Annika

2004-01-01

In patients with genital prolapse involving several compartments simultaneously, radiologic investigation can be used to complement the clinical assessment. Contrast medium in the urinary bladder enables visualization of the bladder base at cystodefecoperitoneography (CDP). The aim of the present study was to evaluate the correlation between clinical examination using the Pelvic Organ Prolapse Quantification system (POP-Q) and CDP. Thirty-three women underwent clinical assessment and CDP. Statistical analysis using Pearson's correlation coefficient ( r) demonstrated a wide variability between the current definition of cystocele at CDP and POP-Q ( r=0.67). An attempt to provide an alternative definition of cystocele at CDP had a similar outcome ( r=0.63). The present study demonstrates a moderate correlation between clinical and radiologic findings in patients with anterior vaginal wall prolapse. It does not support the use of bladder contrast at radiologic investigation in the routine preoperative assessment of patients with genital prolapse.

Testing of Alternative Materials for Advanced Suit Bladders

NASA Technical Reports Server (NTRS)

Bue, Grant; Orndoff, Evelyne; Makinen, Janice; Tang, Henry

2011-01-01

Several candidate advanced pressure bladder membrane materials have been developed for NASA Johnson Space Center by DSM Biomedical for selective permeability of carbon dioxide and water vapor. These materials were elasthane and two other formulations of thermoplastic polyether polyurethane. Each material was tested in two thicknesses for permeability to carbon dioxide, oxygen and water vapor. Although oxygen leaks through the suit bladder would amount to only about 60 cc/hr in a full size suit, significant amounts of carbon dioxide would not be rejected by the system to justify its use. While the ratio of carbon dioxide to oxygen permeability is about 48 to 1, this is offset by the small partial pressure of carbon dioxide in acceptable breathing atmospheres of the suit. Humidity management remains a possible use of the membranes depending on the degree to which the water permeability is inhibited by cations in the sweat. Tests are underway to explore cation fouling from sweat.

Contouring and Constraining Bowel on a Full-Bladder Computed Tomography Scan May Not Reflect Treatment Bowel Position and Dose Certainty in Gynecologic External Beam Radiation Therapy

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

Yaparpalvi, Ravindra, E-mail: ryaparpa@montefiore.org; Mehta, Keyur J.; Bernstein, Michael B.

Purpose: To evaluate, in a gynecologic cancer setting, changes in bowel position, dose-volume parameters, and biological indices that arise between full-bladder (FB) and empty-bladder (EB) treatment situations; and to evaluate, using cone beam computed tomography (CT), the validity of FB treatment presumption. Methods and Materials: Seventeen gynecologic cancer patients were retrospectively analyzed. Empty-bladder and FB CTs were obtained. Full-bladder CTs were used for planning and dose optimization. Patients were given FB instructions for treatment. For the study purpose, bowel was contoured on the EB CTs for all patients. Bowel position and volume changes between FB and EB states were determined.more » Full-bladder plans were applied on EB CTs for determining bowel dose-volume changes in EB state. Biological indices (generalized equivalent uniform dose and normal tissue complication probability) were calculated and compared between FB and EB. Weekly cone beam CT data were available in 6 patients to assess bladder volume at treatment. Results: Average (±SD) planned bladder volume was 299.7 ± 68.5 cm{sup 3}. Median bowel shift in the craniocaudal direction between FB and EB was 12.5 mm (range, 3-30 mm), and corresponding increase in exposed bowel volume was 151.3 cm{sup 3} (range, 74.3-251.4 cm{sup 3}). Absolute bowel volumes receiving 45 Gy were higher for EB compared with FB (mean 328.0 ± 174.8 vs 176.0 ± 87.5 cm{sup 3}; P=.0038). Bowel normal tissue complication probability increased 1.5× to 23.5× when FB planned treatments were applied in the EB state. For the study, the mean percentage value of relative bladder volume at treatment was 32%. Conclusions: Full-bladder planning does not necessarily translate into FB treatments, with a patient tendency toward EB. Given the uncertainty in daily control over bladder volume for treatment, we strongly recommend a “planning-at-risk volume bowel” (PRV{sub B}owel) concept to account for bowel motion between FB and EB that can be tailored for the individual patient.« less

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.

Personalized medicine for targeted and platinum-based chemotherapy of lung and bladder cancer

PubMed Central

Cimino, George D; Pan, Chong-xian; Henderson, Paul T

2013-01-01

The personalized medicine revolution is occurring for cancer chemotherapy. Biomarkers are increasingly capable of distinguishing genotypic or phenotypic traits of individual tumors, and are being linked to the selection of treatment protocols. This review covers the molecular basis for biomarkers of response to targeted and cytotoxic lung and bladder cancer treatment with an emphasis on platinum-based chemotherapy. Platinum derivatives are a class of drugs commonly employed against solid tumors that kill cells by covalent attachment to DNA. Platinum–DNA adduct levels in patient tissues have been correlated to response and survival. The sensitivity and precision of adduct detection has increased to the point of enabling subtherapeutic dosing for diagnostics applications, termed diagnostic microdosing, prior to the initiation of full-dose therapy. The clinical status of this unique phenotypic marker for lung and bladder cancer applications is detailed along with discussion of future applications. PMID:23394702

[Urinary incontinence].

PubMed

Kuhn, Annette

2010-01-01

Incontinence is a common age-dependent and increasing problem in women that may mainly present as stress incontinence, overactive bladder, mixed incontinence or other forms. A thorough history, gynaecological and neurological examination and urinalysis as initial step will lead to the diagnosis and treatment. If midstream urine is difficult to receive, a catheter urine will be easy to obtain. Further investigations as urodynamics, cystoscopy and ultrasound may be required. As initial step, stress incontinence should be treated with physiotherapy and pelvic floor exercises, if not successful with operations as suburethral slings. Slings have good long-term success rates of approximately 85 % with a low morbidity and can even be inserted under local anaesthetic. The treatment of idiopathic overactive bladder consists of bladder training, a behavioural therapy, and mainly anticholinergics. Anticholinergics may cause side effects particularly in the elderly who are under several medications that may add anticholinergic effects as antidepressants, antibiotics or antihistaminics.

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.

Combined Bladder Neck Reconstruction and Continent Stoma Creation as a Suitable Alternative for Continence in Bladder Exstrophy: a Preliminary Report.

PubMed

Kasprenski, Matthew; Benz, Karl; Jayman, John; Lue, Kathy; Maruf, Mahir; Baumgartner, Timothy; Gearhart, John

2018-05-25

To explore the use of concomitant BNR and creation of a continent stoma (CS) in patients that are not quite eligible for BNR, but still strongly desire volitional voiding. The authors retrospectively reviewed an institutional database of EEC patients for those who underwent BNR-CS between 2000 and 2015. Indications for a BNR-CS, perioperative outcomes, and continence status were evaluated. Method of voiding and continence status were analyzed for patients with greater than six months of follow-up after the BNR-CS. A total of 24 EEC patients (15 male and 9 female) underwent BNR-CS at a median age of 8.9 years (range 5.4-17.4). This included, 18 patients with classic bladder exstrophy (CBE), 5 with epispadias, and 1 with a cloacal exstrophy variant. There were 5 (20.1%) surgical complications following the BNR-CS, including 3 febrile urinary tract infections, 1 superficial wound infection, and 1 urethrocutaneous fistula. The median follow-up time from the time of BNR-CS was 1.1 years (range 0.1-14.1). Seventeen of 24 patients (71%) had a follow-up greater than 6 months and were evaluated for continence. Twelve patients (71%) were completely dry for intervals greater than 3 hours following BNR-CS. Five (29%) did not achieve continence with BNR-CS. Of those 5 patients, 3 (60%) underwent subsequent bladder neck transection. Combined BNR and CS is a suitable alternative to achieve urinary continence in patients that are not ideal candidates for BNR alone. This approach can offer a select group of patients the opportunity for volitional voiding. Copyright © 2018. Published by Elsevier Inc.

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

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.

Hormone replacement therapy and risk of malignancy.

PubMed

Diamanti-Kandarakis, Evanthia

2004-02-01

The fact that today our concern is oriented towards the risks rather than the benefits of hormone replacement therapy could be the clearest message about our current position. The safety of hormone replacement therapy, an estrogen-progestin combination which has been sympathetic to and supportive of disturbing menopausal symptoms of women, is seriously challenged. Four randomized trials have now reported on the results of hormone replacement therapy in major potentially fatal conditions, in more than 20,000 women studied for about 5 years. The main concern regarding the increased risk of malignancy in healthy postmenopausal women in western countries has been breast cancer. It is estimated to cause an extra case in about six per 1000 users aged 50-59 and 12 per 1000 aged 60-69. Over the same period the estimated risk of endometrial cancer rates are not increased, with a relative risk of 0.76 per 1000 users aged 50-59. Overall, however, the increased incidence of malignancies is greater than any reduction, one per 230 users aged 50-59 and one per 150 aged 60-69. Randomized trials examining other important but rarer malignancies, like ovarian, gall bladder and urinary bladder cancer, are either nonexistent or too small to reliably describe any effects of hormone replacement therapy. Conclusively epidemiological evidence suggests that hormone replacement therapy is associated with a small but substantial increase in breast cancer risk and combined estrogen-progesterone regimens further increase this hazard. Additionally, the evidence from the recent double blind placebo controlled randomized trial on the slight increase in the incidence of adverse cardiovascular events, has turned our orientation away from hormone replacement therapy as a long term therapy in postmenopausal women. In this review, the effort is to approach comprehensively and globally the information on the risks of hormone replacement therapy on several cancer sites.

Position statement: a clinical approach to the management of adult non-neurogenic overactive bladder.

PubMed

Chung, Eric; Lee, Dominic; Gani, Johan; Gillman, Michael; Maher, Christopher; Brennan, Janelle; Johns Putra, Lydia; Ahmad, Laura; Chan, Lewis Lw

2018-01-15

Overactive bladder (OAB) is a highly prevalent medical condition that has an adverse impact on various health-related quality-of-life domains, including a significant psychosocial and financial burden. This position statement, formulated by members of the Urological Society of Australia and New Zealand and the UroGynaecological Society of Australasia, summarises the current recommendations for clinical diagnosis and treatment strategies in patients with non-neurogenic OAB, and guides clinicians in the decision-making process for managing the condition using evidence-based medicine. Main recommendations: Diagnosis and initial management should be based on thorough clinical history, examination and basic investigations to exclude underlying treatable causes such as urinary tract infection and urological malignancy. Initial treatment strategies for OAB involve conservative management with behavioural modification and bladder retraining. Second-line management involves medical therapy using anticholinergic or β3 agonist drugs provided there is adequate assessment of bladder emptying. If medical therapy is unsuccessful, further investigations with urodynamic studies and cystourethroscopy are recommended to guide further treatment. Intravesical botulinum toxin and sacral neuromodulation should be considered in medical refractory OAB. Changes in management as a result of this statement: OAB is a constellation of urinary symptoms and is a chronic condition with a low likelihood of cure; managing patient expectations is essential because OAB is challenging to treat. At present, the exact pathogenesis of OAB remains unclear and it is likely that there are multiple factors involved in this disease complex. Current medical treatment remains far from ideal, although minimally invasive surgery can be effective. Further research into the pathophysiology of this common condition will hopefully guide future developments in disease management.

Herbal tea extract combined with light-induced significant in vitro cytotoxicity of human bladder cancer cells

NASA Astrophysics Data System (ADS)

Nseyo, Unyime; Kim, Albert; Stavropoulos, Nicholas E.; Skalkos, Dimitris; Nseyo, U. U.; Chung, Theodore D.

2005-04-01

The anti-inflammatory, anti-microbial, antiviral, and antidepressant activities of the Greek herb, Hypericum Perforatum L, HP L, have been attributed to the total extract or single constituents. We investigated the use of the extract,specifically of the polar methanolic fraction (PMF) of Epirus"HPL in photodynamic therapy (PDT) alone and in combination with recombinant Interferon-a2b (IFN) and gemcitabine (GCB) in the treatment of human bladder cancer cells. The PMF was extracted from the dry herb with methanol, followed by liquid-liquid extraction with petroleum ether. T-24 bladder cancer cells were plated (105 cells/well) and placed in the incubator (370 C, 5%CO) for 24 hours prior to addition of drugs. PMF 60ug/ml was added and incubation continued. After 24 hours, the cells were subjected to laser light (630nm) treatment with 0, 1, 4 and 8 Joules. After reincubation for 24 hours, IFN, (50,000 IU) or GCB, (2ug/ml) was added to the PDT-treated cells. After this incubation cell survival was assessed by the MTT assay. PMF-PDT alone-induced percent cell kill of 0%, 8%, 44% and 80% versus 31%, 64 and 86 % for PMF-PDT and IFN, versus 63%, 80% and 88% for MPF-PDT plus GCB at 1, 2, 4 and 8 Joules respectively. IFN and GCB induced 20% and 53% cell kill respectively. Our data suggest that MPF may be an effective agent for in vitro photodynamic therapy. PMF-PDT combined with Intron A, or gemcitabine achieved improved kill of cultured bladder cancer cells. Confirmation of these results in preclinical studies may lead to clinical trials.

Emerging role of immunotherapy in urothelial carcinoma - immunobiology/biomarkers

PubMed Central

Sweis, Randy F.; Galsky, Matthew D.

2017-01-01

Urothelial bladder cancer is one of the first cancers recognized to be immunogenic since 40 years ago when the use of bacillus Calmette–Guerin (BCG) was shown to prevent recurrence. Since that time, our knowledge of immune biology of cancer has expanded tremendously, and bladder cancer patients finally have new active immunotherapeutic drugs with on the horizon. Anti-programmed cell death-1 (PD-1)/(programmed cell death ligand-1 (PD-L1) therapy has shown impressively durable responses in urothelial bladder cancer (UBC), but the reported response rates warrant improvement. To outline potential strategies to overcome tumor immune resistance, herein, we summarize current models of tumor immunology with a specific focus on bladder cancer. Recognition of tumor-specific antigens through cross-presentation, T cell priming and activation, and trafficking of immune cells to the tumor microenvironment are some of the critical steps we now understand to be necessary for an effective anti-tumor immune response. Many of the involved steps are important targets for therapeutic interventions. As new immunotherapies are developed, predictive biomarkers will also be important to select patients most likely to respond and to better understand tumor biology. Several potential biomarkers are reviewed including PD-L1 expression, identification of T cell-inflamed/non-T cell-inflamed tumors based on immune gene expression, intrinsic molecular subtyping based on luminal/basal or the cancer genome atlas (TCGA) groups, T cell receptor (TCR) sequencing, and somatic mutational density. Within even the past few years our current knowledge of immune biology has exploded, and we are highly optimistic about the future of UBC therapy that will be available to patients. PMID:27836246

Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs.

