Expert consensus on treatment of intravesical therapy in non-muscle invasive bladder cancer / 中华肿瘤杂志

Bladder cancer is one of the common malignant tumors in China. Three-quarter bladder cancer is non-muscle invasive bladder cancer with a high recurrence rate. Intravesical therapy can reduce the risk of recurrence and progression in bladder cancer. According to the recent updates of evidence-based medical evidence at home and abroad, as well as the deepening of domestic experts' research on the diagnosis and treatment of bladder cancer, the consensus has summarized the current intravesical therapy for non-muscle invasive bladder cancer in China, including the indications, contraindications and methods for intravesical therapy, as well as commonly used drugs in bladder cancer.

Expert consensus on treatment of intravesical therapy in non-muscle invasive bladder cancer / 中华肿瘤杂志

Bladder cancer is one of the common malignant tumors in China. Three-quarter bladder cancer is non-muscle invasive bladder cancer with a high recurrence rate. Intravesical therapy can reduce the risk of recurrence and progression in bladder cancer. According to the recent updates of evidence-based medical evidence at home and abroad, as well as the deepening of domestic experts′ research on the diagnosis and treatment of bladder cancer, the consensus has summarized the current intravesical therapy for non-muscle invasive bladder cancer in China, including the indications, contraindications and methods for intravesical therapy, as well as commonly used drugs in bladder cancer.

Pretreatment Features to Influence Effectiveness of Intravesical Hyaluronic Acid Instillation in Refractory Interstitial Cystitis/Painful Bladder Syndrome / 대한배뇨장애요실금학회지

PURPOSE: To determine the efficacy of intravesical hyaluronic acid (HA) instillation in treating patients with refractory interstitial cystitis/painful bladder syndrome (IC/PBS) and to identify any related factors that influence its therapeutic effect. METHODS: Thirty-three female IC/PBS patients who demonstrated poor or unsatisfactory responses to previous treatments between December 2010 and October 2012 were enrolled. Despite previous treatments, the enrolled patients had visual analogue scale (VAS) pain scores > or =4 and total scores (symptom and bother scores) > or =13 on the pelvic pain and urgency/frequency (PUF) questionnaire and > or =12 on the O'Leary-Sant interstitial cystitis symptoms index (ICSI)/problems index (ICPI). All patients received once weekly intravesical instillations of 40-mg HA diluted in 50-mL saline for 4 weeks. The efficacy of the HA instillation was evaluated by comparing the mean changes in the scores of the VAS and questionnaires from baseline to 4 weeks after treatment. Improvement was defined as a > or =2 decrease in the VAS. Moreover, we investigated the effects of the presence of Hunner's ulcer and previous treatment modalities on the therapeutic outcome of HA instillation. RESULTS: The mean age was 57.0+/-1.8 years (range, 28-75 years). The VAS score significantly decreased from baseline to 4 weeks after treatment (-2.5, P<0.001). The mean changes in the PUF, ICSI, and ICPI from baseline to 4 weeks after the treatment were -3.8 (P<0.001), -2.3 (P<0.001), and -2.7 (P<0.001), respectively. Twenty patients (61%) showed improvements. Previous treatment modalities did not affect the efficacy of HA instillation and the presence of Hunner's ulcer was unrelated to outcomes. No complications were observed. CONCLUSIONS: These results show that intravesical HA instillation is an effective and safe treatment for patients with refractory IC/PBS. Previous treatment modalities and presence of Hunner's ulcer do not affect the efficacy of HA instillation.

Tumor Establishment Features of Orthotopic Murine Bladder Cancer Models

PURPOSE: Animal tumor models are important for the evaluation of novel therapeutic modalities. Since the initial report of an orthotopic bladder tumor model, several modifications have been proposed to improve the tumor take rate. Here we compared the HCl-pretreated and electrocauterization-pretreated orthotopic murine bladder tumor models. MATERIALS AND METHODS: MBT-2 murine bladder cancer cells were transurethrally implanted in the bladder of syngeneic C3H/He mice. The mice were divided into three groups according to pretreatment methods (electrocautery, HCl, and control group) and were subjected to pretreatment before instillation of MBT-2 tumor cells into the bladder. Mice were sacrificed on day 21, and bladders were harvested, weighed, and examined histopathologically. RESULTS: The tumor take rate of the control, electrocautery, and HCl groups was 0%, 54%, and 100%, respectively. The tumor take rate of the HCl group was significantly higher than that of the control group (p<0.01) and the electrocautery group (p=0.01). Pathologic reports revealed that all established bladder tumors were high-grade papillary urothelial carcinomas. CONCLUSIONS: The HCl pretreatment model was a preferable murine bladder tumor model for evaluating further therapeutic interventions.

