Prospective evaluation of the RT-PCR based urinary marker Bladder Epicheck® as a diagnostic tool in upper urinary tract tumor.

BACKGROUND: Upper-tract-urothelial-carcinoma (UTUC) represents 5-10% of all urothelial-neoplasms with increasing incidence in the last decades. Current standard tools for diagnosis of UTUC include cytology, computed tomography (CT) urography and ureterorenoscopy (URS). The aim of this study was to evaluate the impact of Bladder Epicheck® Test as diagnostic tool for UTUC diagnosis and recurrence. METHODS: Overall, 136 urine samples, selective collected from upper-urinary-tract before URS for suspicion of UTUC were analyzed with cytology and Bladder Epicheck® Test. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of both markers were calculated and compared to URS and/or histology as reference. RESULTS: UTUC was detected in 40 cases (33.3%), among them 30 were classified as low-grade (LG) and 10 as high-grade (HG). Overall sensitivity of Bladder Epicheck® for UTUC detection was 65% compared to 42.5% for cytology, increasing to 100% for Bladder Epicheck® and 90% for cytology if considering only HG tumors. Overall specificity of Bladder Epicheck® was 81.2% and of cytology 93.7%. PPV and NPV were 63.4% and 82.2% for Bladder Epicheck® and 77.2% and 76.5% for cytology. Considering an EpiScore cut-off >75, instead of 60, specificity of Bladder Epicheck® improves to 89% and PPV to 74.2%. Limitations include the use of a marker validated only for bladder-cancer and the relatively small number of cases. CONCLUSIONS: Due to its high sensitivity for HG tumors, the Bladder Epicheck® Test can be used in diagnosis and treatment decision-making of UTUC. Furthermore, it could be very useful in follow-up of UTUC, after endoscopic treatment to postpone or avoid unnecessary endoscopic exploration. Even if further studies are needed to validate these findings, Bladder Epicheck® could be a promising clinical tool for detection of UTUC.

Use of the Nuclear Matrix Protein 22 BladderChek Test for the Detection of Primary and Recurrent Urothelial Carcinoma.

OBJECTIVE: To evaluate the performance of the nuclear matrix protein 22 (NMP22) BladderChek test in urothelial carcinoma (UC). METHODS: We retrospectively analyzed 1318 patients who performed the NMP22 BladderChek tests. Of them, 103 were primary UC patients, 90 were surgical treatment UC patients, and 1125 were benign disease patients. The performance of the NMP22 BladderChek test for the diagnosis of primary and recurrent UC was evaluated. Moreover, the performance of urine cytology and the NMP22 BladderChek test for the diagnosis of primary UC was compared in 90 available subjects including 48 primary UC patients and 42 benign disease patients. RESULTS: The sensitivity and specificity of the NMP22 BladderChek test were 37.9% and 95.8%, respectively, for the diagnosis of primary UC (n = 1228). The corresponding parameters of the NMP22 BladderChek test were 31.0% and 88.5%, respectively, for the diagnosis of recurrent UC (n = 90). The sensitivity and specificity of urine cytology were 54.2% and 97.6%, respectively, for the diagnosis of primary UC (n = 90); the corresponding parameters of the NMP22 BladderChek test were 41.7% and 83.3%, respectively; the corresponding parameters of the two tests combination were 64.6% and 83.3%, respectively. There was a significant difference in the performance between the NMP22 BladderChek test and urine cytology or the combination of two tests (P = 0.017 and 0.001, respectively). CONCLUSIONS: The NMP22 BladderChek test has a low sensitivity for detecting primary and recurrent UC. Urine cytology is superior to the NMP22 BladderChek test, and combined use of the two tests improves the sensitivity in the detection of primary UC.

Preoperative Pyuria Predicts for Intravesical Recurrence in Patients With Urothelial Carcinoma of the Upper Urinary Tract After Radical Nephroureterectomy Without a History of Bladder Cancer.

