Bladder Neoplasia in Pediatric Patients-A Single-Center Experience Including a Case Series.

Objective: Bladder lesions like urothelial carcinoma are rare in the first two decades of life. A biopsy of the bladder or urinary cytological examination is seldom required. Gross painless hematuria is the most relevant clinical syndrome. Methods: A retrospective analysis of surgical pathology records collected between 1984 and 2014 at our institution was performed in a search for cases of urothelial neoplasms originating within the urinary bladder in pediatric patients. Diagnoses were confirmed based on pathologic examination using the 2004 World Health Organization (WHO) classification system. We selected keywords such as bladder neoplasia, bladder lesion, urothelial neoplasia, rhabdomyosarcoma, and children. In addition, we describe clinical presentation and diagnostic procedures as well as treatment and follow-up of two patients. A review of the literature was performed to analyze recommendations concerning diagnostic staging, treatment, and follow-up examinations as well as surveillance of urothelial tumors in the pediatric population. Results: Screening the pathology database of the Institute of Medical Genetics and Pathology of the University Hospital Basel between 1988 and 2014 yielded 287 samples involving the urinary bladder, 110 autopsies, 135 biopsies, and 42 cytology specimens. Of these, most samples originated from malformations and inflammation. Only five were tumors: two were urothelial tumors and three were rhabdomyosarcomas. The majority of specimens comprised resections of the diverticula or distal ureter. Our case reports include two patients with a urothelial tumor. Among the urothelial tumors, one was a papillary urothelial neoplasm of low malignant potential (PUNLMP). Painless hematuria was the directing clinical symptom. The tumor was investigated by FISH, and a 9p21 deletion was found. The second tumor-like lesion was a fibroepithelial polyp arising from the bladder neck. Conclusions: Bladder tumors in children are rare and mostly consist of urothelial and mesenchymal neoplasms. Rhabdomyosarcoma is the most common malignant bladder tumor in childhood. Similar to adult urothelial neoplasms, the loss of 9p21 is also implicated in urothelial neoplasms in childhood. Despite an increasing number of case reports and small series published within the last 2 decades, general treatment protocols including recommendations for staging, tumor markers, and follow-up examinations are still not yet available for this tumor entity in the pediatric population.

Decision regret related to urinary diversion choices after cystectomy among Chinese bladder cancer patients.

AIM: To explore factors associated with decision regret after cystectomy among Chinese bladder cancer patients. METHODS: This cross-sectional study involved 112 patients, who had received radical bladder cancer resection. Participants were recruited from August 2021 until January 2022. The decision regret scale (DRS), decision conflict scale (DCS), and the Functional Assessment of Cancer Therapy-Bladder cancer (FACT-BL) form were used to measure decision regret, decision conflict, and quality of life. Investigator-designed items further explored perceptions involved in decision-making participation and outcomes. RESULTS: The average score for decision regret was 26.21 (SD 15.886), while decision conflict was 20.27 (SD 13.375) and quality of life was 94.74 (SD 20.873). 57.1% of our participants had a little knowledge about the quality of life of patients who chose an alternate urinary diversion method; however, only 13.4% reported having a clear understanding. In addition, 8.9%, 26.8%, and 36.6% thought that quality of life related to alternate decisions was poor, average, or good, respectively. Multiple regression analysis suggested that decision regret is associated with decision conflict, quality of life, and the perceptions that others (who took alternate urinary diversion decisions) had a better quality of life. CONCLUSION: Decision regret is common among Chinese bladder cancer patients, after cystectomy. The prevalence of regret appears to be much higher in Chinese bladder cancer patients compared to similar studies from other regions. Decisions in mainland China are often made by the treating physician or by family members which may cause more profound regret. However, education and economic status are positively related to higher levels of regret which creates questions around knowing, participation, and expectations, which must be explored.

Hyperthermic Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: Results of the HIVEC-1 Trial.

