The combination cytology/epichek test in non muscle invasive bladder carcinoma follow-up: Effective tool or useless expence?

OBJECTIVE: To identify in which cases after cytological diagnosis, the Bladder EpiCheck test could represent an effective tool in non-muscle invasive bladder carcinoma or an useless expence. MATERIALS AND METHODS: 375 patients diagnosed with non-muscle invasive bladder cancer, 269 with high grade urothelial carcinoma and 106 with carcinoma in situ, were treated and followed for 1 year. The treatment was an intravesical instillation of Bacillus Calmette-Guerin in 305 patients and Mitomycin-C in 70 patients. During the follow-up patients were evaluated by voided urine cytology and white-light cystoscopy, according to the European Association of Urology Guidelines. Bladder EpiCheck test was performed together with cytology in all cases. RESULTS: Analyzing Bladder Epicheck results for each category defined by the Paris System for Reporting Urinary Cytology, we found that the Episcore >60 correlates with histological diagnosis of high grade urothelial carcinoma (HGUC) in atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma (P = 0.0002 Odds Ratio 0.05926 95% Confidence Interval from 0.01127 to 0.3116 and P = 0.0009 Odds Ratio 0.03155 95% Confidence Interval from 0.001683 to 0.5914, Fisher's exact test, respectively), while in Negative for high grade urothelial carcinoma and HGUC patients Episcore is not helpful to identify cases with histological diagnosis of HGUC (P = 0.101 and P = 0.58 Fisher's exact test, respectively). Considering an Episcore ≥ 90 in the HGUC cytological group, this seems not to be correlated with a histological diagnosis of HGUC (P = 0.090 Fisher's exact test). CONCLUSIONS: Cytology and Bladder EpiCheck test in combination may have the potential to reduce cystoscopies in the follow-up of non-muscle invasive bladder cancer only for cytological diagnoses of atypical urothelial cells and Suspicious for High Grade Urothelial Carcinoma . Moreover, in patients with a cytological diagnosis of Negative for high grade urothelial carcinoma or HGUC, cytology alone seems to be safe and cost-effective.

High-Grade Urothelial Carcinoma on Urine Cytology Resembling Umbrella Cells.

CONTEXT: High-grade urothelial carcinoma (UC) cells have many appearances on urine cytology, but according to The Paris System, they can be easily distinguished from umbrella cells. OBJECTIVE: We aimed to define the incidence and appearance of high-grade UC cells that resemble umbrella cells in Cytospin preparations on urine cytology. RESULTS: Cytospin preparations from 331 cases with biopsy follow-up (230 benign/low-grade and 101 malignant [22 carcinoma in situ, 52 papillary, 19 invasive UC, 8 other] cases) were reviewed. A total of 18 cases with malignant cells resembling umbrella cells were identified (17.8% of the malignant cases) and were the only type of malignant cell in 3% of the cases. Two patterns were identified. Tumor cells were either identifiable by at least 20 abnormal cells which were large, had abundant cytoplasm but an elevated nuclear-to-cytoplasmic ratio, and markedly enlarged, round-to-elongated nucleoli, or else rare cells with abundant cytoplasm but obviously malignant nuclei. Cells without nucleoli or obviously malignant nuclei were not specific. CONCLUSIONS: Malignant cells resembling umbrella cells can be seen in up to 17% of urine cytology specimens.

Analysis of the Cytomorphological Features in Atypical Urine Specimens following Application of The Paris System for Reporting Urinary Cytology.

BACKGROUND: This study investigates the use of The Paris System (TPS) for Reporting Urinary Cytopathology and examines the performance of individual and combined morphological features in atypical urine cytologies. METHODS: We reviewed 118 atypical cytologies with subsequent bladder biopsies for the presence of several morphological features and reclassified them into Paris System categories. The sensitivity and specificity of individual and combined features were calculated along with the risk of malignancy. RESULTS: An elevated nuclear-to-cytoplasmic ratio was only predictive of malignancy if seen in single cells, while irregular nuclear borders, hyperchromasia, and coarse granular chromatin were predictive in single cells and in groups. Identification of coarse chromatin alone yielded a malignancy risk comparable to 2-feature combinations. The use of TPS criteria identified the specimens at a higher risk of malignancy. CONCLUSION: Our findings support the use of TPS criteria, suggesting that the presence of coarse chromatin is more specific than other individual features, and confirming that cytologic atypia is more worrisome in single cells than in groups.

