OBJECTIVE: Immune checkpoint inhibitors (ICI) have significantly improved the treatment efficacy of a variety of malignant tumors. However, patients may experience a series of special side effects during treatments with ICI. Immune-related myositis after ICI treatment is characterized by autoimmune rheumatic and musculoskeletal damage, which is relatively rare. To analyze the clinical characteristics and outcomes of ICI-associated myositis in urological tumors, we summarized the clinical manifestations, electrophysiological and pathological characteristics, treatments and outcomes in 8 patients. METHODS: The clinical data of the 8 patients with immune-related myositis after ICI treatment for urological tumors treated in the Department of Urology, Peking University First Hospital from March 2018 to March 2022 were retrospectively analyzed for demographic characteristics, drug regimen, clinical symptoms, laboratory indices, electromyography examination, pathological manifestations and outcomes. RESULTS: The eight patients included 2 females and 6 males with a median age of 68 years, all treated with ICI for urological neoplasms, including 2 upper tract urothelial carcinoma (UTUC), 3 renal cell carcinoma (RCC), and 3 bladder cancer (BCa). The median time between the first ICI treatment and the detection of immune-related myositis was 39.5 days, and the median duration of treatment was 2 sessions. The main symptoms were muscle pain and weakness, 5 cases with ptosis, 3 cases with secondary rhabdomyolysis, 5 cases with myocarditis, 1 case with myasthenia gravis, and 1 case with enterocolitis. Among them, patients with immune-related myocarditis had a shorter interval from the first anti-programmed cell death protein-1 (PD-1) therapy to the onset of immune-related myositis (P=0.042) compared with patients without myocarditis. The 8 patients had significant elevation of transaminases and muscle enzyme profile indexes, and 5 patients showed positive auto-antibodies. 3 patients had perfected muscle biopsies and showed typical skeletal muscle inflammatory myopathy-like pathological changes with CD3⁺, CD4⁺, CD8⁺, CD20⁺ lymphocytes and CD68⁺ macrophage infiltration. After the diagnosis of immune-related myositis, all the 8 patients immediately discontinued ICI therapy and improved after intravenous administration of methylprednisolone alone or in combination with gamma-globulin. CONCLUSION Immune-related myositis after ICI treatment is an immune-related adverse reactions (irAEs) with unique clinical and pathological features, commonly combined with cardiovascular adverse reactions. Immediate discontinuation of ICI and initiation of glucocorticoid therapy may improve the patient's condition in a timely manner.
Aged ; Antineoplastic Agents, Immunological/adverse effects* ; Carcinoma, Transitional Cell ; Female ; Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Kidney Neoplasms/drug therapy* ; Male ; Myocarditis/drug therapy* ; Myositis/pathology* ; Retrospective Studies ; Urinary Bladder Neoplasms

PURPOSE: OnabotulinumtoxinA has demonstrated efficacy and safety in the treatment of urinary incontinence (UI) associated with neurogenic detrusor overactivity (NDO) and idiopathic overactive bladder (OAB); however, real-world evidence is limited. This postmarketing surveillance study aimed to assess the effectiveness and safety of onabotulinumtoxinA in Korean patients with UI associated with NDO or OAB with an inadequate response or intolerance to anticholinergics. METHODS: Patients received 200 U (NDO) or 100 U (OAB) of onabotulinumtoxinA. Effectiveness (assessed using the validated International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF]) and safety were assessed for 1–4 months after onabotulinumtoxinA administration. RESULTS: Overall, 686 patients (NDO, 161; OAB, 525) comprised the safety population; of these, 612 patients were analyzed for effectiveness. There was a significant decrease (P<0.0001) in the mean (standard deviation) ICIQ-SF scores in the NDO (–6.8±5.5) and OAB (–6.0±6.4) groups after onabotulinumtoxinA administration. A decrease of >5 points from baseline in the ICIQ-SF score was observed in 64.9% and 47.3% of patients in the NDO and OAB groups, respectively. Following treatment, 59.9% in the NDO group and 43.0% in the OAB group were dry. There was no effect of age on effectiveness in either group. Only 10 adverse drug reactions (ADRs) were reported in 5.6% of NDO patients and 20 ADRs in 3.2% of OAB patients. Most ADRs in both groups were related to the lower urinary tract such as dysuria (NDO, 1.2%; OAB, 0.6%) and urinary retention (NDO, 0.6%; OAB, 1.5%). CONCLUSIONS: Effectiveness and safety of onabotulinumtoxinA in Korea in a real-world setting was demonstrated.
Cholinergic Antagonists ; Drug-Related Side Effects and Adverse Reactions ; Dysuria ; Humans ; Korea ; Outcome Assessment (Health Care) ; Urinary Bladder, Neurogenic ; Urinary Bladder, Overactive ; Urinary Incontinence ; Urinary Retention ; Urinary Tract

