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Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin.

OBJECTIVES: To study TRPV1 immunoreactivity in the urothelium of patients with neurogenic detrusor overactivity (NDO) before and after treatment with resiniferatoxin (RTX) and controls. Functional capsaicin TRPV1 receptors have been demonstrated in urothelial cells of rodent urinary bladder, and TRPV1-knockout mice exhibit diminished nitric oxide and stretch-evoked adenosine triphosphate release from urothelial cells. In patients with NDO, TRPV1 suburothelial nerve density is increased, which is reversed by successful treatment with intravesical RTX. However, the role of urothelial TRPV1 in human bladder disorders is unknown. METHODS: Flexible cystoscopic bladder biopsies were obtained from 14 patients with NDO before and after treatment with RTX and from 8 control patients. Using a specific antibody for immunostaining, TRPV1 immunoreactivity in the urothelium was quantified by image analysis. RESULTS: TRPV1 immunoreactivity was observed in basal and apical urothelial cells. Basal cell layer TRPV1 immunoreactivity was significantly increased in NDO compared with control bladders (P = 0.003). In 5 patients who responded clinically to RTX, basal cell layer and total urothelial TRPV1 immunoreactivity decreased significantly after treatment (P = 0.032 and P = 0.016, respectively). The decreases in the basal cell layer TRPV1 immunoreactivity after RTX were comparable to the decreases in suburothelial TRPV1 nerve fibers in the biopsies previously studied from the same patients. CONCLUSIONS: Increased urothelial TRPV1 in patients with NDO may play a role in the pathophysiology, in concert with increased TRPV1 nerve fibers. Although it is not known whether similar pathogenic mechanisms are involved in the increase of urothelial and neuronal TRPV1, both may be targeted by successful RTX therapy.

Administration, Intravesical↗

Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis.

OBJECTIVES: To compare the current recommended dose of pentosan polysulfate sodium (PPS) with doses two to three times higher. METHODS: We evaluated three dosages (300, 600, and 900 mg) of PPS in a randomized, double-blind, double-dummy, parallel-group, multicenter, 32-week study. Adults (n = 380) with a diagnosis of interstitial cystitis (IC) as determined by a positive cystoscopic examination combined with bladder pain and urgency or a history of IC symptoms for at least 6 months were enrolled. Participants completed the Patient's Overall Rating of Symptom Index (PORIS) and the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) at baseline (ICSI only) and during follow-up visits at 4, 8, 12, 16, 24, and 32 weeks. RESULTS: Mean ICSI scores improved significantly during the 32 weeks for all dosages (baseline 11.2, 11.9, and 11.9 to endpoint 8.2, 8.1, 8.6 for 300, 600, and 900 mg, respectively; P <0.001) but the response to treatment was not dose dependent (no statistically significant difference in response among the three dosages). At baseline, 3.2%, 62.2%, and 34.6% reported mild, moderate, and severe symptoms, respectively, as assessed by the ICSI. At study end, 27.5%, 56.9%, and 15.7% reported mild, moderate, and severe symptoms, respectively. The PORIS scores improved within 4 weeks with 15.8% to 21.1% of all patients classified as responders (50% or greater improvement on PORIS). At 32 weeks, 49.6%, 49.6%, and 45.2% of all patients were responders at a dose of 300, 600, and 900 mg, respectively. Most adverse events were mild and resolved without intervention. CONCLUSIONS: For all three dosages of PPS, a clinically significant but similar response was demonstrated. The duration of therapy appears to be more important than the dosage.

Adolescent↗

Combined radical prostatectomy and bladder augmentation for concomitant prostate cancer and detrusor instability.

