Intravesical Therapy blog

Related Articles

Pros and cons of radical cystectomy in the treatment of T1G3 bladder cancer.

Indian J Urol. 2008 Jan;24(1):77-83

Authors: Agarwal PK, Kamat AM

The management of T1G3 (or high-grade T1) bladder cancer poses a challenging clinical dilemma to the urologist. There are good data supporting bladder conservative therapy with repeat transurethral resection and administration of Bacille Calmette-Guérin (BCG) intravesical therapy but this must include maintenance regimens since only maintenance BCG has been shown to decrease tumor recurrence and progression. Concern over worse survival with a delay in definitive therapy has prompted many to recommend immediate cystectomy for T1G3 disease. Ultimately, the decision needs to be individualized and although certain pathologic factors (T1b disease, early recurrence or progression within three months of BCG therapy, lymphovascular invasion and variant histology) are prognostic of progressive disease, no definitive risk factors for tumor progression have been identified.

PMID: 19468365 [PubMed - in process]

]]>

View the Original article

Related Articles

Bladder contracture: review for intravesical bacillus Calmette-Guerin complication.

Can J Urol. 2007 Dec;14(6):3745-9

Authors: Hameed A, Sezian N, Thwaini A

INTRODUCTION: We are reporting a case of bladder contracture post intravesical bacillus Calmette-Guerin (BCG) therapy; to our knowledge only two cases were reported. We present the clinical history/presentation investigation and the outcome of the treatment. Approximately 75%-85% of patients with bladder cancer present with disease confined to the mucosa (stage Ta-CIS) or submucosa (stage T1). The management of non-muscle invasive bladder cancer has become more complex with regard to initial investigation, treatment and follow-up. In high-grade tumors, BCG therapy has proven to be superior to intravesical chemotherapy. BCG therapy prevents, or at least delays, tumor progression. METHODS AND RESULTS: A case of high grade superficial bladder caner treated with intravesical BCG which has successfully cleared her bladder cancer nevertheless has lead to bladder contracture for which case she may need bladder reconstruction/augmentation surgery if she remained disease free added to her psychological and social effects on her life. CONCLUSION: Although BCG is considered a very effective treatment; consensus exists that not every patient with superficial bladder cancer should be treated with BCG due to its increased risk of toxicity. Ultimately, the choice of treatment will depend upon the patient's risk of recurrence and progression. Assuming that maintenance therapy is necessary for optimal efficacy, the issue of BCG toxicity becomes more relevant. Due to the more pronounced side effects of BCG compared to intravesical chemotherapy, reluctance still exists about BCG use. However, with increased experience in applying BCG, the side effects now appear to be less prominent and few. Serious side effects are encountered in less than 5% of patients and this case carries one of the rarest, yet drastic, side effects of intravesical BCG.

PMID: 18163926 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer.

Clin Cancer Res. 2008 Jan 1;14(1):224-9

Authors: Sabichi AL, Lerner SP, Atkinson EN, Grossman HB, Caraway NP, Dinney CP, Penson DF, Matin S, Kamat A, Pisters LL, Lin DW, Katz RL, Brenner DE, Hemstreet GP, Wargo M, Bleyer A, Sanders WH, Clifford JL, Parnes HL, Lippman SM

PURPOSE: The study aims to evaluate the efficacy and toxicity of fenretinide in preventing tumor recurrence in patients with transitional cell carcinoma (TCC) of the bladder. EXPERIMENTAL DESIGN: We conducted a multicenter phase III, randomized, placebo-controlled trial of fenretinide (200 mg/day orally for 12 months) in patients with non-muscle-invasive bladder TCC (stages Ta, Tis, or T1) after transurethral resection with or without adjuvant intravesical Bacillus Calmette-Guerin (BCG). Patients received cystoscopic evaluation and bladder cytology every 3 months during the 1-year on study drug and a final evaluation at 15 months. The primary endpoint was time to recurrence. RESULTS: A total of 149 patients were enrolled; 137 were evaluable for recurrence. The risk of recurrence was considered to be "low" in 72% (no prior BCG) and intermediate or high in 32% (prior BCG) of the evaluable patients. Of the lower-risk group, 68% had solitary tumors and 32% had multifocal, low-grade papillary (Ta, grade 1 or grade 2) tumors. The 1-year recurrence rates by Kaplan-Meier estimate were 32.3% (placebo) versus 31.5% (fenretinide; P = 0.88 log-rank test). Fenretinide was well tolerated and had no unexpected toxic effects; only elevated serum triglyceride levels were significantly more frequent on fenretinide (versus placebo). The Data Safety and Monitoring Board recommended study closure at 149 patients (before reaching the accrual goal of 160 patients) because an interim review of the data showed a low likelihood of detecting a difference between the two arms, even if the original accrual goal was met. CONCLUSIONS: Although well tolerated, fenretinide did not reduce the time-to-recurrence in patients with Ta, T1, or Tis TCC of the bladder.

PMID: 18172274 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Prevention of adverse effects of BCG immunotherapy in bladder cancer.

South Med J. 2008 Jan;101(1):17-8

Authors: Naoe M, Ogawa Y

PMID: 18176285 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Four cases of disseminated Mycobacterium bovis infection following intravesical BCG instillation for treatment of bladder carcinoma.