Aged ; China ; Humans ; Ileum ; surgery ; Male ; Middle Aged ; Treatment Outcome ; Urinary Bladder Neoplasms ; surgery ; Urinary Diversion ; adverse effects ; Urinary Incontinence ; diagnosis ; drug therapy ; surgery ; therapy ; Urinary Reservoirs, Continent

Urinary tract infection (UTI) is one of the most common complications after radical cystectomy and orthotopic neobladder reconstruction. This study investigated the incidence and implicated pathogen of febrile UTI after ileal neobladder reconstruction and identify clinical and urodynamic parameters associated with febrile UTI. From January 2001 to May 2015, 236 patients who underwent radical cystectomy and ileal neobladder were included in this study. Fifty-five episodes of febrile UTI were identified in 46 patients (19.4%). The probability of febrile UTI was 17.6% and 19.8% at 6 months and 24 months after surgery, respectively. While, Escherichia coli was the most common implicated pathogen (22/55, 40.0%), Enterococcus spp. were the most common pathogen during the first month after surgery (18/33, 54.5%). In multivariate logistic regression analysis, ureteral stricture was an independent risk factor associated with febrile UTI (OR 5.93, P = 0.023). However, ureteral stricture accounted for only 6 episodes (10.9%, 6/55) of febrile UTI. Most episodes of febrile UTI occurred within 6 months after surgery. Thus, to identify risk factors associated with febrile UTI in the initial postoperative period, we assessed videourodynamics within 6 months after surgery in 38 patients. On videourodyamic examination, vesicoureteral reflux (VUR) was identified in 16 patients (42.1%). The rate of VUR presence in patients who had febrile UTI was not significantly different from those in patients without febrile UTI (50% vs. 39.3%, P = 0.556). Patients with febrile UTI had significantly larger residual urine volume (212.0 ± 193.7 vs. 90.5 ± 148.2, P = 0.048) than those without. E. coli and Enterococcus spp. are common pathogens and ureteral stricture and residual urine are risk factors for UTI after ileal neobladder reconstruction.
Aged ; Anti-Bacterial Agents/therapeutic use ; Cystectomy/adverse effects ; Enterococcus/isolation & purification ; Escherichia coli/isolation & purification ; Female ; Humans ; Ileum/*surgery ; Incidence ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Postoperative Complications ; Reconstructive Surgical Procedures ; Retrospective Studies ; Risk Factors ; Urinary Bladder Neoplasms/*surgery ; Urinary Tract Infections/drug therapy/*epidemiology/etiology/microbiology ; Urodynamics

Glucocorticoid receptor (GR) is identified as a member of nuclear receptor family. To exert its biological action, the ligand bound GR is translocated from the cytoplasm into the nucleus by regulating transcriptional signals of related genes. In clinical practice, the effects of glucocorticoid are often mediated by GR signaling pathways. An increasing number of studies have indicated that GR signaling pathways play an essential role in the proliferation, invasion and prognosis of bladder cancer. Meanwhile, the new-generation selective GR activator improves its anti-tumor effects, and at the same time reduces the adverse reactions of hormones, which probably raises the prospect for the treatment of bladder cancer.
Animals ; Antineoplastic Agents ; pharmacology ; Cell Nucleus ; genetics ; Humans ; Prognosis ; Protein Transport ; genetics ; Receptors, Glucocorticoid ; agonists ; physiology ; Signal Transduction ; genetics ; Transcriptional Activation ; drug effects ; physiology ; Urinary Bladder Neoplasms ; genetics ; physiopathology

ObjectiveTo evaluate the effect and safety of phloroglucinol combined with parecoxib on cystospasm after transurethral resection of the prostate (TURP).

METHODSWe conducted a prospective randomized case-control study on 98 patients treated by TURP. After operation, the patients were randomly assigned to a treatment (n=50) and a control group (n=48), the former treated by intravenous injection of 80 mg phloroglucinol qd plus 40 mg parecoxib bid while the latter given 80 mg phloroglucinol only, both for 3 successive days. Then we recorded the frequency and duration of cystospasm, visual analogue scales (VAS), adverse reactions, post-operative bladder irrigation time, catheter-indwelling time, and hospital stay and compared them between the two groups of patients.

