[Prophylaxis of recurrent urinary tract infections]. / Prophylaxe rezidivierender Harnwegsinfektionen.

BACKGROUND: Recurrent urinary tract infections (rUTI), defined as ≥ 3 UTIs per year, mostly affect young and postmenopausal women. Treatable predisposing factors are rare. METHODS: General recommendations to reduce rUTIs lower the recurrence rate by up to approximately two thirds. Continuous long-term prophylaxis (LP) with low dose antibiotics or single postcoital doses can reduce the recurrence rate of rUTIs to as low as 5%. According to the European Association of Urology guidelines nitrofurantoin, trimethoprim and co-trimoxazole are the first-line drugs and cephalosporins or fluoroquinolones should be restricted to specific indications. Oral and parenteral immunotherapy were found to be effective in several controlled studies for prevention of rUTIs and can be combined with acute antibiotic therapy. CONCLUSIONS: Vaginal prophylaxis with estriol has proven its positive effect without serious gynecological side effects and there is also increasing evidence that cranberries prevent rUTIs but the exact mode of this therapy remains to be defined. There are also other promising modalities, such as phytotherapeutics, mannose, urine acidification, influencing bacterial intestinal and vaginal flora and the general immune response by e.g. acupuncture and inpatient rehabilitation, the therapeutic value of which still has to be proven.

Prevention of recurrent urinary tract infections.

Urinary tract infections (UTI) are among the most frequent bacterial infections in the community and health care setting. Mostly young and, to some extent, postmenopausal women are affected by recurrent UTI (rUTI) defined as ≥3 UTI/year or ≥2 UTI/half year. In contrast, rUTI is rare in healthy men. On the other hand, rUTI are frequently found in female and male patients with complicating urological factors, e.g. urinary catheters, infection stones. Remediable predisposing factors in uncomplicated rUTI in women are rare. In complicated rUTI the success depends mainly on the possibility to eliminate or at leastimprove the complicating risk factors. Continuous antibiotic prophylaxis or postcoital prophylaxis, if there is close correlation with sexual intercourse, are most effective to prevent rUTI. Nitrofurantoin, trimethoprim (or cotrimoxazole), and fosfomycin trometamol are available as first-line drugs. Oral cephalosporins and quinolones should be restricted to specific indications. Antibiotic prophylaxis reduces the number of uropathogens in the gut and/or vaginal flora and reduces bacterial "fitness". Given the correct indication, the recurrence rate of rUTI can be reduced by about 90%. Due to possible adverse events and the concern of selecting resistant pathogens, according to the guidelines of the European Association of Urology antimicrobial prophylaxis should be considered only after counselling, behavioural modification and non-antimicrobial measures have been attempted. In postmenopausal patients vaginal substitution of oestriol should be started first. Oral or parenteral immunoprophylaxis is another option in patients with rUTI. Other possibilities with varying scientific evidence are prophylaxis with cranberry products, specific plant combinations or probiotics. The prophylaxis of catheter-associated UTI should employ strategies which result in a reduction of frequency and duration of catheter drainage of the urinary tract. The currently available catheter materials have only little influence on reducing catheter-associated rUTI.

[Primary and secondary prevention of urinary tract infections]. / Primär- und Sekundärprävention von Harnwegsinfektionen.

Urinary tract infections (UTI) are among the most frequent bacterial infections in the community and health care setting. Mostly young and, to some extent, postmenopausal women are affected by recurrent UTI (rUTI) defined as ≥3 UTI/year. On the other hand rUTI are frequently found in patients with complicating urological factors, e.g. urinary catheters. Modifiable predisposing factors in uncomplicated rUTI in women are rare. Continuous antibiotic prophylaxis or postcoital prophylaxis, if there is close correlation with sexual intercourse, are most effective to prevent rUTI. Nitrofurantoin, trimethoprim (or cotrimoxazole), and fosfomycin trometamol are available as first-line drugs. Oral cephalosporins and quinolones should be restricted to specific indications. Antibiotic prophylaxis reduces the number of uropathogens in the gut and/or vaginal flora and reduces bacterial"fitness". Given the correct indication, the recurrence rate of rUTI can be reduced by about 90%. In postmenopausal patients vaginal substitution of oestriol should be started first. Oral or parenteral immunoprophylaxis is another option in patients with rUTI. Other possibilities with varying scientific evidence are prophylaxis with cranberries or probiotics. The prophylaxis of catheter-associated UTI or asymptomatic bacteriuria should employ strategies which result in a reduction of frequency and duration of catheter drainage of the urinary tract. The currently available catheter materials have only little influence on reducing catheter-associated rUTI.

