Clinical analysis of patients with occupational urothelial tumors

The incidence of occupational urothelial tumor and the accompanied problems were studied on the workers who had manufactured or handled aromatic amines at a certain chemical factory. Twenty-five out of 398 dyestuff workers, who were examined at regular intervals, were found to have urothelial tumors and the incidence rate was 63%. The mean age at onset, the mean period of aromatic exposure and the mean latent period from the initial exposure until tumor development were 61 year-old, 7.2 years and 30 years, respectively. A high incidence rate was found in the long exposed workers and the smoking group. The negative correlation was observed between the age of first exposure to carcinogens and the latent period. The workers who had been exposed to two or three kinds of aromatic amines had the highest incidence followed by those exposed to benzidine and those to alpha-naphthylamine. No urothelial tumor occurred in the workers exposed to beta-naphthylamine. Ninety-four percent of the initial tumors were superficial and transurethral resection of tumors was performed as the initial surgery for the patients with bladder tumors. The recurrence rate in the bladder cavity after the surgery was 39%, which was almost the same rate as that of non-occupational bladder tumors, however, the recurrence rate in the upper urinary tract was high (26%). The positive rate in the examination of urine cytology was 60% for initial tumors, 74% for recurrent tumors. The urine cytology was a significant method for the detection and monitoring of the patients with occupational urothelial tumors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Positive urinary cytology after tumor resection: an indicator for concomitant carcinoma in situ

Concomitant urothelial atypia (grade II atypia or carcinoma in situ) is predictive of new tumor growth after transurethral tumor resection. Concomitant urothelial atypia can be demonstrated by pre-selected site mucosal biopsies. However, a number of patients have new tumors despite normal pre-selected site biopsies. To investigate whether urinary cytology is a better indicator for concomitant urothelial atypia than pre-selected site biopsies, we studied in bladder tumor patients the correlation between the findings of pre-selected site biopsies (8 per patient) at tumor resection and urinary cytology (2 per patient) after successful resection. Concomitant urothelial atypia was demonstrated by biopsies in 52 per cent of the patients, of whom 60 per cent had grade II atypia and 40 per cent had carcinoma in situ. All patients with concomitant carcinoma in situ in biopsies had positive cytology findings. Of the patients with concomitant grade II atypia in biopsies 15 per cent had negative cytology studies. In 48 per cent of the patients no urothelial atypia in pre-selected site biopsies was demonstrable. However, cytology was positive, that is neoplastic cells were present, in 64 per cent of these specimens (19 patients). Of the 19 patients 16 currently have had demonstrable urothelial atypia in pre-selected site mucosal biopsies at a later occasion. We conclude that urinary cytology seems to be a better indicator for the presence of concomitant urothelial atypia than pre-selected site mucosal biopsies and, therefore, it can be used as a screening procedure for patients without demonstrable concomitant carcinoma in situ at tumor resection.     

The clinical significance of urine cytology after a radical cystectomy for urothelial cancer

Objectives: To evaluate the impact of urine cytology on the prediction of the upper urinary tract recurrence (UTR) of urothelial cancer after a radical cystectomy (RC) with urinary diversion. Methods: A total of 125 patients who underwent RC from 1987 to 2005 were retrospectively identified. The median follow‐up period was 64 months. The specimens for urine cytology were obtained from the urine voided or obtained through a catheter or a conduit. The relationship between a positive urine cytology result and UTR detection was determined. Results: UTR was diagnosed in eight patients (6.4%) at a median follow‐up of 63.3 months. The overall rate of a positive urine cytology result was 12.3% for the urine in an ileal conduit, 18.8% in a continental reservoir and 10.5% in an orthotopic neobladder. The overall sensitivity and specificity of the urine cytology for the detection of UTR were 75.0% and 90.6%, respectively. However, UTR could be diagnosed earlier by using urinary cytology, rather than by radiological examinations and/or related symptoms in only 5.9% (1/17 positive urine cytology) of cases. Eleven (64.7%) of 17 patients with positive urine cytology were false positive and eight (72.7%) of the 11 patients with no UTR had a positive urine cytology result only once. Conclusions: Urine cytology after RC was not a potent screening tool for the early detection of UTR because of the difficulty in distinguishing the cancer cells from degenerated intestinal epithelial cells in the urinary diversion urine.     

