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Background and Purpose: A novel 2-microm continuous wave (CW) thulium laser device for interventional treatment of benign prostatic hyperplasia was recently introduced into clinical practice and is postulated to have several advantages over more established laser devices. A systematic ex-vivo evaluation of the thulium laser was undertaken to compare the results to transurethral resection of the prostate (TURP) and the potassium-titanyl-phosphate (KTP) laser as reference standard methods., Materials and Methods: The RevoLix CW thulium laser system was evaluated in the well-established model of the isolated blood-perfused porcine kidney to determine its tissue ablation capacity and hemostatic properties at different power settings. Histologic examination of the ablated tissue followed. The results were compared to the reference standards, TURP and 80-W KTP laser., Results: At a power setting of 70 W, the CW thulium laser displays a higher tissue ablation rate, reaching 6.56+/-0.69 g after 10 minutes, compared to the 80 W KTP laser (3.99+/-0.48 g; P<0.05). Only 30 seconds were needed to resect tissue with the same surface area using TURP, resulting in 8.28+/-0.38 g of tissue removal. With a bleeding rate of 0.16+/-0.07 g/min, the CW thulium laser offers hemostatic properties equal to those of the KTP laser (0.21+/-0.07 g/min), and a significantly reduced bleeding rate compared to TURP (20.14+/-2.03 g/min; P<0.05). The corresponding depths of the coagulation zones were 264.7+/-41.3 microm for the CW thulium laser, 666.9+/-64.0 microm for the KTP laser (P<0.05), and 287.1+/-27.5 microm for TURP., Conclusion: In this standardized ex-vivo investigation, the 2-microm CW thulium laser offered a higher tissue ablation capacity and similar hemostatic properties as those of the KTP laser, and in comparison to TURP both tissue ablation and the bleeding rate were significantly reduced.

Cystinuria is a rare hereditary disease resulting in recurrent stone formation and the need for repeated invasive interventions. So far, two responsible genes have been identified which encode the two transporters, rBAT and b(0,+)AT forming a heterodimer to transport cystine in proximal tubular cells (PTC) and whose defect results in increased excretion of cystine. A human cell line mimicing the phenotype of cystinuria in vitro is yet to be developed. Human kidney (HK)-2 is a PTC line derived from normal HK. After determining the presence of rBAT gene by RT-PCR and Western blot analysis, radioactively labeled cystine (S(35)) was used to evaluate the functional presence of the amino acid transport in HK-2 cells when cultured in vitro. To achieve a cystinuria type I phenotype in HK-2 cells, the rBAT gene was silenced using antisense oligonucleotides complimentary to human rBAT mRNA. The reduced transport activity of cystine was then determined by radiolabeled cystine uptake measurements. RT-PCR and Western blot confirmed the expression of the rBAT gene in HK-2 cells. Considerable transport of the radio labeled cystine was observed in HK-2 cells and was linearly dependent on the incubation time with the amino acid. The cystine transport in rBAT knockdown cells after incubation with antisense oligonucleotides was significantly lower compared to control (0.76 vs. 0.98%; P=0.0008), proving a transient knock-down of the rBAT gene. This study demonstrates the presence of the b(0,+) amino acid transport system in human proximal tubular HK-2 cells when cultured in vitro. Inhibition of this transport system is possible by using antisense technology. A permanent inhibition of the cystine transport, based on our model, would be useful for the development and evaluation gene therapeutic approaches.

Background and Purpose: The use of flexible ureteroscopy for diagnosis and management of upper urinary tract diseases is limited both by loss of maximum active deflection through the inserted working probes and a high frequency of damage with consequent costs. A newly developed ureteroscope (Flex-X, Karl Storz) with a maximized angle of deflection was introduced to overcome these problems. The aim of our study was to compare this new ureteroscope with an established device in vitro, ex vivo, and in a clinical approach., Materials and Methods: Angles of maximum active deflection and maximum irrigation flow were measured for both scopes in vitro with an empty working channel and after introduction of different lithotripsy and stone extraction probes. In addition, the loss of maximum active deflection and broken optical fibers of the scopes were assessed after 100 flexible ureteroscopies in an ex-vivo pig cadaver model. The clinical performance of both ureteroscopes was evaluated in 32 patients for management of lower pole stones., Results: The new ureteroscope displays highly improved deflection compared with the standard scope; deflection angles as much as 270 degrees with an empty working channel were achieved. Thin probes did not inhibit maximum deflection. Durability in ex vivotrials was high. Only minimal loss of maximum deflection and three broken optical fibers were observed. In clinical usage, a stone-free rate of 100% was achieved after 4 weeks. In three patients, the opening mechanism of a basket did not work with maximum deflection because of high friction., Conclusion: The new ureterorenoscope facilitates retrograde stone management and might diminish repair intervals. Further development of comparable devices will support flexible ureterorenoscopy as a standard stone management procedure.

Objective: The wavelength 980 nm of a recently introduced diode laser system for treatment of benign prostatic enlargement offers a high simultaneous absorption in water and haemoglobin, and is postulated to combine high tissue ablative properties with a good haemostasis., Methods: The Ceralas HPD150 diode laser system was evaluated in the well-established ex vivo model of the isolated blood-perfused porcine kidney to evaluate tissue ablation capacity and haemostatic properties at different generator settings. A histological examination of the ablated renal tissue followed. The results were compared with the reference standards transurethral resection of the prostate (TURP) and potassium-titanyl-phosphate (KTP) laser., Results: The diode laser displays a higher tissue ablation capacity, reaching 7.24+/-1.48 g after 10 min, compared with the KTP laser (3.99+/-0.48 g; p<0.05), whereas only 30s are needed to resect the tissue in the same surface area using TURP, resulting in 8.28+/-0.38 g of tissue removal. With a bleeding rate of 0.14+/-0.07 g/min, the diode laser offers haemostatic properties equivalent to the KTP laser (0.21+/-0.07 g/min) and a significantly reduced bleeding compared with TURP (20.14+/-2.03 g/min; p<0.05). The corresponding depths of the coagulation zones are 290.1+/-46.9 microm for the diode laser, 666.9+/-64.0 microm for the KTP laser (p<0.05), and 287.1+/-27.5 microm for TURP., Conclusions: In the standardised ex vivo investigation, the 980-nm diode laser offers a higher tissue ablation capacity and similar haemostasis compared with the KTP laser. In comparison with TURP, both tissue ablation and bleeding are significantly reduced. The promising ex vivo results warrant further clinical investigation.

Unlabelled: There has been controversy over whether extracorporeal shock wave lithotripsy (ESWL) can cause damage to the endocrine cells of the pancreas, leading to the later development of diabetes mellitus. Authors from Germany prospectively evaluated acute endocrine pancreatic injury as collateral damage caused by the ESWL for treating upper urinary tract stones. In a careful study they showed that there was no effect on serum levels of variables indicating exocrine and endocrine pancreatic tissue damage, suggesting that the idea that ESWL might lead to future diabetes mellitus is unlikely to be correct., Objective: To detect acute damage to pancreatic cells by extracorporeal shock wave lithotripsy (ESWL), with a focus on endocrine function, as recently the development of diabetes mellitus has been suggested to be a late complication of treatment of upper urinary tract stones, and injury to pancreatic tissue by ESWL, leading to insufficient endocrine function, has been proposed as an explanation of this effect., Patients and Methods: The study included 12 consecutive patients treated with ESWL for proximal ureteric or kidney stones, using a third-generation electromagnetic lithotripter. To evaluate pancreatic tissue injury caused by ESWL we determined blood variables known to indicate exocrine and endocrine pancreatic cell damage; blood samples were taken before, during, immediately after, and 1 h and 24 h after ESWL to determine the serum levels of amylase, lipase, insulin, glucose, c-peptide and glucagon. Eight patients treated with ESWL for distal ureteric stones were evaluated in the same way and served as the control group., Results: Neither the variables indicating islet cell damage (c-peptide, insulin and glucagon), nor those indicating damage of exocrine pancreatic cells (amylase and lipase) changed significantly over the time course in both groups., Conclusion: We could detect no immediate effect on the serum levels of variables indicating exocrine or endocrine pancreatic tissue damage caused by ESWL for urinary tract stones. The hypothesis that ESWL leads to pancreatic trauma with consecutive development of diabetes mellitus therefore seems unlikely.

