Diagnosis Of Urothelial Cell Carcinoma Research Articles

Chemotherapy of Locally Advanced or Metastatic Urothelial Cell Carcinoma: Monocentric Real-Life Data.

Background/AimUp to 30% of all patients will present with an advanced or a metastatic stage (mUCC) at the moment of the initial diagnosis of urothelial cell carcinoma of the bladder (UCC). We investigated the numbers, the efficacy and toxicity of different chemotherapies for mUCC in daily practice and “real-life” conditions and evaluated them substance-specifically.Patients and MethodsAll patients with a mUCC, who were treated between January 1, 2006 and October 31, 2016 at the Department of Urology and Pediatric Urology at University Hospital Marburg (Germany), were retrospectively analyzed. We set the focus on demographic and tumor-specific data as well as on effectiveness, therapy sequences, and drug tolerance.ResultsForty-one patients were identified. Of the 41 patients, 85.4% of the patients in first-line therapy received gemcitabine/cisplatin. A large proportion of 85.4% received a second-line therapy and 40% a third-line therapy due to progress or relapse. Median overall survival (mOS) was 18 months including all patients and increased up to 29.5 months in the cases of three therapy lines.ConclusionOur data reveal that chemotherapy of mUCC is effective and side effects are manageable in daily clinical practice.

National trends and pathologic outcomes of neoadjuvant chemotherapy among patients with micropapillary variant urothelial carcinoma of the bladder.

477 Background: Micropapillary variants of urothelial cell carcinoma (UCC) are associated with aggressive clinical behavior including an increased risk of regional and distant metastasis. Although neoadjuvant chemotherapy (NAC) improves survival for patients with UCC who achieve a complete pathologic response (pT0), less is known regarding the uptake of this practice in patients with micropapillary variant (MV) or its effect on pathologic response. Methods: We queried the National Cancer Database to identify all patients with a diagnosis of UCC including MV from 2004-2014. We restricted our analysis to patients who underwent radical cystectomy with or without NAC. We compared clinical, demographic, and pathologic characteristics and evaluated time trends associated with use of NAC. Following propensity score matching to balance covariates associated with the receipt of NAC, we used logistic regression models to study the association of NAC use and pT0 rate. Dual analyses were performed among patients with clinical stage II (cT2) disease, as well as the entire cohort (all stages). Results: We identified 102,266 patients, including 101,272 (99.03%) pure UCC and 994 (0.97%) MV. Patients with MV were younger (Median 70 years vs 73 years, p < 0.001), more commonly male (79.0 vs 73.6% p < 0.001), were more commonly treated in academic centers (66.43% vs 44.77%), there was no difference between urban/rural areas. Use of NAC among patients with cT2 increased in the entire cohort from 27% on 2004 to 49.7% in 2014 for UCC, and from 50% to 58% for MV. Among patients with cT2 disease, 38.4% of UCC received NAC and 49% MV received NAC (P < 0.001). Following propensity score matching, receipt of NAC was associated with pT0 for both histological diagnoses (OR 2.13 95% CI: 1.65-2.78 p < 0.001). This effect persisted on restriction to patients with cT2 (OR 3.32, 95% CI: 2.32-4.75, p < 0.001). Conclusions: There has been increased use of NAC among patients with micropapillary variant. Patients with cT2 micropapillary variant were equally like to be achieve a pathologic complete response to NAC as were patients without histologic variants of urothelial cell carcinoma.

Ureteral pseudodiverticulosis and urothelial cell carcinoma: rethinking the association.