Urothelial carcinoma related to exposure to aromatic amines

Clinical and statistical observations were made on a group of 438 persons who had worked with aromatic amines (benzidine, 2-naphthylamine, 1-naphthylamine and dianisidine) with reference to their carcinogenic properties in the urinary tract. Urinary tract tumors developed in 68 (15.5%), with an average latent period of 22 years and 11 months. In these 68 cases, upper urinary tract tumors were found in 16 cases, 8 of which had bilateral lesions. The average age of onset was 48.1 ranging from 24 to 79. The incidence of tumors increased with the length of exposure to the amines. There was no finding that smoking habit increased the incidence of tumors in this group. Of the 49 new patients with bladder tumor, urine cytology was positive in 24 (49.0%) and suspicious of malignancy in 10 (20.4%), respectively. This indicated that it could be a useful screening test. Transurethral surgery was most frequently performed as an initial treatment. Recurrence occurred in 50 cases (73.5%), but 5-, 10- and 20-year-survival rates were 89.0 79.3 and 64.7%, respectively, showing a good prognosis. Malignant tumors in other organs developed in 18 (4.1%) of the 438 workers. The incidence of such malignant tumors was significantly higher in the workers who had been exposed to 2-naphthylamine than in others. Our data indicate that close observation is still necessary for early detection of patient with new or recurrent urothelial carcinoma in this group.     

Significance of atypical urinary cytology in the evaluation of patients with end‐stage renal disease for kidney transplantation – a retrospective study

To determine what percentage of renal transplant candidates have atypical urinary cytology, what proportion have urothelial carcinoma and whether cystoscopy is necessary with atypical cytology. All end‐stage renal disease (ESRD) patients (703) presenting for renal transplantation at our institution were retrospectively reviewed. Individuals producing sufficient urine were screened with urine cytology and those with atypical cytology or risk factors for bladder cancer underwent cystoscopy. Four hundred and thirty patients had available urinary cytology and, of these, 151 (35%) had atypical cytology. Of patients with atypical cytology, three were identified to have urothelial carcinoma. However, three additional patients with urothelial carcinoma did not present with atypical cytology. In total, 6 of 703 (0.85%) patients had bladder cancer. All were treated with transurethral resection and eventually underwent renal transplant. One patient has had disease progression post‐transplant to distant metastases. This is the largest study to date evaluating the incidence of urothelial carcinoma in ESRD patients presenting for transplant workup. We found the incidence of bladder cancer to be higher than in the general Canadian population, however, most lesions were low grade. We found atypical cytology in transplant candidates to be a poor predictor for these low‐grade lesions and do not recommend routine cystoscopy for atypical cytology.     

Natural history of positive urinary cytology after radical cystectomy

PURPOSE: The natural history and risk of disease progression in patients with positive urine cytology after radical cystectomy for urothelial carcinoma has not been adequately elucidated. MATERIALS AND METHODS: An institutional review board approved, retrospective review in patients undergoing radical cystectomy was performed to identify those with positive urinary cytology after radical cystectomy. Cox proportional hazards regression was used to determine factors associated with positive cytology after radical cystectomy and upper tract recurrence after positive cytology. Survival curves and probabilities were examined by Kaplan-Meier analysis. RESULTS: A total of 101 patients with at least a single positive urinary cytology result after radical cystectomy were identified. Ureteral involvement in the radical cystectomy specimen was significantly associated with subsequent positive cytology. At the first positive urinary cytology only 9 of 101 patients (9%) had documented urothelial recurrence but eventually 57 of 101 had radiographic evidence of urothelial recurrence. Median freedom from radiological evidence of urothelial recurrence after positive cytology was 2.1 years and ureteral involvement was associated with a higher likelihood of urothelial recurrence. Despite surgical and chemotherapeutic interventions median survival after urothelial recurrence was 2.1 years. CONCLUSIONS: Urine cytology may have a valuable role for detecting upper tract recurrence after radical cystectomy. Most patients with positive cytology after radical cystectomy eventually have radiological evidence of urothelial recurrence. These data may help clarify natural history in patients with positive cytology after radical cystectomy. Additionally, these data indicate the need for diligent evaluation for recurrent disease and potentially the role of early adjuvant therapy in patients with positive cytology after radical cystectomy.     