UBC® Rapid Test for detection of carcinoma in situ for bladder cancer.

UBC® Rapid Test is a test that detects fragments of cytokeratins 8 and 18 in urine. We present results of a multicentre study measuring UBC® Rapid Test in bladder cancer patients and healthy controls with focus on carcinoma in situ (CIS) and high-grade bladder cancer. From our study with N = 452 patients, we made a stratified sub-analysis for carcinoma in situ of the urinary bladder. Clinical urine samples were used from 87 patients with tumours of the urinary bladder (23 carcinoma in situ, 23 non-muscle-invasive low-grade tumours, 21 non-muscle-invasive high-grade tumours and 20 muscle-invasive high-grade tumours) and from 22 healthy controls. The cut-off value was defined at 10.0 µg/L. Urine samples were analysed by the UBC® Rapid Test point-of-care system (concile Omega 100 POC reader). Pathological levels of UBC Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p < 0.001). Sensitivity was calculated at 86.9% for carcinoma in situ, 30.4% for non-muscle-invasive low-grade bladder cancer, 71.4% for nonmuscle-invasive high grade bladder cancer and 60% for muscle-invasive high-grade bladder cancer, and specificity was 90.9%. The area under the curve of the quantitative UBC® Rapid Test using the optimal threshold obtained by receiveroperated curve analysis was 0.75. Pathological values of UBC® Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumours and the healthy control group. UBC® Rapid Test has potential to be more sensitive and specific urinary protein biomarker for accurate detection of high-grade patients and could be added especially in the diagnostics for carcinoma in situ and non-muscle-invasive high-grade tumours of urinary bladder cancer.

Improved risk stratification for patients with high-grade urothelial carcinoma following application of the Paris System for Reporting Urinary Cytology.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) requires 4 cytomorphologic criteria for a definitive diagnosis of high-grade urothelial carcinoma (HGUC) in urinary tract cytology (UTC) specimens: an elevated nuclear-to-cytoplasmic (N/C) ratio (at or above 0.7), markedly atypical nuclear borders, moderate to severe hyperchromasia, and coarse chromatin. However, malignant UTC specimens often contain degenerative changes, and this limits the number of malignant cells meeting all 4 TPS cytomorphologic criteria. METHODS: One hundred twelve UTC specimens from patients with a subsequent diagnosis of HGUC were reviewed and reclassified according to TPS criteria. The presence of TPS cytomorphologic criteria for HGUC in each specimen was recorded, as was the proportion of atypical cells meeting all 4 criteria. RESULTS: The number of specimens definitively diagnosed as HGUC did not significantly change upon reclassification. However, approximately 40% of indeterminate specimens (21 of 51) were reclassified into a higher risk category. The most restrictive cytomorphologic criterion was an N/C ratio of 0.7 or higher (seen in 78% of specimens), and approximately half of specimens containing all 4 cytomorphologic criteria did not meet TPS's numerical criterion for HGUC (at least 5 malignant cells). In the majority of specimens qualifying for HGUC by TPS standards, only a small fraction of atypical cells (10%-20%) met all the criteria. CONCLUSIONS: When applied to malignant UTC specimens, TPS criteria improved specimen risk stratification by upgrading approximately 40% of indeterminate specimens into higher risk categories while not significantly changing the frequency of HGUC diagnoses. Cancer Cytopathol 2017;125:427-34. © 2017 American Cancer Society.

A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer.

