Urothelial neoplasms of the urinary bladder occurring in young adult and pediatric patients: a comprehensive review of literature with implications for patient management

Bladder urothelial carcinoma is typically a disease of older individuals and rarely occurs below the age of 40 years. There is debate and uncertainty in the literature regarding the clinicopathologic characteristics of bladder urothelial neoplasms in younger patients compared with older patients, although no consistent age criteria have been used to define "younger" age group categories. Use of the World Health Organization 2004/International Society of Urological Pathology 1998 grading nomenclature and recent molecular studies highlight certain unique features of bladder urothelial neoplasms in young patients, particularly in patients below 20 years of age. In this meta-analysis and review, the clinical, pathologic, and molecular features and risk factors of bladder urothelial neoplasms in patients 40 years or less are presented and analyzed according to decades of presentation. Similar to older patients, bladder urothelial neoplasms in patients 40 years or younger occur more common in male patients, present mainly with gross painless hematuria, and are more commonly located at bladder trigone/ureteral orifices, but in contrast have a greater chance for unifocality. Delay in diagnosis of bladder urothelial neoplasms seems not to be uncommon in younger patients probably because of its relative rarity and the predominance of benign causes of hematuria in this age group causing hesitancy for an aggressive work-up. Most tumors in patients younger than 40 years were low grade. The incidence of low-grade tumors was the lowest in the first 2 decades of life, with incremental increase of the percentage of high-grade tumors with increasing age decades. Classification according to the World Health Organization 2004/International Society of Urological Pathology grading system identified papillary urothelial neoplasms of low malignant potential to be relatively frequent among bladder tumors of young patients particularly in the teenage years. Similar to grade, there was marked predominance of low stage tumors in the first 2 decades of life with gradual inclusion of few higher stage and metastatic tumors in the 2 older decades. Bladder urothelial neoplasms occurring in patients <20 years of age lack or have a much lower incidence of aberrations in chromosome 9, FGFR3, p53, and microsatellite instability and have fewer epigenetic alterations. Tumor recurrence and deaths were infrequent in the first 2 decades and increased gradually in each successive decade, likely influenced by the increased proportion of higher grade and higher stage tumors. Our review of the literature shows that urothelial neoplasms of the bladder occurring in young patients exhibit unique pathologic and molecular features that translate to its more indolent behavior; this distinction is most pronounced in patients <20 years. Our overall inferences have potential implications for choosing appropriate noninvasive diagnostic and surveillance modalities, whenever feasible, and for selecting suitable treatment strategies that factor in quality of life issues vital to younger patients.

Refractory Hematuria in an Oliguric Patient After Pancreas Transplantation with Exocrine Pancreas Bladder Drainage

A 52-yr-old man presented with hematuria and clot retention. He had undergone simultaneous pancreas-kidney transplantation with exocrine pancreas bladder drainage 16 yr ago. The patient suffered from progressive transplant kidney failure with gradually decreasing urine output and needed hemodialysis every other day. Gross hematuria persisted after removal of all blood clots. Cystoscopy showed multiple small, flat ulcers of the bladder mucosa. Some bled discretely and were coagulated cautiously. However, hematuria was refractory to multiple urological interventions, which eventually necessitated an enteric diversion of the exocrine pancreas. Hematuria ceased following an uneventful postoperative course.

MicroRNAs may mediate the down-regulation of neurokinin-1 receptor in chronic bladder pain syndrome

Bladder pain syndrome (BPS) is a clinical syndrome of pelvic pain and urinary urgency-frequency in the absence of a specific cause. Investigating the expression levels of genes involved in the regulation of epithelial permeability, bladder contractility, and inflammation, we show that neurokinin (NK)1 and NK2 tachykinin receptors were significantly down-regulated in BPS patients. Tight junction proteins zona occludens-1, junctional adherins molecule -1, and occludin were similarly down-regulated, implicating increased urothelial permeability, whereas bradykinin B(1) receptor, cannabinoid receptor CB1 and muscarinic receptors M3-M5 were up-regulated. Using cell-based models, we show that prolonged exposure of NK1R to substance P caused a decrease of NK1R mRNA levels and a concomitant increase of regulatory micro(mi)RNAs miR-449b and miR-500. In the biopsies of BPS patients, the same miRNAs were significantly increased, suggesting that BPS promotes an attenuation of NK1R synthesis via activation of specific miRNAs. We confirm this hypothesis by identifying 31 differentially expressed miRNAs in BPS patients and demonstrate a direct correlation between miR-449b, miR-500, miR-328, and miR-320 and a down-regulation of NK1R mRNA and/or protein levels. Our findings further the knowledge of the molecular mechanisms of BPS, and have relevance for other clinical conditions involving the NK1 receptor.

