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We studied whether flow cytometric determination of proliferative cell activity estimated by the bromodeoxyuridine in vitro labeling technique provides significant prognosticators beyond the classical histological evaluation in the patient with bladder cancer. We evaluated 81 patients with transitional cell carcinoma of the bladder using fresh bladder specimens. Clinical followup of at least more than 24 months was requested, with the mean followup being 37.9 +/- 10.5 months. Tumor grade and stage were the histological prognostic parameters. Flow cytometric bivariate measurements of deoxyribonucleic acid (DNA) ploidy and bromodeoxyuridine labeled cell index were evaluated. Tumors with a bromodeoxyuridine labeled cell index of more than 10.7%, which was the value of the mean plus 2 times the standard deviation obtained in grade 1 bladder tumors, were designated as high bromodeoxyuridine labeled cell index tumors. A total of 51 patients with low bromodeoxyuridine labeled cell index tumors demonstrated a 98.0% 3-year actuarial survival rate estimated by the Kaplan-Meier method, compared to 42.9% for those with high index tumors. Multivariate survival analysis was performed with Cox's proportional regression model to study statistical individual prognostic values of histological and flow cytometric parameters. Histological tumor grade was the single most important prognostic factor (risk ratio 13.2, p < 0.05), with tumor stage being the second most important (risk ratio 9.2, p < 0.05), followed by bromodeoxyuridine labeled cell index status (risk ratio 6.9, p < 0.05). DNA ploidy status did not influence the clinical outcome. When grade 3 tumors were classified as low and/or high bromodeoxyuridine labeled cell index tumors, 3-year actuarial survival rates were 85.7% and 27.3%, respectively. These results indicate that DNA/bromodeoxyuridine bivariate analysis can be used as an effective adjunct to histological examination for prognostication and decision-making in treatment of bladder cancer patients.

An evaluation was made of the long-term results and risk factors of tumor recurrence in patients with superficial bladder cancer who were treated with intravesical bacillus Calmette-Guerin (BCG) and who had a mean follow-up period of 57 months. Eligible for the study were a total of 102 patients who were treated by transurethral resection of tumors and were considered to be free from tumor from 1984 to 1989. A suspension containing 80 mg Tokyo 172 strain BCG in 50 ml normal saline was given intravesically to 50 patients once a week for six weeks without further maintenance instillation. To the other 52 patients was additionally given monthly intravesical BCG instillation for 12 months. The actuarial nonrecurrent rates according to sex, different BCG treatment protocol, tumor grade, tumor status including primary or recurrent tumors, and solitary or multiple tumors were estimated by Kaplan-Meier method. The estimated three-, five- and seven-year actuarial nonrecurrent rates in all 102 cases were 77.3%, 68.5% and 60.6%, respectively. When nonrecurrent rates were compared to tumor characteristics, no statistically significant differences were observed between primary and recurrent tumors or between solitary and multiple tumors estimated by generalized Wilcoxon method. On the other hand, when nonrecurrent rates were compared with tumor grades, grade 3 tumor showed a 40.0% three-year nonrecurrent rate. The differences between grade 3 and grade 1 and between grade 3 and grade 2 were statistically significant (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

We studied whether flow cytometry provides significant prognosticators beyond the classical histological evaluation in the patient with bladder cancer. A total of 203 patients with untreated bladder cancer was evaluated using fresh bladder tumor specimens. Tumor grading and stage were the histological prognostic parameters. Deoxyribonucleic acid (DNA) index, percentage S-phase cells, percentage G2/M-phase cells and hypertetraploid cell presence were assessed as flow cytometric prognostic parameters. Multivariate survival analysis was performed using Cox's proportional regression model to study statistical individual prognostic values of histological and flow cytometric parameters. Hypertetraploid cell presence was the single most important prognostic factor (p less than 0.01), with tumor grade being nearly as important (p less than 0.01), followed by tetraploidy (p less than 0.01) and tumor stage (p less than 0.05). No other parameters, including the DNA index or cell phase fractions, contributed to the model. These results indicated that combined use of histological and flow cytometric parameters may provide additional information regarding the clinical outcome for bladder cancer patients.