OBJECTIVES: To determine the outcomes of a select cohort of patients with severe voiding dysfunction, refractory to medical management, and a concomitant diagnosis of prostate cancer, who were treated with radical prostatectomy and augmentation enterocystoplasty. METHODS: Four men with biopsy-proven prostatic adenocarcinoma, as well as a diagnosis of severe overactive bladder, underwent combined radical retropubic prostatectomy and augmentation enterocystoplasty. All patients underwent fluorourodynamic testing confirming nonobstructive detrusor instability or hyperreflexia. Three patients underwent nerve-sparing radical retropubic prostatectomy with a clamshell ileocystoplasty, and one with neurogenic hyperreflexia underwent sigmoid cystoplasty with a continent catheterizable stoma at radical retropubic prostatectomy. RESULTS: The mean follow-up was 21.5 months (range 8 to 48). All patients had an undetectable prostate-specific antigen level postoperatively. The average hospitalization was 8 days. Perioperative complications occurred in 2 patients, including a prolonged urine leak managed with catheter drainage and postoperative hematuria requiring cystoscopic clot evacuation. Erectile function was preserved in 2 patients with good preoperative erections. At last follow-up, the 3 patients who voided per urethra had minimal postvoid residual urine volumes and maintained good continence, with only 1 patient describing occasional mild stress incontinence. At last follow-up, the patient with the sigmoid cystoplasty catheterized every 4 hours with volumes of about 300 mL and complete stomal continence. No patient required anticholinergic medications postoperatively. CONCLUSIONS: The concomitant diagnosis of prostate cancer and severe detrusor instability may be difficult to treat. The results of our study have shown that for those desiring surgical management for their prostate cancer, a combined bladder augmentation and radical prostatectomy may be performed with minimal added morbidity and significantly improved voiding function in the properly selected individual.

Adenocarcinoma↗

Assessment of fiberoptic near-infrared raman spectroscopy for diagnosis of bladder and prostate cancer.

OBJECTIVES: To determine whether a fiberoptic Raman system, suitable for in vivo use, is able to differentiate between benign and malignant bladder and prostate pathologic findings in vitro. Raman spectroscopy is an optical technique that provides a measure of the molecular composition of tissue by analyzing the way that tissue scatters laser light. Laboratory studies have shown that the technique can be used to identify and characterize transitional cell carcinoma and prostate adenocarcinoma in vitro. METHODS: A total of 220 Raman spectra were recorded from 29 snap-frozen bladder samples collected at cystoscopic procedures, and 197 Raman spectra were recorded from 38 snap-frozen prostate samples collected at transurethral resection of the prostate. The spectra were correlated with the histologic features and used to construct separate diagnostic algorithms for the bladder and prostate. These algorithms were tested as to their ability to determine the pathologic finding of a sample from its Raman spectrum. RESULTS: The bladder algorithm was able to differentiate benign samples (normal and cystitis) from malignant samples (transitional cell carcinoma), with an overall accuracy of 84%. The prostate algorithm was able to differentiate benign samples (benign prostatic hyperplasia and prostatitis) from malignant samples (prostate cancer), with an overall accuracy of 86%. CONCLUSIONS: The results of this study have demonstrated that the clinical Raman system can provide an accurate and objective method to diagnose prostate and bladder cancer in vitro. Because the Raman probe is suitable for use during endoscopic, laparoscopic, or open procedures, this work paves the way for in vivo studies.

Adenocarcinoma↗

Outpatient laparoscopic pyeloplasty.

OBJECTIVES: To assess the feasibility of ambulatory laparoscopic pyeloplasty. Laparoscopic pyeloplasty aims to reproduce the excellent functional outcomes of open pyeloplasty while diminishing procedural morbidity. METHODS: Six patients fulfilled specific inclusion criteria for outpatient laparoscopic pyeloplasty: informed consent, body mass index of 40 kg/m2 or less, primary ureteropelvic junction obstruction, uncomplicated laparoscopic surgery completed by 12:00 pm, and postoperative pain control by oral analgesics. All patients had a double-J ureteral stent placed cystoscopically before laparoscopic access. No drains were placed postoperatively. RESULTS: All 6 patients successfully underwent laparoscopic dismembered pyeloplasty (3 left, 3 right) using the retroperitoneal (n = 5) or transperitoneal (n = 1) approach. The average patient age was 22 years. The mean surgical time was 223 minutes (range 165 to 270), the mean blood loss was 82 mL (range 10 to 250), and the mean postoperative hospital stay was 359 minutes (range 226 to 424). Postoperative analgesia comprised a mean of 6 mg morphine sulfate and 32 mg of ketorolac. No complications or readmissions occurred postoperatively. Intravenous urography and Lasix technetium-99m mercaptoacetyltriglycine renal scans documented resolution of obstruction. With long-term follow-up (mean 38.4 months), no recurrences have developed. CONCLUSIONS: We report our initial series of ambulatory laparoscopic pyeloplasty. In this well-selected patient population, outpatient pyeloplasty was feasible and safe.

