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Biomedical subjects

W Böcker

Publications and source records attributed to W Böcker.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparative coronary anatomy in six twin pairs with coronary artery disease.

OBJECTIVE: To compare the coronary anatomy and the location of coronary lesions in monozygotic and dizygotic twin pairs affected with coronary artery disease. DESIGN: Coronary angiographic findings were compared with respect to the distribution of coronary blood supply and the location of coronary lesions. MAIN OUTCOME MEASURES: Distribution of coronary blood supply, diameters and length of proximal coronary arteries. RESULTS: The lumen diameters of the left main coronary artery, the left anterior descending coronary artery, the circumflex artery, and the right coronary artery, as well as the lengths of the left main coronary artery, showed similar variability within monozygotic and dizygotic twin pairs. With respect to the dominance pattern of coronary blood supply, two of three monozygotic twin pairs differed, while all dizygotic twin pairs were concordant. Concordant and discordant locations of stenoses were found with similar frequency in monozygotic and dizygotic twin pairs. CONCLUSIONS: The dominance pattern of coronary blood supply and the location of coronary lesions are not strictly hereditary. The high concordance of premature coronary artery disease found in monozygotic twin pairs may largely be related to factors that are independent of the macroanatomic distribution of the coronary blood supply.

Adult↗
PubMed2000

Genetic relation of lobular carcinoma in situ, ductal carcinoma in situ, and associated invasive carcinoma of the breast.

AIMS: The mutual relation of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) of the breast, as accepted precursor lesions of invasive breast cancer, is controversial. Because they display genetic heterogeneity, it is not clear how genetically advanced these entities are and what causes the transition to an invasive carcinoma. METHODS: Six cases of LCIS, four of them with associated lobular invasive carcinoma, four cases of intermediately differentiated DCIS with an associated invasive lobular carcinoma, and nine cases of intermediately and poorly differentiated DCIS with associated ductal invasive carcinoma were investigated by means of comparative genomic hybridisation (CGH) after microdissection and immunohistochemical staining of E-cadherin. RESULTS: LCIS was characterised by a low average rate of copy number changes, no evidence of amplifications, and a high rate of gains and losses of chromosomal material at 1q and 16q, respectively. A high degree of genetic homology with well differentiated DCIS was obvious, as reported previously. The cases of intermediately differentiated DCIS with associated lobular invasive components and lobular differentiation revealed striking homologies, and a significant difference of E-cadherin expression. The comparison of preinvasive and invasive breast lesions, irrespective of differentiation within the same patient, revealed no specific alteration that might be associated with invasion. Genetic alterations seen in invasive carcinoma were not necessarily seen in the adjacent precursor lesions. CONCLUSIONS: These results provide strong evidence that invasive breast cancer is a disease with multiple cytogenetic subclones already present in preinvasive lesions. Moreover, specific CGH alterations associated with invasion were not observed. Furthermore, the close genetic association between well differentiated and a subgroup of intermediately differentiated DCIS and LCIS led to the hypothesis that LCIS and a subgroup of DCIS are different phenotypic forms of a common genotype.

Breast Neoplasms↗
PubMed2000

Correlation of morphologic and cytogenetic parameters of genetic instability with chromosomal alterations in in situ carcinomas of the breast.

Classification of preinvasive breast disease could be better founded using biologic markers, thereby increasing reproducibility. We studied 57 breast ductal and lobular in situ carcinomas by means of comparative genomic hybridization and correlated these findings with quantitative features such as the mean nuclear area, mitotic index (MI), apoptotic index (AI), and the presence or absence of necrosis. Loss of 8p and gains of 8q and 6q were associated, respectively, with a significantly higher MI and AI, whereas loss of 16q was associated with a lower MI and AI. A significantly higher number of alterations per case were seen in tumors with gains of 6q, 8q, and 17q and tumors with loss of 13q. Loss of 16q and gain of 17q correlated with the absence or presence of necrosis, respectively. Our data clearly demonstrate that distinct cytogenetic changes correlate with phenotypic changes, proliferation, and apoptosis. These data may be used to refine existing classification schemes.

Apoptosis↗
PubMed2000

Some effects of non-surgical therapy on gingival inflammatory cell subsets in patients with adult and early-onset periodontitis.

