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Introduction and Objective: Little progress in the management of non-muscle invasive bladder cancer (NMIBC) has been made. We explored the combination of intravesical BCG plus Doc in an orthotopic model. Methods: An orthotopic murine bladder cancer model was used. To assess the antitumoral effect of Doc, intravesical Doc therapy was administered at various dose-escalating concentrations: 0 μg (control: PBS), 25 μg, 50 μg and 100 μg (n = 12 for each group; total of 4 groups). Next, a comparative evaluation of tumor growth among the control group, the BCG-alone group, the Doc-alone group, and three combined BCG + Doc groups (a coincident group [CO] and two sequential groups) was performed (n = 12 for each group; total of 6 groups). The sequential combined groups consisted of SA group (SA; Doc administration followed by BCG administration on the next day) and an SB group (SB; BCG administration followed by Doc administration on the next day). Intravesical therapy was administered at 3-day intervals starting on day 5 and was repeated 5 times. To evaluate proliferation, T cell infiltration and apoptosis among the different groups, the tumor cells in the animal model were stained for Ki-67, CD8 and Cleaved caspase 3 after 4 instillations performed every 3 days. Results: In the Doc groups (12 mice each) treated with a dose of 0 μg (survival period: 32.3 ± 9.4 days), 25 μg (36.8 ± 11.4), 50 μg (38.1 ± 11.0) or 100 μg (40.0 ± 12.7), one, two, two and three mice failed to develop tumors and survived, respectively. The survival advantage for intravesical Doc in the 100 μg administration group was statistically significant when compared with that in the control group (p = 0.04). Out of the 12 mice in each group treated with control, Doc-alone, BCG-alone or combined Doc + BCG (CO, SA, SB), 1, 2, 1, 4, 4 and 1 mice failed to develop tumors and survived, respectively. Significant survival advantages were observed in the combined BCG + Doc group (CO: 50.7 ± 9.0, SA: 51.5 ± 6.9) compared with that in the BCG-alone group (33.1 ± 10.4) and the Doc-alone group (38.8 ± 11.5). The Ki-67 index of the cancer cells was significantly lower in the combined group, compared with that in the BCG-alone group (p < 0.0001), the Doc-alone group (p < 0.05) and the control group (p < 0.0001). BCG-alone significantly increased the number of CD8+ T cells (p < 0.05), while Doc-alone reduced the number of CD8+ T cells (p < 0.05), compared with that in the control. Apoptosis was significantly increased when Doc was administrated to the animals irrespective of the presence (p < 0.05) or absence (p < 0.05) of BCG instillation. Conclusions: Our results suggested that the combination of BCG and Doc treatment decreased the tumor appearance rate and improved the survival period. The enhancement in tumor growth inhibition enabled by combination regimens was presumably associated with a reduction in the tumor proliferation rate and might not depend on either CD8+ T cells or apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2697. doi:10.1158/1538-7445.AM2011-2697

Objectives To evaluate the antitumor effect of the coincident administration of intravesical gemcitabine (Gem) plus bacillus Calmette-Guerin (BCG) in an orthotopic bladder cancer model. Methods We evaluated the cytotoxic effect of gemcitabine against MBT-2 cells in vitro. Orthotopic tumors were established by implanting MBT-2 cells into the bladder of syngeneic female C3H mice. Intravesical Gem administration was evaluated at various doses: 0 mg (control); 1, 2, 4, and 8 mg (n = 8 for each group). Next, a comparative evaluation of tumor growth among the control, Gem-alone, BCG-alone, and combined Gem + BCG groups was performed (n = 16 for each group). Therapy was administered at 3-day intervals starting on day 5 and repeated 6 times. To evaluate the proliferative activity among the groups, Ki-67 immunostaining of the tumor was performed. Results Gemcitabine exhibited a dose-dependent antitumor effect. Of the 8 mice in each group treated with a dose of 0, 1, 2, 4, or 8 mg of Gem, 1, 4, 4, 4, 5, and 4 mice failed to develop tumors and survived, respectively. The combination of Gem + BCG (54.1 ± 9.4 days) provided a significant survival advantage compared with BCG-alone (39.0 ± 16.4 days) ( P = .02). Ki-67 expression, representing tumor proliferation, was significantly lower in the combined Gem + BCG group than in the BCG-alone group ( P Conclusions Our results suggest that intravesical Gem + BCG treatment induces an enhanced antitumor effect against bladder tumors.

