Intravesical Therapy blog

[Continous bladder irrigation with amikacin as adjuvant treatment for emphysematous cystitis]

Arch Esp Urol. 2007 Dec;60(10):1.218-1.220

Authors: Cortés González JR, Ortiz Lara GE, Arratia Maqueo JA, Gómez Guerra LS

OBJECTIVE: To demonstrate that continuos intravesical irrigation with amikacin is an effective adyuvant treatment in Emphisematous Cistitis therapy. METHODS: A 3 way transurethral Foley catheter was placed and a continuous intravesical irrigation was initiated with amikacin 500 mg in 1L of normal saline (500 micrograms per ml) within 6 hours 4 times a day and three consecutive days. RESULTS: After 3 days of treatment the patient showed significant clinical response. A new CT scan showed the absence of gas in the bladder wall compared to the previews CT and negative urine culture was obtained. CONCLUSIONS: We established that treatment using adjuvant continuous intravesical irrigation with amikacin can reduce hospital stay and accelerate the patient's healing process, as well as an earlier negativisation of urine cultures. A comparative prospective study is needed to evaluate if in fact this treatment variant produces a real benefit compared to conventional therapy.

PMID: 18273983 [PubMed - indexed for MEDLINE]

Low-dose instillation therapy with bacille Calmette-Guérin Tokyo 172 strain after transurethral resection: historical cohort study.

Urology. 2008 Jun;71(6):1161-5

Authors: Yoneyama T, Ohyama C, Imai A, Ishimura H, Hagisawa S, Iwabuchi I, Mori K, Kamimura N, Koie T, Yamato T, Suzuki T

OBJECTIVES: To evaluate the effectiveness and side effects of prophylactic low-dose bacille Calmette-Guérin (BCG) Tokyo 172 strain. METHODS: We conducted a historical cohort study to compare the clinical usefulness of standard-dose versus low-dose BCG Tokyo 172 strain. A total of 156 patients with superficial bladder cancer (Stage Ta-T1) were historically allocated to either 40 or 80 mg of BCG after transurethral resection. Of the 156 patients, 89 had received standard-dose (80 mg) BCG from 1988 to 2000 and 67 had received low-dose (40 mg) BCG from 1996 to 2005. BCG was instilled into the bladder once a week for 6 consecutive weeks. We excluded 6 patients who did not complete the BCG treatment course. The median follow-up period was 66.9 months (range 2 to 176). RESULTS: Tumor recurrence developed in 21 (32.3%) of 65 patients in the 40-mg group and 29 (34.5%) of 85 patients in the 80-mg group. No significant difference was found in the incidence of tumor recurrence between the two groups (P = 0.6377). Tumor progression was found in 4 (6.2%) of 65 patients in 40-mg group and 9 (10.6%) of 85 patients in the 80-mg group. No significant difference was found in tumor progression between the two groups (P = 0.5010). The overall incidence of side effects and severity of pollakisuria were significantly lower in the 40-mg group than in the 80-mg group (P = 0.012 and P = 0.013, respectively). CONCLUSIONS: The low-dose BCG Tokyo 172 strain achieved identical recurrence-free and progression-free survival as the standard dose with reduced toxicity.

PMID: 18279920 [PubMed - indexed for MEDLINE]

Activation of muscarinic receptors in rat bladder sensory pathways alters reflex bladder activity.

J Neurosci. 2008 Feb 20;28(8):1977-87

Authors: Kullmann FA, Artim DE, Birder LA, de Groat WC

Antimuscarinic drugs affect bladder sensory symptoms such as urgency and frequency, presumably by acting on muscarinic acetylcholine receptors (mAChRs) located in bladder sensory pathways including primary afferent nerves and urothelium. However, the expression and the function of these receptors are not well understood. This study investigated the role of mAChRs in bladder sensory pathways in vivo in urethane anesthetized rats. Intravesical administration of the mAChR agonist oxotremorine methiodide (OxoM) elicited concentration-dependent excitatory and inhibitory effects on the frequency of voiding. These effects were blocked by intravesical administration of the mAChR antagonist atropine methyl nitrate (5 microM) and were absent in rats pretreated with capsaicin to desensitize C-fiber afferent nerves. Low concentrations of OxoM (5 microM) decreased voiding frequency by approximately 30%, an effect blunted by inhibiting nitric oxide (NO) synthesis with L-NAME (N(omega)-nitro-L-arginine methyl ester hydrochloride; 5 mg/kg; i.v.). High concentrations of OxoM (40 microM) increased voiding frequency by approximately 45%, an effect blunted by blocking purinergic receptors with PPADS (0.1-1 mM; intravesically). mAChR agonists stimulated release of ATP from cultured urothelial cells. Intravenous administration of OxoM (0.01-5 microg/kg) did not mimic the intravesical effects on voiding frequency. These results suggest that activation of mAChRs located near the luminal surface of the bladder affects voiding functions via mechanisms involving ATP and NO release presumably from the urothelium, that in turn could act on bladder C-fiber afferent nerves to alter their firing properties. These findings suggest that the urothelial-afferent nerve interactions can influence reflex voiding function.

PMID: 18287514 [PubMed - indexed for MEDLINE]

The effect of intravesical instillation of antifibrinolytic agents on bacillus Calmette-Guerin treatment of superficial bladder cancer: a pilot study.

J Urol. 2008 Apr;179(4):1307-11; discussion 1311-2

Authors: Pan CW, Shen ZJ, Ding GQ

PURPOSE: We determined whether intravesical instillation of antifibrinolytic agents could improve the antitumor effect of bacillus Calmette-Guerin. We also investigated the impact of these antifibrinolytic agents on the dose of bacillus Calmette-Guerin required for a therapeutic effect. MATERIALS AND METHODS: In this randomized, prospective, double-blind, controlled pilot study 257 patients with superficial bladder cancer were randomized into groups A through E. They received 100 to 120 mg intravesical bacillus Calmette-Guerin plus 100 mg para-aminomethylbenzoic acid, 50 to 60 mg bacillus Calmette-Guerin plus 100 mg para-aminomethylbenzoic acid, 100 to 120 mg bacillus Calmette-Guerin plus 2.0 gm epsilon aminocaproic acid, 50 to 60 mg bacillus Calmette-Guerin plus 2.0 gm epsilon aminocaproic acid and 100 to 120 mg bacillus Calmette-Guerin alone, respectively. Prothrombin time and activated partial thromboplastin time of each patient were determined at 2 hours after instillation, and adverse events were evaluated. Tumor recurrence was assessed every 3 months postoperatively by cystoscopy. Median followup was 26.0, 25.0, 24.5, 25.0 and 25.5 months, respectively. RESULTS: No significant change in prothrombin time or activated partial thromboplastin time was observed, and analysis showed no significant difference in prothrombin time or activated partial thromboplastin time among groups A through E (p = 0.693, 0.756). Recurrence rates at a minimum of median 2 years were 10.6%, 11.1%, 10.0%, 9.3% and 31.8% in groups A through E, respectively. The log rank test showed that recurrence-free probability was statistically different comparing groups A, B, C and D with group E, respectively (p = 0.023, 0.037, 0.031 and 0.020), while pairwise comparisons among groups A, B, C and D showed no significant differences (each p >0.05). The rate of serious adverse events in groups A through E was 9.6%, 3.9%, 15.7%, 5.9% and 13.5%, respectively. However, the differences were not significant (p = 0.222). CONCLUSIONS: Intravesical instillation of para-aminomethylbenzoic acid or epsilon aminocaproic acid is a more effective and safer method to improve the bacillus Calmette-Guerin antitumor effect, and can reduce the dose of bacillus Calmette-Guerin with the same effect as the full dose.

PMID: 18289576 [PubMed - indexed for MEDLINE]

Efficacy of intravesical ropivacaine injection on urinary symptoms following ureteral stenting: a randomized, controlled study.

J Endourol. 2008 Mar;22(3):473-8

Authors: Sur RL, Haleblian GE, Cantor DA, Springhart WP, Albala DM, Preminger GM

PURPOSE: Previous studies suggest that intravesical administration of nonsteroidal anti-inflammatory drugs may reduce the troublesome voiding symptoms and pain related to ureteral stenting. The objective of this study was to investigate the effectiveness of a long-acting local anesthetic, ropivacaine, injected submucosally into the bladder to control ureteral stent-associated symptoms. MATERIALS AND METHODS: A randomized, single-blinded, study approved by our Institutional Review Board of adult patients scheduled for ureteroscopic stone surgery and possible stent placement was conducted. Patients were randomized to either the treatment cohort, who received five injections of 2 mL 0.5% ropivacaine around the ureteral orifice or to the control cohort, who received five injections of 2 mL of 0.9% normal saline in identical locations. Pain scale questionnaires were provided to each subject preoperatively and at postoperative hours 2, 4, 8, 24, and 48 as well as on the day of stent removal. Student's t test and Wilcoxon signed rank sum tests were used for Gaussian and nonparametric data, respectively. RESULTS: Twenty-two patients were randomized evenly into the two cohorts. The ropivacaine group consisted of 11 patients (eight men and three women) with a mean age of 56.2 years (standard deviation [SD] = 12, range 27-69), and the saline group consisted of eleven patients (six men and five women) with a mean age of 47.8 years (SD = 6.6, range 37-58). Intraoperative parameters appeared similar between the two cohorts. Intraoperative and postoperative narcotic usage was not different between the two groups, except at postoperative hour 2 when it favored the ropivacaine cohort (P = 0.05). Trends favoring ropivacaine in flank pain, bladder pain, genitalia pain, and hematuria domains were seen as long as 8 hours and up to the day of stent removal. Trends of less magnitude and duration were seen in the dysuria domain. No differences were seen in the frequency and urgency domains. CONCLUSIONS: Our preliminary investigation with intravesical injection of ropivacaine before ureteroscopic surgery demonstrated trends toward decreased pain and voiding symptoms in this small-sample study. Inclusion of a larger sample should definitively address the effectiveness of intravesical ropivacaine and its impact on stent-related symptoms.

