[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.

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.

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.

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.

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.

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%.

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.

[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.

Inhaled nitric oxide inhibits platelet aggregation after pulmonary embolism in pigs.

BACKGROUND: Inhaled nitric oxide (NO) is reported to prolong bleeding time in animals and humans and to inhibit platelet aggregation in persons with acute respiratory distress syndrome. In pulmonary embolism (PE), inhibition of platelet aggregation appears useful because further thrombus formation may lead to right ventricular dysfunction that results in circulatory failure. In the present study, the effect of inhaled NO on platelet aggregation after acute massive PE was investigated. METHODS: After acute massive PE was induced in 25 anesthetized pigs by injecting microspheres, 5, 20, 40, and 80 parts per million inhaled NO were administered stepwise for 10 min each in 11 animals (NO group). In the control group (n = 14). NO was not administered. Adenosine diphosphate-induced initial and maximal platelet aggregation were measured before PE (10), immediately after induction of PE (PE), at the end of each 10-min NO inhalation interval (t10-t40), and 15 min after cessation of NO inhalation (t55) in the NO group, and at corresponding times in the control group, respectively. RESULTS: Two animals in the control group and one in the NO group died within 10 min after PE induction and were excluded from analysis. Peaking at t40 and t55, respectively, initial (-13 +/- 6%; P < 0.05) and maximal (+44 +/- 17%; P < 0.05) platelet aggregation increased significantly after PE in the control group. In contrast, NO administration after PE led to a significant decrease in initial (maximum decrease, -9 +/- 3% at t40; P < 0.05) and maximal (maximum decrease, -15 +/- 7% at t30; P < 0.05) platelet aggregation. In the NO group, platelet aggregation had returned to baseline levels again at t55. In addition, NO administration significantly decreased mean pulmonary artery pressure and significantly increased end-tidal carbon dioxide concentration and mean systemic blood pressure. CONCLUSIONS: Inhaled NO has a systemic and rapidly reversible inhibitory effect on platelet aggregation after acute massive PE in pigs. This may be beneficial in treating acute massive PE.

Surgical treatment of invasive penile cancer--the Heidelberg experience from 1968 to 1994.

OBJECTIVES: This study was performed to establish oncological guidelines for the surgical treatment of invasive penile cancer. MATERIALS AND METHODS: The medical records of 51 patients with invasive penile cancer seen between 1968 and 1994 were reviewed in respect to treatment and long-term outcome. RESULTS: For stage T1 tumors treated with organ-preserving procedures the local recurrence rats was 56%, whereas no patient experienced a local recurrence after partial amputation. For stage T2 tumors, local recurrence rate was 100% (organ preservation) versus 20% (amputative procedures). There was no significant difference related to regional recurrence between surveillance, inguinal radiation and lymphadenectomy for stage N0 tumors. For N+ stages, survival was related to the extent of inguinal metastasis after dissection (5-year survival rate for N1: 71 vs. 33% for N2/3). CONCLUSIONS: Organ-preserving procedures include a high risk of local and regional recurrence. Adjuvant regional lymphadenectomy seems beneficial only in patients with solitary metastasis.

[Spontaneous kidney ruptures--a complication of panarteritis nodosa]. / Spontane Nierenrupturen--eine Komplikation der Panarteriitis nodosa.

Besides renal cell carcinomas and angiomyolipomas panarteritis nodosa (PAN) is a common underlying disorder for spontaneous perirenal hematomas (SPH). Herein we report on 3 cases with PAN associated kidney ruptures where diagnosis of PAN was not known before in 2 instances. The hematoma was identified by computerized tomography (CT) in all patients, nevertheless CT failed to reveal the underlying disorder in any case. In this situation angiography was extremely valuable visualizing multiple renal microaneurysms that are typical for PAN. Operative exploration and drainage of the hematoma was necessary in two patients because of hemodynamic instability. In one patient bleeding could be controlled after an immediate immunosuppressive therapy with prednisone and cyclophosphamide. Due to the high incidence of PAN associated spontaneous perirenal hematomas angiography should be performed in all cases with unclear SPH after CT evaluation. In our opinion an immediate surgical intervention is only indicated in cases with hemodynamic instability. Otherwise a conservative approach including immediate immunosuppression seems justified. Nephrectomy should be avoided whenever possible.

Transurethral incision of the prostate following renal transplantation.

Urinary retention in male patients after renal transplantation may cause serious complications in terms of graft function and even patient survival. Only few data concerning the management and outcome of these patients are reported in the literature. Therefore, we retrospectively analyzed the outcome of patients who underwent transurethral incision of the prostate immediately after renal transplantation. Between 1990 and 1993, we performed 259 renal transplantations and 15 patients had symptoms of urinary retention postoperatively. These patients underwent a midline transurethral incision of the prostate from the bladder neck to the verumontanum. Median peak flow preoperatively was 7 ml. per second (range 0 to 11.4) and median residual urine volume was 100 ml. (range 30 to 500). Median prostate volume was 28 ml. (range 12 to 45). After transurethral incision of the prostate a significant improvement (p < 0.001) in peak flow rates (19.6 ml. per second, range 8 to 49) as well as a significant decrease in residual urine volumes (40 ml., range 20 to 80) could be achieved. After a median followup of 19 months the effect was still present.

[The value of diagnostic imaging in benign prostatic hyperplasia and prostatic cancer]. / Wertigkeit der bildgebenden Diagnostik bei benigner Prostatahyperplasie und beim Prostatakarzinom.

Diseases of the prostate are of high socioeconomic importance owing to their high incidence and prevalence rates. Benign prostatic hyperplasia (BPH) can be detected in 80% of males over the age of 80. Clinical symptoms do not correlate with organ enlargement. Only 10% of patients with BPH need surgical treatment. The decision for surgical treatment is made as a result of objective findings and the symptoms reported by the patient. Preoperative evaluation of BPH must include digital rectal examination (DRE), measurement of peak flow rate, sonographic estimation of residual urine, transrectal ultrasound (TRUS), urethrocystography and the assessment of subjective complaints using symptom scores. Prostatic carcinoma is the most common malignancy in men. An abnormal DRE, increased PSA level and/or hypoechogenic lesions in TRUS are indications for prostate biopsy. The sensitivity of TRUS is superior to that of CT and MRI. New MRI techniques are promising with regard to local tumour extent. Whereas CT and MRI are not useful in screening of patients, these methods are valuable diagnostic tools in the follow-up of prostate cancer.

Hemodynamic and respiratory effects of pneumoperitoneum and PEEP during laparoscopic pelvic lymphadenectomy in dogs.

Extended laparoscopic operations are being performed increasingly in high-risk patients. To assess the effects of increased intraabdominal pressure (IAP) and positive end-expiratory pressure (PEEP) on the hemodynamic and respiratory system during extended procedures a carbon dioxide pneumoperitoneum was artificially induced in 10 dogs undergoing laparoscopic pelvic lymphadenectomy. An increase in IAP up to 15 mmHg had no negative effect on the cardiovascular system. However, the combination of an increased IAP (10-15 mmHg) with PEEP (8 cmH2O) markedly depressed the hemodynamic variables. Measurement of arterial carbon dioxide and fractional end-tidal carbon dioxide revealed significant CO2 retention. We conclude from the results that laparoscopic pelvic lymphadenectomy should be performed in high-risk patients only under general anesthesia with expanded cardiopulmonary monitoring.