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At least 865 records · Page 48Linked to original sources
PubMed1997

Seromuscular colocystoplasty lined with urothelium protects dogs from acidosis during ammonium chloride loading.

PURPOSE: We compared the metabolism of intravesical ammonium chloride in dogs in which the bladder had been enlarged by seromuscular colocystoplasty lined with urothelium, dogs that had undergone conventional colocystoplasty and control dogs. MATERIALS AND METHODS: Eight adult female mongrel dogs were divided into control (2), colocystoplasty (3) and seromuscular colocystoplasty (3) groups. Serum creatinine, bicarbonate, sodium, chloride, and potassium levels were measured every 2 weeks during the 6-week recovery period. Six weeks after augmentation the dogs were placed under general anesthesia, the bladder was instilled with a hyperosmolar solution of 400 mmol/l. ammonium chloride, the femoral artery and portal vein were cannulated to obtain blood samples and the ureters were divided with the proximal ends diverted to allow serial urine measurements. Blood and urine electrolyte analysis was performed at 0, 60, 120, 180 and 240 minutes after the intravesical instillation of ammonium chloride. RESULTS: During acid loading dogs that had undergone conventional colocystoplasty had a progressive decrease in serum carbon dioxide and arterial pH as well as increased levels of serum chloride and a significant increase in plasma ammonia concentration in the portal vein compared to controls and dogs that had undergone seromuscular colocystoplasty. In contrast, there were no differences in seromuscular colocystoplasty compared to control animals. CONCLUSIONS: Increased ammonia in the portal vein and hyperchloremic acidosis in dogs that underwent conventional colocystoplasty suggest intravesical absorption of ammonium chloride. Dogs that underwent augmentation with seromuscular colocystoplasty lined with urothelium seemed to respond to acute intravesical ammonium in a way similar to that of control dogs and they are protected from these metabolic anomalies.

Acidosis↗
PubMed1989

Intravesical Bacillus Calmette-Guérin treatment for superficial bladder tumours.

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.

Administration, Intravesical↗
PubMed1997

Role of interferon-alpha-2b in the prevention of superficial carcinoma of the bladder recurrence.

In order to study the tolerability, toxicity and therapeutic efficacy of interferon-alpha2b (Intron-A), 20 patients with superficial transitional cell carcinoma (TCC) of the urinary bladder (Ta, T1) were given intravesically a low dose (9 million IU) of the drug mixed with 30 ml physiological saline for 8 weeks, starting 1 week after transurethral resection (TUR). Follow-up included urine cytology, ultrasonography of the abdomen and cystourethroscopy. Eleven patients (55%) had no signs of recurrence during a follow-up of 6-32 months (mean duration 24 months). Four patients (20%) had superficial tumor recurrence and 5 patients (25%) showed recurrence with progression to invasive tumors. Tolerability was very good, while toxicity in the form of mild flu-like symptoms was observed in only 3 patients. This pilot study showed that, at a low dose, intravesical interferon therapy can significantly lower the recurrence rate in superficial TCC of the urinary bladder with good tolerance and practically no side effects.

Administration, Intravesical↗
PubMed1988

[A new animal model for intravesical chemotherapy of bladder cancer].

A new animal model for intravesical chemotherapy of bladder cancer was prepared by transplanting BC-47 cells into the bladder wall of syngenic ACI/N rat and later transurethral cauterization of the urothelium covering the developed solid tumor, and compared with two common models. One of the models was prepared by similarly transplanting the tumor cells without further treatment and another by transurethral instillation of the tumor cells into cauterized bladder. Tumor transplantation and denudation were both 100% successful in the new model and was superior to those in two common models. The new model was more sensitive to peplomycin than the common model prepared by transplanting the tumor cells into bladder wall without cauterization of the urothelium, while the sensitivity to adriamycin were practically the same as that of the common model. This difference may be due to presence of the urothelium, which seemed to inhibit a contact of intravesically administered peplomycin with tumor. It could be considered that the new model with denuded tumor has a high predictivity on the clinical effect for drug candidates.