Background and Purpose: Various improvements in the technique of transurethral resection of the prostate (TURP) have helped to reduce morbidity and mortality over the years. In this retrospective study, developments in the perioperative course in a single center were analyzed., Patients and Methods: A retrospective chart analysis was performed on 399 patients undergoing TURP in our institution between 1987 and 1997, summarized as group 1, and 550 patients operated on between 1997 and 2004, summarized as group 2. Personal data, preoperative findings, intraoperative and postoperative complications, and outcomes in the two groups were compared., Results: Average patient age, preoperative peak flow, residual volume, size of the prostate, and operation time did not differ statistically, whereas the amount of resected tissue was slightly higher in group 1 (30.1 g v 26.5 g). The mortality rate dropped from 0.5% in group 1 to 0 in group 2. Intraoperative bleeding necessitating transfusion (20.3% v 3.8%), capsule perforation (17.3% v 6.2%), and postoperative urinary-tract infections (37.1% v 6.2%) were significantly reduced in group 2. The incidence of TUR syndrome (2.0% v 1.6%) and severe anaesthesiology complications (1.8% v 0.9%) were only insignificantly lower in group 2. Postoperative bleeding, recatheterization, reintervention, and nonspecific complications remained unchanged, while the incidence of grade II or III stress incontinence and the postoperative hospital stay were reduced in group 2., Conclusions: Our study gives data on a contemporary TURP series and outlines a development toward fewer perioperative complications.

Purpose: To develop a training model for simulated percutaneous nephrolithotomy (PCNL) under ultrasound and fluoroscopy-guided access., Materials and Methods: The laboratory model for PCNL described by Hammond and associates (J Urol 2004;172:1950-1952) was modified. We used an ex-vivo perfused porcine kidney (freshly removed after commercial slaughtering), a chicken carcass (supermarket), as well as the standard equipment for PCNL. For imaging, ultrasound (7.5 MHz) and a fluoroscopy unit are necessary. Artificial stone material is implanted in the renal pelvis. The ureter is cannulated for retrograde pyelography and the renal artery and vein for continuous perfusion. The perfused kidney surrounded by ultrasound gel is placed in the eviscerated chicken carcass., Results: The model is low cost and simple to set up, with a preparation time of about 15 minutes. The equipment used in clinical practice can be employed for renal access, tract dilation, nephroscopy, stone disintegration, and stone removal. Imaging is feasible under fluoroscopic and ultrasound guidance., Conclusions: This biological training model simulates realistically the clinical procedure of PCNL under ultrasound and fluoroscopic guidance. Teaching and skill acquisition are practicable.

Purpose: To investigate strategies to achieve confluent kidney-tissue ablation by high-intensity focused ultrasound (HIFU)., Materials and Methods: Our model of the perfused ex-vivo porcine kidney was used. Tissue ablation was performed with an experimental HIFU device (Storz Medical, Kreuzlingen, Switzerland). Lesion-to-lesion interaction was investigated by varying the lesion distance (5 to 2.5 mm), generator power (300, 280, and 260 W), cooling time (10, 20, and 30 seconds), and exposure time (4, 3, and 2 seconds). The lesion rows were analyzed grossly and by histologic examination (hematoxylin-eosin and nicotinamide adenine dinucleotide staining)., Results: It was possible to achieve complete homogeneous ablation of a clinically relevant tissue volume but only by meticulous adjustment of the exposure parameters. Minimal changes in these parameters caused changes in lesion formation with holes within the lesions and lesion-to-lesion interaction., Conclusions: Our preliminary results show that when using this new device, HIFU can ablate a large tissue volume homogeneously in perfused ex-vivo porcine tissue under standardized conditions with meticulous adjustment of exposure parameters. Further investigations in vivo are necessary to test whether large tissue volumes can be ablated completely and reliably despite the influence of physiologic tissue and organ movement.

Although there is an ongoing controversy about the primary site of calcium oxalate stone (CaOx) formation, there is some evidence for extratubular crystallization. However, the mechanisms leading to such interstitial calcifications are not clear. Anatomical studies have demonstrated a close association between the renal vasculature and renal tubules. It has been hypothesized that disorders of the vasculature may contribute to renal stone formation. The exceptional papillary environment with low oxygen and high carbon dioxide is of interest in this context and its impact on CaOx toxicity to renal cells has to be evaluated. LLC-PK1, Madin-Darby canine kidney (MDCK), human umbilical vein endothelial (HUVEC) and fibroblast cell lines were exposed to hypoxia (3% O2) alone, hypercapnia combined with hypoxia (3% O2, 18% CO2) or standard culture conditions (20% O2) for 72 h. Cell survival rates were determined microscopically after 4 h of incubation with CaOx at final concentrations of 1, 2 and 4 mM. DAPI staining and western blot were used to evaluate the induction of apoptosis. We confirmed that CaOx leads to concentration-dependent effects on the viability of the cell lines. HUVECs were most vulnerable to CaOx among the four cell lines. Incubation under hypoxia alone had no impact on CaOx toxicity to any of the cell lines in terms of survival. However, under combined hypoxic and hypercapnic conditions, all cell lines displayed a significant reduction of cell survival compared to room air incubation. Again, this effect was most pronounced for HUVECs. The induction of apoptosis could not be demonstrated in any experimental setting. Combined hypoxia and hypercapnia clearly aggravate CaOx toxicity to renal cell lines. As we could not demonstrate the induction of apoptosis, this effect may be a result of toxic necrosis. Especially the CaOx effect on interstitial cell lines might be of interest in the chronic ischemic papillary environment. An increased toxicity may lead to recurrent stone formation, and vice versa, diseases of the vasculature, like arteriosclerosis, may further promote stone formation by induction of local ischemia. This issue has to be clarified by further studies.

Background and Purpose: Today, the holmium:YAG laser is the gold standard in endourologic stone treatment because of its high efficacy. However, guidewires and stone-extraction tools often are close to the fiber and may be damaged accidentally by the laser. The aim of our study was to evaluate the duration of laser application required to disrupt wires at different energy settings., Materials and Methods: Two standard wires (0.035-inch guidewire and 0.025-inch hydrophilic Terumo wire) and two baskets (1.9F Nitinol tipless and 3F stone extraction) were investigated. We used a holmium:YAG laser (Auriga; Wavelight Laser Technologie AG, Erlangen, Germany) and two fibers (230 and 365 microm) at 800 and 2000 mJ and a 5-Hz pulse rate. The laser was brought into direct contact with the wires., Results: The average time required for transection was 55 to 103 seconds for a safety wire. The Terumo wire broke after 20 to 40 seconds of direct laser application; 15 to 34 seconds was required for a Dormia basket. Thin Nitinol basket wires were disrupted after only 1 to 4 seconds. One- and two-factorial variance analysis showed a high degree of significance (P < 0.0001) of the energy level and type of wire., Conclusion: The disruption of stone-extraction tools occurs in a remarkably short time with laser exposure, especially in case of Nitinol baskets, whereas guidewires are more resistant. Attention should be paid to avoiding contact of laser energy with wires and baskets during stone fragmentation.