PURPOSE: Imiquimod is a toll-like receptor agonist with proven antitumor activity as a topical treatment for skin cancer. TMX-101 (Vesimune) is a novel liquid formulation of imiquimod optimized for intravesical delivery. The agent demonstrated safety as an intravesical treatment for non-muscle-invasive bladder cancer in a phase 1 clinical trial. We report the results of a phase 2 prospective multicenter clinical trial assessing the safety and activity of TMX-101. MATERIALS AND METHODS: Patients with non-muscle-invasive bladder cancer containing carcinoma in situ were eligible for inclusion. Enrolled patients received 6 weekly intravesical administrations of 200mg/50ml TMX-101 0.4%. End points included rate of adverse events, changes in urinary cytokine levels following treatment, and clinical response at 6 weeks following final instillation, defined as negative posttreatment bladder biopsy and urine cytology results. RESULTS: A total of 12 patients were enrolled, with 10 available for efficacy analysis. Half of the patients (6/12) had received≥2 prior induction courses of bacillus Calmette-Guerin. All patients received all 6 doses of TMX-101 per protocol. Overall, 75% of patients experienced treatment-related adverse events, only 1 of which was>grade 2 (urinary tract infection). Furthermore, 2 patients demonstrated a negative cytology and biopsy result at 6 weeks following treatment. Significant increases in urinary cytokines, including IL-6 and IL-18, were seen following treatment. CONCLUSION: In this phase 2 pilot study in patients with carcinoma in situ bladder cancer, intravesical TMX-101 was safe and well tolerated with common, mild genitourinary adverse effects. Clinical activity was suggested by the increase in posttreatment urinary cytokines. Complete responders were seen. Further investigation of the agent is warranted.

Diagnostic approach for cancer cells in urine sediments by 5-aminolevulinic acid-based photodynamic detection in bladder cancer.

Bladder urothelial carcinoma is diagnosed and followed up after transurethral resection using a combination of cystoscopy, urine cytology and urine biomarkers at regular intervals. However, cystoscopy can overlook flat lesions like carcinoma in situ, and the sensitivity of urinary tests is poor in low-grade tumors. There is an emergent need for an objective and easy urinary diagnostic test for the management of bladder cancer. In this study, three different modalities for 5-aminolevulinic acid (ALA)-based photodynamic diagnostic tests were used. We developed a compact-size, desktop-type device quantifying red fluorescence in cell suspensions, named "Cellular Fluorescence Analysis Unit" (CFAU). Urine samples from 58 patients with bladder cancer were centrifuged, and urine sediments were then treated with ALA. ALA-treated sediments were subjected to three fluorescence detection assays, including the CFAU assay. The overall sensitivities of conventional cytology, BTA, NMP22, fluorescence cytology, fluorescent spectrophotometric assay and CFAU assay were 48%, 33%, 40%, 86%, 86% and 87%, respectively. Three different ALA-based assays showed high sensitivity and specificity. The ALA-based assay detected low-grade and low-stage bladder urothelial cells at shigher rate (68-80% sensitivity) than conventional urine cytology, BTA and NMP22 (8-20% sensitivity). Our findings demonstrate that the ALA-based fluorescence detection assay is promising tool for the management of bladder cancer. Development of a rapid and automated device for ALA-based photodynamic assay is necessary to avoid the variability induced by troublesome steps and low stability of specimens.

ProEx C as an adjunct marker to improve cytological detection of urothelial carcinoma in urinary specimens.

BACKGROUND: ProEx C is an antibody cocktail targeting the expression of topoisomerase IIα and minichromosome maintenance protein-2. ProEx C staining is being used to assist in diagnoses of the gynecological specimens. This study was designed to determine the utility of ProEx C in urine cytology samples for improving the detection of urothelial carcinomas where a significant number of urine cytology specimens are diagnosed as "atypia." METHODS: Sixty urinary specimens (12 negative, 13 positive, and 35 atypical cases) were stained with ProEx C, and ProEx C results were recorded as positive when nuclear staining was only seen in at least one morphologically atypical urothelial cell. RESULTS: All 12 benign cytology samples showed negative staining with ProEx C. Twelve of 13 cases that had a malignant cytologic diagnosis showed a positive nuclear staining of the malignant cells. Eighteen of 35 cases with atypical cytologic diagnoses showed positive nuclear staining. Of the 35 cases with "atypia," 17 had a malignant histopathologic follow-up. In this study, ProEx C stain had an overall sensitivity of 78.4%, specificity of 95.7%%, positive predictive value of 96.7%, and negative predictive value of 73.3% for the detection of urothelial carcinoma. CONCLUSIONS: ProEx C stain is a useful adjunct test to urine cytologic analysis, even in specimens with limited cellularity. In urinary smears, this test is most useful in stratification of the "atypical" diagnoses into benign and malignant subsets. To the authors' knowledge, this is the first study of ProEx C application in urine cytology as an adjunct marker for detection of urothelial carcinoma.