Urinary cytology studied during 10 days after transurethral resection of bladder tumour and its relation to tumour recurrence

Whether or not recurrence is related to the results of urinary cytology examined within 10 days after transurethral resection of bladder tumour was studied retrospectively in 47 patients with superficial bladder tumour. Of 7 cases with positive cytology during the postoperative 10 day period, 4 cases had a later recurrence of tumour and 2 cases had a residual tumour due to incomplete resection of original tumour. By microscopic chromocystoscopy, in 11 patients concurrent urothelial atypia (carcinoma in situ or dysplasia) was found in the apparently normal mucosa. Nine of the 11 cases had a later recurrence of tumour or a residual tumour. Of in total 15 patients combined with abnormal cytology and concurrent urothelial atypia, 12 (80%) were found with recurrence of tumor cystoscopically 4 approximately 64 months (mean; 20.6 months) after TUR. This recurrence rate was significantly (p less than 0.05) higher than that (42.4%) in patients without positive cytology and concurrent urothelial atypia. These results suggest that positive urinary cytology during 10 days subsequent to TUR and/or association with concurrent urothelial atypia are indicative of later tumour recurrence, incomplete resection of tumour or presence of additional occult tumour foci.     

A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma

PURPOSE: We determine the relative sensitivities of cytology and fluorescence in situ hybridization (FISH) for the detection of urothelial carcinoma. MATERIALS AND METHODS: A mixture of fluorescent labeled probes to the centromeres of chromosomes 3, 7 and 17, and band 9p21 (P16/CDKN2A gene) was used to assess urinary cells for chromosomal abnormalities indicative of malignancy. A total of 280 urine specimens from 265 patients, including 150 with a history of urothelial carcinoma and 115 without a history of urothelial carcinoma, were analyzed. FISH analysis was performed without prior knowledge of clinical findings, that is biopsy, cystoscopy and cytology results. A positive result was defined as 5 or more urinary cells with gains of 2 or more chromosomes. RESULTS: A total of 75 biopsies showed urothelial carcinoma at FISH analysis among the 265 patients. The sensitivity of urine cytology for pTa (36 cases), pTis (18) and pT1-pT4 (15) tumors was 47%, 78% and 60%, respectively, for an overall sensitivity of 58%. The sensitivity of FISH for pTa (37 cases), pTis (17) and pT1-pT4 (19) tumors was 65%, 100% and 95%, respectively, for an overall sensitivity of 81%. FISH was significantly more sensitive than cytology for pTis (p = 0.046), pT1-pT4 (p = 0.025), grade 3 (p = 0.003) and all tumors (p = 0.001). The specificity of cytology and FISH among patients without cystoscopic evidence of urothelial carcinoma and no history of urothelial carcinoma was 98% and 96%, respectively (p = 0.564). CONCLUSIONS: The sensitivity of FISH for the detection of urothelial carcinoma is superior to that of cytology, and the specificity of FISH and cytology for urothelial carcinoma are not significantly different. Further prospective studies are required but FISH has the potential to improve significantly the management of urothelial carcinoma.     

Two cases of ureteral tumors occurring after operation on bladder tumors

Among 116 patients with bladder tumors treated during a 17-year period, 2 patients were found to have ureteral tumors (1.7%). The first case was found 8 years after transurethral resection (T.U.R.) and the second case was diagnosed as multiple ureteral tumors 3 years after six T.U.R.s. Long term follow-up by urinary cytology should be performed for patients with bladder tumors to find upper urinary tract tumors, especially for the patient with multiple bladder tumors.     

High mortality from urothelial carcinoma despite regular tumor screening in patients with analgesic nephropathy after renal transplantation