The female patient underwent multiple extracorporal shockwave treatments and an ureterorenoscopy during which an amorphous renal mass was found. A retroperitoneoscopy was performed with extraction of a large amorphous matrix calculus. Today, the prevalence of matrix calculi is very low. They are associated with and caused by urinal-infections. Delayed diagnosis in radiological-imaging procedures is typical for these stones. The minimal-invasive approach via retroperitoneoscopy seems to be an intriguing alternative to the established procedures like percutaneous nephrolitholapaxy.

Objective: To investigate the technical characteristics of a newly developed device for bipolar and multipolar radiofrequency ablation (RFA) of kidney tissue with a resistance-controlled power output., Materials and Methods: The standardized model of the isolated perfused ex vivo porcine kidney was used. Two different applicators (20 and 30 mm active length) were selected for bipolar RFA, and one pair of applicators (2 x 30 mm active length) for multipolar RFA. RF energy was applied at different power levels (20, 30, 60 W) depending on the total active length of the electrodes. Treatment times were 1, 3, 5 and 9 min. The ablation cycles were recorded in continuous digital real-time and displayed on a monitor showing pre-set power, actual applied power, applied energy, tissue resistance, and impedance. Lesion sizes were measured macroscopically. A coagulation coefficient (coagulated tissue volume per applied energy unit) was calculated., Results: There was a dosage-effect relationship between the generator power/treatment time and the sizes of the lesions. With increasing treatment time, less tissue volume was coagulated per unit of applied energy. The actual applied energy was lower than that calculated theoretically. The resistance and impedance values for the 30-W applicator were lower than those of the 20-W applicator., Conclusions: The technical features of this RFA device, with internally cooled bipolar and multipolar applicators and a resistance-controlled power output, represents an innovative improvement in RF technology. In vivo studies are needed to confirm the expected advantages and the suitability of this device for complete and reliable ablation of renal tumours.

Purpose: We investigated a newly developed bipolar and multipolar RF ablation system with an internally cooled electrode and resistance controlled power output in a standardized model of perfused ex vivo kidney tissue., Materials and Methods: RF energy was applied at different power levels (20, 30 and 60 W) for 1, 3, 5 and 9 minutes. Each treatment parameter was repeated 5 times. For the 20/30 W levels a bipolar electrode with an active conducting part of 20/30 mm was selected. At 60 W 2 bipolar electrodes with an active conducting part (30 mm each) were connected. Lesion volumes and shapes were calculated by measuring the maximum vertical, long axis and short axis diameters of the macroscopic lesion., Results: Lesion volume increased significantly with the treatment time and generator power applied (p < 0.0001). Lesion size in multipolar ablated zones was larger than that in bipolar ablated zones. A reliable dose-effect relationship existed between the generator power/applied treatment time and ablated tissue lesion size. All lesions were elliptical., Conclusions: Bipolar and multipolar RF ablation with an internally cooled electrode and tissue resistance control represent an interesting advance in RF technology. The development of lesion size and volume is predictable, while a uniform lesion shape can be achieved in perfused ex vivo kidney tissue. Further in vivo trials are required to test whether complete and reliable tumor tissue ablation is possible with this system.

Purpose: To evaluate the efficacy of endourethrotomy with the holmium:YAG laser as a minimally invasive treatment for urethral stricture., Patients and Methods: Between January 2002 and January 2004, 32 male patients with symptomatic urethral strictures (8 bulbar, 9 penile, 9 combined) were treated with Ho:YAG-laser urethrotomy in our department. The stricture was iatrogenic in 60% (N = 18), inflammatory in 16.6% (N = 5), traumatic in 13.3% (N = 4), and idiopathic in 7% (N = 3). The stricture was incised under vision at the 12 o'clock location or the site of maximum scar tissue or narrowing in asymmetric strictures. Laser energy was set on 1200 to 1400 mJ with a frequency of 10 to 13 Hz. Postoperatively, drainage of the bladder was performed for 4 days using a 18F silicone catheter. Triamcinolone was instilled intraurethrally after removal of the catheter in all patients. Patients were followed up by mailed questionnaire, including International Prostate Symptom Score and quality of life., Results: Retrograde endoscopic Ho:YAG laser urethrotomy could be performed in all 32 patients. Most patients (22; 68.7%) did not need any reintervention. Ten patients developed recurrent strictures that were treated by another laser urethrotomy in 4 patients (12.5%), while 6 patients (18.7%) needed open urethroplasty with buccal mucosa. Including 2 patients treated with repeat laser urethrotomy, 24 patients (75%) were considered successful after a mean follow-up of 27 months (range 13-38 months). No intraoperative complications were encountered, although in 5% of patients, a urinary-tract infection was diagnosed postoperatively. No gross hematuria occurred., Conclusions: The Ho:YAG laser urethrotomy is a safe and effective minimally invasive therapeutic modality for urethral stricture with results comparable to those of conventional urethrotomy. Further data from long-time follow-up are necessary to compare the success rate with that of conventional urethrotomy and urethroplasty. Nevertheless, the Ho:YAG laser urethrotomy might at least be an alternative to urethroplasty in patients with high comorbidity who are not suitable for open reconstruction.

Objective: To evaluate the frequency of adverse events and possible risk factors after the administration of an intravenous contrast medium (CM), iobitridol, in a large multicentre postmarketing surveillance study., Subjects and Methods: A total of 49,975 patients undergoing intravenous urography were included in this study. A water-soluble, non-ionic CM (iobitridol, 1 ml/kg body weight) was administered. Age, sex, indication for the actual examination and adverse events were documented. Also, high-risk patients were identified., Results: Of the 49,975 patients, 28,336 (56.7%) were males and 21,639 (43.3%) females. Indications for urography were mainly urolithiasis (39.1%), inflammatory diseases (25.6%) and tumours (13.9%). Additionally, 7.4% were risk patients: 1.9% with creatinine >1.5 mg/dl (0.1% were on haemodialysis); 0.8% had a history of previous allergic reactions to CM, 3.7% pre-existing asthma or allergies and 2% other risk factors against CM examination. Only 0.9% of the patients experienced acute adverse events that were non-serious and transient. Less than 0.1% of the patients experienced vomiting, dizziness or cardiovascular problems. Only 1 patient developed an anaphylactic shock but recovered fully under treatment. A chi(2) analysis revealed that adverse reactions occurred in patients with pre-existing renal insufficiency or allergies. Significantly more females had contrast-agent-related symptoms compared to men. Patients undergoing urography for urolithiasis had significantly fewer symptoms compared to patients with other indications., Conclusion: Iobitridol is clinically safe and well tolerated in urography as demonstrated in this study of a large patient population, producing mainly minor symptoms as adverse events. However, caution is advised when administering iobitridol to high-risk patients.

We present the case of a unique accumulation of complications 55 years after ureterosigmoidostomy for bladder exstrophy and discuss possible implications for follow-up strategies.

