OBJECTIVE: To investigate the efficacy and safety of intravesical instillation of heparin/alkalized lidocaine (lidocaine mixed with sodium bicarbonate) combined with hydrodistension and transurethral fulguration in the treatment of female interstitial cystitis (IC). METHODS: Female patients who attended the Department of Urology at the First Hospital of China Medical University between January 2012 and December 2020 and met the diagnostic criteria proposed in the guidelines of the American Urological Association with a new diagnosis of IC were selected for retrospective analysis. Cystoscopy and biopsy of suspicious lesions were performed at the time of diagnosis. All the patients were treated with an intravesical instillation regimen of 2% lidocaine 10 mL + 5% sodium bicarbonate 5 mL + heparin 25 000 IU for a continuous period of 12 months, with or without water dilatation and transurethral electrocautery according to the patient's preference, categorized as hydrodistension and transurethral fulguration (HD/TF) group and non-HD/TF group. The patients were evaluated before and 1, 6, and 12 months after treatment for O'Leary-Sant interstitial cystitis patient symptom index scores (ICSI), interstitial cystitis patient problem index scores (ICPI), visual analog scale (VAS) of suprapubic pain, and functional bladder capacity (FBC) changes. RESULTS: A total of 79 patients were collected in this study. Four (5.1%) of these patients underwent cystectomy due to pathological diagnosis of cancer or treatment failure. The remaining patients were followed up 1, 6 and 12 months after treatment. Repeated-measures ANOVA showed a significant decrease in ICPI, ICSI and VAS and an increase in FBC after treatment compared with before treatment (P < 0.05). FBC continued to decrease during the 1, 6 and 12 months' post-treatment follow-ups, with statistically significant differences; ICSI continued to decrease during the 1 and 6 months post-treatment follow-ups, with statistically significant differences, while the difference between ICSI at 6 months post-treatment and at 12 months' post-treatment was not statistically significant. In the HD/TF group, ICPI continued to decrease in the follow-up from 1 and 6 months after treatment, and the difference was statistically significant, while the difference between ICPI 6 months after treatment and 12 months after treatment was not statistically significant. There was no statistically significant difference between the remaining indicators 1, 6 and 12 months after treatment. ICPI, ICSI, VAS and FBC improved earlier and the changes in VAS and FBC were more significant in the HD/TF group compared with the non-HD/TF group (P < 0.05). CONCLUSION Heparin/alkalized lidocaine combination of intravesical instillation with hydrodistension and transurethral fulguration for IC is an effective treatment option. Heparin/alkalized lidocaine combination of intravesical instillation may be the first choice of treatment, which can significantly reduce the economic burden of patients and medical insurance system. If patients can accept it, transurethral fulguration with hydrodistension may be considered.
Humans ; Female ; Cystitis, Interstitial/drug therapy* ; Administration, Intravesical ; Retrospective Studies ; Sodium Bicarbonate/therapeutic use* ; Treatment Outcome ; Lidocaine/therapeutic use* ; Heparin/therapeutic use* ; Electrocoagulation

INTRODUCTION: Usage of metformin is associated with improved survival in lung, breast and prostate cancer, and metformin has been shown to inhibit cancer cell growth and proliferation in in vitro studies. Given the lack of clinical data on metformin use in patients with bladder cancer, we aimed to evaluate the role of metformin in their oncological outcomes. METHODS: Medication use data from a prospectively maintained database of 122 patients with non-muscle-invasive bladder cancer treated with intravesical Bacille Calmette-Guerin (BCG), who were recruited under a randomised, double-blinded, controlled clinical trial, was collected and analysed. Kaplan-Meier curves were used to assess overall survival (OS) and disease-specific survival (DSS). RESULTS: At a median follow-up duration of 102 (range 3-357) months, 53 (43.4%) patients experienced disease recurrence and 21 (17.2%) experienced disease progression. There was no significant difference in mortality between patients with and without diabetes mellitus. There was significant difference in OS between patients without diabetes mellitus, patients with diabetes mellitus on metformin and patients with diabetes mellitus but not on metformin (p = 0.033); patients with diabetes mellitus on metformin had the best prognosis. Metformin use was associated with significantly lower DSS (p = 0.042). Other oral hypoglycaemic agents, insulin or statins were not associated with disease recurrence or progression. CONCLUSION Metformin use was associated with improved oncological outcomes in patients with non-muscle-invasive bladder cancer treated with intravesical BCG. Prospective studies with larger patient populations are needed to validate the role of metformin as potential therapy for bladder cancer.
Adjuvants, Immunologic/therapeutic use* ; Administration, Intravesical ; BCG Vaccine/therapeutic use* ; Diabetes Mellitus ; Disease Progression ; Humans ; Male ; Metformin/therapeutic use* ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prospective Studies ; Retrospective Studies ; Urinary Bladder Neoplasms/drug therapy*