South Med J. 2008 Jan;101(1):91-5

Authors: Nadasy KA, Patel RS, Emmett M, Murillo RA, Tribble MA, Black RD, Sutker WL

Intravesical BCG (bacillus Calmette-Guérin) instillation is a first-line treatment for superficial transitional cell carcinoma of the bladder. A rare but severe complication of BCG immunotherapy is the development of disseminated BCG disease, which can result in miliary pneumonitis, granulomatous hepatitis, soft tissue infections, bone marrow involvement, and sepsis. Symptoms can present as early as a few hours or as late as several months following the BCG therapy. The key finding in disseminated BCG disease is the formation of caseating granulomas in distant organs; detection of BCG organisms from tissue samples can be difficult. Recommended treatment for disseminated BCG disease includes a combination of antituberculous medications (with the exception of pyrazinamide, to which BCG is typically resistant) and a tapering course of steroids. We present the cases of four patients who developed granulomatous infection consistent with disseminated disease after intravesical BCG treatment and provide a summary of current clinical management recommendations.

PMID: 18176300 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

[Anticholinergic drugs in overactive bladder]

Gynecol Obstet Fertil. 2008 Jan;36(1):90-6

Authors: Muhlstein J, Deval B

The overactive bladder syndrome (OAB) associates urgency, frequency, nycturia, more or less associated with urinary incontinence. Its frequency is between 16 to 45 %, in the general population; the number of affected people in the USA being estimated at 34 million. Symptomatology is primarily marked by the abrupt, irrepressible need to urinate, impossible to defer, but also by a diurnal and night high mictional frequency. This OAB is more frequent when patients age increases, and affects indifferently men and women. The OAB induces a known negative impact on the quality of life and can lead to depression, sexual disorders, sleep disorders and a professional absenteism. The OAB medical treatment is actively concerned by the research since the discovery of oxybutinine. Tolterodin, solifenacin, darifenacin, trospium chloride supplement the therapeutic arsenal. New formulations (immediate and extended releases), new administration mediums (intravesical, transdermic, vaginal, rectal), new active ingredients (botulinic toxin, capsaicine, resiniferatoxine) are currently tested. The therapeutic options multiply, aiming at reducing to the maximum symptomatology, as well as the induced side effects.

PMID: 18178506 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

A role of intravesical capsaicin instillation in benign prostatic hyperplasia with overactive bladder symptoms: the first reported study in the literature.

J Med Assoc Thai. 2007 Sep;90(9):1821-7

Authors: Mahawong P, Chaiyaprasithi B, Soontrapa S, Tappayuthapijarn P

OBJECTIVE: To study the efficacy of capsaicin in treating overactive bladder symptoms in benign prostatic hyperplasia patients. MATERIAL AND METHOD: A prospective study of 20 benign prostatic hyperplasia patients whose overactive bladder symptoms were not improved by alpha1 blocker Alpha1 blocker was taken about 22.9 +/- 17.2 months before and continued throughout 6 months duration of the present study. All of them had undergone intravesical capsaicin instillation at the Faculty of Medicine Siriraj Hospital, Bangkok, from 2004 to 2006. Both clinical and urodynamic data were evaluated before and after treatment. RESULTS: Mean urgency decreased from 6.7 +/- 5.1 at baseline to 2.0 +/- 2.3 (p < 0.005), 1.4 +/- 2.4 (p < 0.005), 1.3 +/- 2.2 (p < 0.005) at 1, 3 and 6 months. Mean urge incontinence decreased from 1.7 +/- 3.5 at baseline to 0.5 +/- 1.3 (p = 0.148), 0.4 +/- 1.2 (p = 0.114), 0.3 + 1.1 (p = 0.085) at 1, 3 and 6 months. Mean urinary frequency decreased from 13.7 +/- 3.3 at baseline to 10.5 +/- 2.8 (p < 0.005), 9.6 +/- 2.0 (p < 0.005), 9.5 +/- 2.6 (p < 0.005) at 1, 3 and 6 months. Mean nocturia decreased from 4.7 +/- 2.4 at baseline to 3.1 +/- 2.2 (p < 0.005), 2.7 +/- 1.2 (p < 0.005), 2.9 +/- 1.6 (p < 0.005) at 1, 3 and 6 months. Mean first desire to void increased from 172.5 +/- 100.4 ml at baseline to 210.6 +/- 99.5 ml (p = 0.016) at 1 month. Mean maximal cystometric capacity increased from 350.3 +/- 165.9 ml at baseline to 397.4 +/- 165.7 ml (p = 0.012) at 1 month. Peak flow rate, detrusor pressure, and postvoid residual urine were not affected. No serious adverse effect occurred in the present study. CONCLUSION: Intravesical capsaicin instillation is an effective treatment for overactive bladder symptoms in benign prostatic hyperplasia patients.

PMID: 17957925 [PubMed - indexed for MEDLINE]

]]>

View the Original article

View the Original article

View the Original article

Related Articles

Vesical varices and telangiectasias in a patient with ataxia telangiectasia.

