Bladder and upper tract urothelial cancer

PURPOSE: While there are data available indicating the incidence and prevalence of bladder and upper tract urothelial cancer, population level data on resource use, costs and patterns of care for these cancers are limited. We quantified the economic impact of caring for patients with bladder and upper tract urothelial cancer, and determined the primary drivers for such costs in the population in the United States. MATERIALS AND METHODS: The analytical methods used to generate these results have been described previously. RESULTS: An increasing proportion of patients with bladder and upper tract urothelial cancer were being treated in the outpatient setting. Most care was provided by urologists and visit frequency was directly related to disease stage. Only a small proportion of patients potentially eligible for chemotherapy, ie those with advanced disease, sought specialized care from oncologists. Office based diagnostic tests such as cytology were not commonly done, although a substantial number of patients with bladder cancer underwent cystoscopy. The use of excretory urography in these patients was decreasing, while the use of computerized tomography was increasing. Ileal conduits were the most frequently performed type of urinary diversion following cystectomy. The cystectomy rate remained unchanged for a decade. Intravesical therapy was done infrequently in patients with bladder cancer. Annual costs for treating bladder and upper urinary tract cancers were $1 billion and $64 million, respectively, in 2000. These costs represented a $164 million increase over 1994 levels, which outpaced inflation. CONCLUSIONS: The costs of treating bladder cancer increased steadily during a 6-year period despite a decrease in inpatient care. Coupled with a lack of substantial change in transurethral resection and cystectomy rates, this suggests that the primary cost drivers are increased outpatient testing, eg computerized tomography and cystoscopy, and an increase in the number of diagnosed cases. Greater focus on selective use of testing modalities, preventive care such as smoking cessation and earlier identification of patients at risk may help curtail further expenditure with regard to managing bladder and upper urinary tract cancers.     

Clinical panurothelial disease in patients with superficial bladder tumors: therapeutic implications

PURPOSE: We established the prognostic and therapeutic implications of panurothelial involvement in patients with superficial bladder tumors for optimizing therapeutic approaches in those at risk for panurothelial involvement. MATERIALS AND METHODS: We studied the records of 35 patients with clinical panurothelial disease. Since all of these patients presented with high risk superficial bladder cancer during followup, they were included in specific therapeutic and followup regimens. Radical procedures or conservative therapies were indicated mainly according to pathological examination and the recurrence pattern. RESULTS: Panurothelial involvement was a late stage of a recurrent and diffuse process that essentially developed in sequences, in which all patients presented with high risk superficial bladder tumors. This process involved continued relapse after panurothelial involvement developed. Notably 19 patients (79.1%) at risk for recurrence had repeat relapse in the urothelium. In the upper urinary tract 12 patients (34.3%) had bilateral involvement, including 7 (41.2%) of 17 patients after cystectomy. We identified 2 subgroups of patients. The subgroup with a better prognosis included 27 patients in whom late panurothelial disease developed step by step after a complete response to intravesical therapy, including 14 (51.8%) who were free of disease. The other subgroup with a poor prognosis included 8 patients with concurrent bladder carcinoma in situ and prostate involvement as well as early panurothelial disease, of whom only 2 (25%) were disease-free. All patients underwent many therapeutic approaches. A mean of 7.5 surgical procedures per patient were done, including a mean of 5.5 transurethral resections, a mean of 1 conservative approach to the upper urinary tract and a mean of 1.1 radical procedures. At a median followup of 111 months 10 patients (28.5%) were disease-free but only 7 (20%) retained the bladder, while 19 (54.3%) died of tumor. CONCLUSIONS: Patients with high risk superficial bladder multifocal tumors and associated bladder carcinoma in situ are at high risk for panurothelial involvement. Radical cystectomy may be recommended in these patients when initially or during followup, concurrent high risk superficial bladder tumors and prostate involvement develop or prostate involvement recurs. For the upper urinary tract conservative therapies may be advisable when noninfiltrating tumors are diagnosed even after cystectomy due to the high rate of bilateral new onset disease. When cystectomy is performed, extended excision of the upper urinary tract and pyelo-intestinal anastomosis may be considered.     

