Prospective multicentre randomized double-blind placebo-controlled parallel group study on the efficacy and tolerability of StroVac® in patients with recurrent symptomatic uncomplicated bacterial urinary tract infections.

PURPOSE: To evaluate efficacy and safety of vaccination with StroVac compared to placebo in patients with recurrent urinary tract infections (rUTI). MATERIAL AND METHODS: We performed a prospective, double-blinded, placebo-controlled study in patients with uncomplicated rUTI. Patients received three single intramuscular injections with StroVac every two weeks. Primary endpoint was the number of bacterial urinary tract infections (UTI) over 13.5 months after randomization and adjusted by the respective "baseline" value when comparing verum and placebo group. Secondary endpoints were the number of patients with non-recurrence, time to first recurrence, frequency of recurrences, and patients' self-assessment of quality of life using a validated questionnaire. RESULTS: 376 patients were randomized to both groups between January 2012 and March 2015. Mean age was 44.4 years. Patients were mainly female (98.4%). In the StroVac group (n = 188), the number of UTIs was reduced from 5.5 to 1.2, in the placebo group (n = 188) from 5.4 to 1.3 (p = 0.63). In patients with ≥ 7 UTIs prior to study inclusion, StroVac was statistically significantly superior to placebo (p = 0.048). However, in all other secondary endpoints, no statistical differences between the two groups could be seen (all p > 0.3). CONCLUSION: StroVac reduced the number of clinically relevant UTIs like in former studies but did not show statistically significant better results than the chosen placebo. Most likely, that was due to a, since confirmed, prophylactic effect of the chosen placebo itself. Therefore, placebo-controlled and double-blinded studies using a different ineffective placebo preparation are needed to determine the importance of StroVac in prophylaxis of rUTI.

[Robot-assisted laparoscopic partial nephrectomy: functional and oncological outcomes]. / Robotisch assistierte laparoskopische partielle Nephrektomie : Funktionelle und onkologische Ergebnisse.

BACKGROUND: In recent years, small renal masses (SRM) have been increasingly detected as an incidental finding of radiological or ultrasound studies for other indications. Organ-sparing renal tumor resection as open partial nephrectomy (OPN) is the international standard for renal tumors <7 cm. RESULTS: Due to technical developments, minimally invasive procedures have emerged as an alternative to OPN. In experienced hands, conventional laparoscopic partial nephrectomy (LPN) has achieved good functional and oncological results comparable to OPN. Robot-assisted laparoscopic partial nephrectomy (RAPN) has been performed since 2004. Compared to LPN, RAPN provides a faster learning curve, better visualization and more versatile instrumentation due to the degrees of freedom of the articulated instruments. After about 30 procedures, a level of experience is reached, which is characterized by good functional results, less blood loss, and shorter warm ischemia time of the kidney as compared to LPN. This can relate to a shorter hospital stay and faster recovery. Complications according to the Clavien classification are mostly grade I and II and are mainly treated conservatively. CONCLUSION: Oncological long-term results are not available yet; so that RAPN cannot be considered as an equivalent treatment to LPN and OPN. Until long-term evidence is available, decisions regarding the surgical technique for organ-sparing renal tumor resection will be determined by patient's wishes and surgeon's preference.

Robot-Assisted Transvesical Enucleation of Benign Prostatic Hyperplasia: Lessons from a Single Surgeon's Learning Curve.

INTRODUCTION: Open simple prostatectomy is a well-established and effective operation for prostate volumes greater than 80 gm but also associated with bleeding and urinary incontinence. To benefit from the advances of laparoscopy, robot-assisted simple prostatectomy was established. We determined the learning curve of this minimally invasive surgery by evaluating the first procedures by an experienced robotic surgeon. METHODS: Patients presenting for surgical therapy with prostate volumes greater than 80 gm were considered for the study. Evaluation included validated questionnaires preoperatively, and at 6 and 12 weeks postoperatively. Blood loss, transfusions, operation time and pad use after catheter removal were documented. The experience based on the results from 18 cases treated with robot-assisted simple prostatectomy by one of us (JWT) is presented. RESULTS: Mean age of the 18 patients was 71.2 years, mean enucleated prostate volume was 91 gm and mean preoperative flow was 9.0 ml/second. I-PSS and QoL values improved significantly from 25 to 6.1 (p <0.005) and from 5 to 1.1 (p <0.005), respectively, and flow rate increased to 28.2 ml/second (p <0.005) postoperatively. There were no significant changes in sexual performance based on IIEF (p = 0.73). Of the 18 patients 14 had complete continence immediately after catheter removal, and at 6 weeks postoperatively 17 were completely continent. Decreases in operation time from 250 to 150 minutes and blood loss from 400 to 200 ml were noted after 5 procedures. Only minor complications occurred and 1 patient required transfusion postoperatively (Clavien-Dindo II). CONCLUSIONS: Robot-assisted simple prostatectomy is a safe and effective operation for benign prostatic hyperplasia, which can be learned with good results in a rather short time.

