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Background: Intravesical chemotherapy and bacillus Calmette-Guérin (BCG) reduce the recurrence rate in patients with stage Ta T1 urothelial bladder cancer; however, the benefit of BCG relative to chemotherapy for long-term end points is controversial, especially in intermediate-risk patients., Objective: The aim of the study was to compare the long-term efficacy of BCG and epirubicin., Design, Setting, and Participants: From January 1992 to February 1997, 957 patients with intermediate- or high-risk stage Ta T1 urothelial bladder cancer were randomized after transurethral resection to one of three treatment groups in the European Organization for Research and Treatment of Cancer Genito-Urinary Group phase 3 trial 30911., Intervention: Patients received six weekly instillations of epirubicin, BCG, or BCG plus isoniazid (INH) followed by three weekly maintenance instillations at months 3, 6, 12, 18, 24, 30, and 36., Measurements: End points were time to recurrence, progression, distant metastases, overall survival, and disease-specific survival., Results and Limitations: With 837 eligible patients and a median follow-up of 9.2 yr, time to first recurrence (p<0.001), distant metastases (p=0.046), overall survival (p=0.023), and disease-specific survival (p=0.026) were significantly longer in the two BCG arms combined as compared with epirubicin; however, there was no difference for progression. Three hundred twenty-three patients with stage T1 or grade 3 tumors were high risk, and the remaining 497 patients were intermediate risk. The observed treatment benefit was at least as large, if not larger, in the intermediate-risk patients compared with the high-risk patients., Conclusions: In patients with intermediate- and high-risk stage Ta and T1 urothelial bladder cancer, intravesical BCG with or without INH is superior to intravesical epirubicin not only for time to first recurrence but also for time to distant metastases, overall survival, and disease-specific survival. The benefit of BCG is not limited to just high-risk patients; intermediate-risk patients also benefit from BCG., Trial Registration: This study was registered with the US National Cancer Institute clinical trials database [protocol ID: EORTC-30911]. http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=77075&version=HealthProfessional&protocolsearchid=6540260., (Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To ascertain which variables of bladder urothelial carcinoma (UC) might be useful in predicting either UC involving the prostate (UCP) or incidental prostate adenocarcinoma in radical cystoprostatectomy specimens., Methods: The bladder and whole-mount prostate sections of 248 radical cystoprostatectomy specimens were reviewed. Stepwise discriminant analysis was used to predict UCP or incidental prostate adenocarcinoma., Results: UCP was present in 94 patients (37.9%). UC originated from the prostatic urethra and periurethral ducts in 78 (31.45%), and isolated direct extension of UC from the bladder was present in 16 patients (6.45%). The periurethral ducts coexisted with direct extension of bladder UC in 11 patients (4.4%). Prostate adenocarcinoma was identified in 123 patients (49.6%). Carcinoma in situ and high-grade urothelial papillary carcinoma were seen in 8 (3.2%) and 5 (2.0%) patients, respectively. In 57 (23%), 64 (25.8%), and 87 (35.1%) patients, UC had invaded the subepithelial connective tissue, muscularis propria, and perivesical tissue, respectively. UC was multifocal in 53 patients (21.4%). The tumor was in the trigone and bladder neck in 160 patients (64.5%). Of the 248 patients, 98 (39.5%) had a history of recurrence. Stepwise discriminant analysis selected 3 variables of bladder UC (previous recurrence and location and number of foci) and correctly predicted the group in 72.2% of patients without and with UCP. Discriminant analysis selected 2 variables of bladder UC (focality and previous recurrence) and correctly predicted the group in 57.7% of patients without and with prostate adenocarcinoma., Conclusions: Our approach can identify bladder UC variables that could guide urologists in the selection of the most appropriate surgical procedure.