Background and Purpose: Bipolar resection systems for transurethral resection of the prostate (TURP) offer some advantages over conventional monopolar devices. As both the active and the return electrode are placed on the tip of the resectoscope, current flow is locally limited, and negative effects caused by the current flow through the patient's body in the monopolar array can theoretically be reduced. Furthermore, bipolar resectoscopes use 0.9% sodium chloride solution as irrigation fluid, and therefore, the risk of TUR syndrome is theoretically eliminated. In this trial, we evaluated a new bipolar resectoscope in an ex-vivo model and in vivo and compared it with a standard monopolar resection device., Materials and Methods: The modified model of the isolated blood perfused porcine kidney was used to determine cutting qualities, ablation rate, blood loss, and coagulation depth of the bipolar resection device compared with a monopolar resectoscope. A measurement system placed in the line between the generator and the patient was used to determine electric parameters when both resectoscopes were used in vivo., Results: The ex-vivo evaluation showed worse cutting ability of the bipolar resection device compared with the monopolar resectoscope, with essential difficulties in starting a cut. The ablation rate was equal, as both resectoscopes had the same loop diameter. The bleeding rate was lower in bipolar (15.16+/-3.31 g/min) than monopolar (20.78+/-1.52 g/min) resection, whereas bipolar cutting resulted in marginally deeper coagulation zones (236.25+/-36.69 microm 216.0+/-42.25 microm). The in-vivo measurements made it clear that more power and more current is delivered to the patient during bipolar resection. The reason lies in a period at the beginning of each cut, when the patient's impedance is low and current flow high., Conclusion: Our results suggest that bipolar resection offers an alternative to conventional monopolar TURP. The advantage of a more localized energy field is at least in part compensated for by the higher generator output power during the procedure. Our ex-vivo results indicate a reduced bleeding rate compared with monopolar resection. Clinical studies have to be performed to prove the significance of our findings for patient treatment.

Objectives: Radiofrequency Ablation is an investigational treatment option for RCC. The aim of our study was to test the ablation algorithms of four different RF systems in a standardized ex vivo perfused porcine kidney model., Materials and Methods: A multiline monopolar dry electrode (impedance-based system), a multiline monopolar dry electrode (temperature-based system), a single monopolar wet electrode (impedance-based system) and a single monopolar dry, internally-cooled electrode (impedance-based system) were selected. RF energy was applied at different treatment parameters (power with and without control, tissue temperature, saline enhancement) for 1, 3, 5 and 9 minutes in healthy perfused ex vivo porcine tissue. Each treatment parameter was repeated 5 times. Maximum vertical, long-axis and short-axis diameters of the macroscopic lesion were measured and lesion volumes/ shapes were calculated., Results: Lesion volumes increased significantly with the pre-selected tissue temperature and saline enhancement. Saline enhancement created larger, but irregular shaped lesions. The impedance-based system created lesion volumes that were predictable by treatment time and generator power. Lesions were unpredictable when uncontrolled generator power was applied. The created lesion shape was dependent on the selected electrode configuration., Conclusions: The currently available monopolar RFA systems offer different specific technical features to control tissue ablation. Detailed knowledge of the specific characteristics of each RF system is necessary to provide a higher chance of successful clinical outcome by complete and reliable ablation.

Objective: To report our experience with over 300 patients treated with percutaneous nephrolithotomy (PNL), for although PNL was established as a treatment in the 1970s, its use diminished with the introduction of extracorporeal shockwave lithotripsy (ESWL); clinical experience with ESWL showed its limitations, and the role of PNL for treating urolithiasis was redefined, which with improvements in instruments and lithotripsy technology has expanded the capability of percutaneous stone disintegration., Patients and Methods: The study included 315 patients (156 males, 159 females, aged 13-85 years) treated with PNL in our department between 1987 and 2002. The mean (range) stone diameter was 27 (7-52) mm. The kidney was punctured under ultrasonography guidance via a lower-pole calyx whenever possible. The working channel was dilated using an Alken dilator under X-ray control. If necessary, a flexible renoscope was used. Ultrasonic, pneumatic and laser probes were used for lithotripsy., Results: Four weeks after treatment the total stone-free rate was 96.5%; 45.7% of all patients were primarily stone-free, 21.3% had clinically insignificant residual stones that passed spontaneously within 4 weeks after PNL, and 33% of the patients needed auxiliary measures (a second PNL, ESWL, ureterorenoscopy). Overall, the early complication rate was 50.8%, the most common complications being transient fever (27.6%), clinically insignificant bleeding (7.6%) or both (3.2%); 3.5% of the patients developed urinary tract infections (with no signs of urosepsis), 3.2% had renal colic and 2.9% upper urinary tract obstruction. One patient (0.3%) developed acute pancreatitis after PNL; one died from urosepsis and one needed selective angiographic embolization of the punctured kidney due to bleeding. No patient required transfusions and there were no injuries to neighbouring organs., Conclusions: These results show that PNL causes no significant blood loss or major complications in almost all patients. Two aspects may especially reduce the potential complications: ultrasonography-guided renal puncture and using PNL in an experienced centre. PNL is a highly efficient procedure that provides fast and safe stone removal.

Objective: To evaluate donor-site complications of buccal mucosa urethroplasty and whether there is a difference in morbidity between harvesting the mucosa graft from the inner cheek or the lower lip., Patients and Methods: Twenty-four consecutive patients with recurrent urethral strictures were treated with buccal mucosa urethroplasty in our department between September 2002 and April 2004. In 12 patients the graft was harvested from the lower lip or cheek and lower lip (group 1), and in 12 patients from the cheek (group 2). The mean (range) age of patients was 51 (26-66) years in group 1 and 53 (32-75) years in group 2. The mean (range) graft length was 6.2 (2-16) cm in group 1 and 5.7 (2-13) cm in group 2. All patients were followed up using a mailed questionnaire that asked about pain, numbness, difficulties in mouth opening or ingestion, and satisfaction, monthly for the first 3 months and then every 6 months. The mean (range) follow-up was 12.5 (6-23) months., Results: There were no bleeding complications or disturbances in wound healing. All of the patients reported numbness in the area of the mental and buccal nerves, and graft-site tenderness after surgery. In group 1, the pain lasted for a mean (range) of 5.9 (0.5-22) months, compared to 1 (0.1-7) months in group 2 (P = 0.022). Perioral numbness lasted for a mean (range) of 10.3 (0.5-23) months in group 1 and 0.85 (0.1-3) months (P = 0.0027) in group 2. There were no statistically significant differences in problems with mouth opening or food intake between the two groups, but the patients in group 1 seemed to be less satisfied (6/12 patients satisfied) than those in group 2 (11/12 patients satisfied)., Conclusions: Buccal mucosa graft harvesting from the lower lip and the inner cheek are both feasible, but harvesting from the lower lip resulted in a significantly greater long-term morbidity, which resulted in a lower proportion of satisfied patients. This seems to be due to a long-lasting neuropathy of the mental nerve. We therefore have changed our technique entirely from lower lip to inner cheek graft harvesting, whenever possible.

Objectives: To evaluate the outcome of training both urological novices and experts, using the recently developed UroMentor (Simbionix Ltd, Israel) trainer, that provides a realistic simulation of rigid and flexible ureterorenoscopy (URS)., Subjects and Methods: Twenty experienced urologists (total number of previous flexible URSs 21-153) were monitored during simulated flexible URS for treating a lower calyceal stone, and the outcome was correlated with individual experience. A score was compiled based on the variables recorded, including total operation time, stone contact time, complications such as bleeding or perforation, and treatment success. A further five urological residents with no endourological experience were trained on the UroMentor in rigid URS for ureteric stone treatment. Their acquired clinical skills were subsequently compared to those of five urological residents who received no simulator training., Results: All 20 experienced urologists disintegrated the stone on the simulator, and the score achieved was related to their personal experience; there was a significant difference in performance in those with < 40 and > 80 previous flexible URSs. For the five urological residents with no endourological experience, simulator training improved their skills, and comparison with urological residents who had received no simulator training showed advantages for the trained residents. After being trained on the simulator, the group performed better in the first four URSs on patients., Conclusions: Individual experience correlates with individual performance on the simulator. Simulator training was helpful in improving clinical skills. Although the distribution of computer-based simulators is limited by high prices, virtual reality-based training has the potential to become an important tool for clinical education.

