Endoscopic Intravesical Fibrin Glue Application in the Treatment of Refractory Hemorrhagic Radiation Cystitis: A Single Cohort Pilot Study.

OBJECTIVE: To evaluate the clinical value of endoscopic fibrin glue (FG) application therapy in treating hemorrhagic radiation cystitis (HRC). PATIENTS AND METHODS: This is a single-cohort, prospective pilot study. We collected data from patients with HRC who were treated at our urology unit from May 2014 to December 2016. Patients with grade ≥2 HRC for whom conventional therapy and transurethral endoscopic electrocoagulation had failed were treated with endoscopic intravesical FG. The mean follow-up was 26.2 ± 9.78 months. Our analysis included data on patient demographics, pelvic malignancies, radiotherapy regimens, total dose of radiation received, time of onset and severity of hematuria, and previous intravesical management. Following FG intervention, patients' clinical status was defined as: (1) clinical response; absence of dysuria, urgency, and frequency; discontinuation of analgesic medication; and Foley catheter removal, but with ongoing hematuria grade <2; (2) complete response, clinical response, and no further hematuria; or (3) no response, no clinical response, and sustained hematuria. RESULTS: A total of 20 patients (12 women and 8 men; mean age, 69 ± 7.5 years) were treated with 12 mL FG intravesically, using endoscopic application. Of the 20 patients, 16 (80%) had a complete response and 4 (20%) had a clinical response. In the case of four patients (20%), treatment was carried out twice. Mean hospital stay was 6 ± 2.5 days. The intervention showed good tolerability in all patients. No major adverse events were reported. Bladder spasms were the only minor adverse events reported in six patients (30%). CONCLUSION: Application of FG is an effective, practical, affordable, and repeatable procedure for the treatment of grade ≥2 HRC.

Keap1/Nrf2 pathway in kidney cancer: frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma.

The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal cell carcinoma (RCC), but data concerning the molecular basis and the clinical effect of its deregulation remain incomplete.Here we present a molecular profiling of the KEAP1 and NFE2L2 genes in five different Renal Cell Carcinoma histotypes by analysing 89 tumor/normal paired tissues (clear cell Renal Carcinoma, ccRCCs; Oncocytomas; Papillary Renal Cell Carcinoma Type 1, PRCC1; Papillary Renal Cell Carcinoma Type 2, PRCC2; and Chromophobe Cell Carcinoma).A tumor-specific DNA methylation of the KEAP1 gene promoter region was found as a specific feature of the ccRCC subtype (18/37, 48.6%) and a direct correlation with mRNA levels was confirmed by in vitro 5-azacytidine treatment. Analysis of an independent data set of 481 ccRCC and 265 PRCC tumors corroborates our results and multivariate analysis reveals a significant correlation among ccRCCs epigenetic KEAP1 silencing and staging, grading and overall survival.Our molecular results show for the the first time the epigenetic silencing of KEAP1 promoter as the leading mechanism for modulation of KEAP1 expression in ccRCCs and corroborate the driver role of Keap1/Nrf2 axis deregulation with potential new function as independent epigenetic prognostic marker in renal cell carcinoma.

Fibrin glue therapy for severe hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

Hemorrhagic cystitis (HC) occurring after allogeneic transplantation significantly affects quality of life and, in some cases, becomes intractable, increasing the risk of death. To date, its therapy is not established. We used the hemostatic agent fibrin glue (FG) to treat 35 patients with refractory post-transplantation HC. Of 322 adult patients undergoing an allogeneic transplantation for hematological malignancy, 35 developed grade ≥ 2 HC refractory to conventional therapy and were treated with FG, diffusely sprayed on bleeding mucosa by an endoscopic applicator. The cumulative incidence of pain discontinuation and complete remission, defined as regression of all symptoms and absence of hematuria, was 100% at 7 days and 83% ± 7%, respectively, at 50 days from FG application. The 6-month probability of overall survival for all 35 patients and for the 29 in complete remission was 49% ± 8% and 59% ± 9%, respectively. In the matched-pair analysis, the 5-year probability of overall survival for the 35 patients with HC and treated with FG was not statistically different from that of the comparative cohort of 35 patients who did not develop HC (32% ± 9% versus 37% ± 11%, P = not significant). FG therapy is a feasible, effective, repeatable, and affordable procedure for treating grade ≥2 HC after allogeneic transplantation.

Early and late urodynamic assessment of Padua ileal bladder.

OBJECTIVES: To report the data from a single series of 46 patients who underwent cystectomy and Padua ileal bladder (PIB) substitution during a 48-month period. Data are lacking concerning the changes in urodynamic characteristics of the orthotopic ileal neobladder. METHODS: From January 2002 to April 2003, 46 consecutive male patients underwent radical cystectomy and PIB substitution for muscle-invasive bladder cancer. Uroflowmetry, cystometry, and urethral pressure profilometry were analyzed at 12 and 48 months after surgery. All patients were asked to complete a questionnaire regarding quality of life (the European Organization for Cancer Research and Treatment of Cancer Quality of Life Questionnaire and the bladder cancer-specific module). RESULTS: Of the 46 patients, 8 were lost to follow-up because of cancer-related death. When comparing the 12- and 48-month urodynamic characteristics, no significant changes were observed in cystometric capacity or urethral closing pressure. However, the end-filling pressure, peak flow pressure, and postvoid residual urine volume were significantly lower at the 48-month evaluation (P = .0005, P = .0007, and P = .013, respectively). The number of involuntary contractions at 48 months had increased significantly (P = .0012), and the amplitude of the contractions was comparable (P = .084). The daytime continence rate was 96% and 90% at 12 and 48 months, respectively. The nighttime continence rate was 60% at the 48-month evaluation. The questionnaires about the quality of life highlighted the excellent results. CONCLUSIONS: An ileal tone is maintained despite detubularization and most likely prevents enlargement of the neobladder. PIB was revealed to maintain an adequate capacity and low pressure during a 48-month period. The urodynamics results and quality of life support this urinary diversion as a valid treatment option for muscle-invasive bladder cancer.

Bacteriuria in patients with an orthotopic ileal neobladder: urinary tract infection or asymptomatic bacteriuria?

OBJECTIVE: To investigate the prevalence of asymptomatic bacteriuria (ABU) and urinary tract infection (UTI), and the local and systemic inflammatory response, in patients with ileal neobladder. PATIENTS AND METHODS: The study included 40 patients who had a radical cystectomy and ileal neobladder. Two urine samples, one for chemical and physical analysis, and cytofluorimetry, and one for urine culture, were collected every 3 months for 9 months after surgery. RESULTS: Of 119 urine cultures, 69 (57%) were positive for bacteria. Only nine of the 40 patients had no bacteriuria on urine culture. Escherichia coli strains were cultured from eight of 10 patients with persistently positive urine. The incidence of bacteriuria was different according to gender. There was a high concentration of leukocytes (0-6 microL) in 118 of 119 samples. The mean concentration of leukocytes in sterile urine culture was 1181/microL, while in patients with ABU the mean was 491 (P < 0.05). CONCLUSION: A positive urine culture is a very common finding in patients with an orthotopic bladder. The most interesting results was the absence of elevated inflammatory indices and/or symptoms, even in those patients with high levels of bacteriuria. Probably this is due to the completely different inflammatory response of ileal mucosa against bacteria than has bladder mucosa. Indeed, the leukocyte concentration detected in urinary sediment was inversely association with bacterial growth in urine cultures. These findings suggest a redefinition of ABU and UTI in patients with an orthotopic neobladder.