Pediatr Nephrol. 2008 Jun;23(6):1005-8

Authors: Suzuki K, Tsugawa K, Oki E, Morio T, Ito E, Tanaka H

A Japanese boy with ataxia telangiectasia (AT) developed severe gross hematuria and recurrent bladder tamponade, requiring an extensive blood transfusion. He had received intermittent intravenous cyclophosphamide pulse therapy (cumulative dose of 1.3 g) for refractory steroid-resistant and intravenous immunoglobulin-resistant severe autoimmune thrombocytopenia 3 years previously. A cystoscopy revealed multiple varices and severe telangiectasias in the bladder wall. The intensive treatment, such as repeatedly selective embolization of the vesical arteries, proved to be partially effective. Finally, a surgical cystotomy resulted in a gradual improvement in clinical symptoms. To the best of our knowledge, this is the first report of a patient with AT who developed refractory bladder hemorrhage caused by widespread vesical telangiectasias.

PMID: 18193295 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Evaluation of an orthotopic rat bladder urothelial cell carcinoma model by cystoscopy.

BJU Int. 2008 Apr;101(7):889-93

Authors: Hendricksen K, Molkenboer-Kuenen J, Oosterwijk E, Hulsbergen-van de Kaa CA, Witjes JA

OBJECTIVES: To enable preclinical testing of intravesical therapies against non-muscle-invasive bladder cancer (NMIBC) in an orthotopic rat bladder tumour model, augmented by the use of serial cystoscopy for in vivo tumour assessment and follow-up. MATERIALS AND METHODS: Fischer F344 rats had a 16-G transurethral cannula placed. The bladder mucosa was conditioned with an acid rinse, followed by a 1-h instillation of 1.5 x 10(6) AY-27 rat bladder urothelial cell carcinoma (UCC) cells (day 0). Cystoscopy (1 mm) was done on day 0 (control) and at 3, 4, 5, 6, 7, 10, 13 and 17 days. At the scheduled times the rats were killed after cystectomy (four at each time) for histopathological examination of the bladder. RESULTS: Overall, tumour establishment was >80%, with predominantly carcinoma in situ preceding or concomitant with invasive tumour growth. All tumours were formed at 3-5 days, and remained non-muscle-invasive up to 5 days. From 6 days, tumours progressed to muscle-invasive disease in 40% of the rats. Visibility at cystoscopy was excellent and tumours were apparent in >90% of rats from 5 days on, with a specificity and sensitivity of >90%. Cystoscopy could not distinguish NMIBC from muscle-invasive disease. CONCLUSIONS: This is a reliable model of orthotopic rat bladder UCC, with early high-grade NMIBC growth, immediately followed by muscle-invasive growth, i.e. the recommended time to start intravesical therapy would be 5 days after tumour cell inoculation. Tumour growth can easily be monitored by cystoscopy, but cannot be used to distinguish NMIBC from muscle-invasive bladder cancer.

PMID: 18201266 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Intravesical bacillus Calmette-Guérin therapy for T1 superficial bladder cancer.

Urol Int. 2008;80(1):74-9

Authors: Demkow T, Alter A, Wiechno P

INTRODUCTION: The management of transitional bladder cancer, which invades the lamina propria (pT1) and has a marked propensity for recurrence and progression, is controversial. Without adjuvant treatment the recurrence rate can be up to 80% and progression up to 50%. We retrospectively analyzed the incidence of recurrence and progression of pT1 transitional bladder cancer (grade 1-3) after complete transurethral resection of a bladder tumor (TURBT) and adjuvant immunotherapy with bacillus Calmette-Guérin (BCG). MATERIALS AND METHODS: 77 patients with stage pT1 transitional cell carcinoma underwent TURBT of all visible tumors and adjuvant BCG intravesical instillations. Before BCG therapy, 12 patients presented with stage pT1 G1 tumors, 50 presented with pT1, and 15 with pT1 G3 tumors. RESULTS: 51 patients (66.2%) were disease-free throughout the BCG instillation and follow-up period (median of 45 months); 8 patients (10.4%) experienced recurrence during the BCG instillations, but were disease-free following the last instillation; 16 patients (20.8%) experienced recurrence at a median of 17 months, and 2 patients (2.6%) with pT1 G3 died because of progression. CONCLUSIONS: Adjuvant intravesical BCG therapy following TURBT appears to be an effective primary treatment for patients with pT1 transitional cell carcinoma.

PMID: 18204238 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Cell proliferation and DNA content in rat urothelial lesions after repeat intravesical instillations of mitomycin C and bacillus Calmette-Guérin.

Urol Int. 2008;80(1):90-7

Authors: Oliveira P, Palmeira C, Colaço A, De la Cruz P LF, Lopes C

AIM: To study cell proliferation and DNA content in urothelial lesions identified after repeated intravesical instillations of mitomycin C (MMC) and bacillus Calmette-Guérin (BCG) in normal rat urothelium. MATERIAL AND METHODS: A total of 45 rats were divided into nine equal groups: those intravesically instilled with MMC; those receiving BCG intravesically, and a control group intravesically instilled with a physiological solution of sodium chloride (SF). Animals were killed 1, 4 or 8 weeks after the last intravesical instillation. An immunohistochemical streptavidin-biotin-peroxidase technique was performed to investigate Ki-67 expression and the DNA ploidy status was measured using static cytometry. RESULTS: In urothelium exposed to MMC lesions such as simple hyperplasia, dysplasia, carcinoma in situ(CIS), and squamous cell metaplasia were identified. The proliferation index presented values of 11.73, 22.43 and 31.46% in hyperplasias, dysplasias, and CIS, respectively (p < 0.05). The frequency of abnormal DNA content amongst those animals exhibiting simple hyperplasias 25% were aneuploid, in the dysplasia 85.2% were aneuploid (p = 0.041). CIS were all multiploid, and squamous cell metaplasias were all diploid. Animals treated with BCG and SF presented no urothelial lesions and a diploid DNA content. CONCLUSIONS: The aneuploid and multiploid DNA content and proliferation index observed in urothelial lesions identified after repeated intravesical instillations of MMC reflect a high degree of genomic instability in such lesions which in itself may lead to rapid regeneration of new phenotypes.