BACKGROUND: Optimising therapeutic strategies of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC) is needed. OBJECTIVE: To compare recurrence-free survival (RFS) with adjuvant intravesical mitomycin C (MMC) at normothermia or hyperthermia using the COMBAT bladder recirculation system at 43 °C for 30 and 60 min. DESIGN, SETTING, AND PARTICIPANTS: A prospective open-label, phase 3 randomised controlled trial (HIVEC-1) accrued across 13 centres between 2014 and 2020 in Spain. After complete transurethral resection of the bladder and immediate postoperative MMC instillation, patients with IR-NMIBC were randomised (1:1:1) to four weekly followed by three monthly 40-mg MMC instillations at normothermia (control; n = 106), 43 °C for 30 min (n = 107), or 43 °C for 60 min (n = 106) were investigated. Therapeutic compliance was defined as four or more instillations. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was RFS at 24 mo in the intention-to-treat (ITT) and per-protocol (PP) populations. The secondary outcomes included progression-free survival at 24 mo, safety outcome measures, and changes in health-related quality of life. Log-rank, Fisher, χ2, and analysis of variance tests were used. RESULTS AND LIMITATIONS: The ITT 24-mo RFS was 77% for control, 82% for 43 °C-30 min, and 80% for 43 °C-60 min (p = 0.6). The PP 24-mo RFS was 77% for control, 83% for 43 °C-30 min, and 80% for 43 °C-60 min (p = 0.59). Six patients progressed to muscle-invasive disease in the ITT population (four in the control, 43 °C-30 min, and 43 °C-60 min groups each) and four in the PP population (all controls). Serious adverse events occurred in 26 patients (8.1%), and we were unable to demonstrate a difference between groups (p = 0.5). Adverse events, mainly dysuria and spasms, occurred in 124 patients (33% in control, 35% in 43 °C-30 min, and 48% in 43 °C-60 min; p = 0.05). The total International Prostate Symptom Score worsened by 1.2 ±â€¯7.3 points, similarly across groups (p = 0.29). The Functional Assessment of Cancer Therapy-Bladder domains and indexes showed no significant change. CONCLUSIONS: Four-month adjuvant hyperthermic MMC using the COMBAT system for 30 and 60 min in IR-NMIBC is well tolerated, but we did not find it to be superior to normothermic MMC at 24 mo. PATIENT SUMMARY: We were unable to demonstrate the effectiveness of hyperthermia using the COMBAT system in intermediate-risk non-muscle-invasive bladder cancer. Further evaluation of long-term recurrence and progression, and maintenance regimens appears mandatory.

Immune checkpoints inhibitors in the management of high-risk non-muscle-invasive bladder cancer. A scoping review.

PURPOSE: Provide the current state of trials investigating the effectiveness and safety of checkpoint inhibitors in patients with non-muscle invasive bladder cancer. METHODS: We conducted this scoping review following the recommendations of the Joanna Briggs Institute. We searched for MEDLINE, EMBASE, CENTRAL databases, and clinical trials in search engines such as clinicaltrials.gov and clinicaltrialsregister.eu. We included clinical trials in patients over 18 years of age diagnosed with high-risk non-muscle-invasive bladder cancer who suffer treatment failure with Bacillus Calmette-Guérin (BCG). Even those who have not received prior therapy. Those clinical trials also evaluated intravenous- or intravesical-administered immune checkpoint inhibitors and those associated with BCG. RESULTS: Thirteen clinical trials are currently being developed with immune checkpoint inhibitors as a therapeutic alternative in patients diagnosed with non-muscle-invasive urothelial carcinoma of the bladder. Five of these have not received prior therapy with bacillus Calmette-Guérin. The remaining eight studies in patients who received BCG immunotherapy with a poor response are classified as persistent, refractory, or non-responders to BCG therapy. Also, in patients who do not accept surgical management with radical cystectomy. Preliminary results from studies such as SWOG S1605 (NCT02844816) show encouraging antitumor activity and long-lasting response patients with carcinoma in situ with or without papillary disease in terms of disease-free survival and rate free of adverse events. Recently, Keynote-057 (NCT02625961) evidenced that after 36 months of follow-up, Pembrolizumab as monotherapy was tolerable and showed promising antitumor activity in patients with BCG-unresponsive non-muscle-invasive bladder cancer. CONCLUSION: The checkpoint inhibitor response may offer a therapeutic alternative for patients diagnosed with high-risk non-muscle-invasive bladder cancer. However, the complete response rate documented in this scoping review is limited to patients with carcinoma in situ, with mild adverse effects, without reporting severity or death from the intervention.

Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain.

(1) Background: Intravesical mitomycin-C (MMC) combined with hyperthermia is increasingly used in non-muscle invasive bladder cancer (NMIBC), especially in the context of a relative BCG shortage. We aim to determine real-world data on the long-term treatment outcomes of adjunct hyperthermic intravesical chemotherapy (HIVEC) with MMC and a COMBAT® bladder recirculation system (BRS); (2) Methods: A prospective observational trial was performed on patients with NMIBC treated with HIVEC using BRS in nine academic institutions in Spain between 2012-2020 (HIVEC-E). Treatment effectiveness (recurrence, progression and overall mortality) was evaluated in patients treated with HIVEC MMC 40mg in the adjuvant setting, with baseline data and a clinical follow-up, that comprise the Full Analysis Set (FAS). Safety, according to the number and severity of adverse effects (AEs), was evaluated in the safety (SAF) population, composed by patients with at least one adjunct HIVEC MMC instillation; (3) Results: The FAS population (n = 502) received a median number of 8.78 ± 3.28 (range 1-20) HIVEC MMC instillations. The median follow-up duration was 24.5 ± 16.5 (range 1-81) months. Its distribution, based on EAU risk stratification, was 297 (59.2%) for intermediate and 205 (40.8%) for high-risk. The figures for five-year recurrence-free and progression-free survival were 50.37% (53.3% for intermediate and 47.14% for high-risk) and 89.83% (94.02% for intermediate and 84.23% for high-risk), respectively. A multivariate analysis identified recurrent tumors (HR 1.83), the duration of adjuvant HIVEC therapy <4 months (HR 1.72) and that high-risk group (HR 1.47) were at an increased risk of recurrence. Independent factors of progression were high-risk (HR 3.89), recurrent tumors (HR 3.32) and the induction of HIVEC therapy without maintenance (HR 2.37). The overall survival was determined by patient age at diagnosis (HR 3.36) and the treatment duration (HR 1.82). The SAF population (n = 592) revealed 406 (68.58%) patients without AEs and 186 (31.42%) with at least one AE: 170 (28.72%) of grade 1-2 and 16 (2.7%) of grade 3-4. The most frequent AEs were dysuria (10%), pain (7.1%), urgency (5.7%), skin rash (4.9%), spasms (3.7%) and hematuria (3.6%); (4) Conclusions: HIVEC using BRS is efficacious and well tolerated. A longer treatment duration, its use in naïve patients and the intermediate-risk disease are independent determinants of success. Furthermore, a monthly maintenance of adjunct MMC HIVEC diminishes the progression rate of NMIBC.

The coexpression of fibroblast activation protein (FAP) and basal-type markers (CK 5/6 and CD44) predicts prognosis in high-grade invasive urothelial carcinoma of the bladder.

High-grade urothelial carcinoma (UC) of the bladder is a heterogeneous disease with dismal prognosis. Bladder tumors with basal phenotype are intrinsically aggressive, and morphological parameters that define disease staging remain main prognosticators. We intend to evaluate the role of cancer-associated fibroblasts (CAFs) in the prognosis of bladder cancer and its association with basal and luminal phenotypes. Clinical and pathological parameters, including the immunohistochemical expression of fibroblast activation protein (FAP) and markers of basal (CK5/6, CD44) and luminal (CK20, GATA3) phenotypes, have been investigated in a series of 121 patients with UC of the bladder treated by radical cystectomy with lymph node dissection, and their implication in long-term cancer-specific survival has been evaluated. A cytoplasmic immunostaining of FAP in CAFs implies worse disease-specific survival (hazard ratio [HR] = 1.68; P = .048). FAP expression is associated with tumor staging (P < .0001), with best discrimination at T2a/T2b level, and with negative expression of markers of luminal phenotype, such as CK20 (P < .0001) and GATA3 (P = .005). In the multivariate analysis, simultaneous expression of FAP, CK5/6, and CD44 is a strong prognosticator of disease-specific survival (HR = 2.3; P = .001), together with nodal invasion (HR = 3.47; P < .0001) and bladder infiltration up to deep muscle or beyond (HR = 2.47; P = .02). There is no association between positive FAP expression in primary tumor and nodal disease (P = .22). FAP expression in CAFs favors tumor invasion in high-grade invasive UC of the bladder with basal phenotype. This new immunohistochemical marker could be added to the routine immunohistochemical protocol to predict clinical behavior in these patients.

