Does primary melanoma of the bladder exist?

Primary melanoma of the urinary bladder is a rare neoplasm to which very strict diagnostic criteria apply. Although reports of previous cases exist, these criteria have yet to be met. We report a case of a young lady from whom a malignant melanoma of the bladder was resected. This was presumed to be primary as detailed investigation failed to find any other site from which metastases could have originated. We discuss the diagnostic criteria of this entity and stress the difficulty in conclusively demonstrating that, despite some of these criteria being met, a lesion such as this is primary in origin. This case could be the longest surviving patient with primary melanoma of the bladder, however we will never be able to prove that spontaneous regression of an undiagnosed extravesical primary malignant melanoma did not occur.     

Expression of β-tubulin isotypes in urothelial carcinoma of the bladder

Purpose

Our study aims to investigate the expressions of β-tubulin isotypes and their significances in urothelial carcinoma of the bladder (UCB) as altered expression of a specific β-tubulin isotype is associated with chemoresistance and poor prognosis in other malignancies.

Materials and methods

Expression of β-tubulin isotypes was retrospectively examined in 342 UCB samples obtained from 1995 to 2010 by immunohistochemistry.

Results

TUBB1 (307/342, 89.8 %) was most frequently overexpressed in the cytoplasm of UCB cases, followed by TUBB4 (101/342, 29.5 %), TUBB2 (85/342, 24.9 %), and TUBB3 (60/342, 17.5 %). TUBB1 overexpression was associated with older age (p = 0.032), high WHO grade (p = 0.001), and advanced TNM stage (p = 0.006). High levels of TUBB2 expression were associated with high WHO grade (p < 0.001), advanced TNM stage (p < 0.001), and non-papillary growth pattern (p = 0.007). TUBB3 overexpression was related to high WHO grade (p = 0.029). In univariate and multivariate survival analyses, TUBB1 overexpression was associated with poor recurrence-free survival (RFS) rates of all cases (hazard ratio 1.98, p = 0.031) and of the patients with transurethral and/or partial resection (hazard ratio 2.12, p = 0.031). TUBB2 overexpression was correlated with a short RFS of the patients with T2–T4 stages (hazard ratio 3.48, p = 0.007). TUBB3 overexpression was related to a poor RFS of the patients undergoing radical cystectomy (hazard ratio 5.90, p = 0.002).

Conclusions

High TUBB1, TUBB2, and TUBB3 expressions are associated with unfavorable clinicopathologic factors and are independent prognostic factors for recurrence-free survival of UCB.     

Does cystoscopy correlate with the histology of recurrent papillary tumours of the bladder?

OBJECTIVE: To correlate the cystoscopic appearance of recurrent papillary bladder tumours with the histology after transurethral resection, and thus ascertain whether cystoscopy can reliably identify low-grade, noninvasive papillary tumours suitable for outpatient fulguration. PATIENTS AND METHODS: In all, 150 recurrent papillary tumours of the bladder identified at outpatient flexible cystoscopy were classified as either low-grade and noninvasive (TaG1), high-grade and noninvasive (TaG3), or invasive (TIG3) tumours, and correlated with urine cytology and histology of tumour stage and tumour grade after transurethral resection. RESULTS: Cystoscopy classified 84 of the 150 papillary tumours as TaG1 and 66 as either TaG3 or T1G3. Cystoscopy correctly predicted the histology of 78 of 84 (93%) TaG1 tumours, 71 of 72 (98%) TaG1 tumours associated with a negative urine cytology, and 92% of TaG3 or T1G3 tumours. CONCLUSIONS: A skilled urologist can identify noninvasive, low-grade recurrent papillary bladder tumours on follow-up cystoscopy that do not require biopsy and that may be treated by outpatient fulguration alone.     

Does the presence of muscularis propria on transurethral resection of bladder tumour specimens affect the rate of upstaging in cT1 bladder cancer?

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? It is already known and accepted that the presence of mucularis propria (MP) on bladder biopsy is incremental to the clinical staging process for this disease entity. This study establishes that the lack of MP also portends a higher risk of pathologic upstaging at the time of radical cystectomy. OBJECTIVE

• ? To determine how the presence of MP on T1 biopsy specimens affects the outcome of patients undergoing RC as compared to when no MP is identified in the TURBT specimen.

PATIENTS AND METHODS

• ? Patients were retrospectively identified from the Columbia University Urologic Oncology Database.
• ? From January 1986 to October 2009, 114 patients diagnosed with cT1N0M0 bladder cancer who underwent RC within 4 months of their last biopsy were identified.
• ? Patients were stratified based on the presence of MP on T1 biopsy, and upstaging was defined as any tumor T2 or greater, N+, or M+ at the time of radical cystectomy.
• ? The rate of upstaging was assessed using univariate and multivariate regression models; Kaplan meier curves were also extrapolated for each cohort to compare disease specific and overall survival patterns.