PMID: 18204241 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Methionine and its derivatives increase bladder excitability by inhibiting stretch-dependent K(+) channels.

Br J Pharmacol. 2008 Mar;153(6):1259-71

Authors: Baker SA, Hennig GW, Han J, Britton FC, Smith TK, Koh SD

BACKGROUND AND PURPOSE: During the bladder filling phase, the volume of the urinary bladder increases dramatically, with only minimal increases in intravesical pressure. To accomplish this, the smooth muscle of the bladder wall must remain relaxed during bladder filling. However, the mechanisms responsible for the stabilization of bladder excitability during stretch are unclear. We hypothesized that stretch-dependent K(+) (TREK) channels in bladder smooth muscle cells may inhibit contraction in response to stretch. EXPERIMENTAL APPROACHES: Bladder tissues from mouse, guinea pig and monkey were used for molecular, patch clamp, mechanical, electrical, Ca(2+) imaging and cystometric responses to methionine and its derivatives, which are putative blockers of stretch-dependent K(+) (SDK) channels. KEY RESULTS: SDK channels are functionally expressed in bladder myocytes. The single channel conductance of SDK channels is 89pS in symmetrical K(+) conditions and is blocked by L-methionine. Expressed TREK-1 currents are also inhibited by L-methioninol. All three types of bladder smooth muscle cells from mouse, guinea pig and monkey expressed TREK-1 genes. L-methionine, methioninol and methionine methyl ester but not D-methionine increased contractility in concentration-dependent manner. Methioninol further increased contractility and depolarized the membrane in the presence of blockers of Ca(2+)-activated K(+) conductance. L-methionine induced Ca(2+) waves that spread long distances through the tissue under stretched conditions and were associated with strong contractions. In cystometric assays, methioninol injection increased bladder excitability mimicking overactive bladder activity. CONCLUSIONS AND IMPLICATIONS: Methioninol-sensitive K(+) (SDK, TREK-1) channels appear to be important to prevent spread of excitation through the syncitium during bladder filling.

PMID: 18204472 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Efficacy of a novel device for assessment of autonomic sensory function in the rat bladder.

J Urol. 2008 Mar;179(3):1167-72

Authors: Abouassaly R, Liu G, Yamada Y, Ukimura O, Daneshgari F

PURPOSE: We developed and tested the efficacy of an implantable bladder device which, when combined with the Neurometer, can be used to assess fiber specific afferent bladder sensation in the rat. MATERIALS AND METHODS: We developed an implantable bladder device that applies selective nerve fiber stimuli (250 Hz for small myelinated Adelta fibers and 5 Hz for unmyelinated C fibers) to the bladder mucosa in the rat to determine bladder sensory perception threshold values. We performed 3 experiments in 55 female Sprague-Dawley rats to examine the effects of our device on voiding habits, assess the interobserver reliability of the sensory perception threshold and determine the effects of intravesical administration of resiniferatoxin (Sigma) and lidocaine on the sensory perception threshold. RESULTS: Sensory perception threshold values obtained by 2 blinded, independent observers were not different from each other (p = 0.41). Sensory perception threshold values obtained at the 2 stimulation frequencies remained constant for at least 3 weeks after device implantation. A significant increase in sensory perception threshold values after resiniferatoxin instillation was noted at a stimulus frequency of 5 Hz (p = 0.02), whereas intravesical lidocaine led to an immediate increase in the sensory perception threshold at 250 and 5 Hz. Device implantation led to an early decreased voided volume and increased frequency of voids, although these parameters returned to normal after 4 days. CONCLUSIONS: Assessment of bladder afferent sensation with our newly developed device is feasible in rats. It provides sensory perception thresholds that appear to be fiber-type selective for autonomic bladder afferent nerves.

PMID: 18206176 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Botulinum A toxin intravesical injection in patients with painful bladder syndrome: 1-year followup.