Objectives: After SWL treatment, many patients have residual fragments in the kidney or ureter. Fragments 2 stones episodes. These patients and their referring urologist received follow-up questionnaires which contained questions about stone clearance, late complications, auxillary measures and dietary or drug metaphylaxis., Results: Most residual stone fragments were located within the lower calyx (17%) and the renal pyelon (14%). Stone analysis was available in 142 patients with CIRF and revealed calciumoxalate calculi in 93.6% of the cases. In 78.6%, CIRF cleared spontaneously within few weeks and did not recur within 5 years. However, residual stones led to stone recurrence and need of re-treatment in 21.4%. Renal pyelon (23%) and calices showed comparable growth of former CIRF (lower calices 26.5%, middle calices 27%, upper calices 26%). Only 48% of the patients with recurrent stone formation followed dietary metaphylaxis. However, a significant correlation between a general or specific metaphylaxis and stone growth of CIRF could not be demonstrated., Conclusions: Most of the CIRF after SWL pass spontaneously without any complications. But considering that one fifth of the patients developed new stones at the side of residual fragments, it is obvious that close follow-up is required. Although we could not demonstrate a relation between metaphylaxis and stone re-growth, it is conceivable that adequate metaphylaxis can reduce stone recurrences.

The introduction of percutaneous nephrolithotomy (PNL) marked a turning point in the interventional treatment of nephrolithiasis. For the first time, the minimally invasive removal of larger kidney stones, which had previously required open surgery, became possible. With the increasing use of extracorporeal shock wave lithotripsy (SWL) during the 1980s, PNL lost clinical importance. However, since SWL has revealed its limitations, and both the patients' wishes and economic demand require a fast stone removal, the importance of PNL has risen again. Given the correct indications and performance, PNL is an efficient treatment modality reaching stone free rates of up to 100%. When PNL is performed by an experienced urologist, complications are low and can be managed conservatively in most cases. The most important step in the performance of a PNL is the anatomically correct puncture of the kidney gaining optimal access to the stone. To reach this, a lower calyx is punctured whenever possible, under combined sonographic and fluoroscopic guidance.

More than 30 % of all admissions to an urologic clinic are for the treatment of urinary stones. In almost all cases, the treatment is minimally invasive employing extracorporeal shock wave lithotripsy (ESWL), ureterorenoscopy (URS) or percutaneous nephrolithotomy (PCNL). Technical advances in endourology and a growing expertise in ESWL led to a decline in ESWL and an increase in endoscopic techniques. In comparison with ESWL, the endoscopic techniques are more invasive but in most cases achieve a stone free state faster. With the introduction of diagnosis related groups (DRG), the economic aspect of stone therapy is gaining in importance. Stone prevention leads to a cost reduction in the health care system, justifying the use of an appropriate stone metaphylaxis. This review article presents the current recommendations for interventional urinary stone therapy and lists the options of conducting both medical and economically rational therapy.

The management of prostate cancer is one of the core tasks for urologists today. This review focuses on therapeutic options for the curative and palliative treatment of prostate cancer. Within the area of urological competence, radical prostatectomy remains the standard procedure for the curative treatment of localised prostate cancer. Recently, interest in minimally-invasive procedures such as brachytherapy, focused ultrasound and cryotherapy has increased considerably. Established palliative treatment strategies include hormonal treatment schemes as the gold standard. Chemotherapeutic regimes are used for the hormone refractory disease. In addition to both the standard and new urological therapeutic options, promising experimental systemic strategies for the generalised disease are presented in this review.

Cystinuria, an autosomal-recessive disorder of a renal tubular amino acid transporter, is the cause of about 10% of all kidney stones observed in children. Different genetic characteristics are not represented by different phenotypes. The stones are formed of cystine, which is relatively insoluble at the physiological pH of urine. Without any preventive measures, the patients will suffer from recurrent stone formation throughout their life. Even with medical management, long-term outcome is poor due to insufficient efficacy and low patient compliance. Many patients suffer from renal insufficiency as a result of recurrent stone formation and repeated interventions. However, regular follow-up and optimal pharmacotherapy significantly increase stone-free intervals. Medical management is mainly based on hyperhydration and urine alkalinization. Sulfhydryl agents such as tiopronin can be added. Recurrent stone formation necessitates repeated urological interventions. These mostly minimally invasive procedures carry the risk of impairment of renal function. In adults, extracorporeal shockwave lithotripsy (SWL) as well as intracorporeal lithotripsy is often unsuccessful. However, in children SWL shows excellent results for cystine stones. In cases with large stone burden, percutaneous nephrolithotripsy (PNL) or even open surgical nephrolithotomy are preferred. This review discusses the underlying pathogenetic mechanisms and provides guidance for the diagnosis, therapy, and management of cystinuria following the recommendations of the International Cystinuria Consortium and the European Association of Urology.

Objectives: Prostate cancer (PCa) is a heterogeneous tumour entity with known interindividual differences in biological behaviour regarding tumour aggressiveness and metastatic potentiaL To date, the prediction of the metastatic status of patients with PCa has not been possible. To identify the molecular causes behind these differences, the gene expression profiles of two cell lines (LNCaP and LNCaP C4-2) with different metastatic potentials were examined using DNA microarray technology., Materials and Methods: LNCaP and LNCaP C4-2 cells were cultured under standard conditions. RNA was isolated using Trizol extraction. After processing the total RNA according to the manufacturer's instructions, we performed Affymetrix GeneChip analysis with HG-U133A chips. Data analysis was performed using NetAffx, dChip, GenMAPP and OMIM software., Results: After statistical evaluation of the raw data, we obtained a set of 158 differently expressed probe sets in the LNCaP and LNCaP C4-2 cells. The search for genes associated with proliferation, cell metabolism, growth factors, metastatic potential and tumour progression in this list revealed a number of 42 differently expressed probe sets. The comparison of this list of probe sets with the literature resulted in a list of 14 differently expressed genes which could well contribute to the metastatic potential and progression of PCa. Of these 14 genes only 6 (Cip1, IGF-1, NK4, CXCL 12, ILGF2R, RHOE) have already been associated with PCa, whereas the other 8 genes (FSTL-1, SOCS-2, Midkine, Thrombospondin 1, Secretory leukocyte protease inhibitor, Desmoglein 2, MLT 1, PTPRF) had not been previously related to PCa., Conclusion: DNA microarray technology offers the possibility of screening a large number of genes with regard to alterations in the expression level or mutations. In this study, we identified 14 genes that are most probably associated with the higher metastatic potential of LNCaP C4-2 cells as compared to LNCaP cells. Eight of these 14 genes are potential new molecular markers for assessing the metastatic potential of PCa, or may serve as therapeutical targets.

Background and Purpose: The therapeutic application of noninvasive tissue ablation by high-intensity focused ultrasound (HIFU) requires precise physical definition of the focal size and determination of control parameters. The objective of this study was to measure the extent of ex-vivo porcine kidney tissue ablation at variable generator parameters and to identify parameters to control lesion size., Materials and Methods: The ultrasound waves generated by a cylindrical piezoceramic element (1.04 MHz) were focused at a depth of 100 mm using a parabolic reflector (diameter 100 mm). A needle hydrophone was used to measure the field distribution of the sound pressure. The morphology and extent of tissue necrosis were examined at generator powers of up to 400 W (P(el)) and single pulse durations of as long as 8 seconds., Results: The two-dimensional field distribution resulted in an approximately ellipsoidal focus of 32 x 4 mm (-6 dB). A sharp demarcation between coagulation necrosis and intact tissue was observed. Lesion size was controlled by both the variation of generator power and the pulse duration. At a constant pulse duration of 2 seconds, a generator power of 100 W remained below the threshold doses for inducing a reproducible lesion. An increase in power to as high as 400 W induced lesions with average dimensions of as much as 11.2 x 3 mm. At constant total energy (generator power x pulse duration), lesion size increased at higher generator power., Conclusions: This ultrasound generator can induce defined and reproducible necrosis in ex-vivo kidney tissue. Lesion size can be controlled by adjusting the generator power and pulse duration. Generator power, in particular, turned out to be a suitable control parameter for obtaining a lesion of a defined size.