To compare frequency of new and recurrent urothelial cell carcinoma (UCC) among patients with and without pseudodiverticulosis on imaging. This retrospective case-control study compared all 113 sequential patients with ureteral pseudodiverticulosis on radiographic urography between 1/1/2002 and 12/31/2012. Six patients were lost to follow-up. 107 patients without pseudodiverticulosis were matched by imaging modality, clinical indication, and tumor grade. Known UCC and primary outcome of new or recurrent UCC were determined through pathology on cystoscopy or clinical follow-up. Nearly half of patients with pseudodiverticulosis had known UCC at the time of imaging (49/107, 46%). Mean cystoscopy follow-up was 7.0 and 4.6years for pseudodiverticulosis cases with and without known UCC, respectively, and 7.5 and 7.3years for controls, respectively. Mean clinic follow-up was 7.5 and 6.0years for pseudodiverticulosis cases with and without known UCC, respectively, and 6.4 and 7.6years for controls, respectively. Among patients with known UCC at the time of imaging, similar rates of recurrent UCC were demonstrated on follow-up among patients with pseudodiverticulosis (6/49, 12%) and without (7/49, 14%). Among patients with no known history of UCC at the time of imaging, no patients with pseudodiverticulosis developed UCC on follow-up and 5% (3/58) of patients without pseudodiverticulosis developed UCC. Although half of patients with ureteral pseudodiverticulosis have a known diagnosis of UCC, the presence of pseudodiverticulosis did not signify an increased likelihood of developing new or recurrent UCC over the follow-up period.

Artificial neural network in diagnosis of urothelial cell carcinoma in urine cytology.

To build up an artificial neural network (ANN) model in the diagnosis of urothelial cell carcinoma (UCC) in urine cytology smears. We randomly selected a total of 115 urine cytology samples, out of which 59 were histopathology proven UCC cases and remaining 56 were benign cases from routine cytology samples. All the carcinoma cases were proven on histopathology. Image morphometric analysis was performed on Papanicolaou's stained smears to study nuclear area, diameter, perimeter, standard deviation of nuclear area, and integrated gray density. Detailed cytological features were also studied in each case by two independent observers and were semi-quantitatively graded. The back propagation ANN model was designed as 17-11-3 with the help of heuristic search. The cases were randomly partitioned as training, validation, and testing sets by the program. There were 79 cases for training set, 18 cases for validation set and 18 cases for test set. In the training set, ANN was able to diagnose all the malignant and benign cases. In the test set, all the benign and malignant cases were diagnosed correctly. However, one of the low grade cases was diagnosed as high grade UCC by ANN model. We successfully built an ANN model in urine from the visual and morphometric data to identify the benign and malignant cases. In addition, the system can also identify the low grade and high grade UCC cases.

Confocal Laser Endomicroscopy of Bladder Tumors Associated With Photodynamic Diagnosis: An Ex Vivo Pilot Study

To improve the sensitivity of white light cystoscopy, photodynamic diagnosis (PDD) is useful but has low specificity. Recently, confocal laser endomicroscopy (CLE) has been used for the diagnosis of urothelial cell carcinoma. The main objective was to examine the feasibility of simultaneous PDD and CLE. A secondary objective was to determine whether hexyl aminolevulinic acid (HAL) can be used just as fluorescein for CLE. In the present prospective single-center study with a same-patient comparison, patients with suspected urothelial cell carcinoma underwent surgical exploration after receiving a bladder instillation of HAL. After resection of suspected lesions under blue light, the samples were inspected ex vivo using CLE with and without fluorescein. Simultaneous blue light CLE inspection was performed. All samples were then transferred to the pathology laboratory for the classic analysis. Of the 12 patients studied, blue light cystoscopy revealed suspect lesions in 11; 10 had pathology proven urothelial cell carcinoma. CLE analysis was not modified by sample exposure to blue light, which facilitated orientation of the fiber toward the suspect red fluorescence areas. The fluorescence obtained with HAL-CLE was insufficient for microscopic histologic analysis, unlike the resolution obtained with fluorescein. Comparing CLE and the pathologic findings was possible and conclusive for 4 of 12 samples. Combining PDD and CLE ex vivo demonstrated the usefulness of HAL for guiding blue light CLE. HAL was insufficient to allow histologic CLE, which required the use of fluorescein. The results of this pilot study have indicated the feasibility of CLE. However, an in vivo method incorporating fluorescein and PDD will be required to improve the diagnostic specificity of PDD alone.