Objectives: In 1998, a revised system of classifying noninvasive papillary urothelial neoplasms of the urinary bladder was proposed and subsequently formally adopted by the World Health Organization (WHO). The introduction of this new system was justified as being potentially superior on a number of levels to the 1973 WHO classification system that it replaced. Specifically, a new category of neoplasms, designated papillary urothelial neoplasm of low malignant potential (PUNLMP), was considered advantageous for several reasons. The new system was expected to gain widespread acceptance, improve reproducibility of diagnoses among pathologists, and enhance the correlation between urine cytology and tumor histology. We examine the history of the changes in terminology for these lesions, the relative merits of PUNLMP terminology, the extent to which the expectations accompanying the new grading system have been met, and the extent to which the new system has enhanced the management of patients with noninvasive papillary urothelial neoplasms of the bladder., Methods: A PubMed literature search after the introduction of this new classification was performed and relevant papers reviewed., Results and Conclusions: The 2004 WHO classification is a positive initiative in attempting to standardize urothelial tumor grading by expanding and clearly defining the morphologic characteristics of noninvasive papillary urothelial neoplasms. The new terminology used in this system is of questionable validity and utility. Full-genome searches for prognostic and predictive molecular gene expression signatures, GeneChip technology and proteomics techniques, and several new biomarkers and molecular tests may be useful in future grading schemes after their clinical utility is better established.

Transitional cell carcinoma (TCC) is a multifocal disease of the urinary tract that can also involve the prostatic urethra (PU). The exact incidence of superficial involvement of the PU in patients with bladder TCC is not well known. Bladder TCC may involve the prostate in 12-40% of the patients and the degree of involvement can include urethral mucosa, ducts, acini, and stroma of the gland, which has been shown to affect the outcome. Risk factors for superficial urothelial cancer in the PU are high-grade, multifocal bladder TCC and presence of carcinoma in situ (CIS) in the bladder. While visible tumors are easy to detect and resect, controversy still exists regarding the optimal technique to identify prostatic involvement by TCC. Prostatic urethral sampling by a transurethral resection biopsy or a cold-cup biopsy, particularly in the high-risk group of bladder cancer patients, has been recommended for detecting prostatic urethral involvement. Management of superficial prostatic involvement by TCC is also unclear. Currently, there is increasing recognition of the value of conservative treatment options with intravesical agents when there is superficial involvement of the PU. Particularly, intravesical bacillus Calmette-Guèrin (BCG) seems to be an effective treatment alternative in the management of superficial involvement of the PU by TCC. Close follow-up by cystoscopy and PU biopsy at 3-month intervals, particularly in intermediate and high-risk patients who respond to intravesical therapy and in whom cystectomy is appropriate, is recommended in order to detect persistent tumor, recurrences, or progression.

Objective: Prostatic transitional cell carcinoma (TCC) may involve urethral mucosa, ducts, acini and stroma of the gland. In this study, we evaluated the risk factors for mucosal prostatic urethral (PU) involvement in superficial TCC of the bladder., Methods: The data of 340 consecutive male patients with the diagnosis of primary superficial TCC of the bladder who were treated at our institution were reviewed. Median age of the patients was 64 years and median follow-up was 66 months. The impact of pathological stage, grade, tumour multiplicity and presence of carcinoma in situ (CIS) on mucosal PU involvement were evaluated., Results: Twenty one patients (6.2%) had mucosal involvement of the PU and concomitant multifocal TCC of the bladder. Of those, 12 patients (3.5%) had macroscopic mucosal involvement of the PU while the other 9 patients (2.7%) had microscopic tumour. Increased pathological stage, grade and tumour multiplicity were found to be risk factors for mucosal PU involvement in patients with superficial bladder cancer. Multivariate analysis showed that only the tumour multiplicity was found to be an independent risk factor for mucosal PU involvement by TCC (p=0.001)., Conclusions: The incidence of mucosal PU involvement increases as the stage, grade and number of tumours increase in patients with superficial TCC of the bladder. We recommend PU sampling particularly in patients with multiple bladder tumours which may have an impact on further management of these patients.