Patients with end-stage renal failure due to analgesic nephropathy have an increased risk of developing a urothelial carcinoma. To determine the impact of renal transplantation on the frequency of urothelial carcinomas, we analyzed 2072 patients who underwent 2371 renal transplantations between 1968 and 1993, including 78 (3.8%) with clinically proven analgesic nephropathy. Before and after transplantation a regular tumor screening was performed in patients with analgesic nephropathy by urine cytology and abdominal sonography. In 11 of the 78 patients with analgesic nephropathy (14.1%; age 51–66 years, 40–108 months after initiation of dialysis treatment, 5–77 months after transplantation), a urothelial carcinoma of the native urinary tract, especially the kidneys, was diagnosed. Therapy comprised nephroureterectomy (n=6), transurethral resection (n=6) and/or cystectomy (n=2). Seven patients died due to tumor progression 16.3 (4–33) months postoperatively and one patient died due to a perioperative complication. Despite regular tumor screening after transplantation, the diagnosis of a urothelial carcinoma was made very late, leading to a high tumor-related mortality. As a consequence, we suggest that a bilateral nephroureterectomy should be performed prophylactically in patients with proven analgesic nephropathy. In addition, a cystoscopy with lavage cytology testing of the bladder should be performed twice a year.     

Transitional cell carcinoma of the upper urinary tract following total cystectomy for bladder cancer]

From 1975 to 1990, we treated 118 patients with urinary epithelial cancer, including 100 with primary bladder cancer, 13 with primary upper urinary tract cancer, and 5 with both diseases. Thirty-five patients with primary bladder cancer underwent total cystectomy. Upper urinary tract urothelial cancer developed in 4 patients (4.0%) and was detected only after cystectomy. Three patients had multiple bladder tumors before cystectomy and recurrent tumors under long-term bladder-preserving treatment. The other patient had had cystectomy for the primary bladder lesion. Our present policy is to perform urinary cytology once a month and intravenous urography once a year in patients with bladder cancer for early detection of secondary upper urinary tract cancer.     

Evaluation of usefulness of urinary nuclear matrix protein 22 (NMP22) in the detection of urothelial transitional cell carcinoma

We evaluated the usefulness of urinary nuclear matrix protein 22 (NMP22) compared to urinary cytology in the detection of urothelial transitional cell carcinoma (TCC). Between July 1999 and March 2000, 227 patients complaining of microscopic or gross hematuria were analyzed. Twenty-four patients (10.6%) had urothelial TCC. The urinary NMP22 level was significantly higher in the patients with urinary TCC compared to the other patients. The sensitivity and specificity of the results obtained with urinary NMP22 were 58.3% and 84.2%, respectively, and those obtained by urinary cytology were 45.8% and 98.0%, respectively. False-positive results were obtained with urinary NMP22 in the patients with urinary diversion using intestine, bladder invasion from other cancers, urinary tract infection, and urolithiasis. The urinary NMP22 level was significantly associated with tumor stage, suggesting its usefulness for detection of urothelial TCC. However, although urinary NMP22 showed equal sensitivity for the detection of TCC, it was not superior to urinary cytology.     

Changing paradigm in the management of hepatocellular carcinoma improves the survival benefit of early detection by screening

OBJECTIVE: To evaluate the impact of improved surgical management of hepatocellular carcinoma (HCC) on the survival of patients with screened HCC. SUMMARY BACKGROUND DATA: It is unclear whether the advent of new treatment modalities such as liver transplantation and radiofrequency ablation (RFA) in recent years have improved the long-term survival in patients with HCC detected by screening. METHODS: A prospective database of 1366 patients with known chronic hepatitis B or C virus infection diagnosed with HCC either by screening or symptomatic presentation from January 1991 to December 2004 was reviewed. The long-term survival of HCC patients in the screened and symptomatic groups was compared. The management and survival of patients in two 7-year periods (1991-1997 vs. 1998-2004) were further compared. RESULTS: Long-term survival was significantly better in the screened group than in the symptomatic group (median survival 61.9 vs. 11.5 months, P < 0.001). The proportion of patients with curative treatment increased from 50.5% in the first period to 67.8% in the second period in the screened group, but there was no significant change in the symptomatic group. Improved long-term survival was observed in patients with HCC detected by screening and treated in the second period compared with the first period (median survival 68.5 vs. 38.7 months, P = 0.022), but no significant improvement was observed for symptomatic patients. CONCLUSION: Survival of patients with HCC detected by screening has improved in recent years due to increased chance of curative treatment with the advent of liver transplantation and RFA.     