Narrow-band imaging flexible cystoscopy in the detection of clinically unconfirmed positive urine cytology.

INTRODUCTION: The objective of this study was to investigate the value of narrow-band imaging (NBI) cystoscopy in the detection of patients with positive voided urine cytology (VUC) who have no evidence of disease after standard initial investigations. PATIENTS AND METHODS: Between February 2009 and December 2010, 12 patients with positive or suspicious VUC but no regular endoscopic evidence of cancer were investigated with NBI flexible cystoscopy. All the specimens were biopsied both under NBI and white light imaging (WLI). Random biopsies of bladder and prostatic urethra were performed in cases without suspect lesions. RESULTS: Fourteen NBI cystoscopies were carried out in 12 patients. Non-muscle-invasive bladder cancer was diagnosed in 5 of 12 (42%) patients on the first NBI. One patient had carcinoma in situ diagnosed on repeat NBI 3 months later. The sensitivity and specificity in diagnosing unconfirmed positive VUC was 78 and 91% for NBI vs. 50 and 80% for WLI. CONCLUSIONS: NBI cystoscopy significantly improves detection of unconfirmed positive VUC over WLI. It should be carried out early in the investigation of such patients before random biopsies and ureteroscopy.

A multicolor fluorescence in situ hybridization assay: A monitoring tool in the surveillance of patients with a history of non-muscle-invasive urothelial cell carcinoma: A prospective study.

BACKGROUND: Non-muscle-invasive urothelial cell carcinoma (NMIUCC) has a high tendency to recur and affected patients must be monitored regularly using invasive cystoscopies. The aim of the current study was to compare a multicolor fluorescence in situ hybridization (FISH) assay (UroVysion) with routine follow-up (cystoscopy and cytology) in the monitoring of patients with a previous history of NMIUCC. METHODS: An unselected cohort of patients under surveillance for a previous history of NMIUCC was prospectively studied. A total of 248 examinations in 223 patients were analyzed. Each exploration was comprised of cytological and FISH microscopic examination of voided urine samples and cystoscopy. The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for tumor recurrence of all 3 techniques were determined. RESULTS: The sensitivities of FISH and cystoscopy were not found to be significantly different (92.9% and 82.1%, respectively). The specificities of FISH and cystoscopy were 92.7% and 89.7%, respectively. The PPV and NPV of FISH were 53.5% and 97.2%, respectively, whereas those of cystoscopy were 63.4% and 98.9%, respectively. No significant differences were found between these 2 tests. In contrast, the sensitivity and specificity of cytology were 14.3% and 99.5%, respectively. CONCLUSIONS: Given the lack of statistically significant differences with regard to FISH and cystoscopy results, the authors propose that FISH could be a useful monitoring tool in the surveillance of patients with a previous history of NMIUCC.

Clinical experience with survivin as a biomarker for urothelial bladder cancer.

OBJECTIVES: This study was carried out as a prospective pilot study to evaluate the potential of survivin mRNA measurement in patients suspicious for urothelial bladder cancer (BC). Data were also analyzed for possible influences of secondary urological findings on survivin measurements. METHODS: Survivin was measured by an mRNA assay in voided urine samples of 50 patients with suspicion of new or recurrent BC prior to transurethral resection. Sample evaluation was possible in 49 cases. Histopathology revealed no malignancy in 17 (35%) and BC in 32 (65%) patients. Survivin mRNA was quantitated by real-time PCR from frozen cell pellets of centrifuged urine samples. A ROC analysis of the survivin data was performed. RESULTS: ROC analysis identified the best cut-off level at 10,000 mRNA copies, resulting in a sensitivity of 53% and a specificity of 88%. Seven of the 20 pTa tumors (35%), all four pT1 (100%) and all four muscle-invasive tumors (100%) were detected. Of four patients with carcinoma in situ (Cis), 50% could be identified. Only two patients (4%) were assessed as false positive. Histologically confirmed cystitis and concomitant urological findings (inflammatory cells in urine, microhematuria and others) had no detectable influence on survivin measurements. CONCLUSION: In present group of patients, survivin was a reliable biomarker for high-grade urothelial BC (sensitivity 83%), but not for low grade (sensitivity 35%) urothelial BC with a high specificity (88%). No confounders influencing the results of survivin measurements could be identified.

