Gunnar Wendt-Nordahl

Cystinuria in childhood and adolescence: recommendations for diagnosis, treatment, and follow-up

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.

480 UROLITHIASIS THROUGH THE AGES: DATA FROM MORE THAN 200,000 URINARY STONE ANALYSES

From the Departments of Urology, Sindelfingen-Boeblingen Medical Center, University of Tubingen (TK, GWN), Tubingen, Zeisigwald Clinics Bethanien (DF), Chemnitz and Malteser Hospital St. Hildegardis (DBL), Cologne and Department of Traumatology and Orthopaedics, Vivantes Klinikum Spandau (ABS) and Urinary Stone Laboratory, Institute of Laboratory Diagnostics, Vivantes Klinikum Friedrichshain (GS), Berlin, Germany

Do Patients Benefit from Miniaturized Tubeless Percutaneous Nephrolithotomy? A Comparative Prospective Study

BACKGROUND AND PURPOSE A benefit of miniaturized percutaneous nephrolithotomy (MPCNL) compared with conventional percutaneous nephrolithotomy (PCNL) has not been demonstrated as yet. Thus, the aim of this study was to evaluate the outcome of conventional vs MPCNL and to determine if MPCNL offers an advantage for the patient. PATIENTS AND METHODS A prospective, nonrandomized series of 50 consecutive patients with solitary calculi (lower pole or the renal pelvis) were treated either by conventional PCNL (26F) or MPCNL (18F). Ultrasound or holmium laser were used for lithotripsy. Patients were treated tubeless after uncomplicated MPCNL, with thrombin-matrix tract closure and antegrade Double-J catheter placement. After PCNL, all patients received 22F nephrostomies. Demographic data, stone characteristics, perioperative course, and complication rates were assessed. RESULTS Patients characteristics were comparable in both groups, except for stone size, which was 18 +/- 8 mm (MPCNL) and 23 +/- 9 (PCNL; P = 0.042). Operative time was comparable in both groups (48 +/- 17 vs 57 +/- 22 min, not significant [NS]). After MPCNL, 96% were stone free at day 1 vs 92% after PCNL (NS). Significant complications did not occur in both groups. Minor complications were: Fever, 12% (MPCNL) vs 20% (PCNL; NS); bleeding, 4% vs 8%; perforations, 0% vs 4% (all NS). Overall outcome was not influenced by body mass index. Calcium oxalate stones were predominant with 75%. Patients after tubeless MPCNL had less pain (visual analogue score, 3 +/- 3 vs 4 +/- 3; P = 0.048.) and needed slightly less additional pain medication (25 +/- 12 mg/d vs 37 +/- 10 mg/d piritramid; NS). Hospital stay was significantly shorter after MPCNL (3.8 +/- 28 vs 6.9 +/- 3.5 d; P = 0.021.). CONCLUSIONS Both techniques were safe and effective for the management of renal calculi. While stone-free rates were comparable in our series, MPCNL showed advantages in terms of shorter hospital stay and postoperative pain. The lower stone burden and the tubeless fashion of MPCNL, however, might have influenced these results.

Systematic Evaluation of a Recently Introduced 2-μm Continuous-Wave Thulium Laser for Vaporesection of the Prostate

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.

Human Cardiac Inwardly-Rectifying K+ Channel Kir2.1b Is Inhibited by Direct Protein Kinase C-Dependent Regulation in Human Isolated Cardiomyocytes and in an Expression System