PMID: 18290733 [PubMed - indexed for MEDLINE]

Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: a case series with 15-year follow-up.

Am J Kidney Dis. 2008 Mar;51(3):471-7

Authors: Lemy A, Wissing KM, Rorive S, Zlotta A, Roumeguere T, Muniz Martinez MC, Decaestecker C, Salmon I, Abramowicz D, Vanherweghem JL, Nortier J

BACKGROUND: Aristolochic acids are nephrotoxins and predispose to upper-tract urothelial carcinoma. The risk of bladder urothelial carcinoma after kidney transplantation and its relationship to upper-tract urothelial carcinoma is not well defined. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Single-center cohort of 38 women given kidney transplants for end-stage aristolochic acid nephropathy. OUTCOMES & MEASUREMENTS: The prevalence of upper urinary tract urothelial carcinoma was determined by collecting pathological results of specimens obtained by means of bilateral ureteronephrectomy. We also established the cumulative incidence of bladder urothelial carcinoma in biopsies performed during prospective screening cystoscopies during a 15-year follow-up. RESULTS: Upper-tract urothelial carcinoma was found in 17 patients with aristolochic acid nephropathy (44.7%). During follow-up, bladder urothelial carcinoma was diagnosed in 15 patients 68 to 169 months after cessation of aristolochic acid exposure (39.5%): 8 urothelial carcinoma in situ, 4 noninvasive low-grade papillary urothelial carcinoma, and 3 infiltrating urothelial carcinoma. 12 of 17 patients (71%) with a history of upper-tract urothelial carcinoma developed bladder urothelial carcinoma during follow-up, whereas this occurred in only 3 of 21 patients (14%) without upper-tract urothelial carcinoma (P < 0.01). Despite local and/or systemic chemotherapy, 3 patients died and 2 radical cystectomies were performed. LIMITATIONS: Small sample size of this case series. CONCLUSIONS: Upper-tract and bladder urothelial carcinoma are dramatic complications in kidney transplant recipients with aristolochic acid nephropathy, confirming the carcinogenic properties of aristolochic acids. We identified upper-tract urothelial carcinoma as a potent risk factor for the subsequent development of bladder urothelial carcinoma after kidney transplantation for aristolochic acid nephropathy. Because this complication may occur years after aristolochic acid discontinuation, we suggest regular cystoscopies in addition to the bilateral ureteronephrectomy in kidney transplant recipients with aristolochic acid nephropathy.

PMID: 18295063 [PubMed - indexed for MEDLINE]

Intravesical nanocrystalline silver decreases experimental bladder inflammation.

J Urol. 2008 Apr;179(4):1598-602

Authors: Boucher W, Stern JM, Kotsinyan V, Kempuraj D, Papaliodis D, Cohen MS, Theoharides TC

PURPOSE: Interstitial cystitis is a sterile bladder inflammatory disease characterized by pelvic pain, urinary urgency and frequency. Nanocrystalline silver has anti-inflammatory properties, prompting us to investigate its effect in experimental bladder inflammation. MATERIALS AND METHODS: Nanocrystalline silver (0.01%, 0.05%, 0.1%, 0.5% or 1%) or phosphate buffered saline (Invitrogen) (0.5 ml) was introduced intravesically in Sprague-Dawley female rat (Charles River Laboratories, Wilmington, Massachusetts) bladders for 20 minutes, followed by vehicle or protamine sulfate (10 mg/ml for 30 minutes) and lipopolysaccharide (Sigma) (2 mg/ml for 45 minutes). Urine was collected throughout for histamine assay. The catheter was removed, the rat was returned to its cage and 4 hours later it was sacrificed. The bladder was harvested, minced and cultured overnight. The medium was collected for tumor necrosis factor-alpha assay. RESULTS: Mean +/- SD total urine histamine increased from 270 +/- 190 ng in 4 controls to 842 +/- 239 ng after protamine sulfate/lipopolysaccharide and it decreased to 505 +/- 187 ng in 6 animals after pretreatment with 1% nanocrystalline silver (p = 0.036). Tumor necrosis factor-alpha release in explant medium increased from 0.02 +/- 0.03 pg/mg in 6 controls to 0.28 +/- 0.15 pg/mg in 14 animals after treatment with protamine sulfate/lipopolysaccharide and it decreased to 0.12 +/- 0.11 pg/mg in 10 animals pretreated with nanocrystalline silver (p = 0.009). Nanocrystalline silver was not effective at less than 1% and at 1% alone it released 0.05 +/- 0.07 pg/mg tumor necrosis factor-alpha in 7 rats (vs phosphate buffered saline in 6, p = 0.387). Nanocrystalline silver (1%) significantly decreased bladder inflammation and mast cell activation. These effects were apparent even 4 days later. CONCLUSIONS: Intravesical administration of nanocrystalline silver (1%) decreased urine histamine, bladder tumor necrosis factor-alpha and mast cell activation without any toxic effect. This action may be useful for interstitial cystitis.

PMID: 18295255 [PubMed - indexed for MEDLINE]

Quality of life in patients undergone oncopreventive intravesical treatment for superficial bladder cancer.

Arch Ital Urol Androl. 2007 Dec;79(4):143-6

Authors: Abbona A, Morabito F, Rossi R, Billia M, Liberale F, Ferrando U

OBJECTIVES: Adjuvant intravesical therapy after TURB for superficial bladder cancer forces the patients to follow prolonged protocols of treatment. In our study we considered the quality of life of these patients. MATERIALS AND METHODS: We created a questionnaire of 52 items in order to analyse free time, working activity, sexual-relational activity, compliance and self esteem of patients undergone intravesical adjuvant therapy. We gave the questionnaires to 63 patients and, on the basis of results, we proposed a psychosexual support therapy according to alteration of Quality of Life (Q.o.L). After the therapy we reproposed the same questionnaires in order to establish the utility of this integrated treatment. RESULTS: We found that quality of life was greatly altered by oncopreventive intravesical therapy. We showed results of questionnaires before and after the multidisciplinary therapy. CONCLUSIONS: The analysis of our data confirme the importance of multidisciplinary approach in adjuvant treatment of superficial bladder cancer. The therapy proposed helps the patients to face neoplastic disease.

PMID: 18303728 [PubMed - indexed for MEDLINE]

Discovery of a novel series of biphenyl benzoic acid derivatives as potent and selective human beta3-adrenergic receptor agonists with good oral bioavailability. Part I.

J Med Chem. 2008 Mar 27;51(6):1925-44

Authors: Imanishi M, Tomishima Y, Itou S, Hamashima H, Nakajima Y, Washizuka K, Sakurai M, Matsui S, Imamura E, Ueshima K, Yamamoto T, Yamamoto N, Ishikawa H, Nakano K, Unami N, Hamada K, Matsumura Y, Takamura F, Hattori K

A novel class of biphenyl analogues containing a benzoic acid moiety based on lead compound 8i have been identified as potent and selective human beta 3 adrenergic receptor (beta 3-AR) agonists with good oral bioavailability and long plasma half-life. After further substituent effects were investigated at the terminal phenyl ring of lead compound 8i, we have discovered that more lipophilic substitution at the R position improved potency and selectivity. As a result of these studies, 10a and 10e were identified as the leading candidates with the best balance of potency, selectivity, and pharmacokinetic profiles. In addition, compounds 10a and 10e were evaluated to be efficacious for a carbachol-induced increase of intravesical pressure, such as an overactive bladder model in anesthetized dogs. This represents the first demonstrated result dealing with beta 3-AR agonists.

PMID: 18307290 [PubMed - indexed for MEDLINE]

Impact of previous bacille Calmette-Guérin failure pattern on subsequent response to bacille Calmette-Guérin plus interferon intravesical therapy.

Urology. 2008 Feb;71(2):297-301

Authors: Gallagher BL, Joudi FN, Maymí JL, O'Donnell MA

OBJECTIVES: To evaluate the effect of the bacille Calmette-Guérin (BCG) failure pattern in patients with non-muscle-invasive bladder cancer on the subsequent response to intravesical immunotherapy. METHODS: Data from the national Phase II multicenter trial for BCG plus interferon-alpha intravesical therapy for non-muscle-invasive bladder cancer were analyzed. The cancer-free rates for BCG-naive (BCG-N) and BCG-failure (BCG-F) patients with different failure patterns were compared using Kaplan-Meier analysis. RESULTS: At a median follow-up of 24 months, the BCG-N and BCG-F patients had a cancer-free rate of 59% and 45%, respectively. The BCG-F patients with immediate recurrence (refractory disease), within 6, 6 to 12, 12 to 24, and longer than 24 months had a cancer-free rate of 34%, 41%, 43%, 53%, and 66%, respectively (P = 0.005 for trend). No statistically significant difference was found in the cancer-free rates between patients with failure after 12 months and those with failure after 24 months or between BCG-N patients and those with failure after 12 and 24 months. A multivariate analysis of patients with failure after 12 months revealed that the number of previous courses of BCG did not significantly affect the treatment response. CONCLUSIONS: Patients with non-muscle-invasive bladder cancer with disease recurrence more than 1 year after BCG treatment and who were treated with low-dose BCG plus interferon-alpha had response rates similar to those of BCG-N patients treated with regular-dose BCG plus interferon. Although cystectomy should still be strongly considered, these patients might benefit from another trial with intravesical immunotherapy. In contrast, recurrence within 1 year of BCG treatment should lead to consideration of either cystectomy or alternative intravesical therapies.

PMID: 18308107 [PubMed - indexed for MEDLINE]

Intravesical chemotherapy of high-grade bladder cancer with HTI-286, a synthetic analogue of the marine sponge product hemiasterlin.