Do liquid-based preparations of urinary cytology perform differently than classically prepared cases? Observations from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

CONTEXT: The cytomorphology of liquid-based preparations in urine cytology is different than classic slide preparations. OBJECTIVES: To compare the performance of liquid-based preparation specimens to classically prepared urine specimens with a malignant diagnosis in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology. DESIGN: Participant responses between 2000 and 2007 for urine specimens with a reference diagnosis of high-grade urothelial carcinoma/carcinoma in situ/dysplasia (HGUCA), squamous cell carcinoma, or adenocarcinoma were evaluated. ThinPrep and SurePath challenges were compared with classic preparations (smears, cytospins) for discordant responses. RESULTS: There were 18 288 pathologist, 11 957 cytotechnologist, and 8086 "laboratory" responses available. Classic preparations comprised 90% (n = 34 551) of urine challenges; 9% (n = 3295) were ThinPrep and 1% (n = 485) were SurePath. Concordance to the general category of "positive-malignant" was seen in 92% of classic preparations, 96.5% of ThinPrep, and 94.6% of SurePath challenges (P < .001). These results were statistically different for the exact reference interpretation of HGUCA (P < .001) but not for adenocarcinoma (P = .22). Cytotechnologists demonstrate statistically better performance for the general category of "positive-malignant" compared with pathologists for all urinary slide types and for the exact reference interpretation of HGUCA (94% versus 91.1%; P < .001) but not adenocarcinoma (96.3% versus 95.8%; P = .77) or squamous cell carcinoma (93.6% versus 87.7%; P = .07). CONCLUSIONS: Liquid-based preparations performed significantly better in urinary cytology challenges when evaluating malignant categories in the College of American Pathologists interlaboratory comparison program. The liquid-based preparation challenges also performed better for the exact reference interpretation of HGUCA, but no difference was observed for adenocarcinoma challenges. Cytotechnologists perform better than pathologists for all slide types, as well as those demonstrating HGUCA. These results suggest that liquid-based preparations facilitate a more accurate diagnosis than conventional preparations.

Urinary metalloproteinases: noninvasive biomarkers for breast cancer risk assessment.

Matrix metalloproteinases (MMP) and a disintegrin and metalloprotease 12 (ADAM 12) can be detected in the urine of breast cancer patients and provide independent prediction of disease status. To evaluate the potential of urinary metalloproteinases as biomarkers to predict breast cancer risk status, urine samples from women with known risk marker lesions, atypical hyperplasia and lobular carcinoma in situ (LCIS), were analyzed. Urine samples were obtained from 148 women: 44 women with atypical hyperplasia, 24 women with LCIS, and 80 healthy controls. MMP analysis was done using gelatin zymography and ADAM 12 analysis was done via immunoblotting with monospecific antibodies and subsequent densitometric measurement. Positive urinary MMP-9 levels indicated a 5-fold risk of atypical hyperplasia and >13-fold risk of LCIS compared with normal controls. Urinary ADAM 12 levels were significantly elevated in women with atypical hyperplasia and LCIS from normal controls, with receiver operating characteristic curve analysis showing an area under the curve of 0.914 and 0.950, respectively. To assess clinical applicability, a predictive index was developed using ADAM 12 in conjunction with Gail risk scores for women with atypia. Scores above 2.8 on this ADAM 12-Gail risk prediction index score are predictive of atypical hyperplasia (sensitivity, 0.976; specificity, 0.977). Our data suggest that the noninvasive detection and analysis of urinary ADAM 12 and MMP-9 provide important clinical information for use as biomarkers in the identification of women at increased risk of developing breast cancer.

[Tumor markers for bladder cancer: up-to-date study by the Kiel Tumor Bank]. / Tumormarker beim Blasenkarzinom : Der aktuelle Stand am Beispiel der "Kieler Blasentumorbank".