[Partial nephrectomy - pro robotic assisted laparoscopic operation]. / Partielle Nephrektomie - pro robotisch assistierte laparoskopische Operation.

An ever increasing use of imaging in medicine during recent years has resulted in accidental detection of an increasing number of asymptomatic small renal masses. To prevent secondary cardiovascular morbidity through loss of renal function, nephron-sparing surgery is performed for most of these masses. Minimally invasive surgery is a way to prevent postoperative complications, such aspneumonia and pain by avoiding wide incisions and by earlier mobilization of the patient. Since 2004 robotic-assisted laparoscopic nephron-sparing surgery has become a feasible alternative. It shows good functional results, less blood loss and shorter warm ischemia time compared to conventional laparoscopy. The complications can be assigned to Clavien scale grades I and II and can be treated conservatively in most cases. New surgical techniques reduce the number of tumors that cannot be operated on robotically because of size and location of the tumor. Robotic-assisted laparoscopic nephron-sparing surgery is a safe and useful alternative to conventional laparoscopy and open surgery for small renal masses.

MAPK-ERK activation in kidney of male rats chronically fed ochratoxin A at a dose causing a significant incidence of renal carcinoma.

Kidney samples of male Fischer 344 (F-344) rats fed a carcinogenic dose of OTA over 7 days, 21 days and 12 months were analysed for various cell signalling proteins known to be potentially involved in chemical carcinogenicity. OTA was found to increase the phosphorylation of atypical-PKC. This was correlated with a selective downstream activation of the MAP-kinase extracellular regulated kinases isoforms 1 and 2 (ERK1/2) and of their substrates ELK1/2 and p90RSK. Moreover, analysis of effectors acting upstream of PKC indicated a possible mobilisation of the insulin-like growth factor-1 receptor (lGFr) and phosphoinositide-dependent kinase-1 (PDK1) system. An increased histone deacetylase (HDAC) enzymatic activity associated with enhanced HDAC3 protein expression was also observed. These findings are potentially relevant with respect to the understanding of OTA nephrocarcinogenicity. HDAC-induced gene silencing has previously been shown to play a role in tumour development. Furthermore, PKC and the MEK-ERK MAP-kinase pathways are known to play important roles in cell proliferation, cell survival, anti-apoptotic activity and renal cancer development.

A toxicogenomics approach to identify new plausible epigenetic mechanisms of ochratoxin a carcinogenicity in rat.

Ochratoxin A (OTA) is a mycotoxin occurring naturally in a wide range of food commodities. In animals, it has been shown to cause a variety of adverse effects, nephrocarcinogenicity being the most prominent. Because of its high toxic potency and the continuous exposure of the human population, OTA has raised public health concerns. There is significant debate on how to use the rat carcinogenicity data to assess the potential risk to humans. In this context, the question of the mechanism of action of OTA appears of key importance and was studied through the application of a toxicogenomics approach. Male Fischer rats were fed OTA for up to 2 years. Renal tumors were discovered during the last 6 months of the study. The total tumor incidence reached 25% at the end of the study. Gene expression profile was analyzed in groups of animals taken in intervals from 7 days to 12 months. Tissue-specific responses were observed in kidney versus liver. For selected genes, microarray data were confirmed at both mRNA and protein levels. In kidney, several genes known as markers of kidney injury and cell regeneration were significantly modulated by OTA. The expression of genes known to be involved in DNA synthesis and repair, or genes induced as a result of DNA damage, was only marginally modulated. Very little or no effect was found amongst genes associated with apoptosis. Alterations of gene expression indicating effects on calcium homeostasis and a disruption of pathways regulated by the transcription factors hepatocyte nuclear factor 4 alpha (HNF4alpha) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were observed in the kidney but not in the liver. Previous data have suggested that a reduction in HNF4alpha may be associated with nephrocarcinogenicity. Many Nrf2-regulated genes are involved in chemical detoxication and antioxidant defense. The depletion of these genes is likely to impair the defense potential of the cells, resulting in chronic elevation of oxidative stress in the kidney. The inhibition of defense mechanism appears as a highly plausible new mechanism, which could contribute to OTA carcinogenicity.