Administration, Intravesical↗
PubMed1989

Intravesical therapy comparing BCG, adriamycin, and thiotepa in 200 patients with superficial bladder cancer: a randomized prospective study.

This report presents the second interim analysis of data from a randomized prospective trial that compares the prophylactic effect of 15 intravesical instillations of 50 mg Doxorubicin (ADM), 50 mg of Thiotepa (TTPA), or 150 mg of Bacillus Calmette-Guérin (BCG) against recurrence and progression of superficial transitional cell bladder cancer. Of 202 enrolled patients, 176 patients are currently evaluable after a mean follow-up of 3 years (range, 3-97 months). The number of patients with recurrence was significantly lower in the BCG group (9/67) than in the ADM group (23/53, p = 0.002) or the TTPA group (20/56, p = 0.003). The overall recurrence index per 100 patient-months was also significantly lower for the BCG group (BCG vs. ADM, p = 0.07; BCG vs. TTPA, p = 0.001; TTPA vs. ADM, not significant). BCG was superior in preventing recurrence and progression of high risk tumors (T1, G2-3, multiple growth, and tumors associated with carcinoma in situ). The recurrence in this group of high risk tumors was for ADM treated patients 12/17, for TTPA treated patients 10/17 and for BCG treated patients 5/23 (BCG vs. ADM, p = 0.002; BCG vs. TTPA, p = 0.016; TTPA vs. ADM, not significant). Toxicity of intravesical BCG was higher than that of the other drugs, but not limiting the treatment. Bladder irritability occurred in 42% of the patients, granulomatous cystitis in 16.4%, and bladder contraction in 1.5% of the patients. Two patients of the ADM group (2/53 = 3.8%) underwent radical cystectomy for local urothelial progression. One patient (1.9%) in the same group died of distant metastases. The preliminary results suggest that BCG is significantly superior to the chemotherapeutic agents ADM and TTPA when used as an adjuvant intravesical therapy in superficial bladder cancer.

Administration, Intravesical↗
PubMed1989

[Superficial bladder tumors. Results of preventive treatment of recurrence by intravesical instillation of BCG].

Two-thirds of newly diagnosed bladder tumors are superficial transitional cell carcinomas. Local relapses occur in more than 2/3 of the patients after transurethral resection of the initial tumor, with a risk of muscle invasion in 1/3 of them. A retrospective study of 100 consecutive patients was performed to assess the role of intravesical BCG-therapy as a prophylaxis against the recurrence of superficial bladder cancer; the treatment protocol is described. Eighty-two patients had previously had recurrent tumors and 18 were given BCG directly because they had multiple, large, high grade or widespread tumors. Seventy patients (70 p. 100) tolerated the treatment well, but 6 experienced serious complications (3 systemic BCG infections and 3 bladder contractures). Of the 18 patients given BCG after their first tumor, 12 (66 p. 100) are tumor-free with a mean follow-up of 13 months. Of the 82 patients with previous recurrent tumors, 52 (63 p. 100) were improved by the treatment. Of the 100 patients, twelve tumors became muscle invasive and required more aggressive intervention. Intravesical BCG is effective in preventing recurrences of superficial bladder cancer. However, the side effects and the risk of muscle invasion require close monitoring.

Administration, Intravesical↗
PubMed1997

Intravesical therapy with vinorelbine tartrate: antitumor activity in orthotopic murine cell carcinoma of the bladder.

OBJECTIVES: To ascertain intravesical vinorelbine tartrate (VNR) antitumor activity against MB-49, a murine transitional cell carcinoma of the bladder (TCC), in an in vivo setting. MATERIALS AND METHODS: C57B1/6J female mice were intravesically implanted with 5 x 10(4) MB-49 cells and treated locally with VNR. Tumor incidence and volume analyses, as well as survival studies were carried out. RESULTS: Tumor incidence was significantly lower in VNR-treated mice (48%, n = 23) than in controls (84%, n = 19), as evaluated sixteen days after MB-49 orthotopic inoculation. Intravesical tumor volume was also significantly smaller in treated mice respect to controls (median [range]: 0.5 [0.4 to 61.8] mm.3 versus 47.7 [4.2 to 179.7] mm.3 respectively, p < 0.001 Kruskal-Wallis test). Median survival duration of the animals treated with VNR was 68 [21 to 68] days, and was significantly greater (p = 0.01, Kruskal-Wallis test) than that of untreated controls (18 [16 to 20] days). CONCLUSION: Intravesical VNR treatment demonstrated an evident antitumor effect against the TCC model assayed. The results obtained suggest a potential use of VNR as intravesical treatment for superficial TCC following transurethral bladder tumor resection to prevent recurrence or retard tumor growth.

