[Role of immunocytology in the evaluation of patients with painless gross hematuria]. / Rolle der Immunzytologie in der Abklärung von Patienten mit schmerzloser Makrohämaturie.

OBJECTIVE: Gross hematuria is a highly worrisome episode in a patient's history mainly due to the fact that the prevalence of bladder cancer is significant in this group of patients. In this prospective study the role of immunocytology in the evaluation of patients with gross hematuria was investigated. MATERIALS AND METHODS: Ucyt is an immunocytological assay based on microscopic detection of tumor-associated antigens on urothelial cells. The study included 103 consecutive patients with a first episode of painless gross hematuria without prior transitional cell carcinoma. Urine samples were obtained from all patients and examined cytologically and immunocytologically. RESULTS: Clinical assessment by physical examination, laboratory tests, endoscopy, and imaging modalities yielded urothelial cancer in 22 cases (21%). Further diagnoses were BPH (30%), inflammation (10%), urolithiasis (7%), and"further conditions" (16%). In 17 patients the reasons for hematuria were not determined. For cystoscopy, immunocytology, and conventional urine cytology a sensitivity of 89 (excluding UUT), 86, and 45% was observed. Specificity was 94, 82, and 89%, respectively. Two and three bladder tumors were not detected by cystoscopy and immunocytology, respectively. CONCLUSIONS: The combination of cystoscopy and immunocytology yielded 100% sensitivity, while combining cystoscopy and cytology only marginally improved the sensitivity of cystoscopy alone. Since sensitivity appears to be of key relevance in the assessment of patients with gross hematuria, the authors suggest the addition of a sensitive noninvasive test to the diagnostic armamentarium in this situation.

5alpha-Reductase inhibitor treatment of prostatic diseases: background and practical implications.

This literature review discusses the theoretical background of 5alpha-reductase inhibitor (5ARI) treatment and the resulting clinical implications. A Medline-based search for peer-reviewed articles addressing 5ARIs, benign prostatic hyperplasia and prostate cancer was performed. The 5ARIs Finasteride and Dutasteride, which specifically inhibit the production of dihydrotestosterone by acting as competitive inhibitors of 5alpha-reductase, are clinically well tolerated and represent an effective treatment option for benign prostatic obstruction. Finasteride is the first compound which has a proven efficacy in chemoprevention of prostate cancer. The aim of this review was to elucidate, if there are sufficient data available to point out clinically relevant differences between the drugs. Both compounds achieve a significant reduction of prostate volume, an improvement of symptoms and a lower risk of acute urinary retention. Whether the different pharmacokinetic and pharmacodynamic properties of Finasteride and Dutasteride are of clinical importance cannot be judged at this time.

Immunocytology in the assessment of patients with asymptomatic hematuria.

Painless hematuria has remained a diagnostic challenge in daily urological practice. Key problem in the assessment of these patients is the discrimination between malignant and non-malignant conditions. In this prospective study the role of immunocytology in the evaluation of patients with hematuria was investigated. Ucyt is a commercially available immunocytological assay based upon microscopical detection of tumor-associated antigens on the membrane of urothelial cells by immunofluorescence. Between October 2000 and July 2007, 301 consecutive patients with a first episode of painless hematuria without prior transitional cell carcinoma were included. Urine samples were obtained from all patients and examined cytologically and immunocytologically. Clinical assessment by physical examination, laboratory tests, endoscopy and imaging in 228 cases with microhematuria and 66 cases with gross hematuria yielded bladder cancer in 10 (4.6%) and 17 (27%) patients, respectively. Clinical workup demonstrated that composition of both groups was entirely different. Sensitivity of cystoscopy and immunocytology was similar in both groups. Furthermore, a negative finding in cystoscopy and immunocytology virtually excluded the presence of urothelial cancer. However, while predictive values of immunocytology were clearly superior to cytology in gross hematuria, cytology performed better in the microhematuria cohort. Combination of cystoscopy and immunocytology yield 100% sensitivity in the assessment of patients with painless hematuria. Based upon performance characteristics the authors recommend to replace urine cytology by a more sensitive marker like immunocytology in gross hematuria. In patients with microhematuria immunocytology could be used to select for patients at risk for urothelial cancer and thus spare negative patients from further examinations.

[Peyronie's disease Current conservative and non-invasive treatment options.] / Die Induratio penis plastica Aktuelle medikamentöse und nicht-invasive Therapiemöglichkeiten.

