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At least 595 records · Page 33Linked to original sources
PubMed2006

[5 years intravesical instillation with mitomycin-C and pirarubicin as a prophylactic treatment for superficial bladder cancer].

PURPOSE: We studied prophylactic intravesical instillation of mitomycin C (MMC) and pirarubicin (THP) following transurethral resection of bladder tumor (TUR-Bt) for superficial bladder cancer. MATERIALS AND METHODS: Forty-six evaluable patients were administered intravesically 20 mg of MMC dissolved in 20 ml saline on day 1 and 20 mg of THP dissolved 20 ml 5% dextrose on day 2. The patients were followed up by cystscopy and urinary cytology. Intravesical instillations were performed once a month and continued for 5 years. RESULTS: The non-recurrence rates at 1, 3 and 5 years were 88.8%, 79.5% and 67.0%, respectively. No significant differences were observed between grade 1-2 and 3, male and female, and solitary and multiple tumors. Although the side effects were relatively mild, 6 patients were stopped intravesical instillation. CONCLUSIONS: Because non-recurrence rates of our report is not better than previous reports with shorter treatment periods, intravesical MMC and THP instillation for 5 years is not beneficial to the patients with superficial bladder cancer.

Administration, Intravesical↗
PubMed1993

Effect of bradykinin and tachykinin receptor antagonist on xylene-induced cystitis in rats.

The effects of the bradykinin receptor selective antagonist, Hoe 140, and of the tachykinin NK-1 receptor antagonist (+/-)CP 96,345 were investigated in a rat model of chemically-induced cystitis (intravesical instillation of xylene in female rats). Intravenous injection of bradykinin (1 mumol./kg.) or substance P (3 nmol./kg.) produced plasma protein extravasation (PPE) in the rat urinary bladder. Bradykinin response was prevented by Hoe 140 (100 nmol./kg. intravenously) and unaffected by (+/-)CP 96,345 (10 mumol./kg. intravenously). Plasma protein extravasation produced by substance P was inhibited by (+/-)CP 96,345 but unchanged by Hoe 140. Catheterization required for intravesical xylene instillation into the female rat bladder produced per se an inflammatory response which was abolished by either Hoe 140 or (+/-)CP 96,345. Intravesical instillation of xylene produced a large PPE response which was reduced by about 65% by Hoe 140 or (+/-)CP 96,345. Combined administration of the two antagonists produced an additive effect on the PPE response to xylene. We conclude that both bradykinin and tachykinins are involved in the inflammatory reaction of the rat urinary bladder to catheterization and xylene irritation.

Administration, Intravesical↗
PubMed2000

Indications for early cystectomy.

Treatment goals for superficial bladder cancer are two-fold: (1) reducing tumor recurrence and the subsequent need for additional therapies (cystoscopy, transurethral resection, intravesical therapy) and the morbidity associated with these treatments; and (2) preventing tumor progression and the subsequent need for more aggressive therapy. The administration of intravesical therapy has become an important component in these treatment goals; however, there remains a group of patients with superficial bladder cancer that are at risk of disease progression, metastases, and death from their disease. The treating urologist must be extremely active and diligent when treating patients with superficial bladder cancer. An understanding of tumor biology and current intravesical therapies is important. Furthermore, and perhaps most important, the timely decision to abandon conservative therapy and proceed with radical cystectomy and urinary diversion should be kept in mind to prevent the potentially lethal sequelae of invasive bladder cancer. In view of the potential for recurrence, stage progression, and significant clinical understaging of patients with superficial bladder cancer, and the fact that radical cystectomy provides excellent results with regard to prevention of local recurrence and overall survival, radical cystectomy should be considered in patients with high-risk factors. Radical cystectomy may also provide important prognostic information and influence the decision for adjuvant therapy based on pathologic criteria. Finally, definite improvements in lower urinary tract reconstruction and nerve-sparing techniques have decreased the social implications of cystectomy for both men and women.

Carcinoma in Situ↗
PubMed1987

Sequential instillation therapy with mitomycin C and adriamycin for superficial bladder tumors.