PubMed

Fulkerson, Christopher M; Dhawan, Deepika; Ratliff, Timothy L; Hahn, Noah M; Knapp, Deborah W

2017-01-01

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

PubMed Central

Fulkerson, Christopher M.; Ratliff, Timothy L.; Hahn, Noah M.

2017-01-01

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed. PMID:28487862

The Role of Genetically Modified Mesenchymal Stem Cells in Urinary Bladder Regeneration.

PubMed

Snow-Lisy, Devon C; Diaz, Edward C; Bury, Matthew I; Fuller, Natalie J; Hannick, Jessica H; Ahmad, Nida; Sharma, Arun K

2015-01-01

Recent studies have demonstrated that mesenchymal stem cells (MSCs) combined with CD34+ hematopoietic/stem progenitor cells (HSPCs) can function as surrogate urinary bladder cells to synergistically promote multi-faceted bladder tissue regeneration. However, the molecular pathways governing these events are unknown. The pleiotropic effects of Wnt5a and Cyr61 are known to affect aspects of hematopoiesis, angiogenesis, and muscle and nerve regeneration. Within this study, the effects of Cyr61 and Wnt5a on bladder tissue regeneration were evaluated by grafting scaffolds containing modified human bone marrow derived MSCs. These cell lines were engineered to independently over-express Wnt5a or Cyr61, or to exhibit reduced expression of Cyr61 within the context of a nude rat bladder augmentation model. At 4 weeks post-surgery, data demonstrated increased vessel number (~250 vs ~109 vessels/mm2) and bladder smooth muscle content (~42% vs ~36%) in Cyr61OX (over-expressing) vs Cyr61KD (knock-down) groups. Muscle content decreased to ~25% at 10 weeks in Cyr61KD groups. Wnt5aOX resulted in high numbers of vessels and muscle content (~206 vessels/mm2 and ~51%, respectively) at 4 weeks. Over-expressing cell constructs resulted in peripheral nerve regeneration while Cyr61KD animals were devoid of peripheral nerve regeneration at 4 weeks. At 10 weeks post-grafting, peripheral nerve regeneration was at a minimal level for both Cyr61OX and Wnt5aOX cell lines. Blood vessel and bladder functionality were evident at both time-points in all animals. Results from this study indicate that MSC-based Cyr61OX and Wnt5aOX cell lines play pivotal roles with regards to increasing the levels of functional vasculature, influencing muscle regeneration, and the regeneration of peripheral nerves in a model of bladder augmentation. Wnt5aOX constructs closely approximated the outcomes previously observed with the co-transplantation of MSCs with CD34+ HSPCs and may be specifically targeted as an alternate means to achieve functional bladder regeneration.

PDT for malignant tumors: a clinical analysis of 152 cases

NASA Astrophysics Data System (ADS)

Zhuang, Shi-Zhang; Wang, Yun-Zhen; Li, Xin; Zhang, Changjun; Wang, Jian-Zhao; Zhang, Da-Ren

1993-03-01

Hematoporphyrin derivative (HPD) laser photodynamic therapy (PDT) was applied for the patients of 152 cases of malignant tumors, including tumors of the lip, tongue, esophagus, urinary bladder, skin, larynx, vagina, etc. Since early 1981 good results have been obtained.

Pneumovesicoscopic treatment of congenital bladder diverticula in children: our experience.

PubMed

Marte, Antonio; Sabatino, Maria D; Borrelli, Micaela; Del Balzo, Biago; Nino, Fabiano; Prezioso, Maurizio; Parmeggiani, Pio

2010-02-01

In this article, we report our experience with diverticulectomies of symptomatic congenital bladder diverticula in children, which was performed by utilizing pneumovesicoscopy. Six boys, 4-8 years of age (mean, 5.6) underwent pneumovesicoscopic diverticulectomy at our institution from June 2007 to June 2008. There were 4 right-single diverticula and 2 double-left diverticula. Under cystoscopic control, after the cystopexy to the abdominal wall, a midline 5-mm trocar for a 0-degree telescope and two lateral 3-mm reusable trocars through the anterolateral wall of the bladder in the midclavicular line were introduced, insufflating the bladder with carbondioxide to 10-12 mm Hg pressure. The diverticulum/a were inverted into the bladder and the mucosa around the neck was circumcized by using scissors and a monopolar hook. The defect was sutured with interrupted sutures and the bladder was drained with a Foley catheter, which was introduced at the site of the 5-mm port, and a urethral catheter. Mean operative time was 110 minutes. No major peri- or postoperative complications were recorded, except that the displacement of one of the lateral trocars that resulted in gas leakage in 1 case. The trocar was replaced and the procedure was completed. An ultrasound and a voiding cystourethrogram, performed from 3 to 6 months after the operation, showed the disappearance of the diverticulum/a. In our experience, pneumovesicoscopic diverticulectomy is an easy, safe procedure and can be considered a valid alternative to the open or laparoscopic procedures. It also provides no postoperative discomfort and a good cosmetic result.

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.

Fertility outcomes after laparoscopic partial bladder resection for deep endometriosis: Retrospective analysis from two expert centres and review of the literature.

PubMed

Nyangoh Timoh, Krystel; Ballester, Marcos; Bendifallah, Sofiane; Fauconnier, Arnaud; Darai, Emile

2018-01-01

To evaluate fertility outcomes after laparoscopic partial bladder resection in women with bladder endometriosis and to review the literature. A retrospective study conducted at two tertiary referral centres -Tenon University Hospital and Poissy University Hospital (Canadian Task Force Classification Level II-2)-from July 2006 to November 2015. Patients with bladder endometriosis who underwent either laparoscopic partial bladder resection (PBR) alone for those without posterior endometriotic lesions (PBR group) or both laparoscopic PBR and associated posterior deep infiltrating endometriosis (DIE) resection (PBR-PDIE group) were included. Pregnancy and live birth rates according to prior infertility, and associated posterior DIE resection were analysed. Thirty-four patients were included; 15 in the PBR group and 19 in the PBR-PDIE group. The median age (range) was 31 years (25-37), Seventeen patients (50%) had prior infertility. The median follow-up after bladder resection was 60.6 months (12-116). Overall, of the 25 (73.5%) patients who wished to conceive, 17 (68%) achieved pregnancies resulting in a live birth rate of 76.4%. Among the 17 patients with prior infertility, nine (52.9%) conceived. Overall, eight patients (53.3%) in the PBR group conceived and nine (47.3%) in the PBR-PDIE group (difference not significant). The present study demonstrates that laparoscopic PBR results in a high pregnancy rate in patients with prior infertility as well as in those with associated posterior DIE suggesting that surgery could be an acceptable alternative to first-line assisted reproductive technology. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of fibronectin in intravesical BCG therapy for superficial bladder cancer.

PubMed

Ratliff, T L; Kavoussi, L R; Catalona, W J

1988-02-01

Intravesical bacillus Calmette-Guerin (BCG) has been demonstrated to be effective both for prophylaxis and treatment of superficial bladder cancer. In order to identify the progression of events that result in BCG-mediated antitumor activity, studies were performed to evaluate the mechanism of binding of BCG within the bladder. Histological and quantitative studies in a mouse model revealed that BCG attached to the bladder wall only in areas of urothelial damage. Preliminary in vitro data showed that BCG attached to surfaces coated with extracellular matrix proteins. Further studies were then performed using purified extracellular matrix proteins to identify the proteins responsible for attachment. BCG were observed to attach to surfaces coated only with purified fibronectin (FN) but not to other purified proteins including laminin, collagen or fibrinogen. The attachment of BCG to purified FN in vitro was dose dependent and was inhibited by anti-FN antibodies. Moreover, BCG attachment in vivo to bladders with damaged urothelial surfaces was inhibited more than 95% by anti-FN antibodies, but binding was not affected by anti-laminin antibodies or preimmune serum. A survey of commercially available BCG vaccines (Pasteur, Tice, Glaxo, Connaught) showed that only Glaxo BCG did not attach to FN-coated surfaces. Glaxo BCG also was shown to express inferior antitumor activity suggesting that the absence of FN binding by Glaxo may have been associated with the absence of antitumor activity of the vaccine.

The management of non-invasive bladder tumours with Doxorubicin intravesical instillation after transurethral resection.

PubMed

Al-Gallab, Musa I; Naddaf, Louai A; Kanan, Mohamad R

2009-04-01

Evaluation of the intravesical instillation of doxorubicin for its effect on disease recurrence for patients with non-invasive bladder tumour. The study was performed at Al Assad University Hospital in Lattakia, Syria and included patients with non-invasive bladder tumours who were managed with transurethral resection and induction and maintenance therapy with intravesical doxorubicin. They were followed up by cystoscopy every 3 months for 2 years and every 6 months thereafter with special emphasis on recurrence rates. The study included 85 patients with non-invasive bladder tumours: 23 with non-invasive papillary carcinoma (Stage Ta), 62 with tumour invading subepithelial connective tissue (Stage T1). Twelve patients had well differentiated tumours (Grade 1), 48 had moderately differentiated (Grade 2), 25 had poorly differentiated (Grade 3) tumours. The total recurrence rate was 23%. The rates of recurrence were 56% in Grade 3 and 0% in Grade 1. The recurrence rate was 41% in patients with large tumours versus 17% in those with small tumours; 44% in those with multiple tumours compared to 18% in those with solitary tumours; 30% of Stage Ta tumours recurred and 21% of Stage T1 tumours. In short term follow-up, our rate of recurrence was 23%. Adjuvant intravesical doxorubicin was shown to reduce the recurrence of superficial bladder cancer. Tumour grade, size and number were shown to be prognostic factors for recurrence.

Current role of transcatheter arterial embolization for bladder and prostate hemorrhage.

PubMed

Loffroy, R; Pottecher, P; Cherblanc, V; Favelier, S; Estivalet, L; Koutlidis, N; Moulin, M; Cercueil, J P; Cormier, L; Krausé, D

2014-11-01

Intractable hematuria from the bladder or the prostate can be life-threatening and its management remains a difficult clinical problem. Severe bleeding can arise as a result of radiation cystitis, bladder carcinoma, cyclophosphamide-induced cystitis, severe infection, transurethral resection of the prostate and prostate cancer. When irrigation of the bladder through a three-way catheter and fulguration of the bleeding lesions fail to stop the hematuria, a life-threatening situation can develop, when blood transfusion fails to keep pace with the rate of blood loss. Patients with massive uncontrollable hematuria are often elderly and unfit for cystectomy as a treatment. Many urologists have had to manage this difficult problem, and several different treatments have been attempted and described, with varying degrees of success. Transcatheter arterial embolization of the vesical or prostatic arteries is occasionally indicated in these patients when all other measures have failed. There is limited published experience with this procedure, but success in 90% of patients is reported when the vesical or prostatic arteries can be identified. The aim of this review is to describe the current place of transcatheter arterial embolization in the management of severe bladder or prostate bleeding after failed conservative therapy, and to review its efficacy and morbidity. Copyright © 2014 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

An animal model to study lower urinary tract symptoms and erectile dysfunction: the hyperlipidaemic rat.

PubMed

Rahman, Nadeem U; Phonsombat, Surat; Bochinski, Derek; Carrion, Rafael E; Nunes, Lora; Lue, Tom F

2007-09-01

To present evidence that rats fed a high-fat diet could serve as a useful animal model to study both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), as recent epidemiological studies have shown a strong association between LUTS and ED but the physiological basis behind this relationship is unknown. In all, 24 male Sprague-Dawley rats were divided into two groups: nine controls were fed a 'normal' diet and 15 were fed a high-fat diet (hyperlipidaemic rats). After 6 months all the rats had bladder and erectile functions evaluated using awake cystometry and cavernosal nerve electrostimulation, respectively. After the functional studies were completed, the penis, prostate and bladder were collected for immunohistochemical analysis. The hyperlipidaemic rats had significantly higher serum cholesterol and low-density lipoprotein than the controls (P < 0.05). The hyperlipidaemic rats also had significantly worse erectile function (P = 0.004) and developed more bladder overactivity (P = 0.004) than the controls. In the hyperlipidaemic rats there was significant muscle hypertrophy in the peri-urethral lobe of the prostate (P < 0.001) and in the bladder (P < 0.05). There was also greater P2X(1) (purinoceptor) staining as well as other molecular changes in the bladder of the hyperlipidaemic rats. In this hyperlipidaemic rat model three abnormalities were consistently detected: prostatic enlargement, bladder overactivity, and ED. This rat model could be a useful research tool for understanding the common causes of LUTS and ED, as well as facilitating the development of preventive measures and better therapies to treat both conditions.

Dietary flavonoid luteolin attenuates uropathogenic Escherichia. Coli invasion of the urinary bladder.

PubMed

Shen, Xiao-Fei; Teng, Yan; Sha, Kai-Hui; Wang, Xin-Yuan; Yang, Xiao-Long; Guo, Xiao-Juan; Ren, Lai-Bin; Wang, Xiao-Ying; Li, Jingyu; Huang, Ning

2016-11-12

Uropathogenic Escherichia coli (UPEC), the primary uropathogen, adhere to and invade bladder epithelial cells (BECs) to establish a successful urinary tract infection (UTI). Emerging antibiotic resistance requires novel nonantibiotic strategies. Our previous study indicated that luteolin attenuated adhesive and invasive abilities as well as cytotoxicity of UPEC on T24 BECs through down-regulating UPEC virulence factors. The aims of this study were to investigate the possible function of the flavonoid luteolin and the mechanisms by which luteolin functions in UPEC-induced bladder infection. Firstly, obvious reduction of UPEC invasion but not adhesion were observed in luteolin-pretreated 5637 and T24 BECs sa well as mice bladder via colony counting. The luteolin-mediated suppression of UPEC invasion was linked to elevated levels of intracellular cAMP induced by inhibiting the activity of cAMP-phosphodiesterases (cAMP-PDEs), which resulting activation of protein kinase A, thereby negatively regulating Rac1-GTPase-mediated actin polymerization. Furthermore, p38 MAPK was primarily and ERK1/2 was partially involved in luteolin-mediated suppression of UPEC invasion and actin polymerization, as confirmed with chemical activators of p38 MAPK and ERK1/2. These data suggest that luteolin can protect bladder epithelial cells against UPEC invasion. Therefore, luteolin or luteolin-rich products as dietary supplement may be beneficial to control the UPEC-related bladder infections, and cAMP-PDEs may be a therapy target for UTIs treatment. © 2016 BioFactors, 42(6):674-685, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Localization of hypericin-induced fluorescence after Hypericum perforatum polar fraction instillation in normal rat urinary bladder

NASA Astrophysics Data System (ADS)

Stavropoulos, Nikos E.; Skalkos, Dimitris; Tsimaris, Ioannis; Kalogeras, D.; Nseyo, Unyime O.; Batistatou, A.; Agnantis, N. J.