BACKGROUND: Limited information is available to determine if there is a distinction in local cellular immunity between adult and early-onset periodontitis. Furthermore, the effect of scaling and root planing on various lymphocyte subsets is sparsely described. METHODS: Clinical measurements were recorded and gingival biopsies were performed before and after scaling and root planing in 10 subjects with adult (AP) and in 10 with early-onset periodontitis (EOP). The specimens were cut into serial sections and, using the alkaline phosphatase-anti-alkaline phosphatase technique, monoclonal antibodies to CD20 (B-cells), CD30 (plasma cells), and CD45RO (T-memory cells) were applied, as well as polyclonal antibodies to alpha, gamma, and mu chains (Ig A, G, and M). Areas showing the largest infiltration cells were counted. RESULTS: Mean counts of all cell phenotypes in the AP versus the EOP group did not show any significant differences before therapy (P >0.05). Following scaling and root planing, numbers of all phenotypes decreased in both groups. Comparing the data before and after therapy, P values were >0.05 in the AP group, except for IgA-positive cells. In the EOP group, the differences before and after therapy reached statistical significance (P<0.05) for all cell counts, except for IgM-positive cells. Furthermore, reduction of probing depth and gain of clinical attachment reached the 0.05 level of statistical significance only in EOP subjects. CONCLUSIONS: Local cellular immunity in patients with adult onset periodontitis does not appear to differ from the immune response in patients with early onset periodontitis. Scaling and root planing causes a decrease in the inflammatory cells subsets tested, however, this decline seems to be more pronounced in EOP than in AP subjects.

Adult↗
PubMed1999

Automated comet assay analysis.

BACKGROUND: Recently the "comet assay" or "single-cell gel electrophoresis assay" has been established as a sensitive method for the detection of DNA damage and repair. Most of the software now available to quantify various parameters for DNA damage requires the interaction of a human observer. In this report, we describe an automated analysis system that is based on self-developed software and hardware and needs minimal human interaction. METHODS: The image analysis is divided into two parts: 1) automatic cell recognition and comet classification and 2) quantification of desired comet parameters. Image preprocessing, segmentation, and feature classification were developed with algorithms based on mathematical morphology. To enhance evaluation speed, we have introduced parallel processing of data under the Windows NT operating system (Microsoft Corporation, Redmond, WA). Use of an analogue real-time autofocus unit (Böcker et al.: Phys Med Biol 1997;42:1981-1992) allows for faster analysis. RESULTS: Our recognition software shows a sensitivity of 95.2% and a specificity of 92.7% when tested on test samples from routine work with DNA damage by low-dose radiation (0-2 Gy). The parallel hardware and software concept enables us to analyze 100 comets on one slide in less than 15 min. CONCLUSIONS: A comparison of measurements made on the same samples by manual and automated analysis systems revealed that there are no significant differences. The slope of the dose-response curves and the repair kinetics are very similar and demonstrate that automatic comet assay analysis is possible.

Algorithms↗
PubMed1999

Optimization and standardization of the "comet assay" for analyzing the repair of DNA damage in cells.

BACKGROUND: The "comet assay" has become an interesting and a very useful tool for the analysis of the induction and amount of DNA damage in single cells thus offering the opportunity to measure the effectiveness of DNA repair. On the basis of the Ostling and Johanson protocol we have developed a modified method with increased sensitivity and high reproducibility. MATERIAL AND METHODS: Human tumor cells or isolated human peripheral blood lymphocytes were analyzed in the experiments. The amount of DNA damage and the effectiveness of DNA repair was measured after X-irradiation using the "comet assay" technique. RESULTS: In this presentation the influences of different methodological factors like agarose concentration, buffer pH, electrophoresis time, electric field strength on the applicability of the "comet assay" are described in detail and optimum conditions for "comet assay" experiments have been evaluated. Additionally the authors will show a comparison of different fluorescent DNA dyes pointing out their advantages or disadvantages for "comet" analysis. The usefulness of this technique and its capabilities are exemplified by showing DNA repair kinetics of human lymphocytes of different healthy or radiosensitive donors after in-vitro irradiation with 2 Gy X-rays. CONCLUSIONS: This paper presents data on the optimization and standardization of the original "comet assay" leading to an extremely fast and practicable protocol in the field of single cell gel electrophoresis. After irradiation with 0.1 Gy an increase in the amount of DNA damage can be measured with high statistical significance and the DNA repair capacity of individual cells after X-ray doses of 2 Gy can be analyzed with high reproducibility. The results comparing DNA repair capacities of different donors point out that the "comet assay" may have the potential for the estimation of individual radiosensitivity.

