Use of a self-designed bladder controller for restoring bladder function in paraplegic dogs

Objective: To evaluate the results of a self-designed bladder controller for restoring micturition function in paraplegic dogs. Methods : The spinal cords of 4 dogs were transected above the cone. Electrodes were implanted in S2 bilaterally and connected to the subcutaneous receivers for external activation. Microsurgical technique was employed to perform dorsal rhizotomy of S1-3 intradurally. The dogs were stimulated daily to observe micturition. Urodynamic testing and vesicography were performed. Results: All the dogs acquired micturition under the control of electric stimulation, with urine volume 80-140 ml per time. The mode of micturition was post-stimulus voiding. Vesicography revealed that the bladder was rifled well and the bladder neck was open in the micturition course of electric stimulation. Residual urine volume was 15-20 ml. Urodynamic testing found that the bladder pressure and intraurethral pressure increased simultaneously, but when the intraurethral pressure was greater than the bladder pressure, no micturition occurred.The pressure decreased to baseline rapidly and the bladder pressure decreased slowly between two bursts. Micturition occurred when the bladder pressure was greater than the intraurethral pressure. Conclusions: The self-designed bladder controller together with a sacral deafferentation procedure can restore micturition function of paraplegic dogs.     

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.     

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.     

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.

     

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.     

Photodynamic therapy of bladder cancer —uptake and phototoxicity of photosan in vitro

Summary The uptake of photosan and the intracellular sites of photoradiation-induced damage were investigated in vitro in bladder carcinoma cells and in normal bladder cells. Cells were examined by phase contrast, fluorescence and electron microscopy. The concentration of photosan, measured in g/10⁶ cells, showed a good correlation to the incubation time. At all incubation times, control cells showed a lower uptake when compared with tumor cells. Following photodynamic therapy (PDT), phase-contrast microscopy revealed marked changes in tumor cells, whereas only minor effects could be detected at the cell membrane of the control cells. Following PDT, most of the investigated cells showed onanges of the mitochondria and cytoplasma. These changes consisted of dissolution of the cristae, predominantly in the central part of the mitochondria. Twenty-four hours after PDT the shape of the mitochondria had changed markedly and the cristae were found to be completely destroyed. Moreover, the cystoplasma showed numerous vacuoles, and the number of mitochondria was decreased compared to non-treated cells.Supported by Deutsche Forschungsgemeinschaft Ha 131/1-2     

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.     

Management of superficial bladder cancer: what is new?

The management of superficial bladder cancer has not changed much during the last years. Transurethral resections with adjuvant intravesical instillation to risk groups have been standard therapy. Cystoscopy and cytology have been used for follow-up. Recently combinations of drugs for instillation and new urinary markers for diagnosis and follow-up have been tested. The role of these new modalities has not been easily judged. Thus the timely advent of guidelines with policy recommendations will play an important part in improving the care of patients in the future.     

Bailing out the bowel and bladder – A rare case report of rectal impalement injury with iatrogenic bladder rupture

Introduction and importanceRectal perforations due to foreign body impalement are infrequently encountered in practice. Accidental or intentional foreign body insertions pose a diagnostic challenge to surgeons and put them in demanding circumstances for successful extraction.Case presentationWe report a case of a 60-year-old male with alleged history of accidental foreign body insertion into the rectum. Radiographs showed a linear metallic foreign body with crooked end. Computed Tomography (CT) with rectal contrast revealed contrast extravasation indicating anterior wall perforation of upper rectum. Patient was taken urgently for exploration and foreign body removal. Intra-operatively, bladder was injured inadvertently. Primary repair of enterotomy and loop sigmoid-ostomy was done besides bladder repair. Patient tested positive for COVID-19. Patient was observed in critical care unit for two days. Post-operative period was unremarkable apart from midline abdominal wound gape for which secondary closure was done. Patient was discharged with urinary catheter in-situ. Patient followed-up with a normal cystourethrogram and a well-functioning stoma. Stoma closure after two months was uneventful.Clinical discussionA thorough history and clinical examination is required and one should raise a high index of suspicion of perforation in patients with rectal foreign bodies, which should be managed appropriately and promptly to prevent sepsis and multi-organ dysfunction. Inadvertent bladder injuries are common with lower-midline incisions. However, give good results when repaired suitably.ConclusionThe rationale behind this report is to explicate the complexity and hurdles in the surgical management of rectal foreign bodies causing impalement injury.