Introduction and Objective: Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) is currently the most successful adjuvant agent for the treatment and/or prophylaxis of superficial bladder tumors. However, superficial bladder tumors recur in 60 to 70% of all cases, and 30 % of these recurrent tumors present with a higher grade with invasive properties. We evaluated the combination of intravesical MMC plus BCG treatment against bladder tumors in a model of orthotopic murine bladder cancer. Methods: An orthotopic murine bladder cancer model was established using the simple instillation of 1 × 106 MBT-2 cells into the lumen of the bladder of a female C3H/HeN mouse through a urethral catheter. To assess the antitumoral effect of MMC, intravesical MMC therapy was administered at various dose-escalating concentrations: 0μg (control: PBS), 25μg, 50μg, 100μg, and 200μg, (n = 8 for each group; a total of 5 groups). Next, a comparative evaluation of tumor growth in a control group(PBS), a MCC-alone group, a BCG-alone group(100μg), and a combined MMC plus BCG (100μg) group were performed (n= 8 for each group; a total of 4 groups). Intravesical therapy was administered at 3-day intervals starting on day 5 and repeated 5 times. On day 60 after the initial implantation of the MBT-2 cells, all the surviving mice were sacrificed and necropsied. To evaluate macrophage infiltration in the tumor and the proliferative activity among the different groups, immunohistochemical staining analysis of the tumor cells utilizing CD68 and Ki-67 was performed in animal model. Results: In the MMC groups of 8 mice each treated with a dose of 0μg (survival; 26.4 ± 3.2 days), 25μg (34.8 ± 7.0 days) and 50μg (40.0 ± 13.2 days), 0, 0 and 2 of the mice failed to develop tumor and survived, respectively. In both the 100μg (17.3 ± 2.8 days) and 200μg (11.9 ± 3.0 days) groups, all eight mice died from adverse events. A significant survival advantage was observed in the combined MMC (50μg) plus BCG (100μg) group (51.5 ± 8.1 days), compared with that in the BCG-alone group (33.4 ± 16.8 days; p = 0.03) and the MMC-alone group (39.5 ± 13.5 days; p = 0.04). BCG significantly suppressed while MMC increased macrophage infiltration in the tumors, compared with in the control groups. The Ki-67 expression level, which is regarded as a proliferation index was significantly lower in the combined MMC (50μg) plus BCG (100μg) group (31.1 ± 5.2%) than in the BCG-alone group (50.9 ± 4.1%; p Conclusion: Combining BCG plus MMC treatment decreased the tumor appearance rate, improved the survival period and reduced the proliferation rate in tumors, as compared with BCG-alone and MMC-alone treatment, possibly providing a greater therapeutic benefit over either agent alone. Immunochemotherapy with a combination of intravesical MMC plus BCG may be a promising alternative treatment for bladder tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1903.

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 56-year-old woman underwent laparoscopic right nephrectomy due to pyonephrosis associated with right ureteral stones. Moreover, the patient developed a brain stem hemorrhage and became bedridden. At the time of nephrectomy, a renal tumor, with a size of 24 × 24 × 20 mm, was observed in the left renal hilum; the tumor did not show contrast enhancement on computed tomography. After 3 years, the tumor gradually grew to a size of 45 × 35 × 34 mm, and therefore, laparoscopic non-clamping tumor enucleation was performed. Pathological examination confirmed a diagnosis of renal schwannoma.

By September 1988, we performed 58 ureterorenoscopies (52 for primary ureteral calculi, 3 for ureteral biopsy, 2 for ureteral stricture and 1 for ureteral foreign body) using a Ureteromat (Uromat Storz, West Germany). Continuous saline irrigation with the Ureteromat has obviated mechanical dilation of the ureteral orifice in 93.1% of the cases, which made this endoscopy as easy as the conventional cystourethroscopy. In 4 cases (6.9%), however, balloon dilation of the ureteral orifice was necessary for the passage of a rigid ureterorenoscope. Of 52 ureteral calculi, 37 were assigned for transurethral ureterolithotripsy (TUL), whereas transurethral ureterorenoscopy (TUURS) was indicated to flush the remaining 15 calculi up into renal pelvis for later extracorporeal shock wave lithotripsy. TUL was successful in 81.1% (30/37). The causes of failure were stone migration in 6 cases and ureteral avulsion by electrohydraulic lithotripsy necessitating open surgery in 1 case. The irrigation with the Ureteromat facilitated the manipulation of intraluminal ureteral lesions always under clear vision; by-passing the impacted stone with a guide wire and flushing-up of the calculi were successfully performed in 100%, in spite of the co-existing edematous and inflammatory mucosal changes. In 7 cases where ureteroscope could not be advanced well up to the lesion because of spasm in the iliac ureter, the irrigation pressure was transiently increased up to 200 mmHg to allow safe and easy dislodgement of impacted calculi under fluoroscopic guidance. This procedure was also effective to introduced a ureteral stent over a guide wire in 2 cases of ureteral stricture, which could not be achieved by conventional cystoscopic procedure. Immediate postoperative complications were fever in 8.6% and gross hematuria lasting for more than 4 days in 8.6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Most bladder tumors are derived from the urothelium. Benign mesenchymal tumors are rare. Leiomyoma of the bladder is the most common benign neoplasm. We present a case of leiomyoma of the bladder presenting with acute urinary retention in a female patient and report on the post-operative change in urodynamic findings. To our knowledge, few cases of this kind have been reported. Case Presentation A 56-year-old woman presented with acute urinary retention. Evaluations including ultrasound, magnetic resonance imaging, cystoscopy, and urodynamics contributed to a diagnosis of leiomyoma of the bladder. Various medications were ineffective for solving her lower urinary tract symptoms; therefore, a transurethral resection was performed. The final pathological report was leiomyoma. After the operation, her symptoms resolved; this improvement was confirmed by an urodynamic analysis. The postoperative urodynamics demonstrated a lower frequency of detrusor overactivity during filling cystometry and an increase in the uroflow rate, with reduced detrusor pressure in a pressure flow study. Conclusions Leiomyoma of the bladder can cause female outlet obstruction. A review of the literature and disease management is discussed.