Adult↗
PubMed1999

Transgenic rats expressing the human ET-2 gene: a model for the study of endothelin actions in vivo.

Previous studies have characterized the endothelin peptides (ET-1, ET-2, ET-3) as strong vasoconstrictors which are possibly involved in the pathogenesis of cardiovascular disease. Whereas ET-1 and ET-3 have been characterized using a number of approaches, little is known about the function of ET-2. The aim of this study was to define the role of ET-2 in physiology and pathophysiology using a transgenic approach. Transgenic rats expressing a genomic construct of the human ET-2 gene were generated by microinjection of fertilized oocytes from Sprague-Dawley rats. Two transgenic lines were generated, and one line was further characterized in detail. Studies on mRNA expression demonstrated that the transgene is expressed predominantly in kidney, gastrointestinal tract, adrenal gland, lung, and brain. Plasma endothelin levels were elevated 2-fold, and big-endothelin levels were elevated 2.5-fold. Despite these alterations blood pressure in transgenic rats remained normal. Further analysis of transgenic animals revealed that endothelin receptors were not downregulated, and that infusion of exogenous human ET-2 results in an enhanced blood pressure response. These observations suggest the presence of counterregulatory mechanisms influencing the effects of endothelin on blood pressure. One of these mechanisms may involve the nitric oxide system since infusion of an inhibitor of nitric oxide synthase resulted in a greater blood pressure response than in non-transgenic littermates. Despite unchanged blood pressure, alterations were observed in organ development and function, namely of hearts and kidneys, indicating an interference between transgene expression and growth processes. Male rats seem to be more susceptible to endothelin actions. These data show that the elevation in endothelin-2 expression in this transgenic model does not induce hypertension but leads to changes at the end-organ level. Normotension is most likely due to compensatory mechanisms such as increased nitric oxide formation.

Animals↗
PubMed1999

The cardiac endothelin system in established pressure overload left ventricular hypertrophy.

In normal hearts, endothelin-1 (ET-1) has been shown to initiate myocyte growth and to modulate cardiac function. However, regulation of the various components of the system and the functional effects of ET-1 in established left ventricular hypertrophy (LVH) are less clear. We thus studied ET-1, ET(A) receptor, and endothelin converting enzyme (ECE-1) mRNA regulation as well as the effects of ET-1 on coronary resistance, LV contractility and relaxation in hypertrophied rat hearts. Cardiac pressure overload, secondary to banding of the ascending aorta, resulted in a transient increase of cardiac ET-1 and ET(A) receptor mRNAs that reached a maximum at 2 days (+75% and +40%, respectively, P<0.05, each). ET-1 mRNA levels reached a second peak at 84 days of pressure overload (+60%, P<0.05), at the later time point in conjunction with elevated ECE-1 mRNA levels (+20%, P<0.05). The functional implications of ET-1 were examined in a study of isolated perfused hearts. Both hearts with established LVH and sham control hearts responded to ET-1 perfusion (10(-1)] to 10(-9) M) with an increase of coronary perfusion pressure (CPP; +85+/-15 and +75+/-8 mm Hg; P<0.001 each) and a slight decrease of LV systolic pressure (LVP; -12+/-9 and -9+/-7 mm Hg; P = NS). In contrast, ET-1 increased LV end-diastolic pressure (LVEDP) only in LVH hearts (+22+/-7 mm Hg, P<0.05 versus baseline and +20+/-7 mm Hg, P<0.05 versus sham). Direct stimulation of protein kinase C mimicked the effects of ET-1, whereas inhibition of this kinase or the Na+ -H+ exchanger blunted the effects of ET-1 on CPP, LVP, and LVEDP. Interestingly, coadministration of the vasodilator and the nitric oxide (NO) donor nitroglycerin not only prevented the increase of CPP and LVEDP, but also uncovered a slight positive inotropic effect of ET-1 in LVH hearts. Thus, the cardiac expression of ET-1, ET(A), and ECE-1 mRNAs displays a distinct pattern during early and advanced cardiac pressure overload. Furthermore, ET-1 mediates a slight depression of systolic, and a profound depression of diastolic, functional parameters in hearts with established LVH, effects that appear to be secondary to ET-1-related coronary vasoconstriction. The data suggest a functional role of the endothelin system in hearts with established pressure overload hypertrophy.