Objective: Vitamin D receptors (VDR) have been detected in normal tissues and in a number of cancer types. This study was undertaken to determine the VDR expression status and to elucidate the prognostic significance of VDRs in superficial transitional cell carcinoma (TCC) of the human bladder., Methods: VDR expression was investigated in the tumour tissue blocks which were obtained by transurethral resection from 105 patients with superficial TCC without concomitant carcinoma in situ and in 30 control subjects. Median follow-up of the patients was 40 months. The expression of nuclear VDR was evaluated immunohistochemically using avidin-biotin-peroxidase method and a monoclonal VDR antibody. VDR staining intensity in samples were assessed semi-quantitatively and graded as [-] if VDR was lacking, [+] if <33% of cells were stained, [++] if 33-66% of cells and [+++] if >66% were stained. Staining characteristics were compared with the clinico-pathologic results., Results: VDRs were detected in 85.7% of the patients with superficial TCC and in 66.6% of the controls (p = 0.02). No correlation was found between VDR expression and pathological stage and grade (p = 0.05 and p = 0.09, respectively). Progression in pathologic stage was significantly higher in VDR[+++] tumours (p = 0.001). Also, disease-free survival was significantly lower and tumour size was significantly greater in VDR [+++] tumours than [-], [+] and [++] ones (p = 0.02, p = 0.008 and 0.007, respectively). No significant difference was found between patient age, sex, tumour multiplicity in terms of VDR expression. Survival was not affected by VDR expression. In multivariate analysis VDR expression was not found to be an independent prognostic factor., Conclusion: Superficial TCC of the bladder express VDRs. The association of increased VDR expression and higher disease progression may be useful in discriminating less differentiated superficial TCCs with poor outcome.

Objective: Treatment of patients with mucosal prostatic urethral transitional cell carcinoma (TCC) is controversial. In this study, we evaluated the outcome of patients with mucosal prostatic urethral TCC who were managed conservatively., Methods: The data of 290 consecutive male patients with superficial TCC of the bladder who were treated at our institution were reviewed. Median age was 63 years and median follow-up was 63 months. Initially, all patients with mucosal PU involvement without evidence of ductal and/or stromal involvement underwent intravesical BCG or Epirubicin therapy., Results: Nineteen patients (6.6%) had mucosal involvement of the prostatic urethra (PU) and concomitant multifocal TCC of the bladder. Of those, 12 patients (12/19, 4.2%) had macroscopic mucosal involvement of the PU, while the other 7 patients (7/19, 2.4%) had microscopic PU tumor. Seven of 12 patients who were treated with BCG and 2 of 7 patients who were treated with Epirubicin achieved complete response. Progression occurred in 3 patients who received BCG and no patients progressed in the Epirubicin group., Conclusions: Prostatic urethral sampling should be considered necessary in intermediate and high risk patients with superficial TCC of the bladder. Intravesical therapy, especially with BCG seems to be an effective treatment alternative in the management of mucosal PU involvement.

Background: Gemcitabine (GEM) is an alternative chemotherapeutic agent for patients with metastatic bladder cancer. It is believed to be a well-balanced agent, having acceptable toxicity and enhanced antitumor activity. The integration of GEM into the initial chemotherapy plan for these patients is still being developed., Case Report: The patient, male, aged 56 years, was suffering from a transitional cell carcinoma of the bladder. Due to frequent local superficial recurrences, radical cystectomy with pelvic lymphadenectomy and continent ileal diversion was performed. Four years after the operation a left inguinal lymphadenopathy was noted and metastatic bladder carcinoma was confirmed on biopsy. Cytotoxic therapy combining GEM and cisplatin and local external irradiation therapy was initiated. The patient developed extensive necrotising vasculitis with muscle damage after the second course of therapy. Chemotherapy was stopped immediately but this was not enough to relieve the symptoms of severe myalgia and swelling, and additional treatment consisting of cyclophosphamide and prednisolone was initiated., Conclusion: Although GEM seems to be relatively safe, some unexpected complications may occur during treatment. This case is not common, but it reinforces the need for careful attention to any new symptoms that seem to be unassociated with the primary disease. Prompt evaluation of such symptoms should be carried out in patients receiving GEM therapy.

We report a case of a urothelial carcinoma with trophoblastic differentiation of the bladder that occured in a 23-year-old man. The patient presented with hematuria. Multiple papillary masses were resected transurethrally. Histopathologically, grade III urothelial cell carcinoma contained giant cells that were positive for human chorionic gonadotrophin (HCG), placental alkalen phosphatase, and human placental lactogen. HCG secreting tumors are reported to be highly aggressive. The patient is alive and well without evidence of recurrent disease or metastasis at 10 months from transurethral resection. To our knowledge, this case is the youngest patient in the literature so far.