2005-04-01

The photodynamic action of the Hypericum perforatum L. extract, mainly its polar methanolic fraction (PMF) has recently been substantiated by our group. The herb contains a number of naphthodianthrones - photosensitizers mainly hypericin and pseudohypericin. The concentration of hypericins in PMF was found to be 1.37 %. The distribution of hypericins fluorescence in sections of normal rat bladder tissues after the intravesical instillation of the polar methanolic fraction of hypericum (PMF) was studied by the use of fluorescence microscopy. PMF was dissolved in normal saline containing 0.5 μg/ml concentration of hypericins, and was then instilled in rat bladder for 15, 30, 60 and 120 minutes respectively. PMF solutions were withdrawn, bladders were rinsed through the catheter with normal saline and rats were sacrificed. Bladders were then removed, cut open and immediately mounted in medium, and immersed in liquid nitrogen. Two consecutive 3-μm frozen sections were cut with a cryostat. The first section was examined by fluorescence microscopy and the second section was stained with hematoxylin and eosin. For fluorescence imaging the filter set used included a 535/50 nm bandpass excitation filter and a 610/75 nm emission filter. Fluorescence images were acquired and documented using photography. Fluorescene could be detected in bladder samples after only 15 minutes of instillation with the above described solution. The urothelium / muscle fluorescence ratio ranged from 5/1 to 11/1 in various sites of the samples examined. No fluorescence originating from the muscle could be detected. PMF should be further studied towards the direction of its use in photodynamic therapy.

Selective binding of lectins to normal and neoplastic urothelium in rat and mouse bladder carcinogenesis models.

PubMed

Zupančič, Daša; Kreft, Mateja Erdani; Romih, Rok

2014-01-01

Bladder cancer adjuvant intravesical therapy could be optimized by more selective targeting of neoplastic tissue via specific binding of lectins to plasma membrane carbohydrates. Our aim was to establish rat and mouse models of bladder carcinogenesis to investigate in vivo and ex vivo binding of selected lectins to the luminal surface of normal and neoplastic urothelium. Male rats and mice were treated with 0.05 % N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water and used for ex vivo and in vivo lectin binding experiments. Urinary bladder samples were also used for paraffin embedding, scanning electron microscopy and immunofluorescence labelling of uroplakins. During carcinogenesis, the structure of the urinary bladder luminal surface changed from microridges to microvilli and ropy ridges and the expression of urothelial-specific glycoproteins uroplakins was decreased. Ex vivo and in vivo lectin binding experiments gave comparable results. Jacalin (lectin from Artocarpus integrifolia) exhibited the highest selectivity for neoplastic compared to normal urothelium of rats and mice. The binding of lectin from Amaranthus caudatus decreased in rat model and increased in mouse carcinogenesis model, indicating interspecies variations of plasma membrane glycosylation. Lectin from Datura stramonium showed higher affinity for neoplastic urothelium compared to the normal in rat and mouse model. The BBN-induced animal models of bladder carcinogenesis offer a promising approach for lectin binding experiments and further lectin-mediated targeted drug delivery research. Moreover, in vivo lectin binding experiments are comparable to ex vivo experiments, which should be considered when planning and optimizing future research.

Functional and histological bladder damage in mice after photodynamic therapy: the influence of sensitiser dose and time of administration.

PubMed Central

Stewart, F. A.; Oussoren, Y.

1993-01-01

The bladders of anaesthetised mice were illuminated with red laser light (630 nm) at intervals of 1 day to 4 weeks after i.p. administration of Photofrin. Light was delivered intravesically by inserting a fibre optic, with a diffusing bulb tip, into the centre of fluid filled bladders. A single light dose of 11.3 J cm-2 applies 1 day after 10 mg kg-1 Photofrin caused a severe acute response, with increased urination frequency (five to seven times control) and hematuria. Recovery was good, however, and by 10 weeks only a mild (approximately two-fold) increase in frequency remained. There was no reduction in the amount of acute bladder damage or in the rate of healing when the interval between Photofrin and light was increased from 1 to 7 days but a 2 to 3 week interval lead to a significant reduction in damage. For an interval of 4 weeks there was only a mild (less than two-fold) increase in urination frequency during the first week. A drug dose of 2.5 mg kg-1 given 1 day before illumination caused transient haematuria but no increase in urination frequency. Doses of 5, 7.5 or 10 mg kg-1 all caused photosensitisation and the amount of bladder damage was drug dose dependent. The bladder seems to be well able to recover from severe acute damage induced by PDT. Occasional incidences of pyelonephritis were seen, however, suggesting that urinary tract infection during the acute period may lead to permanent renal damage. Images Figure 5 PMID:8398691

Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy.

PubMed

Palou-Redorta, J; Solsona, E; Angulo, J; Fernández, J M; Madero, R; Unda, M; Martínez-Piñeiro, J A; Portillo, J; Chantada, V; Moyano, J L

2016-01-01

To compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumours; however, a number of experts still question the need for maintenance BCG. We retrospectively analysed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumour (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n=108), re-TURBT (n=153), induction with 27mg of BCG (Connaught strain) (n=87), induction with 81mg of BCG (n=489) or induction with 81mg of BCG+maintenance (n=202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan-Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. The mean follow-up was 62±39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81mg of BCG than in the other treatment groups (P<.001). The risk of tumour progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27mg of BCG (P=.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; P=.003). In the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Brain Mechanisms Underlying Urge Incontinence and its Response to Pelvic Floor Muscle Training.

PubMed

Griffiths, Derek; Clarkson, Becky; Tadic, Stasa D; Resnick, Neil M

2015-09-01

Urge urinary incontinence is a major problem, especially in the elderly, and to our knowledge the underlying mechanisms of disease and therapy are unknown. We used biofeedback assisted pelvic floor muscle training and functional brain imaging (functional magnetic resonance imaging) to investigate cerebral mechanisms, aiming to improve the understanding of brain-bladder control and therapy. Before receiving biofeedback assisted pelvic floor muscle training functionally intact, older community dwelling women with urge urinary incontinence as well as normal controls underwent comprehensive clinical and bladder diary evaluation, urodynamic testing and brain functional magnetic resonance imaging. Evaluation was repeated after pelvic floor muscle training in those with urge urinary incontinence. Functional magnetic resonance imaging was done to determine the brain reaction to rapid bladder filling with urgency. Of 65 subjects with urge urinary incontinence 28 responded to biofeedback assisted pelvic floor muscle training with 50% or greater improvement of urge urinary incontinence frequency on diary. However, responders and nonresponders displayed 2 patterns of brain reaction. In pattern 1 in responders before pelvic floor muscle training the dorsal anterior cingulate cortex and the adjacent supplementary motor area were activated as well as the insula. After the training dorsal anterior cingulate cortex/supplementary motor area activation diminished and there was a trend toward medial prefrontal cortex deactivation. In pattern 2 in nonresponders before pelvic floor muscle training the medial prefrontal cortex was deactivated, which changed little after the training. In older women with urge urinary incontinence there appears to be 2 patterns of brain reaction to bladder filling and they seem to predict the response and nonresponse to biofeedback assisted pelvic floor muscle training. Moreover, decreased cingulate activation appears to be a consequence of the improvement in urge urinary incontinence induced by training while prefrontal deactivation may be a mechanism contributing to the success of training. In nonresponders the latter mechanism is unavailable, which may explain why another form of therapy is required. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer: Implications for Adjuvant Radiation Therapy

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

Reddy, Abhinav V.; Pariser, Joseph J.; Pearce, Shane M.

2016-04-01

Purpose: In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy. Methods and Materials: Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined usingmore » follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariate analysis for association with LF and overall survival. Results: A total of 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 years old, and median follow-up was 11 months. On univariate analysis, margin status, pT stage, and pN stage, were all associated with LF (P<.05), however, on multivariate analysis, only pT and pN stages were significantly associated with LF (P<.05). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence. Conclusions: Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.« less

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.

Risk of Late Urinary Complications Following Image Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: Refining Bladder Dose-Volume Parameters.

PubMed

Manea, Elena; Escande, Alexandre; Bockel, Sophie; Khettab, Mohamed; Dumas, Isabelle; Lazarescu, Ioana; Fumagalli, Ingrid; Morice, Philippe; Deutsch, Eric; Haie-Meder, Christine; Chargari, Cyrus

2018-06-01

To study correlations between dose-volume parameters of the whole bladder and bladder trigone and late urinary toxicity in locally advanced cervical cancer patients treated with pulsed-dose-rate brachytherapy. Patients with locally advanced cervical cancer treated with chemoradiation therapy and pulsed-dose-rate brachytherapy from 2004 to 2015 were included. Cumulative dose-volume parameters of the whole bladder and bladder trigone were converted into 2-Gy/fraction equivalents (EQD2, with α/β = 3 Gy); these parameters, as well as clinical factors, were analyzed as predictors of toxicity in patients without local relapse. A total of 297 patients fulfilled the inclusion criteria. The median follow-up period was 4.9 years (95% confidence interval 4.5-5.3 years). In patients without local relapse (n = 251), the Kaplan-Meier estimated grade 2 or higher urinary toxicity rates at 3 years and 5 years were 25.4% and 32.1%, respectively. Minimal dose to the most exposed 2 cm 3 of the whole bladder [Formula: see text] , bladder International Commission on Radiation Units & Measurements (ICRU) (B ICRU ) dose, and trigone dose-volume parameters correlated with grade 2 or higher toxicity. At 3 years, the cumulative incidence of grade 2 or higher complications was 22.8% (standard error, 2.9%) for bladder [Formula: see text]  < 80 Gy EQD2 versus 61.8% (standard error, 12.7%) for [Formula: see text]  ≥ 80 Gy EQD2 (P = .001). In the subgroup of patients with bladder [Formula: see text]  ≤ 80 Gy EQD2 , a trigone dose delivered to 50% of the volume (D 50% ) > 60 Gy EQD2 was significant for grade 2 or higher toxicity (P = .027). The probability of grade 3 or higher toxicities increased with bladder [Formula: see text]  > 80 Gy EQD2 (16.7% vs 1.6%; hazard ratio [HR], 5.77; P = .039), B ICRU dose > 65 Gy EQD2 (4.9% vs 1.3%; HR, 6.36; P = .018), and trigone D 50%  > 60 Gy EQD2 (3.1% vs 1.2%; HR, 6.29; P = .028). Pearson correlation coefficients showed a moderate correlation between bladder [Formula: see text] , B ICRU dose, and bladder trigone D 50% (P < .0001). These data suggest that [Formula: see text]  ≤ 80 Gy EQD2 should be advised for minimizing the risk of severe urinary complications (<15%). Bladder trigone dose was also predictive of severe late urinary toxicity. These constraints need further confirmation in a multicenter prospective setting. Copyright © 2018 Elsevier Inc. All rights reserved.

Preoperative Radiation in the Treatment of Cancer

PubMed Central

Stein, Justin J.

1968-01-01

In the treatment of advanced cancer of the hypopharynx, preoperative radiation therapy has proven to be of value for the prevention of recurrences in the operative area following radical neck dissection for cancer of the head and neck. Also it has been of value in the planned combined therapy of certain patients with lung, bladder, breast, esophagus, bone, endometrial and rectal cancers. Preoperative radiation therapy should be advantageous in patients who have malignant disease where the possibility exists for the cancer cells to be disseminated during the surgical procedure. PMID:5681499

[Intradiverticular bladder tumours: review of the Cancer Committee of the French Association of Urology].

PubMed

Neuzillet, Y; Comperat, E; Rouprêt, M; Larre, S; Roy, C; Quintens, H; Houede, N; Pignot, G; Wallerand, H; Soulie, M; Pfister, C

2012-07-01

Cancer Committee of the French Association of Urology (CCAFU) conducted a review of the epidemiology, diagnosis and treatment of intradiverticular bladder tumours (TVID) and proposed therapeutic management. A bibliographic research in French and English using Medline(®) with the keywords "tumor", "bladder" and "diverticulum" was performed. TVID are more frequently of stage T ≥ 3a and with non urothelial histology than classical bladder tumors. At diagnosis, the risk of underestimation of the extent and multifocality of the tumor was described. Their prognosis, that was more pejorative than conventional tumors, should impelled to limit the indications of conservative treatment. The evidence levels of analyzed publications were low, with C level according to Sackett score. the specificities of the TVID have lead the CCAFU to propose specific therapeutic guidelines, based on poor evidence level. Ta-T1 low grade TVID can be treated by transurethral resection alone or followed by BCG therapy in cases of associated carcinoma in situ. High-grade TVID, unifocal and without associated carcinoma in situ, can be treated by diverticulectomy associated with pelvic lymphadenectomy. High grade TVID, multiple or associated with carcinoma in situ, warranted total cystectomy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

A Toll-Like Receptor 9 Antagonist Improves Bladder Function and White Matter Sparing in Spinal Cord Injury

PubMed Central

David, Brian T.; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E.; Elkabes, Stella

2014-01-01

Abstract Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI. PMID:24936867

A toll-like receptor 9 antagonist improves bladder function and white matter sparing in spinal cord injury.

PubMed

David, Brian T; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E; Elkabes, Stella; Heary, Robert F

2014-11-01

Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI.

A Review on the Relationship between SGLT2 Inhibitors and Cancer

PubMed Central

Lin, Hao-Wen; Tseng, Chin-Hsiao

2014-01-01

Risk of increasing breast and bladder cancer remains a safety issue of SGLT2 (sodium glucose cotransporter type 2) inhibitors, a novel class of antidiabetic agent. We reviewed related papers published before January 29, 2014, through Pubmed search. Dapagliflozin and canagliflozin are the first two approved SGLT2 inhibitors for diabetes therapy. Although preclinical animal toxicology did not suggest a cancer risk of dapagliflozin and overall tumor did not increase, excess numbers of female breast cancer and male bladder cancer were noted in preclinical trials (without statistical significance). This concern of cancer risk hindered its approval by the US FDA in January, 2012. New clinical data suggested that the imbalance of bladder and breast cancer might be due to early diagnosis rather than a real increase of cancer incidence. No increased risk of overall bladder or breast cancer was noted for canagliflozin. Therefore, the imbalance observed with dapagliflozin treatment should not be considered as a class effect of SGLT2 inhibitors and the relationship with cancer for each specific SGLT2 inhibitor should be examined individually. Relationship between SGLT2 inhibition and cancer formation is still inconclusive and studies with larger sample size, longer exposure duration, and different ethnicities are warranted. PMID:25254045

Comparison of the safety and efficacy of conventional monopolar and 2-micron laser transurethral resection in the management of multiple nonmuscle-invasive bladder cancer.