From October 1983 to September 1985, 84 patients with superficial bladder tumor (Ta, Tl, Tis) were treated with sequential instillation of mitomycin C (MMC) and adriamycin (ADM). Doses of 20 mg MMC on day 1 and 40 mg ADM on day 2 were instilled into the bladder and retained for at least 2 h; this was repeated once a week for 5 consecutive weeks. Patients who achieved complete response (CR), were randomized and underwent prophylactic treatment taking the form of either intermittent instillation of MMC or daily oral administration of 5-fluorouracil. Of 79 evaluable patients, 72 (91%) had received prior treatment for superficial bladder tumors, 69 (87%) had high-grade tumors, and 18 (23%) had non-papillary Tis. The overall response rate was 68%, made up of CR in 43 patients (54%) and partial response (PR) in 11 (14%). Patients with either five or more tumors or tumors larger than 1 cm showed a significantly lower response rate than those with fewer than five tumors and tumors smaller than 1 cm, respectively. There was no correlation between tumor growth pattern, tumor grade and response rate, though non-papillary Tis appeared to respond better than papillary tumors. A history of prior instillation therapy or of toxicity to this treatment had no significant influence on the response rate. Although no systemic toxicity was observed, 62 patients (74%) experienced cystitis and the treatment had to be discontinued within 4 weeks in 13 of 33 cases with severe symptoms. The preliminary conclusion of prophylactic treatment was that intermittent instillation of MMC was superior to 5-FU medication in reducing the recurrence rate for at least 2 years after the treatment.

Administration, Intravesical↗
PubMed1991

Magnetic resonance imaging for detecting and treatment monitoring of orthotopic murine bladder tumor implants.

We assessed the feasibility of magnetic resonance imaging (MRI) for detection and treatment monitoring of early stage orthotopic murine bladder (MBT-2) tumor implants. Thirty mice were scheduled for imaging at six, 14, 18 and 21 days after tumor implantation. Using a volume imaging coil, MRI demonstrated very early orthotopic tumors, the detection of which would otherwise have been impossible by clinical signs only. Sequential accurate assessment of tumor size was achieved by inflation of the bladders with a fixed volume of Gadolinium-DTPA contrast. The presence of established MBT-2 intravesical tumors was confirmed by gross pathology and light microscopy of the corresponding whole mount bladder sections. Histological examination of the corresponding tumor specimens revealed the presence of transitional cell bladder carcinoma which correlated very well with the topography and depth of tumor involvement as indicated on MRI. The The mice tolerated repeated MR imaging well. Early tumors at day 14 were detectable on MRI (with serial tumor growth to day 21), with no clinical signs of disease. In a subsequent study, response to intravesical tumor necrosis factor alpha (TNF-alpha) immunotherapy was monitored with serial MRI. The serial MR images from six tumor-bearing mice (three controls and three TNF-alpha treated) have been selected to illustrate the consistent findings of this study. Sequential MRI scans of TNF-alpha treated mice revealed retardation of tumor growth that correlated well with the corresponding histologic examination. The orthotopic tumor and MRI model described is ideal for preclinical evaluation of new potential intravesical chemotherapy and immunotherapy agents.

Administration, Intravesical↗
PubMed2001

Human bladder cancer invasion model using rat bladder in vitro and its use to test mechanisms and therapeutic inhibitors of invasion.

As well as being a passive support, the extracellular matrix also regulates key biological processes such as invasion, differentiation and angiogenesis. We have therefore developed an in vitro model of bladder cancer invasion using de-epithelialized rat bladder to allow for tumour cell-extracellular matrix interactions. Onto this we have seeded a panel of human bladder cancer cell lines (RT4, RT112, 253J and EJ28 (T24)) representing progression from well to poorly differentiated phenotypes and used as models of superficial to invasive bladder cancer. The better differentiated cell lines RT4 and RT112 reproducibly grew as stratified epithelium, whereas poorly differentiated EJ28 cells invaded across a broad front. Invasion was not simply related to proliferation rate, measured either as doubling time on plastic (non-invasive 253J and invasive EJ28 having the same doubling time) or by Ki-67 proliferation index within the model. We used the model to test the ability of 4 compounds that interfere with tumour cell-extracellular matrix interactions (suramin, N-acetylcysteine and the urokinase plasminogen activator pathway antagonists A5 compound and monoclonal antibody Mab 3936) to inhibit invasion. At non-toxic concentrations, all significantly inhibited invasion (P< 0.05), although to varying degrees, suramin and A5 almost completely and N-acetylcysteine the least. In conclusion, this model shows the urokinase system is important for bladder invasion and can be used to investigate other mechanisms of bladder cancer invasion and also for the testing of intravesical drugs.