The use of doxorubicin as a chemotherapeutic agent is hindered by its toxic side effects on the normal cells of the body. The objective of this study was to determine if micelle-delivered doxorubicin could increase the effectiveness of doxorubicin against prostate carcinoma cells. Rat prostate carcinoma cells (MatLu) were cultured under standard conditions. Phosphate-buffered saline (PBS), doxorubicin and/or micelle solution (Pluronic 10500 solution) was added to the cell suspensions and incubated for 3 h. After incubation, cells were washed twice. Analysis consisted of: 1) immediate cell count and 2) proliferation assay at 24 and 144 h. After 24 h, samples with micelle-incorporated doxorubicin had 75% (10% pluronic with 10 microg/ml doxorubicin) and 80% (1% pluronic with 10 microg/ml doxorubicin) cell proliferation results compared with the control group. After 144-h incubation, these same two groups demonstrated cell proliferation results of only 30 and 43% of the control group. The in vitro cytotoxicity of doxorubicin against prostate carcinoma cells was dramatically increased by incorporating the molecule with polymeric micelles., (Copyright 2004 Springer-Verlag)

Most renal stones in humans are composed of calcium oxalate. An increase in urinary oxalate levels has been shown to result in renal epithelial cell injury and crystal retention. However, the underlying mechanisms are unclear. Although the localization of primary stone formation and the associated cells playing the pivotal role in stone formation are still unknown, renal epithelial cells and interstitial cells seem to be involved in this process. The aim of this study was to evaluate the effects of oxalate on distinct renal epithelial and endothelial cells as well as fibroblasts. The first part focused on the toxicity of oxalate on the cells and a potential time- and dose-dependency. In the second part, renal epithelial cells were cultured in a two-compartment model to examine the vulnerability of the tubular or basolateral side to oxalate. LLCPK1, MDCK, renal fibroblast and endothelial cell lines were cultured under standard conditions. In part 1, cells were grown in standard culture flasks until confluent layers were achieved. Sodium oxalate was delivered at final concentrations of 1, 2 and 4 mM to either the apical or basolateral side (plain medium was delivered to the contralateral side). Cell survival was assessed microscopically by trypan blue staining after 1, 2 and 4 h. The influence of oxalate on proliferation and apoptosis induction was also investigated. In the second part, MDCK and LLCPK1 cells were grown in 6-well plates until confluent layers were achieved. Sodium oxalate at the above concentrations was applied, to either the apical or basolateral side and plain medium was delivered to the opposite side. The same protocol was then followed as in part 1. Part 1: sodium oxalate led to a time- and concentration-dependent decline in cell survival that was comparable in LLCPK1 and MDCK. Non-tubular cell lines like fibroblasts and endothelial cells were significantly more vulnerable to oxalate. These observations were reflected by significant impairment to cell proliferation. We could not demonstrate an induction of apoptosis in any cell line. Part 2: both cell lines were more vulnerable to oxalate on the basolateral side. This effect was more pronounced in MDCK cells at high oxalate concentrations (4 mM). Cells are apparently more resistant on the apical (tubular) side. Our results show that sodium oxalate has a negative effect on the growth and survival of renal epithelial cells and, to a greater extent, also fibroblasts and endothelial cells. We could not demonstrate any induction of apoptotic processes which implies a direct induction of cell necrosis. The finding of interstitial calcification and the proximity of tubules, vessels and interstitial cells make involvement of non-tubular renal cells in tissue calcification processes possible. Renal epithelial cells are apparently more vulnerable to oxalate on their basolateral side. Therefore, calcification processes within the interstitium may exert pronounced toxic effects to these cells, leading to inflammation and necrosis. These observations further support the idea of the interstitium as a site of primary stone formation., (Copyright 2004 Springer-Verlag)

Background: Clinical use of gene therapy is limited by the poor efficacy and accuracy of intracellular DNA delivery. Known concepts of DNA transfection have not yet become clinical routine in the treatment of human disorders. We therefore focused on new transfection methods using different forms of acoustic energy as potentially safe and topographically applicable methods for gene delivery in the field of urology., Materials and Methods: Three different cell lines (prostatic and urothelial cancer, benign kidney) were transfected by different forms of acoustic energy. The effect of several parameters of electromagnetic shock wave treatment (number and frequency of impulses, energy flow density and plasmid concentration) as well as focused ultrasound on the transfection rate was assessed in a standardized experimental setup. The transfection rate was measured through reporter genes (pEGFP) by FACScan. Transfection by lipofectamine and electroporation served as positive controls., Results: All cell lines were transfectable by acoustic energy. Maximum transfection rate was achieved using focused ultrasound (49.5o%; 200 W, 500 ms, 200 microg/ml DNA). 31.3% of kidney cells were transfected by electromagnetic shock waves (1500 impulses, 200 microg/ml DNA, 0.5 mJ/mm2 energy density, 2 Hz). Plasmid strand breaks were identified as a limiting factor of the transfection rate., Conclusion: Transfection by acoustic energy, especially focused ultrasound, can be achieved at a high level in different cell lines. The possible topical application to urological organs and the low level of side-effects make acoustic energy a promising new gene therapy treatment option in urology.

Cystinuria is the cause of 1-2% of stones observed in adults and about 10% of those occurring in children. Recurrent stone formation and multiple operations cause considerable morbidity. We investigated the transfection efficiency of naked plasmid DNA in porcine kidney cells by applying holmium laser (Ho:YAG) energy in vitro as well as ex vivo in a porcine kidney papilla model. In the in vitro experiments, naked plasmid DNA was added to LLC-PK1 cells suspended in a medium and Ho:YAG laser applied with varying pulses. The transfection efficiency was measured by the expression of EGFP reporter gene in the cells by FACScan analysis and fluorescence microscopy. Ex vivo, papilla from porcine kidney was excised and naked plasmid DNA was added to the tissue in the medium. The laser was then applied and the cryosectioned tissue observed under fluorescence microscope. The efficiency of transfection in vitro significantly improved with the increase in impulses (P<0.01). Transfection at 50 impulses averaged 0.7+/-0.3%, at 200 impulses 28.3+/-7.7%, and at 500 impulses 36.1+/-3.1%. The cell mortality rate increased with higher pulse rate up to 70%. Ex vivo trials showed transfection in extended regions of the tissue and also in the peripheral layers of the papilla. Our study indicates that the transfection of benign kidney cells by Ho:YAG is a promising new gene transfer strategy. The ex vivo trials showed that peripheral renal tissue layers are susceptible to transfection by Ho:YAG applied from the papillary surface.

Background: The microvessel density (MVD) is often used as a quantitative parameter for angiogenesis. The aim of this study was to evaluate the three most commonly used endothelial markers of microvessels, CD31, CD34 and vWF, in benign and malignant prostatic tissue., Materials and Methods: Fifteen benign hyperplastic prostate and 54 prostate cancer specimens were immunohistochemically stained for CD31/CD34/vWF. The MVD obtained by each marker was quantified by a vessel count in standardized grids within the area of maximum angiogenesis. The data on MVD was interrelated and compared to tumor staging, grading and clinical follow-up., Results: A significant correlation of the CD31/CD34/vWF-MVD data was observed in BPH tissue, but not in PCa. In PCa, the most sensitive marker for newly derived blood vessels was CD34. While CD34-MVD demonstrated a significant association with tumorgrading and PSA follow-up, CD31- or vWF-MVD did not., Conclusion: CD34 is a suitable marker for the immunohistochemical visualization of microvessels in benign and malignant prostate tissue.