Clin Cancer Res. 2008 Mar 1;14(5):1510-8

Authors: Hadaschik BA, Adomat H, Fazli L, Fradet Y, Andersen RJ, Gleave ME, So AI

PURPOSE: HTI-286 is a fully synthetic analogue of the natural tripeptide hemiasterlin that inhibits tubulin polymerization and has strong cytotoxic potential. In this study, we evaluate the inhibitory effects of HTI-286 on human bladder cancer growth, both in vitro and as an intravesical agent in an orthotopic murine model. EXPERIMENTAL DESIGN: Various bladder cancer cell lines were treated with HTI-286 and mitomycin C (MMC) in vitro. Human KU-7 bladder tumor cells that stably express firefly luciferase were inoculated in female nude mice by intravesical instillation and quantified using bioluminescence imaging. Mice with established KU-7-luc tumors were given HTI-286 or MMC intravesically twice a week for 2 h. Pharmacokinetic data was obtained using high-performance liquid chromatography-mass spectrometry analyses. RESULTS: In vitro, HTI-286 was a potent inhibitor of proliferation in all tested cell lines and induced marked increases in apoptosis of KU-7-luc cells even after brief exposure. In vivo, HTI-286 significantly delayed cancer growth of bladder tumors in a dose-dependent fashion. HTI-286, at a concentration of 0.2 mg/mL, had comparable strong cytotoxicity as 2.0 mg/mL of MMC. The estimated systemic bioavailability of intravesically given HTI-286 was 1.5% to 2.1% of the initial dose. CONCLUSIONS: Intravesical HTI-286 instillation therapy showed promising antitumor activity and minimal toxicity in an orthotopic mouse model of high-grade bladder cancer. These findings provide preclinical proof-of-principle for HTI-286 as an intravesical therapy for nonmuscle-invasive bladder cancer and warrant further evaluation of efficacy and safety in early-phase clinical trials.

PMID: 18316576 [PubMed - indexed for MEDLINE]

Bacterial cystitis is accompanied by increased peripheral thermal sensitivity in mice.

J Urol. 2008 Feb;179(2):759-63

Authors: Bjorling DE, Wang ZY, Boldon K, Bushman W

PURPOSE: Visceral inflammation and pain associated with chemical cystitis produce increased sensitivity to noxious stimuli in the sacral dermatomes. We determined whether a similar sensitization occurs in response to bacterial cystitis. MATERIALS AND METHODS: Bacterial cystitis was induced by intravesical instillation of Escherichia coli 1677 in female C57BL/6N and C3H/OuJ mice (Jackson Laboratories, Bar Harbor, Maine). C3H/HeJ mice (Jackson Laboratories) served as a control because C3H/HeJ mice lack functional toll-like receptor 4, which is an essential component of cellular recognition of bacterial lipopolysaccharide. Hind paw sensitivity to thermal stimulus was quantitatively determined 1, 2, 7 and 14 days after infection. RESULTS: Intravesical instillation of E. coli produced infection in all strains of mice. Infection persisted in all C3H/OuJ and C3H/HeJ mice but it spontaneously cleared in some C57BL/6N mice. Increased sensitivity to thermal stimuli was observed in C57BL/6N and C3H/OuJ mice starting 1 to 2 days after E. coli instillation and it was still present 14 days after instillation. Increased sensitivity to thermal stimuli did not occur in C3H/HeJ mice. CONCLUSIONS: E. coli induced cystitis produced increased sensitivity to peripheral thermal stimuli in mice with competent toll-like receptor 4.

PMID: 18082197 [PubMed - indexed for MEDLINE]

Followup of patients with interstitial cystitis responsive to treatment with intravesical bacillus Calmette-Guerin or placebo.

J Urol. 2008 Feb;179(2):552-5

Authors: Propert KJ, Mayer R, Nickel JC, Payne CK, Peters KM, Teal V, Burks D, Kusek JW, Nyberg LM, Foster HE,

PURPOSE: We evaluated the longer term response in patients with interstitial cystitis who initially responded to intravesical bacillus Calmette-Guerin or placebo in a randomized clinical trial. MATERIALS AND METHODS: Patients with interstitial cystitis who responded positively to treatment with bacillus Calmette-Guerin or placebo after 34 weeks of followup in a double-blind clinical trial were followed for an additional 34 weeks in an observational study to assess response durability. Outcomes at 68 weeks included a patient reported global response assessment, 24-hour voiding diary, and pain, urgency and validated interstitial cystitis symptom indexes. RESULTS: Of responders to bacillus Calmette-Guerin or placebo in the clinical trial 38 continued extended followup in the observational study. A total of 12 (75%) responders who received placebo and 19 (86%) who received bacillus Calmette-Guerin considered themselves to remain moderately or markedly improved at week 68. Improved symptom outcomes were also generally maintained during followup in the 2 groups. CONCLUSIONS: Most patients who respond to therapy with intravesical bacillus Calmette-Guerin or placebo maintain improved symptoms for up to 68 weeks after the initiation of therapy. However, initial response rates are low and placebo responders demonstrated essentially the same durability of response as bacillus Calmette-Guerin responders. These results argue against the routine use of bacillus Calmette-Guerin in this patient group.

PMID: 18082224 [PubMed - indexed for MEDLINE]

Re: The increasing use of intravesical therapies for stage T1 bladder cancer coincides with decreasing survival after cystectomy.

BJU Int. 2008 Jan;101(1):127

Authors: Gazzaniga P, Silvestri I, Gradilone A, Aglianò AM

PMID: 18086103 [PubMed - indexed for MEDLINE]

Bladder tuberculosis after BCG therapy.

Saudi J Kidney Dis Transpl. 2008 Jan;19(1):80-1

Authors: Bouhabel A, Takoucht F, Bousbia W, Hamada B, Lemaiaci N

The initial treatment of bladder cancer is transurethral resection (TUR), but this cancer recurs at an important rate, and has 14% chance of progression after TUR alone. Intravesical chemotherapy with Bacillus Calmette-Guerin (BCG) is effective against recurrence and progression of bladder cancer. However, this therapeutic expose to many local and systemic side-effects. We report a case of 63-year-old man who presented bladder tuberculosis after a BCG therapy, which required 6 months of antitubercular therapy.

PMID: 18087129 [PubMed - indexed for MEDLINE]

The neurogenic bladder: medical treatment.

Pediatr Nephrol. 2008 May;23(5):717-25

Authors: Verpoorten C, Buyse GM

Neurogenic bladder sphincter dysfunction (NBSD) can cause severe and irreversible renal damage and bladder-wall destruction years before incontinence becomes an issue. Therefore, the first step in adequate management is to recognize early the bladder at risk for upper- and lower-tract deterioration and to start adequate medical treatment proactively. Clean intermittent catheterization combined with anticholinergics (oral or intravesical) is the standard therapy for NBSD. Early institution of such treatment can prevent both renal damage and secondary bladder-wall changes, thereby potentially improving long-term outcomes. In children with severe side effects or with insufficient suppression of detrusor overactivity despite maximal dosage of oral oxybutynin, intravesical instillation is an effective alternative. Intravesical instillation eliminates systemic side effects by reducing the first-pass metabolism and, compared with oral oxybutynin, intravesical oxybutynin is a more potent and long-acting detrusor suppressor. There is growing evidence that with early adequate treatment, kidneys are saved and normal bladder growth can be achieved in children so they will no longer need surgical bladder augmentation to achieve safe urinary continence in adolescence and adulthood.

PMID: 18095004 [PubMed - indexed for MEDLINE]

Electromotive drug administration with mitomycin C for intravesical treatment of non-muscle invasive transitional cell carcinoma.

Expert Opin Drug Deliv. 2008 Jan;5(1):137-45

Authors: Kalsi J, Harland SJ, Feneley MR

This article reviews the use and application of electromotive drug administration for the intravesical treatment of bladder cancer. Strong evidence supports the use of passive intravesical chemotherapy in the management of non-muscle invasive bladder cancer. More recently, two published randomised trials have shown therapeutic advantage with protocols that use electromotive drug administration to enhance urothelial penetration of intravesical mitomycin C. The results suggest that the passive intravesical administration of chemotherapeutic drugs may be suboptimal. Further studies are required to demonstrate the feasibility and advantage of electromotive intravesical mitomycin C in the wider uro-oncological community.

PMID: 18095933 [PubMed - indexed for MEDLINE]

Hyaluronan treatment of interstitial cystitis/painful bladder syndrome.

Int Urogynecol J Pelvic Floor Dysfunct. 2008 May;19(5):717-21

Authors: Riedl CR, Engelhardt PF, Daha KL, Morakis N, Pflüger H

The aim of this study is to evaluate the efficacy of intravesical hyaluronan therapy in interstitial cystitis/painful bladder syndrome (IC/PBS). One hundred twenty-six patients with IC/PBS and an average disease duration of 6.1 years were treated with weekly instillations of a 50-cm3 phosphate-buffered saline solution containing 40 mg sodium hyaluronate. To be eligible for hyaluronan treatment, a positive modified potassium test was requested as a sign of a urine-tissue barrier disorder. Data were obtained by a visual analogue scale (VAS) questionnaire rating from 0 to 10 that asked for global bladder symptoms before and after therapy. Additional questions evaluated the therapeutic impact on quality of life. A positive and durable impact of hyaluronan therapy on IC/PBS symptoms was observed--103 (85%) of the patients reported symptom improvement (> or =2 VAS units). The mean initial VAS score of 8.5 decreased to 3.5 after therapy (p < 0.0001). Out of 121 patients, 67 (55%) remained with no or minimal bladder symptoms after therapy (VAS 0-2). The majority (101, 84%) reported significant improvement of their quality of life. Intravesical therapy had to be initiated again with good success in 43 patients (34.5%) as symptoms recurred after discontinuation of treatment, while the rest stayed free of symptoms for up to 5 years. In general, hyaluronan therapy was well tolerated and, with the exception of mild irritative symptoms, no adverse reactions were reported for a total of 1,521 instillations. Timely hyaluronan instillation therapy may lead to complete symptom remission or even cure in part of the IC/PBS patients, while some responders need continuous intravesical therapy. The present results suggest that selection of patients for hyaluronan therapy by potassium testing improves the outcome of intravesical therapy with a response rate of >80%.