The aim of this study was to investigate the incidence of erectile dysfunction (ED) in nonmuscle-invasive bladder cancer (NMIBC) patients before and after transurethral resection (TUR) in China. Clinical data from 165 male patients with NMIBC who received adjuvant intravesical chemotherapy after TUR in Neijiang First People's Hospital (Neijiang, China) between January 2010 and June 2019 were retrospectively reviewed. The sexual function of these patients was evaluated before and 1.5 years after initial TUR by the International Index of Erectile Function-5 (IIEF-5). An age-specific subanalysis was performed among the patients: <45 years old (Group 1, n = 19) and ≥45 years old (Group 2, n = 146). Before and 1.5 years after TUR, the incidence rates of ED in Group 1 were 15.8% and 52.6%, and those in Group 2 were 54.1% and 61.0%, respectively. The difference between groups was statistically significant at the preoperative stage (15.8% vs 54.1%, P = 0.002) but not at the postoperative stage (52.6% vs 61.0%, P = 0.562). Compared with the preoperative stage, the incidence of ED at the postoperative stage was increased significantly in Group 1 (15.8% vs 52.6%, P = 0.017) but not in Group 2 (54.1% vs 61.0%, P = 0.345). In conclusion, the incidence of ED increased in male NMIBC patients under the age of 45 years after TUR in China. These patients should be offered professional counseling during the follow-up period.
Administration, Intravesical ; Erectile Dysfunction ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Retrospective Studies ; Urinary Bladder Neoplasms

Bladder cancer is one of the common malignant tumors in China, with 75% of bladder cancer being non-muscle invasion with a high recurrence rate after surgery. Intravesical therapy is an useful methods to either directly kill tumor cells by infusing cytotoxic drugs into the bladder or directly or indirectly induce local immune responses of the body through infusing immune agents, such as bacillus calmette guerin, and thus reduce the risk of tumor recurrence and progression. In 2019, the Urological Chinese Oncology Group issued the "Expert consensus on intravesical therapy on non-muscle invasive bladder cancer" . Recently, great progress in the clinical diagnosis and treatment of non-muscle invasive bladder cancer has been achieved domestically and abroad, including the risk assessment of non-muscle invasive bladder cancer, the therapeutic choice of intravesical drugs, the adverse reactions and treatment experience of intravesical therapy, and clinical research on new types of intravesical drugs. This consensus is made according to domestic and overseas evidence-based medicine in combination with current clinical practice and experience of intravesical therapy for non-muscle invasive bladder cancer in China. It is an update of the 2019 expert consensus, with the wish to provide a guidance for domestic clinical standardized intravesical therapy for non-muscle invasive bladder cancer.
Adjuvants, Immunologic/therapeutic use* ; Administration, Intravesical ; Consensus ; Humans ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/drug therapy* ; Urinary Bladder Neoplasms/drug therapy*

Although intravesical instillation of Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most successful cancer immunotherapy for superficial bladder cancer, the serious side effects are frequently arisen by using live mycobacteria. To allow less toxic and more potent immunotherapeutic agents following intravesical BCG treatment for superficial bladder cancer, noninfectious immunotherapeutic drug instead of live BCG would be highly desirable. Recently, immune-enhancing adjuvants are considered an effective vaccine immunotherapy for cancer, providing enhanced antitumor effects and boosted immunity. The BCG-cell wall skeleton (BCG-CWS), the main immune active center of BCG, is a potent candidate as a noninfectious immunotherapeutic drug instead of live BCG against bladder cancer. However, the most limited application for anticancer therapy, it is difficult to formulate a water-soluble BCG-CWS due to the aggregation of BCG-CWS in both aqueous and nonaqueous solvents. To overcome the insolubility and improve the internalization of BCG-CWS into bladder cancer cells, it should be developed the lipid nanoparticulation of BCG-CWS, resulting in improved dispensability, stability, and small size. In addition, powerful technology of delivery systems should be applied to enhance the internalization of BCG-CWS, such as encapsulated into lipid nanoparticles using novel packaging methods. Here, we describe the progress in research on effects of BCG-CWS for cancer immunotherapy, development of lipid-based solvent, and packaging method using nanoparticles with drug delivery system.
Administration, Intravesical ; Bacillus ; Cell Wall Skeleton ; Drug Delivery Systems ; Immunotherapy ; Methods ; Mycobacterium bovis ; Nanoparticles ; Product Packaging ; Skeleton ; Solvents ; Urinary Bladder Neoplasms ; Urinary Bladder