Peyronie's disease is an aetiologically poorly understood disease of the tunica albuginea, characterized by pain during erection, development of fibrous plaques and penile curvature. Due to incomplete understanding of the pathophysiology of the disease, no causal treatment exists. In the literature, there are many conservative treatment proposals. This report describes the conservative and minimally invasive treatment options for Peyronie's disease.

Increased expression of connexin 43 in the overactive neurogenic detrusor.

PURPOSE: The cellular mechanisms involved in unstable uncontrolled detrusor contractions in the human bladder remain unknown. One hypothesis, based on electron microscopical observations and animal studies, is that gap junctions are present in the human detrusor and are increased in patients with detrusor overactivity. Thus intercellular electrical coupling between adjacent detrusor cells would be increased allowing electrical activity to spead more easily within the detrusor muscle mass and more readily generate significant contractions. The aim of this study was to prove this hypothesis. MATERIAL AND METHODS: Detrusor biopsies have been obtained from videourodynamically evaluated patients with neurogenic detrusor overactivity (NDO) (n = 19) [group I] and from patients with stress urinary incontinence (SUI) with stable, non-obstructed detrusors (n = 5) [group II] serving as controls. Specimens were fixed, paraffin embedded, sectioned, stained with a monoclonal connexin 43 antibody and evaluated by two blinded examiners using a semiquantitative scale. Connexin 43 mRNA levels were evaluated using quantitative RT-PCR with primers for connexin 43 and for 18S rRNA. The results were correlated with the patients' groups. RESULTS: Connexin 43 could be identified in cross sections of every detrusor biopsy. In all biopsies from patients with NDO a widespread presence of connexin 43 staining was observed, whereas only a limited presence of connexin 43 staining was observed in the specimen from patients with SUI. Connexin 43 mRNA levels within the detrusor were 3.7 fold higher in the NDO group than in the SUI group (p = 0.017). CONCLUSIONS: A limited amount of gap junctions seems to be present in every detrusor independently from its urodynamic stability or instability. But there is a significant increase in connexin 43 protein and RNA levels in patients with neurogenic detrusor overactivity underlining their role in intercellular electrical coupling.

Impaired bone metabolism following augmentation cystoplasties in growing rats.

OBJECTIVE: The aim of this study was to evaluate the possible risk of impaired bone metabolism following augmentation cystoplasties with different gastrointestinal segments. METHOD: 60 young rats underwent augmentation cystoplasties using gastric, ileal or sigma segments, or sham operations. An additional group undergoing sigma-cystoplasty received the bisphosphonate ibandronate to inhibit osteoclast-mediated bone resorption. Bone mass in the lumbar spine and tibia was analyzed monthly by in vivo densitometry. Bone turnover was assessed monthly using current bone metabolism markers for a period of 16 weeks. Bone ashing and serum analyses of the osteotropic hormones parathyroid hormone (PTH), and 25-OH vitamin D3 were performed at study conclusion. RESULTS: Following ileocystoplasty, reduced bone mineral density (BMD) was seen throughout the observation period; this was pronounced in the trabecular bone. The decline in BMD was associated with decreased serum 25-OH vitamin D3 levels. Following sigmacystoplasty, bone calcium content was significantly decreased; this could be prevented by ibandronate. No skeletal changes occurred in the gastrocystoplasty group. Serum pH was not altered in any group, and markers of bone resorption indicated normal bone resorption rates. CONCLUSION: There is a significant correlation between impaired bone metabolism and the type of segment used for bladder augmentation. While the use of the ileum (and probably the colon too) causes osteopenia, gastrocystoplasties seem to have little influence on bone turnover.

Failure of subureteral bovine collagen injection for the endoscopic treatment of primary vesicoureteral reflux in long-term follow-up.