Educational Case: Bladder Carcinoma In Situ.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Equine idiopathic hemorrhagic cystitis: Clinical features and comparison with bladder neoplasia.

BACKGROUND: A new syndrome of hematuria in horses has been documented. HYPOTHESIS/OBJECTIVES: Hemorrhagic cystitis is a novel cause of stranguria and hematuria in horses. This syndrome may be difficult to differentiate from bladder neoplasia because they share several clinical features. ANIMALS: Eleven horses with idiopathic hemorrhagic cystitis and 7 horses with bladder neoplasia. METHODS: Retrospective cohort study. RESULTS: Hemorrhagic cystitis was detected on cystoscopy of affected horses, with hemorrhagic and thickened apical bladder mucosa. Clinical signs and endoscopic appearance of the bladder resolved within 3-8 weeks. Histopathology of bladder mucosal biopsy specimens featured neutrophilic and hemorrhagic cystitis. Histopathology was suggestive of dysplasia or neoplasia in 3 horses with hemorrhagic cystitis, yet the horses experienced complete resolution, suggesting that small biopsy specimens obtained by endoscopy can be difficult to interpret. Horses with bladder neoplasia had lower hematocrits, were older, more likely to be female, and more likely to have a mass detected on ultrasonographic examination of the bladder than horses with hemorrhagic cystitis syndrome. CONCLUSIONS AND CLINICAL IMPORTANCE: Hemorrhagic cystitis represents a novel differential diagnosis for horses with hematuria, and is associated with a favorable prognosis. Although histopathology may suggest a neoplastic process, affected horses should be monitored cystoscopically, because complete resolution of hemorrhagic cystitis occurs. The cause of this disease is unknown, and warrants investigation.

Urothelial neoplasms in pediatric and young adult patients: A large single-center series.

PURPOSE: Bladder cancer is the sixth most common cancer in the United States, but is exceedingly rare in young patients, leading to a lack of accepted standards for diagnosis, treatment, and surveillance. We review our institutional experience with bladder urothelial neoplasms in pediatric and young adult patients summarizing presentation, treatment, and outcomes. METHODS: Surgical pathology records at our institution were searched for cases of urothelial neoplasms among patients ≤25 years of age treated between January 1997 and September 2016. Cases submitted exclusively for pathology review were excluded. Diagnoses were confirmed based on pathologic examination using the 2004 World Health Organization classification system. RESULTS: Thirty-four patients were identified with a mean age of 21.1 years (range 8-25 years), and median follow-up was 25.1 months (1-187 months). The male to female ratio was 1.83:1. The most common presenting symptom was hematuria (n=26; 76%). Diagnoses were invasive urothelial carcinoma (n=3), noninvasive urothelial carcinoma (n=24), PUNLMP (n=6), and urothelial papilloma (n=1). Noninvasive lesions were resected by cystoscopy, after which 12% (n=4) experienced complications (grade II or greater). One patient with stage IV invasive disease at diagnosis died, and 2 patients developed recurrences. Of those with noninvasive carcinoma, 29% (n=7) required repeat cystoscopy soon after initial TURBT at outside institutions, and 17% (n=4) had tumors downgraded from high-grade to low-grade after pathology review. CONCLUSION: Hematuria is the most common sign of bladder neoplasia in children and young adults and should be investigated by cystoscopy. The majority of urothelial neoplasms in these patients are noninvasive and can be successfully treated with transurethral resection. LEVEL OF EVIDENCE: Level IV (Retrospective study with no comparison group).

Skeletal Metastasis of Canine Urothelial Carcinoma: Pathologic and Computed Tomographic Features.

