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Objective To clarify the oncological benefit of zoledronic acid for hormone-naive metastatic prostate cancer, patient outcome of androgen deprivation therapy with zoledronic acid (ADT + Z) and androgen deprivation therapy alone (ADT) was compared. Methods Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade (goserelin and bicalutamide) with zoledronic acid (4 mg every 4 weeks for 24 months). A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts (both from ADT + Z and from historical control cohorts who had undergone ADT alone), and patient outcomes were compared. Results Patients with ADT + Z had significantly longer time to progression (TTP) than those with ADT (median TTP; 24.2 vs. 14.0 months, p = 0.0092), while no significant difference of overall survival between two groups ( p = 0.1502). Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor (HR: 1.724, 95% CI: 1.06–2.86, p = 0.0297). Conclusion Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer.

To determine the impact of patient age on outcome following bladder-preserving treatment for non-muscle-invasive bladder cancer (NMIBC).This study examined 491 patients treated with transurethral resection and/or intravesical bacillus Calmette-Guerin (BCG) therapy for primary NMIBC at our institution between 1985 and 2005. The patients' age at treatment was classified into categories of younger than 50, 50-59, 60-69, 70-79, and 80 years or older. Recurrence-free survival and progression-free survival were estimated by the Kaplan-Meier method and analyzed using Cox proportional hazard models.Tumors of broad-based, multiple, and higher grades were more frequent with increasing patient age. Intravesical BCG therapy was less frequently performed on elderly patients. At a median follow-up of 45 months, patients 80 years or older had the lowest recurrence-free survival and progression-free survival among the age groups (log-rank P0.001 and P = 0.019, respectively). On Cox proportional hazard model, age was an independent risk factor for tumor recurrence and progression after controlling for all confounding variables. The recurrence risk was 2.3 times higher for patients 80 years or older than those aged 60-69 years (P0.001).Older age adversely affected the outcome of patients with NMIBC, which is particularly apparent in patients 80 years or older. Further prospective studies to confirm these findings are warranted.

AIM In order to clarify the initial step of the mechanism by which bacillus Calmette-Guerin (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)-alpha, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and IL-12. RESULTS After the BCG therapy, various cytokines, such as GM-CSF, TNF-alpha, G-CSF, IL-1beta, IL-8, IFN-gamma, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-alpha 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-gamma or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-alpha 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-alpha might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence.

OBJECTIVES We investigated whether preoperative parameters predict pathological stage at radical prostatectomy for patients with clinically localized prostatic cancer. MATERIALS AND METHODS We studied a total of 160 men with clinically localized prostatic cancer (less than or equal to clinical T2) who underwent radical rertropubic prostatectomy at Wakayama Medical University. Clinical Ts patients are not included in this study. Preoperative parameters include patient age, Body Mass Index, preoperative serum PSA value, biopsy Gleason score, clinical stage, the percent of positive biopsy cores (%PosBx) and the percent of positive biopsy cores on the dominant side (%DomPosBx). Univariate and multivariate analysis were performed to examine the prognostic significance of these preoperative parameters. Significant independent factors were combined to create a table to predict pathologically organ confined disease. RESULTS Univariate analysis showed preoperative serum PSA value (p< 0.001), biopsy Gleason score (p =0.001), clinical stage (p = 0.026), %PosBx (p= 0.002) and %DomPosBx (p=0.003) were significantly related to the pathological stage. On multivariate analysis, serum PSA value (p< 0.01), biopsy Gleason score (p

This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-naïve bone-metastatic prostate cancer.Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks.A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5-49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71-15.62; P0.001). Median time to biochemical progression for patients with serum bone-specific alkaline phosphatase level higher than 26 μg/L was 12.7 months. Multivariate analysis indicated that higher serum C-terminal telopeptide of type I collagen independently increased the risk of death (hazard ratio 9.62; 95 % confidence interval 2.11-43.89; P = 0.003). Median overall survival for patients with serum C-terminal telopeptide of type I collagen level higher than 8.0 ng/ml was 31.1 months.Baseline bone markers can be useful as predictors for disease progression and survival time in patients with bone metastasis from treatment-naïve prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.