Superficial transitional cell carcinoma of the ureteral orifice: Higher risk of developing subsequent upper urinary tract tumors

AIM: Reports specifically addressing transitional cell carcinoma (TCC) of the ureteral orifice are scarce. This paper presents our experiences of such tumors, including the characteristics of the disease and the incidence of subsequent upper urinary tract recurrence. METHODS: This study included 572 new cases of TCC of the urinary bladder diagnosed in our institute during a period of 5 years. Thirty-one (5.4%) patients had superficial tumors involving ureteral orifices. All 31 patients underwent transurethral resection of the bladder tumors, including the involved ureteral orifices. After the surgery, patients received regular follow up with cystourethroscopy, urine cytology and periodic intravenous pyelography (IVP). Ureterorenoscopy was performed in cases of suspicious IVP or urine cytology findings. RESULTS: Thirty-one patients with superficial tumors involving the ureteral orifice were followed up for 5-8 years or until death. The pathological stage was Ta in 16 cases and T1 in 15 cases. Bladder tumor recurrence was noted in three (18.8%) of the pTa patients and in seven (46.7%) of the pT1 patients. Subsequent upper urinary tract tumors developed in four (12.9%) patients between 33 and 67 months (mean: 33.5) after the first transurethral resection. All four cases of upper tract recurrence had pT1 primary bladder tumor, which recurred for 1-3 times (mean 1.8) before upper tract recurrence. None of these patients had ureteral stenting after bladder tumor resection. Three of four patients with upper tract recurrence had single lower ureteral tumor, while the remaining one patient had multiple tumors. Patients with subsequent upper urinary tract tumors underwent nephroureterectomy and bladder cuff excision. One died of the disease; the other three cases were free of the disease after the therapy. CONCLUSIONS: Patients with primary superficial bladder transitional cell carcinoma involving the ureteral orifice have a higher risk of developing subsequent upper urinary tract tumors, particularly for pT1 primary bladder tumors. Frequent and close follow up is recommended.     

Urinary nuclear matrix protein 22 as a new marker for the screening of urothelial cancer in patients with microscopic hematuria

PURPOSE: The aim of the present study was to determine the clinical usefulness of nuclear matrix protein 22 (NMP22) as a new urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. METHODS: Patients with microscopic hematuria detected at a health examination, who were advised by a consulted urologist to have a cystoscopical examination, were asked to enter this study. Urine samples were collected before cystoscopy and divided into two portions for NMP22 test and voided urine cytology. RESULTS: Of the 309 patients with microscopic hematuria, 22 cases (7.1%) of urothelial cancer and one case of prostate cancer were detected. For the other cases, 128 (41.4%) were of benign diseases and 158 (51.1%) were designated as having no evidence of disease (NED). The median NMP22 values for urothelial cancer, other diseases and NED were 35.5, 6.7 and 6.0 U/mL, respectively, with 95% confidence intervals of 19.9-228.2, 5.1-9.3 and 5.4-7.2, respectively. The sensitivity of the NMP22 test for urothelial cancer was 90.9% (20/22), whereas the sensitivity of voided urine cytology was only 54.5% (12/22). CONCLUSIONS: The present study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria.     

Present status and background of occupational uroepithelial tumors

The incidence of urothelial cancers in a group of 231 dyestuff plant workers who had been exposed to benzidine (BZ) or to beta-naphthylamine (BNA) was surveyed from 1962 to 1988. Fifteen out of 231 patients (6.5%) were found to have bladder cancer with the mean age at onset of 57.1 +/- 8.7 years. The estimated average period of engaging in this dyestuff exposure for these 15 patients was 92.4 +/- 47.3 months. The mean latent periods from the initial and last exposure until tumor development were 28.8 +/- 5.7 years and 16.6 +/- 7.0 years, respectively. Good negative correlation was observed between exposure periods and latent periods from the last exposure to onset (R = -0.06814). All 15 patients demonstrated tumors in the bladder, and one patient had a metachronous upper urinary tract cancer after treatment for bladder cancer. All tumors were histologically transitional cell carcinomas except for one adenocarcinoma. For initial treatment, five underwent total cystectomy, eight had transurethral resection (TUR) of the tumor, and one had partial cystectomy. Five out of 8 patients who had TUR have developed recurrent bladder tumors, and two of those patients underwent total cystectomy for second treatments. The mean follow-up period was 8.6 +/- 5.2 years, with two dying of cancer. For detection and monitoring, flow cytometric (FCM) analyses were available in five cases with bladder tumor and in two follow-up cases after bladder preserving treatments.(ABSTRACT TRUNCATED AT 250 WORDS)     