Invasive urothelial (transitional cell) carcinoma (UC) is the most common cancer in the canine urinary tract. Prolonged survival of dogs with UC due to better management of the primary tumor and prevention of urethral obstruction might have contributed to an apparent increase in distant metastasis. Metastasis to bone is particularly concerning because the ensuing pain often leads to euthanasia; however, little is known of the frequency, site, or nature of UC skeletal metastasis. In a retrospective analysis, 17 (9%) of 188 canine UC cases had histologically confirmed skeletal metastasis, mainly to the vertebrae. In a prospective analysis of 21 dogs with UC that underwent total body computed tomography (CT) at euthanasia followed by a standardized pathologic examination, skeletal lesions detected on CT were suspected to be metastatic in 4 dogs and were confirmed as metastatic UC histologically in 3 (14%) dogs. In all 3 cases, skeletal metastasis had been suspected based on history and physical examination; however, 1 dog had additional CT-detected skeletal metastases in a clinically unsuspected location, and 2 dogs had histologically confirmed skeletal metastases that corresponded to nonspecific osseous lesions on CT. These findings suggest that total body CT could be helpful in detecting skeletal metastasis as a cause of bone pain in dogs with UC as well as in identifying clinically "silent" sites of skeletal metastasis.

Fulguración con láser de la recidiva de tumores vesicales superficiales bajo anestesia local: diseño de procesos / Laser fulguration of superficial bladder tumor recurrence under local anesthesia. design process

Introduction: The process design is one of the most interesting tools to ensure the quality of health care before the start of an activity. Although the gold standard treatment of superficial bladder tumors remains transurethral resection (TUR), the onset of laser energy source with better endourological systems allows us to adopt alternative therapies. The aim of this pilot study is to describe the design and protocol in 37 patients with a novel process consisting of outpatient treatment under local anesthesia of bladder tumors with holmium laser. Material and Methods: Pilot study includes 37 patients between January 2012 and December 2013, for the development of a process of holmium laser bladder fulguration without anesthetic infiltration in outpatient study. It analyzes and studies the procedure tolerance, development of immediate complications, visual analog scale (VAS) of pain, patient satisfaction, hospital stays avoided, problems during the application process and development. Results: The mean age of the patients was 69.2 +/- 10.3 years, 100 percent of patients prefer this procedure instead conventional transurethral resection and VAS rating presenting ≤ 3. There were no important complications. Only one patient was admitted at hospital due to hematuria resolved without surgical treatment. Conclusions: The development and implementation of fulguration of superficial papillary bladder tumors with holmium laser process is simple, well tolerated, ambulatory and without complications, with no need of hospital stay.

Introducción: El diseño de procesos es una de las herramientas de mayor interés para asegurar la calidad de la asistencia sanitaria antes del comienzo de una determinada actividad. Aunque el gold standard del tratamiento de los tumores vesicales superficiales sigue siendo la resección transuretral (RTU), la aparición de la fuente de energía láser con mejores medios endourológicos nos permite adoptar otras alternativas terapéuticas. El objetivo de este estudio piloto es describir el diseño y protocolo en 37 pacientes de un proceso novedoso consistente en el tratamiento en régimen ambulatorio y bajo anestesia local intravesical de los tumores de vejiga con láser de holmium. Material y Métodos: Estudio piloto que incluye 37 pacientes entre enero de 2012 y diciembre de 2013, para la elaboración de un proceso de fulguración vesical con láser de holmium sin infiltración anestésica en régimen ambulatorio. Se analiza y estudia tolerancia al procedimiento, desarrollo de complicaciones inmediatas, escala visual analógica (EVA) del dolor, satisfacción del paciente, estancias hospitalarias evitadas, problemas durante la aplicación del proceso y desarrollo del mismo. Resultados: La edad media de los pacientes fue 69,2 +/- 10,3 años, presentando puntuación EVA ≤ 3. No existieron complicaciones importantes. Hubo un ingreso por hematuria tardía que se resolvió de forma conservadora. Conclusiones: La elaboración y aplicación del proceso de fulguración de tumores vesicales papilares superficiales con láser holmium es una técnica sencilla, con buena tolerancia, ambulatoria y sin complicaciones de interés, con eliminación de estancias hospitalarias.