[Obstructive uropathy in adults]. / Obstruktive Uropathie bei Erwachsenen.

Urinary tract obstruction is a common clinical problem. The obstruction of the urinary flow may be acute or chronic, partial or complete, unilateral or bilateral, and may occur at any site of the urinary tract. The major causes of urinary tract obstruction vary with the age of the patient. Anatomic abnormalities, e. g. ureteropelvic junction obstruction, account for the majority of cases in children. In comparison, calculi are most common in young adults, while prostatic hyperplasia or carcinoma, retroperitoneal or pelvic neoplasms, and calculi are the primary causes in older patients. Urinary tract obstruction results in different pathophysiological changes causing various symptoms. In addition to the aetiology, pathophysiology and clinical presentation of obstructive uropathy in adults, modern diagnostic and therapeutic options are presented in this review.

[Catheter drainage of the urinary tract. Status of the technique and prospects]. / Katheterdrainage des Harntrakts. Stand der Technik und Perspektiven.

In the last few years, progress in the field of catheter drainage of the urinary tract was limited to the introduction of some new devices, materials, and catheter coatings as well as specific points of technique [37]. At the same time a substantial number of evidence-based guidelines for the use of urinary catheters have been developed by various institutions [9, 13, 15, 17, 23, 28, 39], aiming at a reduction of catheter-associated nosocomial urinary tract infections. Based on these guidelines, this article provides a detailed overview of the current state of the art of catheter drainage of the urinary tract, focussing on practical aspects and hygiene. Urinary tract infections (UTI) still account for 30-40% of all nosocomial infections nowadays, while 90% of these nosocomial UTIs are associated with urinary catheters! The prevention of catheter-associated nosocomial UTIs, therefore, is an individual as well as infectiological and socioeconomic issue of utmost importance requiring cost-effective surveillance strategies and modern individualized concepts for the catheter drainage of the urinary tract in a multidisciplinary approach. Continuous training and education must ensure the above-mentioned medical standards since nurses, outpatient health care networks, and patients themselves increasingly assume the management of catheter drainage of the urinary tract. Because of their unique and specific expertise, urologists have to take responsibility and must play a key role in these projects.

[Gemcitabine/cisplatin vs. MVAC. 5 year survival outcome of the phase III study of chemotherapy of advanced urothelial carcinoma in Germany]. / Gemcitabin/Cisplatin vs. MVAC. 5-Jahres-Ergebnisse der Phase-III-Studie zur Chemotherapie des fortgeschrittenen Urothelkarzinoms in Deutschland.

Of 405 patients with stage IV transitional cell carcinoma from an international multicenter phase III trial, 70 were randomized in Germany to receive either gemcitabine/cisplatin or standard MVAC systemic chemotherapy for locally advanced or metastatic urothelial cancer. Overall survival as the primary endpoint of the study was similar in both arms (median survival GC 15.4 months vs MVAC 16.1 months), as were tumor-specific survival and time to progressive disease. In the intent-to-treat analysis, the 5-year overall survival rate was 10% for patients randomized to GC and 18% randomized to MVAC. Tumor overall response rates (GC 54%, MVAC 53%) were similar. The toxic death rate was 0% in the GC arm and 3% (one patient) in the MVAC arm. Significantly more GC than MVAC patients experienced grade 3/4 anemia (GC 52%, MVAC 20%) with significantly more red blood cell transfusions in the GC arm.Significantly more GC than MVAC patients had grade 3/4 thrombocytopenia (GC 54%, MVAC 17%) without grade 3/4 hemorrhage or hematuria in either arm. More MVAC patients experienced grade 3/4 neutropenia (GC 56%, MVAC 61%, p=1.000), neutropenic or leukopenic fever (GC 0%, MVAC 10%, p=0.237), mucositis (GC 0%, MVAC 7%, p=0.495), and alopecia (GC 6%, MVAC 36%, p=0.004). GC represents a reasonable alternative for the palliative treatment of patients with locally advanced and metastatic transitional cell carcinoma. Sustained long-term survival was only found for patients with locally advanced cancer, lymphatic metastases, or solitary distant metastasis but not for visceral metastatic disease.