J Urol. 2008 Mar;179(3):1031-4

Authors: Giannantoni A, Porena M, Costantini E, Zucchi A, Mearini L, Mearini E

PURPOSE: We evaluated the 1-year efficacy and tolerability of botulinum A toxin intravesically injected in patients with painful bladder symptoms associated with increased urinary frequency, refractory to conventional treatments. MATERIALS AND METHODS: Three men and 12 women were prospectively included in the study. Under short general anesthesia the patients were given injections of 200 U commercially available botulinum A toxin diluted in 20 ml 0.9% NaCl. Injections were performed submucosally in the bladder trigone and lateral walls under cystoscopic guidance. A voiding chart and the visual analog scale for pain were used, and urodynamics were performed before treatment, and 1, 3, 5 and 12 months later. RESULTS: Overall 13 patients (86.6%) reported subjective improvement at the 1 and 3-month followups. The mean visual analog scale score, and daytime and nighttime urinary frequency were significantly decreased (p <0.05, <0.01 and <0.05, respectively). At the 5-month followup the beneficial effects persisted in 26.6% of cases but increased daytime and nighttime urinary frequency, and an increased visual analog scale score were observed compared to baseline. At 12 months after treatment pain recurred in all patients. Nine patients complained of dysuria 1 month after treatment. Dysuria persisted in 4 cases at the 3-month followup and in 2 at the 5-month followup. CONCLUSIONS: Intravesically injected botulinum toxin A is effective for short-term management of refractory painful bladder syndrome. The beneficial effects decreased progressively within a few months after treatment. Thus, repeat injections of the neurotoxin are required for efficacious treatment in patients with the disease.

PMID: 18206941 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

The schedule and duration of intravesical chemotherapy in patients with non-muscle-invasive bladder cancer: a systematic review of the published results of randomized clinical trials.

Eur Urol. 2008 Apr;53(4):709-19

Authors: Sylvester RJ, Oosterlinck W, Witjes JA

OBJECTIVES: Intravesical chemotherapy has been studied in randomized clinical trials for >30 yr; however, the optimal schedule and duration of treatment are unknown. The objective is to determine the effect of schedule and duration of intravesical chemotherapy on recurrence in patients with stage Ta T1 bladder cancer. METHODS: A systematic review was conducted of the published results of randomized clinical trials that compared intravesical instillations with respect to their number, frequency, timing, duration, dose, or dose intensity. RESULTS: One immediate instillation after transurethral resection (TUR) is recommended in all patients. In low-risk patients, no further treatment is recommended before recurrence. In patients with multiple tumors, one immediate instillation is insufficient treatment. Additional instillations may further reduce the recurrence rate; however, no recommendations can be made concerning their optimal duration. A short intensive schedule of instillations within the first 3-4 mo after an immediate instillation may be as effective as longer-term treatment schedules (grade C). Instillations during > or =1 yr in intermediate-risk patients seem advisable only when an immediate instillation has not been given (grade C). Higher drug concentrations and optimization of the drug's concentration in the bladder may provide better results (grade C). CONCLUSIONS: The optimal schedule and duration of intravesical chemotherapy after an immediate instillation remain unknown. Future studies should focus on the eradication of residual disease after TUR and the prevention of late recurrences.

PMID: 18207317 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

The use of intravesical chemotherapy and possibilities for improving its efficacy.

Eur Urol. 2006 Aug;50(2):233

Authors: Sylvester RJ

PMID: 18219714 [PubMed - indexed for MEDLINE]

]]>

View the Original article

View the Original article

Related Articles

Celecoxib has potent antitumour effects as a single agent and in combination with BCG immunotherapy in a model of urothelial cell carcinoma.

Eur Urol. 2008 Sep;54(3):621-30

Authors: Dovedi SJ, Kirby JA, Davies BR, Leung H, Kelly JD

OBJECTIVES: Prostaglandin E2 (PGE2) is a potent immune modulator and known to suppress both tumour antigen-specific helper T (TH1) cells and the generation of cytotoxic T lymphocytes (CTLs). We hypothesised that a combination of the cyclooxygenase 2 (COX-2) selective inhibitor celecoxib and intravesical bacillus Calmette-Guérin (BCG), an effective tumour immunoprophylaxis and ablative therapy for non-muscle-invasive bladder cancer, would be more effective than BCG alone. METHODS: We assessed urinary levels of PGE2 in humans receiving BCG and in a murine model of urothelial cell carcinoma (UCC). The cytokine response to BCG plus celecoxib was assessed in murine dendritic cells (DCs) in vitro and tumour ablation was assessed in an orthotopic MBT2 murine bladder cancer model. RESULTS: Administration of intravesical BCG resulted in elevated urinary PGE2 levels in patients with high-grade superficial UCC and in a mouse model of UCC. In vitro, activation of DCs with BCG stimulated COX-2 up-regulation and release of the archetypal tolerogenic factors, PGE2 and interleukin 10. In a superficial mouse model of UCC, combination of celecoxib and intravesical BCG therapy resulted in increased tumour infiltration of CD4+ T cells and improved efficacy when compared to BCG alone. Further, celecoxib demonstrated marked antitumour efficacy when administered in the absence of BCG immunotherapy. CONCLUSIONS: This study demonstrates that a combination strategy involving BCG immunotherapy and celecoxib may be more therapeutically beneficial than stand-alone intravesical therapy.

PMID: 18222600 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

The effects of intravesical pentosanpolysulfate treatment on the symptoms of patients with bladder pain syndrome/interstitial cystitis: preliminary results.