PubMed

Liu, H; Wu, J; Xue, S; Zhang, Q; Ruan, Y; Sun, X; Xia, S

2013-08-01

To compare the safety and efficacy of conventional monopolar transurethral resection of bladder tumour (TURBT) and 2-micron continuous-wave laser resection (2-µm laser) techniques in the management of multiple nonmuscle-invasive bladder cancer (NMIBC), and to investigate long-term effects on tumour recurrence. Patients with multiple NMIBC were randomized to receive TURBT or 2-µm laser in a nonblinded manner. All patients received intravesical chemotherapy with epirubicin (40 mg/40 ml) for 8 weeks, beginning 1 week after surgery, followed with monthly maintenance therapy for 12 months. Three-year follow-up data of preoperative, operative and postoperative management were recorded. In total, 120 patients were included: 56 in the TURBT group and 64 in the 2-µm laser group. Intra- and postoperative complications (including bladder perforation, bleeding and irritation) were less frequently observed in the 2-µm laser group compared with the TURBT group. There were no significant differences in first time to recurrence, overall recurrence or occurrence of urethral strictures. The 2-µm laser resection method was more effective than TURBT in reducing rates of intra- and postoperative complications, but offered no additional benefit regarding tumour recurrence.

Effects of ageing and streptozotocin-induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder.

PubMed

Suadicani, Sylvia O; Urban-Maldonado, Marcia; Tar, Moses T; Melman, Arnold; Spray, David C

2009-06-01

To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X(1)R, and increase in P2X(7)R expression. There was decreased Cx43 and increased P2Y(4)R expression in the ageing control rat bladder. There was a significant negative correlation between erectile capacity and P2X(1)R expression levels, and a positive correlation between bladder spontaneous activity and P2Y(4)R expression levels. There was already development of erectile dysfunction and bladder overactivity at 2 months after inducing diabetes, the earliest sample measured in the study. The development of these urogenital complications was accompanied by significant decreases in Cx43, P2Y(2)R, P2X(4)R and increase in P2X(1)R expression in the corpora, and by a doubling in Cx43 and P2Y(2)R, and significant increase in P2Y(4)R expression in the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin therapy. Ageing and diabetes mellitus markedly altered the expression of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile corpora and urinary bladder. These changes in Cx43 and P2R expression provide the molecular substrate for altered gap junction and purinergic signalling in these tissues, and thus probably contribute to the early development of erectile dysfunction and higher detrusor activity in ageing and in diabetic rats.

Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer.

PubMed

Singla, Nirmish; Haddad, Ahmed Q; Passoni, Niccolo M; Meissner, Matthew; Lotan, Yair

2017-01-01

To evaluate whether anti-inflammatory agents affect outcomes in patients receiving intravesical BCG therapy for high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). We reviewed the records of 203 patients in a prospective database of HG NMIBC from 2006 to 2012 at a single institution. Patients who had muscle-invasive disease (n = 32), low-grade pathology (n = 4), underwent early cystectomy within 3 months (n = 25), had <3 months of follow-up (n = 11), or did not receive an induction course of intravesical BCG (n = 32) were excluded. Clinicopathologic data were tabulated including demographics, comorbidities, pathologic stage and grades, intravesical therapy, and concomitant use of aspirin, NSAIDs, COX inhibitors, and statins. Multivariate Cox regression analysis explored predictive factors for recurrence, progression (stage progression or progression to cystectomy), cancer-specific survival (CSS), and overall survival (OS). Ninety-nine patients with HG NMIBC who received at least one induction course of intravesical BCG were identified, with median follow-up of 31.4 months. There were 20 (20.2 %) deaths, including 6 (6.1 %) patients with bladder cancer-related mortality. 13 % patients experienced tumor progression and 27 % underwent cystectomy following failure of intravesical therapy. Anti-inflammatory use included statins (65 %), aspirin (63 %), or non-aspirin NSAIDs/COX inhibitors (26 %). Anti-inflammatory use was not significantly predictive of recurrence, progression, or mortality outcomes on Cox regression. CIS stage was associated with higher progression, while age, BMI, and Charlson score were independent predictors of overall mortality. Despite speculation of inhibitory effects on BCG immunomodulation there was no evidence that anti-inflammatory agents impacted oncologic outcomes in patients receiving BCG for HG NMIBC.

Physical therapy for urinary incontinence in postmenopausal women with osteoporosis or low bone density: a randomized controlled trial.

PubMed

Sran, Meena; Mercier, Joanie; Wilson, Penny; Lieblich, Pat; Dumoulin, Chantale

2016-03-01

To assess the effectiveness of 12 weekly physical therapy sessions for urinary incontinence (UI) compared with a control intervention, for reducing the number of UI episodes measured with the 7-day bladder diary, at 3 months and 1 year postrandomization. A single parallel-group randomized controlled trial was conducted at one outpatient public health center, in postmenopausal women aged 55 years and over with osteoporosis or low bone density and UI. Women were randomized to physical therapy (PT) for UI or osteoporosis education. The primary outcome measure was number of leakage episodes on the 7-day bladder diary, assessed at baseline, after treatment and at 1 year. The secondary outcome measures included the pad test and disease-specific quality of life and self-efficacy questionnaires assessed at the same timepoints. Forty-eight women participated (24 per group). Two participants dropped out of each group and one participant was deceased before 3-month follow-up. Intention-to-treat analysis was undertaken. At 3 months and 1 year, there was a statistically significant difference in the number of leakage episodes on the 7-day bladder diary (3 mo: P = 0.04; 1 y: P = 0.01) in favor of the PT group. The effect size was 0.34 at 1 year. There were no harms reported. After a 12-week course of PT once per week for UI, PT group participants had a 75% reduction in weekly median number of leakage episodes, whereas the control group's condition had no improvement. At 1 year, the PT group participants maintained this improvement, whereas the control group's incontinence worsened.

Common questions about the diagnosis and management of benign prostatic hyperplasia.

PubMed

Pearson, Ryan; Williams, Pamela M

2014-12-01

Benign prostatic hyperplasia (BPH) is a common condition that increases in prevalence with age. A history should include onset, duration, and severity of lower urinary tract symptoms and medication use to rule out other causes of symptoms. Physical examination includes a digital rectal examination and assessment for bladder distention or neurologic impairment. Recommended tests include serum prostate-specific antigen measurement and urinalysis to help identify infection, genitourinary cancer, or calculi as an alternative cause of lower urinary tract symptoms. BPH severity is assessed using validated, self-administered symptom questionnaires such as the American Urological Association Symptom Index or International Prostate Symptom Score. Mild or nonbothersome symptoms do not require treatment. Bothersome symptoms are managed with lifestyle modifications, medications, and surgery. Alpha blockers are first-line medications for BPH. Surgical referral is indicated if BPH-related complications develop, medical therapy fails, or the patient chooses it. Dietary supplements, such as saw palmetto, pygeum, cernilton, and beta sitosterols, and acupuncture are not recommended for the management of BPH.

[Urethral pain syndrome: fact or fiction--an update].

PubMed

Dreger, N M; Degener, S; Roth, S; Brandt, A S; Lazica, D A

2015-09-01

Urethral pain syndrome is a symptom complex including dysuria, urinary urgency and frequency, nocturia and persistent or intermittent urethral and/or pelvic pain in the absence of proven infection. These symptoms overlap with several other conditions, such as interstitial cystitis bladder pain syndrome and overactive bladder. Urethral pain syndrome may occur in men but is more frequent in women. The exact etiology is unknown but infectious and psychogenic factors, urethral spasms, early interstitial cystitis, hypoestrogenism, squamous metaplasia as well as gynecological risk factors are discussed. These aspects should be ruled out or confirmed in the diagnostic approach. Despite the assumption of a multifactorial etiology, pathophysiologically there is a common pathway: dysfunctional epithelium of the urethra becomes leaky which leads to bacterial and abacterial inflammation and ends in fibrosis due to the chronic impairment. The therapeutic approach should be multimodal using a trial and error concept: general treatment includes analgesia, antibiotics, alpha receptor blockers and muscle relaxants, antimuscarinic therapy, topical vaginal estrogen, psychological support and physical therapy. In cases of nonresponding patients intravesical and/or surgical therapy should be considered. The aim of this review is to summarize the preliminary findings on urethral pain syndrome and to elucidate the diagnostic and therapeutic options.

The use of complementary and alternative medicine by women transitioning through menopause in Germany: results of a survey of women aged 45-60 years.

PubMed

Buhling, K J; Daniels, B V; Studnitz, F S G V; Eulenburg, C; Mueck, A O

2014-02-01

To describe prevalence rates of complementary and alternative medicine therapies (CAM) for the relief of menopausal complaints among German women. Furthermore, to investigate the perceived effectiveness of these therapies. A self-administered questionnaire was sent to 9785 randomly selected women in Germany aged between 45 and 60 years. A total of 1893 (19.3%) questionnaires have been sent back. The mean age of all participants was 52.6±4.3 years. 81% (n=1517) of the responding women stated that they had experienced menopausal complaints at least once. Symptoms ranged from vasomotor symptoms, including hot flushes and night sweats, in 71.2% of cases, to bladder problems in 42.7%. The average symptom score (MRS II total score, range 1-44) among the respondents was 12.76±9.6. More than half (56%; n=1049/1872) of the responding women had used some form of therapy to alleviate their symptoms at least once. The majority of women undertaking a therapy (64.8%; n=679/1049) had used only CAM interventions (either one or more type of CAM), 14.2% (n=149) had used hormone replacement therapy (HRT) only, while 21.1% (n=221/1049) had tried both CAM and HRT. Popular CAM interventions by the respondents were an alteration of lifestyle (28.7%), St. John's wort (18.3%) and homoeopathy (14.9%). An alteration in lifestyle was rated as the most effective CAM treatment with 84.9% (n=457). Other treatments like hormone yoga (79.2%; n=42), homoeopathy (73.7%; n=205) and TCM (59.1%; n=94) were also perceived to be effective. Phytoestrogens were rated as the most ineffective (45.5%; n=50). CAM interventions to alleviate menopausal complaints are popular among German women, with 48.2% (n=900/1872) of respondents reporting having used CAM either alone or in combination with HRT. However, the users rated the effects of CAM differently, with some reporting CAM to be highly effective, while others indicate lower effectiveness. Nevertheless, women with a significantly higher symptom scoring tend to use both CAM and a conventional therapy (HRT). Copyright © 2013 Elsevier Ltd. All rights reserved.

Proton Radiotherapy for Pediatric Bladder/Prostate Rhabdomyosarcoma: Clinical Outcomes and Dosimetry Compared to Intensity-Modulated Radiation Therapy

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

Cotter, Shane E.; Herrup, David A.; Friedmann, Alison

Purpose: In this study, we report the clinical outcomes of 7 children with bladder/prostate rhabdomyosarcoma (RMS) treated with proton radiation and compare proton treatment plans with matched intensity-modulated radiation therapy (IMRT) plans, with an emphasis on dose savings to reproductive and skeletal structures. Methods and Materials: Follow-up consisted of scheduled clinic appointments at our institution or direct communication with the treating physicians for referred patients. Each proton radiotherapy plan used for treatment was directly compared to an IMRT plan generated for the study. Clinical target volumes and normal tissue volumes were held constant to facilitate dosimetric comparisons. Each plan wasmore » optimized for target coverage and normal tissue sparing. Results: Seven male patients were treated with proton radiotherapy for bladder/prostate RMS at the Massachusetts General Hospital between 2002 and 2008. Median age at treatment was 30 months (11-70 months). Median follow-up was 27 months (10-90 months). Four patients underwent a gross total resection prior to radiation, and all patients received concurrent chemotherapy. Radiation doses ranged from 36 cobalt Gray equivalent (CGE) to 50.4 CGE. Five of 7 patients were without evidence of disease and with intact bladders at study completion. Target volume dosimetry was equivalent between the two modalities for all 7 patients. Proton radiotherapy led to a significant decrease in mean organ dose to the bladder (25.1 CGE vs. 33.2 Gy; p = 0.03), testes (0.0 CGE vs. 0.6 Gy; p = 0.016), femoral heads (1.6 CGE vs. 10.6 Gy; p = 0.016), growth plates (21.7 CGE vs. 32.4 Gy; p = 0.016), and pelvic bones (8.8 CGE vs. 13.5 Gy; p = 0.016) compared to IMRT. Conclusions: This study provides evidence of significant dose savings to normal structures with proton radiotherapy compared to IMRT and is well tolerated in this patient population. The long-term impact of these reduced doses can be tested in future studies incorporating extended follow-up, objective outcome measures, and quality-of-life analyses.« less

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

PubMed

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

2017-11-15

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

Dosimetric advantages of a clinical daily adaptive plan selection strategy compared with a non-adaptive strategy in cervical cancer radiation therapy.

PubMed

van de Schoot, Agustinus J A J; de Boer, Peter; Visser, Jorrit; Stalpers, Lukas J A; Rasch, Coen R N; Bel, Arjan

2017-05-01

Radiation therapy (RT) using a daily plan selection adaptive strategy can be applied to account for interfraction organ motion while limiting organ at risk dose. The aim of this study was to quantify the dosimetric consequences of daily plan selection compared with non-adaptive RT in cervical cancer. Ten consecutive patients who received pelvic irradiation, planning CTs (full and empty bladder), weekly post-fraction CTs and pre-fraction CBCTs were included. Non-adaptive plans were generated based on the PTV defined using the full bladder planning CT. For the adaptive strategy, multiple PTVs were created based on both planning CTs by ITVs of the primary CTVs (i.e., GTV, cervix, corpus-uterus and upper part of the vagina) and corresponding library plans were generated. Daily CBCTs were rigidly aligned to the full bladder planning CT for plan selection. For daily plan recalculation, selected CTs based on initial similarity were deformably registered to CBCTs. Differences in daily target coverage (D 98%  > 95%) and in V 0.5Gy , V 1.5Gy , V 2Gy , D 50% and D 2% for rectum, bladder and bowel were assessed. Non-adaptive RT showed inadequate primary CTV coverage in 17% of the daily fractions. Plan selection compensated for anatomical changes and improved primary CTV coverage significantly (p < 0.01) to 98%. Compared with non-adaptive RT, plan selection decreased the fraction dose to rectum and bowel indicated by significant (p < 0.01) improvements for daily V 0.5Gy , V 1.5Gy , V 2Gy , D 50% and D 2% . However, daily plan selection significantly increased the bladder V 1.5Gy , V 2Gy , D 50% and D 2% . In cervical cancer RT, a non-adaptive strategy led to inadequate target coverage for individual patients. Daily plan selection corrected for day-to-day anatomical variations and resulted in adequate target coverage in all fractions. The dose to bowel and rectum was decreased significantly when applying adaptive RT.

Medical and Surgical Treatment Modalities for Lower Urinary Tract Symptoms in the Male Patient Secondary to Benign Prostatic Hyperplasia: A Review

PubMed Central

Macey, Matthew Ryan; Raynor, Mathew C.