RESULTSCompared with the controls, the patients in the treatment group showed a significantly lower frequency of cystospasm (［1.95±0.14］ vs ［0.70±0.65］ times, P<0.01), duration of cystospasm (［0.44±0.21］ vs ［0.12±0.14］ min, P<0.01), and VAS score (2.70±1.80 vs 1.90±1.30, P<0.01) at 48－72 hours after TURP, but no statistically significant differences were found between the control and treatment groups in the post-operative bladder irrigation time (［2.75±0.87］ vs ［2.64±0.83］ d, P>0.05), catheter-indwelling time (［3.52±0.32］ vs ［3.44±0.42］ d, P>0.05), and hospital stay (［5.23±0.81］ vs ［5.10±0.73］ d, P>0.05), and no obvious adverse reactions were observed in either of the two groups.

CONCLUSIONSPhloroglucinol combined with parecoxib is more effective and safer than phloroglucinol alone in relieving postoperative cystospasm after TURP.

Aged ; Case-Control Studies ; Drug Therapy, Combination ; Humans ; Isoxazoles ; administration & dosage ; therapeutic use ; Length of Stay ; Male ; Middle Aged ; Phloroglucinol ; administration & dosage ; therapeutic use ; Postoperative Period ; Prospective Studies ; Prostatic Hyperplasia ; Spasm ; drug therapy ; Therapeutic Irrigation ; Transurethral Resection of Prostate ; Treatment Outcome ; Urinary Bladder ; drug effects ; physiopathology

This study aimed to provide evidence of persistent uropathogenic Escherichia coli (UPEC) in female patients with recurrent urinary tract infection (UTI) after antibiotic therapy. We collected biopsies of the bladder, and clean-catch urine samples from 32 women who had episodes of recurrent UTI and were given antibiotic therapy. Urine samples and biopsies were analyzed by conventional bacteriological techniques. Phylogenetic group and 16 virulence factors (VFs) of UPEC were determined using polymerase chain reaction (PCR). The infection capability of UPEC was confirmed in a mouse model. Immunofluorescence and electron microscopy were used to detect intracellular bacterial communities (IBCs) in the mouse model. The results showed that all urine specimens were detected sterile. E. coli was found in 6 of 32 biopsies (18.75%), and was identified to be UPEC by PCR. Different VFs associated with the formation of IBCs were identified in all six UPEC isolates. Each UPEC isolate was capable of forming IBCs within the bladder epithelial cells of mice. In conclusion, UPEC with distinctive pathological traits and the capability of IBC formation was first found in the bladders of women after antibiotic therapy, suggesting that the IBC pathogenic pathway may occur in humans and it plays an important role in UTI recurrence.
Adult ; Animals ; Anti-Bacterial Agents ; administration & dosage ; Biopsy ; Escherichia coli Infections ; drug therapy ; microbiology ; Female ; Humans ; Mice ; Middle Aged ; Phylogeny ; Urinary Bladder ; drug effects ; microbiology ; pathology ; Uropathogenic Escherichia coli ; drug effects ; genetics ; pathogenicity