A new suprapubic cystostomy trocar system.

We describe a newly developed suprapubic catheterization set with a defined sigmoidal, geometrically and functionally tripartite tip and grooved trocar shaft. The device was designed to enhance the handling and safety features of the current commercially available sets to promote the broader application of suprapubic catheterization.

Homologous bladder augmentation in dog with the bladder acellular matrix graft.

OBJECTIVE: To determine the functional potential and antigenicity of the homologous bladder acellular matrix graft (BAMG) in a dog model. MATERIALS AND METHODS: Seven mongrel dogs underwent partial cystectomy (20-50%) and grafting with an equal-sized BAMG; two control animals underwent partial cystectomy (40%) only. The dogs were killed after 30 (one), 120 (one) and 210 days (five dogs). Blood samples were obtained before and at 1, 2, 4, 7, 14, 30, 90 and 210 days after surgery. The dogs underwent cystography, intravenous pyelography and ultrasonography before and after surgery, and on the day they were killed, with cystoscopy carried out just before death. The grafted tissue was assessed using routine and immunohistochemical techniques. RESULTS: All the dogs survived surgery; a complete blood cell count, chemical panel and white blood cell count showed no significant difference between the experimental and control animals. Cystography, cystoscopy and ultrasonography revealed no pathological changes in the upper urinary tract. After 7 months, the mean bladder capacity in the augmented dogs was significantly higher (P = 0.035) than in the controls (264 vs 172 mL). Histological evaluation showed an invasion of all bladder wall components during the first month; at 7 months, the morphological examination showed essentially complete regeneration. CONCLUSION: In this dog model, the potential of the BAMG as a bladder augmentation graft was confirmed, having minimal antigenicity with maximal acceptance. The reconstructed bladder matched the morphological and functional properties of the normal bladder.

[Diagnosis of interstitial cystitis]. / Diagnostik der interstitiellen Zystitis.

Interstitial cystitis (IC) represents a rare and complex inflammatory bladder condition in which diagnostics can be challenging. Strict NIH criteria for its diagnosis were designed for research purposes. Their routine application would miss large proportions of IC patients. When IC is suspected, history and physical exam are followed by an evaluation of long-term voiding diaries. Large voided volumes (functional capacity > 250 cc) or longer micturition intervals (> 2 h.), absence of nocturia or symptom-free periods reduce the likelihood of IC. Further exclusion diagnostics include urine tests (infection), cytology (in-situ carcinoma), ultrasound (calculi, bulks, anomalies) and urodynamics in selected cases. Bladder capacity measurements under sedoanalgesia are of limited value, since functional low-volume bladders can be mechanically extendable. Cystoscopy under general anesthesia represents the diagnostic standard procedure for IC during which 90% of IC-patients present with characteristic mucosal glomerulations after bladder distension. Biopsies are recommended for exclusion of malignancy. Potassium-leak testing plays no relevant role in routine diagnostics due to its poor sensitivity. Similarly, complex determinations of novel IC markers (histamine, tryptase, cytokines, growth factors, substance P, nitric oxide) are of no relevance in clinical settings and should be restricted to research projects.

[Oral therapy of interstitial cystitis]. / Orale Therapie der interstitiellen Zystitis.

Up to now there is no specific treatment targeting the ultimate cause of interstitial cystitis (IC), since its pathogenesis and etiology are still unknown. Most studies focussing on oral medication have not been randomized, double-blinded or placebo-controlled. Numerous case reports and intent-to-treat trials are lacking a systematic approach and do not meet evidence-based medicine criteria. Consequently there is as yet no standard oral therapy available for the treatment of IC. However, only a few oral substances have shown a potential to improve symptoms such as frequency and pain. The best results were obtained from monotherapeutic use of pentosanpolysulfate, amitriptylin and hydroxycin. The true benefit of these substances alone should be compared to analgesics and anticholinergics in the course of controlled clinical trials.

