Seido Jitsukawa

Efficacy of gadolinium-diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging for differentiation between superficial and muscle-invasive tumor of the bladder: A comparative study with computerized tomography and transurethral ultrasonography

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.

Multivariate Analysis of Flow Cytometric Deoxyribonucleic Acid Parameters and Histological Features for Prognosis of Bladder Cancer Patients

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 Coxs 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.

Antiandrogenic effects of spironolactone: hormonal and ultrastructural studies in dogs and men.

A decrease in the level of plasma testosterone and an increase in the level of plasma progesterone were noted after spironolactone had been administered for 20 days in 5 patients with prostatic carcinoma, as well as in 8 male dogs. Electron microscopic observation disclosed myelin-like bodies in the cytoplasm of Leydig and adrenocortical cells in dogs, contributing to a resolution of the mode of antiandrogenic action of spironolactone.

THE VALUE OF SERUM CARBOXYTERMINAL PROPEPTIDE OF TYPE 1 PROCOLLAGEN IN PREDICTING BONE METASTASES IN PROSTATE CANCER

PURPOSE Carboxyterminal propeptide of type 1 procollagen (P1CP) is believed to be a marker of new bone formation. We investigated the possible application of serum P1CP as a biochemical marker for bone metastases in patients with prostate cancer. MATERIALS AND METHODS Prostate specific antigen (PSA), prostatic acid phosphatase (PAP), P1CP and alkaline phosphatase were measured in 136 serum samples from 79 patients with untreated prostate cancer, 29 with stage D2 disease in remission and 28 with progressive stage D2 carcinoma. RESULTS Serum P1CP and alkaline phosphatase were significantly elevated in untreated patients with a positive bone scan (278.9 +/- 61.9 ng./ml. and 826.5 +/- 176.3 international units per 1., respectively) compared to those with a negative bone scan (104.2 +/- 4.2 and 200.8 +/- 9.1, respectively, p <0.05). The areas under receiver operating characteristics curves were 0.86 for P1CP, 0.87 for alkaline phosphatase, 0.88 for PSA and 0.85 for PAP. The best accuracy rates for P1CP, alkaline phosphatase, PSA and PAP to predict bone lesions were 84, 87, 86 and 84%, respectively. P1CP provided a greater specificity and positive predictive value. These serum markers correlated significantly with the extent of disease on bone scan (p <0.05). The incidence of positive serum P1CP and alkaline phosphatase decreased significantly in response to endocrine therapy in patients with bone metastasis, and increased progressively in association with progression of the tumor (p <0.05) parallel to PSA and PAP. CONCLUSIONS These findings suggest that serum P1CP is a useful indicator for predicting bone metastases.

Prognostic Significance of Bromodeoxyuridine High Labeled Bladder Cancer Measured by Flow Cytometry: Does Flow Cytometric Determination Predict the Prognosis of Patients with Transitional Cell Carcinoma of the Bladder

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 Coxs 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.

One-stage total cystectomy and ileal loop diversion in patients over eighty years' old with bladder carcinoma: Pre- and postoperative functional reserve of various organs

During the period from 1976 to 1981, 364 patients with bladder carcinoma were seen at the Keio University Hospital. Extensive preoperative investigation of pulmonary, cardiovascular, and renal function was obtained in all patients. Of the 12 patients studied, 9 underwent a one-stage total cystectomy and ileal loop diversion and the remaining 3 a two-stage procedure. Of the 9 patients, decreased FEV 1.0 per cent by spirometry was noted in 5, ECG abnormality such as bundle branch blocks in 8, and diminished creatinine clearance ranging from 28 to 68 ml/min were observed in all 9. Major postoperative complications included pyelonephritis in 2 patients, pneumonia in 1, pelvic abscess in 2, renal insufficiency in 3, and paralytic ileus in 2. There was no immediate postoperative death. In these elderly patients, functional reserve of the lung, heart, and kidney is less than optimal and is further decreased by major surgical procedures. Therefore, total cystectomy in the elderly patients is justifiable only in a selected group of patients, when functional status of the vital organ is thoroughly worked up and prophylactic and therapeutic measures are instituted promptly if indicated.

Disappearance of metastatic renal cell carcinoma to the base of the tongue after systemic administration of interferon-alpha

We describe a 41-year-old Japanese man with metastases of the lung, bone, lymph nodes and the base of the tongue 34 months after right radical nephrectomy. One month after systemic administration of human lymphoblastoid interferon (IFN), the metastasis to the base of the tongue completely disappeared, while other metastases increased both in size and number. Though the true effect of IFN-alpha on the metastatic renal cell carcinoma to the base of the tongue is still unknown, our case indicates that the tongue is a possible sensitive site to IFN-alpha therapy.

Quantification of cell kinetic characteristics using flow cytometric measurements of deoxyribonucleic acid and bromodeoxyuridine for bladder cancer

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.

Multimodal treatment of advanced adult Wilms tumor.

We report 2 cases of advanced adult Wilms tumor that were treated with surgery, radiation and chemotherapy. The first patient had relapse of a Wilms tumor in the liver 2 years after nephrectomy. Combination chemotherapy, consisting of actinomycin D and vincristine, radiation therapy and final resection of the liver metastasis were successful and the patient has been free of disease for 4 years. The second patient had undergone transcatheter embolization of the renal artery elsewhere with the tentative diagnosis of an inoperable renal cell carcinoma metastatic to both lungs. A left renal tumor, weighing 4,500 gm., and a tumor thrombus in the vena cava extending to the right atrium were removed, and histologically diagnosed as a Wilms tumor. Subsequent chemotherapy and radiotherapy resulted in complete disappearance of the lung metastases. We conclude that multimodal treatment, namely a well timed combination of surgery, chemotherapy and radiotherapy, could potentially eradicate the disease even at an advanced stage.

SCID Mice: A Suitable Model for Experimental Studies of Urologic Malignancies

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.