Amiloride↗
PubMed1999

Standardized in situ AgNOR analysis in breast pathology: diagnostic and cell kinetic implications.

The aim of the present study was to assess the diagnostic value of the recently standardized morphometric analysis of silver-stained nucleolar organizer region-associated proteins (AgNORs) [30] in a variety of 155 routinely processed benign and malignant breast lesions. 5 normal breast samples, 21 adenoses, 20 ductal hyperplasias, 10 atypical ductal hyperplasias, 20 in situ and 43 invasive ductal carcinomas, 10 in situ and 26 invasive lobular carcinomas were investigated. A statistically highly significant difference was found between normal/ordinary hyperplastic and neoplastic breast lesions with all 4 consensus AgNOR parameters (mean area, mean number, CV of area, CV of number) evaluated. AgNOR quantity was significantly related to histological grade of both in situ and invasive carcinomas. However, variable overlap was found between AgNOR values in different diagnostic groups. We conclude that standardized AgNOR analysis is a prerequisite for objective and reproductible AgNOR assessment in archival tissues. Despite its limited diagnostic utility for individual breast lesions, standardized AgNOR analysis bears a significant potential for characterizing cell kinetic and metabolical activity of breast lesions. This may give insight into the biological background of breast carcinogenesis, differentiation and tumor progression and may also underlie the independent prognostic value of AgNORs in breast cancer.

Breast↗
PubMed1999

Telomerase activity distinguishes between neuroblastomas with good and poor prognosis.

BACKGROUND: Treatment of neuroblastoma has remained a major challenge in pediatric oncology because the assessment of the individual prognosis, particularly in disseminated disease is still obscure. Previous studies have correlated clinical outcome with activity levels of telomerase, a cellular reverse transcriptase which has been detected in the majority of human malignant tumors. PATIENTS AND METHODS: In this blind-trial study, a non-radioactive telomeric repeat amplification protocol (TRAP) with an internal telomerase-assay standard was used on an automated laser fluorescence sequencer for the detection and semiquantitative analysis of telomerase activity (TA) in 67 neuroblastomas of all clinical stages from the German Neuroblastoma Trial and 2 ganglioneuromas. TA levels were correlated with event-free and overall survival rates and established prognostic markers such as MYCN. RESULTS: TA was present in 14 of 69 (20%) samples, including 3 of 22 stage IVS, 8 of 14 stage IV, 1 of 10 stage III, 1 of 7 stage II and 1 of 14 stage I neuroblastomas and 0 of 2 ganglioneuromas. We found a strong statistical correlation between the presence of TA and poor clinical prognosis with regard to all tumor stages. Multivariate analysis revealed TA as an independent prognostic marker. In particular, the analysis of TA in IVS neuroblastomas distinguished two different prognostic groups. CONCLUSIONS: Our data suggest that TA is an independent prognostic marker in neuroblastoma which, in combination with other markers such as MYCN, may proof useful in assessing the individual patient's prognosis.

Amino Acid Sequence↗
PubMed1999

Tumors of the papilla of Vater--inadequate diagnostic impact of endoscopic forceps biopsies taken prior to and following sphincterotomy.