Bladder acellular matrix graft: in vivo functional properties of the regenerated rat bladder.

The purpose of this study was to determine whether the rat urinary bladder augmented by an acellular matrix graft can restore the bladder's low-pressure reservoir function and preserve normal micturition. After partial cystectomy (> 50%) and grafting with the bladder acellular matrix graft (BAMG), storage and voiding functions were monitored in 20 rats by means of a specially designed "micturition cage," leak-point cystography, and cystometry. After 4 months, sections (n = 6) were examined histologically to evaluate regeneration of bladder wall components within the BAMG. Bladder capacity and compliance increased progressively and were significantly higher in the grafted animals than in controls (partial cystectomy only), and volumes per void were significantly higher than in either control or normal animals. At 4 months, the regenerated urothelium, smooth muscle, blood vessels and nerves within the BAMG were qualitatively identical to normal bladder wall. Augmentation cystoplasty with the homologous BAMG leads to morphologic and functional rat bladder regeneration, thus enhancing low-pressure reservoir function and preserving normal micturition.

Composition and biomechanical properties of the bladder acellular matrix graft: comparative analysis in rat, pig and human.

OBJECTIVE: To compare the composition and mechanical properties of the newly developed bladder acellular matrix graft (BAMG) with the normal urinary bladder in rat, pig and human. MATERIALS AND METHODS: Rat, pig and human urinary bladders were harvested and divided into control and experimental groups. For the latter, BAMGs were prepared, and light and transmission electron microscopic studies performed. Strips from the normal bladders and the BAMGs (10 in each group) were tested under tension, and the ultimate tensile strength, maximum strain, and elastic modulus were determined from stress/strain curves. RESULTS: Both types I and III collagen, as well as elastic fibres, were observed as major components of the matrix scaffold. There were more collagen type I fibres in the rat than in the pig and human BAMGs, whereas the pig, and particularly the human, both showed higher levels of type III collagen and elastic fibres. These different matrix scaffold patterns were confirmed by electron microscopy. Results from biomechanical testing showed no significant differences for strength, strain or elastic modulus between BAMG and control bladder strips, except in the rat where the maximum strain values were significantly lower. CONCLUSION: There are variations in the acellular matrix structure with similar biomechanical properties between the BAMG and the normal urinary bladder in three different species. These results may underscore the potential of the BAMG. Furthermore, this in vitro model provides a suitable method to study the mechanical properties of the urinary bladder and may serve as a diagnostic tool for various investigations.

Functional rat bladder regeneration through xenotransplantation of the bladder acellular matrix graft.

OBJECTIVE: To determine the decreased antigenicity of the bladder acellular matrix graft (BAMG) through xenotransplantation and to assess the in vivo and in vitro functional properties of the rat urinary bladder thus regenerated. MATERIALS AND METHODS: After partial cystectomy (> 50%), BAMGs prepared from hamster, rabbit and dog urinary bladders were grafted to male and female Sprague-Dawley rats; 10 control rats underwent partial cystectomy only. Urinary storage and voiding function were monitored in 15 animals using a specially designed 'micturition cage' and cystometry. After 4 months, organ-bath studies and histological techniques were used to evaluate bladder regeneration in vitro in the grafted animals. RESULTS: Clinically relevant antigenicity was not evident; no animal died from rejection and all bladder wall components regenerated in all BAMG xenografts. However, the degree and quality of regeneration varied. Muscularization, peak pressure, and bladder capacity were higher in the hamster BAMG-grafted animals, whereas in vitro contractility and compliance were best in the dog BAMG-regenerated bladders. All grafted bladders had significantly better capacity and compliance than the autoregenerated bladders after partial cystectomy alone. CONCLUSIONS: The present in vivo and in vitro studies show that BAMG-augmentation cystoplasty can lead to morphological and functional regeneration of the rat bladder, preserving its low-pressure reservoir function. Because BAMG-regenerated bladders show functional innervation that is similar to normal bladders, they can work in coordination with the host bladder components, thus generating adequate intravesical pressure to produce sustained voiding. The decreased antigenicity makes heterologous BAMG transplants feasible without immunosuppression.