BACKGROUND: We assessed preoperative pyuria as a significant predictor of intravesical recurrence (IVR) in patients with upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). PATIENTS AND METHODS: We evaluated the data from 268 patients with UTUC without a history of bladder cancer who had undergone RNU from 2006 to 2016 at 4 academic institutions. The associations between the clinical variables and the presence of pyuria were evaluated by univariate analysis. IVR was assessed using the Kaplan-Meier method and Cox regression analysis. RESULTS: The median postoperative follow-up of patients with IVR-free survival was 29.1 months (interquartile range, 15.4-55.3 months). The rate of IVR was significantly greater in the patients with than in those without pyuria (P = .025). Multivariate analysis showed that preoperative pyuria (hazard ratio [HR], 1.70; P = .007), a ureteral tumor site (HR, 1.64; P = .012), and positive surgical margins (HR, 2.70; P = .013) were associated with a significantly increased risk of IVR. A postoperative risk stratification model using these factors showed significant differences among the 3 subgroups of patients with low, intermediate, and high risk. The 5-year IVR-free survival rates for the patients with low, intermediate, and high risk were 69.1%, 51.8%, and 18.8%, respectively (P = .004). CONCLUSION: Preoperative pyuria, a ureteral tumor site, and positive surgical margins were associated with a significantly increased risk of IVR. Although external validation is required, the presence of preoperative pyuria could be a significant predictor of IVR in patients with UTUC after RNU.

Does urinary cytology have a role in haematuria investigations?

OBJECTIVES: To determine the diagnostic accuracy of urinary cytology to diagnose bladder cancer and upper tract urothelial cancer (UTUC) as well as the outcome of patients with a positive urine cytology and normal haematuria investigations in patients in a multicentre prospective observational study of patients investigated for haematuria. PATIENT AND METHODS: The DETECT I study (clinicaltrials.gov NCT02676180) recruited patients presenting with haematuria following referral to secondary case at 40 hospitals. All patients had a cystoscopy and upper tract imaging (renal bladder ultrasound [RBUS] and/ or CT urogram [CTU]). Patients, where urine cytology were performed, were sub-analysed. The reference standard for the diagnosis of bladder cancer and UTUC was histological confirmation of cancer. A positive urine cytology was defined as a urine cytology suspicious for neoplastic cells or atypical cells. RESULTS: Of the 3 556 patients recruited, urine cytology was performed in 567 (15.9%) patients from nine hospitals. Median time between positive urine cytology and endoscopic tumour resection was 27 (IQR: 21.3-33.8) days. Bladder cancer was diagnosed in 39 (6.9%) patients and UTUC in 8 (1.4%) patients. The accuracy of urinary cytology for the diagnosis of bladder cancer and UTUC was: sensitivity 43.5%, specificity 95.7%, positive predictive value (PPV) 47.6% and negative predictive value (NPV) 94.9%. A total of 21 bladder cancers and 5 UTUC were missed. Bladder cancers missed according to grade and stage were as follows: 4 (19%) were ≥ pT2, 2 (9.5%) were G3 pT1, 10 (47.6%) were G3/2 pTa and 5 (23.8%) were G1 pTa. High-risk cancer was confirmed in 8 (38%) patients. There was a marginal improvement in sensitivity (57.7%) for high-risk cancers. When urine cytology was combined with imaging, the diagnostic performance improved with CTU (sensitivity 90.2%, specificity 94.9%) superior to RBUS (sensitivity 66.7%, specificity 96.7%). False positive cytology results were confirmed in 22 patients, of which 12 (54.5%) had further invasive tests and 5 (22.7%) had a repeat cytology. No cancer was identified in these patients during follow-up. CONCLUSIONS: Urine cytology will miss a significant number of muscle-invasive bladder cancer and high-risk disease. Our results suggest that urine cytology should not be routinely performed as part of haematuria investigations. The role of urine cytology in select cases should be considered in the context of the impact of a false positive result leading to further potentially invasive tests conducted under general anaesthesia.