Adolescent↗

Intravesical hydatid cyst.

A case of intravesical hydatid cyst is reported. The cyst was completely evacuated cystoscopically with intravesical instillation of a scolicidal agent (hydrogen peroxide) to destroy scolices and daughter cysts. The postoperative course was uneventful, and follow-up did not show evidence of recurrence. Because this is the first case, to our knowledge, to be reported, little is known about the nonoperative management of such hydatid localization. A recommendation is made, however, to adopt this minimally invasive procedure.

Adult↗

The diagnosis and staging of bladder cancer: from RBCs to TURs.

Timely and accurate diagnosis and staging of bladder cancer is critical for the successful management of patients with this disease. We review the literature on screening, signs and symptoms, cystoscopic evaluation, diagnostic tests, transurethral resection, and imaging. We highlight emerging areas, such as markers and fluorescence cystoscopy. Suspicion, accuracy, and technologic advances are key factors in ensuring the best outcomes for patients with bladder cancer.

Cystectomy↗

The management of superficial transitional cell carcinoma of the bladder.

Superficial transitional cell carcinomas (TCC) of the urinary bladder, defined as those that are restricted to the mucosa or the lamina propria, represent a common condition with a wide spectrum of biologic significance. High-grade superficial TCC, particularly in the presence of lamina propria invasion, has a significant risk of occult or subsequent progression to muscle-invasive or metastatic disease. Such high-risk lesions merit aggressive therapy with repeat resection followed by intravesical therapy, usually in the form of bacille Calmette-Guérin. Criteria for failure of intravesical therapy are not well defined, but persistent cytologic or cystoscopic abnormalities at 6 months are worrisome. Salvage intravesical therapy may sometimes be successful, but early cystectomy should be strongly considered, especially in younger patients. Close surveillance of patients with high-risk superficial TCC is essential.

Carcinoma, Transitional Cell↗

Holmium: yttrium-aluminum-garnet laser puncture of ureteroceles in neonatal period.

OBJECTIVES: The use of the holmium:yttrium-aluminum-garnet (YAG) laser to incise a ureterocele in children has been reported. However, its use to puncture ureteroceles in neonates has not. Therefore, we evaluated the effectiveness and safety of ureterocele puncture using a holmium-YAG laser in neonatal patients. METHODS: We reviewed our experience of all neonates (ie, children younger than 28 days old) who underwent transurethral puncture of a ureterocele. The preoperative data collected included age at presentation, mode of presentation, ureterocele location, and weight and age at the procedure. A holmium:YAG laser was used to incise the ureterocele, and a 200, 365, or 550-microm laser fiber was passed through a 6F or 7.5F cystoscope. RESULTS: A total of 4 neonates (2 boys and 2 girls) underwent transurethral holmium laser puncture of five ureteroceles. All patients were initially diagnosed with prenatal ultrasound findings confirmed after birth with additional imaging. The mean age at the initial puncture was 13.8 days, with a mean patient weight of 3.9 kg. The mean follow-up was 2.8 years (range 1.7 to 3.4). Four (80%) of five ureteroceles were adequately decompressed after one attempt. One patient required a second puncture of the ureterocele at 46 days of age because of incomplete decompression. None of the patients experienced an intraoperative or postoperative complication, including new vesicoureteral reflux after laser puncture. CONCLUSIONS: Holmium:YAG laser puncture of ureterocele is a safe, efficacious, and viable option for children in the neonatal period. However, this technique in these young children requires additional evaluation.

Decompression, Surgical↗

Transitional cell carcinoma of bladder with lamina propria invasion in a 10-year-old boy.

Transitional cell carcinoma of the bladder is a rare entity in childhood. We report on a 10-year-old boy with transitional cell carcinoma of the bladder who presented with gross hematuria. Ultrasonography revealed a papillary lesion in the bladder. Cystoscopic evaluation showed a papillary lesion with a thick stalk located just above the right ureteral orifice. Because the lesion was suspicious for at least lamina propria invasion, a single dose of mitomycin C was instilled after resection. Pathologic evaluation of the specimen was reported as grade 2 transitional cell carcinoma of the bladder with lamina propria invasion. Immunohistochemical staining with p53 and Ki-67 was performed for further evaluation.