The aim of the study was to quantify the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in prostate cancer and adjacent non-tumorous tissue in a standardized experimental set-up and to evaluate the paracrine effects of three endothelial stimuli on neovascularisation. Immunohistochemical staining of prostate cancer (PCa) specimens for VEGF, bFGF, EGF and the endothelial marker CD31 was performed (n=56). Sections were analyzed for growth factor-positive cancer/epithelial cells as well as staining intensity in (I) malignant and (II) non-tumorous tissue. Within PCa the topographic relationship (TR) of maximum microvessel density (MWD) and maximum expression of each growth factor was assessed. The number of VEGF- and EGF-positive cells in PCa was significantly enhanced compared with non-tumorous tissue (p<0.0001), whereas there was no difference in staining intensity. In contrast, the staining intensity of bFGF sections revealed a stronger expression in non-tumorous tissue compared with PCa (p<0.0001). In benign glands, VEGF, EGF and bFGF expression is chiefly restricted to basal cells. VEGF and EGF displayed a close TR in 65 and 57% of cases, respectively, whereas bFGF revealed a close TR in only 43% of PCa specimens. The results outline the relationship of the investigated growth factors and angiogenesis in PCa, which is strongest for VEGF and EGF. The relevance of VEGF and EGF is underlined by the increased number of positive cancer cells. Although previously reported to be a pro-angiogenic growth hormone, bFGF appears to play an assimilably minor role in the angiogenesis of PCa.

Objective: Aim of study was to evaluate the urodynamic findings in patients with infantile cerebral palsy., Material and Methods: In 29 patients (aged 3-53), a videourodynamic investigation was performed after evaluation of urological anamnesis, clinical assessment and sonographic determination of residual urine. The patients were divided into group 1 (23 symptomatic patients aged 5 years and older with recurrent urinary tract infection, pollakiuria or urinary incontinence) and group 2 (6 asymptomatic patients)., Results: In group 1, 21/23 patients (91%) had reduced compliance (0.6 - 16.4 ml/cmH(2)O) and 16/23 patients (70%) increased leak point pressure (> 40 cmH(2)O). In all 23 patients, detrusor instability and detrusor sphincter dyssynergia (during voiding) was found. Fluoroscopy showed bladder trabeculation or diverticula in 14 patients (61%) and 2nd-3rd degree vesicoureterorenal reflux in 2 patients (9%). In group 2, 2/6 patients (33%) had reduced compliance (0.7 and 5.8 ml/cmH(2)O) and 4/6 (67%) increased leak point pressure (> 40 cmH(2)O). In 5/6 patients (83%), detrusor instability and detrusor sphincter dyssynergia was seen. Fluoroscopy showed bladder trabeculation in 3 patients (50%), whereas no reflux was observed. Only one of the 29 patients (3 %) showed no pathological videourodynamic or anamnestic findings., Conclusions: We conclude that videourodynamic assessment should be performed in all patients with infantile cerebral palsy. The decision should not be based on clinical symptoms such as pollakiuria, recurrent urinary tract infection or urinary incontinence.

New approaches in the treatment of transitional cell carcinoma (TCC) are using gene therapy to influence the disease at the genetic level. Technical advances in genomics, the availability of tissue-specific gene promoters and other developments have made this approach more realistic. Transporting the gene into the target cell is still the major problem. Several transfection techniques have been introduced. Transfection of naked DNA is one of the simplest to perform but transfection rates have been very poor. We investigated the influence of laser energy on transfection efficacy in urothelial cancer cells in vitro with two types of medical lasers. A suspension of human transitional cancer cells (UM-UC3; 3.5 million cells/ml) was mixed with 200 microg of plasmid DNA (pEGFP-N1). Two types of laser energy, neodymium:YAG (Nd:YAG) and holmium:YAG (Ho:YAG), were applied to the cell suspension in different energy settings. Twenty four hours after treatment, transfection rates were measured with FACS analysis. Energy setting parameters that determine the efficacy of laser were investigated. The significance of different transfection rates was estimated with the student's t-test. We demonstrated that the Nd:YAG laser was not suitable for achieving significant transfection of the reporter gene to the cells. In contrast, the Ho:YAG laser produced satisfactory transfection rates. There was an increase in transfection with increasing frequency of laser pulses, from 16% with 2 Hz up to 40% with 10 Hz (p < 0.0005). Pulse frequency was therefore stabilised at 10 Hz. Pulse energy (mJ) showed the same dependency: a transfection rate of 18.3% was achieved with 1,000 mJ and 53.8% with 2,000 mJ (p > 0.0005). Additionally, we investigated the impact of total pulse number (imp) with different pulse energies. At 1,000 mJ, a transfection rate of 18.3% was estimated with 200 imp and 48.56% with 750 imp, (p < 0.0005). At 2,000 mJ, a transfection rate of 53.8% was achieved with 200 imp and 58.26% with 500 imp. The optimal laser setting observed in this experiment was 10 Hz, 2,000 mJ and 500 imp. This study indicates that the efficacy of naked DNA delivery into TCC in vitro is improvable by application of Ho:YAG laser energy. The Nd:YAG laser did not increase transfection rates in our model. Our results with the Ho:YAG laser are encouraging for further studies to optimise DNA delivery. As TCC tissue is relatively easy to access, this method could become an effective and minimally invasive procedure in urothelial cancer treatment.

Background: The objective of this study was to examine and quantify the shock-wave-induced transfection of human bladder carcinoma cells., Materials and Methods: Cell suspensions were transfected with different concentrations of the pEGFP-N1 plasmid. Shock-waves were applied in a degassed water bath with different numbers of impulses at different energy levels. Additionally, the effects of different DNA concentrations, frequencies and the absence/presence of a liquid air border were examined., Results: After shock-wave application, the transfection rate increased up to a maximum of 27.10% after 1000 impulses at an energy level of 0.5 mJ/mm2. In comparison negative control groups were transfected significantly below 1%. An increase in acoustic power and frequency and of DNA concentration and the presence of a liquid-air border resulted in an increasing transfection rate., Conclusion: The results demonstrate that naked plasmid DNA can easily and effectively be delivered to malignant urothelial cells in vitro upon exposure to lithotripter-generated shock-waves.

Introduction: Approximately 5 - 7 % of germ cell tumors are of extragonadal origin. Biology and genetics are unclear, especially when the primary location is in the retroperitoneum. Chemotherapy is the initial treatment of choice for extragonadal germ cell tumors (EGGCTs), followed by surgical resection of the residual tumor mass. A primary testicular tumor must be ruled out by sonographic investigation and biopsy. The rate of metachronous testicular cancer in men with primary EGGCT is largely unknown., Case Report: We present the first patient in the literature who developed a metachronous testicular cancer 10 months after primary occurrence of EGGCT in the retroperitoneum., Conclusions: This case report emphasizes the importance of follow-up examinations of patients with primary EGGCTs. They should include careful sonographic investigation of the testis in order to detect metachronous testicular cancer early. Suspicious findings require open surgery biopsy. Intraoperative histopathology can be false-negative for cancer detection, as an immunohistochemical examination is not available.