2016-01-01

Benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS) is one of the most common ailments affecting aging men. Symptoms typically associated with BPH include weak stream, hesitancy, urgency, frequency, and nocturia. More serious complications of BPH include urinary retention, gross hematuria, bladder calculi, recurrent urinary tract infection, obstructive uropathy, and renal failure. Evaluation of BPH includes a detailed history, objective assessment of urinary symptoms with validated questionnaires, and measurement of bladder function parameters, including uroflowmetry and postvoid residual. In general, treatment of LUTS associated with BPH is based on the effect of the symptoms on quality of life (QOL) and include medical therapy aimed at reducing outlet obstruction or decreasing the size of the prostate. If medical therapy fails or is contraindicated, various surgical options exist. As the elderly population continues to grow, the management of BPH will become more common and important in maintaining patient's QOL. PMID:27582609

Targeting Hsp90 in urothelial carcinoma

PubMed Central

Skotnicki, Kamil; Landas, Steve; Bratslavsky, Gennady; Bourboulia, Dimitra

2015-01-01

Urothelial carcinoma, or transitional cell carcinoma, is the most common urologic malignancy that carries significant morbidity, mortality, recurrence risk and associated health care costs. Despite use of current chemotherapies and immunotherapies, long-term remission in patients with muscle-invasive or metastatic disease remains low, and disease recurrence is common. The molecular chaperone Heat Shock Protein-90 (Hsp90) may offer an ideal treatment target, as it is a critical signaling hub in urothelial carcinoma pathogenesis and potentiates chemoradiation. Preclinical testing with Hsp90 inhibitors has demonstrated reduced proliferation, enhanced apoptosis and synergism with chemotherapies and radiation. Despite promising preclinical data, clinical trials utilizing Hsp90 inhibitors for other malignancies had modest efficacy. Therefore, we propose that Hsp90 inhibition would best serve as an adjuvant treatment in advanced muscle-invasive or metastatic bladder cancers to potentiate other therapies. An overview of bladder cancer biology, current treatments, molecular targeted therapies, and the role for Hsp90 inhibitors in the treatment of urothelial carcinoma is the focus of this review. PMID:25909217

Malakoplakia of the Urinary Bladder in a Patient with Chronic Lymphocytic Leukemia Under Ibrutinib Therapy: A Case Report.

PubMed

Sachanas, Sotirios; Pangalis, Gerassimos A; Karouzakis, Petros; Koulieris, Efstathios; Moschogiannis, Maria; Kalpadakis, Christina; Yiakoumis, Xanthi; Rontogianni, Dimitra

2016-09-01

Malakoplakia, a rare granulomatous disease of infectious etiology, is commonly observed in immunocompromised patients. Chronic lymphocytic leukemia (CLL) is characterized by profound immune dysregulation resulting in significant infection-related morbidity and mortality, and several drugs used in CLL treatment have a severe immunosuppressive effect. Ibrutinib, has become a new standard-of-care in patients with CLL, especially for those harboring unfavorable genetic characteristics such as 17 p deletion, with however, unknown long-term immunological consequences. Here we report a case of a patient with CLL with 17 p deletion diagnosed with malakoplakia of the urinary bladder under ibrutinib therapy who developed severe hypogammaglobulinemia during treatment administration. Presumably, ibrutinib might contribute to the development of malakoplakia on the grounds of induced immunosuppression. This case report highlights the need for regular assessment of immunogammaglobulin adequacy during treatment with ibrutinib, considering that it should be given on a permanent basis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Emphysematous cystitis: a rare cause of gross hematuria.

PubMed

Chang, Chirn-Bin; Chang, Chia-Chu

2011-05-01

Emphysematous cystitis is a relatively rare infectious condition of the urinary bladder. The mortality rate is high if the diagnosis is delayed or if the treatment is inadequate. We present an uncommon case of emphysematous cystitis and highlight the risk factors for this disease. An 81-year-old man with a past medical history of type 2 diabetes and a central pontine infarction presented to the Emergency Department due to gross hematuria. Computed tomography (CT) and plain radiography revealed localized gas within the bladder that was compatible with the diagnosis of emphysematous cystitis. A Foley catheter was inserted. Urine culture grew Klebsiella pneumoniae; 2 g cefotaxime daily was initiated. Subsequent plain radiography and CT scan showed regression of intraluminal gas. We recommend CT for the definitive diagnosis of emphysematous cystitis. Adequate antibiotic therapy, strict blood glucose control, adequate drainage of urine, and early goal-directed therapy for suspected sepsis are suggested to prevent the complications of emphysematous cystitis. Copyright © 2011 Elsevier Inc. All rights reserved.

Preclinical studies of vascular acting photosensitizer bacteriopheophorbide for the treatment of prostate cancer

NASA Astrophysics Data System (ADS)

Hetzel, Fred W.; Chen, Qun; Luck, David; Beckers, Jill; Huang, Zheng

2004-06-01

Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad), is investigated as an alternative modality for the total ablation of prostate cancer. In vivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the IV infused photosensitizer drug. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week post PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Prostate lesions could be detected by MRI scan as early as 48 h post PDT. Maximum lesion size of 1.5 cm3 and 2.9 cm3 could be achieved at 50 J/cm and 100 J/cm, respectively, with interstitial treatment using a single 1-cm diffuser fiber, suggesting the Tookad-PDT is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat localized prostate cancer.

Therapeutic Yoga: Symptom Management for Multiple Sclerosis

PubMed Central

MacDonald, Megan

2015-01-01

Abstract Multiple sclerosis (MS) is the most common autoimmune inflammatory demyelinating disease of the central nervous system, affecting over 2.3 million people worldwide. According to the National Institute of Neurological Disorders and Stroke, the age of disease onset is typically between 20 and 40 years, with a higher incidence in women. Individuals with MS experience a wide range of symptoms, including declining physical, emotional, and psychological symptoms (e.g., fatigue, imbalance, spasticity, chronic pain, cognitive impairment, bladder and bowel dysfunction, visual and speech impairments, depression, sensory disturbance, and mobility impairment). To date, both the cause of and cure for MS remain unknown. In recent years, more individuals with MS have been pursuing alternative methods of treatment to manage symptoms of the disease, including mind-body therapies such as yoga, meditation, breathing, and relaxation techniques. It has been suggested that the practice of yoga may be a safe and effective way of managing symptoms of MS. Therefore, the purpose of this paper is to summarize the most relevant literature on exercise and mind-body modalities to treat MS symptoms and, more specifically, the benefits and potential role of yoga as an alternative treatment of symptom management for individuals with MS. The article also discusses future directions for research. PMID:26270955

Vesicoscopic Treatment of Symptomatic Congenital Bladder Diverticula in Children: A 7-Year Experience.

PubMed

Marte, Antonio; Cavaiuolo, Silvia; Esposito, Maria; Pintozzi, Lucia

2016-06-01

Introduction The objective of this study was to report on the use of vesicoscopy in the treatment of symptomatic congenital bladder diverticula (CBD) in children. Material and Methods In this study, 16 males, aged 4 to 12 years (median age, 6.25 years), were treated for symptomatic CBD; 3 patients presented double diverticulum and 13 presented single diverticulum. The presenting symptoms were recurrent urinary tract infection, hematuria, lower abdominal pain, and voiding dysfunctions as urgency, frequency alone, or in association. A first midline 5-mm trocar was introduced for a 0-degree telescope at the dome of the bladder, and two left and right 3- or 5-mm trocars were inserted through the anterolateral wall. The bladder was then insufflated with carbon dioxide to 10 to 12 mm Hg pressure. The diverticula were inverted into the bladder and the mucosa around the neck was circumcised by using scissors and hook. The defect was sutured and the bladder was drained. Vesicoureteral reflux (VUR) of third grade or higher was treated endoscopically. Results Mean operative time was 90 minutes for procedures. At 6-month follow-up, ultrasound and voiding cystourethrogram (VCUG) showed the disappearance of the diverticulum in 15 out of the 16 patients. The patient, with huge double diverticulum and fourth grade right VUR, presented recurrence of a small left diverticulum. Patients with voiding disorders presented a gradual improvement of their urgency. VUR disappeared at VCUG in all patients. Conclusion Vesicoscopic diverticulectomy resulted a safe and effective procedure and can be considered a valid alternative to the open or laparoscopic procedures. In our opinion, routine use of vesicoscopy could become the gold standard for the treatment of CBD in children. Georg Thieme Verlag KG Stuttgart · New York.

Development of a wearable microwave bladder monitor for the management and treatment of urinary incontinence

NASA Astrophysics Data System (ADS)

Krewer, F.; Morgan, F.; Jones, E.; Glavin, M.; O'Halloran, M.

2014-05-01

Urinary incontinence is defined as the inability to stop the flow of urine from the bladder. In the US alone, the annual societal cost of incontinence-related care is estimated at 12.6 billion dollars. Clinicians agree that those suffering from urinary incontinence would greatly benefit from a wearable system that could continually monitor the bladder, providing continuous feedback to the patient. While existing ultrasound-based solutions are highly accurate, they are severely limited by form-factor, battery size, cost and ease of use. In this study the authors propose an alternative bladder-state sensing system, based on Ultra Wideband (UWB) Radar. As part of an initial proof-of-concept, the authors developed one of the first dielectrically and anatomically-representative Finite Difference Time Domain models of the pelvis. These models (one male and one female) are derived from Magnetic Resonance images provided by the IT'IS Foundation. These IT'IS models provide the foundation upon which an anatomically-plausible bladder growth model was constructed. The authors employed accurate multi-pole Debye models to simulate the dielectric properties of each of the pelvic tissues. Two-dimensional Finite Difference Time Domain (FDTD) simulations were completed for a range of bladder volumes. Relevant features were extracted from the FDTD-derived signals using Principle Component Analysis (PCA) and then classified using a k-Nearest-Neighbour and Support Vector Machine algorithms (incorporating the Leave-one-out cross-validation approach). Additionally the authors investigated the effects of signal fidelity, noise and antenna movement relative to the target as potential sources of error. The results of this initial study provide strong motivation for further research into this timely application, particularly in the context of an ageing population.

Percutaneous cystolithotripsy using self-retaining laparoscopic trocar for management of large bladder stones.

PubMed

Elbahnasy, Abdelhamid M; Farhat, Yasser A; Aboramadan, Ahmad R; Taha, Mohamed Rasheed

2010-12-01

Percutaneous endoscopic management of bladder stones is not new. The ideal technique to establish suprapubic access, however, is still not justified. In this study, we used the 12-mm self-retaining laparoscopic trocar for access during management of large bladder stones. With the patient in the lithotomy position, a 12-mm self-retaining laparoscopic trocar was inserted in a full bladder under cystoscopic visual control. A 28F nephroscope was used to fragment the stone using ultrasound and pneumoclast lithotriptors. After stone treatment, the trocar was left in place, and transurethral resection of the prostate (TURP) was completed when indicated. Both urethral and suprapubic catheters were left at the end of the procedure. Clinical examination, urinalysis, and ultrasonographic examination were routinely performed during follow-up visits. The mean stone size was 4.07 + 0.20 cm (2.8-6 cm). The average time for stone fragmentation was 32.78 + 2.16 minutes (range 8-53 min). A concomitant TURP was performed in 12 patients. The mean hospital stay was 2.56 + 0.15 days (range 1-4 days). All patients were stone free, and a total of six complications occurred, including extravasation, one patient; hematuria, two patients; and fever, three patients. All were treated conservatively. The mean follow-up time was 15.65 + 1.51 months (range 9-36 mos). Suprapubic percutaneous cystolithotripsy is a safe, minimally invasive alternative for management of large bladder stones. The use of a self-retaining trocar facilitates access and allows use of a large nephroscope for rapid fragmentation and extraction of the stone fragments. The presence of specific trocars for suprapubic access into the urinary bladder will encourage more transvesical end-laparoscopic procedures.

Complementary and alternative medical therapies in multiple sclerosis--the American Academy of Neurology guidelines: a commentary.

PubMed

Yadav, Vijayshree; Narayanaswami, Pushpa

2014-12-01

Complementary and alternative medicine (CAM) use in individuals with multiple sclerosis (MS) is common, but its use has been limited by a lack of evidence-based guidance. In March 2014, the American Academy of Neurology published the most comprehensive literature review and evidence-based practice guidelines for CAM use in MS. The guideline author panel reviewed and classified articles according to the American Academy of Neurology therapeutic scheme, and recommendations were linked to the evidence strength. Level A recommendations were found for oral cannabis extract effectiveness in the short term for spasticity-related symptoms and pain and ineffectiveness of ginkgo biloba for cognitive function improvement in MS. Key level B recommendations included: Oral cannabis extract or a synthetic cannabis constituent, tetrahydrocannabinol (THC) is probably ineffective for objective spasticity improvement in the short term; Nabiximols oromucosal cannabinoid spray is probably effective for spasticity symptoms, pain, and urinary frequency, but probably ineffective for objective spasticity outcomes and bladder incontinence; Magnetic therapy is probably effective for fatigue reduction in MS; A low-fat diet with fish oil supplementation is probably ineffective for MS-related relapses, disability, fatigue, magnetic resonance imaging lesions, and quality of life. Several Level C recommendations were made. These included possible effectiveness of gingko biloba for fatigue; possible effectiveness of reflexology for MS-related paresthesias; possible ineffectiveness of the Cari Loder regimen for MS-related disability, symptoms, depression, and fatigue; and bee sting therapy for MS relapses, disability, fatigue, magnetic resonance imaging outcomes, and health-related quality of life. Despite the availability of studies evaluating the effects of oral cannabis in MS, the use of these formulations in United States may be limited due to a lack of standardized, commercial US Food and Drug Administration-regulated preparations. Additionally, significant concern about prominent central nervous system-related adverse effects with cannabis was emphasized in the review. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Comparison of the efficacy and feasibility of en bloc transurethral resection of bladder tumor versus conventional transurethral resection of bladder tumor: A meta-analysis.

PubMed

Wu, Yu-Peng; Lin, Ting-Ting; Chen, Shao-Hao; Xu, Ning; Wei, Yong; Huang, Jin-Bei; Sun, Xiong-Lin; Zheng, Qing-Shui; Xue, Xue-Yi; Li, Xiao-Dong

2016-11-01

The aim of this meta-analysis was to compare the feasibility of en bloc transurethral resection of bladder tumor (ETURBT) versus conventional transurethral resection of bladder tumor (CTURBT). Relevant trials were identified in a literature search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and Google Scholar using appropriate search terms. All comparative studies reporting participant demographics, tumor characteristics, study characteristics, and outcome data were included. Seven trials with 886 participants were included, 438 underwent ETURBT and 448 underwent CTURBT. There was no significant difference in operation time between 2 groups (P = 0.38). The hospitalization time (HT) and catheterization time (CT) were shorter in ETURBT group (mean difference[MD] -1.22, 95% confidence interval [CI] -1.63 to -0.80, P < 0.01; MD -0.61, 95% CI -1.11 to -0.11, P < 0.01). There was significant difference in 24-month recurrence rate (24-month RR) (odds ratio [OR] 0.66, 95% CI 0.47-0.92, P = 0.02). The rate of complication with respect to bladder perforation (P = 0.004), bladder irritation (P < 0.01), and obturator nerve reflex (P < 0.01) was lower in ETURBT. The postoperative adjuvant intravesical chemotherapy was evaluated by subgroup analysis, and 24-month RR in CTURBT is higher than that in ETURBT in mitomycin intravesical irrigation group (P = 0.02). The first meta-analysis indicates that ETURBT might prove to be preferable alternative to CTURBT management of nonmuscle invasive bladder carcinoma. ETURBT is associated with shorter HT and CT, less complication rate, and lower recurrence-free rate. Moreover, it can provide high-qualified specimen for the pathologic diagnosis. Well designed randomized controlled trials are needed to make results comparable.