Urinary tract infections and bladder dysfunction after renal transplantation in children

PURPOSE: Urinary tract infection remains a major cause of morbidity in pediatric renal transplant recipients. In otherwise healthy children bladder dysfunction increases the susceptibility to urinary tract infection. The aims of this study were to determine whether bladder dysfunction affects the incidence of urinary tract infection after renal transplantation, and to assess the impact of recurrent urinary tract infections on graft function. MATERIALS AND METHODS: We evaluated bladder function with a questionnaire, uroflowmetry and bladder ultrasound, and renal function with clearance of inulin or iohexol (glomerular filtration rate) in 68 recipients of renal transplants 5 to 20 years old, at 1 to 15 years after transplantation, with and without recurrent urinary tract infections. RESULTS: Bladder dysfunction was equally common in children with and without recurrent urinary tract infections (68% vs 74%, not significant). Therefore, it had no effect on the incidence of recurrent urinary tract infections. Graft function deteriorated at a faster rate in patients with recurrent urinary tract infections than in those without (mean glomerular filtration rate 45 vs 57 ml per minute per 1.73 m(2) at 4 years after transplantation, p=0.02). CONCLUSIONS: Bladder dysfunction did not predispose patients to recurrent urinary tract infections. Graft function declined with time in all patients but the rate of deterioration was faster in the group with recurrent urinary tract infections.     

Cystitis glandularis in children

OBJECTIVE: To assess the characteristics of cystitis glandularis in children. PATIENTS AND METHODS: Three cases of cystitis glandularis in children are described, occurring in boys aged 9-13 years. The presenting symptoms were gross haematuria in the first patient and frequency and urgency in the second. The third patient was asymptomatic and the lesion appeared as a wide thickening of the bladder wall on follow-up ultrasonography for previous surgery. In all patients, a polypoid bladder mass was found at cystoscopy and diagnosed at histology. The endoscopic resection, with long-term antibiotic prophylaxis, was the treatment of choice, with no recurrence at 12-30 months of follow-up. CONCLUSION: Cystitis glandularis has been rarely described in children, and is probably related to chronic or recurrent infections or an inflammatory reaction. Its potential premalignant significance is still the subject of debate.     

Recognition of bladder instability on voiding cystourethrography in infants with urinary tract infection

PURPOSE: We evaluate voiding cystourethrography as a method for identifying bladder instability in infants. MATERIALS AND METHODS: Cystometry was combined with voiding cystourethrography in 79 male and 64 female infants with first time urinary tract infection. Bladder wall irregularity, elongation of bladder shape, and filling of the posterior urethra were transient radiological signs occurring during bladder filling and were considered to reflect bladder instability. A pediatric radiologist looked for these signs on all 480 films exposed during bladder filling. The results were correlated to simultaneous detrusor pressure recordings. The analysis was repeated independently by a urologist to evaluate the reliability of the radiological signs used. RESULTS: The sensitivity and specificity were both 90% in the evaluation of radiological signs of bladder instability. Filling of the posterior urethra was the least frequently reported radiological sign, which was seen at 53% of unstable contractions. However, when this sign was reported, instability was usually correctly detected (85%). Evaluation accuracy had improved with increasing numbers of noted signs per film. This accuracy had included 29%, 67% and 91% of unstable contractions that were correctly diagnosed when 1, 2 or 3 signs were noted, respectively. The number of noted signs was positively related to the strength of the unstable detrusor contraction. Urologist evaluations had similar results to the radiologist, although the sensitivity was somewhat lower (79% and 90%, respectively). CONCLUSIONS: Unstable detrusor contractions could be identified in infants by evaluation of radiological signs on voiding cystourethrography. Findings of bladder wall irregularity, elongation of bladder shape and filling of the posterior urethra indicated unstable detrusor contraction. The more such findings are observed, the stronger the indication.     