Background—Protein kinases A (PKA) and C (PKC) are activated in ischemic preconditioning and heart failure, conditions in which patients develop arrhythmias. The native inward rectifier potassium current (IK1) plays a central role in the stabilization of the resting membrane potential and the process of arrhythmogenesis. This study investigates the functional relationship between PKC and IK1. Methods and Results—In whole-cell patch-clamp experiments with isolated human atrial cardiomyocytes, the IK1 was reduced by 41% when the nonspecific activator of PKC phorbol 12 myristate 13-acetate (PMA; 100 nmol/L) was applied. To investigate the effects of PKC on cloned channel underlying parts of the native IK1, we expressed Kir2.1b heterologously in Xenopus oocytes and measured currents with the double-electrode voltage-clamp technique. PMA decreased the current by an average of 68%, with an IC50 of 0.68 nmol/L. The inactive compound 4-&agr;-PMA was ineffective. Thymeleatoxin and 1-oleolyl-2-acetyl-sn-glycerol, 2 specific activators of PKC, produced effects similar to those of PMA. Inhibitors of PKC, ie, staurosporine and chelerytrine, could inhibit the PMA effect (1 nmol/L) significantly. After mutation of the PKC phosphorylation sites (especially S64A and T353A), PMA became ineffective. Conclusions—The human IK1 in atrial cardiomyocytes and one of its underlying ion channels, the Kir2.1b channel, is inhibited by PKC-dependent signal transduction pathways, possibly contributing to arrhythmogenesis in patients with structural heart disease in which PKC is activated.

Three-dimensional laparoscopic imaging improves surgical performance on standardized ex-vivo laparoscopic tasks.

PURPOSE Conventional two-dimensional (2D) laparoscopy has been limited by the lack of depth perception and spatial orientation. This disadvantage may affect surgical performance, operative time, or morbidity. Depth perception, spatial resolution, and accuracy may be improved by three-dimensional (3D) vision. This study was designed to evaluate the effect of 3D imaging on the performance of novice and experienced laparoscopic surgeons executing standardized laparoscopic tasks in an ex-vivo setting. MATERIALS AND METHODS A 3D imaging system with a digital 3D full high definition (HD) and a 2D imaging with a conventional HDTV camera were used. A total of 10 laparoscopic experts and 10 novices were evaluated while performing standardized skill tasks in a pelvic trainer. Participants were divided into two groups working either with 2D or 3D imaging. The parameters measured were time until completion of each skill and total procedure time, number of losses of working material, number of missed grasps, and number of needed support. Statistical analysis was performed using the Wilcoxon test. RESULTS The results showed a significant difference in favor of the 3D system for the amount of missed grasps in the experts as well as the novice group (P<0.0001). A slightly significant difference was also seen for the loss of working materials (P=0.0381 and P=0.0693). The study is limited by its small sample size. CONCLUSION The 3D imaging system significantly improves spatial orientation and depth perception during laparoscopy under ex-vivo conditions.

Does Open Stone Surgery Still Play a Role in the Treatment of Urolithiasis? Data of a Primary Urolithiasis Center

OBJECTIVE The introduction and continuous development of percutaneous nephrolithotomy, the achievement of extracorporeal shock-wave lithotripsy, and the advancements in ureterorenoscopy have led to a revolution in the interventional management urolithiasis. The indications for open stone surgery have been narrowed significantly making it a second- or third-line treatment option. We report on patients undergoing open stone surgery for nephrolithiasis in our department during the last 10 years to examine our indications at a primary urolithiasis center and to determine the clinical situations in which open surgery is a reasonable alternative. PATIENTS AND METHODS We reviewed all patients undergoing open stone surgery for upper urinary tract stones from 1997 until 2007 at the Department of Urology, University Hospital Mannheim. A retrospective chart analysis was performed on these patients to identify factors and indications for open stone surgery. Indications for stone surgery, type of surgery performed, stone complexity, anatomical abnormities present, and the residual stone burden were reviewed. RESULTS During a 10-year period 26 open stone operations were performed in our high-volume center. Indications for open stone removal were complex stone mass with complete or partial staghorn stones, concomitant open surgery, nonfunctioning stone-bearing lower poles, the desire to facilitate future stone passages in cystine stone formers, multiple stones in peripheral calyces, and failed minimal invasive procedures. Procedures performed for stone removal included radial nephrotomies, extended pyelolithotomy, lower pole resection, partial nephrectomy, and ileum ureter replacement. Immediate stone-free rate after a single procedure was 69% (18/26 patients). CONCLUSIONS Although today most stone cases can be handled by minimally invasive treatment, open stone surgery maintains a mandatory role in very selected cases. The most common indication in our series though was complex stones with a high stone burden especially in combination with anatomical variations.