Voided urine versus bladder washing cytology for detection of urothelial carcinoma: which is better?

OBJECTIVE: Cytology is recommended as part of the follow-up of high-grade non-muscle-invasive bladder cancer (NMIBC). However, currently there are no solid guideline recommendations regarding the use of voided urine versus bladder washing for cytology as part of the diagnosis or follow-up of NMIBC. The aim of this study was to investigate whether the cytological outcome was equal regarding the two techniques. MATERIALS AND METHODS: The authors reviewed all outpatient flexible cystoscopies carried out in their department in 2013. Patient records in the registry of pathology were examined and those with simultaneous urine and bladder washing cytology were included. Previous urothelial disease and positive histology within 3 months after the cystoscopy were registered. RESULTS: A total of 1458 patients had both voided urine and bladder washing cytology and were included in the study, of whom 643 (44%) had a history of urothelial disease. An equal outcome of urine and bladder washing cytology was found in 1447 patients (99.2%). For the remaining 11 patients, only four patients underwent further examinations based on cytology findings in addition to what had already been planned after cystoscopy. Of the included patients, 100 (6.9%) had a positive histological outcome within 3 months. CONCLUSIONS: In most patients, no relevant difference between voided urine and bladder washing cytology was observed. Therefore, if cytology is indicated, it is recommended to use the test that is most readily available locally. The additional gain in using both urine and bladder wash is minimal, and can therefore be discarded.

Fluorescence in situ hybridization (FISH) in the diagnosis of bladder and upper tract urothelial carcinoma: the largest single-institution experience to date.

INTRODUCTION: We evaluated the UroVysion (Abbott Molecular, IL, USA) fluorescence in situ hybridization (FISH) assay for the diagnosis of urothelial cancer in patients diagnosed with or suspected to have bladder, upper tract urothelial carcinoma (UTUC), and combined upper and lower tract urothelial carcinoma (BC). MATERIALS AND METHODS: A single institution retrospective analysis comparing sensitivity, specificity, positive predictive value, and negative predictive values for FISH and urinary cytology. FISH within 6 months of endoscopic evaluation were obtained from outpatient voided urine samples. Our institutional pathology department confirmed pathologic disease from specimens obtained during endoscopic evaluations for lower tract disease. For upper tract disease, disease was confirmed by retrograde ureteroscopy, biopsies of visual lesions, and site-specific upper tract cytology. RESULTS: A total of 415 patients submitted FISH specimens. Overall, FISH was more sensitive than cytology 54.9% in comparison with cytology 42.2% (p = 0.01), specificity favored cytology 92.9% compared to 73.5% with FISH (p < 0.01). For BC only patients, the same significant finding of increased sensitivity and decreased specificity was identified, but for UTUC alone and combined UTUC and BC, there was no significant difference. Cytology had improved positive predictive value (PPV) over FISH, 76.9% in comparison to 64.6% (p = 0.02). Negative predictive value (NPV) also favored cytology 74.2% versus 64.9% (p = 0.02). When analyzing individual cohorts, cytology had improved PPV for BC alone patients. UTUC showed no difference for PPV and NPV. For both UTUC and BC, NPV was slightly favored for FISH over cytology 93.2% versus 91.2% (p = 0.03). CONCLUSIONS: Voided urine FISH testing does offer a higher detection of urothelial carcinoma for BC compared to voided cytology; however, specificity was worse. FISH does not appear to improve detection of urothelial carcinoma in patients with either UTUC only or both BC and UTUC.

Investigating upper urinary tract urothelial carcinomas: a single-centre 10-year experience.