In vitro functional properties of the rat bladder regenerated by the bladder acellular matrix graft.

PURPOSE: To assess the response of rat urinary bladder regenerated by the homologous bladder acellular matrix graft (BAMG) to in vitro electrical and pharmacologic stimuli. MATERIALS AND METHODS: In Sprague-Dawley rats, partial cystectomy (>50%) was performed, followed by BAMG augmentation cystoplasty. After 4 months, organ bath studies of tissue strips in 10 were used to compare the contractility of the BAMG regenerates and the corresponding host detrusor smooth muscle. RESULTS: The BAMG regenerates exhibited contractile activity to electrical field stimulation and a qualitatively identical pattern of response to muscarinic, purinergic, alpha- and beta-adrenergic drug administration and nitric oxide. At 4 months after surgery, the maximum forces of contraction of the BAMG regenerates to carbachol stimulation amounted to close to 80% of the host bladder response. With electrical field stimulation, they equaled 44% and 62% of the host bladder response after 2.5 and 4 months, respectively. Histological and immunohistochemical studies confirmed the presence of receptors for neurotransmitters that these functional in vitro studies implied. CONCLUSIONS: The present study provides further evidence that augmentation cystoplasty with the BAMG leads to functional regeneration of the rat bladder detrusor smooth muscle.

Bladder acellular matrix graft in rats: its neurophysiologic properties and mRNA expression of growth factors TGF-alpha and TGF-beta.

To assess the neurophysiologic properties and molecular mechanisms of the bladder acellular matrix graft (BAMG), we performed cystometric and neurophysiologic studies in male Sprague-Dawley rats (n = 46) at varying intervals. The animals were assigned to 3 groups: 1) normal, 2) partial cystectomy (>50%), and 3) partial cystectomy (>50%) and grafting with a BAMG of equal size. Additionally, matrix-grafted and host bladders were processed for analysis of mRNA expression of transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, and TGF-beta3 by reverse transcriptase polymerase chain reaction. Matrix-grafted bladders showed a significantly higher bladder capacity at 3 and 6 weeks and 4 months than those with partial cystectomy alone, and a significantly higher bladder capacity at 4 months than in normal controls (P < or = 0.01). Residual urine volume was significantly increased at 4 months. Electrostimulation of the pelvic nerve provoked generalized bladder contractions, a response that was reduced by atropine and hexamethonium. Variable induction of TGF-alpha, TGF-beta1, TGF-beta2, and TGF-beta3 gene transcription was evident in the BAMG, with prominent mRNA expression of TGF-alpha and TGF-beta1 6 months after surgery. These cystometric results and detrusor responses to stimulation provide further evidence that graft components do not interfere with host components. Matrix-grafted rat bladders generate, although not increased over time, adequate intravesical pressure responses to produce sustained voiding. Gene expression of different growth factors may be significant in understanding their role in the development and differentiation of the BAMG for partial bladder replacement.

Free ureteral replacement in rats: regeneration of ureteral wall components in the acellular matrix graft.

OBJECTIVES: To evaluate ureteral replacement by a free homologous graft of acellular matrix in a rat model. METHODS: In 30 male Sprague-Dawley rats, a 0.3 to 0.8-cm midsegment of the left ureter was resected and replaced with an acellular matrix graft of equal length placed on a polyethylene stent. The animals were killed at varying intervals, and the grafted specimens were prepared for light and electron microscopy. RESULTS: In all animals, the acellular matrix graft remained in its original position without evidence of incrustation or infection, and histologic examination showed complete epithelialization and progressive infiltration by vessels. At 10 weeks, smooth muscle fibers were observed; at 12 weeks, nerve fibers were first detected; at 4 months, smooth muscle cells had assumed regular configuration. CONCLUSIONS: The ureteral acellular matrix graft appears to promote the regeneration of all ureteral wall components.