Looking for gall bladder disease in the patient's iris.

PubMed Central

Knipschild, P.

1988-01-01

In alternative health care iridology is used as a diagnostic aid. The diagnosis of gall bladder disease was used to study its validity and interperformer consistency. The presence of an inflamed gall bladder containing gall stones is said to be easily recognised by certain signs in the lower lateral part of the iris of the right eye. Stereo colour slides were made of the right eye. Stereo colour slides were made of the right eye of 39 patients with this disease and 39 control subjects of the same sex and age. The slides were presented in a random order to five leading iridologists without supplementary information. The prevalence of the disease was estimated at 56%. The median validity was 51% with 54% sensitivity and 52% specificity. These results were close to chance validity (iota = 0.03). None of the iridologists reached a high validity. The median interperformer consistency was 60%. This was only slightly higher than chance consistency (kappa = 0.18). This study showed that iridology is not a useful diagnostic aid. PMID:3147081

Looking for gall bladder disease in the patient's iris.

PubMed

Knipschild, P

1988-12-17

In alternative health care iridology is used as a diagnostic aid. The diagnosis of gall bladder disease was used to study its validity and interperformer consistency. The presence of an inflamed gall bladder containing gall stones is said to be easily recognised by certain signs in the lower lateral part of the iris of the right eye. Stereo colour slides were made of the right eye. Stereo colour slides were made of the right eye of 39 patients with this disease and 39 control subjects of the same sex and age. The slides were presented in a random order to five leading iridologists without supplementary information. The prevalence of the disease was estimated at 56%. The median validity was 51% with 54% sensitivity and 52% specificity. These results were close to chance validity (iota = 0.03). None of the iridologists reached a high validity. The median interperformer consistency was 60%. This was only slightly higher than chance consistency (kappa = 0.18). This study showed that iridology is not a useful diagnostic aid.

Embryonic kidney function in a chronic renal failure model in rodents.

PubMed

Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

2017-08-01

Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system.

PubMed

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

2012-01-01

The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72-18.55 Gy) and 5.17 Gy (range 0.72-15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system.

A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system

PubMed Central

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

2012-01-01

Aim The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. Background The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Materials and methods Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. Results The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72–18.55 Gy) and 5.17 Gy (range 0.72–15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. Conclusion In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system. PMID:24377037

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.

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

Li Xiong; Viswanathan, Akila; Stewart, Alexandra J.

Cumulative dose distributions in fractionated radiation therapy depict the dose to normal tissues and therefore may permit an estimation of the risk of normal tissue complications. However, calculation of these distributions is highly challenging because of interfractional changes in the geometry of patient anatomy. This work presents an algorithm for deformable structure registration of the bladder and the verification of the accuracy of the algorithm using phantom and patient data. In this algorithm, the registration process involves conformal mapping of genus zero surfaces using finite element analysis, and guided by three control landmarks. The registration produces a correspondence between fractionsmore » of the triangular meshes used to describe the bladder surface. For validation of the algorithm, two types of balloons were inflated gradually to three times their original size, and several computerized tomography (CT) scans were taken during the process. The registration algorithm yielded a local accuracy of 4 mm along the balloon surface. The algorithm was then applied to CT data of patients receiving fractionated high-dose-rate brachytherapy to the vaginal cuff, with the vaginal cylinder in situ. The patients' bladder filling status was intentionally different for each fraction. The three required control landmark points were identified for the bladder based on anatomy. Out of an Institutional Review Board (IRB) approved study of 20 patients, 3 had radiographically identifiable points near the bladder surface that were used for verification of the accuracy of the registration. The verification point as seen in each fraction was compared with its predicted location based on affine as well as deformable registration. Despite the variation in bladder shape and volume, the deformable registration was accurate to 5 mm, consistently outperforming the affine registration. We conclude that the structure registration algorithm presented works with reasonable accuracy and provides a means of calculating cumulative dose distributions.« less

Differentiation‐associated urothelial cytochrome P450 oxidoreductase predicates the xenobiotic‐metabolizing activity of “luminal” muscle‐invasive bladder cancers

PubMed Central

Arlt, Volker M.; Indra, Radek; Joel, Madeleine; Stiborová, Marie; Eardley, Ian; Ahmad, Niaz; Otto, Wolfgang; Burger, Maximilian; Rubenwolf, Peter; Phillips, David H.; Southgate, Jennifer

2018-01-01

Extra‐hepatic metabolism of xenobiotics by epithelial tissues has evolved as a self‐defence mechanism but has potential to contribute to the local activation of carcinogens. Bladder epithelium (urothelium) is bathed in excreted urinary toxicants and pro‐carcinogens. This study reveals how differentiation affects cytochrome P450 (CYP) activity and the role of NADPH:P450 oxidoreductase (POR). CYP1A1 and CYP1B1 transcripts were inducible in normal human urothelial (NHU) cells maintained in both undifferentiated and functional barrier‐forming differentiated states in vitro. However, ethoxyresorufin O‐deethylation (EROD) activity, the generation of reactive BaP metabolites and BaP‐DNA adducts, were predominantly detected in differentiated NHU cell cultures. This gain‐of‐function was attributable to the expression of POR, an essential electron donor for all CYPs, which was significantly upregulated as part of urothelial differentiation. Immunohistology of muscle‐invasive bladder cancer (MIBC) revealed significant overall suppression of POR expression. Stratification of MIBC biopsies into “luminal” and “basal” groups, based on GATA3 and cytokeratin 5/6 labeling, showed POR over‐expression by a subgroup of the differentiated luminal tumors. In bladder cancer cell lines, CYP1‐activity was undetectable/low in basal PORlo T24 and SCaBER cells and higher in the luminal POR over‐expressing RT4 and RT112 cells than in differentiated NHU cells, indicating that CYP‐function is related to differentiation status in bladder cancers. This study establishes POR as a predictive biomarker of metabolic potential. This has implications in bladder carcinogenesis for the hepatic versus local activation of carcinogens and as a functional predictor of the potential for MIBC to respond to prodrug therapies. PMID:29323757

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.

Acute radiation impacts contractility of guinea-pig bladder strips affecting mucosal-detrusor interactions.

PubMed

McDonnell, Bronagh M; Buchanan, Paul J; Prise, Kevin M; McCloskey, Karen D

2018-01-01

Radiation-induced bladder toxicity is associated with radiation therapy for pelvic malignancies, arising from unavoidable irradiation of neighbouring normal bladder tissue. This study aimed to investigate the acute impact of ionizing radiation on the contractility of bladder strips and identify the radiation-sensitivity of the mucosa vs the detrusor. Guinea-pig bladder strips (intact or mucosa-free) received ex vivo sham or 20Gy irradiation and were studied with in vitro myography, electrical field stimulation and Ca2+-fluorescence imaging. Frequency-dependent, neurogenic contractions in intact strips were reduced by irradiation across the force-frequency graph. The radiation-difference persisted in atropine (1μM); subsequent addition of PPADs (100μM) blocked the radiation effect at higher stimulation frequencies and decreased the force-frequency plot. Conversely, neurogenic contractions in mucosa-free strips were radiation-insensitive. Radiation did not affect agonist-evoked contractions (1μM carbachol, 5mM ATP) in intact or mucosa-free strips. Interestingly, agonist-evoked contractions were larger in irradiated mucosa-free strips vs irradiated intact strips suggesting that radiation may have unmasked an inhibitory mucosal element. Spontaneous activity was larger in control intact vs mucosa-free preparations; this difference was absent in irradiated strips. Spontaneous Ca2+-transients in smooth muscle cells within tissue preparations were reduced by radiation. Radiation affected neurogenic and agonist-evoked bladder contractions and also reduced Ca2+-signalling events in smooth muscle cells when the mucosal layer was present. Radiation eliminated a positive modulatory effect on spontaneous activity by the mucosa layer. Overall, the findings suggest that radiation impairs contractility via mucosal regulatory mechanisms independent of the development of radiation cystitis.

Dosimetric and radiobiologic comparison of 3D conformal versus intensity modulated planning techniques for prostate bed radiotherapy.

PubMed

Koontz, Bridget F; Das, Shiva; Temple, Kathy; Bynum, Sigrun; Catalano, Suzanne; Koontz, Jason I; Montana, Gustavo S; Oleson, James R

2009-01-01

Adjuvant radiotherapy for locally advanced prostate cancer improves biochemical and clinical disease-free survival. While comparisons in intact prostate cancer show a benefit for intensity modulated radiation therapy (IMRT) over 3D conformal planning, this has not been studied for post-prostatectomy radiotherapy (RT). This study compares normal tissue and target dosimetry and radiobiological modeling of IMRT vs. 3D conformal planning in the postoperative setting. 3D conformal plans were designed for 15 patients who had been treated with IMRT planning for salvage post-prostatectomy RT. The same computed tomography (CT) and target/normal structure contours, as well as prescription dose, was used for both IMRT and 3D plans. Normal tissue complication probabilities (NTCPs) were calculated based on the dose given to the bladder and rectum by both plans. Dose-volume histogram and NTCP data were compared by paired t-test. Bladder and rectal sparing were improved with IMRT planning compared to 3D conformal planning. The volume of the bladder receiving at least 75% (V75) and 50% (V50) of the dose was significantly reduced by 28% and 17%, respectively (p = 0.002 and 0.037). Rectal dose was similarly reduced, V75 by 33% and V50 by 17% (p = 0.001 and 0.004). While there was no difference in the volume of rectum receiving at least 65 Gy (V65), IMRT planning significant reduced the volume receiving 40 Gy or more (V40, p = 0.009). Bladder V40 and V65 were not significantly different between planning modalities. Despite these dosimetric differences, there was no significant difference in the NTCP for either bladder or rectal injury. IMRT planning reduces the volume of bladder and rectum receiving high doses during post-prostatectomy RT. Because of relatively low doses given to the bladder and rectum, there was no statistically significant improvement in NTCP between the 3D conformal and IMRT plans.

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

SU-E-T-129: Are Knowledge-Based Planning Dose Estimates Valid for Distensible Organs?

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

Lalonde, R; Heron, D; Huq, M

2015-06-15

Purpose: Knowledge-based planning programs have become available to assist treatment planning in radiation therapy. Such programs can be used to generate estimated DVHs and planning constraints for organs at risk (OARs), based upon a model generated from previous plans. These estimates are based upon the planning CT scan. However, for distensible OARs like the bladder and rectum, daily variations in volume may make the dose estimates invalid. The purpose of this study is to determine whether knowledge-based DVH dose estimates may be valid for distensible OARs. Methods: The Varian RapidPlan™ knowledge-based planning module was used to generate OAR dose estimatesmore » and planning objectives for 10 prostate cases previously planned with VMAT, and final plans were calculated for each. Five weekly setup CBCT scans of each patient were then downloaded and contoured (assuming no change in size and shape of the target volume), and rectum and bladder DVHs were recalculated for each scan. Dose volumes were then compared at 75, 60,and 40 Gy for the bladder and rectum between the planning scan and the CBCTs. Results: Plan doses and estimates matched well at all dose points., Volumes of the rectum and bladder varied widely between planning CT and the CBCTs, ranging from 0.46 to 2.42 for the bladder and 0.71 to 2.18 for the rectum, causing relative dose volumes to vary between planning CT and CBCT, but absolute dose volumes were more consistent. The overall ratio of CBCT/plan dose volumes was 1.02 ±0.27 for rectum and 0.98 ±0.20 for bladder in these patients. Conclusion: Knowledge-based planning dose volume estimates for distensible OARs are still valid, in absolute volume terms, between treatment planning scans and CBCT’s taken during daily treatment. Further analysis of the data is being undertaken to determine how differences depend upon rectum and bladder filling state. This work has been supported by Varian Medical Systems.« less

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

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.

[A Case of Hyperammonemia Caused by Urinary Tract Infection Due to Urease-Producing Bacteria].

PubMed

Emura, Masahiro; Tsuchihashi, Kazunari; Shimizu, Yosuke; Kanamaru, Sojun; Matoba, Shun; Ito, Noriyuki

2016-08-01

We present here a rare case of hyperammonemia without liver dysfunction or portal-systemic shunting. The patient was an 80-year-old woman with a history of neurogenic bladder. She was admitted to a nearby hospital for vomiting, diarrhea and consciousness disturbance. Two days after admission, she was transferred to our hospital because of persistant consciousness disturbance. Laboratory data revealed hyperammonemia, but there was no indication of liver dysfunction. Moreover abdominal computed tomography did not reveal any clear finding of liver disease or portal-systemic shunting, but we noted multiple large bladder diverticula. Antibiotic therapy, tracheal intubation, ventilator management and bladder catheterization were performed. The patient's level of consciousness improved rapidly. Urinary culture revealed Bacteroides ureolyticus (urease-producing bacteria). The patient was diagnosed with hyperammonemia and a urinary tract infection due to urease-producing bacteria. Thus, physicians should be aware that obstructive urinary tract infections due to urease-producing bacteria can also be the cause of hyperammonemia.

TVT-O vs TVT: a randomized trial in patients with different degrees of urinary stress incontinence.

PubMed

Araco, F; Gravante, G; Sorge, R; Overton, J; De Vita, D; Sesti, F; Piccione, E

2008-07-01

TVT-O and TVT were compared in patients stratified according the severity of Stress Urinary Incontinence (SUI). Those patients with intrinsic sphincter deficiencies, overactive bladders, associated prolapses, neurovegetative disorders and recurrent SUI or under rehabilitative/medical therapies were all excluded. There were 208 women included. Operating times were longer, and postoperative pain greater for TVT (p < 0.001). TVT produced longer hospitalizations in severe SUI patients (p < 0.001). After 1 year of follow-up, incontinence was cured in all mild SUI patients with both techniques, in all severe SUI patients when treated with TVT and in 66% of them when treated with TVT-O (p < 0.001). Vaginal perforations occurred during the TVT-O (p = 0.01), bladder perforations during TVT (p = NS), bladder obstructions in mild SUI patients after TVT (p < 0.001). The severity of SUI is an important parameter that influences results after TVT-O and TVT, and could be used to guide surgeons in selecting the most effective intervention.

Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer

PubMed Central

Shang, Zhiqun; Li, Yanjun; Hsu, Iawen; Zhang, Minghao; Tian, Jing; Wen, Simeng; Han, Ruifa; Messing, Edward M.; Chang, Chawnshang; Niu, Yuanjie; Yeh, Shuyuan

2016-01-01

Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence. PMID:27092883

Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer.