OBJECTIVES: Evidence of the accuracy of predictive tests in confirming the presence and grade of upper urinary tract urothelial carcinomas (UUTUC) is limited. We present the largest series evaluating the diagnostic value of pre- and intra-operative parameters in the detection of UUTUC. MATERIALS AND METHODS: We retrospectively analysed records of patients who underwent diagnostic ureteroscopy between 2005 and 2014 for suspected UUTUC. Pre-operative workup included voided urine cytology and CT imaging. Intra-operative assessments involved ureteroscopy to directly visualise suspicious lesions, and where possible selective cytology and biopsy. Primary outcomes were the visualisation of UUTUC and histopathological confirmation of tumour. RESULTS: Hundred out of 160 (63 %) patients presenting with suspected upper tract malignancy had UUTUC. Voided and selective urine cytology and CT individually predicted UUTUC with a sensitivity/specificity of 63/67, 76/73, and 95/26 %, respectively. Forty out of 48 (83 %) patients who had abnormal CT and abnormal voided urine cytology had UUTUC, while 100 % of those with normal CT and normal voided cytology (investigated for ongoing symptoms) were normal. Comparing endoscopic biopsy to nephroureterectomy specimen grade, 19 (46 %), 18 (44 %), and 4 (10 %) were identical, upgraded, and downgraded, respectively. CONCLUSION: Pre-operative investigations can predict UUTUCs. When these investigations were normal, the risk of UUTUC is negligible. In selective patients with abnormal investigations, ureteroscopy should be performed to confirm and predict the grade of UUTUC, in order to guide future management. Selective cytology is unlikely to significantly contribute to the diagnostic workup of UUTUC.

TERT promoter mutations are associated with distant metastases in upper tract urothelial carcinomas and serve as urinary biomarkers detected by a sensitive castPCR.

TERT promoter C228T and C250T mutations occur in various malignancies including bladder cancer (BC) and may serve as urinary tumor markers. However, the mutation association with clinical variables in upper tract urothelial carcinomas (UTUCs) is unclear. There is also a lack of sensitive tools to detect the minor mutant TERT promoter in bulk urinary DNA. Here we analyzed 220 UTUC patients [98 with renal pelvic carcinoma (RPC) and 122 with ureter carcinoma (UC)] and developed a Competitive Allele-Specific TaqMan PCR (castPCR) for urinary assay. We identified C228T or C250T mutations in 42 of 98 (43%) RPC and 23 of 122 (19%) UC tumors. Distant metastases were significantly correlated with UTUC patients harboring TERT promoter mutations (P = 0.001). C228T were detected in 6/10 and 9/10 of urine samples from patients with mutation-carrying tumors using Sanger sequencing and castPCR, respectively. When urine samples from 70 BC patients were analyzed together, the sensitivity of urinary C228T assay was 89% and 50% for castPCR and Sanger sequencing, respectively (P < 0.001). Collectively, TERT promoter mutations occur in UTUCs with a high frequency in RPCs and predict distant metastasis. castPCR assays of the mutation are a useful tool for urine-based diagnostics of urological malignancies.

FISH analysis of washing urine from the upper urinary tract for the detection of urothelial cancers.

INTRODUCTION: To evaluate FISH analysis of washing urine from the upper urinary tract (UUT) in comparison with cytology (Cyt) for the detection of urothelial cancers. PATIENTS AND METHODS: In 82 patients with symptoms or abnormalities of the UUT sampling of washing urine for FISH and Cyt and a stepwise diagnostic work-up (e.g. retrograde ureteropyelography, ureterorenoscopy and endoscopic biopsy) were performed. In case of endoscopically and/or histologically proven malignancy patients either underwent nephroureterectomy, partial ureterectomy or local treatment. Sensitivity and specificity for FISH and Cyt as well as its combination were determined. RESULTS: Urothelial cancer of the UUT was detected in 20 patients. Eleven patients underwent nephroureterectomy, six partial ureterectomy and three endoscopic tumour treatment. This revealed nine pTa, three pT1 and seven muscle-invasive tumours. Twelve tumours were classified as low and seven as high-grade tumours. In one patient with a macroscopic unequivocal finding of tumour, endoscopic laser ablation without histologic confirmation was performed. FISH was evaluable in 76 patients and detected 16 tumours with a sensitivity and specificity of 84.2 and 91.1 %, respectively. Cyt was performed in 79 and was evaluable in 78 patients. It detected ten tumours with a sensitivity and specificity of 52.6 and 91.4 %, respectively. Cyt and FISH together detected 19 tumours with (sensitivity 100 % and specificity 83.6 %). CONCLUSION: FISH was more sensitive than and equally specific to Cyt in the detection of urothelial cancers of the UUT. Both markers in combination revealed the best sensitivity, making it a possible approach in future settings.