Neurostimulation for bladder evacuation: is sacral root stimulation a substitute for microstimulation?

OBJECTIVE: To determine by anatomical and functional studies whether stimulation of sacral rootlets might permit selective stimulation of autonomic fibres, thus avoiding the detrusor/sphincter dyssynergia characteristic of current techniques of neurostimulation for bladder evacuation. MATERIALS AND METHODS: In 10 male mongrel dogs, the S2 root was isolated and its constituent rootlets followed from their origin in the spinal cord to the point of exit from the dura. The entire root and the individual rootlets were then stimulated, including intra- and extra-dural stimulation and at proximal, mid and distal levels. RESULTS: Neuroanatomical and histological findings showed that rootlets of ventral S2 maintain their identity throughout their intradural course; some carry predominantly autonomic fibres, some predominantly somatic and some a mixture of the two. CONCLUSION: It appears surgically feasible to identify, isolate and sever the predominantly somatic rootlets intradurally, sparing the predominantly autonomic rootlets for inclusion in extradural electrode placement around the entire sacral root, thus eliminating sphincteric interference with detrusor contraction for voiding at low pressure.

Vesicourethral function in mice with genetic disruption of neuronal nitric oxide synthase.

PURPOSE: Nitric oxide is thought to play an important role in neuromodulation of the lower urinary tract. We therefore studied the lower urinary tract function of mice in whom the gene encoding for neuronal nitric oxide synthase had been disrupted (nNOS knockout). METHODS: Female mice, both control and nNOS knockout, underwent voiding, urodynamic and muscle strip testing as well as histologic studies. Neuronal mechanisms assessed histologically included nitric oxide, cholinergic, adrenergic, vasoactive intestinal polypeptide (VIP), and nonspecific neuronal protein (protein gene product 9.5 [PGP 9.5]). RESULTS: No differences in voiding were observed between normals and nNOS knockout mice. On urodynamic studies, bladder capacity was higher in the experimental than in the normal animals (25.3 +/- 11.8 vs. 17.4 +/- 5.6 ml./gm. x 1000, p < 0.05) as was the maximal bladder pressure at leakage (70.1 +/- 15.9 vs. 59.5 +/- 12.8 cm. H20, p < 0.05). After treatment with L-NAME or L-Arginine, there was no significant difference between the groups. Muscle bath studies showed no differences in bladder contractility or relaxation after chemical and electrical stimulation. Histologic studies confirmed virtually no nNOS or nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase in the nNOS knockout mice, but no difference in the total number of nerves (PGP 9.5) and of cholinergic, adrenergic or VIP-staining nerves was detected between groups. CONCLUSIONS: Despite disruption of the main pathway for synthesis of neuronal nitric oxide, nNOS knockout mice voided normally, demonstrate normal muscle bath responses, and have normal numbers of all nerves studied (except those staining for NO). Further studies are underway to elucidate the compensatory mechanisms in these animals.

[Rational diagnosis and surgical therapy of renal cell carcinoma with tumor thrombosis in the vena cava]. / Rationelle Diagnostik und operative Therapie des Nierenzellkarzinoms mit Tumorthrombus in der V. cava.

Venous involvement in renal cell carcinoma (RCC) represents an advanced state of disease. Nonetheless, its influence on survival is rather secondary compared with that of local tumor growth, grading and metastasis. Since conservative treatment in advanced RCC is mainly ineffective, surgical management offers the most promising approach for potential cure. Only patients without metastasis, however, seem to benefit from an aggressive surgical intervention. The surgical technique itself is determined by the vena caval extent of the tumor thrombus. Preferably, noninvasive imaging techniques should provide information about metastasis and the extent of the tumor thrombus. Diagnostic efforts should be adapted to therapeutic feasibility and prognosis in every individual patient in order to avoid fatiguing and costly over-examination. The standards requested above can be realized by use of modern sonographic and computed-tomographic imaging techniques or by magnetic resonance imaging alone. Thus, nowadays, the essential diagnostics in RCC with vena caval involvement may dispense with angiographic examinations.