PMID: 18097627 [PubMed - indexed for MEDLINE]

The safety and efficacy of different doses of bacillus Calmette Guérin in superficial bladder transitional cell carcinoma.

Urology. 2007 Dec;70(6):1075-8

Authors: Agrawal MS, Agrawal M, Bansal S, Agarwal M, Lavania P, Goyal J

OBJECTIVES: To conduct a trial using three different doses of bacillus Calmette-Guérin (BCG) to determine whether lowering the dose of BCG could reduce toxicity without compromising its efficacy in the treatment of superficial bladder cancer. METHODS: From July 2002 to June 2005, 152 patients with superficial bladder cancer entered the trial. The patients were randomized to receive three different doses of BCG: 40, 80, and 120 mg. There were no significant differences in clinical and pathologic characteristics among the three groups. Twenty-four patients could not be followed to the end of the study because of poor compliance. At completion of the study, 40 patients could be evaluated in group A (40 mg), 48 in group B (80 mg), and 40 in group C (120 mg). RESULTS: After treatment patients were evaluated for a mean follow-up period of 36 months (range 18 to 52 months). No significant difference in recurrence rate (20% versus 25% versus 20% respectively; P >0.05) was observed among the groups, and no progression of the disease was seen. Significant differences were observed among groups A, B, and C in local toxicity (30% versus 41.7% versus 70%, respectively; P <0.01). Systemic toxicity was more common in group C compared with groups B and A (P <0.01). CONCLUSIONS: Reduction in the dose of intravesical BCG can reduce the toxicity associated with the treatment of superficial bladder cancer without affecting the efficacy of therapy.

PMID: 18158020 [PubMed - indexed for MEDLINE]

Bladder and penile lesions with inguinal adenopathy after intravesical Bacillus Calmette-Guerin (BCG) treatment.

Urology. 2007 Dec;70(6):1223.e15-7

Authors: Yates J, Stein B

Intravesical Bacillus Calmette-Guerin (BCG) is usually a well-tolerated treatment strategy for transitional cell cancer of the bladder. We report a patient with penile and bladder mucosal lesions with inguinal adenopathy after six instillations of intravesical BCG. Pathology demonstrated inflammation with granulomatous changes. The lesions and adenopathy resolved with antituberculous drug treatment. We describe the patient's clinical presentation and review the complications of intravesical BCG treatment.

PMID: 18158061 [PubMed - indexed for MEDLINE]

RDP58 inhibits T cell-mediated bladder inflammation in an autoimmune cystitis model.

J Autoimmun. 2008 Jun;30(4):257-65

Authors: Liu W, Deyoung BR, Chen X, Evanoff DP, Luo Y

Interstitial cystitis (IC) is a chronic inflammatory condition of the urinary bladder with a strong autoimmune component. Currently, the major challenge in IC treatment is the development of effective therapies. RDP58 is a novel d-amino acid decapeptide with potent immunosuppressive activity. In this study, we investigated whether RDP58 was effective as an intravesical agent for treating bladder autoimmune inflammation in a transgenic mouse model (URO-OVA mice). URO-OVA mice were adoptively transferred with syngeneic activated splenocytes of OT-I mice transgenic for the OVA-specific CD8(+) TCR for cystitis induction and treated intravesically with RDP58 at days 0 and 3. Compared with controls, the RDP58-treated bladders showed markedly reduced histopathology and expressions of mRNAs and proteins of TNF-alpha, NGF and substance P. To determine whether the inhibition of bladder inflammation by RDP58 was due to the interference with effector T cells, we treated the cells with RDP58 in vitro. Cells treated with RDP58 showed reduced production of TNF-alpha and IFN-gamma as well as apoptotic death. Collectively, these results indicate that RDP58 is effective for treating T cell-mediated experimental autoimmune cystitis and may serve as a useful intravesical agent for the treatment of autoimmune-associated bladder inflammation such as IC.

PMID: 18162370 [PubMed - indexed for MEDLINE]

Effects of intravesical instillation of resiniferatoxin on bladder function and nociceptive behavior in freely moving, conscious rats.

J Urol. 2008 Jan;179(1):359-64

Authors: Saitoh C, Chancellor MB, de Groat WC, Yoshimura N

PURPOSE: A new animal model in which to concurrently evaluate bladder function and nociceptive behavior was developed using freely moving, noncatheterized, conscious rats to assess the nociceptive behavior responses induced by intravesical instillation of resiniferatoxin (Sigma) and its relationship with bladder dysfunction. MATERIALS AND METHODS: In female Sprague-Dawley rats resiniferatoxin (0, 0.3 and 3 microM) was instilled via a catheter that was temporarily inserted into the bladder through the urethra. After removing the catheter the incidence of nociceptive behavior (lower abdominal licking and freezing) was scored. Voided urine was collected continuously to measure bladder capacity. In some rats the pudendal nerves were transected bilaterally to eliminate the activation of urethral afferents by resiniferatoxin. RESULTS: Intravesical instillation of resiniferatoxin induced decreased bladder capacity and increased nociceptive behaviors, such as licking and freezing, which were blocked by the transient receptor potential vanilloid receptor 1 antagonist BCTC (Biomol). In rats with pudendal nerve transection the early phase of resiniferatoxin induced licking was decreased without affecting the resiniferatoxin induced decrease in bladder capacity and late phase licking behavior. Resiniferatoxin induced late phase licking in the water unloaded group was observed to a lesser extent than in the water loaded diuresis group. CONCLUSIONS: The intravesical instillation of resiniferatoxin, which decreases bladder capacity, acts by at least 3 distinct mechanisms to induce licking behavior, including 1) an immediate response mediated by the activation of urethral afferents in the pudendal nerve, 2) a late response evoked by the direct stimulation of C-fiber afferents in the bladder and 3) gradual facilitation of the response elicited by the bladder wall distention induced by rapid bladder filling.

PMID: 18006008 [PubMed - indexed for MEDLINE]

Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder.

Eur Urol. 2008 Feb;53(2):391-9

Authors: Streng T, Axelsson HE, Hedlund P, Andersson DA, Jordt SE, Bevan S, Andersson KE, Högestätt ED, Zygmunt PM

OBJECTIVES: To investigate the distribution of the transient receptor potential (TRP) A1 ion channel in the rat urinary bladder, and to study the effects of hydrogen sulfide (H(2)S) and known TRPA1 activators on micturition in conscious rats and on heterologously expressed ion channels. METHODS: The expression of TRPA1 in urinary bladder was studied with fluorescence immunohistochemistry and real-time PCR in female Sprague-Dawley rats. Cystometric investigations were performed in conscious animals subjected to intravesical administration of sodium hydrogen sulfide (NaHS, donor of H(2)S), allyl isothiocyanate (AI), and cinnamaldehyde (CA). Fluorometric calcium imaging was used to study the effect of NaHS on human and mouse TRPA1 expressed in CHO cells. RESULTS: TRPA1 immunoreactivity was found on unmyelinated nerve fibres within the urothelium, suburothelial space, and muscle layer as well as around blood vessels throughout the bladder. All TRPA1 immunoreactive nerves fibres also expressed TRPV1 immunoreactivity and vice versa. TRPA1 was also detected in urothelial cells at both transcriptional and protein levels. AI increased micturition frequency and reduced voiding volume. CA and NaHS produced similar changes in urodynamic parameters after disruption of the urothelial barrier with protamine sulfate. NaHS also induced calcium responses in TRPA1-expressing CHO cells, but not in untransfected cells. CONCLUSIONS: The expression of TRPA1 on C-fibre bladder afferents and urothelial cells together with the finding that intravesical TRPA1 activators initiate detrusor overactivity indicate that TRPA1 may have a role in sensory transduction in this organ. The study also highlights H(2)S as a TRPA1 activator potentially involved in inflammatory bladder disease.

PMID: 18031925 [PubMed - indexed for MEDLINE]

[Botulinum toxin for the treatment of overactive bladder--an overview]

Urologe A. 2008 Jan;47(1):46-53

Authors: Seif C, Boy S, Wefer B, Dmochowski R, Braun PM, Jünemann KP

This article shall give a state-of-the-art review about the treatment of neurogenic and idiopathic detrusor overactivity with botulinum toxin injections into the detrusor muscle. We searched PubMed for original articles up to December 2006. Abstracts published at international congresses were also considered if they provided substantial new information. Based on this review it appears that a majority of patients with spinal cord injury regains continence after botulinum toxin A injection and that in children with myelomeningocele a significant improvement in continence can also be achieved. A concomitant reduction of intravesical pressure protects the upper urinary tract in these patients. In idiopathic detrusor overactivity, injection of botulinum toxin A also resulted in improvement of continence and reduction of daily micturition frequency. For both indications a high success rate could be achieved with an average duration of the effect of 6 months. Repeated injections into the detrusor seem to have no adverse effects in terms of duration or strength of the effect. Side effects were marginal and systemic side effects were experienced only in individual cases; in some patients with idiopathic detrusor overactivity intermittent self-catheterization was required. Overall intradetrusor injections of botulinum toxin seem to be a new, highly effective, and safe alternative in the treatment of neurogenic and idiopathic detrusor overactivity.

PMID: 18034331 [PubMed - indexed for MEDLINE]

Gemcitabine in bladder cancer.