TERT promoter mutations in renal cell carcinomas and upper tract urothelial carcinomas.

TERT promoter mutations are identified in many malignancies including bladder cancer (BC) and upper tract urothelial carcinoma (UTUC). In contrast, no mutations were found in renal cell carcinoma (RCC) as reported in a recent study. Because the mutant TERT promoter in urine DNA was recently tested as a marker for BC, it is important to ascertain whether these mutations are truly absent in RCCs. Here we determined TERT promoter mutations in 109 patients with RCC and 14 patients with UTUC. The mutations were found in 9/96 (9.3%) clear cell RCC (ccRCC) tumors and 1/8 (13%) chromophobe RCC tumors. Among ccRCC patients, the mutation was correlated with the advanced stages and metastasis, and higher TERT expression. Among UTUCs, the mutation was detected in tumors from 3/5 (60%) patients with renal pelvic cancer and 1/9 (11%) patients with ureter cancer. The mutation was also detected in 1 of 4 urine samples from patients with mutation+ UTUC. Collectively, TERT promoter mutations do occur in RCCs and are associated with aggressive disease. The mutation is more frequent in renal pelvic cancer. Thus, the mutant TERT promoter found in urine may come from not only BC, but also RCC or UTUC.

Comparison of urine cytology and fluorescence in situ hybridization in upper urothelial tract samples.

BACKGROUND: The cytologic diagnosis of urothelial carcinoma (UC) of the upper urothelial tract (UT) is challenging. Using the UroVysion probe set adds diagnostic value for the detection of bladder cancer in voided urine. In instrumented UT specimens, the authors encountered positive UT cytology and fluorescence in situ hybridization (FISH) cases that did not demonstrate subsequent UT carcinoma. METHODS: The performance of cytology and FISH in the presence or absence of concomitant bladder cancer within 2 years was compared in 61 patients (112 samples) from 2003 through 2009. The mean follow-up was 3.2 years. The authors also compared the performance of near-tetrasomy versus hypertetrasomy. Biopsy confirmation of UTUC in 21 patients was considered the gold standard. RESULTS: Cytology alone was found to be poorly sensitive (38%) but highly specific (89%) for the detection of UTUC. FISH was found to increase the sensitivity of cytology and decrease specificity. Tetrasomy FISH resulted in many false-positive cases. Other false-positive FISH results were likely due to the presence of bladder cancer cells contaminating the UT specimen. CONCLUSIONS: Caution should be used when evaluating instrumented urine specimens of the UT from patients with a previous history of bladder carcinoma, and tetrasomy FISH results should not be interpreted as abnormal because it significantly lowers the specificity of the test. The combination of cytology and FISH appears to have good specificity while maintaining good sensitivity in evaluating UTUC when using modified scoring criteria for the appropriate patient population.

[Urinary BLCA-4 level is useful to detect upper urinary tract urothelial cell carcinoma]. / El nivel de BLCA-4 urinario es útil para la detección del carcinoma de células uroteliales de vía urinaria superior.