PubMed

Shang, Zhiqun; Li, Yanjun; Hsu, Iawen; Zhang, Minghao; Tian, Jing; Wen, Simeng; Han, Ruifa; Messing, Edward M; Chang, Chawnshang; Niu, Yuanjie; Yeh, Shuyuan

2016-05-10

Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette-Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence.

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.

The effectiveness of transcutaneous electrical neural stimulation therapy in patients with urinary incontinence resistant to initial medical treatment or biofeedback.

PubMed

Tugtepe, H; Thomas, D T; Ergun, R; Kalyoncu, A; Kaynak, A; Kastarli, C; Dagli, T E

2015-06-01

While there are many options for children with treatment refractory urinary incontinence, there is no single accepted method. This study's aim was to prospectively evaluate the effect of transcutaneous electrical nerve stimulation in children with urinary incontinence resistant to standard medical, urological therapy and/or biofeedback. This study was performed at a university hospital. For inclusion, patients >5 years of age first underwent evaluation with urinary ultrasonography, uroflow-electromyogram and voiding diaries. Treatment with biofeedback, alpha adrenergic blockers, anticholinergics and/or urotherapy was commenced according to uroflow-EMG and voiding diary findings. Patients with partial or no response to this standard therapy were then included in this study, performed between April 2012 and February 2014. Patients with anatomical or neurological causes for urinary incontinence were excluded. TENS was performed on S3 dermatome, every day for 3 months. Each session lasted 20 min with a frequency of 10 Hz and generated pulse of 350 μs. Intensity was determined by the child's sensitivity threshold. Medical treatment and urological therapy was continued during TENS. Uroflow parameters (voiding volume as percentage of expected bladder capacity, Qmax, Qave, flow and voiding time, postvoiding residual urine) and urinary system symptoms (presence of urinary tract infection, frequency, urge incontinence, fractionated voiding and constipation) were compared immediately before commencement and immediately after the completion of 3 months of TENS. Twenty-seven patients were included in this study (4 males, 23 females). Patients' average age was 7.2 years, 11 had overactive bladder and 16 had dysfunctional voiding. Comparison of urinary system symptoms and uroflow parameters before and after TENS are shown in Table. After 3 months of TENS; a statistically significant decrease was observed in the number of patients with frequency, urge incontinence, urinary tract infections and constipation. There was a decrease in the number of patients with fractionated voiding, although this change was not statistically significant. Similarly, for uroflow-EMG parameters; bladder capacity, Qmax, Qave and flow time increased while voiding time and PVR decreased. Changes seen in bladder capacity, Qmax and PVR were statically significant, while other changes were not. Patients' response rates after 3 months of TENS were; complete response in 70.4%, partial response in 22.2% and no response in 7.4%. This study has shown that transcutaneous electrical nerve stimulation is a promising treatment option for standard-treatment refractory children with urinary incontinence. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

[Bladder endometriosis. Diagnostic and therapeutic approximation].

PubMed

Monllor Gisbert, J; Merino Hernaez, C; Olivier Gómez, C; Carballido Rodríguez, J

1991-01-01

Endometriosis is defined by the presence of functionally active endometria in ectopic position; so when its clinical behaviour adopts the characteristics of tumoration, endometrioma is accepted as an alternative name. Location of this pathology in the urinary apparatus is uncommon in terms of incidence, since the bladder is a selected site. This condition implies a high morbidity rate because it requires a high level of suspicion in order to be diagnosed. It is acknowledged that no image study (CAT, Echography, MNR, etc.) is pathognomonic for endometriosis and it is necessary to perform endoscopy and biopsy to achieve a correct diagnosis. The paper includes the strategy to follow, both with regard to diagnosis and the current therapeutic approaches.

SU-F-J-69: The Dosimetric Impact of Interfraction Anorectum and Bladder Variability in Prostate Radiation Therapy

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

Patel, V; Chinea, F; Abramowitz, M

Purpose: In the era of dose escalation and numerous protocols evaluating radiation delivery to the prostate, it is imperative to achieve accurate and standardized daily set up. At the Sylvester Comprehensive Cancer Center, patients are instructed to drink 8 ounces of water 30 minutes prior to RT and follow a low residue diet to ensure that the anorectum is not distended and the bladder is adequately filled. If daily CBCT imaging shows any variation, the patient is removed from the table and drinks water or evacuates their rectum prior to a repeat CBCT. Here we attempt to quantify the efficacymore » of this procedure. Methods: CBCTs were collected for 5 patients receiving 40 fractions of definitive treatment for prostate cancer. CBCTs were imported into MIM (v6.5.7, Cleveland OH) and the bladder, anorectum, and prostate were contoured. Using the daily registration reviewed by the attending physician, the planning dose was rigidly transferred to the daily CBCT. On days that multiple CBCTs were performed due to inadequate anorectum or bladder preparation, the repeated and final CBCTs were evaluated for variations in V40Gy and V65Gy to both the anorectum and bladder. Results: A high level of variability in doses to the anorectum and bladder was found in the scans that were not utilized for treatment. The aggregate lower quartile for the unused versus used CBCTs was 27.2% vs. 16.83% for V40Gy and 8.53% vs. 5.66% for V65Gy bladder. The upper quartiles showed to be 48.88% vs. 41.92% and 21.05% vs. 20.55%. The combined lower quartile for the unused vs. used CBCTs was 8.24% vs. 5.49% for V40Gy and 0.57% vs. 0.0% for V65Gy anorectum. The upper quartiles were 34.35% vs. 33.25% and 18.37% vs. 16.11%. Conclusion: This study shows that daily imaging is insufficient and that proper bladder and anorectum preparation are essential to deliver proper treatment.« less

Dose to the Bladder Neck Is the Most Important Predictor for Acute and Late Toxicity After Low-Dose-Rate Prostate Brachytherapy: Implications for Establishing New Dose Constraints for Treatment Planning

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

Hathout, Lara; Folkert, Michael R.; Kollmeier, Marisa A.

2014-10-01

Purpose: To identify an anatomic structure predictive for acute (AUT) and late (LUT) urinary toxicity in patients with prostate cancer treated with low-dose-rate brachytherapy (LDR) with or without external beam radiation therapy (EBRT). Methods and Materials: From July 2002 to January 2013, 927 patients with prostate cancer (median age, 66 years) underwent LDR brachytherapy with Iodine 125 (n=753) or Palladium 103 (n=174) as definitive treatment (n=478) and as a boost (n=449) followed by supplemental EBRT (median dose, 50.4 Gy). Structures contoured on the computed tomographic (CT) scan on day 0 after implantation included prostate, urethra, bladder, and the bladder neck, defined asmore » 5 mm around the urethra between the catheter balloon and the prostatic urethra. AUT and LUT were assessed with the Common Terminology Criteria for Adverse Events, version4. Clinical and dosimetric factors associated with AUT and LUT were analyzed with Cox regression and receiver operating characteristic analysis to calculate area under the receiver operator curve (ROC) (AUC). Results: Grade ≥2 AUT and grade ≥2 LUT occurred in 520 patients (56%) and 154 patients (20%), respectively. No grade 4 toxicities were observed. Bladder neck D2cc retained a significant association with AUT (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.03-1.04; P<.0001) and LUT (HR, 1.01; 95% CI, 1.00-1.03; P=.014) on multivariable analysis. In a comparison of bladder neck with the standard dosimetric variables by use of ROC analysis (prostate V100 >90%, D90 >100%, V150 >60%, urethra D20 >130%), bladder neck D2cc >50% was shown to have the strongest prognostic power for AUT (AUC, 0.697; P<.0001) and LUT (AUC, 0.620; P<.001). Conclusions: Bladder neck D2cc >50% was the strongest predictor for grade ≥2 AUT and LUT in patients treated with LDR brachytherapy. These data support inclusion of bladder neck constraints into brachytherapy planning to decrease urinary toxicity.« less

Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-Mercaptobenzothiazole Part I: Fathead minnow

EPA Science Inventory

Development of adverse outcome pathways linking specific chemical-induced pathway perturbations to adverse outcomes relevant to regulatory decision-making has potential to support the development of alternatives to traditional whole organism toxicity tests, such as the fish early...

Evaluation of volume change in rectum and bladder during application of image-guided radiotherapy for prostate carcinoma

NASA Astrophysics Data System (ADS)

Luna, J. A.; Rojas, J. I.

2016-07-01

All prostate cancer patients from Centro Médico Radioterapia Siglo XXI receive Volumetric Modulated Arc Therapy (VMAT). This therapy uses image-guided radiotherapy (IGRT) with the Cone Beam Computed Tomography (CBCT). This study compares the planned dose in the reference CT image against the delivered dose recalculate in the CBCT image. The purpose of this study is to evaluate the anatomic changes and related dosimetric effect based on weekly CBCT directly for patients with prostate cancer undergoing volumetric modulated arc therapy (VMAT) treatment. The collected data were analyzed using one-way ANOVA.

The Changing Treatment Landscape for Metastatic Urothelial Carcinoma.

PubMed

Flaig, Thomas W

2018-05-01

Urothelial carcinoma is the predominant histologic type of bladder cancer. After 30 years of minimal progress in the treatment of advanced-stage disease, recent advances in the genomic characterization of urothelial cancer and breakthroughs in bladder cancer therapeutics have rejuvenated the field. Nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab are among the exciting recent novel therapeutic advances gaining approvals by the FDA for treatment of advanced-stage urothelial carcinoma. Yet the challenge for clinicians is to determine the optimal choice of agents as first-line or second-line therapy and which offers the best chance for overall survival for the individual patient in this rapidly changing field. Copyright © 2018 by the National Comprehensive Cancer Network.

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.

Tibial nerve stimulation to inhibit the micturition reflex by an implantable wireless driver microstimulator in cats

PubMed Central

Li, Xing; Liao, Li-Min; Chen, Guo-Qing; Wang, Zhao-Xia; Lu, Tian-Ji; Deng, Han; Loeb, Gerald-E

2016-01-01

Abstract Background: Traditional tibial nerve stimulation (TNS) has been used to treat overactive bladder syndrome (OAB), but there are some shortcomings. Thus, a novel alternative is needed for the treatment of OAB. The study investigated the effects of a new type of tibial nerve microstimulator on the micturition reflex in cats. Methods: An implantable wireless driver microstimulator was implanted around the tibial nerve in 9 α-chloralose anesthetized cats. Cystometry was performed by infusing 0.9% normal saline (NS) or 0.25% acetic acid (AA) through a urethral catheter. Multiple cystometrograms were performed before, during, and after TNS to determine the inhibitory effect of the microstimulator on the micturition reflex. Results: TNS at 2 threshold (T) intensity significantly increased the bladder capacity (BC) during NS infusion. Bladder overactivity was irritated by the intravesical infusion of 0.25% AA, which significantly reduced the BC compared with the NS infusion. TNS at 2 T intensity suppressed AA-induced bladder overactivity and significantly increased the BC compared with the AA control. Conclusion: The implantable wireless driver tibial nerve microstimulator appears to be effective in inhibiting the micturition reflex during physiologic and pathologic conditions. The implantable wireless driver tibial nerve microstimulator could be used to treat OAB. PMID:27537576

Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

NASA Astrophysics Data System (ADS)

Geng, Hongquan; Song, Hua; Qi, Jun; Cui, Daxiang

2011-12-01

We fabricated a novel vascular endothelial growth factor (VEGF)-loaded poly(lactic- co-glycolic acid) (PLGA)-nanoparticles (NPs)-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA) system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.

Technologic developments in the field of photonics for the detection of urinary bladder cancer.

PubMed

Palmer, Scott; Sokolovski, Sergei G; Rafailov, Edik; Nabi, Ghulam

2013-12-01

Bladder cancer is a common cause of morbidity and mortality worldwide in an aging population. Each year, thousands of people, mostly men, are diagnosed with this disease, but many of them present too late to receive optimal treatment. As with all cancers, early diagnosis of bladder cancer significantly improves the efficacy of therapy and increases survival and recurrence-free survival rates. Ongoing research has identified many limitations about the sensitivity of standard diagnostic procedures in detecting early-stage tumors and precancerous changes. The consequences of this are often tumor progression and increased tumor burden, leading to a decrease in patient quality of life and a vast increase in treatment costs. The necessity for improved early detection of bladder cancer has spurred on research into novel methods that use a wide range of biological and photonic phenomena. This review will broadly discuss standard detection methodologies and their major limitations before covering novel photonic techniques for early tumor detection and staging, assessing their diagnostic accuracy for flat and precancerous changes. We will do so in the context of both cystoscopic examination and the screening of voided urine and will also touch on the concept of using photonic technology as a surgical tool for tumor ablation. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of ageing and streptozotocin–induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder

PubMed Central

Suadicani, Sylvia O.; Urban–Maldonado, Marcia; Tar, Moses T.; Melman, Arnold; Spray, David C.

2012-01-01

OBJECTIVE To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. MATERIALS AND METHODS Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. RESULTS In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X1R, and increase in P2X7R expression. There was decreased Cx43 and increased P2Y4R expression in the ageing control rat bladder. There was a significant negative correlation between erectile capacity and P2X1R expression levels, and a positive correlation between bladder spontaneous activity and P2Y4R expression levels. There was already development of erectile dysfunction and bladder overactivity at 2 months after inducing diabetes, the earliest sample measured in the study. The development of these urogenital complications was accompanied by significant decreases in Cx43, P2Y2R, P2X4R and increase in P2X1R expression in the corpora, and by a doubling in Cx43 and P2Y2R, and significant increase in P2Y4R expression in the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin therapy. CONCLUSION Ageing and diabetes mellitus markedly altered the expression of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile corpora and urinary bladder. These changes in Cx43 and P2R expression provide the molecular substrate for altered gap junction and purinergic signalling in these tissues, and thus probably contribute to the early development of erectile dysfunction and higher detrusor activity in ageing and in diabetic rats. PMID:19154470

Herpes Simplex Virus-based gene Therapy Enhances the Efficacy of Mitomycin-C in the Treatment of Human Bladder Transitional Cell Carcinoma

PubMed Central

Mullerad, Michael; Bochner, Bernard H.; Adusumilli, Prasad S.; Bhargava, Amit; Kikuchi, Eiji; Hui-Ni, Chen; Kattan, Michael W.; Chou, Ting-Chao; Fong, Yuman

2005-01-01

Purpose Oncolytic replication-competent herpes simplex virus type-1 (HSV) mutants have the ability to replicate in and kill malignant cells. We have previously demonstrated the ability of replication-competent HSV to control bladder cancer growth in an orthotopic murine model. We hypothesized that a combination of a chemotherapeutic agent used for intravesical treatment - mitomycin-C (MMC) - and oncolytic HSV would exert a synergistic effect in the treatment of human transitional cell carcinoma (TCC). Materials and Methods We used the mutant HSV NV1066, which is deleted for viral genes ICP0 and ICP4 and selectively infects cancer cells, to treat TCC lines, KU19-19 and SKUB. Cell survival was determined by lactate dehydrogenase (LDH) assay for each agent as well as for drug-viral combinations from days 1 to 5. The isobologram method and the combination index method of Chou-Talalay were used to assess for synergistic effect. Results NV1066 enhanced MMC mediated cytotoxicity at all combinations tested for both KU19-19 and SKUB. Combination of both agents demonstrated a synergistic effect and allowed dose reduction by 12 and 10.4 times (NV1066) and by 3 and 156 times (MMC) in the treatment of KU19-19 and SKUB respectively, while achieving an estimated 90% cell kill. Conclusion These data provide the cellular basis for the clinical investigation of combined mitomycin-C and oncolytic HSV therapy in the treatment of bladder cancer. PMID:16006968

Use of botulinum toxin in individuals with neurogenic detrusor overactivity: State of the art review

PubMed Central

Linsenmeyer, Todd A.