Acetylcysteine↗
PubMed1998

Intravesical instillation of mitomycin-C in 242 patients with superficial bladder cancer at high risk of recurrence: long-term results.

OBJECTIVE: The present study evaluated the long-term results of intravesical mitomycin C (MMC) instillation after transurethral resection (TUR) in 242 consecutive patients with superficial bladder cancer at high risk of recurrence (stage Ta, grade 1-3, or stage T1, grade 1 and 2, primary multiple or recurrent tumor). MATERIALS AND METHODS: 242 patients were treated with weekly instillations of 40 mg MMC for 8 weeks after TUR. Tumor-free patients then followed a maintenance course with monthly instillations for 3 months. RESULTS: Median follow-up of disease-free patients is 43.5 (range 23-112) months. The incidence of first recurrence is 59.5% (144/242 patients) with a median time to first recurrence of 29 months. 95 patients (39.3%) remained disease-free. Three had disease progression as the first event. The risk of recurrence was significantly higher for multifocal tumors (p = 0.0023, hazard ratio 1.79, 95% CI 1.23-2.59). Overall, patients have been followed for a median time of 57 (range 10-114) months. During this period the recurrence rate was 4.9. Eleven more patients had disease progression. The progression rate is 5.8% (14/242), with a mean time to progression of 34 months. At present 209 patients are alive, 6 have died of bladder cancer, 16 of causes unrelated to the disease and 11 (4.5%) have been lost to follow-up. Thus the crude survival rate is 86.4%, disease-specific mortality 2.5%, and non-disease-specific mortality 6.6%. CONCLUSIONS: Patients with multiple tumors seem to benefit the least from MMC instillation. Probably recurrent disease could be better prevented with intravesical bacillus Calmette-Guérin.

Administration, Intravesical↗
PubMed2005

Importance of urinary interleukin-18 in intravesical immunotherapy with bacillus calmette-guérin for superficial bladder tumors.

OBJECTIVE: Intravesical immunotherapy with bacillus Calmette-Guérin (BCG) remains the most efficient modality for the treatment of carcinoma in situ and prevention of recurrences of Ta and T1 bladder tumors. Although elevations in a variety of urinary cytokines have been reported after BCG instillation, the mechanism by which BCG mediates antitumor activity has not been clearly established. Based upon our murine study, we reevaluated urinary cytokines before and after BCG instillations from the point of T helper (Th) 1/2 lymphocyte cytokine profiles. METHODS: Urinary interleukin (IL)-2, interferon (IFN)-gamma, IL-12, and IL-18 for Th1, and IL-4 for Th2 cytokines were measured by enzyme-linked immunosorbent assay just before and 4 h after the 4th or 5th instillation of 8 weekly instillations of 40-80 mg BCG, Tokyo strain, in 12 patients with superficial stages Ta and T1 bladder cancer, and carcinoma in situ. RESULTS: Two representative Th1 cytokines, IL-2 and IFN-gamma, significantly increased in urine after intravesical BCG instillations. Interestingly, IL-12, a strong inducer of Th1 cytokines, did not increase in the urine after BCG instillations. Instead, IL-18, that has recently been reported to induce IFN-gamma production in T and NK cells in synergy with IL-12, obviously elevated in urine after BCG instillations. Urinary IL-4, a representative of Th2 cytokines, did not change at all after intravesical BCG instillations. CONCLUSION: Our results clearly show the predominant importance of IL-18 followed by increases in Th1 cytokines, such as IL-2 and IFN-gamma, in the mechanisms of intravesical immunotherapy with BCG.

Administration, Intravesical↗