332 Diagnosis of urothelial cell carcinoma by immunocytochemical detection of minichromosome maintenance protein 2 (MCM-2) in cells retrieved from urine

332 Diagnosis of urothelial cell carcinoma by immunocytochemical detection of minichromosome maintenance protein 2 (MCM-2) in cells retrieved from urine

Altered expression of cell adhesion molecules leads to differential uptake of hypericin in urothelial cancer

ObjectiveTo elucidate the mechanism behind selective uptake of hypericin in bladder cancer after intravesical instillation for photodynamic diagnosis of urothelial cell carcinoma of bladder. Patients and methodsClinical studies were done on a series of 60 bladder cancer biopsies obtained from 28 patients who received intravesical instillations with 8 μM hypericin. Serial 5 μm cryosections were cut from 43 biopsies, and expression of the E-cadherin and associated catenins were determined using immunohistochemical and immunofluorescence staining. Hypericin was assessed using fluorescence confocal laser scanning microscopy. In addition, mRNA expression of these cell-adhesion molecules was analyzed in 17 biopsies using reverse transcription-PCR. ResultsIncreased variability in the expression of E-cadherin and associated molecules was found in high-grade, advanced stage bladder carcinoma. An inverse association was found between immunoreactivity for E-cadherin, β- and γ-catenin, and both stage and grade of cancer (P < 0.05). A positive association was observed between the hypericin fluorescence and tumor grade. There was a significant down-regulation of E-cadherin and β-catenin mRNA in grade 2 and 3 tumors. Although a small sample size was studied, it provided sufficient proof to support the hypothesis that altered expression of cell adhesion molecules would lead to preferential hypericin uptake in urothelial cell carcinoma. ConclusionsOur study has unraveled one of the many factors contributing to the selective uptake of hypericin in bladder cancer. We have thus identified the effects of alteration of E-cadherin–catenin complex and transformed intercellular junction in the modified paracellular uptake of hypericin that provides the rationale for using this photosensitizer in photodynamic diagnosis of bladder carcinoma.

FGFR3 and TP53 mutations in urothelial cell carcinoma: two molecular pathways and diagnostic value

FGFR3 and TP53 mutations are frequent in superficial papillary and invasive disease urothelial cell carcinoma respectively. This high frequency of FGFR3 and TP53 mutations, led us to compare these two genetic alteration in 81 bladder cancer tumors of all stages and grades at initial diagnosis, to determine whether they correspond to different disease pathways and could be used for molecular classification of these tumors. Moreover, the role and the position of FGFR3 mutations in the current models of bladder carcinogenesis need to be clarified. We used denaturing high-performance liquid chromatography and sequencing to screen for FGFR3 and TP53 mutations in 81 newly diagnosed urothelial cell carcinomas. FGFR3 mutations were associated with low-stage (P < 0.0001), lowgrade (P < 0.008) tumors, whereas TP53 mutations were associated with high-stage (P < 0.003), high-grade (P < 0.02) tumors. Mutations in these two genes were almost mutually exclusive. Our results suggest that FGFR3 and TP53 mutations define separate pathways at initial diagnosis of urothelial cell carcinoma. On the other hand, given the high frequency of FGFR3 mutations and the possible implication of this receptor in the development of UCC, it was important to develop a simple, fast, and reliable method to identify these mutations in greater detail as a potential tool for the diagnosis and follow-up of UCC patients. Ten different FGFR3 mutations have been described in UCC, but 4 of them (R248C, S249C, G372C, and Y375C) account for 95% of cases. Therefore in this study we developed an allele specific PCR (AS-PCR) for the detection of these mutations in tumors and urine. For the 95 tumors examined, AS-PCR had a specificity of 90% and a sensitivity of 88%. The test correctly identifies FGFR3 mutations in the 20 tumors and the corresponding urine samples investigated. However, because our study was carried out on primary tumors rather on recurrent tumors, which are usually smaller, a prospective study of the diagnostic value of this test for the detection of recurrences should be undertaken. from 2009 American University in Cairo Research Conference Cairo, Egypt. 5 April 2009

Comparative Evaluation of the Nuclear Matrix Protein, Fibronectin, Urinary Bladder Cancer Antigen and Voided Urine Cytology in the Detection of Bladder Tumors