荧光原位杂交技术在尿路上皮癌预警诊断中的应用

目的：探讨使用荧光原位杂交技术对尿路上皮癌进行预警诊断的可行性和有效性。方法：采用3、7、17号染色体着丝粒探针和9p21区带探针对30例影像学检查、膀胱镜检查、尿脱落细胞学检查均为阴性的高度可疑的尿路上皮癌的血尿患者尿液脱落细胞核行荧光原位杂交检测。结果：30例血尿患者中,11例FISH结果阳性。随访3～13个月。有5例确诊为膀胱尿路上皮癌,2例确诊为肾盂癌。19例FISH检测阴性的患者无一例患病。结论：尿脱落细胞荧光原位杂交技术对膀胱镜和尿脱落细胞学检查阴性的早期尿路上皮癌患者有预警诊断作用．具有重要的临床应用价值。     

Association between urinary cytology and pathology for nontransitional cell malignancies of the urinary tract

PURPOSE: Because nontransitional cell carcinoma neoplasms of the urinary tract are rare in Western countries, we examined the association between urinary cytology and pathology evaluations for these tumors. MATERIALS AND METHODS: An institutional review board approved, retrospective review of a total of 55,946 cytology evaluations in 12,705 patients between 1992 and 2004 was performed for correlation with subsequent histopathology findings. Documented urothelial neoplasms were then correlated with previous cytology results. Nontransitional cell carcinomas were categorized as adenocarcinoma, squamous cell carcinoma and other, including small cell disease, sarcoma, melanoma or lymphoma. RESULTS: All 108 patients with cytology evaluations showing adenocarcinoma had histological evidence of cancer and 86% had adenocarcinoma in the urinary tract. All 110 patients with squamous cell carcinoma on cytology had cancer, including 47% with primary squamous cell disease. All 42 patients with other nontransitional cell carcinomas on cytology evaluation had cancer, of whom 64% had histological concordance. In a separate analysis of 70 patients who had pathologically confirmed adenocarcinoma 57% had positive prior cytology findings, of whom 19% had histological concordance. Of 85 patients with squamous cell carcinoma 81% had positive prior cytology findings, of whom 60% had histological concordance. Of 83 patients with other nontransitional cell carcinomas 70% had positive prior cytology findings, of whom 31% had histological concordance. CONCLUSIONS: In our series all patients with nontransitional cell carcinoma cytological results had cancer in the urinary tract. Thus, nontransitional cell carcinoma cytology findings mandate careful urinary tract evaluation. Concordance with histological subclassification on subsequent pathology evaluation ranges from 49% for squamous cell carcinoma to 86% for adenocarcinoma. A majority of patients with nontransitional cell carcinoma malignancies had positive prior cytology findings. However, the concordance with histological subclassification on prior cytology results ranges from 19% for adenocarcinoma to 60% for squamous cell carcinoma.     

Tumors of the upper urinary tract: 10 years of experience

We reviewed 108 patients with upper urinary tract tumors who underwent surgical treatment during a 10-year period (87 men and 21 women with a mean age of 63.5 years). Of the tumors 97% were unilateral and only 3 patients had bilateral tumors. Two-thirds of the patients had a single tumor focus and a third had 2 or more tumor foci. Additionally, there were 31 patients (28.7%) with previous and/or simultaneous bladder tumors. Nephroureterectomy was performed in 92 cases, nephrectomy in 6 and a conservative operation in 13. In 65 cases lymphadenectomy was added. The survival rates at 5 and 10 years were 67 and 65%, respectively. Of the patients 90% with cancer-related deaths had high grade tumors. Of the 15 patients with positive lymph nodes 87% died of metastasis compared to 8% of the 50 patients with negative lymph nodes. Nine patients (8.7%) had relapse in the upper urinary tract, 6 (5.8%) in the ipsilateral ureter and 3 (2.9%) in the contralateral ureter. Of these 3 patients 2 had recurrent multifocal bladder tumors. For patients who present with an upper urinary tract tumor the risk of a bladder cancer was approximately 9% and that of a contralateral urothelial tumor was 1%.