BACKGROUND: It has been proposed that adenomas of the papilla of Vater are precursors of adenocarcinomas. Duodenoscopy with ERCP and forceps biopsies have substantially improved the morphologic exploration of the major duodenal papilla. Yet there is little and contradictory information as to the diagnostic accuracy of endoscopic biopsies in tumors of the papilla. Moreover, after endoscopic sphincterotomy data on the diagnostic impact of endoscopic biopsies from the papilla are scarce and, in most cases, retrospectively obtained. Thus, the aim of the present prospective and histopathologically controlled study was to assess the diagnostic accuracy of endoscopic biopsies taken from tumors of the papilla before and after sphincterotomy. PATIENTS AND METHODS: Forty patients with tumors of the papilla of Vater were included in the study. In each case, a comparison was made between endoscopic forceps biopsy diagnoses prior to and following sphincterotomy and the definitive histological diagnosis after surgical tumor resection. RESULTS: Resected tumors were diagnosed histomorphologically as follows: 19 adenocarcinomas (47%), 6 tubular adenomas (15%), 7 villous adenomas (17%), 7 inflammatory non-neoplastic lesions (pseudotumors) (17%), and one adenomyoma (2%). Overall accuracy for preoperative histopathological diagnosis was 62% (25 of 40, 95% CI: 47%-76%) prior to sphincterotomy while it was 70% (28 of 40, 95% CI: 55%-81%) following the procedure. Regarding adenocarcinomas, sensitivity was found to be 21% (4 of 19, 95% CI: 8%-43%) prior to and 37% (7 of 19, 95% CI: 19%-58%) after sphincterotomy while specificity was 100% at both times. CONCLUSIONS: Endoscopic forceps biopsies do not allow for reliable preoperative diagnosis of tumors of the papilla of Vater.

Adenocarcinoma↗
PubMed1999

Postoperative death should be followed by autopsy - an analysis of the autopsy findings of the years 1990 and 1991 in a heart surgery center.

BACKGROUND: In this retrospective analysis of all autopsies performed in 1990 and 1991 on cardiac surgery patients who died before discharge from our university hospital, we intended to test the use of postmortem examination among cardiac surgery patients. METHODS: Perioperative data of all patients who underwent autopsy because of postoperative death during this time period were collected using a retrospective analysis of hospital and autopsy records. RESULTS: In 1990 and 1991 a total of 2407 patients underwent cardiac surgery with extracorporeal circulation at our institution. The in-hospital mortality was 2.9% (n=36) in 1990 and 3.3% (n=40) in 1991. For most of all patients who died during the postoperative course, we found a highly symptomatic cardiac disease and significant co-morbid conditions. The autopsy rate was 46.1% (35/76 patients). Cardiac failure with shock symptoms was the leading course of death (68.6%). In 22.9% of these patients (n=8) the autopsy provided information which had not been clinically recognized (e.g. myocardial infarction, thrombosis of bypass grafts, pneumonia) but might have altered the postoperative therapy if it had been. CONCLUSIONS: Despite the well-known trend of decreasing autopsy rates in the western world we believe that the postmortem examination is a most valuable diagnostic tool in the setting of a university cardiac surgery unit. Our results confirm the importance of autopsies for all patients who die after the operation, because a significant part of autopsies reveals major discrepancies between clinical and postmortem diagnoses. In an effort to maintain a high quality of treatment and education the autopsy rate of a hospital is of utmost interest.

Adolescent↗
PubMed1999

PCR based detection of mycobacteria in paraffin wax embedded material routinely processed for morphological examination.

BACKGROUND: The incidence of mycobacterial infections has increased during the past five years. A prompt diagnosis is indispensable for initiating appropriate treatment. Because culturing of mycobacteria takes three to six weeks and sensitivity of microscopic detection of acid fast bacilli is low, amplification methods provide promising possibilities. Recently, the polymerase chain reaction (PCR) has been shown to be useful for confirming a mycobacterial infection, especially in cases with unexpected histological findings or lack of suitable material for culturing. AIMS: To evaluate the impact of PCR based techniques in the detection of mycobacterial infections in uncultured routine histological specimens as an alternative to surgical pathology. METHODS: Two hundred and twenty nine formalin fixed and paraffin wax embedded samples from 141 patients with clinical or histological suspicion of a mycobacterial infection were investigated using three different PCR assays and Southern blotting. PCR results were compared with histology and culture and the patients' clinical findings. RESULTS: When using culture as the reference method, the sensitivity for the detection of mycobacteria of the tuberculosis complex was 90%, specificity was 92%, the positive predictive value was 81%, and the negative predictive value was 96%. The sensitivity for the detection of nontuberculous mycobacteria was 100% and specificity was 78%, the positive predictive value was 26%, and the negative predictive value was 100%. The patients' clinical findings supported the PCR positive results, indicating a mycobacterial infection in 11 of 18 initially culture negative cases and in 21 of 35 PCR positive cases without culture results. CONCLUSIONS: These results indicate that PCR based techniques are sensitive, specific, and rapid methods for the detection of mycobacteria in routinely processed paraffin wax embedded and formalin fixed histological samples.