Administration, Intravesical↗
PubMed2002

Effect of diagnostic hydrodistension and four intravesical hyaluronic acid instillations on bladder ICAM-1 intensity and association of ICAM-1 intensity with clinical response in patients with interstitial cystitis.

OBJECTIVES: To study the clinical effect of diagnostic overdistension plus hyaluronic acid (HA) instillations in interstitial cystitis and the association of the clinical response with the intensity of intercellular adhesion molecule (ICAM)-1 expression. HA is an important component in the urothelium. It inhibits adherence of immune complexes to polymorphonuclear cells, leukocyte migration, and aggregation. HA binds to lymphocytes and endothelial cells expressing ICAM-1. METHODS: Eleven patients with interstitial cystitis who fulfilled the diagnostic criteria of the National Institutes of Health were selected for the trial. The bladder was distended for 1 minute with a pressure of 80 cm H2O and biopsies were taken from the petechial areas. The patients were treated with four weekly intravesical HA instillations (40 mg/50 mL NaCl solution). Biopsies were repeated 2 weeks after the instillations. The ICAM-1 intensity was blindly determined in the lymphocytes and endothelial cells of the vessels from the histologic biopsies. A semiquantitative scoring index was used to measure the inflammatory effect of ICAM-1 receptors. RESULTS: In the long-term responders (2 women and 1 man) and short-term responders (5 women), the pretreatment ICAM-1 index was 3.7 (range 3 to 4); it was 1.8 (range 1.5 to 2) in the nonresponders. Two weeks after the final instillation, the index was 3.5 (range 3 to 4) in the long-term responders and 3.4 (range 3 to 4) in the short-term responders; in the nonresponders, it had increased to 2.8 (range 2.5 to 3.5). CONCLUSIONS: Increased ICAM-1 intensity was found in patients with interstitial cystitis; it was higher in those who responded to overdistension plus HA instillations. By blocking the ICAM-1 receptors, HA presumably alleviates the inflammatory processes, but repeated instillations are needed to maintain the response.

Administration, Intravesical↗
PubMed1996

[Characteristic and effective usage of adriamycin].

The utility of adriamycin (doxorubicin), an anti-cancer antibiotic, for the treatment of transitional cell carcinoma of the bladder has been appreciated. Adriamycin is still used intravesically for superficial bladder cancer to avoid implantation of floating cancer cells after transurethral resection, to decrease the incidence of recurrence and treat an unresected part of the tumor. On the other hand, cisplatin-based multi-drug chemotherapies including adriamycin have proven effective in treating locally and systemically advanced bladder cancer.

Administration, Intravesical↗
PubMed1989

A practical guide to the use of intravesical BCG for the management of stage Ta, T1, CIS, transitional cell cancer.

Intravesical instillations of BCG are effective in preventing tumor recurrence, eliminating existing tumor and treating CIS in a substantial number of patients. As with any type of therapy, side effects can occur. Because a live organism is being used, care must be taken in the handling and administration of the product. Patients should be informed about the common types of reactions so that these may be reported to the urologist. In turn, the urologist must decide if the treatment plan needs to be modified or the patient started on medications which can prevent or reduce the severity of the side effects. At times a decision must be made regarding withholding or delaying treatment and there are situations when BCG should be stopped.

Administration, Intravesical↗
PubMed1995

A phase I study of intravesical continuous perfusion of recombinant interleukin-2 in patients with superficial bladder cancer.