PURPOSE: Poloxamer 407 (P407) thermo-sensitive hydrogel formulations were developed to enhance the retention time in the urinary bladder after intravesical instillation. MATERIALS AND METHODS: P407 hydrogels (P407Gels) containing 0.2 w/w% fluorescein isothiocyanate dextran (FD, MW 4 kDa) as a fluorescent probe were prepared by the cold method with different concentrations of the polymer (20, 25, and 30 w/w%). The gel-forming capacities were characterized in terms of gelation temperature (G-Temp), gelation time (G-Time), and gel duration (G-Dur). Homogenous dispersion of the probe throughout the hydrogel was observed by using fluorescence microscopy. The in vitro bladder simulation model was established to evaluate the retention and drug release properties. P407Gels in the solution state were administered to nude mice via urinary instillation, and the in vivo retention behavior of P407Gels was visualized by using an in vivo imaging system (IVIS). RESULTS: P407Gels showed a thermo-reversible phase transition at 4℃ (refrigerated; sol) and 37℃ (body temperature; gel). The G-Temp, G-Time, and G-Dur of FD-free P407Gels were approximately 10℃–20℃, 12–30 seconds, and 12–35 hours, respectively, and were not altered by the addition of FD. Fluorescence imaging showed that FD was spread homogenously in the gelled P407 solution. In a bladder simulation model, even after repeated periodic filling-emptying cycles, the hydrogel formulation displayed excellent retention with continuous release of the probe over 8 hours. The FD release from P407Gels and the erosion of the gel, both of which followed zero-order kinetics, had a linear relationship (r²=0.988). IVIS demonstrated that the intravesical retention time of P407Gels was over 4 hours, which was longer than that of the FD solution ( < 1 hour), even though periodic urination occurred in the mice. CONCLUSIONS: FD release from P407Gels was erosion-controlled. P407Gels represent a promising system to enhance intravesical retention with extended drug delivery.
Administration, Intravesical* ; Animals ; Dextrans ; Drug Liberation ; Fluorescein ; Hydrogel* ; Hydrogels* ; In Vitro Techniques ; Kinetics ; Methods ; Mice* ; Mice, Nude ; Microscopy, Fluorescence ; Optical Imaging ; Phase Transition ; Poloxamer* ; Polymers ; Urinary Bladder* ; Urination

PURPOSE: This study aimed to evaluate the prognostic significance of smoking status in muscle invasive bladder cancer (MIBC) and non-MIBC in recurrence-free (RFS), progression-free (PFS), disease-free survival (DFS), and cancer-specific survival (CSS). MATERIALS AND METHODS: We retrospectively evaluated 541 patients with MIBC and non-MIBC who were surgically treated during 2002–2013. Smoking status was defined as never smokers (NS; n=160, 30%), former smokers (FS; smoking cessation for ≥1 year, n=176, 33%), and current smokers (CS; >100 cigarettes, n=198, 37%). We statistically compared these groups' clinicopathological facCtors for the predictive factors for RFS and PFS for non-MIBC (NMIBC) and DFS for MIBC, and CSS using multivariate model. RESULTS: The CS, FS, and NS groups exhibited insignificantly different pathological staging, grades, and immunohistological characteristics (p>0.05). Among the 441 patients with NMIBC, pathologic tumor size was a significant risk factor for RFS (1–3 cm: hazard ratio [HR], 1.88; >3 cm: HR, 2.21; p < 0.05); age (HR, 1.06), intravesical therapy (HR, 0.25), and high-grade cancer (HR, 8.33) significant for PFS; and age (HR, 1.08), intravesical instillation (HR, 0.26), and smoking status (FS: HR, 0.40; CS: HR, 0.44) significant for CSS (p < 0.05). The 93 patients with MIBC had no significant risk factors for DFS, although their significant risk factors for CSS were age (HR, 1.05), female sex (HR, 2.64), and carcinoma in situ (HR, 4.72) (p < 0.05). CONCLUSIONS: Smoking status only significantly affected CSS in patients with NMIBC.
Administration, Intravesical ; Carcinoma in Situ ; Disease-Free Survival ; Female ; Humans ; Muscles ; Prognosis ; Retrospective Studies* ; Risk Factors ; Smoke* ; Smoking Cessation ; Smoking* ; Tobacco Products ; Urinary Bladder Neoplasms* ; Urinary Bladder*