Blotting, Southern↗
PubMed1998

Micronuclei-biological indicator for retrospective dosimetry after exposure to ionizing radiation.

Micronuclei can be measured through a conventional method after staining with Giemsa or fluorescence dyes for DNA. However, a technique with cell proliferation control should be preferred. This is done by incubation with cytochalasin B and counting the micronuclei in binucleated cells. Satisfactory dose relationships are observed after irradiation of human lymphocytes in vitro. The RBE for fast neutrons is around three. An automatic analysis is possible by image analysis. The dose range in which significant increases can be observed is 0.3 to 5 Gy X-rays. The assay becomes more sensitive when the micronuclei are determined only in B-lymphocytes. Another possibility exists by determination of the number of micronuclei with centromeres. For this purpose the hybridization with pancentromeric DNA probes and fluorescence labelling is of advantage. By this technique a radiation dose of 0.1 Gy X-rays can be detected. It is apparently also possible under these conditions to detect radiation exposures which have taken place decades before the measurements.

Cell Division↗
PubMed1998

Possible relationship between heat shock protein 70, cardiac hemodynamics, and survival in the early period after heart transplantation.

BACKGROUND: Heat shock proteins (HSPs) are produced by cells in response to a wide variety of stresses. To determine a possible relationship between hemodynamic parameters and HSP 70 in the early postoperative period after heart transplantation, we examined immunohistochemically the inducible HSP 70 (anti-HSP 72) response in human heart biopsies, as well as the effect of myocardial rejection on HSP. METHODS: A total of 105 routinely processed endomyocardial biopsies from 15 consecutive patients who underwent heart transplantation were examined. Analysis of hemodynamic and echocardiographic parameters were performed within 30 min and 12 hr after the biopsies. RESULTS: Immunohistochemically detected inducible HSP 70 was mainly located in the cytoplasm and nucleus/nucleolus of cardiomyocytes. Two specimens additionally showed HSP 70-positive interstitial cells and smooth muscle cells of arteries, whereas lymphocytes were consistently negative. There was a significant relation between the echocardiographically determined increased relaxation time and positive HSP 70 staining (P < 0.011). Patients with elevated right atrial pressure (P < 0.098), as well as those with increased left ventricular end systolic diameter (P < 0.06), showed a trend to higher HSP expression. Three patients who died of sepsis or multiorgan failure showed significantly higher cytoplasmic HSP 70 expression compared with 12 patients with stable clinical course. In case of rejection, significantly more patients showed no HSP expression. CONCLUSION: Although only five patients showed organ rejection, our results suggest an inverse relationship between HSP expression and rejection with the possibility of a role for HSP 70 as a graft marker to assess graft function.

Biopsy↗
PubMed1998

Chromosomal aberrations associated with invasion in papillary superficial bladder cancer.

Non-invasive and invasive papillary transitional cell carcinomas of stages pTa and pT1 represent the first steps of tumour progression in bladder cancer. In order to analyse different chromosomal alterations of pTa and pT1 superficial bladder cancer, 46 tumour specimens were examined by comparative genomic hybridization (CGH). Losses of chromosome 9 material (11/20) and gains of chromosome 17 material (6/20) were frequently found in pTa tumours. Stage pT1 tumours were characterized by gains of chromosome 1q (14/26; including amplification at 1q21-q24 in three cases) and chromosome 17 material (15/26), as well as by losses of 11p (15/26) and 11q (13/26). Other loci frequently showing losses in pT1 tumours were 2q (9/26), 4q (10/26), 5q (9/26), 8p (10/26), 9p (9/26), 9q (12/26), 10q (8/26), 17p (7/26), and 18q (8/26). Amplifications were detected at 8q21/22, 5q21, 7q36, 10p14, 10p12, 10q25, 12q12, and 12q14. The most striking differences between grade 2 pTa and pT1 tumours were gains of 1q (P < 0.01) and losses at 2q (P < 0.025), 10q (P < 0.05), 11p (P < 0.01), 11q (P < 0.01), and 17p (P < 0.05), as well as the total number of aberrations (pTa grade 2: 4.1; pT1 grade 2: 8.6 aberrations per tumour). These data show characteristic chromosomal aberrations associated with invasion in superficial bladder cancer.

Carcinoma, Transitional Cell↗