Int Urogynecol J Pelvic Floor Dysfunct. 2008 Jul;19(7):987-90

Authors: Daha LK, Lazar D, Simak R, Pflüger H

The objective of the study was to determine whether intravesical pentosanpolysulfate (PPS) reduces symptoms associated with bladder pain syndrome/interstitial cystitis (BPS/IC). In a prospective, uncontrolled, open-label study, 29 female patients with BPS/IC received 300 mg PPS intravesically twice a week for 10 weeks and thereafter a voluntary maintenance therapy once a month. Treatment response was assessed by Visual Analog Scale (VAS) for quality of life and O'Leary-Sant Symptom and Problem Index (OSPI). Patients were tested before treatment, after 5 weeks of treatment, and 1 week, 3, 6, and 12 months after termination of the initial treatment. Twenty-five patients underwent the 10-week treatment and the 3-month follow-up. Mean reduction of VAS/OSPI was from 8.8/26.4 before to 4/15.3 after treatment, 3.8/15.2 after 3 months, 3.8/14 after 6 months, and 3.4/12.1 after 12 months. In 21 patients, renewed instillation or maintenance therapy was necessary. Intravesical treatment with PPS reduces both the VAS and the OSPI in patients with BPS/IC.

PMID: 18227956 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Transvesical intra-abdominal pressure measurement using minimal instillation volumes: how low can we go?

Intensive Care Med. 2008 Apr;34(4):746-50

Authors: De laet I, Hoste E, De Waele JJ

OBJECTIVE: To determine the minimal instillation volume at which an intra-abdominal pressure (IAP) curve can be obtained and to compare this with the IAP measured at 20 ml instilled volume. DESIGN AND SETTING: Prospective cohort study in the Intensive Care Unit of Ghent University Hospital. PATIENTS: Twenty-five critically ill sedated and ventilated patients at risk for intra-abdominal hypertension (IAH). INTERVENTIONS: IAP was measured transvesically using a custom-designed IAP monitoring set. Measurement was started without any additional instillation of saline and was continued at 1-ml increments up to 10 ml. Finally, IAP was measured with 20 ml instillation volume. MEASUREMENTS AND RESULTS: After each instillation an "oscillation test" was performed. The minimal volume at which the oscillation test was positive was recorded. These values were compared to the IAP obtained using 20 ml saline (IAP20 ml). At 2 ml installed saline volume an oscillation curve could be obtained in all patients. Mean IAP2 ml) was 11.2+/-3.2 mmHg, IAP10 ml) 11.4+/-3.7 mmHg, and IAP20 ml) 11.7+/-3.2 mmHg. In four patients (16%) there was a clinically significant difference of 2 mmHg or more between IAP2 ml and IAP20 ml. The mean difference between IAP20 ml) and IAP2 ml was 0.60+/-0.91 mmHg (95% CI 0.22-0.98). CONCLUSIONS: In this sample of patients at risk for IAH 2 ml saline was sufficient for IAP signal transduction. Higher volumes for transvesical IAP measurement resulted in higher pressure readings in some patients.

PMID: 18227998 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Induction of COX-2 expression by acrolein in the rat model of hemorrhagic cystitis.

Exp Toxicol Pathol. 2008 Apr;59(6):425-30

Authors: Macedo FY, Baltazar F, Mourão LC, Almeida PR, Mota JM, Schmitt FC, Ribeiro RA

AIM: Acrolein (ACR) is a urinary metabolite of cyclophosphamide (CPS) and ifosfamide (IFS), which has been demonstrated to be the causative agent of hemorrhagic cystitis (HC), induced by these compounds. In this study, we investigate the participation of cyclooxygenase-2 (COX-2) on ACR-induced HC. METHODS: Male Wistar rats (150-200g; six rats per group) were treated with distilled water or intravesical ACR and analyzed by changes in bladder wet weight, macroscopic and microscopic parameters and COX-2 expression. RESULTS: COX-2 immunohistochemical expression was significant 12h after ACR administration mainly in subepithelial cells. ACR injection also alters some macroscopic and microscopic parameters in bladder of rats analyzed by Gray's criteria. CONCLUSIONS: COX-2 participates in the pathogenesis of ACR-induced HC first seen 12h after initial contact between ACR and urothelium.

PMID: 18234483 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Patient perceived outcomes of treatments used for interstitial cystitis.

Urology. 2008 Jan;71(1):62-6

Authors: Hill JR, Isom-Batz G, Panagopoulos G, Zakariasen K, Kavaler E

OBJECTIVES: Interstitial cystitis (IC) is a challenging disease complex. Patients' perception of their outcomes after different treatment modalities may be the best measure of therapeutic efficacy. Our study focused on a large group of women with a diagnosis of IC who reported on perceived outcomes after undergoing invasive and pharmaceutical treatments for their disease. METHODS: Seven hundred fifty patients with a diagnosis of IC completed a computerized survey that queried each patient about their demographics, symptoms, concomitant diagnoses, treatments, and their perceived treatment outcomes. The patients were surveyed on therapies used to treat IC and whether they perceived their condition to be improved, not affected or having deteriorated at a mean follow-up of 6 months. Pearson chi-squared tests were used in the statistical analyses. RESULTS: Invasive and medical therapies were surveyed. The most commonly performed procedures were hydrodistention (61.9%), intravesical therapy (40.1%), and urethral dilatation (26.5%). Of these procedures, 24.4% to 45.3% of patients were improved by these procedures; whereas 27.0% to 49.8% felt no effect and 25.9% to 30.7% worsened. A comparison of the number of patients who improved with those who deteriorated while on medical therapy was found to be significant for all drugs (P <0.001). The majority of patients reported that medications improved their condition, perceptively. CONCLUSIONS: Medical therapy is perceived to be superior to invasive therapy in the treatment of IC. Medication should be considered the first line therapy for IC. Several medications showed a large percentage of patients with improvement in symptoms. These medications were calcium glycerophosphate (Prelief, AkPharma Inc, Pleasantville, NJ), phenazopyridine, and pentosan polysulfate sodium.