Association between the interaction polymorphisms of interleukin-l0 and smoking on patients with bladder cancer risk from a case-control study / 中华流行病学杂志

Objective To investigate the relationship between both polymorphisms of interleukin-10 (IL-10),smoking and the susceptibility to bladder cancer.Methods A case-control study was conducted to study the promoter polymorphisms of IL-10 gene by allele specific PCR amplification (AS-PCR) and to explore the possible genetic and environmental factors on bladder cancer,based on data from a hospital which included 400 patients with bladder cancer and another 400 healthy controls.Results The genotypes of IL-10 gene might be associated with the susceptibility to bladder cancer.Homozygous mutant of IL-10 gene at the point of 1082,819 and 592 could enhance the risk of bladder cancer (OR value is 2.058,1.979,1.979,respectively).No statistically significant correlation was found between the divergence of IL-10 genotype and the different clinical stages and pathological grade of bladder cancer (P＞0.05).Interactions were noticed between polymorphisms in IL-10 gene and their correlation with smoking on bladder cancer.The positive interaction of 1082 site homozygous variant (AA),819 site homozygous variant (TT),592 site homozygous variant (AA) and smoking were revealed in the occurrence rates of bladder cancer (OR=2.264,γ=l0.213;OR=2.438,γ=6.750; OR=2.438,y=6.750).Conclusion Our research findings showed that the significant interactions between IL-10 gene with homozygous mutant and smoking might increase the risk of bladder cancer.

Cistectomia radical videolaparoscópica com neobexiga ileal ortotópica: experiência inicial / Laparoscopy radical cystectomy with ileal orthotopic blad - der: A preliminary experience

Apesar de ser o padrão-ouro no tratamento dos tumores invasivos de bexiga, a cistoprostatectomia ainda apresenta significativo impacto na qualidade de vida dos pacientes. As abordagens minimamente invasivas têm ganhado cada vez mais espaço no tratamento das neoplasias urológicas. Ainda são poucas as séries na literatura sobre o acesso videolaparoscópico para confecção de neobexiga ortotópica após a cistoprostatectomia radical. Relata-se um caso de câncer invasor de bexiga tratado de forma laparoscópica com ótimo resultado. As vantagens do acesso laparoscópico, assim como alguns detalhes técnicos, são discutidas.

Although it is not considered a gold standard in treating invasive bladder tumors, cystoprostatectomy still has significant impacts on patients? life quality. The minimally invasive approaches have gained importance in the treatment of bladder neoplasia. There are sill few reports on the use of laparoscopy for providing orthotopic bladder upon radical cystoprostatectomy. This is a case report of invasive bladder cancer that was treated with laparoscopy and yielded optimal result. The advantages of laparoscopy and some technical details are herein discussed.

Malignancy after gastrointestinal augmentation in childhood.

INTRODUCTION: To review the incidence and risks of bladder cancer following gastrointestinal augmentations done for congenial anomalies in childhood. MATERIALS AND METHODS: A literature search using PubMed and Ovid Medline search engines was performed. MeSH terms evaluated were; bladder augmentations, enterocystoplasty, gastrocystoplasty, spina bifida, spinal dysraphism, myelodysplasia, neural tube defects, posterior urethral valves and bladder exstrophy were cross referenced with the terms, bladder cancer and urinary bladder neoplasm. All patients who developed a bladder cancer following a bladder augmentation for a congenital anomaly were reviewed. RESULTS: A total of 20 cases of bladder cancer following augmentations for congential anomalies, were identified, 9 arose following ileal cystoplasty, 3 following colocystolasty and 8 following gastrocystoplasty. The incidence of cancer developing per decade following surgery was 1.5% for ileal/colonic and 2.8% for gastric bladder augmentations. The majority of cancers developing within the augmented bladder are at advanced stages at the time of diagnosis (60%; 12/20 cases were ≥T3 at diagnosis). Several of the cases that developed occurred in patients exposed to known carcinogenic stimuli and/or arose in bladders with a known predisposition to carcinoma. CONCLUSION: Patients augmented with ileal or colonic segment for a congenital bladder anomaly have a 7-8 fold and gastric augments a 14-15 fold increased risk for the development of bladder cancer over standard norms. Published data is however unable to determine if gastrointestinal bladder augmentation is an independent risk factor for cancer over the inherent risk of cancer arising from a congenitally abnormal bladder.