PURPOSE: To evaluate the early histological effects of the intravesical instillation of platelet-rich plasma (PRP) in rabbit models of interstitial and hemorrhagic cystitis. METHODS: Thirty-six rabbits were classified into 6 groups: saline (S), S+PRP, hydrochloric acid (HCl), HCl+PRP, cyclophosphamide (CyP), and CyP+PRP. At 48 hours after induction, PRP was prepared and intravesically administered to the S+PRP, HCl+PRP, and CyP+PRP groups. Bladder sections were stained with toluidine blue for mast cell counting and with hematoxylin and eosin for histopathology and mitotic index determination. The proliferation index was determined by proliferating cell nuclear antigen (PCNA) immunolabeling. The nonparametric Mann-Whitney U-test was used for statistical analysis. RESULTS: No abnormalities were observed in the S group, whereas increased interstitial edema and increased average mitotic and proliferation indices were observed in the S+PRP group (P=0.023, P=0.004, and P=0.009, respectively). Intense epithelial loss, hemorrhage, and leukocyte infiltration were detected in the HCl and HCl+PRP groups, whereas a significantly increased average mitotic index was observed in the HCl+PRP group (P=0.002). When compared with its CyP counterpart, a significant reduction in hemorrhage and an increase in leukocyte infiltration and mitotic index were observed in the CyP+PRP group (P=0.006, P=0.038, and P=0.002, respectively). In addition, PCNA staining revealed a significantly increased proliferation index in the HCl+PRP and CyP+PRP groups (P=0.032 and P=0.015, respectively). CONCLUSIONS: The intravesical instillation of PRP increased the mitotic index in the saline and cyclophosphamide groups while decreasing macroscopic bleeding.
Administration, Intravesical* ; Cyclophosphamide ; Cystitis* ; Cystitis, Interstitial ; Edema ; Eosine Yellowish-(YS) ; Hematoxylin ; Hemorrhage ; Hydrochloric Acid ; Leukocytes ; Mast Cells ; Mitotic Index ; Platelet-Rich Plasma* ; Proliferating Cell Nuclear Antigen ; Rabbits ; Tolonium Chloride ; Urinary Bladder

The efficacy of intravesical onabotulinumtoxinA (BTXA) in the treatment of overactive bladder (OAB) has been well documented. The use of BTXA injection in orthotopic neobladders is yet to be studied. We present 4 cases of patients injected with intravesical BTXA for overactive orthotopic ileal neobladder. We recorded patient demographics, presenting and follow-up symptoms, urodynamic profiles, and Patient Global Impression of Improvement (PGI-I) scores. The 4 patients reported varying degrees of subjective improvements in the symptoms, including urgency, urge incontinence, and pad usage. Mean follow-up duration was 8.3 months (range, 5-14 months). Average PGI-I score was 3 ("a little better") (range, 2-4). To our knowledge, the current study is the first case series examining BTXA injection for orthotopic neobladder overactivity. BTXA injection yielded varying degrees of objective and subjective improvements, without significant complications. Intravesical BTXA injection is feasible and may be considered as a potential treatment alternative for OAB in orthotopic neobladders, although further study is warranted.
Administration, Intravesical ; Demography ; Follow-Up Studies ; Humans ; Urinary Bladder, Overactive ; Urinary Diversion ; Urinary Incontinence, Urge ; Urinary Reservoirs, Continent ; Urodynamics

Overactive bladder (OAB) is a symptom-driven condition characterized by urinary urgency with or without urinary incontinence and a common problem that can significantly affect quality of life. Drugs that prevent acetylcholine-mediated involuntary detrusor contractions are the mainstay of OAB treatment, but several alternative therapeutic options have become established treatments for OAB. Mirabegron (a β3-adrenoceptor agonist) has a different mechanism of action from antimuscarinic agents. Recently published randomized controlled trials have shown that mirabegron is an effective and safe drug for the symptomatic treatment of OAB patients. Mirabegron represents a valid option both for patients with OAB who are antimuscarinics treatment-naïve, as well as for those who are unresponsive or intolerant to antimuscarinics. Intravesical injection of botulinum toxin A is an effective treatment for OAB that is refractory to antimuscarinics. Treatment with botulinum toxin A showed clinically relevant improvement in all OAB symptoms and health-related quality of life. It was generally well tolerated by most patients, and most treatment-related complications were acceptable. However, increased risk of a larger volume of post-void residual urine was noted in several patients and the possibility of chronic catheterization requires careful evaluation before treatment. In sum, recent options for management of OAB, mirabegron and intravesical injection of botulinum toxin A, expand the treatment options for the optimal treatment of each patient.
Administration, Intravesical ; Botulinum Toxins* ; Catheterization ; Catheters ; Drug Therapy* ; Humans ; Muscarinic Antagonists ; Quality of Life ; Urinary Bladder, Overactive* ; Urinary Incontinence