RESULTS

• ? Of the 114 patients evaluated in this study, 24 (20.2%) did not have MP on their T1 biopsy before RC. The rate of upstaging (>=pT2) stratified by the presence of MP on biopsy was 50% and 78%, respectively (p = 0.017).
• ? On univariate analysis, lack of MP on biopsy was associated with an increased risk of upstaging (HR 3.52, p = 0.021, CI 1.2–10.3), however did not reach significance as an independent predictor (HR 2.9, p = 0.056, CI 0.97–8.9).
• ? At a mean follow‐up of 33.5 months, there was no difference in disease specific (p = 0.41) and overall survival (p = 0.68) between groups.

CONCLUSIONS

• ? The lack of MP on TURBT for high grade cT1N0M0 bladder cancer portends a high likelihood of upstaging at RC, although this risk did not translate into a detectable increased risk of disease specific mortality.

     

Does avulsion of the puborectalis muscle affect bladder function?

Introduction and hypothesis  The levator ani muscle is generally thought to play a role in urinary continence, with incontinence assumed to be due to abnormal muscle function or morphology. This study examined whether avulsion of the puborectalis muscle is associated with symptoms or signs of bladder dysfunction. Methods  In a retrospective observational study, we reviewed the records of 425 women who had attended a urogynecological unit for independent flowmetry, multichannel urodynamic testing, and 4D pelvic floor ultrasound. Results  Mean age was 55 years (range, 17–87 years). Of 420 women with complete datasets, 104 (25%) were diagnosed with a puborectalis muscle avulsion. These women were less likely to suffer from stress urinary incontinence (SUI; P < 0.001) and urodynamic stress incontinence (USI; P = 0.065) and more likely to present with symptoms of prolapse (P < 0.001) and show signs of voiding dysfunction (P = 0.005). The negative association between avulsion and SUI persisted in multivariate models. Conclusion  Puborectalis muscle trauma is not associated with an increased risk of SUI or USI in a urogynecological population, even when controlling for symptoms or signs of prolapse and previous surgery.     

Lamina propria: The functional center of the bladder?

The bladder mucosa consists of the urothelium, basement membrane, and lamina propria (LP). Although the urothelium has been given much attention, it may be regarded as one part of a signaling system involving another equally important component of the bladder mucosa, namely, the LP. The LP lies between the basement membrane of the mucosa and the detrusor muscle and is composed of an extracellular matrix containing several types of cells, including fibroblasts, adipocytes, interstitial cells, and afferent and efferent nerve endings. In addition, the LP contains a rich vascular network, lymphatic vessels, elastic fibers, and smooth muscle fascicles (muscularis mucosae). The roles of the LP and its components in bladder function have not been definitively established, though it has been suggested to be the capacitance layer of the bladder, determining bladder compliance and enabling adaptive changes to increasing volumes. However, the bladder LP may also serve as a communication center, with an important integrative role in signal transduction to the central nervous system (nociception, mechanosensation). The LP may also, by means of its different components, make it possible for the urothelium to transmit information to other components of the bladder wall, contributing to activation of the detrusor muscle. In addition, the LP may serve as a source for production of factors influencing the growth of both the overlying urothelium and the underlying detrusor muscle. Neurourol. Urodynam. 33:9–16, 2014. © 2013 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.     

Is there a role for bladder preserving strategies in the treatment of muscle-invasive bladder cancer?

Single modality bladder sparing therapy for muscle-invasive bladder cancer, including transurethral resection, systemic chemotherapy or radiotherapy have been demonstrated to result in insufficient local control of the primary tumor as well as decreased long-term survival of the patients when compared to radical cystectomy. Therefore, multimodality treatment protocols that aim at bladder preservation and involve all of the aforementioned approaches have been established. Arguments for combining systemic chemotherapy with radiation are to sensitize tumor tissue to radiotherapy and to eradicate occult metastases that have already developed in as many as 50% of patients at the time of first diagnosis. It has been shown that the clinical outcome observed with this approach approximates that after radical cystectomy. Additionally, a substantial number of patients survive with an intact bladder. However, bladder preserving approaches are costly, and require close co-operation between different clinical specialists as well as very close follow-up. The good long-term results obtained after cystectomy and creation of an orthotopic neobladder make the possible advantage of a bladder preservation strategy questionable in consideration of quality of life issues. Additionally, side effects related to bladder sparing therapy may result in an increased morbidity and mortality in those patients who in fact need to undergo surgery due to recurrent or progressive disease. Multimodality bladder sparing treatment is a therapeutic option that can be offered to the patient at centres that have a dedicated multidisciplinary team at their disposal. However, radical cystectomy remains the standard of care for muscle-invasive bladder tumors.     