Expert Opin Pharmacother. 2007 Dec;8(18):3251-6

Authors: El Karak F, Flechon A

Gemcitabine, a deoxycytidine analogue, is an inhibitor of DNA synthesis. With myelosupression being its most serious toxicity, gemcitabine has, however, a favourable toxicity profile. It was tested in urothelial bladder cancer at different stages of the disease. In superficial Bacillus Calmette-GuErin (BCG)-resistant bladder cancer as well as in BCG-intolerant patients, intravesical gemcitabine instillation has demonstrated a significant activity. In the adjuvant setting, the combination of gemcitabine and cisplatin (GC) has proved to be a feasible protocol. In locally advanced and metastatic disease, GC is admitted as a standard alternative first-line regimen. Gemcitabine is also an interesting choice for unfit patients when used as a single treatment or in combination with other chemotherapeutic agents as carboplatin or taxanes. This article reviews most of the studies performed in order to promote the usefulness of gemcitabine in bladder cancer.

PMID: 18035967 [PubMed - indexed for MEDLINE]

The best treatment for high-grade T1 bladder cancer is cystectomy.

Urol Oncol. 2007 Nov-Dec;25(6):523-5

Authors: Skinner EC

OBJECTIVES: To evaluate the role of initial cystectomy in the management of high-grade T1 bladder cancer. METHODS: A selected review of the literature was performed to evaluate outcomes with intravesical therapy vs. initial cystectomy in this patient population, with a focus on identifying risk factors for failure of conservative therapy. RESULTS: Many studies in the literature fail to include central pathologic review and re-TUR clinical staging, and there are no randomized studies comparing outcomes with these two initial approaches. Retrospective studies of patients with high-grade T1 tumors treated with initial intravesical therapy suggest that approximately 30% of patients will ultimately require cystectomy, and 30% will die of their disease with or without cystectomy. The risk of progression continues for the life of the patient, and late recurrence and progression is common. Initial clinical and pathologic factors can be identified that predict a high risk of progression and are reasonable indicators for initial cystectomy. CONCLUSION: Radical cystectomy can provide a very high cure rate for these patients and should be considered early in the treatment plan.

PMID: 18047965 [PubMed - indexed for MEDLINE]

Effects of intravenously and orally administered solifenacin succinate (YM905) on carbachol-induced intravesical pressure elevation and salivary secretion in mice.

Biol Pharm Bull. 2007 Dec;30(12):2324-7

Authors: Okutsu H, Noguchi Y, Ohtake A, Suzuki M, Sato S, Sasamata M

Solifenacin succinate is a novel muscarinic receptor antagonist used for the treatment of overactive bladder (OAB). We investigated the effects of solifenacin by oral and intravenous administration on carbachol (CCh)-induced intravesical pressure (IVP) elevation and compared its efficacy with that on CCh-induced salivary secretion in anesthetized mice. Additionally, we also investigated the change in effects between single and repeated oral administration of solifenacin on CCh-induced IVP elevation. Results showed that intravenous administration of solifenacin dose-dependently inhibited the IVP elevation and salivary secretion. The ratio of bladder response to salivary response (ratio of ID(50) values) was 2.1. Oral administration of solifenacin (0.3-30 mg/kg) also inhibited CCh-induced IVP elevation and salivary secretion. Although inhibition of these responses by solifenacin (10, 30 mg/kg) was comparable at early time points (0.5 and 1 h after administration at 10 mg/kg and 0.5 to 2 h after administration at 30 mg/kg), inhibition of CCh-induced IVP elevation was stronger at later time points (2 to 8 h after administration at 10 mg/kg and 4 to 24 h after administration at 30 mg/kg). No significant difference in ID(50) values for IVP elevation was observed between single and repeated (11 d) oral administration of solifenacin (1-30 mg/kg), suggesting no change in efficacy on chronic administration. In conclusion, intravenous and oral solifenacin inhibits CCh-induced IVP elevation more potently than salivary secretion. These results provide further evidence for the clinical use of solifenacin as a promising therapeutic drug for OAB with a low incidence of dry mouth.

PMID: 18057720 [PubMed - indexed for MEDLINE]

Inhibitory effects of nicorandil, a K ATP channel opener and a nitric oxide donor, on overactive bladder in animal models.

BJU Int. 2008 Feb;101(3):360-5

Authors: Kamiyama Y, Muto S, Masuda H, Ide H, Ishizuka N, Saito K, Horie S

OBJECTIVES: To investigate the effects of nicorandil, an ATP-sensitive potassium (K(ATP)) channel opener with a nitric oxide (NO) donor property, on overactive bladder (OAB) in animal models. Nicorandil is currently used clinically to treat ischaemic heart disease. MATERIALS AND METHODS: Three animal OAB models were used: (i) C-fibre mediated bladder overactivity by infusion of a low concentration of acetic acid (AA) into the bladder in female Wistar rats; (ii) bladder outlet obstruction (BOO) created by partial urethral obstruction in female Wistar rats; and (iii) neuronal NO synthase (nNOS) knockout (KO) mice with urinary frequency. The effects of nicorandil and KRN2391, both of which act as K(ATP) channel openers and NO donors, on the OAB models were examined. RESULTS: Cystometry showed that intravesical instillation of nicorandil and KRN2391 successfully inhibited OAB induced by intravesical instillation of AA. In the BOO model compared with untreated BOO rats, both nicorandil (1 and 3 mg/kg, orally) and KRN2391 (1 mg/kg, orally) significantly reduced the voiding frequency. Compared with wild-type mice, nNOS KO mice had urinary frequency with no change in the total urine volume. Nicorandil (3 mg/kg, orally) and KRN2391 (1 mg/kg, orally) significantly reduced the voiding frequency in nNOS KO mice. CONCLUSIONS: Our in vivo results show that nicorandil, a K(ATP) channel opener with a NO donor property, can suppress OAB from both neurogenic and myogenic causes. Nicorandil appears to be a promising candidate for clinical use in patients with OAB.

PMID: 18070173 [PubMed - indexed for MEDLINE]

Activity of different phospholipids in attenuating hyperactivity in bladder irritation.

BJU Int. 2008 Mar;101(5):627-32

Authors: Tyagi P, Chancellor M, Yoshimura N, Huang L

OBJECTIVE: To evaluate the effect of liposomes prepared from various natural and synthetic lipids in a rat bladder injury model in the absence or the presence of cholesterol and to elucidate the key structural elements necessary for the efficacy of liposomes required for alleviating bladder hyperactivity. MATERIALS AND METHODS: The intravesical pressure was recorded using a transurethral catheter in adult female Sprague-Dawley rats anaesthetized with urethane (1.0 g/kg subcutaneously). Continuous cystometrograms (CMGs) were obtained by slowly filling the bladder with solutions of varying compositions after obtaining a baseline CMG with saline. Rat urothelium was injured with protamine sulphate (PS) and irritated by subsequent infusion of KCl (500 mm) for 1 h. Thereafter, liposomes prepared in KCl using several natural and synthetic phospholipids were infused for 2 h. The percentage reduction in bladder contraction frequency (BCF) was used as a comparative variable for judging the activity of different phospholipids. RESULTS: Exposure of rat bladder to sequential infusion of PS and KCl increased its BCF and empty liposomes of uncharged zwitterionic phospholipids markedly attenuated the PS-induced irritation and decreased the raised BCF. But empty liposomes prepared with either cationic or anionic charged lipids were not able to achieve the same effect. Addition of cholesterol did not significantly increase their efficacy. Optimal efficacy of liposomes was achieved with phosphatidylcholines with longer acyl chains and saturation in only one of the two acyl chains. CONCLUSIONS: These in vivo studies show that phospholipids attenuate the bladder irritation from KCl after PS-induced bladder injury.

PMID: 18070198 [PubMed - indexed for MEDLINE]

Prevention of recurrence with epirubicin and lactobacillus casei after transurethral resection of bladder cancer.

J Urol. 2008 Feb;179(2):485-90

Authors: Naito S, Koga H, Yamaguchi A, Fujimoto N, Hasui Y, Kuramoto H, Iguchi A, Kinukawa N,

PURPOSE: A prospective, randomized, controlled trial was done to evaluate whether oral administration of a preparation of the probiotic agent Lactobacillus casei (Yakult Honsha, Tokyo, Japan) could enhance the prevention of recurrence by intravesical instillation of epirubicin after transurethral resection for superficial bladder cancer. MATERIALS AND METHODS: Between August 1999 and December 2002, 207 patients clinically diagnosed with superficial bladder cancer were included as study candidates and underwent transurethral resection, followed by intravesical instillation of 30 mg epirubicin/30 ml saline twice during 1 week. After histological confirmation of superficial bladder cancer they were again included as study participants with 102 randomized to receive treatment with 6 additional intravesical instillations of epirubicin during the 3-month period after transurethral resection (epirubicin group) and 100 randomized to intravesical chemotherapy on the same schedule as the epirubicin group plus oral administration of 3 gm Lactobacillus casei preparation per day for 1 year (epirubicin plus Lactobacillus casei group). Patients were evaluated for intravesical recurrence, disease progression, prognosis and adverse drug reactions. RESULTS: The 3-year recurrence-free survival rate was significantly higher in the epirubicin plus Lactobacillus casei group than in the epirubicin group (74.6% vs 59.9%, p = 0.0234), although neither progression-free nor overall survival differed between the groups. The incidence of adverse drug reactions did not significantly differ between the groups and there were no serious adverse drug reactions. CONCLUSIONS: Intravesical instillation of epirubicin plus oral administration of Lactobacillus casei preparation is a novel, promising treatment for preventing recurrence after transurethral resection for superficial bladder cancer.

PMID: 18076918 [PubMed - indexed for MEDLINE]

Intravesical botulinum toxin type A in chronic interstitial cystitis: results of a pilot study.

Surgeon. 2007 Dec;5(6):331-3

Authors: Ramsay AK, Small DR, Conn IG

AIM: To assess the efficacy of intravesical botulinum toxin type A (BTX-A) in interstitial cystitis (IC). METHODS: Eleven patients with IC were injected with BTX-A. Primary outcome measures were: Bristol Female Lower Urinary Tract Symptom Score, Kings Health Questionnaire and 24-hour frequency-volume chart. They had urodynamics done before and six weeks after injection. Detrusor contractility was assessed using the modified PIP1 (projected isovolumetric detrusor pressure).