OBJECTIVES: To evaluate the long-term efficacy of subureteral glutaraldehyde cross-linked collagen injection (GAX 35) for endoscopic treatment of primary vesicoureteral reflux (VUR). METHODS: We prospectively studied 36 patients (58 ureteral renal units), 30 girls and 6 boys with a median age of 6 years (range 2 months to 18 years). All patients had primary VUR and were treated with a single subureteral collagen injection (GAX 35). The patients were followed up by voiding cystography. RESULTS: According to the International Reflux Study Classification, we found the following reflux grades preoperatively: grade I, 2 ureteral units; grade II, 21 units; grade III, 28 units; grade IV, 4 units, and grade V, 3 units. All patients were treated with subureteral bovine collagen injection (GAX 35, mean volume 1.7 mL, range 0.7 to 3.5). All but 3 cases of reflux resolved initially. The mean follow-up was 13 months (range 1 to 108). After 37 months of follow-up, only 5 (9%) of 57 treated units remained reflux free. One unit was followed up for 17 months and also remained reflux free. CONCLUSIONS: These data suggest that a single endoscopic subureteral collagen injection is not effective in the long-term follow-up of patients with primary VUR. In the future, it will be important to determine whether the new, currently used, and soon be approved bulking agents show better long-term clinical results to prevent VUR recurrence than bovine collagen does.

Pitfalls of repeat subureteral bovine collagen injections for the endoscopic treatment of vesicoureteral reflux.

PURPOSE: Collagen has been used for the endoscopic subureteral treatment of vesicoureteral reflux since the late 1980s. We evaluated the long-term efficacy of repeat subureteral glutaraldehyde bovine cross-linked collagen injections for the endoscopic management of vesicoureteral reflux. MATERIALS AND METHODS: We prospectively evaluated 14 girls and 2 boys (21 ureteral units) 6 months to 16 years old (median age 6 years). In all patients initial treatment failed or reflux recurred after a single subureteral collagen injection and injection was repeated. Patients were followed with voiding cystography. Reflux-free periods after each injection and reflux grade were documented. RESULTS: All patients were treated twice with subureteral bovine collagen injection. Mean injected collagen volume of injections 1 and 2 was 1. 5 ml. (range 0.7 to 3.0) and 1.6 ml. (range 1.0 to 2.3), respectively, at a concentration of 35 mg./ml. In all but 4 cases reflux disappeared after injection 2. Mean followup was 11 months (range 1 to 41) after treatment 2. However in 10 patients (13 ureteral units) treatment failed or reflux recurred a mean of 10 months after injection 2. The reflux-free period after injection 2 was prolonged compared to that after injection 1 (p <0.05). CONCLUSIONS: Our results suggest that repeat endoscopic subureteral bovine collagen injections prolong the reflux-free period but remain ineffective at long-term followup for correcting vesicoureteral reflux.

Dosage escalation of intravesical oxybutynin in the treatment of neurogenic bladder patients.

OBJECTIVE: We prospectively analyzed the dose dependent outcome and side effects of neurogenic bladder patients with intravesical application of oxybutynin at our centre. MATERIALS AND METHODS: We examined the data of 32 patients with neurogenic bladders and detrusor hyperreflexia. We registered clinical outcome, continence situation, side effects and urodynamic data of patients with (A) standard dosages of intravesical oxybutynin (0.3 mg/kg bodyweight per day) and (B) with increasing dosages in steps of 0.2 mg/kg bodyweight per day up to 0.9 mg/kg bodyweight per day. RESULTS: We examined 32 patients aged 1 to 34 years, mean age 12 years. 21/32 patients became totally continent with the dosage (A). They showed a significant (P<0.01) decrease in the median max detrusor pressure (MDP) and a significant (P<0.01) increase in the median compliance and the median age adjusted bladder capacity (AABC). Eleven out of 32 patients remained incontinent under this dosage (A). Their median MDP, their median compliance and their median AABC remained nearly unchanged. Seven out of 11 incontinent patients under dosage (A) were treated efficiently with the higher dosages (B). Their median necessary dosage escalation to achieve treatment success was 0.7 mg/kg bodyweight per day (range 0.5 to 0.9 mg/kg bodyweight per day). Their median MDP was significantly (P<0.05) decreased and their median compliance and median AABC were significantly (P<0.05) increased. Four out of 11 patients remained incontinent and showed only little improvement in urodynamic data. Two out of 11 patients with the dosage escalation (B) showed side effects at a dosage of 0. 9 mg/kg bodyweight per day. CONCLUSIONS: The intravesical application of oxybutynin was a well tolerated and efficacious therapy. The topical oxybutynin therapy dosage (A) was efficient in 66% of our selected patients, the escalating dosage titration (B) could increase the efficiency to 87%.

Long-term efficacy of subureteral collagen injection for endoscopic treatment of vesicoureteral reflux in neurogenic bladder cases.