Impact of tumor size on the oncological outcome of high-grade nonmuscle invasive bladder cancer – examining the utility of classifying Ta bladder cancer based on size

PurposeTo examine survival rates and to calculate the risk of disease recurrence, progression, overall, and cancer-specific mortality in patients diagnosed with high-risk NMIBC using a multi-institutional dataset to evaluate differences between the guidelines of the European Association of Urology and the guidelines of the National Comprehensive Cancer Network (NCCN) with regard to tumor size in risk stratification.Methods and MaterialIn total 1,116 individuals diagnosed with high-risk NMIBC between 2001 and 2013 were included in the analysis. Patients were stratified to NCCN guideline recommendations (high-grade T1, high-grade Ta ≤ 3 cm, and high-grade Ta > 3 cm). Recurrence and progression rates were calculated. Kaplan-Meier curves were fitted to examine differences in recurrence-free (RFS) and progression-free survival (PFS). Multivariable Cox proportional hazards regression models were employed to calculate differences in the RFS, PFS, overall, and cancer-specific survival (CSS).ResultsThe majority of patients were diagnosed with high-grade T1 disease (N = 576, 51.6%), while 34.2% and 14.2% of patients were diagnosed with high-grade Ta ≤ 3 cm and Ta > 3 cm NMIBC, respectively. The 1- and 5-year RFS (1-year: 80.5% vs. 64.9%; 5-year: 58.6% vs. 48.3%, P = 0.048) and PFS (1-year: 99.1% vs. 98.6%; 5-year: 97.7% vs. 92.4%, P = 0.054) rates were higher in patients with Ta ≤ 3 cm. Patients diagnosed with high-grade Ta > 3 cm experienced unfavorable progression-free, and cancer-specific survival compared to high-grade Ta ≤ 3 cm, respectively (PFS: 2.41, 95% confidence interval [CI] 1.05–5.56, P = 0.038; CSS: hazard ratios [HR] 2.22, 95% CI 1.02–4.89, P = 0.048).ConclusionPatients diagnosed with high-grade Ta NMIBC ≤3 cm demonstrated a favorable progression-free, and cancer-specific survival compared to patients diagnosed with high-grade Ta > 3 cm and high-grade T1 NMIBC.     

Tumours of the bladder: What does the urologist expect from imaging?

Cancer of the bladder is the seventh most common of all cancers observed in France, and is the second urological cancer after prostate cancer. It is mainly related to nicotine addiction. When doing the initial tests, ultrasound examination of the bladder can enable the clinician to diagnose a polypoid tumour and thus avoid his having to organise diagnostic fibroscopy. When the bladder tumour infiltrates the detrusor muscle, the situation becomes life-threatening for the patient and radical treatment is envisaged. Uro-CT is the standard examination to characterise the lesion and describe its relationship with neighbouring organs. It is essential, and must be performed before endoscopic resection of the tumour, to be correctly interpreted. It is imperative for imaging to look for a synchronous lesion in the upper urinary tract (ureters, renal pelvis), because the presence of such a lesion changes the prognosis of the disease and the sequence of therapy, which is decided by the urologist in a multidisciplinary consultation.     

Traumatic rupture of the urinary bladder: is the suprapubic tube necessary?

BACKGROUND: Although surgical principles are well accepted for the treatment of an intraperitoneal or extraperitoneal rupture of the urinary bladder, the type and number of drainage catheters needed to obtain a satisfactory outcome with minimal patient morbidity have yet to be determined. METHODS: This was a retrospective review of data on injured patients with the diagnosis of an intraperitoneal or extraperitoneal rupture of the urinary bladder from penetrating or blunt trauma. RESULTS: Of the 51 patients identified, 28 were treated with suprapubic and transurethral catheters, whereas 23 received a transurethral catheter only. Complications and catheter duration times were similar regardless of type of bladder injury or drainage catheter used (p > 0.5). CONCLUSION: These data suggest that there are similar outcomes and complication rates for patients treated with suprapubic and transurethral catheters versus transurethral catheter only. Transurethral catheters alone seem effective in draining all types of bladder injuries.     