PMID: 18242366 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Dyspareunia response in patients with interstitial cystitis treated with intravesical lidocaine, bicarbonate, and heparin.

Urology. 2008 Jan;71(1):67-70

Authors: Welk BK, Teichman JM

OBJECTIVES: To test the dyspareunia response of patients with interstitial cystitis/painful bladder syndrome treated with an intravesical therapeutic solution of lidocaine, heparin, and sodium bicarbonate. METHODS: We studied consecutive patients with interstitial cystitis/painful bladder syndrome who were sexually active and were treated with an intravesical therapeutic solution. All patients provided their medical history, underwent a physical examination, and completed the Pelvic Pain Urgency Frequency symptom scale, voiding diary, and the pain domain (questions 17 to 19) of the Female Sexual Function Index before and after therapy. The patients were treated with intravesical instillations three times weekly for 3 weeks. The patients returned for follow-up 3 weeks later. The patients rated their response using a Patient Objective Rating of Improvement of Symptom scale. RESULTS: A total of 23 patients (mean age 38 years) were included in this study. Of the 23 patients, 15 (65%) reported improvements of greater than 50% on the Patient Objective Rating of Improvement of Symptom scale. Before and after instillation, nocturia was 4 +/- 2 versus 2 +/- 1 (P <0.001), the voided volume was 98 +/- 59 mL versus 169 +/- 80 mL (P <0.001), the Pelvic Pain Urgency Frequency score was 21 +/- 6 versus 15 +/- 6 (P <0.001), and the Female Sexual Function Index pain domain score was 1.9 +/- 0.9 versus 3.7 +/- 1.6 (P <0.001), respectively. Of the 23 patients, 13 (57%) reported resolution of dyspareunia. Of the 13 patients with bladder tenderness only versus the 7 with multiple tender locations on the vaginal examination, 11 (85%) versus 2 (29%) had resolution of dyspareunia (P <0.01) and 12 (92%) versus 2 (29%) had successful overall outcomes (P <0.01). CONCLUSIONS: The results of this study have demonstrated that an intravesical therapeutic solution provides relief of voiding symptoms, pain, and dyspareunia in patients with interstitial cystitis/painful bladder syndrome. A randomized, prospective trial is warranted.

PMID: 18242367 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Effective treatment of neurogenic detrusor dysfunction by combined high-dosed antimuscarinics without increased side-effects.

Eur Urol. 2008 May;53(5):1021-8

Authors: Amend B, Hennenlotter J, Schäfer T, Horstmann M, Stenzl A, Sievert KD

OBJECTIVES: Patients with neurogenic bladder dysfunction demonstrate an insufficient treatment outcome under dosage-escalated monotherapy. With the objectives of continence and normalised bladder pressure, safe and tolerable non-invasive treatment alternatives were evaluated by using combined antimuscarinics. METHODS: Twenty-seven patients who were previously registered in a doubled antimuscarinics study were enrolled in this study. The patients demonstrated urodynamic-proven neurogenic bladder dysfunction with incontinence, reduced bladder capacity, and increased intravesical pressure, resulting from spinal cord injury (n=21); spinal cord dysplasia (myelomeningocele; n=3); multiple sclerosis (n=2), and viral encephalomyelitis (n=1). On the basis of the initial study treatment, they were allocated into three groups and treated with two antimuscarinics. Before enrollment, at 4 wk, and at 6 mo, patients underwent urodynamics and recorded bladder diaries, including side-effects. RESULTS: In all three groups, significant changes were noted at the 4-wk follow-up. Incontinence events decreased from an average of 7 to 1 event per day. The average median bladder capacity (180-393 ml) and reflex volume (125-335 ml) increased; detrusor compliance also improved (average, 15-33 ml/cm H2O). Seven patients reported side-effects; two discontinued the successful treatment. Two other patients did not reach satisfactory amelioration of the detrusor dysfunction. CONCLUSION: With combined high-dosage antimuscarinic medications, 85% of the patients who previously demonstrated unsatisfactory outcome with dosage-escalated monotherapy were treated successfully. The appearance of side-effects was comparable to that of normal-dosed antimuscarinics. Further studies are required to investigate the long-term pharmacological and physiological background of our findings.

PMID: 18243516 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Comparison of three schedules of intravesical epirubicin in patients with non-muscle-invasive bladder cancer.