PURPOSE: We evaluated the long-term efficacy of subureteral glutaraldehyde cross-linked collagen injection (GAX 35) for endoscopic treatment of vesicoureteral reflux in patients with neurogenic bladder dysfunction due to meningomyelocele. MATERIALS AND METHODS: We prospectively studied 12 women and 8 men (26 ureteral renal units) with a median age of 8 years (range 1 to 51) who had neurogenic bladder due to meningomyelocele. Reflux into single collecting systems was treated with subureteral collagen injection (GAX 35). Followup with video urodynamics included voiding cystography. RESULTS: All patients performed intermittent catheterization to control the bladder. During the study all bladders were areflexic with normal compliance. Preoperative reflux according to the International Reflux Study Classification was grade I in 1, II in 9, III in 10, IV in 4 and V in 2 ureteral renal units. All patients were treated with subureteral collagen injection (mean volume 1.9 ml., range 0.7 to 3.5). Reflux resolved initially in all but 2 cases. Mean followup was 16 months (range 1 to 71). Reflux was still absent in only 15% of treated units after 24 months. CONCLUSIONS: Our data suggest that endoscopic subureteral collagen injection in neurogenic bladder cases is not effective with long-term followup. New biocompatible and biodegradable materials should be tested to control vesicoureteral reflux.

[Spontaneous kidney rupture after delivery due to an urothelial carcinoma]. / Spontanruptur einer Niere post partum aufgrund eines urothelialen Karzinoms. Bedeutung für die bildgebende Diagnostik.

The case of a spontaneous kidney rupture due to an urothelial carcinoma one week after delivery is presented. Diagnosis was made during operation. In comparison to the carcinoma, which is diagnosed and treated in time, the prognosis is poor. The patient deserved continuous gynecological follow-up and showed the classic symptoms of an urothelial carcinoma for six months. In spite of regular sonographic controls during pregnancy the tumor was not diagnosed. Diagnosis and management of renal carcinomas during pregnancy are discussed.

Ureteral complications in renal transplantation with more than one donor ureter.

BACKGROUND: The purpose of this study was to evaluate the ureteral complications of renal transplant recipients with more than one donor ureter METHODS: Between 1967 and 1997, 19 patients (median age 34 years, range 6-62 years) received renal transplants from donors with more than one ureter. There were 18 donor organs with two ureters, and one patient underwent en bloc renal transplantation with four donor ureters. In nine patients, the ureters were implanted separately at the bladder dome according to the extravesical technique of Witzel, Sampson, Lich and Röhl. In 10 patients, we performed a modification of this extravesical technique according to Nghiem with a side-to-side anastomosis of the ureters before completing the ureteroneocystostomy. RESULTS: After a median follow-up of 55 months (range 2-218 months), no graft loss due to ureteral complications was noted. One patient died due to myocardial infarction, seven patients returned to dialysis without ureteral complications. There were two patients (one patient after side-to-side ureteral anastomosis, one patient with separate implantation of the two ureters) with ureteral obstruction of one donor ureter. Both patients underwent open surgical revision with temporarily placement of internal ureteral stents. CONCLUSIONS: The presence of multiple ureters from donor kidneys is associated with a higher complication rate in our patient population compared with donor kidneys with one ureter. There was no difference in the long-term outcome between the two implantation techniques used.

Expression of the MRP2 gene-encoded conjugate export pump in human kidney proximal tubules and in renal cell carcinoma.

Human kidney proximal tubule epithelia express the ATP-dependent export pump for anionic conjugates encoded by the MRP2 (cMRP/cMOAT) gene (symbol ABCC2). MRP2, the apical isoform of the multidrug resistance protein, is an integral membrane glycoprotein with a molecular mass of approximately 190 kD that was originally cloned from liver and localized to the canalicular (apical) membrane domain of hepatocytes. In this study, MRP2 was detected in human kidney cortex by reverse transcription-PCR followed by sequencing of a 826-bp cDNA fragment and by immunoblotting using two different antibodies. Human MRP2 was localized to the apical brush-border membrane domain of proximal tubules by double and triple immunofluorescence microscopy including laser scanning microscopy. The expression of MRP2 in renal cell carcinoma was studied by reverse transcription-PCR and immunoblotting in samples from patients undergoing tumor-nephrectomy without prior chemotherapy. Clear-cell carcinomas, originating from the proximal tubule epithelium, expressed MRP2 in 95% (18 of 19) of cases. Immunofluorescence microscopy of MRP2 in clear-cell carcinoma showed a lack of a distinct apical-to-basolateral tumor cell polarity and an additional localization of MRP2 on intracellular membranes. MRP2, the first cloned ATP-dependent export pump for anionic conjugates detected in human kidney, may be involved in renal excretion of various anionic endogenous substances, xenobiotics, and cytotoxic drugs. This conjugate-transporting ATPase encoded by the MRP2 gene has a similar substrate specificity as the multidrug resistance protein MRP1, and may contribute to the multidrug resistance of renal clear-cell carcinomas.