2013-01-01

Background Botulinum neurotoxin (BoNT) injection into the bladder wall has been shown to be an effective alternative to anticholinergic (antimuscarinic) medications and more invasive surgery in those with multiple sclerosis and spinal cord injury with neurogenic detrusor overactivity (NDO) and urinary incontinence who are not tolerating anticholinergic medications. In August 2011, Botox® (onabotulinumtoxinA) received Food and Drug Administration (FDA) approval for this use. Clinically, intradetrusor injection of BoNT has been found to decrease urinary incontinence and improve quality of life. Its impact on urodynamic parameters is an increase in the maximum cystometric (bladder) capacity and decrease in the maximum detrusor pressures. The most common side effects are urinary tract infections and urinary retention. There have been rare reports and a black box warning of distant spread of BoNT. BoNT has gained popularity because of its effectiveness and long duration of action, relative ease of administration, easy learning curve, reproducibility of results on repeated administration, and low incidence of complications. Objective To discuss the structure and function, mechanisms of action, clinical and urodynamic studies, injection technique, potential beneficial and adverse effects, and potential areas of research of BoNT. Methods Literature search focused on botulinum toxin in MEDLINE/PubMed. Search terms included botulinum toxin, neurogenic bladder, NDO, botox bladder, botox spinal cord injury, botox, FDA, botox side effects. All papers identified were English language, full-text papers. In addition, English abstracts of non-English papers were noted. The reference list of identified articles was also searched for further papers. Conclusion Botulinum toxin is an alternative treatment for individuals with NDO who fail to tolerate anticholinergic medications. Its popularity has increased because of the literature, which has supported its effectiveness, safety, easy use and learning curve, reproducibility of results on repeated use, and recent FDA approval of Botox® (onabotulinumtoxinA). PMID:23941788

Individual receptor profiling as a novel tool to support diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC).

PubMed

Neuhaus, Jochen; Schulte-Baukloh, Heinrich; Stolzenburg, Jens-Uwe; Speroni di Fenizio, Pietro; Horn, Lars-Christian; Rüffert, Henrik; Hartenstein, Siegurd; Burger, Maximilian; Schulze, Matthias; Schwalenberg, Thilo

2012-10-01

Dysregulation of neurotransmitter receptors may contribute to bladder overactivity (OAB) symptoms. To address the question whether specific receptor expression patterns are associated with bladder pain syndrome/interstitial cystitis (BPS/IC), we examined the expression of muscarinic, purinergic and histamine receptors in the detrusor. Detrusor receptor expression was investigated in bladder biopsies of female BPS/IC patients (n = 44; age 60.64 ± 13.78, mean ± SD) and carcinoma patients (n = 11; age 58.91 ± 12.72) undergoing cystectomy. Protein expression of muscarinic (M2, M3), purinergic (P2X1-3) and histamine receptors (H1, H2) was analysed by confocal immunofluorescence, and gene expression was quantified by real-time polymerase chain reaction (qPCR). M2, P2X1, P2X2 and H1 receptor immunoreactivity (-IR) was significantly enhanced in BPS/IC compared to the control group, while there was no difference for M3-, P2X3- and H2-IR. We calculated a score, which separated BPS/IC from control patients with an AUC of 89.46%, showing 84.09% sensitivity and 90.91% specificity. Patients had a 9.25 times enhanced calculated risk for BPS/IC. In addition, two patient subgroups (M2 > M3 and M3 > M2) were observed, which differed in associated purinergic and histamine receptor expression. M2, P2X1, P2X2 and H1 were significantly upregulated in BPS/IC patients, and H2 was occasionally highly overexpressed. There was no significant correlation between receptor protein and gene expression, implying posttranslational mechanisms being responsible for the altered receptor expressions. On the basis of individual receptor profiles, upregulated receptors could be targeted by monotherapy or combination therapy with already approved receptor inhibitors, thereby promoting tailored therapy for patients suffering from BPS/IC-like symptoms.

SPIRE - combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer: study protocol for a phase Ib/randomised IIa open label clinical trial.

PubMed

Crabb, Simon; Danson, Sarah J; Catto, James W F; McDowell, Cathy; Lowder, James N; Caddy, Joshua; Dunkley, Denise; Rajaram, Jessica; Ellis, Deborah; Hill, Stephanie; Hathorn, David; Whitehead, Amy; Kalevras, Mihalis; Huddart, Robert; Griffiths, Gareth

2018-04-03

Urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer , Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder cancer. However, cisplatin resistance remains a critical cause of treatment failure and a barrier to therapeutic advance in UBC. Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC and potentially other cancers. The addition of SGI-110 (guadecitabine, a DNA methyltransferase inhibitor) to conventional doublet therapy of gemcitabine and cisplatin (GC) is being tested within the phase Ib/IIa SPIRE clinical trial. SPIRE incorporates an initial, modified rolling six-dose escalation phase Ib design of up to 36 patients with advanced solid tumours followed by a 20-patient open-label randomised controlled dose expansion phase IIa component as neoadjuvant treatment for UBC. Patients are being recruited from UK secondary care sites. The dose escalation phase will determine a recommended phase II dose (RP2D, primary endpoint) of SGI-110, by subcutaneous injection, on days 1-5 for combination with GC at conventional doses (cisplatin 70 mg/m 2 , IV infusion, day 8; gemcitabine 1000 mg/m 2 , IV infusion, days 8 and 15) in every 21-day cycle. In the dose expansion phase, patients will be randomised 1:1 to GC with or without SGI-110 at the proposed RP2D. Secondary endpoints will include toxicity profiles, SGI-110 pharmacokinetics and pharmacodynamic biomarkers, and pathological complete response rates in the dose expansion phase. Analyses will not be powered for formal statistical comparisons and descriptive statistics will be used to describe rates of toxicity, efficacy and translational endpoints by treatment arm. SPIRE will provide evidence for whether SGI-110 in combination with GC chemotherapy is safe and biologically effective prior to future phase II/III trials as a neoadjuvant therapy for UBC and potentially in other cancers treated with GC. EudraCT Number: 2015-004062-29 (entered Dec 7, 2015) ISRCTN registry number: 16332228 (registered on Feb 3, 2016).

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

PubMed

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

2016-07-01

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

Pore forming channels as a drug delivery system for photodynamic therapy in cancer associated with nanoscintillators

PubMed Central

Pacheco, Paulo Furtado; Mendivelso, Edith Alejandra Carreño; Teixeira, Pedro Celso Nogueira; Faria, Robson Xavier

2018-01-01

According to the World Health Organization (WHO), cancer is one of main causes of death worldwide, with 8.2 million people dying from this disease in 2012. Because of this, new forms of treatments or improvement of current treatments are crucial. In this regard, Photodynamic therapy (PDT) has been used to successfully treat cancers that can be easily accessed externally or by fibre-optic endoscopes, such as skin, bladder and esophagus cancers. In addition, this therapy can used alongside radiotherapy and chemotherapy in order to kill cancer cells. The main problem in implementing PDT is penetration of visible light deeper than 10 mm in tissues, due to scattering and absorption by tissue chromophores. Unfortunately, this excludes several internal organs affected by cancer. Another issue in this regard is the use of a selective cancer cell-photosensitizing compound. Nevertheless, several groups have recently developed scintillation nanoparticles, which can be stimulated by X-rays, thereby making this a possible solution for light production in deeper tissues. Alternative approaches have also been developed, such as photosensitizer structure modifications and cell membrane permeabilizing agents. In this context, certain channels lead to transitory plasma membrane permeability changes, such as pannexin, connexin hemmichannels, TRPV1-4 and P2×7, which allow for the non-selective passage of molecules up to 1,000 Da. Herein, we discuss the particular case of the P2×7 receptor-associated pore as a drug delivery system for hydrophilic substances to be applied in PDT, which could also be carried out with other channels. Methylene blue (MB) is a low cost dye used as a prototype photosensitizer, approved for clinical use in several other clinical conditions, as well as photodynamic therapy for fungi infections. PMID:29861876

Pore forming channels as a drug delivery system for photodynamic therapy in cancer associated with nanoscintillators.

PubMed

Alves, Luiz Anastacio; Ferreira, Leonardo Braga; Pacheco, Paulo Furtado; Mendivelso, Edith Alejandra Carreño; Teixeira, Pedro Celso Nogueira; Faria, Robson Xavier

2018-05-18

According to the World Health Organization (WHO), cancer is one of main causes of death worldwide, with 8.2 million people dying from this disease in 2012. Because of this, new forms of treatments or improvement of current treatments are crucial. In this regard, Photodynamic therapy (PDT) has been used to successfully treat cancers that can be easily accessed externally or by fibre-optic endoscopes, such as skin, bladder and esophagus cancers. In addition, this therapy can used alongside radiotherapy and chemotherapy in order to kill cancer cells. The main problem in implementing PDT is penetration of visible light deeper than 10 mm in tissues, due to scattering and absorption by tissue chromophores. Unfortunately, this excludes several internal organs affected by cancer. Another issue in this regard is the use of a selective cancer cell-photosensitizing compound. Nevertheless, several groups have recently developed scintillation nanoparticles, which can be stimulated by X-rays, thereby making this a possible solution for light production in deeper tissues. Alternative approaches have also been developed, such as photosensitizer structure modifications and cell membrane permeabilizing agents. In this context, certain channels lead to transitory plasma membrane permeability changes, such as pannexin, connexin hemmichannels, TRPV1-4 and P2×7, which allow for the non-selective passage of molecules up to 1,000 Da. Herein, we discuss the particular case of the P2×7 receptor-associated pore as a drug delivery system for hydrophilic substances to be applied in PDT, which could also be carried out with other channels. Methylene blue (MB) is a low cost dye used as a prototype photosensitizer, approved for clinical use in several other clinical conditions, as well as photodynamic therapy for fungi infections.

Reverse Vesicouterine Fold Dissection for Laparoscopic Hysterectomy After Prior Cesarean Deliveries.

PubMed

Nezhat, Camran; Grace, Lindsey A; Razavi, Gity M; Mihailide, Catalina; Bamford, Holden

2016-09-01

Cesarean delivery adhesions, during laparoscopic hysterectomy, can present surgical challenges, including distortion of anatomy, prolonged operating time, and inadvertent injury to nearby structures. At the time of laparoscopic hysterectomy, in patients with significant adhesions from prior cesarean deliveries, we use a reverse inferior to superior vesicouterine fold dissection to mobilize the scarred bladder. We use this as an alternative to the commonly practiced technique of mobilizing the bladder in a superior to inferior fashion at the time of laparoscopic hysterectomy. Fifty-two patients with a median age of 42.5 years are presented. Forty-eight patients were discharged within 3-6 hours postoperatively. Sixteen patients were discharged with Foley catheters, because they were unable to void within the protocol for a fast-track discharge. The catheters were removed between postoperative days 1 and 5. There were no gastrointestinal or genitourinary complications. One patient experienced a delayed vaginal cuff abscess and bleeding, which were managed conservatively. Reverse vesicouterine fold dissection is a useful alternative technique for laparoscopic hysterectomy in women with a history of prior cesarean deliveries.

Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

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

Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.

Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicitymore » questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.« less

Novel multi-system functional gains via task specific training in spinal cord injured male rats.

PubMed

Ward, Patricia J; Herrity, April N; Smith, Rebecca R; Willhite, Andrea; Harrison, Benjamin J; Petruska, Jeffrey C; Harkema, Susan J; Hubscher, Charles H

2014-05-01

Locomotor training (LT) after spinal cord injury (SCI) is a rehabilitative therapy used to enhance locomotor recovery. There is evidence, primarily anecdotal, also associating LT with improvements in bladder function and reduction in some types of SCI-related pain. In the present study, we determined if a step training paradigm could improve outcome measures of locomotion, bladder function, and pain/allodynia. After a T10 contusive SCI trained animals (adult male Wistar rats), trained animals began quadrupedal step training beginning 2 weeks post-SCI for 1 h/day. End of study experiments (3 months of training) revealed significant changes in limb kinematics, gait, and hindlimb flexor-extensor bursting patterns relative to non-trained controls. Importantly, micturition function, evaluated with terminal transvesical cystometry, was significantly improved in the step trained group (increased voiding efficiency, intercontraction interval, and contraction amplitude). Because both SCI and LT affect neurotrophin signaling, and neurotrophins are involved with post-SCI plasticity in micturition pathways, we measured bladder neurotrophin mRNA. Training regulated the expression of nerve growth factor (NGF) but not BDNF or NT3. Bladder NGF mRNA levels were inversely related to bladder function in the trained group. Monitoring of overground locomotion and neuropathic pain throughout the study revealed significant improvements, beginning after 3 weeks of training, which in both cases remained consistent for the study duration. These novel findings, improving non-locomotor in addition to locomotor functions, demonstrate that step training post-SCI could contribute to multiple quality of life gains, targeting patient-centered high priority deficits.

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer.

PubMed

Inman, Brant A; Longo, Thomas A; Ramalingam, Sundhar; Harrison, Michael R

2017-04-15

Atezolizumab (Tecentriq, MPDL3280A; Genentech/Roche) is an FcγR binding-deficient, fully humanized IgG1 mAb designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironment and, consequently, increases T-cell-mediated immunity against the tumor. Atezolizumab has been FDA approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase II trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses. In subjects whose tumors progressed on first-line platinum-based chemotherapy, the objective response rate was 15%, the complete response rate was 5%, and 1-year overall survival was 36%. In subjects that were chemotherapy naïve and cisplatin ineligible, the objective response rate was 24%, the complete response rate was 7%, and 1-year overall survival was 57%. Better responses were associated with higher PD-L1 expression on the tumor-infiltrating leukocytes. These data suggest that patients with advanced bladder cancer treated with atezolizumab have significantly better response rates and survival than historical controls treated with other second-line regimens. The toxicity profile of atezolizumab is also favorable. Trials are currently assessing whether atezolizumab is effective in earlier bladder cancer stages and in the first-line metastatic setting. Clin Cancer Res; 23(8); 1886-90. ©2016 AACR . ©2016 American Association for Cancer Research.