Effects of Combination Treatment of Intravesical Resiniferatoxin Instillation and Hydrodistention in Patients with Refractory Painful Bladder Syndrome/Interstitial Cystitis: A Pilot Study / 대한배뇨장애요실금학회지

PURPOSE: Painful bladder syndrome/interstitial cystitis (PBS/IC) is a disabling disease of the urinary bladder, and its etiology and treatment are not yet established. Current medications used in the treatment of PBS/IC have shown limited efficacy. This prospective study investigated the efficacy of intravesical resiniferatoxin (RTX) in PBS/IC refractory to medical treatment. METHODS: Patients with proven PBS/IC refractory to traditional medical treatment were enrolled. By randomized trial, a total of 18 consecutive patients were divided into two groups: treatment with hydrodistention and intravesical RTX (group 1) or treatment with hydrodistension only (group 2). We assessed bladder pain by use of a visual analogue pain scale, the maximal urine flow rate, post-void residual urine volume, and a voiding diary before and 3 months after treatment. RESULTS: The median age of the 18 patients was 55.8+/-6.9 years, and the median duration of symptoms before diagnosis was 3.6+/-1.6 years. Frequency, functional bladder capacity, and score on a 5-point pain scale were significantly improved at 3-month after treatment in both groups. Intravesical RTX instillation plus hydrodistention, compared with hydrodistention only, did not have a significant effect on the voiding symptoms or uroflowmetry of the patients but significantly improved scores on the pain scale. CONCLUSIONS: Intravesical RTX instillation plus hydrodistention was effective in relieving pain but was not effective in improving lower urinary tract symptoms. Further larger studies are needed to clarify the efficacy of combination treatment of intravesical RTX instillation and hydrodistention.

Experimental Study on Yinhuang Solution on Bladder Mucosal Injury in Rat / 中国康复理论与实践

@#ObjectiveTo investigate the effects of Yinhuang solution on the bladder mucosal before and/or after mucosal injury.Methods32 SPF female SD rats were randomly divided into 4 groups with 8 rats in each group. Group A was used for the normal control group, group B for the model control group, group C for preventive group, group D for preventive and therapeutic group. Injured rats were created by hydrochloric acid applied on bladder mucosa. After the models were established or before and after the models were established, bladders were perused with Yinhuang solution. Severity of inflammatory infiltration were observed by HE staining, histological score and heat shock protein 70 (HSP70) expressed in the mucosa.ResultsEndoscopic pathological change showed that group B had a large number of inflammatory cell infiltration, significant expansion of capillary, epithelial cell necrosis. Group C had a small amount of expansion of capillary, inflammatory cell infiltration. Group D scattered in expansion of capillary, a small amount of inflammatory cell infiltration. Concerning the results of histological score and HSP70 expression, there was a significant difference between group A and groups B, C or D (P<0.01); there was a significant difference between group B and groups C or D (P<0.01); there was a significant difference between group C and group D (P<0.05).ConclusionYinhuang solution can evidently improve the repair capability of bladder mucosa after injury.

Anticancer Activity of Intravesical Glyceryl Monooleate (GMO)-Paclitaxel Therapy in Murine Superficial Transitional Cell Carcinoma Model Induced by BBN / 대한비뇨기과학회지