Carcinoma, Transitional Cell↗

Intravesical injection of botulinum toxin type A: management of neuropathic bladder and bowel dysfunction in children with myelomeningocele.

OBJECTIVES: To evaluate the efficacy of botulinum toxin A in the treatment of children with detrusor hyperreflexia caused by myelomeningocele and the effects of this treatment on neuropathic bladder and bowel dysfunction. METHODS: In a prospective study, 26 children with myelomeningocele (20 boys and 6 girls, mean age 6.9 years) were included. All patients had been nonresponders to medical treatment and required clean intermittent catheterization. Under cystoscopic guidance, 10 IU/kg of botulinum toxin A was injected into the detrusor muscle, sparing the trigone and ureteral orifices. In each patient, urinary incontinence grade and improvement in parameters of interest in the evaluation of bowel dysfunction were assessed before and 4 months after injection. Conventional urodynamic studies to determine maximal bladder capacity and maximal detrusor pressure and voiding cystoureterography were also performed. RESULTS: Four months after procedure, 19 patients (73%) had become completely dry between clean intermittent catheterizations, and the total improvement in urine incontinence was 88%. The mean maximal detrusor pressure was decreased to 83.2 +/- 4.6 cm H2O from the baseline of 139.3 +/- 11.2 (P <0.01). The average maximal bladder capacity increased from 102.8 +/- 6.3 mL to 270.2 +/- 9.5 mL (P <0.01). Of the 15 patients who had varying degrees of vesicoureteral reflux before the procedure, 11 (73%) had decrease in the vesicoureteral reflux grade. Also, bowel dysfunction improved in 10 (66%) of the 15 patients. CONCLUSIONS: Botulinum toxin A appears to be a safe, minimally invasive procedure for the management of neuropathic bladder and bowel dysfunction in children with myelomeningocele.

Administration, Intravesical↗

Benchmarks achieved in the delivery of radiation therapy for muscle-invasive bladder cancer.

Radiation therapy has a multifaceted role in the treatment of muscle-invasive bladder cancer, from being a component of bladder sparing regimens to adjuvant therapy for patients after partial cystectomy, to palliative treatment in patients with metastatic disease. Here, we review the techniques currently used and the settings in which these techniques are applied. Advances in imaging and radiation delivery have allowed for definition of more precise treatment volumes, permitting the delivery of higher tumor doses and lesser doses to critical targets. Better tumor control, fewer therapeutic complications, and better quality of life outcomes are anticipated. In the United States, the most rapidly growing use of radiation in the treatment of bladder cancer is as a component of selective bladder conservation. It uses trimodality therapy, consisting of a maximal transurethral resection followed by concurrent chemotherapy and radiation. Careful cystoscopic surveillance by an experienced urologist ensures a prompt cystectomy at the fist sign of treatment failure. The majority of patients retain a well-functioning bladder with no survival decrement. Radiation therapy is also used as adjuvant therapy after partial cystectomy in select patients. In this setting, it decreases the risk of local or incisional recurrence. It is also used in patients with pelvic recurrences after cystectomy, often combined with concurrent chemotherapy. Radiation is a very effective palliative agent for patients with locally advanced or metastatic disease. It can palliate bleeding and pain for patients with local progression or alleviate pain from bony metastases.

Benchmarking↗

In situ detection of global DNA hypomethylation in exfoliative urine cytology of patients with suspected bladder cancer.

Global DNA hypomethylation is a common phenomenon in bladder cancer. Therefore we investigated whether it is possible to detect and assess global DNA hypomethylation in bladder cancer using a specific monoclonal antibody for 5-methyl-cytosine. Cytospins from exfoliative urine cytology specimens of patients with bladder cancer or a history of bladder cancer, control patients with benign urological diseases and of young healthy volunteers were analyzed. Urothelial carcinoma (UC) cells showed various degrees of nuclear destaining indicating global DNA hypomethylation whereas all specimens from healthy volunteers showed granular nuclear staining indicating regular methylation of repeated DNA sequences. Lowest 5-methylcytosine immunostaining scores were observed in carcinoma cells and a statistically significant difference was observed between urothelial cells of healthy controls or patients with benign disease compared to bladder cancer patients (p<0.01, p<0.05, respectively). In UC cases even morphologically normal urothelial cells often displayed evident hypomethylation. Likewise, in patients with a history of UC, but no cystoscopic evidence of recurrence, morphologically non-malignant urothelial cells presented with some degree of demethylation. Our results strongly support the hypothesis of early global demethylation in bladder cancer. Immunocytochemical staining with the 5-methylcytosine antibody allows simultaneous individual assessment of nuclear morphology and methylation status of a given sample.