PMID: 18080606 [PubMed - indexed for MEDLINE]

Mycobacterium bovis abdominal aortic and femoral artery aneurysms following intravesical bacillus Calmette-Guérin therapy for bladder cancer.

Cardiovasc Pathol. 2010 Mar-Apr;19(2):e29-32

Authors: Costiniuk CT, Sharapov AA, Rose GW, Veinot JP, Desjardins M, Brandys TM, Suh KN

BACKGROUND: Infectious complications of intravesical bacillus Calmette-Guérin (BCG) therapy are rare, but these have included a handful of cases of mycotic aneurysm. METHODS AND RESULTS: We present the case of a patient with a ruptured abdominal aortic aneurysm and a femoral artery aneurysm who had previously received intravesical BCG therapy for bladder carcinoma. Histopathologic examination of resected tissue revealed numerous acid-fast bacilli, and subsequent mycobacterial culture of blood and resected tissue revealed BCG strain Mycobacterium bovis. CONCLUSIONS: Clinicians should be aware of the possible extravesical complications, albeit rare, of BCG therapy. Therapy should consist of combined medical and surgical management.

PMID: 19026573 [PubMed - indexed for MEDLINE]

Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins.

BMC Cancer. 2007;7:204

Authors: Saban MR, Hellmich HL, Simpson C, Davis CA, Lang ML, Ihnat MA, O'Donnell MA, Wu XR, 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 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 repeated intravesical BCG therapy. METHODS: Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH). Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR) was used to validate SSH-selected transcripts. RESULTS: Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH) and representatives of two IFNgamma-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5) and the p47GTPases (IIGTP1, IIGTP2, and TGTP). Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2), SPRR2G, GSTM5, and RSP 19. CONCLUSION: Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially serving to mount a resistance to the replication of the Mycobacterium. It will be of tremendous future interest to determine whether these immune response cascades play a role in the anti-cancer effects exerted by BCG.

PMID: 17980030 [PubMed - indexed for MEDLINE]

The effectiveness of intravesical oxybutynin, propantheline, and capsaicin in the management of neuropathic bladder following spinal cord injury.

ScientificWorldJournal. 2007;7:1683-90

Authors: George J, Tharion G, Richar J, Macaden AS, Thomas R, Bhattacharji S

The objective of this study was to compare the therapeutic response of intravesical oxybutynin, propantheline, and capsaicin in the treatment of neurogenic detrusor overactivity. Carried out in the Department of Physical Medicine and Rehabilitation at a university teaching hospital in India, patients acted as their own controls. Oxybutynin 5 mg in solution or propantheline 15 mg in solution and capsaicin were instilled intravesically in each patient. Urodynamic studies were done before and after the intravesical instillation of each drug. The nonparametric tests were used for statistical analysis. The efficacy of intravesical capsaicin in the treatment of neurogenic detrusor overactivity was statistically significant for reflex volume (RV) (p = 0.018), cystometric capacity (CC) (p = 0.0440), leak volume (LV) (p = 0.000), and leak frequency (LF) (p = 0.009). The Kruskal-Wallis test for paired sample comparing pre- and post-LV and LF for intravesical capsaicin was significant at 2nd week (p = 0.002 and 0.054, respectively). There was a significant difference in therapeutic response between intravesical oxybutynin, propantheline, and capsaicin in the treatment of detrusor overactivity for LV and LF at 2nd week (p = 0.017 and 0.003, respectively). When comparing responses of oxybutynin and propantheline, more subjects demonstrated improvement with intravesical propantheline than oxybutynin for RV, detrusor leak point pressure (LPP), clean intermittent catheterization volume (CICV), and LV. This study suggests that intravesical agents may be used as effective adjuvants in the management of incontinence due to neurogenic detrusor overactivity following spinal cord injury.

PMID: 17982563 [PubMed - indexed for MEDLINE]

Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: a translational study.

Br J Cancer. 2007 Dec 3;97(11):1499-504

Authors: Gunelli R, Bercovich E, Nanni O, Ballardini M, Frassineti GL, Giovannini N, Fiori M, Pasquini E, Ulivi P, Pappagallo GL, Silvestrini R, Zoli W

Intravesical gemcitabine (Gem) has shown promising activity against transitional cell carcinomas (TCC) of the bladder, with moderate urinary toxicity and low systemic absorption. The present phase II study evaluated the activity of biweekly intravesical treatment with Gem using a scheme directly derived from in vitro preclinical studies. Patients with Bacille Calmette-Guérin (BCG) -refractory Ta G3, T1 G1-3 TCC underwent transurethral bladder resection and then intravesical instillation with 2000 mg Gem diluted in 50 ml saline solution on days 1 and 3 for 6 consecutive weeks. Thirty-eight (95%) of the 40 patients showed persistent negative post-treatment cystoscopy and cytology 6 months after Gem treatment, while the remaining 2 patients relapsed at 5 and 6 months. At a median follow-up of 28 months, recurrences had occurred in 14 patients. Among these, four had downstaged (T) disease, three had a lower grade (G) lesion and three had a reduction in both T and G. Urinary and systemic toxicity was very low, with no alterations in biochemical profiles. In conclusion, biweekly instillation of Gem proved active in BCG-refractory Ta G3, T1 G1-3 TCC. Our results highlight the importance of preclinical studies using in vitro systems that adequately reproduce the conditions of intravesical clinical treatment to define the best therapeutic schedule.

PMID: 17987035 [PubMed - indexed for MEDLINE]

Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update.

J Urol. 2007 Dec;178(6):2314-30

Authors: Hall MC, Chang SS, Dalbagni G, Pruthi RS, Seigne JD, Skinner EC, Wolf JS, Schellhammer PF

PMID: 17993339 [PubMed - indexed for MEDLINE]

A single instillation of epirubicin after transurethral resection of bladder tumors prevents only small recurrences.

J Urol. 2008 Jan;179(1):101-5; discussion 105-6

Authors: Berrum-Svennung I, Granfors T, Jahnson S, Boman H, Holmäng S

PURPOSE: We studied whether a single instillation of epirubicin after transurethral bladder tumor resection would influence the interval to and size of the first recurrence. MATERIALS AND METHODS: A total of 404 patients from 13 hospitals were randomized to 1 instillation of 50 mg epirubicin or placebo within 6 hours after transurethral resection of bladder tumors. RESULTS: Of 155 evaluable patients in the epirubicin group 79 (51.0%) had recurrence compared to 95 of 152 (62.5%) in the placebo group (p = 0.04). Of the recurrences 63.3% were small (1 to 5 mm). Tumor size was unknown in 5 patients. Of 79 patients with recurrence in the epirubicin arm 33 (42.9%) vs 29 (31.5%) of 95 in the placebo arm had larger (more than 5 mm) first recurrences (p = 0.12). Approximately half of the patients with first recurrences were treated as outpatients and the other half spent a total of 145 days in the hospital with no difference between the groups. CONCLUSIONS: We confirmed the results of previous studies showing that 8.5 patients must be treated with a single instillation to prevent 1 recurrence. Furthermore, our data may indicate that only small recurrences are prevented, which could easily be fulgurated using local anesthesia at followup cystoscopy. The benefit of single instillations can be questioned if this finding is confirmed by others.

PMID: 17997459 [PubMed - indexed for MEDLINE]

Levobupivacaine intravesical injection for superficial bladder tumor resection--possible, effective, and durable. Preliminary clinical data.

Int Urol Nephrol. 2008;40(3):637-41

Authors: Stravodimos KG, Mitropoulos D, Salvari A, Lampadariou A, Kapetanakis T, Zervas A

BACKGROUND: General and spinal anesthesia are currently in widespread use during transurethral bladder tumor resection. However, local anesthetic methods are claimed to provide sufficient intra-operative analgesia and satisfactory post-operative pain management. We evaluated whether local levobupivacaine infiltration of the tumor would result in outcomes, in terms of intra-operative analgesia, similar to those for utilization of general anesthesia. Post-operative analgesia and patient satisfaction were also assessed. PATIENTS AND METHODS: Twenty patients with recurrent solitary bladder tumors were randomly allocated in two groups. Group A, underwent tumor resection under general anesthesia and group B was treated with resection after local levobupivacaine infiltration. Post-operative analgesia was evaluated with utilization of a visual analogue scale, ranging from 0 to 10, with higher scores indicating more intense pain perception. RESULTS: Group A patients demonstrated significantly lower visual analogue scale scores at t=0, which peaked at 4 h post-operatively. Group B scores were higher at t=0, declined over a 2 h interval and reached zero after t=4 h. Patients younger than 60 years and women benefitted more. Local anaesthesia was the method of pain control preferred by 90% of patients. CONCLUSION: Local levobupivacaine infiltration for transurethral bladder tumor resection seems feasible, providing intra and post-operative pain control. In this preliminary setting, general anesthesia provided a higher level of pain control in the immediate post-operative period (<4 h) while local levobupivacaine infiltration demonstrated excellent late post-operative analgesia (>4 h). Also, patients seem to prefer local to general anesthesia in future surgery.

PMID: 17999160 [PubMed - indexed for MEDLINE]

Safety and efficacy of the use of intravesical and oral pentosan polysulfate sodium for interstitial cystitis: a randomized double-blind clinical trial.