In vivo studies on human malignant tumors are limited because of a lack of suitable animal models. In this study, the usefulness of SCID (severe combined immunodeficiency) mice, deficient in functions of both T- and B-lymphocytes, was evaluated. Inbred SCID mice were kept in isolated cages and 2 x 10(7) cells of KU-7, an established bladder carcinoma cell line, were inoculated in the subcutaneous tissue of the flank region of six SCID mice. Athymic nude mice were inoculated by the same method and served as the controls. The KU-7 cells were taken within 14 days in the injected region in all six SCID mice, while in only five out of eight nude mice. Tumors subsequently formed at the site of inoculation in these mice were confirmed to be transitional cell carcinomas histologically and intra-abdominal metastases were noted in two SCID mice. We conclude that SCID mice provide an ideal in vivo model for experimental studies of human urologic malignant tumors.

Gadolinium-labeled diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) was evaluated in an effort to clarify whether MRI could replace or be proved to be superior to computerized tomography (CT) and/or transurethral ultrasonography. A total of 57 bladder cancer patients was evaluated. MRI was performed with a superconducting magnet operating at 1.5 Tesla. The images acquired were multisections, having a fast spin-echo pulse sequence of less than a 14-second breath holding. Serial scans were performed before and immediately after Gd-DTPA venous injection. The findings on different imaging techniques were compared with the histological stagings. A proper diagnosis was made in 42 of 57 cases (73.7%) by Gd-DTPA-enhanced MRI, in 27 of 57 (47.4%) by CT and in 31 of 57 (54.4%) by transurethral ultrasonography when comparing the histological findings. The sensitivity and specificity for differentiating superficial and muscle-invasive tumor of each imaging method were, respectively, 96.2 and 83.3% in Gd-DTPA-enhanced MRI, 96.0 and 58.3% in CT, and 88.0 and 66.7% in transurethral ultrasonography. These data suggest that the staging of bladder cancer by Gd-DTPA-enhanced MRI appears to be superior and more accurate than the staging obtained by CT and transurethral ultrasonography.

A total of 56 human bladder tumors that were histologically proved to be transitional cell carcinoma was analyzed by simultaneous flow cytometric 2-color measurements of deoxyribonucleic acid (DNA) and bromodeoxyuridine. Bromodeoxyuridine in vitro labeling was performed by sample incubation with bromodeoxyuridine under high atmospheric pressure oxygen. Grade 1 tumors showed 33.3% aneuploidy with a mean bromodeoxyuridine positive stained ratio (labeling index) of 5.1 +/- 3.4%. Grade 2 tumors featured 51.7% aneuploidy with a mean labeling index of 8.9 +/- 7.7%. On the other hand, a markedly increased labeling index of 15.2 +/- 8.2% with aneuploidy was observed in all but 1 grade 3 tumors. When DNA ploidy and labeling indexes were compared according to the presence or absence of muscular invasion of tumors, all 16 muscle invasive tumors showed aneuploidy (mean labeling index 18.7 +/- 8.0%), while 17 of 40 nonmuscle invasive tumors showed aneuploidy (mean labeling index 8.6 +/- 5.4%). This labeling index difference was statistically significant (p less than 0.01). These results indicate that bromodeoxyuridine/DNA 2-color flow cytometry may provide an objective parameter for quantification of the malignant potential of bladder cancers.