5-Methylcytosine↗

Recurrence of vaginal implantation of transitional cell carcinoma of the urinary tract.

BACKGROUND: Vaginal recurrence of bladder carcinoma is extremely rare, with only two cases already reported. We have experienced a third case with the same characteristics of the first one, which was a vaginal recurrence with a prior resected urothelial vaginal tumor. CASE: An 82-year-old woman first presented in 1994 with frequency and gross hematuria. Cystoscopic evaluation revealed a single superficial tumor of the bladder which was treated by endoscopic resection. During the following 7 years, she underwent endoscopic procedures to remove recurrent Ta G2 tumor. In 2002, a cystoscopy revealed a papillary lesion, and a physical examination demonstrated multiple papillary lesion on the vaginal wall. Histology of excised genital lesions showed a Grade 2 transitional cell carcinoma. Two years later, the patient presented with a 1-cm solitary lesion on the right vaginal wall, which was then excised. Histological examination showed high-grade transitional cell carcinoma, infiltrating the chorion of the vagina. CONCLUSION: Implantation of shed tumor cells in tissues during micturition or resection seems the only plausible cause of the first implantation. For the second recurrence in the vagina, the possibility is of an incomplete locally excision or a relapse, tied to lymphatic micro metastasis, due to involvement of its own lamina propia.

Aged↗

Can MRI rule out bladder and rectal invasion in cervical cancer to help select patients for limited EUA?

OBJECTIVES: Although invasion of the bladder or rectum is rare in cervical carcinoma, endoscopic assessment of both organs is part of the standard FIGO clinical staging system, with associated increase in cost and risk of complications. Our objective was to evaluate whether MRI could be used to select patients who did not require invasive staging of the bladder or rectum. METHODS: Two observers, blinded to the results of cystoscopy and endoscopic examination of the rectum, retrospectively reviewed the MR images of 112 patients with cervical carcinoma. A 5-point invasion score was used to determine bladder and rectal invasion (1 = no invasion, 5 = definite invasion). A confidence score of 3 or above was used to identify patients with possible bladder or rectal involvement. The results of cystoscopy and endoscopic examination of the rectum were recorded and correlated with the MR findings. RESULTS: MRI was negative for both bladder and rectal invasion in 94/112 patients. Cystoscopy and endoscopic examination of the rectum were confirmed to be normal in all 94 cases. MRI identified 12 patients with possible rectal invasion, 2 confirmed at endoscopy. MRI identified 14 patients with possible bladder invasion, one confirmed at cystoscopy. Using a low threshold cut-off score of >3 to predict invasion resulted in a 100% negative predictive value (NPV) in detection of bladder and rectal invasion. CONCLUSION: The absence of bladder or rectal invasion can be diagnosed with sufficient confidence using an MRI scoring system to safely obviate the need for invasive cystoscopic or endoscopic staging in the majority of patients with cervical cancer. This could potentially lead to a reduction in staging costs and morbidity.

Adult↗

Treatment of detrusor sphincter dyssynergia by transperineal injection of botulinum toxin.

Detrusor-sphincter dyssynergia is an involuntary contraction of the external urethral sphincter during the detrusor contraction. It causes voiding dysfunction and can lead to urologic complications such as hydroureteronephrosis and renal failure. Patients with spinal cord injuries are particularly vulnerable. Botulinum toxin has been used via cystoscopy to decrease the activity of the external urethral sphincter. This report describes the treatment of 5 tetraplegic patients by single transperineal injections of botulinum toxin for detrusor-sphincter dyssynergia, proved by a urodynamic study with electromyography. A total of 15 injections was given, resulting in improved bladder function in all patients. Urodynamic assessment after treatment showed an increase of the functional detrusor capacity and a decrease of the maximal detrusor pressure during voiding. These results confirm the consideration of botulinum toxin as a treatment for detrusor sphincter dyssynergia. A single transperineal injection is a valuable, less invasive treatment using a cystoscopic technique.

Adult↗