The efficacy of zoledronic acid in patients with treatment-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefits of combined zoledronic acid and androgen deprivation therapy in treatment-naïve prostate cancer with bone metastasis. The primary endpoint was skeletal-related event-free survival at 24 months.Subjects were treatment-naïve patients with histologically confirmed adenocarcinoma of the prostate and radiological evidence of bone metastasis. Treatment consisted of bicalutamide 80 mg daily, goserelin acetate 10.8 mg every 12 weeks, and zoledronic acid 4 mg every 4 weeks. Zoledronic acid was continued for 24 months.Of the patients enrolled between July 2008 and April 2010, 52 were included in the analyses. The median age of the patients was 72 years. The median baseline prostate-specific antigen level was 249.4 ng/mL. The median follow-up period was 33.3 months. The 24-month skeletal-related event-free survival rate was 84.4 % (95 % confidence interval 71.2-91.9). The median time to prostate-specific antigen progression was 25.9 months (95 % confidence interval 14.7-36.3). The median overall survival time was not reached. Improvement in pain or maintenance of no pain during the first 12 weeks was observed in 70 % of patients and the extent of bone disease was decreased in 10 % of patients at 12 months. Grade 3 osteonecrosis of the jaw was observed in three patients (5.8 %).Zoledronic acid concomitant with androgen deprivation therapy as initial treatment in patients with treatment-naïve prostate cancer with bone metastasis resulted in an encouraging skeletal-related event-free survival rate at 24 months.

We report a case of leiomyoma of the seminal vesicle in a 74-year-old man who presented with left hemilumbago. Computed tomography and magnetic resonance imaging revealed a mass containing coarse calcification and low signal intensity areas on T1- and T2-weighted images. The clinical features of previously reported cases of leiomyoma of the seminal vesicle are presented, including those of the present case. There remains a lack of consensus regarding surgical resection of leiomyoma of the seminal vesicle.

Intravesical instillation of Tokyo 172 strain bacillus Calmette-Guerin (BCG) was performed on 137 patients with superficial bladder cancer (Ta and T1) after transurethral tumor resection as a prophylaxis against tumor recurrence. The recurrence rate of tumors was compared with that of historical controls and was estimated by the person-years method. There were statistically significant decreases in recurrent tumors following BCG therapy. To clarify the efficacy of intravesical BCG therapy, prognostic significance of several factors were evaluated in 90 patients with initial bladder cancer treated with TUR and BCG instillation, and compared to those of controls. Prophylactic effects were statistically better for those with multiple tumors, grade 3 lesions or Ta lesions than for control patients. No correlation between purified protein derivative responsiveness and favorable results could detected. There were no marked side effects or fatal complications of BCG therapy during the observation periods. Our results suggest that BCG is able to change the biological behavior of superficial bladder cancers with multiple, high grade or low stage lesions. The intravesical BCG instillation seems to be effective and safe as a prophylaxis against the recurrence of superficial bladder tumors.

Urachal carcinoma is a rare cancer. This is the first report of a case of squamous cell carcinoma of the urachus producing granulocyte colony-stimulating factor. The patient underwent partial cystectomy with urachal remnant resection and pelvic lymphadenectomy. No evidence of tumor recurrence or metastasis was found at 17 months after surgery.

Thirty-seven patients who had undergone radical cystectomy and pelvic node dissection for pathologic stage pT2-4 and/or N+ disease received adjuvant chemotherapy involving the injection of cis-platinum alone or in its combination from June 1982 to April 1989. Adjuvant chemotherapy was performed using the following three protocols. Protocol 1 entails the administration of cis-platinum alone. Protocol 2, involving the administration of a combination of cis-platinum, adriamycin and 5-fluorouracil (CAF), was used for deeply invasive bladder cancer. Protocol 3, consisting of cis-platinum, vp-16 and adriamycin (CVA), was employed in patients with deeply invasive bladder cancer instead of protocol 2 from July 1987. Of the 37 patients, 27 were alive with no evidence of disease for an average of 42 months. One patient died as a result of factors unrelated to cancer. Local recurrence and/or distant metastases occurred in 9 patients and all died of cancer progression. The survival rate for all 37 patients at 87 months was 64.4%. The rates were 75% in pT2, 80% in pT3a, 50.8% in pT3b, and 44.4% in pT4. Although adjuvant chemotherapy combined with radical cystectomy seemed to be effective in cases with pathological stage pT3a or less, more intensive chemotherapy is needed in an attempt to improve poor prognosis in cases with pathological stages pT3b-4 or node involvement.