Purpose: Paclitaxel, on systemic administration, is widely known to be effective in the treatment of bladder cancer. However, the intravesical use of paclitaxel has not been attempted because of its liposolubility and direct toxicity to the bladder mucosa. The purpose of this study was to evaluate the efficacy and toxicity of paclitaxel-loaded glyceryl monooleate (GMO) in the intravesical treatment of superficial bladder cancer, by enhancing its bioadhesiveness and bioavailability. Materials and Methods: 12 mice were divided into two groups, and bladder carcinomas induced by the addition of 0.05% BBN to their drinking water for 12 weeks. Group 1 received an intravesical instillation of 0.1ml GMO-paclitaxel-free buffer and Group 2 an intravesical instillation of 0.1ml GMO-paclitaxel. On day 21, the tumor incidence, bladder weight and toxicity were evaluated. Results: The incidence of cancer in groups 1 and 2 were 83 and 17%, respectively. The incidence of cancer was significantly reduced in group 2 compared to group 1 (p<0.05). There was a tendency for the average bladder weight in group 1 to be heavier than that in group 2, but there was no significant difference (p=0.375). There were no liver, kidney or bone marrow toxicities in either group. Conclusions: Intravesical GMO-paclitaxel therapy may have an inhibitory effect on the growth of superficial bladder cancer in a BBN-induced bladder cancer model; therefore, it could potentially be used in those patients showing little to no response to intravesical Bacillus Calmette- Guerin (BCG) or other anticancer drug therapies.

Efficacy of Paclitaxel-Loaded Bioadhesive Drug Deliver System Based on Glyceryl Monooleate Nanoparticle in an Orthotopic Murine Bladder Cancer Model / 대한비뇨기과학회지

Purpose: The purpose of this study was to evaluate the efficacy of paclitaxel-loaded glyceryl monooleate (GMO) in the intravesical treatment of superficial transitional cell carcinomas of the bladder by enhancing the bioadhesiveness and bioavailability. Materials and Methods: A mucoadhesive oily paclitaxel formulation was prepared using GMO, tricaprylin, Tween(8) 80 and paclitaxel. The bioactivity of the GMO/paclitaxel formulation was confirmed by assessing its cytotoxicity on MBT-2, a bladder cancer cell line. An in vivo study was performed in C3H2 mice after induction of bladder cancer by an intravesical bladder tumor implantation. The efficacy of the intravesical administration of the GMO/paclitaxel was assessed by the histology and bladder weight. Results: The average particle size of the GMO/paclitaxel was 600nm. Only 2.6% of the MBT-2 cells were viable after 24 hours of treatment with GMO/paclitaxel at a paclitaxel concentration of 10microgram/ml. In the orthotopic bladder cancer model the tumor incidence rate was significantly decreased by intravesical administration of the GMO/paclitaxel compared to the controls. The average bladder weight of the GMO/paclitaxel group was significantly lower than that of controls. No toxicity was observed in either of the groups. Conclusions: Intravesical administration of the GMO/paclitaxel formulation had an inhibitory effect on the bladder tumor in an orthotopic bladder cancer model. This formulation may be a promising approach for intravesical chemotherapy of superficial bladder cancer.

Bioadhesive Drug Delivery System for the Intravesical Administration of Paclitaxel in Rabbits / 대한비뇨기과학회지

PURPOSE: Many reports have shown that the efficacy of intravesical therapy for bladder cancer is, in part, limited by the poor penetration of drugs into the urothelium. The present study evaluated the effect of glyceryl monooleate (GMO) on the delivery and penetration of paclitaxel into the bladder of rabbits, when given as an intravesical dose. MATERIALS AND METHODS: The urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120min with paclitaxel (500g/20ml) by an intravesical instillation. Two formulation of GMO/paclitaxel were evaluated, according to the proportion of water, 15% and 30%, with Taxol was used as a control. The animals were observed for clinical signs of toxicity, and necropsy performed. RESULTS: At 120min post-instillation, the bladders were emptied and excised. The urine paclitaxel concentrations were decreased by 39.6 and 41.2% in the two experimental groups, and by 25.2% in the control group. The paclitaxel concentrations in the urothelium were 53 and 56% of the urine concentration in the two experimental groups, respectively, but by only 11% in the control group. The concentration then declined exponentially in the underlying capillary perfused tissues, reaching equilibrium at a depth of 1,400-1,700um. The plasma concentrations were extremely low compared with those in the urine and bladder tissues, and were not associated with clinical toxicity. CONCLUSIONS: These results indicate that GMO improves the delivery of paclitaxel and increases the concentration in the bladder tissue. These results suggest that the intravesical delivery of GMO/paclitaxel/water provide a significant bladder tissue targeting advantage, and that paclitaxel represents a viable candidate drug for intravesical bladder cancer therapy.