Changes in prostaglandin E2 in patients with idiopathic overactive bladder syndrome after botulinum toxin type A treatment: is there a clinical benefit?

BACKGROUND: The causality of overactive bladder syndrome (OAB) is still not fully understood. Several studies indicate a significant increase of prostaglandin E2 (PGE2) in patients with OAB. However, in order to clarify whether these compounds can help to objectify the clinical diagnosis, further studies are needed. This prospective study aims to analyze PGE2 blood levels (sPGE2) in patients with OAB before and after botulinum toxin type A (BoNT-A) therapy. METHODS: Blood samples were obtained from 56 patients (52y, 18-87) with idiopathic OAB. sPGE2 levels were measured before and 4 weeks after BoNT-A treatment by enzyme linked immunosorbent assay (ELISA). 31 healthy persons with normal bladder function served as control group (59 y, 21-72). sPGE2 was set in relation to clinical data and the severity of OAB (wet/dry). The statistical data analysis was performed by using the non-parametric Mann-Whitney U test and paired t-test. RESULTS: Significant higher sPGE2 levels were detected in patients with OAB compared to members of the control group (2750 pg/ml vs. 1674 pg/ml, p < 0.005). Furthermore sPGE2 levels were increased in patients with OAB wet compared to OAB dry (p <0.01). In 30 patients sPGE2 levels decreased significantly after BoNT-A treatment compared to baseline (2995 pg/ml vs. 1486 pg/ml, p <0.005). Patients reported an average drug effect of 9 month (0-19); incontinence pads were needed significantly less frequent (p < 0.05). 3 patients reported no postoperative effect. sPGE2 increased in two patients compared to initial levels, a single patient showed a remotely decreased sPGE2. Six patients were treated repeatedly with BoNT-A after showing an sPGE2 re-rise. CONCLUSIONS: sPGE2-level is increased in patients with OAB. We could prove a significant decrease of sPGE2 after BoNT-A treatment. In this small cohort we could demonstrate a correlation between OAB and sPGE2, especially in the non-responder group. The use of sPGE2 as a biomarker in diagnostics and follow-up after therapy seems promising. To what extent sPGE2 can be useful as such needs to be examined prospectively in a larger population.

TOT approach in stress urinary incontinence (SUI) - outcome in obese female.

BACKGROUND: Only limited data are available on the outcome of tension-free obturator tape (TOT) procedures in overweight and obese women. We would like to verify the objective and subjective outcomes of TOT in women with a higher body mass index (BMI). METHODS: We evaluated the records of 116 patients who had undergone TOT, stratifying by BMI into normal weight (n = 31), overweight (n = 56), and obese (n = 29) groups. We compared pre- and postoperative evaluations, including subjective and objective outcome of TOT, complications, and quality of life assessed by validated questionnaires (ICIQ-SF and KHQ). RESULTS: The median follow-up was 21 months. There were no significant differences between different groups in terms of objective cure rate and subjective success, quality of life scores and postoperative complications. CONCLUSIONS: Our data demonstrate that TOT procedure is safe and effective. BMI did not influence the outcome of TOT procedures at a median of 21 months after surgery and represents no contraindication for continence surgery. The success of the outcome of TOT procedure in females and the occurrence of complications are not negatively affected by obesity.

Antibodies after botulinum toxin A injection into musculus detrusor vesicae: incidence and clinical relevance.

OBJECTIVES: Botulinum toxin A (BTX-A) injection into the detrusor muscle has changed therapy options for patients with overactive bladder (OAB). However, in some patients, therapy fails or the effects of BTX-A decrease. The aim of this prospective study was to evaluate the incidence of BTX-A antibodies (BTX-A Abs) after injection of BTX-A and its clinical relevance. METHODS: 31 patients (27 women, 4 men) were treated with BTX-A for OAB between January 2009 and August 2010. Eleven patients were treated once, 16 patients were treated twice and 4 patients were treated three times. Blood was collected before and 3 months after the BTX-A injection and BTX-A Abs were determined. RESULTS: In 5 patients (16%) BTX-A Abs were detectable after the BTX-A injection. The BTX-A Ab titer was clearly positive in 1 patient (3.2%). This patient showed complete failure of BTX-A therapy. In 4 patients (13%) BTX-A Abs were slightly positive after the first BTX-A injection. The second BTX-A injection showed no positive effects in only 1 patient with borderline BTX-A Ab titers; the second BTX-A injection was successful in 2 patients. CONCLUSIONS: The incidence of BTX-A Abs should be verified in nonresponders. More data are necessary to check the clinical relevance and risk of BTX-A Ab formation, especially in long-term follow-up, to optimize patient selection for this minimally invasive treatment option in OAB.

Urinary collecting system invasion in renal cell carcinoma: incidence and long-term prognosis.

OBJECTIVES: Current data on the prognostic impact of urinary collecting system (UCS) invasion by renal cell carcinoma (RCC) are highly conflicting. The aim of the present study was to assess incidence and long-term prognosis of RCC patients with and without UCS involvement. METHODS: We evaluated 780 patients who had undergone renal surgery between 1990 and 2005. The mean follow-up was 5.44 years. RESULTS: Sixty-seven patients (8.6%) demonstrated UCS invasion. These patients had a significant increase in the likelihood of cancer-related death (hazard ratio [HR] 1.9, 95% confidence interval: 1.4-2.7; P = 0.001). Their median 5-year tumor-specific survival rate was 61%, as opposed to 79% for patients without UCS invasion (P = 0.001). UCS invasion was significantly associated with tumor stage, grade, clinical symptoms, lymph node and visceral metastasis at diagnosis, but not with age, gender, histologic subtype or body mass index. However, by means of multivariate analysis, UCS invasion was disqualified as an individual prognostic marker for RCC. CONCLUSION: We do not advocate the inclusion of UCS invasion into upcoming Tumor-Nodes-Metastasis staging systems. In contrast, future research should focus on the prognostic role of novel molecular tumor markers and/or specific immunological characteristics of RCC patients.

Negative regulation of the mammalian UV response by Myc through association with Miz-1.

The Myc oncoprotein represses initiator-dependent transcription through the POZ domain transcription factor Miz-1. We now show that transactivation by Miz-1 is negatively regulated by association with topoisomerase II binding protein (TopBP1); UV irradiation downregulates expression of TopBP1 and releases Miz-1. Miz-1 binds to the p21Cip1 core promoter in vivo and is required for upregulation of p21Cip1 upon UV irradiation. Using both c-myc(-/-) cells and a point mutant of Myc that is deficient in Miz-1 dependent repression, we show that Myc negatively regulates transcription of p21Cip1 upon UV irradiation and facilitates recovery from UV-induced cell cycle arrest through binding to Miz-1. Our data implicate Miz-1 in a pathway that regulates cell proliferation in response to UV irradiation.