A Phase I study was started to evaluate the locoregional and/or systemic toxic effects of the continuous perfusion of recombinant interleukin-2 (rIL-2) in superficial bladder cancer. Three different dose levels were used: 3 x 10(6) IU/day (3 patients), 9 x 10(6) IU/day (3 patients) and 27 x 10(6) IU/day (3 patients). Two patients (one treated with 3 x 10(6) and another with 27 x 10(6) IU/day of rIL-2) had hematuria after the end of the treatment, one patient had fever (grade I) and 7 of 9 patients experienced hypotension (grade I-II). All effects were not dose related. Routine laboratory tests indicated that no significant variations of biochemical parameters occurred. A phenotypic analysis of white blood cells detectable in the bladder, showed an evident locoregional activation of lymphoid cells. In particular, T lymphocytes expressed activation antigens (such as CD25 and HLA-DR) following treatment with rIL-2. A 6- to 12-month clinical follow-up, showed that all patients but one (which recurred after 5 months) are alive and disease-free. This therefore indicates that the locoregional perfusion of rIL-2 is safe and gives clinical results similar to those obtained using Calmette-Guérin bacillus locoregional instillation, in patients who underwent a transurethral resection of superficial bladder cancer.

Administration, Intravesical↗
PubMed1988

Results of 6 weekly intravesical bacillus Calmette-Guerin instillations on the treatment of superficial bladder tumors.

We evaluated 104 patients with superficial bladder tumors for response to intravesical bacillus Calmett-Guerin therapy. Patients received 6 weekly intravesical bacillus Calmette-Guerin instillations and they were followed for response every 3 months with urinary cytology, cystoscopy and bladder biopsy. Patients were considered treatment failures if either the cytology studies or biopsies were positive for tumor. Of 65 patients who failed the initial treatment course 57 were given an additional 6-week course of therapy. One 6-week course of bacillus Calmette-Guerin was successful in 20 of 55 patients (36 per cent) treated for prophylaxis, 12 of 32 (37 per cent) treated for carcinoma in situ and 7 of 17 (41 per cent) treated for residual tumor. The response rate for the total patient population treated with 1, 6-week course was 37.5 per cent (39 of 104). A second 6-week course was successful in 19 of 29 patients (65 per cent) treated for prophylaxis, 11 of 18 (71 per cent) treated for carcinoma in situ and 4 of 10 (40 per cent) treated for residual tumor. The response rate for all patients receiving a second course of bacillus Calmette-Guerin was 59.6 per cent (34 of 57). Of 6 patients who refused another 6-week course of bacillus Calmette-Guerin 4 had additional recurrences and 3 of these 4 suffered invasive disease. The over-all therapeutic response rate for patients treated with either 6 or 12 weeks of therapy was 70 per cent. These results suggest that 6 weeks of intravesical bacillus Calmette-Guerin do not provide optimal therapy for superficial bladder tumors. The data further suggest that more intensive regimens may increase therapeutic efficacy.

Administration, Intravesical↗
PubMed2000

Pilot study of the tolerability and toxicity of intravesical valrubicin immediately after transurethral resection of superficial bladder cancer.

OBJECTIVES: To assess in a pilot study the safety, tolerability, and technical feasibility of administering intravesical valrubicin immediately after transurethral resection of bladder tumors (TURBT) in patients with superficial bladder cancer and to evaluate the optimal dose of valrubicin and its systemic absorption. METHODS: Twenty-two patients with recurrent or newly diagnosed Stage Ta or T1 transitional cell tumors received a single dose of 400 mg, 600 mg, or 800 mg of intravesical valrubicin immediately after TURBT. Four patients thought to be at high risk of recurrence were followed up with five additional doses of 800 mg valrubicin, given weekly. RESULTS: The use of valrubicin after TURBT was generally well tolerated. Little evidence was found to suggest a direct relationship among the dose of valrubicin, the time between the end of TURBT and drug instillation, and the occurrence of most bladder symptoms. The most commonly reported adverse events included dysuria (77%), hematuria (59%), and urgency/frequency (23%). Pharmacokinetic analyses revealed that the mean systemic exposure to valrubicin and its metabolites depended on the extent of the TURBT and the damage to the bladder wall. CONCLUSIONS: The results of this study indicated that administration of valrubicin immediately after TURBT is feasible.