INTRODUCTION: The number of noninvasive diagnostic tests for bladder cancer has increased tremendously over the last years with a large number of experimental and commercial tests. Comparative analyses of tests for diagnosis, follow-up, and recurrence detection of bladder cancer were performed retrospectively as well as prospectively, unicentrically, and multicentrically. METHODS: An analysis of multicentric studies with large patient numbers compared with our own Kiel Tumor Bank data is presented. The Kiel Tumor Bank data looked prospectively at 106 consecutive bladder tumor patients from the year 2006. Special focus was put on urine cytology as a reference test, as well as the commercial NMP 22 Bladder Chek. RESULTS: The analysis of the NMP 22 Bladder Chek showed an overall sensitivity of 69% for all tumor grades and stages, with a specificity of 76%. Comparison to multicentric data with an overall sensitivity of 75% for all tumor grades and stages, with a specificity of 73%, showed results similar to those in the literature. Urine cytology showed a comparable overall sensitivity of 73% for all tumor grades and stages, with a specificity of 80%. CONCLUSIONS: A large number of noninvasive tests for bladder cancer follow-up with reasonable sensitivity and specificity can currently be used. Because of limited numbers of prospective randomized multicentric studies, no single particular marker for bladder cancer screening can be recommended at this point in time.

Is urinary tract cytology still useful for diagnosis of bladder carcinomas? A large series of 592 bladder washings using a five-category classification of different cytological diagnoses.

BACKGROUND: The aim of this study was to estimate the efficiency of a recent five-category urinary cytological classification. METHODS: A total of 592 bladder washings were fixed immediately with Saccomanno's fixative. All samples were centrifuged in a Hettich cyto-centrifuge. For each sample, the reference standard was the histology when a lesion was present at the time of cystoscopy. A five-category cytological classification was used: negative, suspicious of low (S-Lg) or high (S-Hg) grade neoplasia and consistent with low (Lg) or high (Hg) grade neoplasia. RESULTS: For cytological diagnoses of S-Lg and Lg, sensitivity was 37% and specificity was 95% for the histological diagnosis of low-grade non-invasive urothelial papillary tumour (Lg-UPT), which included papillary urothelial neoplasm of low malignant potential and low-grade urothelial carcinoma. For cytological diagnosis of S-Hg and Hg, sensitivity was 44% for high-grade non-invasive urothelial papillary carcinoma (Hg-UPC), 70% for carcinoma in situ (CIS) and 81% for invasive carcinoma (T1 and higher). Specificity was 99% in each case. Cytological diagnosis of S-Hg or Hg was not found for Lg-UPT (0/59) and no cytological diagnosis of S-Lg or Lg was found for invasive carcinoma, but was seen for Hg-UPC in 10% (3/28) and for CIS in 6% (3/50) of cases. CONCLUSION: Despite the absence of international consensus, the recent five-category cytological classification for urine is accurate for current urological practice.

The value of the ImmunoCyt/uCyt+ test in the detection and follow-up of carcinoma in situ of the urinary bladder.

BACKGROUND: Urine bound tests, which have been developed for the early detection of urothelial cancer (UC), do not seem to match cytology in the detection of carcinoma in situ (CIS) as their sensitivity in the case of CIS is poor. ImmunoCyt/uCyt+ in CIS seems promising, but the number of analysed CIS is still small. The aim of the present study was to assess the value of this test in the detection and follow-up of carcinoma in situ of the urinary bladder. PATIENTS AND METHODS: Thirty-five patients, with histologically verified CIS of the urinary bladder, were included in the study. At the first diagnosis, patients underwent cytology, cystoscopy, bioptical bladder mapping and ImmunoCyt/uCyt+. All patients underwent BCG instillation therapy. The patients were followed with cytology, ImmunoCyt/uCyt+, cystoscopy and bladder mapping after every BCG cycle and then every 3 months. RESULTS: At the first CIS diagnosis, the sensitivity of cytology and ImmunoCyt/uCyt+ was 100%. At the first control after therapy, cytology detected 81.8% of recurrences and ImmunoCyt/uCyt+ detected 90.9%. At the second control, both tests each detected 50% of recurrences. At every control, the combination of both the tests together gave a sensitivity of 100%. The specificity of cytology after therapy improved from 88.2% at the first control up to 100% at the third control. The specificity of ImmunoCyt/uCyt+ after BCG initially decreased from 70.6% to 55.5% and finally increased to 88.9%. CONCLUSION: ImmunoCyt/uCyt+ is as sensitive as cytology in the first diagnosis of CIS. In the follow-up, even if it is less sensitive, its combination with cytology leads to detection of 100% of the recurrences. Despite decreasing specificity after therapy, the value remains acceptable and increases during maintenance therapy. The ImmunoCyt/uCyt+ test could play an important role in controlling the response of patients to instillation therapies or in the modification of their application schedules.