Pelvic lymph nodes: distribution and nodal tumour burden of urothelial bladder cancer

To evaluate the number of lymph nodes and the lymph node tumour burden in different anatomical pelvic regions to better asses the impact of variations in the extent of lymphadenectomy on reported LN parameters and pelvic tumour clearance.

Individualized seminal vesicle sparing cystoprostatectomy combined with ileal orthotopic bladder substitution achieves good functional results

We review the functional and oncologic outcomes of seminal vesicle and prostate capsule sparing cystectomy combined with ileal orthotopic bladder substitution.

A new multimodality technique accurately maps the primary lymphatic landing sites of the bladder

Pathoanatomic studies have failed to map accurately the primary lymphatic landing sites of the urinary bladder.

Do patients benefit from routine follow-up to detect recurrences after radical cystectomy and ileal orthotopic bladder substitution?

The need for and intensity of follow-up to detect disease recurrence after radical cystectomy (RC) for transitional cell carcinoma (TCC) remains a matter for debate.

Prognostic significance of apoptotic cell death in bladder cancer: a tissue microarray study on 179 urothelial carcinomas from cystectomy specimens

To assess the prognostic significance of apoptosis related markers in bladder cancer.

Sonographic transvaginal bladder wall thickness: Does the measurement discriminate between urodynamic diagnoses?

Measurement of bladder wall thickness (BWT) using transvaginal ultrasound has previously been shown to discriminate between women with confirmed detrusor overactivity and those with urodynamic stress incontinence. Aim of the current study was to determine if vaginally measured BWT correlates with urodynamic diagnoses in a female population.

Induction chemotherapy for unresectable urothelial carcinoma of the bladder

• To analyse the outcome in selected patients with initially unresectable or minimally metastatic muscle-invasive urothelial bladder cancer who underwent induction chemotherapy (IC) followed by radical cystectomy (RC).

How should bladder wall thickness be measured? A comparison of vaginal, perineal and abdominal ultrasound

Measurement of bladder wall thickness using transvaginal ultrasound has previously been shown to discriminate between women with diagnosed detrusor overactivity and those with urodynamic stress incontinence. So far, no comparison has been made between abdominal, perineal and vaginal route for the measurement of bladder wall thickness. The aim of this prospective study was to determine if abdominal, perineal and vaginal ultrasound measurements of bladder wall thickness are comparable with each other.

High CD10 expression predicts favorable outcome in surgically treated lymph node-positive bladder cancer patients

CD10 predicts survival in different cancers. The prognostic significance in bladder cancer still has to be documented. One hundred fifty lymph node-positive bladder cancer patients were treated by cystectomy and standardized pelvic lymphadenectomy in curative intent. CD10 expression was evaluated in tissue microarrays (TMAs) constructed from histopathological normal urothelium, primary tumor (tumor center and invasion front), and corresponding lymph node metastases and correlated with tumor characteristics (stage, extracapsular extension, number, and total diameter of metastases) and survival. CD10 expression was successively lost from normal urothelium to primary tumor to metastases (P < .05) and decreased from the tumor center to the invasion front (P < .002). High CD10 expression in tumor center or invasion front (P < .05) but not in the metastases predicted favorable outcome; the prognostic information in the tumor center was independent from tumor stage and lymph node parameters. High CD10 expression level was not associated with specific tumor characteristics. A well-defined sampling strategy for TMAs allows detection of specific biomarker expression patterns and may generate prognostic information inherent in particular tumor areas. The favorable outcome in bladder cancer patients with high CD10 expression might suggest a tumor suppressive function of CD10.

MMP-2 and MMP-9 in lymph-node-positive bladder cancer

Matrix metalloproteinases (MMP), particularly MMP-2 and MMP-9, participate in tumour progression and metastasis in various cancers. Their significance in urothelial cancer of the bladder (UCB) is unclear. Expression analysis of MMP-2 and MMP-9 in tissue microarrays (TMA) constructed of corresponding samples from histopathological normal urothelium, tumour centre and invasion front of primary tumours and lymph-node (LN) metastases might help to elucidate their relevance in UCB.