Transitional cell carcinoma (TCC) of ureter and renal pelvis is relatively uncommon. Smoking, occupational carcinogens, analgesic abuse, Balkan nephropathy are the risk factors. Cytogenetic studies revealed that the most frequent aberration is the partial or complete loss of chromosome 9. Approximately 20-50% of patients with upper urinary tract (UUT) TCC have bladder cancer at some point on their course, whereas the incidence of UUT TCC after primary bladder cancer is 0.7-4%. Excretory urography and retrograde pyelography are the conventional diagnostic tools; however, ureteropyeloscopy combined with cytology and biopsy is more accurate. Grade and stage of the disease have the most significant impact on survival. Nephroureterectomy with bladder cuff excision has been the mainstay of treatment. Local resection may be appropriate for distal ureteral lesions especially when the disease is low grade and stage. Advances in endourology have made it possible to treat many tumors conservatively. Ureteroscopic and to a certain extent percutaneous surgical approaches are widely used today especially in patients with low grade, low stage disease. Endoscopic close surveillance is mandatory for these patients. Adjuvant topical therapies appear to be safe but confirmation of any benefits awaits the results of further large studies. More recently, laparoscopic techniques have become a viable alternative to open surgery, but long term cancer control data are lacking. Aggressive surgical resection does not affect the outcome of patients with advanced disease. Adjuvant radiotherapy is ineffective, and systemic chemotherapy results in a low complete response rate for patients with metastases.

The purpose of this study is to evaluate the expression of p53 and mdm2 and to determine whether they may be used as additional predictors of recurrence in superficial transitional cell carcinoma of the bladder. Paraffin sections of 80 patients with superficial transitional cell carcinoma of the bladder, who were treated with transurethral resection, were stained with p53 and mdm2 antibodies using the standard avidin biotin immunoperoxidase method. Nuclear staining for both p53 and mdm2 was calculated as the percentage of labeled nuclei out of a total number of tumor cells counted. The percentage of p53- and mdm2-positive cells showed a significant relationship with tumor grade and recurrence (p = 0.002 and p = 0.016; p = 0.01 and p = 0.003, respectively). In addition, a weak inverse relationship was found between p53 and mdm2 values (r = -0.184). p53 and mdm2 reactivities are valuable parameters in predicting recurrence in superficial bladder cancer. Thus, mdm2 expression appears to play a role in predicting biologic behavior in superficial transitional carcinoma of the bladder.

Objectives: The role of estrogens in human bladder cancer still remains to be resolved. This study was undertaken to determine the estrogen receptor (ER) expression status and to elucidate the prognostic significance of ER in superficial transitional cell carcinoma (TCC) of the human bladder., Methods: Tumor tissue blocks which were obtained by transurethral resection (TUR) from 121 patients with superficial TCC and 30 control subjects were investigated. Median follow-up was 40 months. The expression of nuclear ER was evaluated by immunohistochemistry using avidin-biotin-peroxidase method and a monoclonal ER antibody. ER staining intensity in samples was assessed semi-quantitatively. Staining characteristics were compared with the clinico-pathological results., Results: ERs were detected in 12.4% of the superficial TCC patients and in 10% of the controls (P = 0.73). No association was found between ER immuno-reactive score and patients' age, sex, tumor multiplicity or tumor size. An association between the ER staining intensity and higher tumor grade was observed (P = 0.01). Grades I, II and III tumors showed 10.6, 8.7 and 44.4% staining, respectively. Survival was not affected by ER expression. In multivariate analysis ER expression was not an independent prognostic factor., Conclusion: Superficial TCC of the bladder shows low ER expression and it appears that ERs do not have any direct role on the prognosis of patients with superficial TCC.

Objective: To investigate the expression and possible role of pS2 protein as a predictor of tumor recurrence in superficial transitional cell carcinoma of the bladder and to determine its relation with tumor stage, grade, size, number, recurrence and proliferative activity., Methods: Paraffin sections of transurethral resection material from 80 patients with superficial transitional cell bladder carcinoma were stained with pS2 and Ki-67 antibodies using the standard streptavidin biotin immunoperoxidase method. Cytoplasmic pS2 staining was scored on a scale of 1-3 and the Ki-67-labelling index was determined as a percentage of positively staining tumor cells., Results: An inverse relationship was found between pS2 expression and Ki-67 index (p<0.001). pS2 expression showed no relation with any clinicopathological prognostic parameters as well as the recurrence rate. The recurrence rate was only associated with increased tumor number (p = 0.05), while the time to first recurrence was significantly related to tumor size, proliferative activity and tumor grade (p = 0.04, p<0.001, and p = 0.03, respectively). On the other hand, higher tumor grade was correlated with increased tumor number, Ki-67 index and tumor stage (p = 0.016, p = 0.006, and p<0.001, respectively)., Conclusion: pS2 expression is associated with a low proliferative potential of superficial transitional cell carcinoma of the bladder, while it does not seem to be related to the recurrence rate of the tumor and other prognostic factors. Tumor size and proliferative activity may aid in the estimation of the time to the first recurrence.