120 W Lithium Triborate Laser for Photoselective Vaporization of the Prostate: Comparison with 80 W Potassium-Titanyl-Phosphate Laser in an Ex-Vivo Model

PURPOSE To evaluate the ablative and hemostatic properties of the recently introduced 120 W lithium triborate (LBO) 532 nm laser and compare the results against the conventional 80 W potassium-titanyl-phosphate (KTP) laser. MATERIALS AND METHODS The ex-vivo model of the isolated blood-perfused porcine kidney was used to determine the ablation capacity, hemostatic properties, and coagulation depth of the GreenLight HPS laser system (American Medical System, Minnetonka, MN) that used an output power of 120 W. The results were compared with the KTP laser that used output power levels of 30 W, 50 W, and 80 W. Unperfused kidneys were weighed before and after 10 minutes of laser ablation in an area of 3 x 3 cm; the weight difference marked the amount of removed tissue. Bleeding was determined by the weight difference of a swab before and after it was placed on the bleeding surface for 60 seconds after ablating a surface area of 9 cm(2) on blood-perfused kidneys. RESULTS With a tissue removal of 7.01 +/- 1.83 g after 10 minutes of laser ablation at 120 W, the LBO laser offered a significantly higher ablation capacity compared with 3.99 +/- 0.48 g reached with the conventional KTP laser at 80 W in the same time interval (P < 0.05). The bleeding rate was also significantly increased using the LBO at 120 W compared with the conventional device at 80 W (0.65 +/- 0.26 g/min vs 0.21 +/- 0.07 g/min; P < 0.05). The corresponding depths of the coagulation zones were 835 +/- 73 microm and 667 +/- 64 microm (P < 0.05), respectively. CONCLUSION The 120 W LBO laser offers a significantly higher tissue ablation capacity compared with the conventional 80 W KTP laser. Because the increased efficacy of the device is accompanied by a higher bleeding rate and a slightly deeper coagulation zone, the user has to select the appropriate output power levels carefully for a safe and efficient treatment. Nevertheless, the bleeding rate compared with previous studies of transurethral resection of the prostate is significantly reduced.

Bertosamil blocks HERG potassium channels in their open and inactivated states

Bertosamil is chemically related to the class‐III anti‐arrhythmic drug tedisamil and has been developed as a bradycardic, anti‐ischemic and anti‐arrhythmic drug. Its anti‐arrhythmic properties might in part be attributed to its block of voltage‐dependent potassium channels Kv1.2, Kv1.4. and Kv1.5. However, HERG‐potassium channel block as an important target for class‐III drugs has not yet been investigated. We investigated the effect of bertosamil on the HERG potassium channel heterologously expressed in Xenopus oocytes with the two‐electrode voltage‐clamp technique. Bertosamil (70 μM) inhibited HERG tail currrent after a test pulse to 30 mV by 49.3±8.4% (n=5) and the IC50 was 62.7 μM. Onset of block was fast, i.e. 90% of inhibition developed within 180±8.22 s (n=5), and block was totally reversible upon washout within 294±38.7 s (n=5). Bertosamil‐induced block of HERG potassium channels was state‐dependent with block mainly to open‐ and inactivated channels. Half‐maximal activation voltage was slightly shifted towards more negative potentials. Steady‐state inactivation of HERG was not influenced by bertosamil. Bertosamil block elicited voltage–but no frequency‐dependent effects. In summary, bertosamil blocked the HERG potassium channel. These blocking properties may contribute to the anti‐arrhythmic effects of bertosamil in the treatment of atrial and particular ventricular arrhythmias.

Ureteroscopy for Stone Treatment Using New 270° Semiflexible Endoscope: In Vitro, Ex Vivo, and Clinical Application

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.