Eur Urol. 2008 May;53(5):984-91

Authors: Hendricksen K, Witjes WP, Idema JG, Kums JJ, van Vierssen Trip OB, de Bruin MJ, Vergunst H, Caris CT, Janzing-Pastors MH, Witjes JA

OBJECTIVES: To study the additive effect of either an early instillation or maintenance instillations of adjuvant intravesical epirubicin, as compared to the epirubicin "standard" treatment schedule only, in patients with non-muscle-invasive bladder cancer. METHODS: Patients with intermediate- and high-risk urothelial cell carcinoma of the bladder, except carcinoma in situ, were randomised for adjuvant intravesical instillations with 50mg epirubicin/50 ml NaCl for 1h. Group 1 received 4 weekly and 5 monthly instillations (standard schedule), group 2 received the same schedule as group 1, but with an additional instillation <48 h after transurethral resection of bladder tumour (TURBT), and group 3 received the same scheme as group 1, but with additional instillations at 9 and 12 mo (maintenance schedule). Standard follow-up was 5 yr and consisted of cystoscopy, cytology, and registration of adverse events. RESULTS: A total of 731 patients were eligible for quasi intention-to-treat analysis. Side-effects were minimal for all treatment groups. After 5-yr follow-up, respectively, 44.4%, 42.7%, and 45.0% (log-rank test, p=0.712) of the patients in groups 1, 2, and 3 were recurrence free, and 90.0%, 87.7%, and 88.2% (log-rank test, p=0.593) of the patients, respectively, were progression free. CONCLUSIONS: In the quasi intention-to-treat analysis there is no difference in the 5-yr recurrence-free period between the treatment groups, despite one instillation within 48 h of TURBT or two maintenance instillations up to 1 yr, in addition to the "standard" schedule.

PMID: 18248876 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

A total hip replacement infected with mycobacterium bovis after intravesicular treatment with Bacille-Calmette-Guérin for bladder cancer.

J Bone Joint Surg Br. 2008 Feb;90(2):225-7

Authors: Reigstad O, Siewers P

An 86-year-old male presented with a loose total hip replacement (THR) ten years after implantation. At revision for anticipated aseptic loosening, watery pus was found in the joint and Bacille-Calmette-Guérin (BCG) was seen on culture. The bacterial strain was identified and was identical to the BCG used in the intravesicular treatment of superficial bladder carcinoma in this patient ten months earlier. After revision he received a full course of antituberculous treatment. The clinical and radiological results were excellent after follow-up for 30 months with his uncemented THR showing satisfactory incorporation. His inflammatory markers were normal and his Harris hip score was 95 points. The diagnosis of a tuberculous infection can be easily missed, but must be considered, especially if sterile pus is encountered.

PMID: 18256093 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Debulking transplant nephrectomy leaving an intact ureter and instillation of betadine intracapsular is safe nephrectomy: fifteen years' experience.

Transplant Proc. 2008 Jan-Feb;40(1):205-7

Authors: Zomorrodi A, Buhluli A

BACKGROUND: Transplant nephrectomy has been reported to display a high morbidity (17% to 56%) and considerable mortality (13% to 14%). We used a debulking technique leaving an intact ureter with intracapsular instillation of betadine; it was associated with a low rate of complications. MATERIALS AND METHODS: A total of 25 patients (16 males, 9 females) with failed allografted kidneys underwent transplant nephrectomy between 1991 and 2006 (Group 1). All subjects had failed kidneys for 2 months or more posttransplantation. The surgical approach to allograft nephrectomy was via the same oblique incision in the iliac fossa as the original transplantation. The capsule of the allograft was exposed and incised from pole to pole for the renal parenchyma to be bluntly dissected free with an index finger. The kidney parenchyma was pulled outward, and then the pedicle was ligated with silk, and layer by layer the tissue was removed until reaching the pedicle. Again it was transfixed and carefully ligated. After homeostasis, diluted betadine was instilled into the capsule and a drain inserted. The allograft ureter and capsule were left intact. All cases were followed for at least 1 year. Postnephrectomy, small doses of immunosuppressive drugs were continued for at least 2 months. RESULTS: Intracapsular nephrectomy was not associated with a significant complication. CONCLUSION: Intracapsular debulking nephrectomy, leaving the ureter and capsule intact and with intracapsular instillation of betadine, was a safe technique to remove a delayed, failed allograft.

PMID: 18261588 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

What matters - early start or duration of chemotherapy instillation regimens or patient characteristics?

Eur Urol. 2008 May;53(5):882-5; discussion 885-6

Authors: Kaasinen E

PMID: 18262339 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

Aspergillus "fungus ball" of the bladder after hematopoietic transplantation in a pediatric patient: successful treatment with intravesical voriconazole and surgery.

Pediatr Transplant. 2008 Mar;12(2):242-5

Authors: González-Vicent M, Lassaletta A, López-Pino MA, Romero-Tejada JC, de la Fuente-Trabado M, Díaz MA

Aspergillosis is an important cause of mortality in allogeneic HSCT. A "fungus ball" formation of Aspergillus in the bladder has seldom been reported. We report a child that underwent HSCT and developed possible disseminated aspergillosis with an intravesical "fungus ball," diagnosed by genitourinary MRI and PCR of the mass that was removed from the bladder. It is important to consider this complication in a patient with HC after HSCT. The treatment included a combination of systemic antifungal therapy along with intravesical voriconazole and surgical removal.

PMID: 18266800 [PubMed - indexed for MEDLINE]

]]>

View the Original article

Related Articles

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

BMC Immunol. 2008;9:4

Authors: Saban MR, O'Donnell MA, Hurst RE, Wu XR, Simpson C, Dozmorov I, Davis C, Saban R

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-alpha). For this purpose, C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-alpha. 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-alpha, 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/beta-catenin, and cAMP. In addition, a specific detrusor network expressed a high degree of overlap with the development of the lymphatic system. Interestingly, TNF-alpha-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 [PubMed - indexed for MEDLINE]

]]>

View the Original article