OBJECTIVE: Upper urinary tract urothelial cell carcinomas (UUT-UCCs) are rare but usually invasive at diagnosis. Early diagnosis of UUT-UCCs is thus warranted. UUT has the same embryological origin with bladder and BLCA-4 is a highly sensitive and specific marker for bladder cancer. We intend to investigate the viability of BLCA-4 in detecting UUT-UCCs. MATERIAL AND METHODS: Urines from 30 UUT-UCC patients, 10 ureteral polyp patients, 20 infected patients with incarcerated ureteral stones, and 30 normal controls were included. BLCA-4 antibody was produced and applied in an indirect ELISA assay. RESULTS: Urinary BLCA-4 is significantly higher in UUT-UCC group than «Polyp¼ group (P=0.0017), «Infection¼ group (P<0.0001), or « Normal¼ group (P<0.0001). The «Polyp¼ group is also higher than «Infection¼ group (P=0.015), or «Normal¼ group (P=0.0009). ROC curve revealed at cut-off of 5.5×10(-4)A, sensitivity was 93.3% and specificity was 100%. When grouped as ureteral mass vs normal, same cut-off value yielded 93.3% sensitivity and 83.3% specificity. At 2.4×10(-4)A, sensitivity was 56.7% and specificity was 97.2%. CONCLUSIONS: Urinary BLCA-4 is also highly specific in UUT-UCCs detection. For incidentally identified ureteral mass, BLCA-4 can be considered an auxiliary indicator besides biopsy.

In the cystoscopic follow-up of non-muscle-invasive transitional cell carcinoma, NMP-22 works for high grades, but unreliable in low grades and upper urinary tract tumors.

INTRODUCTION AND OBJECTIVES: Two percent of the bladder non-muscle-invasive (NMI) transitional cell carcinomas (TCC) are associated with upper urinary tract (UUT) TCC. We evaluated the role of nuclear matrix protein-22 (NMP-22) (BladderChek) test in the diagnosis of lower urinary tract and UUT-TCC. METHODS: From March 2009 to June 2011, 122 patients with bladder NMI-TCC underwent 205 control cystoscopy. A total of 95 (78 men and 17 women, mean age 60.7 years, range, 27-88) patients who were followed regularly with NMP-22 test and with follow-up cystoscopies (145 episodes; min. 1-max. 5) were included in this study. For routine monitoring of the UUT, IVU or CT urography was used once a year for high grades (HG), and once in every other year for low grades (LG). The sensitivity and specificity of NMP-22 were evaluated by ROC curves, and sensitivity, specificity, and positive and negative predictive values were calculated. Chi-square test was used for the differences between the subgroups. RESULTS: Cystoscopy and NMP-22 results of the patients included in the study revealed the sensitivity (44.4%) of the test was very low and the specificity (98.4%) was quite high (p < 0.001). Among the 10 cystoscopies where NMP-22 was negative, but cystoscopy was positive for tumor, 8 had LG and 2 had HG TCC. NMP-22 was never positive in low-grade tumors, in other words, all of the NMP-22-positive 8 tumors were high grade. On the other hand, in 20% (2/10) of the cases, NMP-22 can be negative although the tumor was high grade. Two (2.1%) HG UUT-TCC were detected in 95 patients. These 2 patients were within the 125 cystoscopies (75 patients) where both NMP-22 and cystoscopy were negative for tumor. CONCLUSIONS: Nuclear matrix protein-22 cannot detect LG TCC. However, it detects overwhelming majority of HG TCC. For this reason, positive NMP-22 test largely indicates HG TCC. NMP-22 is also not reliable in UUT-TCC, even in HG tumors.

Preoperative positive urine cytology is a risk factor for subsequent development of bladder cancer after nephroureterectomy in patients with upper urinary tract urothelial carcinoma.