J Urol. 2008 Jan;179(1):177-85

Authors: Davis EL, El Khoudary SR, Talbott EO, Davis J, Regan LJ

PURPOSE: We examined the safety and the efficacy of a combination of intravesical and oral pentosan polysulfate sodium in comparison to only oral pentosan polysulfate sodium in treating interstitial cystitis. MATERIALS AND METHODS: A total of 41 females diagnosed with interstitial cystitis were randomized to receive a combination of intravesical pentosan polysulfate sodium plus oral pentosan polysulfate sodium (21 in treatment group) or intravesical placebo plus oral pentosan polysulfate sodium (20 in placebo group) for 6 weeks. All subjects continued to receive oral pentosan polysulfate sodium for another 12 weeks. The primary outcome was the change in the O'Leary-Sant Interstitial Cystitis Symptoms/Problem Index from baseline to week 6, 12, and 18. Other outcomes included: the changes in Pelvic Pain and Urgency Frequency questionnaire, Health Related Quality of Life index: SF-36, pain scale, urgency scale, voiding log, patient global assessment, and sexual function scales. RESULTS: The change in the total score of O'Leary-Sant Interstitial Cystitis Symptoms/Problems Index from baseline to week 12 among the treatment group (median -12 or approximately a 46% reduction) was significantly greater compared to the placebo group (median -5.5 or approximately a 24% reduction, p = 0.04). At week 18 the treatment group showed statistically significant improvement in all Health Related Quality of Life domains compared to the baseline (p < or = 0.01), while the placebo group showed significant improvement in only 3 Health Related Quality of Life domains, (p < or = 0.05) compared to the baseline. There were no significant differences within major categories of adverse events between treated and placebo groups. CONCLUSIONS: The use of intravesical pentosan polysulfate sodium simultaneously with oral pentosan polysulfate sodium is a safe and effective therapeutic option. These findings will open a new option for patients with interstitial cystitis to reduce their severely devastating symptoms and to improve their quality of life and well-being.

PMID: 18001798 [PubMed - indexed for MEDLINE]

Reactive oxygen species mediate detrusor overactivity via sensitization of afferent pathway in the bladder of anaesthetized rats.

BJU Int. 2008 Mar;101(6):775-80

Authors: Masuda H, Kihara K, Saito K, Matsuoka Y, Yoshida S, Chancellor MB, de Groat WC, Yoshimura N

OBJECTIVES: To investigate the effects of reactive oxygen species (ROS) on the micturition reflex in vivo, especially in bladder afferent signalling in rats, as several pathophysiological conditions in the urinary bladder (e.g. ischaemia/reperfusion and inflammation) are characterized by the formation of ROS. MATERIALS AND METHODS: Adult female Sprague-Dawley rats under urethane anaesthesia (normal or pretreated with 125 mg/kg capsaicin, subcutaneously, 4 days before) were assessed by continuous cystometrography (CMG) with or without the intravesical administration of H(2)O(2) (0.003-3%) to stimulate ROS damage. To investigate the mechanism of H(2)O(2), catalase (a H(2)O(2) scavenger) was applied intravesically (2000 IU/mL), or rats were given intravenous injections with superoxide dismutase (SOD, 20,000 IU/kg, a superoxide anion scavenger), dimethylthiourea (DMTU, 100 mg/kg, a hydroxyl radical scavenger), deferoxamine (20 mg/kg, an iron-chelator that prevents the formation of hydroxyl radical), indomethacin (3 mg/kg, a cyclooxygenase inhibitor) or ketoprofen (1 mg/kg, a cyclooxygenase inhibitor) just before or during the intravesical administration of H(2)O(2). Prostaglandin (PG) levels (PGE(2) and 6-keto-PGF(1 alpha)) were measured in the bladder of rats treated with intravesical 0.3% H(2)O(2) for 30 min with or without indomethacin. RESULTS: Intravesical administration of H(2)O(2) induced detrusor overactivity, as shown by a reduction in the mean (sem) intercontraction interval (ICI), in a dose-dependent manner in normal rats (0.3% H(2)O(2,) P < 0.01, 36.2 (4.7)% of the control ICI). H(2)O(2)-induced detrusor overactivity was almost abolished by catalase and significantly suppressed by DMTU, deferoxamine, capsaicin pretreatment, indomethacin or ketoprofen but not by SOD. The level of PGs was significantly increased by H(2)O(2) instillation, and indomethacin significantly inhibited the increase in PGs. CONCLUSION: These results indicate that oxidative stress induced by H(2)O(2) activates capsaicin-sensitive C-fibre afferent pathways, at least in part, mediated via stimulation of the cyclooxygenase pathway, thereby inducing detrusor overactivity. Thus, rats treated with intravesical H(2)O(2) appear to be a suitable model for the study of detrusor overactivity.

PMID: 18005207 [PubMed - indexed for MEDLINE]

Intravesical treatments for painful bladder syndrome/ interstitial cystitis.

Cochrane Database Syst Rev. 2007;(4):CD006113

Authors: Dawson TE, Jamison J

BACKGROUND: Painful Bladder Syndrome/Interstitial Cystitis (PBS/IC) occurs predominantly in women. It is a poorly-understood condition with symptoms of bladder pain, urinary frequency, urgency and nocturia. Treatments for PBS/IC include dietary/lifestyle interventions, oral medication, intravesical instillations and, in some cases, surgery. Success rates are generally modest and there is little consensus as to the best form of treatment for this condition. OBJECTIVES: To assess the effectiveness of intravesical treatment for PBS/IC. SEARCH STRATEGY: We searched the Cochrane Incontinence Group specialised trials register (30 May 2006) as well as reference lists of all selected trials. Recognised researchers in the field were contacted for any additional relevant material. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials were included in the review if they had recruited participants with a clinical diagnosis of PBS/IC and if at least one arm of the trial was treatment with an intravesical preparation. Outcome measures were pre-determined, the primary ones being the effect on pain and bladder capacity. Others included symptomatic response to treatment, quality-of-life assessment, economic factors and adverse events. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality, then extracted relevant data from the studies. MAIN RESULTS: Nine eligible trials were identified - six parallel group, one incomplete cross-over and two cross-over trials - with a total of 616 participants. Six trials compared an 'active' instillation with placebo instillation, two compared different types of instillation, and one was a comparison of an instillation plus bladder training versus bladder training alone. Altogether, the review included trials of six different types of intravesical instillation: Resiniferatoxin, Dimethyl sulfoxide, BCG, pentosanpolysulphate, oxybutin, and alkalinisation of urine pH. Confidence intervals were generally wide. Resiniferatoxin was not associated with sustained differences in the review outcomes reported but pain during instillation and withdrawal from treatment was significantly more common. The data available about Dimethyl sulfoxide (DMSO) were very limited but with no apparent differences from placebo. Groups treated with BCG tended to report less pain and fewer general symptoms. Although adverse events were commonly reported, these were no more common after BCG than after placebo instillation. The few data about Pentosanpolysulphate tended to favour the actively treated, but with wide confidence intervals; there was little information about adverse events. Oxybutinin instillation was associated with increased bladder capacity, reduced frequency, improved quality of life scores and fewer drop-outs. Alkalinisation of urine pH did not make any clear difference, but with potentially wide confidence intervals. AUTHORS' CONCLUSIONS: Overall, the evidence base for treating PBS/IC using intravesical preparations is limited and the potential for meta-analysis reduced by variation in the outcome measures used. The quality of trial reports was mixed and in some cases this precluded any meaningful data extraction. BCG and oxybutin are reasonably well-tolerated and evidence is most promising for these. Resiniferatoxin showed no evidence of effect for most outcomes and caused pain, which reduced treatment compliance. There is little evidence for the other treatments included in this review. Randomised controlled trials are still needed and study design should incorporate outcomes that are most relevant to these with PBS/IC and should be standardised.

PMID: 17943887 [PubMed - indexed for MEDLINE]

The expression level of ligands for natural killer cell receptors predicts response to bacillus Calmette-Guerin therapy: a pilot study.

J Urol. 2007 Dec;178(6):2660-4

Authors: Yutkin V, Pode D, Pikarsky E, Mandelboim O

PURPOSE: Up to 90% of patients with high grade superficial bladder tumors experience tumor recurrence and up to 50% have progression despite bacillus Calmette-Guerin treatment. Natural killer cells have a major role in the mechanism of the response to bacillus Calmette-Guerin but the exact mechanisms are still elusive. The recently discovered natural cytotoxicity receptors are linked to the host response to viral infection and to cancer. We tested the hypothesis that tumor expression of natural cytotoxicity receptor ligands can serve as a predictive factor for the response to intravesical bacillus Calmette-Guerin in patients with nonmuscle invasive, high grade bladder cancer. MATERIALS AND METHODS: We developed a histochemical staining method for analysis of the ligands of the 3 known natural cytotoxicity receptors NKp30, NKp44 and NKp46 using genetically engineered fusion proteins and an automated image analysis system. We examined formalin fixed, paraffin embedded sections of specimens of transurethral bladder tumor resection from patients with primary, nonmuscle invasive, high grade bladder cancer who were subsequently treated with bacillus Calmette-Guerin. We compared natural cytotoxicity receptor ligand expression to the response to bacillus Calmette-Guerin immunotherapy. RESULTS: Six of 17 patients (35%) had recurrence despite bacillus Calmette-Guerin treatment. Primary tumors from favorably responding patients expressed higher levels of ligands for all 3 fusion proteins (NKp30, NKp44 and NKp46 p = 0.0026, 0.027 and 0.044, respectively). CONCLUSIONS: Bacillus Calmette-Guerin resistant, high grade, nonmuscle invasive bladder tumors express significantly lower levels of ligands of all 3 natural cytotoxicity receptors compared with bacillus Calmette-Guerin responsive tumors. This suggests that down-regulation of these ligands facilitates escape from the bacillus Calmette-Guerin effect. Furthermore, analysis of ligand expression, which can be performed on formalin fixed, paraffin embedded sections, may serve as a new predictive assay for the response to bacillus Calmette-Guerin.

PMID: 17945285 [PubMed - indexed for MEDLINE]

Botulinum toxin type A in combination with standard urotherapy for children with dysfunctional voiding.