We evaluate the diagnostic efficacy of nuclear matrix protein-22 (NMP22, Matritech, Newton, Massachusetts), fibronectin and urinary bladder cancer antigen (UBC, IDL Biotech, Borlange, Sweden) compared with voided urine cytology in the detection of bladder cancer. A total of 168 patients provided a single voided urine sample for NMP22, fibronectin an ideal monoclonal for urinary bladder cancer and cytology before cystoscopy. Cystoscopy was done for all patients as the reference standard for identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. Of the 168 cases 100 were histologically diagnosed as bladder cancer, whereas the remaining 68 had benign urological disorders. A group of 47 healthy volunteers were also enrolled in this study. Voided urine was evaluated by NMP22, fibronectin and UBC, and their values were expressed relative to mg. creatinine. The optimal threshold values for NMP22, fibronectin and UBC were calculated by receiver operator characteristics curves as 27 units per mg. creatinine, 198 mg./mg. creatinine and 13 ng./mg. creatinine, respectively. The levels and positive rates of the 3 parameters were significantly higher in the malignant group compared to either the benign group or normal controls. Of the entire group NMP22, fibronectin and UBC were positive in 93.2%, 91% and 68.2%, respectively in bladder cancer cases with positive cytology. Moreover, these positive rates were significantly higher in bilharzial bladder cancer cases (58.8%, 67.5%, 58.8%, respectively) compared to nonbilharzial cases (35.6%, 36.3%, 31.1%). Overall sensitivity and specificity were 85% and 91.3% for NMP22, 83% and 82.6% for fibronectin, 67% and 80.8% for UBC and 44% and 100% for voided urine cytology. Combined sensitivity of voided urine cytology with the 3 biomarkers together was higher than either combined sensitivity of voided urine cytology with 1 of the biomarkers or than that of the biomarker alone. Our data indicate that NMP22 and fibronectin had superior sensitivities compared to UBC and voided urine cytology, while NMP22 and voided urine cytology had the highest specificities. The combined use of markers increased the sensitivity of cytology from 44% to 95.3%. The higher sensitivities of markers in bilharzial than nonbilharzial bladder cancer highlight their clinical use in screening patients with urinary bilharziasis.

Comparison of two qualitative assays, the UBC rapid test and the BTA stat test, in the diagnosis of urothelial cell carcinoma of the bladder

Objectives. To compare the diagnostic value of two rapid tests, the bladder tumor antigen (BTA stat) test and the newly developed urinary bladder cancer (UBC) Rapid test, in patients having symptoms suggestive of urothelial cell carcinoma (UCC) and patients being followed up after transurethral resection. Methods. One hundred eighty patients with a mean age of 65.8 years (range 22 to 92) were included in the present study. The tests were performed on voided urine samples. Fifty-seven patients had symptoms suggestive of UCC and 123 patients were being followed up after complete transurethral resection of UCC. The voided urine was evaluated by the BTA stat and UBC Rapid test, which detects cytokeratins 8 and 18. All patients underwent subsequent cystoscopic evaluation and biopsy of any suspicious lesion. Results. In 53 patients with histologically proved UCC, the BTA stat had a sensitivity of 52.8% and the UBC Rapid test of 66%. According to the histologic stage, the sensitivity of the BTA stat was 42.8% in pTa tumors, 61.5% in pT1, and 70% in pT2 or higher tumors. The sensitivity of the UBC test was 60.7% in pTa, 69.2% in pT1, and 80% in pT2 or higher tumors. For histologic grades 1 to 3, the sensitivity was 38.8%, 52.6%, and 68.7% for the BTA stat and 44.4%, 78.9%, and 75% for the UBC Rapid test, respectively. The specificity was 70% and 90% for the BTA stat and UBC Rapid test, respectively. Conclusions. The UBC Rapid test was superior to the BTA stat in both sensitivity and specificity. Both assays are simple office procedures and require no special knowledge. However, they cannot replace, but only lower, the number of cystoscopies during the follow-up of patients with previous UCC of the bladder.