Objective: To evaluate the significance of nuclear morphometry in predicting the clinical course in superficial (pTa and pT1) bladder cancer., Study Design: The study included 73 patients with superficial transitional cell carcinoma of the bladder who were followed for a median of 21 months (range, 1-90). Nuclear morphometry was performed by a computer-assisted image analyzer system on hematoxylineosin-stained histologic sections and characterized by five nuclear variables: area, perimeter, major and minor diameter, and form factor. Patient charts and microscopic slides were reviewed to record tumor stage, grade and size. Tumor proliferative activity was assessed by immunohistochemical staining with Ki-67 antibody., Results: None of the morphometric variables showed a significant relation to tumor progression and recurrence. Higher values of mean nuclear area, perimeter, and major and minor diameter were significantly related to higher grade and proliferative activity. Mean nuclear area and minor diameter were associated with advanced stage. Of established prognostic factors, only histologic grade was significant in predicting progression., Conclusion: The results suggest that nuclear morphometry may be valuable in determining proliferative activity and may be well correlated with histologic grade in superficial bladder cancer. However, like many other potential prognostic factors, it seems to be unreliable in predicting clinical behavior.

Objectives: To investigate the role of angiogenesis in predicting tumor recurrence and its correlation with established clinicopathologic prognostic factors in superficial transitional cell carcinoma of the bladder., Methods: The paraffin sections of 80 superficial papillary transitional cell bladder carcinoma specimens were stained with CD31 antibody to label the vascular endothelium using the standard streptavidin-biotin-immunoperoxidase method. The vascular surface density (VSD) equivalent to the vascular surface area per unit of tissue volume and number of vessels per square millimeter of stroma (NVES) were assessed by means of stereology, and these morphometric parameters of angiogenesis were statistically analyzed to interpret the relation to tumor recurrence in addition to tumor stage, grade, size, and number and the presence of carcinoma in situ., Results: VSD and NVES values showed no statistically significant difference between pTa and pT1 tumors or patients with and without recurrence. In contrast, VSD and NVES values were found to increase in higher grade tumors (P = 0.019). VSD values were also higher in patients with coexisting carcinoma in situ in pTa tumors (P <0.001). Tumor number and size and recurrence number and time to the first recurrence did not correlate with any vascular parameters., Conclusions: Stereologic assessment of angiogenesis does not help to predict recurrence in superficial bladder cancer. Angiogenic parameters appeared to be well correlated with the conventional histologic grading system. Otherwise, the present study did not show any correlation of angiogenesis with any potential prognostic factors. This may be due to the diverse angiogenic pathways occurring in invasive and superficial tumors.

Objective: Elastase is a serine protease which hydrolyses connective tissue components. Laminin and fibronectin also play an important role in progression and invasion of cancer. The purpose of this study is to investigate the relation between tissue elastase, laminin P(1) and fibronectin levels and tumor characteristics, and analyze the potential of these as prognostic factors in transitional cell carcinoma (TCC) of the bladder., Methods: Thirty-four patients with TCC of the bladder and 11 controls were included in this study. Elastase and fibronectin levels in tissue homogenates were determined using an enzyme immunoassay and laminin P(1) by radioimmunoassay. Mean follow-up was 43 months., Results: The mean elastase level in bladder carcinoma tissue was 120+/-11.42 ng/homogenate protein, while normal tissue level was 12.36+/-2.70 (p<0.01). The carcinoma and normal tissue mean laminin P(1) levels were 7.02+/-0.37 U and 0.65+/-0.10 U/mg homogenate protein, respectively (p<0.01). The mean fibronectin level was 19.97+/-1.45 ng/mg homogenate protein in the carcinoma tissue and 2.16+/-0.40 in normal tissue (p<0.01). There was no correlation between tumor stage, grade, size, multiplicity and elastase, laminin P(1) and fibronectin levels., Conclusion: These results provide evidence that tissue elastase, laminin P(1) and fibronectin levels increase in TCC of the human bladder. Further studies including serum and urine levels should be performed in order to analyze their value as tumor markers in a larger group of patients.