[Early diagnosis of bladder carcinoma]. / Wczesna diagnostyka raka pecherza moczowego.

Asymptomatic erythrocyturia is an early symptom of urinary tracts and kidney diseases, including bladder carcinoma. The aim of the research was to compare the diagnostic validity of the cytological urine analysis and the DNA flow cytometry in detecting cancer cells in urine and bladder washings, taken from patients with asymptomatic erythrocyturia, as an early symptom of the bladder carcinoma in situ. The research was conducted on a group of 48 patients (32 male, 16 female, aged 28-55) with asymptomatic erythrocyturia, caused, in 16 cases, by bladder carcinoma in situ, in 18 cases, by bladder carcinoma in situ with urinary tracts infection, and in 14 cases, by the infection alone. Flow cytomery showed a higher sensitivity and a higher negative prediction value in detecting cancer cells in bladder washings. Flow cytometry analysis of DNA and phase S is used for detecting early disturbances in the cell cycle which result in aneuploidia, which is impossible to detect in cytological analysis. However peculiarity and positive prediction value were the same (100%) in both methods. On the basis of the research it has been proved that asymptomatic erythrocyturia classifies patients for further, in-depth diagnostic examination for the presence of bladder carcinoma in situ. Furthermore, morning urine and bladder washings analysis, which are non-intrusive tests, are an outstanding diagnostic material for screening for this disease. Detecting aneuploidia with flow cytometry can be an early-detection screening test for bladder carcinoma, while the cytological tests should still be used for confirming the diagnosis.

Numeric aberrations of HER-2 and chromosome 17 detected by fluorescence in situ hybridization in urine-exfoliated cells from patients with urothelial carcinoma.

OBJECTIVES: To elucidate the clinical significance of the HER-2 gene alterations in urine-exfoliated cells detected by fluorescence in situ hybridization (FISH) in patients with urothelial transitional cell carcinoma. METHODS: The relative increase of HER-2 (RI-HER2) and gain of chromosome 17 (G-17) in urine-exfoliated cells were examined using DNA probes for HER-2 and the chromosome 17 centromere in 103 patients. In addition, FISH analysis was performed using corresponding paraffin-embedded tissue sections from 45 cases to compare the results obtained using urine-exfoliated cells and those obtained using paraffin-embedded tissue. RESULTS: RI-HER2 and G-17 was found in 23 (22.3%) and 46 (44.6%) of 103 patients, respectively. RI-HER2 was significantly more frequent in tumors with two or more recurrences (40.7% versus 15.8%, P = 0.010) and in those with carcinoma in situ (CIS) (35.4% versus 15.9%, P = 0.029). G-17 was more frequent in high-grade tumors (69.1% versus 16.7%, P = 0.032), invasive tumors (63.6% versus 14.3%, P < 0.001), and in patients with CIS (77.1% versus 29.0%, P < 0.001). The positive rate for FISH (presence of RI-HER2 and/or presence of G-17) tended to be more frequent in FISH than in cytology. A comparison of the analyses using urine-exfoliated cells and paraffin-embedded tissue showed identical results in 36 (80.0%) of 45 cases. CONCLUSIONS: Numeric alterations of the chromosome 17 centromere in urine-exfoliated cells detected by FISH may reflect the malignant potential of urothelial carcinoma. In addition, a relative increase in HER-2 was associated with the number of recurrences and the presence of CIS.