OBJECTIVE: To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells. METHODS: For in vitro experiments, T24 cells were stimulated with Andro (0-40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting. RESULTS: Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01). CONCLUSIONS Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.
Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Diterpenes/therapeutic use* ; Humans ; Mice ; NF-kappa B/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Urinary Bladder Neoplasms/drug therapy*

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*

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

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*

Bilateral renal obstruction is a rare critical condition, requiring a prompt diagnostic approach and treatment to restore the renal function. The most commonly observed obstructive uropathy in children is congenital malformation, such as posterior urethral valves and bilateral ureteropelvic junction obstruction. Malignant pelvic masses obstructing the ureter are widely reported in adults but are rarely observed in children. The treatment of ureteral obstruction related to pelvic malignancy is a therapeutic challenge with a median survival duration of 3–7 months in adults; however, pediatric patients with pelvic malignancy leading to ureteral obstruction had better outcomes, with a reported 5-year mortality rate of 20%, than the adult patients. Here, we report a rare case of bilateral ureteral obstruction associated with pelvic rhabdomyosarcoma presenting with acute kidney injury treated by ureteral diversion with double J stent, and concommittent emergency hemodialysis, leading to restoration of good renal function. We suggest that bilateral ureteral obstruction should be released as soon as possible using surgical or interventional approach to minimize the obstruction period, and subsequential chemotherapy may contribute to improvement of survival and recovery of renal function.
Acute Kidney Injury ; Adult ; Child ; Drug Therapy ; Emergencies ; Humans ; Mortality ; Pelvic Neoplasms ; Prognosis ; Renal Dialysis ; Rhabdomyosarcoma ; Stents ; Ureter ; Ureteral Obstruction ; Urinary Bladder Neck Obstruction

Diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI), specifically arising in ileal neobladder, is a rare neoplasm. We present an unusual case of Epstein–Barr virus (EBV)–positive DLBCL-CI arising within neobladder with detailed clinical, histological, and immunophenotypical features in an immunocompetent patient. An 88-year-old male was admitted for gross hematuria. He had undergone radical cystectomy and ileal neobladder 17 years ago for invasive bladder cancer. Computed tomography showed enhancing lesions on dome and posterior wall of neobladder with mucosal thickening and multiple enlarged retroperitoneal lymphadenopathies. Transurethralresection of neobladder lesion revealed the diffuse infiltration of large lymphoid cells which were positive for CD20, CD30, and multiple myeloma oncogen-1 with EBV-encoded small RNAs co-localizing, and diagnosis of EBV-positive DLBCL-CI was made. After multi-agent chemotherapy, the lesion disappeared. We suggest that clinicians should consider the possibility of DLBCL-CI in patients presented with hematuria during follow-up after bladder reconstruction.
Aged, 80 and over ; B-Lymphocytes ; Cystectomy ; Diagnosis ; Drug Therapy ; Follow-Up Studies ; Hematuria ; Humans ; Inflammation ; Lymphocytes ; Lymphoma, B-Cell ; Male ; Multiple Myeloma ; RNA ; Urinary Bladder ; Urinary Bladder Neoplasms

BACKGROUND/AIMS: Because of rarity, role of chemotherapy of bladder adenocarcinoma are still unidentified. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of bladder adenocarcinoma. METHODS: Eligible patients for this retrospective analysis were initially diagnosed with bladder adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up. RESULTS: We retrospectively reviewed 29 patients, who were treated with chemotherapy for bladder adenocarcinoma at 10 Korean medical institutions from 2004 to 2014. The median age of patients was 58 years (range, 17 to 78) and 51.7% of the patients were female. Urachal adenocarcinoma was identified in 15 patients. Of 27 symptomatic patients, 22 experienced gross hematuria. Twelve patients were treated with 5-f luorouracil based chemotherapy, five were gemcitabine based, three were taxane and others. Thirteen of them achieved complete response (10.3%) or partial response (34.5%). Median progression-free survival (PFS) and overall survival (OS) for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6) and 24.5 months (95% CI, 1.2 to 47.8), respectively. The cases of urachal adenocarcinoma exhibited worse tendency in PFS and OS (p = 0.024 and p = 0.046, respectively). CONCLUSIONS: Even though bladder adenocarcinoma had been observed moderate effectiveness to chemotherapy, bladder adenocarcinoma is a highly aggressive form of bladder cancer. PFS and OS were short especially in urachal carcinoma.
Adenocarcinoma* ; Diagnosis ; Disease-Free Survival ; Drug Therapy* ; Female ; Follow-Up Studies ; Gynecology* ; Hematuria ; Humans ; Recurrence ; Retrospective Studies* ; Urinary Bladder Neoplasms ; Urinary Bladder*