Objectives: The goal of this study was to investigate the relation between serum laminin P1 expression and the grade, stage, size, and multiplicity of the tumors to elucidate the potential role of laminin as a diagnostic and prognostic factor in transitional cell carcinoma (TCC) of the bladder., Methods: Serum concentration of laminin P1 was measured by radioimmunoassay in 38 patients with TCC of the bladder and compared with the serum laminin P1 values obtained from 34 healthy control subjects. Patients were grouped according to their tumor stage, grade, size, and multiplicity to compare the serum laminin P1 values., Results: The mean serum laminin P1 level in the patient group was statistically higher than the controls (P = 1.3 x 10(-8); with the destruction of basement membrane (stages pT1 or greater), a significant increase in the serum value was observed (P = 0.00023). Laminin level was found to be positively related to the tumor size and number; however, no correlation was observed with the grade. In tumors invading the lamina propria and beyond, the sensitivity of laminin P1 was 78.9% and specificity was 97.1%. The positive and negative predictive values of laminin P1 were 93.7% and 89.5%, respectively. The patients whose serum laminin P1 levels were above the upper limit of normal (1.6863 U/mL) were found to have a higher recurrence rate (72%) than the patients who had lower serum values in the control cystoscopies performed 3 months after the first admission (P < 0.01)., Conclusions: Serum laminin P1 seems to be a valuable adjunctive marker to predict tumor invasion and recurrence. This warrants further research.

Blood groups of 50 patients with transitional cell carcinoma of the bladder, who were followed up for a minimum of 3 years, were analyzed. The blood group distribution of the patients reflected that of the general population. There was no relationship between blood groups and stage and grade of the tumour at initial presentation. However, patients with blood group O had worse prognosis than the others.

Records of fifteen patients less than 40 years old with carcinoma of the bladder are reviewed. Fourteen patients with transitional cell carcinoma had well or moderately differentiated superficial papillary tumours. One patient with adenocarcinoma died within 4 months with progressive disease. Four patients experienced recurrences and 9 patients had no recurrence of tumour after a mean follow-up of 55 months. It is concluded that the fate of patients younger than 40 years with bladder cancer is not different from those in older age groups.

Androgen receptors were measured in transitional cell carcinoma tissues obtained from 13 patients with bladder tumours and 3 patients with ureteric tumours. Scatchard analysis of binding of mibolerone, a synthetic androgen, was used for receptor measurement. None of the patients were receptor positive. This study suggests that human male hormones do not play any direct role in the malignant transformation of human transitional cell epithelium.

A possible association between HLA antigens and transitional cell carcinoma of the bladder was searched for in 56 patients and 200 healthy kidney donors. Statistical analysis showed that HLA antigens A23, A25, A28, BW4, BW21, BW22 and CW4 are more common in bladder tumor patients, whereas B27 and BW6 were more common in the control group. The relative risk for HLA CW4 was 2.07 (95% confidence interval 1.51-2.48). Except for CW4, these findings are inconsistent with previous reports. We believe this to be due to various misleading factors, and thus not conclusive. Even if such a statistical association exists, this appears to be clinically not relevant and, therefore, should not alter standard practice.

A retrospective analysis of the blood groups of 74 patients with transitional cell carcinoma of the upper urinary tract is presented. The blood group distribution of the patients reflected that of the general population. No relationship was found between blood groups and stage and grade of the tumour or patient survival. Nor were blood groups predictive of bladder tumour recurrence and stump recurrence in patients who had undergone simple nephrectomy.

We present a retrospective 10 year analysis of 76 patients with urothelial tumours of the upper urinary tract. Patients older than 65 years, and female patients, presented with more advanced stages and had a worse prognosis. The grade and stage of the tumour has the greatest impact on survival. No conclusions can be drawn on the efficacy of various types of surgery, but simple nephrectomy gave a 5-year survival of 68%, with a stump recurrence rate of 15%. We observed that patients with urothelial tumours had 4 fold increased chance of developing gastrointestinal cancer.