Role of color-coded Doppler sonography in the assessment of internal ureteral stent patency.

OBJECTIVE: To evaluate the role of color-coded Doppler sonography (CCDS) in the assessment of internal ureteral stent patency. PATIENTS AND METHODS: We compared micturating cystography (MC) and CCDS in 48 patients with internal ureteral stents. Forty-five of these patients had pyelocaliectasis on renal sonography. RESULTS: In all of the 48 patients, the distal end of the internal ureteral stent could be seen sonographically in the bladder. The color images of 30 patients showed typical flow from the distal holes of the stent. Micturating cystography demonstrated patency of the stents in 36 patients. The two procedures showed the same results in 42 of 48 patients. Six patients had no detectable flow by CCDS, but the MCs showed patency of the stents. CONCLUSION: The CCDS is a valid noninvasive method for the assessment of internal ureteral stent patency with a sensitivity of 100%, a specificity of 83%, a positive predictive value of 67%, and a negative predictive value of 100%.

[MR tomographic monitoring of prostate carcinoma after cryotherapy: initial results]. / MR-tomographische Verlaufskontrollen des Prostatakarzinoms nach Cryotherapie: Erste Ergebnisse.

PURPOSE: To assess the morphological changes in the prostate gland and adjacent tissue after cryosurgery by high resolution MRI in patients with histological proven prostatic carcinoma. METHOD: 15 patients (mean age 66 years) with histologically proven prostate carcinoma underwent T2- and contrast-enhanced T1-weighted high-resolution MRI examinations with fat suppression. Follow-up MRI with an identical imaging protocol were performed at different time intervals (24-72 h, 2-6, 12, 26-52 weeks). RESULTS: Mean prostate volume had decreased by 30% in all patients 12-52 weeks after cryosurgery. After cryosurgery, zonal differentiation was lost in all patients with abnormalities in the periprostatic tissue in all patients, and rectal wall thickening in 47% of patients. Cryosurgery-induced changes in the prostate could not be differentiated from tumour recurrence. CONCLUSION: High resolution MRI allows precise recognition of intraprostatic and adjacent tissue alterations after cryosurgery of prostatic carcinoma. However, reliable detection of tumour recurrence was impossible due to cryosurgically induced signal changes.

Effects of carbon dioxide pneumoperitoneum in pigs with impaired pulmonary function.

The objective of our study was to investigate the possible adverse hemodynamic effects of a CO2 pneumoperitoneum in an experimental model in pigs with impaired pulmonary function. Thirteen animals were anesthetized with azaperon/ketamine and ventilated with 67% nitrous oxide in oxygen. By intravenous injection of dextran microspheres, a capillary pulmonary embolism was induced. After embolization, three animals served as controls (Group 1), five underwent open nephrectomy (Group 2), and five underwent laparoscopic nephrectomy (Group 3). Intra-abdominal pressure was kept constant at 15 mm Hg. At intervals, hemodynamic parameters were measured, and blood gas measurements were performed. Data were analyzed using a general linear model analysis of variance for differences between groups, and a paired t-test was applied for differences within groups from one condition to the next. The groupwise comparison revealed a significant rise of cardiac output in the laparoscopy group compared with the open nephrectomy group. No differences were noted for heart rate, systemic arterial pressure, central venous pressure, mean pulmonary arterial pressure, or pulmonary arterial wedge pressure. Impairment of pulmonary function caused no negative hemodynamic effect during laparoscopic nephrectomy.

[Magnetic resonance urography. First clinical results]. / Die Magnetresonanzurographie. Erste klinische Ergebnisse.

We report our preliminary results using a new magnetic resonance imaging technique for visualization of the urinary tract. Using the paramagnetic contrast medium gadolinium diethylene triamine penta-acetic acid (DTPA), we were able to obtain images of the urinary tract comparable to those obtained by conventional excretory urography. The major advantage of our technique is that besides good morphologic visualization, the excretion of gadolinium-DTPA can be studied simultaneously. We demonstrate our preliminary results in selected cases.