Aim:In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. Methods: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-a, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1b, IL-8, interferon (IFN)-g, and IL-12. Results: After the BCG therapy, various cytokines, such as GM-CSF, TNF-a, G-CSF, IL-1b, IL-8, IFN-g, and IL-12 were secreted , comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-a 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-g or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-a level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. Conclusions: We suggested that the urinary levels of TNF-a might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence.

Objectives: To identify the prognostic factors and determine which pT3 prostate cancer patients can be safely followed up after surgery without any adjuvant treatment. Methods: A retrospective review was carried out on 106 patients with pT3 prostate cancer. All preoperative and postoperative parameters, including the postoperative serum prostate-specific antigen (PSA) level at 3 months after surgery, were assessed by univariate and multivariate analyses. Results: Mean follow-up period was 18 months. The overall biochemical recurrence-free rate was 53.7% and 34.1% at 12 and 36 months, respectively. On univariate analysis, all preoperative clinical factors were significantly correlated with biochemical progression. On multivariate analysis, pathological Gleason score, pathological stage and postoperative PSA were significant predictors. Among those with undetectable PSA after surgery, 38 patients (88.4% of 43) did not have disease progression during the follow-up period. On the other hand , of the 27 patients with detectable PSA that was not defined as progressive (range 0.01-0.20), 22 (81.5%) had biochemical disease progression. The progression free probability was significantly different between these two groups (P-value < 0.0001). Conclusions: pT3 prostate cancer patients showing low pathological Gleason score, without seminal vesicle invasion, and undetectable postoperative PSA values have low probability of PSA progression. Careful follow up including periodic PSA assessment and clinical observation represents an adequate strategy in the management of these patients.

Background: This study aimed to immunohistochemically examine the expression of proliferating cell nuclear antigens (PCNA) and p53 protein in transitional cell carcinomas (TCC) of the urinary bladder, and to investigate possible correlations of this expression with the tumor grade or stage, tumor recurrence, and prognosis of the disease. Materials and Methods:The immunohistochemical status of the PCNA and p53 proteins were determined on paraffin-embedded sections from 128 patients with TCC of the urinary bladder, using PC-10 and D O 7 as the primary antibodies. Positive staining were represented by scores (Labeling Index; LI, %) calculated as the percent of positive cells among all neoplastic cells counted. The findings were compared to the patients' histopathological features. Patients who underwent transurethral resection were divided into groups with "low" and "high" scores for PCNA and p53, respectively, and the tumor recurrence rate was compared among the groups. Patients who underwent total cystectomy were similarly divided into "low" and "high" score groups, and survival rates of the groups were compared. Results: PCNA expression was observed in 66 of 128 patients (51.6%), with a mean labeling index of 26.6%. Overexpression of p53 was observed in 65 of 128 patients (50.8%), with a mean labeling index of 35.3%. There were significant correlations of the PCNA and p53 indices with both histological grade and stage of the tumor. In the TUR group, there were no statistically significant differences in recurrence rate between the groups with high or low scores for either PCNA or p53. In the total cystectomy group, there was a significant correlation between survival rate and positive staining for PCNA, but not for p53. The relationship between 2 parameters, PCNA and p53 scores, was not significant (linear correlation coefficient, r = 0.67). Conclusions: PCNA and p53 status in transitional cell carcinomas of the urinary bladder is related to the histopathological findings. We also suggest that immunohistochemical staining for PCNA provides significant clinical information which may be useful in the initial selection of therapy. However, overexpression of p53 does not appear to represent an independent prognostic marker in bladder tumors.

We treated 519 patients with primary bladder cancer, of whom 12 had upper urothelial tumor during followup. Almost all patients had superficial bladder cancer at diagnosis. All but 1 of 12 patients who underwent total cystectomy with ileal conduit diversion also underwent various transurethral procedures for treatment of the primary bladder lesions. The over-all incidence of bladder cancer patients who subsequently had upper urinary tract tumors was 2.3 per cent. Among the patients with treated bladder tumors a higher incidence (13.2 per cent) was observed in dye workers than in the general population (1.1 per cent). The interval between initial treatment of the bladder cancer and diagnosis of the upper urinary tract tumor ranged from 7 to 170 months (mean 70 months). The frequency of upper urinary tract tumors increased with time. We conclude that the appearance of upper urinary tract tumor after diagnosis of primary bladder cancer may be promoted by nonspecific irritation of the urothelium, which previously was made unstable by urinary chemical carcinogens.

Intravesical instillations of Tokyo 172 strain BCG were given to 56 patients with superficial bladder cancer during the 24-month period after transurethral tumour resection as a prophylaxis against tumour recurrence. The recurrence rate of tumours was compared with that of historical controls. Results were estimated by the person-years method and there were statistically significant decreases in recurrent tumours following BCG therapy. Our results suggest that the intravesical Tokyo 172 strain BCG is effective and safe as a prophylaxis against the recurrence of superficial bladder tumours.