J Urol. 2007 Dec;178(6):2599-602; discussion 2602-3

Authors: Petronijevic V, Lazovic M, Vlajkovic M, Slavkovic A, Golubovic E, Miljkovic P

PURPOSE: We investigated the role of botulinum toxin type A and urotherapy in the treatment of children with dysfunctional voiding. MATERIALS AND METHODS: Nine female children with dysfunctional voiding refractory to standard urotherapy and alpha1-adrenergic blocking agents were included in the prospective clinical study. Botulinum toxin type A in a dose of 500 units was injected transperineally into the external urinary sphincter. Bladder rehabilitation was introduced 2 weeks after botulinum toxin type A treatment. Uroflow studies with ultrasound residual urine volumes were obtained before and 6 months after treatment. All children were tested before and 6 months after treatment using the empirically designed International Reflux Study in Children modified questionnaire. RESULTS: After treatment the mean +/- SD voided volume increased from 180 +/- 73 to 228 +/- 94 ml (p <0.05) while post-void residual urine volume decreased from 52 +/- 40 to 19 +/- 18 ml (p <0.05). Significant differences in other uroflowmetry parameters were not found. However, significant symptom score improvement was detected 6 months after treatment, being decreased by 7 vs 20 (p <0.01). No systemic side effects occurred following botulinum toxin type A injection. CONCLUSIONS: Our study demonstrates that the voiding mechanism in children with dysfunctional voiding refractory to standard therapy can be significantly improved and maintained at least 6 months after combined botulinum toxin type A injection and bladder rehabilitation.

PMID: 17945299 [PubMed - indexed for MEDLINE]

Botulinum-A toxin: solo treatment for neuropathic noncompliant bladder.

J Urol. 2007 Dec;178(6):2593-7; discussion 2597-8

Authors: Neel KF, Soliman S, Salem M, Seida M, Al-Hazmi H, Khatab A

PURPOSE: We investigated whether botulinum-A toxin is better used alone or in conjunction with oxybutynin chloride in the management of refractory neuropathic bladder. MATERIALS AND METHODS: Between March 2004 and February 2006 a total of 23 children (mean age 5.6 +/- 2.5 years) with neuropathic bladder refractory to medical treatment underwent cystoscopic treatment with botulinum-A toxin. Patients were randomly assigned postoperatively using closed envelopes (blind randomization) into 2 equal groups. Group 1 (12 patients) continued to receive anticholinergics while in group 2 (11 patients) anticholinergics were discontinued. Clinical and urodynamic evaluations were performed before injection, and at 1 and 6-month intervals. Patients were then followed every 6 months with urodynamic study. The outcomes were compared between groups with a paired t test (2-tailed) and a significant p value <0.025. RESULTS: Maximum bladder capacity increased from 96 +/- 67 (range 15 to 277) to 163 +/- 96 ml (range 50 to 500, p <0.001) and 142 +/- 65 ml (range 21 to 250, p <0.006) at 1 and 6 months, respectively. Maximal detrusor pressure decreased from 76 +/- 36 (range 36 to 209) to 50 +/- 22 cm H2O (range 20 to 100, p <0.001) and 51 +/- 21 cm H2O (range 18 to 104, p <0.001) at 1 and 6 months, respectively. From a clinical point of view 9 of the 16 incontinent patients (56.2%) showed complete continence after treatment while 4 (25%) reported mild to moderate improvement and 3 (18.8%) showed no improvement. None of the patients had side effects related to the procedure or the material used. CONCLUSIONS: We confirmed the beneficial use of botulinum-A toxin for the treatment of refractory neuropathic bladder and have not yet found any augmentative effect of oxybutynin chloride in this study group. Accordingly we can use such a modality as sole treatment for noncompliant neuropathic bladder.

PMID: 17945300 [PubMed - indexed for MEDLINE]

Prognostic factors in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin: multivariate analysis of data from four randomized CUETO trials.

Eur Urol. 2008 May;53(5):992-1001

Authors: Fernandez-Gomez J, Solsona E, Unda M, Martinez-Piñeiro L, Gonzalez M, Hernandez R, Madero R, Ojea A, Pertusa C, Rodriguez-Molina J, Camacho JE, Isorna S, Rabadan M, Astobieta A, Montesinos M, Muntañola P, Gimeno A, Blas M, Martinez-Piñeiro JA,

OBJECTIVES: To evaluate the prognostic factors of recurrence and progression after intravesical adjuvant bacillus Calmette-Guérin (BCG) immunotherapy in patients with non-muscle-invasive bladder tumors. METHODS: From February 1990 to May 1999, the Spanish Club Urológico Español de Tratamiento Oncológico (CUETO) group has performed four randomized phase 3 studies comparing different intravesical treatments in patients with noninvasive bladder cancer. Data from 1062 evaluable patients treated only with BCG were analyzed. Most patients received BCG once weekly for 6 consecutive weeks and a short-term BCG maintenance (once every 2 wk 6 times more). Associated tumor in situ (TIS) was found in 7.5% (n=80) of cases. There were 22.1% (n=235) patients with T1G3 tumors, 22.9% of whom (n=54) were associated with TIS. Stepwise multivariate Cox regression models with stratification by study and dose were used to assess the independent effect of predictive factors and hazard ratios (HRs) were estimated from the Cox model. RESULTS: Multivariate analysis demonstrated that female gender (HR=1.71) compared to male gender, recurrent tumors (HR=1.9) compared to primary tumors, multiplicity, and presence of associated TIS (HR=1.54) increased the risk of recurrence. Recurrent tumors (HR=1.62) compared to primary tumors, high-grade tumors (HR=5.64) compared to G1 tumors, T1 tumors (HR=2.15) compared to Ta tumors, and recurrence at 3-mo cystoscopy (HR=4.6) increased the risk of progression. CONCLUSION: Significant independent predictors for recurrence were female gender, history of recurrence, multiplicity, and presence of associated TIS. Age, history of recurrence, high grade, T1 stage, and recurrence at first cystoscopy were independent predictors of progression by multivariate Cox analysis.

PMID: 17950987 [PubMed - indexed for MEDLINE]

Long-term follow-up of intravesical bacillus Calmette-Guérin treatment for superficial transitional-cell carcinoma of the bladder involving the prostatic urethra.

Clin Genitourin Cancer. 2007 Sep;5(6):386-9

Authors: Taylor JH, Davis J, Schellhammer P

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) is a treatment option for superficial (5-year follow-up. PATIENTS AND METHODS: Twenty-eight patients with high-risk superficial bladder cancer and prostatic urethral involvement were treated with once-weekly BCG for 6 weeks. Patients with prostatic stromal involvement were excluded. Maintenance was not used before 1995. Currently, we use maintenance BCG after induction. Patients were followed by cystoscopy/cytology and repeat biopsy to detect persistent and/or progressive disease. RESULTS: After 1 or 2 courses of once-weekly BCG for 6 weeks, 64.3% (18 of 28 of patients) exhibited a complete response in the bladder and prostate at their 6-month followup. Of those obtaining a complete response, 55.6% (10 of 18) experienced recurrence. Three recurrences were in the prostate: 1 isolated and 2 associated with multifocal bladder involvement. Twenty-eight percent (8 of 28 patients) underwent cystectomy because of failure of treatment to eradicate superficial disease or disease progression. Disease-specific survival was 89% (25 of 28 patients) at a median follow-up of 7.5 years. CONCLUSION: Our long-term data support the durability of intravesical BCG in select patients with superficial bladder transitional cell carcinoma with prostatic urethral involvement. Follow-up biopsy of the prostatic urethra is mandatory and, if positive, cystectomy is indicated. One third of patients will require cystectomy for persistent or progressive disease; therefore, careful surveillance is critical.

PMID: 17956711 [PubMed - indexed for MEDLINE]

[Photodynamic diagnostic of superficial bladder carcinoma]

Dtsch Med Wochenschr. 2007 Nov;132(44):2332-5

Authors: Denzinger S, Rössler W, Otto W

Up to 50-70 % of superficial bladder carcinomas recur. To improve the surgical results of transurethral resection the photodynamic diagnostic with 5-aminolevulinic acid is used. 5-aminolevulinic acid specifically accumulates in malignant cells leading to fluorescence under blue light cystoscopy. After intravesical instillation before transurethral resection also lesions like Carcinoma in situ, hardly to recognize in conventional cystoscopy, are noticed due to their fluorescence. Thus a significantly higher number of tumors can be diagnosed and resected. Also the recurrence rate decreases statistically significant. Long-term results with 5-aminolevulinic acid showed recurrence-free survival rates of 71 % versus 45 % after conventional transurethral resection under conventional white light. A recent cost analysis showed that photodynamic diagnostic reduces the number of stays in hospital thus also leading to cost reduction. Because of 18,000 newly diagnosed diseases in Germany per year this could result in remarkable saving possibilities of the health system.

PMID: 17957598 [PubMed - indexed for MEDLINE]

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]

Granulomatous renal masses following intravesical bacillus Calmette Guérin therapy: the central unaffected calyx sign.

Br J Radiol. 2007 Oct;80(958):e230-3

Authors: Senés AT, Badet L, Lyonnet D, Rouvière O

A 67-year-old man with a history of melanoma, treated surgically 7 years before, was referred for vomiting and right flank pain after three intravesical instillations of bacillus Calmette-Guérin (BCG) for superficial bladder cancer. A CT scan showed a mass on the right kidney, with a normal calyx in its centre. Percutaneous biopsy, obtained because of melanoma history, showed granulomatous reaction caused by BCG infection. The renal mass disappeared after 9 months of anti-tuberculous treatment. The presence of an unaffected calyx in the centre of the renal mass is an interesting finding for both teaching purposes--it clearly illustrates the pathogeny of the disease, with the bacillus invading the renal parenchyma through the papilla--and diagnostic purposes--a malignant tumour is likely to displace or destroy neighbouring calyces rather than leaving them unaffected. However, the diagnostic value of this sign remains to be determined by further research.

PMID: 17959911 [PubMed - indexed for MEDLINE]