Administration, Intravesical↗
PubMed2002

[Urothelial carcinoma. Role of G-protein coupled receptors in cell movement and proliferation].

To develop new therapeutic strategies we examined the expression and signaltransduction of G protein-coupled receptors in a human transitional cell carcinoma cell line. The receptors for lysophosphatidic acid (LPA) and thrombin potently stimulate cell migration. Pretreatment with PTX completely inhibited cell motility induced by LPA. In the model of chemically induced bladder carcinoma in rats the effects of intravesical instillation of PTX or phosphate buffered saline was examined. The incidence of G2-G3 cells in cytology was significantly reduced in rats treated with PTX. To ascertain the side effects of intravesical instillation of PTX a Phase I study was initiated. 15 patients were instilled with PTX at 5 dose levels (14-72 micrograms/100 ml) 3 times a week. Instillation of PTX up to 72 micrograms was without local or systemic side effects. PTX is a substance which potently inhibits tumor cell motility and progression. Intravesical treatment was well tolerated and therefore, the influence of PTX on local tumor should be evaluated in a Phase II study.

Administration, Intravesical↗
PubMed2005

Prospective, randomized, double-blind study of safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC).

OBJECTIVE: To determine the safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC) patients. MATERIALS AND METHODS: IC patients were instilled with 50 cc of test solution containing either placebo, 0.05 microM or 0.10 microM RTX in the bladder. Plasma concentration of RTX and its degradant resiniferonol 9-, 13-, 14-orthophenylacetate was measured. Immediate post-treatment blood sampling and cystoscopy were performed. Symptoms were evaluated before treatment, at 4- and at 12-week follow-ups, using VAS indicator for pain, voiding diary, and O'Leary's IC symptom/problem indices. RESULTS: Among 22 patients observed (ten in 0.10 microM RTX, eight in 0.05 microM RTX, and four in placebo groups), the most commonly reported adverse event was pain during instillation (80.0%, 87.5%, and 25.0%). No serious adverse events were reported. CONCLUSIONS: Use of intravesical RTX in IC patients is associated with important tolerability issues but safe at 0.10 microM and 0.05 microM.

Administration, Intravesical↗
PubMed1990

In vitro and in vivo anti-tumor activity of recombinant mouse tumor necrosis factor (TNF) in a mouse bladder tumor (MBT-2).

Tumor necrosis factor (TNF) has confirmed anti-tumor activity. When used in combination with interferon gamma (IFNG) or chemotherapeutic drugs targeted at DNA topoisomerase II, synergistic cytotoxicity has been observed. Investigations of the anti-tumor activity of recombinant mouse TNF in a mouse bladder tumor model (MBT-2) were performed. The cytotoxicity of TNF and low dose actinomycin-D (AMD) against MBT-2 in vitro was examined alone and following preincubation with IFNG. The activity of TNF/AMD in vivo utilizing an intravesical implantation mode (MBT-2) was also evaluated. TNF alone had no cytotoxic effect in vitro. TNF/AMD was cytotoxic for MBT-2 growth in vitro. Maximum cytotoxicity (86%) occurred at one microgram./ml. TNF/one microgram./ml. AMD with 50% cytotoxicity at .64 micrograms./ml. TNF/one/microgram./ml. AMD. A two hour preincubation with IFNG markedly increased the cytotoxicity of TNF/AMD whereas longer incubations did not enhance cytotoxic activity. TNF alone and in combination with AMD did not significantly reduce the percentage of intravesical tumor outgrowth in vivo compared to controls. This study demonstrated that TNF/AMD exhibits cytotoxicity for MBT-2 cells in vitro but is ineffective in reducing implantation of intravesical tumors in vivo. The in vitro data suggest brief exposure of MBT-2 cells to IFNG augments the subsequent anti-tumor activity of TNF/AMD.

Administration, Intravesical↗