OBJECTIVE: To investigate the effect of osthole on epidermal growth factor receptor tyrosine kinase (EGFR-TPK), matrix-metalloproteinase-2 (MMP-2), aminopeptidase N (APN) in bladder cancer cell and the underlying mechanism.
 METHODS: The T24 cell lines were cultured. The inhibitory effects of osthole on EGFR-TPK, APN and MMP-2 were evaluated by spectrophotometric and MTT assay. The caspase-3 activity and the expression COX-2 and VEGF in T24 were examined. The activity of NF-κB was determined by electrophoretic mobility shift assay.
 RESULTS: The half inhibition concentrations (IC50) of osthole on EGFR-TPK, APN and MMP-2 were (45.33±3.98), (28.21±3.23) and (8.11±0.54) µmol/L, respectively. The growth inhibitory rates for T24 cells were increased in a dose-dependent manner (P<0.05). The caspase-3 activities were significantly increased in T24 cells in the osthole group compared with control group, while the expression of angiogenesis related-protein COX-2, VEGF, and NF-κB in T24 cells were decreased.
 CONCLUSION Through the inhibitory effect on EGFR-TPK, APN and MMP-2, osthole can decrease COX-2, VEGF and NF-κB expression while increase the activity of caspase-3, eventually blocking the growth and invasion of bladder cancer cell.
CD13 Antigens ; metabolism ; Caspase 3 ; metabolism ; Cell Line, Tumor ; drug effects ; Coumarins ; pharmacology ; Cyclooxygenase 2 ; metabolism ; ErbB Receptors ; metabolism ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; NF-kappa B ; metabolism ; Urinary Bladder Neoplasms ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVE: To evaluate the multiphase contrast-enhanced magnetic resonance (MR) imaging features of Bacillus Calmette-Guerin (BCG)-induced granulomatous prostatitis (GP). MATERIALS AND METHODS: Magnetic resonance images obtained from five patients with histopathologically proven BCG-induced GP were retrospectively analyzed for tumor location, size, signal intensity on T2-weighted images (T2WI) and diffusion-weighted images (DWI), apparent diffusion coefficient (ADC) value, and appearance on gadolinium-enhanced multiphase images. MR imaging findings were compared with histopathological findings. RESULTS: Bacillus Calmette-Guerin-induced GP (size range, 9-40 mm; mean, 21.2 mm) were identified in the peripheral zone in all patients. The T2WI showed lower signal intensity compared with the normal peripheral zone. The DWIs demonstrated high signal intensity and low ADC values (range, 0.44-0.68 x 10(-3) mm2/sec; mean, 0.56 x 10(-3) mm2/sec), which corresponded to GP. Gadolinium-enhanced multiphase MR imaging performed in five patients showed early and prolonged ring enhancement in all cases of GP. Granulomatous tissues with central caseation necrosis were identified histologically, which corresponded to ring enhancement and a central low intensity area on gadolinium-enhanced MR imaging. The findings on T2WI, DWI, and gadolinium-enhanced images became gradually obscured with time. CONCLUSION: Bacillus Calmette-Guerin-induced GP demonstrates early and prolonged ring enhancement on gadolinium-enhanced MR imaging which might be a key finding to differentiate it from prostate cancer.
Aged ; Gadolinium/*diagnostic use ; Humans ; Image Enhancement ; Immunotherapy/*adverse effects ; Magnetic Resonance Imaging/*methods ; Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Mycobacterium bovis/*pathogenicity ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms/diagnosis ; Prostatitis/*diagnosis ; Retrospective Studies ; Urinary Bladder Neoplasms/drug therapy

To investigate the urination-reducing effect and mechanism of Zhuangyao Jianshen Wan (ZYJCW). In this study, SI rats were subcutaneously injected with 150 mg · kg(-1) dose of D-galactose to prepare the sub-acute aging model and randomly divided into the model group, the Suoquan Wan group (1.17 g · kg(-1) · d(-1)), and ZYJCW high, medium and low dose groups (2.39, 1.20, 0.60 g · kg(-1) · d(-1)) , with normal rats in the blank group. They were continuously administered with drugs for eight weeks. The metabolic cage method was adopted to measure the 24 h urine volume and 5 h water load urine volume in rats. The automatic biochemistry analyzer was adopted to detect urine concentrations of Na+, Cl-, K+. The ELISA method was used to determine serum aldosterone (ALD) and antidiuretic hormone (ADH). The changes in P2X1 and P2X3 mRNA expressions in bladder tissues of rats were detected by RT-PCR. According to the results, both ZYJCW high and medium dose groups showed significant down-regulations in 24 h urine volume and 5 h water load urine volume in (P <0.05, P <0.01), declines in Na+ and Cl- concentrations in urine (P <0.01), notable rises in plasma ALD and ADH contents (P <0.05, P <0.01) and remarkable down-regulations in the P2X1 and P2X3 mRNA expressions in bladder tissues (P <0.01). The ZYJCW low dose group revealed obvious reductions in Na+ and Cl- concentrations in urine (P <0.01). The results indicated that ZYJCW may show the urination-reducing effect by down-regulating the P2X1 and P2X3 mRNA expressions in bladder tissues of rats with diuresis caused by kidney deficiency.
Aging ; physiology ; Animals ; Diuresis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gene Expression Regulation ; Kidney Diseases ; drug therapy ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P2X1 ; genetics ; Receptors, Purinergic P2X3 ; genetics ; Urinary Bladder ; metabolism