Open surgery was the standard therapy for urinary calculi up to about 30 years ago. This changed upon introduction of extracorporeal shockwave lithotripsy (ESWL) in 1980, a procedure that is now the primary therapy for 70 % of the patients in western countries. Simultaneously, endourological procedures like ureterorenoscopy (URS) and percutaneous nephrolithotripsy (PCNL) have been improved, and now, modern small diameter and highly efficient instruments offer an ideal alternative to shockwave lithotripsy. Today, minimally-invasive stone treatment has replaced open stone surgery almost completely. This article introduces ESWL, URS and PCNL and discusses indications, outcomes and limitations.

Background and Purpose: The architecture of the lower renal pole seems to have a considerable influence on caliceal stone clearance after different therapeutic modalities. The published data are partially inconsistent, and publications on reproducibility are completely lacking. The aim of this study was to evaluate the intraobserver and interobserver reproducibility of different measures of lower-calix anatomy., Materials and Methods: We studied the intraobserver and interobserver reproducibility of parameters describing the lower-pole anatomy that are significant for treatment outcome. Forty renal units without urologic disease were analyzed by five independent urologists. Infundibular length (IL), infundibular width (IW), and lower infundibulopelvic angles (LIP) were measured by the Elbahnasy (LIP I), Keeley (LIP II), and Gupta (LIP III and LIP IV) methods. Statistical analysis of each parameter and investigator was performed., Results: All LIP angles showed low interobserver correspondence: correlation coefficients (CC) did not exceed 0.44 (P < 0.05). Even the relatively clearly defined parameters IW and IL achieved CCs of only 0.63 and 0.49, respectively. The intraobserver correlation achieved better results: 0.73 (LIP I), 0.84 (LIP II), 0.73 (LIP III), 0.65 (LIP IV), 0.88 (IL), and 0.82 (IW). With the Elbahnasy method, almost all renal units were classified as favorable for stone persistence after shockwave lithotripsy. With the Keeley and Gupta methods, more than 50% of the kidneys were defined as having low clearance probability., Conclusions: Assessment of the chosen parameters is difficult and shows high interobserver variation. Inexperience in measuring the specific angles and low imaging quality can limit correct evaluation. The large number of kidneys with anatomy inappropriate for clearance of lower-pole stones may explain the poor outcome of shockwave treatment for stones in a lower calix. Prospective studies will determine the clinical value of anatomic assessments.

Oxidative stress is markedly increased after kidney transplantation and may participate in the development and/or progression of chronic renal allograft nephropathy. In the present study we sought to assess the nephroprotective potential of antioxidative treatment in renal allograft recipients. Experiments were performed in the Fisher-Lewis rat model of chronic renal allograft nephropathy, with isografted Lewis rats serving as controls. Allografted rats were orally treated with carvedilol, an antihypertensive drug with antioxidative properties (25 mg/kg/d), its purely antioxidative derivative BM 91.0228 (5 mg/kg/d), alpha-tocopherol (100 mg/kg/d), a combination of propranolol/doxazosine (10/5 mg/kg/d), or vehicle for 24 weeks. At the end of the study, oxidative status and influence of antioxidative treatment were assessed in transplanted animals. Chronic allograft nephropathy was characterized by a marked increase of markers for oxidative stress (increased plasma and kidney levels of malondialdehyde, reduced glutathione, and tocopherol levels in renal allografts). Treatment with carvedilol, BM 91.0228, and tocopherol significantly improved antioxidative status of allograft kidney recipients. In addition, carvedilol reduced elevated blood pressure in allografted rats. However none of the drugs had a beneficial influence on functional and morphologic renal changes. Our data thus demonstrate that long-term treatment with the antioxidants carvedilol, BM 91.0228, or alpha-tocopherol does not prevent development of chronic transplant nephropathy, despite an improvement of antioxidative status.

We have recently demonstrated up-regulation of renal endothelin (ET) synthesis in a rat model of chronic renal allograft rejection. Treatment with a selective ET-A receptor antagonist improved survival and reduced functional and morphological kidney damage. However, the underlying mechanisms have not yet been elucidated, as ET exhibits both hemodynamic and inflammatory properties. Therefore, in the present study we investigated acute hemodynamic effects of the selective ET-A receptor antagonist LU 302146 (LU) on chronic renal allograft rejection in rats. Experiments were performed in the Fisher-to-Lewis model of chronic renal allograft rejection. Lewis-to-Lewis isografts served as controls. After 2, 12, and 24 weeks, hemodynamic measurements were performed on anesthetized animals. Measurement of mean arterial pressure (MAP) was performed via a catheter in the femoral artery. Renal blood flow (RBF) was measured by an ultrasonic flow probe placed around the renal transplant artery. Medulla blood flow (MBF) and cortex blood flow (CBF) were determined with laser Doppler probes. Hemodynamic response upon intravenous bolus injection of LU (50 mg/kg) was investigated. The application of LU was followed by a decline in MAP that reached statistical significance only in isografts (ISOs) after 12 weeks and allografts (ALLOs) after 24 weeks. RBF slightly decreased in all groups; however, without reaching statistical significance. MBF showed a small increase in ALLO12 and ALLO24 whereas CBF slightly decreased in all groups. Acute ET-A receptor blockade does not induce important hemodynamic effects in kidneys undergoing chronic rejection. The lack of response to ET-A receptor blockade suggests that the beneficial effect of ET receptor antagonists in this model is likely to be due to improvement of renal morphology.

The surgical and medical management of carcinoma of the prostate is a central issue in urology. Radical prostatectomy is the standard procedure in the curative therapy of locally confined carcinoma of the prostate. Recently, alternative minimally invasive options such as brachytherapy and the still experimental focused ultrasound and cryotherapy have gained in interest. Further palliative schemes such as hormonal ablation and chemotherapy have become established in the management of locally advanced and generalized carcinoma or elderly patients. It was our objective to give an account of these established and new urological therapy options in the management of carcinoma of the prostate.

Objective: Aim of this study was to evaluate whether the carbachol test and the nerve lesions responsible for bladder dysfunction possess predictive value in patients with chronic urinary retention who undergo temporary sacral neuromodulation (PNE test)., Material and Methods: In 1999 and 2000, PNE tests were performed in 24 patients with chronic urinary retention and acontractile detrusor previously assessed by urodynamics. In 18 patients, a carbachol test was performed during urodynamics. The diagnosis related to the acontractile detrusor was additionally assessed and compared to the successful outcome of the PNE test., Results: The PNE test was successful in 8 of the 24 patients (33.3 %). The bladder was completely emptied during the PNE test in 3 of the 10 patients with negative carbachol test and in 3 of the 8 patients with positive carbachol test. The highest success rate (80 %) was observed in patients after hysterectomy, whereas after lumbosacral pulposal prolapse or with a CNS tumor, it was only 20 - 33.3 %., Conclusions: We conclude that sacral neuromodulation is an effective treatment option in patients with nonobstructive urinary retention. The carbachol test does not possess any definitive predictive value with respect to the success rate of sacral neuromodulation in patients with chronic urinary retention. The success rate more likely depends on the localisation of the nerve lesion. PNE tests should be performed in all patients with therapy resistent nonobstructive urinary retention, as no other predictive factors exist.

The aim of this study was to evaluate the percutaneous nerve evaluation (PNE) test success in patients with nonobstructive urinary retention. A total of 24 PNE tests were performed in patients with nonobstructive urinary retention and in 18 patients, a carbachol test was performed during urodynamics. The diagnosis relating to the acontractile detrusor was also assessed and compared to the outcome of the PNE test. The PNE test was successful in eight of 24 patients (33.3%) with the the highest success rate being observed in patients after hysterectomy (80%). It was successful in five of 12 patients with negative carbachol tests and in three of six patients with positive carbachol tests. We conclude that sacral neuromodulation is an effective treatment option in patients with nonobstructive urinary retention. PNE tests should be performed in all patients with therapy resistant nonobstructive urinary retention, because predictive factors do not exist.