Summary— Intravesical instillation of Tokyo 172 strain Bacillus Calmette-Guerin (BCG) was performed in 96 patients with initial superficial bladder cancer (Ta andT1) after transurethral resection (TUR) of tumour as a prophylaxis against tumour recurrence. The recurrence rate of tumours was estimated by the person-years method, comparing it with that of historical controls. There were statistically significant decreases in recurrent tumours following BCG therapy. To clarify the efficacy of intravesical BCG therapy, the prognostic significance of several factors was evaluated in patients with bladder cancer treated with TUR and instillation of BCG. The prophylactic effects were statistically better for those with multiple tumours, grade 3 lesions or Ta lesions than for control patients. No correlation between purified protein derivative (PPD) responsiveness and favourable results could be observed. Our results suggest that intravesical BCG instillation can alter the biological behaviour that affects the recurrence of superficial bladder cancer, especially for multiple, high grade or Ta tumours.

Partial urethrectomy (at least to the bulbous portion) was performed simultaneously in 128 consecutive male patients undergoing radical cystectomy for bladder cancer. Transitional cell carcinoma developed subsequently in the distal urethral remnant in 5 patients (4.0%) followed for 2.6 to 5.7 years (mean 4.1 years) postoperatively. These 5 patients originally had nonpapillary, multifocal and histologically high grade (5) and low stage (4) bladder cancer, 4 with associated carcinoma in situ. Our results suggest that simultaneous total urethrectomy should be considered strongly for patients with high grade nonpapillary multifocal bladder cancer associated with carcinoma in situ. Furthermore, the pattern of distal urethral recurrence in our patients may provide information regarding the appropriate management of the male urethra in potential candidates for continent urinary diversion. (J. Urol., 142: 983–987, 1989)

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.

Uterus didelphys with unilateral imperforate vagina is rare. Interestingly, in all reported cases in which the urinary tract was investigated renal agenesis was found on the side of the obstructed hemivagina. We report 2 cases of this unusual and interesting condition, and review the embryogenesis of mullerian duct abnormalities associated with renal agenesis, as well as the clinical findings, diagnosis and management. We stress the importance of prompt and accurate diagnosis, and treatment as a means to avoid unnecessary surgical procedures.

A case of urethral clear cell adenocarcinoma (mesonephric carcinoma) in a 62-year-old woman is reported. The patient consulted our hospital because of acute urinary retention. Fine needle aspiration cytology showed a few atypical cells; loose cluster cells with finely vacuolated cytoplasm, large nuclei and prominent nucleoli, and small cluster cells with finely vacuolated, delicate cytoplasm, small pale nuclei and small nucleoli. Cytologic diagnosis was adenocarcinoma and no diagnosis of clear cell adenocarcinoma was obtained. The neoplasia was localized at the posterior wall of the urethra and deep muscular layer of the vaginal wall. Histologically, the tumor revealed mainly small, elongated glands consisting of single-layered cuboidal or columnar cells with scanty cytoplasm and a focally hobnail appearance. In addition, a small cystic lesion resembling nephrogenic adenoma was observed. This finding raises the possibitily that clear cell adenocarcinoma may be a malignant counterpart of nephrogenic adenoma. ACTA PATHOL JPN 38: 217–223, 1988.

Summary— 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.

From June 1982 through December 1985, 25 patients who had undergone radical cystectomy with pelvic node dissection for pathologic stage-pT3 or -pT4 and/or N+ disease received adjuvant chemotherapy involving the injection of cis-platinum alone or in combination with adriamycin and 5-fluorouracil (CAF). Thirteen patients also received preoperative adjuvant chemotherapy involving the infusion of cis-platinum, adriamycin, and mitomycin C into the bilateral internal iliac arteries. Postoperative adjuvant chemotherapy was performed using the following two protocols. Protocol 1 (18 cases) consisted of cis-platinum alone being administered every week for 3 weeks and then every month for 1 year. In protocol 2 (7 cases), cisplatinum, adriamycin, and 5-fluorouracil were administered at 3-week intervals on three occasions and then every month for 1 year. Eighteen patients were still alive with no evidence of disease after an average of 26 months. One patient died as a result of factors unrelated to cancer. Local recurrence and distant metastasis occurred in 6 patients, of whom 3 were still alive for an average of 20.7 months. Three patients died of cancer progression after 9, 19, and 21 months. The survival rate for all 25 patients at 50 months was 77%. Nausea and vomiting occurred in most patients during the administration of cis-platinum. Mild myelosuppression developed in a few patients subjected to protocol 2. Our results indicate that adjuvant chemotherapy consisting of the administration of cis-platinum alone or in combination with other chemotherapeutic agents appears to be effective in patients with invasive bladder cancer.