Vesicoureteral reflux and bladder dysfunction

The relationship between vesicoureteral reflux and bladder dysfunction is inseparable and has long been emphasized. However, the primary concern of all physicians treating patients with vesicoureteral reflux is the prevention of renal scarring and eventual deterioration of renal function.Bladder dysfunction, urinary tract infection and vesicoureteral reflux are the three important factors which are closely related to each other and contribute to the formation of renal scar. Especially, there is ongoing discussion regarding the role of bladder dysfunction in the prognosis of both medically and surgically treated vesicoureteral reflux. The effect of bladder dysfunction on VUR is mostly via inadequate sphincter relaxation during infancy which is closer to immature bladder dyscoordination rather than true dysfunction. But after toilet training, functional obstruction caused by voluntary sphincter constriction during voiding is responsible through elevation in bladder pressure, thus distorting the architecture of bladder and ureterovesical junction. Reports suggest that voiding phase abnormalities in lower urinary tract dysfunction contributes to lower spontaneous resolution rate of VUR. However, filling phase abnormalities such as involuntary detrusor contraction can also cause VUR even in the absence of dysfunctional voiding. With regards to the effect of bladder dysfunction on treatment, meta-analysis reveals that the cure rate of VUR following endoscopic treatment is less in children with bladder bowel dysfunction but there is no difference for open surgery.The pathophysiology of bladder dysfunction associated with UTI can be explained by the ‘milk-back’ of contaminated urine back into the bladder and significant residual urine resulting from functional outlet obstruction. In addition, involuntary detrusor contraction can decrease perfusion of the bladder mucosa thus decreasing mucosal immunity and creating a condition prone to UTI. In terms of renal scarring, dysfunctional voiding seems to be more closely related to renal damage in association with VUR than overactive bladder. However, studies show that UTI can induce renal scarring even without VUR present and urodynamic abnormalities are quite often detected in these cases. Whether reflux of sterile urine in bladder dysfunction can cause significant renal scarring, especially when intrarenal reflux is present remains controversial. Another issue that warrants further research is the direct relationship between bladder dysfunction and renal scarring, since some reports suggest that these two conditions share a common genotype.Recently some studies have suggest VUR as a causal factor of bladder dysfunction, supported by the fact that bladder dysfunction resolves after injection therapy of VUR. Further study with more objective evaluation of bladder dysfunction may be needed.     

Papillary urothelial neoplasm of low malignant potential: evolving terminology and concepts

PURPOSE: The most controversial aspect of the new WHO 2004/ISUP classification system is the creation of the PUNLMP diagnostic category. We discuss PUNLMP tumors and the WHO 2004/ISUP classification system with an emphasis on tumor morphology and heterogeneity, recurrence and progression rates, tumor genetics, interobserver variability and the usefulness of biomarkers and molecular diagnostic techniques for grading bladder tumors. MATERIALS AND METHODS: A literature search using PubMed was performed. All relevant literature concerning PUNLMP and the WHO 2004/ISUP grading system for urothelial neoplasms was reviewed. RESULTS: The new WHO 2004/ISUP classification reflects work in progress. Low malignant potential terminology may not reflect the true biological behavior of these tumors. Additionally, interobserver variability in making a diagnosis of PUNLMP is high despite detailed histological criteria. Urine cytopathology in the context of the WHO 2004/ISUP classification does not appear to effectively discriminate PUNLMP from low grade carcinoma. CONCLUSIONS: For practical purposes patients with PUNLMP should be treated similarly to patients with low grade, noninvasive urothelial carcinoma. It is our hope that recent advances in the molecular grading of these tumors may eventually supplant traditional morphological classification, allowing a more precise and objective assessment of the biological potential of these tumors.