Denervation supersensitivity of the urethra to α-adrenergics in the chronic neurogenic bladder

Summary The response of the urethral pressure profile to the administration of various autonomic drugs was compared between a group of eight patients with chronic neurogenic bladder as evidenced by denervation supersensitivity to besacholine^R and a group of 10 control subjects. A supersensitive response to the administration of an -stimulant with a rise of maximum urethral pressure of 10 mmHg or more above the control urethral pressure was uniformly observed in the urethra of patients with chronically denervated bladders. Mechanisms of supersensitivity are postulated and the significance of -adrenergic innervation of the urethra are stressed. These results appear to add pharmacological evidence of -adrenergic predominance in the urethra which is now believed to be dually innervated.     

Is neoadjuvant chemotherapy valid in invasive cancer of the bladder?

The role of neoadjuvant chemotherapy for invasive transitional cell carcinoma (TCC) of the bladder is not determined yet. M-VAC and CMV regimens have a complete response rate of 10-47% with an overall response reaching 80%. In 16.7-35% of all the responders and 42.9-92% of the complete responders a functioning bladder can be preserved. The influence of neoadjuvant chemotherapy on long-term survival is questionable. Nevertheless, the authors conclude that neoadjuvant chemotherapy is feasible in patients with invasive TCC as it improves the results of following surgery and in some cases enables an organ sparing operation.     

Dimethyl sulfoxide: does it change the functional properties of the bladder wall?

PURPOSE: Dimethyl sulfoxide (DMSO) is used in a 50% solution to treat interstitial cystitis. Symptomatic relief occurs in about two-thirds of cases. The mechanism of action and effects of DMSO on bladder tissue function are poorly understood. Therefore, the effect of DMSO on bladder muscle compliance and contractility was evaluated. MATERIALS AND METHODS: Contractility and compliance were evaluated in rat bladder strips exposed to various concentrations of DMSO for 7 minutes, followed by 7 to 60-minute washout periods. The effect of DMSO at concentrations of 25%, 30%, 35%, 40% and 50% on electrical field stimulation induced contractions was assessed. Acetylcholine and high KCl (Sigma Chemical Co.) induced contractions were measured after exposure to 30% DMSO. Compliance was evaluated after exposure to 30% and 50% DMSO. RESULTS: Exposure to 40% DMSO completely abolished electrical field stimulation contractions, while 30% DMSO decreased the electrical field stimulation contraction to 40% +/- 6% of the initial force but there was almost complete recovery within 30 minutes. Contractile force was unaltered by 25% DMSO. Acetylcholine and KCl stimulation after exposure to 30% DMSO produced contractile forces of 78% +/- 6% and 39% +/- 6% of pre-DMSO control contractions, respectively. Compliance decreased by 2.4 and 4.6-fold following 30% and 50% DMSO exposure, respectively. CONCLUSIONS: DMSO completely and irreversibly abolishes contractions at a 40% concentration. Compliance is altered at even lower concentrations (30%). These findings bring into question the current practice of treating patients who have IC with 50% DMSO. Lower concentrations (25%) of DMSO may serve as a safe, effective analgesic and anti-inflammatory treatment for IC and other bladder pathologies.     

Is it possible to cure the symptoms of the overactive bladder in women?

Purpose

To evaluate the feasibility of discontinuing treatment with mirabegron once symptoms have subsided in patients with overactive bladder (OAB).

Methods

The present study evaluated a total of 159 female OAB patients (age 62.9 ± 12.36), each of which were prescribed 50 mg/day mirabegron (Time point 1—T1). Data obtained from voiding diaries and patient-reported outcome variables were assessed during follow-up visits at months 1, 3, 6, 12, 18 (T2), and 21 (T4). At the 18-month visit, patients with an Urgency Bother-Visual Analog Scale score of ≤ 50% were advised to stop treatment with mirabegron. Upon re-emergence or worsening of OAB symptoms, patients were allowed to start taking medication again at their discretion (T3). Statistical analysis was performed using a Chi-square test. An ANOVA analysis and a two-sample t test were used to evaluate differences between groups.

Results

A total of 56 out of 159 (35.3%) patients took 50 mg of mirabegron daily between T1 and T2. A total of 17 out of 56 patients (30.4%) did not meet the criteria for mirabegron discontinuation (Group A). A total of 24 out of 56 patients (42.9%) stopped taking the medication temporarily, but later returned to treatment (Group B). The average time span between T2 and T3 was 53.9 days. Fifteen of 56 patients (26.8%) ceased treatment with mirabegron without starting it again before T4 (Group C). The average time span between T2 and T4, in Group C, was 124.7 days.

Conclusion

A small percentage of OAB patients were able to discontinue mirabegron due to symptom cessation.