PURPOSE: To determine the independent risk factors of bladder recurrence in patients with upper urinary tract urothelial carcinoma (UUT-UC). METHODS: A total of 364 patients underwent nephroureterectomy (NUx) for UUT-UC between January 2005 and April 2009 in Okayama University and 17 affiliated hospitals. Patients with concomitant bladder cancer were excluded from the analysis. The clinicopathologic data for the remaining 288 patients with UUT-UC were retrospectively reviewed. Median follow-up after NUx was 20.2 months. The following variables were evaluated for any association with bladder recurrence: sex, age, tumor stage, tumor grade, venous invasion, lymphatic invasion, tumor location, multifocality, surgical modalities, time of ligation of the ureter, and preoperative urine cytology. The significance of each variable was tested univariately using the log-rank test. The simultaneous effects of multiple risk factors were estimated by multiple regression analysis using the Cox proportional hazards model. RESULTS: Bladder recurrence occurred in 103 patients (35.8%). Median time to first bladder recurrence was 6.9 months. Significant risk factors for bladder recurrences on univariate analysis were tumor location (P = 0.046) and preoperative positive urine cytology (P < 0.001). Multivariate analysis revealed that preoperative urine cytology positive was significant for bladder recurrence (HR: 1.977; 95% CI: 1.310-2.983, P = 0.001). CONCLUSION: Risk factor for subsequent development of bladder cancer after NUx was preoperative positive urine cytology.

Idiopathic segmental ureteritis, misdiagnosed as ureteral cancer preoperatively: a case report with literature review.

A 53-year-old man presented with right flank pain for 6 days. Computerized tomography revealed a 3 cm long segment of ureteral narrowing with wall thickening and hydronephrosis, suspicious for ureteral cancer. Under the clinical diagnosis of ureteral carcinoma a right nephroureterectomy was performed. The wall of the distal ureter, 2.5 cm from the bladder cuff, had a luminal-narrowing, firm mass-forming lesion with abrupt transition from the adjacent ureter. Histologically, the resected ureteral mass showed transmural fibrosing, chronic inflammation with numerous plasma cells, epithelioid granulomas, and obliterative phlebitis. Histological findings were consistent with idiopathic segmental ureteritis (ISU) with differential diagnoses of IgG4-related sclerosing disease, including lymphoplasmacytic inflammatory pseudotumor (IPT) and idiopathic retroperitoneal fibrosis. IgG4 immunostaining in this case was barely positive, excluding the possibility of IgG4-related IPT. Although the majority of luminal obliterated segmental lesions of the ureter are neoplastic in nature, non-neoplastic inflammatory processes as seen in this case may occur in the ureter, causing diagnostic confusion with true neoplasms. Herein we report a rare case of ISU that was clinically misdiagnosed as malignancy preoperatively. ISU of the current case may be an IgG4-unrelated subtype of IPT.

Voided urine fluorescence in situ hybridization testing for upper tract urothelial carcinoma surveillance.

PURPOSE: Fluorescence in situ hybridization is gaining popularity for transitional cell carcinoma screening. We determined the accuracy of fluorescence in situ hybridization for identifying upper tract transitional cell carcinoma. MATERIALS AND METHODS: A retrospective review of our upper tract transitional cell carcinoma database from 2005 to 2008 identified 35 patients with upper tract transitional cell carcinoma who submitted voided urine specimens for fluorescence in situ hybridization at commercial laboratory during a routine office visit. Each patient was evaluated endoscopically in the operating room within 3 months of sampling. Suspicious lesions were biopsied and treated. Transitional cell carcinoma in the lower or upper tract was proved by direct visualization, positive biopsy or upper tract cytology read as positive or highly suspicious for malignancy. RESULTS: Of the patients 35 satisfied study inclusion criteria. A total of 67 fluorescence in situ hybridization specimens were submitted. Upper tract transitional cell carcinoma was identified on 51 operative evaluations, of which 23 showed concurrent bladder tumor. For all encounters the sensitivity of fluorescence in situ hybridization was 56% and specificity was 80%. Sensitivity for low and high grade lesions was 68% and 67%, respectively. Only upper tract tumors were noted in 28 patients, in whom there were 2 false-positive and 13 false-negative voided fluorescence in situ hybridization results. In these cases sensitivity was 54% and specificity was 78% compared to the 18% sensitivity and 100% specificity of bladder cytology. Sensitivity for low and high grade upper tract transitional cell carcinoma was 60% and 50%, respectively. CONCLUSIONS: Voided fluorescence in situ hybridization has become an adjunct for bladder transitional cell carcinoma surveillance. However, it has limited value for upper tract tumor surveillance.