The relationship between histopathological characteristics and their long-term prognosis was studied on a total of 110 patients with bladder cancer who underwent total cystectomy from 1978 to 1985 at Keio University Hospital in the period after computer tomography (CT) was initiated for the evaluation of tumor stagings. The actuarial five-year survival rate in the 110 patients estimated by Kaplan-Meier method was 54.3%. Disclosed as histological poor prognostic factors (p less than 0.05) were the presence of non-transitional cell elements (actuarial five-year survival rate: 26.3%), IFN gamma for growth patterns (26.3%), grade-3 for histological grades (39.1%), lymph-duct involvement ly(+) (28.2%), venous involvement v(+) (25.2%), muscle-invaded tumor and extravesical lymphnode involvement. As for the comparative relation among these histological factors, grade-3 tumors tended to have a high incidence of lymph-duct involvement (73.2%), venous involvement (26.8%) and positive lymph-nodes (35.7%) when compared to grade-2 tumors. The analysis of the degree of influence of those histological prognostic factors using the non-proportional hazard model revealed that the major priorities were positive lymphnodes (p = 0.0006), histological types (p = 0.0036) and lymph-duct involvement (p = 0.0839). These results suggest that intensive adjuvant treatment should be indicated for improving the prognosis of patients with bladder cancer who have undergone total cystectomy when non-transitional cell elements and/or vascular involvement are evidenced.

The incidence of transitional cell carcinoma (TCC) of the bladder has been increasing in men with a peak incidence occurring in the sixth decade. However, development of tumors under the age of 30 is relatively rare. In this regard, it has been reported that vesical tumors in the young group is less malignant and rare to recur when compared with those in the elderly group. Recently, flow cytometric DNA histograms (FCM) provides quantitative and objective informations for detection and evaluation of malignant potential of bladder neoplasms. Here we report patients with tumor of the bladder under 30 years old and assess the clinical properties and biological characteristics of their tumors based on FCM. A total of 11 patients from 1975 through 1988 were reviewed. Their mean age at the diagnosis was 22.6 years old (range from 22 to 29 years old). Male/female ratio was 2.7:1. The mean follow-up period was 4 years and 7 months (range from 8 months to over 13 years). An asymptomatic gross hematuria was found in all of the patients, which is the most common sign. Filling defects of the bladder on excretory urograms were observed in six out of the 11 patients (54.5%). Cystoscopically, the size of tumors was less than 2 cm in diameter. Ten patients had a single tumor and one patient had multiple tumors at the time of the initial diagnosis. Endoscopically tumors were papillary in all but one patient, who had a non-papillary tumor. Their urine cytology showed class I in one, class II in eight, class III in one, class IV in one and class V in none.(ABSTRACT TRUNCATED AT 250 WORDS)

A case involving transitional cell carcinoma of the renal pelvis with extension to the main renal vein and inferior vena cava as well as massive involvement of the kidney and ureter is reported. A review of the literature on renal pelvic tumors and patterns of tumor growth is presented.

Flow cytometric (FCM) examination of DNA distribution based on heterogeneity index score (HIS) and ploidy pattern and of bladder irrigation specimens were compared with conventional urine cytologic examinations to evaluate the diagnostic efficacy of each method. Of 56 patients with histologically proved bladder tumors, 24 (43%) had positive urine cytology, 41 (73%) had positive FCM, and 45 (80%) had positive urine cytology and/or positive FCM. When bladder tumors were graded histologically, 8 of 11 patients (73%) with grade I bladder carcinoma, 22 of 28 patients (79%) with grade II, and 15 of 17 patients (88%) with grade III had positive urine cytology and/or positive FCM. Of the 28 patients with grade II, 12 with positive urine cytologic results had higher mean HIS (117.5) when compared with 16 (61.1) in whom urine cytology was negative. Of those who continued to have positive FCM in the face of negative findings on cystoscopic and urine cytologic examinations during follow-up, 3 patients eventually were found to have tumors (2 distal ureter, 1 bladder). These results indicate that FCM examinations for DNA distribution of bladder irrigation specimens are as useful as conventional urine cytology in the management of bladder tumors, can be more sensitive for detection and monitoring of the disease, and can contribute further to accurate diagnosis of the disease when combined with conventional urine cytology.