This article reviewed new trends and controversial issues, including the intensification of chemotherapy and recent brachytherapy (BT) advances, and also reviewed recent consensuses from different societies on the management of locally advanced cervical cancer (LACC). Intensive chemotherapy during and after radiation therapy (RT) was not recommended as a standard treatment due to severe toxicities reported by several studies. The use of positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for pelvic RT planning has increased the clinical utilization of intensity-modulated radiation therapy (IMRT) for the evaluation of pelvic lymph node metastasis and pelvic bone marrow. Recent RT techniques for LACC patients mainly aim to minimize toxicities by sparing the normal bladder and rectum tissues and shortening the overall treatment time by administering a simultaneous integrated boost for metastatic pelvic lymph node in pelvic IMRT followed by MRI-based image guided adaptive BT.
Bone Marrow ; Brachytherapy ; Consensus ; Drug Therapy ; Electrons ; Humans ; Lymph Nodes ; Magnetic Resonance Imaging ; Neoplasm Metastasis ; Pelvic Bones ; Radiotherapy, Intensity-Modulated ; Rectum ; Urinary Bladder ; Uterine Cervical Neoplasms

BACKGROUND: To investigate the clinicopathological characteristics of urinary bladder tumors, a rare malignancy, in patients 20 years or younger. METHODS: Using a retrospective chart review among patients who received bladder surgery at 2 institutions between July 1996 and January 2013, we analyzed the clinicopathological characteristics of urinary bladder tumors in 21 pediatric patients (male:female = 4.25:1.00; mean age, 12.1 years). RESULTS: Pathology revealed 9 urothelial tumors, 6 rhabdomyosarcomas, 1 low-grade leiomyosarcoma, 1 large cell neuroendocrine carcinoma, 1 inflammatory myofibroblastic tumor, and 3 cases of chronic inflammation without tumors (including 1 xanthogranulomatous inflammation). Urothelial tumors (mean patient age, 16.0 years) were benign or low-grade; and only transurethral resection of the bladder tumor was necessary for treatment. Patients with rhabdomyosarcomas (mean age, 5 years) underwent radiotherapy (if unresectable) or transurethral resection of the bladder tumor (if resectable), after chemotherapy. Of these patients, 2 underwent radical cystectomy, with the remaining patients not receiving a cystectomy. With the exception of one patient, all patients are currently alive and recurrence-free. CONCLUSION: Urothelial tumors were the most commonly found pediatric bladder tumor, with embryonal rhabdomyosarcoma being the second most common. Urothelial tumors are common in relatively older age. Since urothelial tumors in children typically have a good prognosis and rarely recur, transurethral resection of the bladder tumor is the treatment of choice. Rhabdomyosarcomas are common in younger patients. Since rhabdomyosarcoma is generally chemosensitive, chemotherapy and radiotherapy are the treatment of choice for bladder preservation in these patients.
Carcinoma, Neuroendocrine ; Child ; Cystectomy ; Drug Therapy ; Humans ; Inflammation ; Leiomyosarcoma ; Myofibroblasts ; Pathology ; Prognosis ; Radiotherapy ; Retrospective Studies ; Rhabdomyosarcoma ; Rhabdomyosarcoma, Embryonal ; Urinary Bladder Neoplasms ; Urinary Bladder*

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