Fluorescence in situ hybridization for detecting upper urinary tract tumors--a preliminary report.

OBJECTIVES: To evaluate fluorescence in situ hybridization (FISH) in voided urine specimens and selective upper urinary tract washings obtained from patients with suspected transitional cell cancer of the upper urinary tract (UT-TCC). METHODS: A total of 16 patients with suspected UT-TCC were included in the study. All patients underwent urinary tract imaging. Endoscopy was also performed. Voided urine specimens from all patients and ureteral washings were subjected to cytologic examination and FISH analysis (UroVysion probe set). If indicated, surgery (nephroureterectomy or ureterectomy) was performed. RESULTS: Of the 16 patients, 9 (56.25%) were diagnosed with UT-TCC. None of the remaining patients was diagnosed with UT-TCC after a mean follow-up of 21.3 months (median 20, range 11 to 36). For FISH analysis, the sensitivity was 87.5% and specificity 80%. FISH analysis was not possible in 1 patient with UT-TCC because of an insufficient number of cells. For cytology, the sensitivity was 60% and specificity 80%. In patients with UT-TCC, the cytologic findings were inconclusive (atypia of uncertain significance) in 4 patients (44.4%). In contrast to the cytology findings, all results of the FISH analysis of the upper urinary tract washings matched those of the voided urine samples. CONCLUSIONS: Our preliminary data suggest that FISH analysis of voided urine might be a useful ancillary test in the detection of UT-TCC with excellent sensitivity and specificity. If confirmed in larger studies, FISH might contribute to a more reliable and less-invasive diagnostic approach to UT-TCC.

Clinical study of urine NMP 22 (nuclear matrix protein 22) as a tumor marker in urinary epithelial cancer.

The prognosis of urinary epithelial cancer is still poor, and early detection of this cancer is strongly desirable. The sensitivity of conventional urinary cytology is not satisfactory enough. It is hoped that a specific tumor marker will be established. In recent years, it has been reported that urine NMP 22 is very useful and that urine BFP is also relatively useful. We have now determined urine NMP22 and BFP and studied their clinical usefulness as a tumor marker. Using patients diagnosed with histologically confirmed urinary epithelial cancer as the subjects, we retrospectively studied the usefulness of NMP 22, BFP and cytology mainly with regard to the sensitivity (positivity rate), and also in relation to atypia, degree of infiltration and clinical course.

The BTA stat test: a tumor marker for the detection of upper tract transitional cell carcinoma.

OBJECTIVES: To conduct a prospective evaluation to determine the utility of the BTA stat test in the detection of upper tract transitional cell carcinoma (UTTCC). Monitoring for UTTCC currently relies on invasive procedures such as upper tract imaging, ureteral washing cytology (UWC) and/or ureteroscopy, or voided urine cytology (VUC). The BTA stat test is a sensitive qualitative immunoassay that detects human complement factor H-related protein in voided urine. METHODS: A total of 81 patients participated, 27 with histopathologically confirmed UTTCC, 26 with upper tract calculi, and 28 with microscopic hematuria but no evidence of urologic disease. Voided specimens collected before surgery or treatment were tested with the BTA stat test and VUC. UWC was performed in specimens collected by a ureteral catheter. RESULTS: The BTA stat test was significantly more sensitive and specific than VUC or UWC. The overall sensitivity for each was 82%, 11%, and 48%; the specificity was 89%, 54%, and 33%. The positive predictive value for the BTA stat test was 79% and the negative predictive value was 91%, both the highest of the three tests. CONCLUSIONS: The BTA stat test was superior to VUC and UWC in the detection of UTTCC. These results may support the adoption of a less aggressive follow-up policy when monitoring for UTTCC when the BTA stat result is negative. If cystoscopy is negative and the BTA stat test is positive, upper tract investigations should be expedited and, if the bladder is in place, bladder biopsies performed.