A longitudinal assessment of miR-122 and GLDH as biomarkers of drug-induced liver injury in the rat.

CONTEXT: There is an ongoing search for specific and translational biomarkers of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) has previously shown potential as a sensitive, specific, and translational biomarker of DILI in both rodent, and human studies. OBJECTIVE: To build on previous work within the field, we examined biomarker kinetics in a rat model of acetaminophen (APAP)-induced liver injury to confirm the sensitivity, and specificity of miR-122 and glutamate dehydrogenase (GLDH). MATERIALS AND METHODS: qRT-PCR and a standard enzymatic assay were used for biomarker analysis. RESULTS: Both miR-122 and GLDH were demonstrated to be more readily-detectable biomarkers of APAP-DILI than alanine aminotransferase (ALT). Peak levels for all biomarkers were detected at 2 days after APAP. At day 3, miR-122 had returned to baseline; however, other biomarkers remained elevated between 3 and 4 days. We were also able to demonstrate that, although miR-122 is present in greater quantities in exosome-free form, both exosome-bound and non-vesicle bound miR-122 are released in a similar profile throughout the course of DILI. DISCUSSION AND CONCLUSIONS: Together, this study demonstrates that both GLDH and miR-122 could be used during preclinical drug-development as complementary biomarkers to ALT to increase the chance of early detection of hepatotoxicity.

Differences in renal stone treatment and outcomes for patients treated either with or without the support of a ureteral access sheath: The Clinical Research Office of the Endourological Society Ureteroscopy Global Study.

PURPOSE: To describe the differences in the treatment and the outcomes of renal stones treated with flexible ureteroscopy (URS) either with or without the support of a ureteral access sheath (UAS). METHODS: The Clinical Research Office of the Endourological Society URS Global Study involved the collection of prospective data from consecutive patients treated with URS at centers around the world over a 1-year period. Baseline characteristics, stone location, treatment details, postoperative outcomes and complications were recorded. Inverse-probability-weighted regression adjustment (IPWRA) analyses were conducted on outcome from patients treated with or without the use of a UAS to determine the impact on stone-free rates (SFRs). RESULTS: Of 2239 patients treated with flexible URS, 1494 (67 %) patients were treated with the use of a UAS and 745 (33 %) without a UAS. The IPWRA analyses conducted on 1827 patients with complete data and based on treatment and outcome models showed that if URS procedures were performed without the use of an UAS, the average stone-free rate would be 0.504 compared with 0.753 with a UAS. This average treatment effect of 0.248 was not significant (P = 0.604). Using IPWRA analysis on only the treated population in the estimations revealed no significant difference between using and not using a UAS (31 %; ATET: 0.311; P = 0.523). CONCLUSIONS: The study showed no difference in SFR when a UAS was used or not. Whereas UAS did not increase the risk of ureteral damage or bleeding, postoperative infectious complications were reduced.

Influence of model and matrix on cytokine profile in rat and human.

OBJECTIVE: Emerging evidence indicates that low-grade inflammation is part of the clinical picture of OA and that there is a need to identify soluble biomarkers of ongoing inflammation in the joint from a translational aspect. The aim of this study was to compare levels of pro-inflammatory biomarkers in SF, serum and/or EDTA plasma. METHODS: SF and blood from rats subjected to Freund's complete adjuvant (FCA; n = 48) or monoiodoacetate (MIA; n = 88) monoarthritis and from control rats were collected over time. SF, EDTA plasma and serum were obtained from six individuals with OA of the knee and healthy controls. Levels of IL-6, KC/GRO, IL-8, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 3α (MIP-3α), IL-1ß, TNF and l(+)-lactate were assessed either by immune assay or by a colorimetric method. RESULTS: Elevated levels of biomarkers were shown in monoarthritic animals in SF compared with the control groups, although with considerably lower magnitude in the MIA groups, which also indicated a biphasic pattern. Levels of KC/GRO and MIP-3α in serum from the FCA model and IL-6 in the MIA model followed the pattern of SF. In serum samples from OA individuals, MIP-3α correlated significantly with levels in SF. CONCLUSION: While we found increased levels of markers in joint fluid and blood, no single systemic biochemical biomarkers that were a common denominator between the animal models and the patient material could be identified. Our data indicate that it is critical to delineate the temporal profile of multiple local and systemic factors in order to pinpoint soluble biomarkers for OA.

Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts.

BACKGROUND & AIMS: There is a demand for more sensitive, specific and predictive biomarkers for drug-induced liver injury (DILI) than the gold standard used today, alanine aminotransferase (ALT). The aim of this study was to qualify novel DILI biomarkers (keratin-18 markers M65/M30, microRNA-122, glutamate dehydrogenase and alpha-foetoprotein) in human DILI. METHODS: Levels of the novel biomarkers were measured by enzyme-linked immunosorbent assay or real-time quantitative reverse-transcription PCR (qRT-PCR) in two human DILI cohorts: a human volunteer study with acetaminophen and a human immunodeficiency virus (HIV)/tuberculosis (TB) study. RESULTS: In the acetaminophen study, serum M65 and microRNA-122 levels were significantly increased at an earlier time point than ALT. Furthermore, the maximal elevation of M65 and microRNA-122 exceeded the increase in ALT. In the HIV/TB study, all the analysed novel biomarkers increased after 1 week of treatment. In contrast to ALT, the novel biomarkers remained stable in a human cohort with exercise-induced muscular injury. CONCLUSIONS: M65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity.

Percutaneous nephrolithotomy under combined sonographic/radiologic guided puncture: results of a learning curve using the modified Clavien grading system.

PURPOSE: Aim of our study was to evaluate the results of percutaneous nephrolithotomy (PNL) with sonographic/fluoroscopic guided puncture during a learning curve and to compare them to an expert. METHODS: The first 75 consecutive patients undergoing conventional PNL or Mini-PNL by a novice percutaneous surgeon without direct supervision by an expert were evaluated and divided into three groups of 25 patients each. The results were compared to 50 cases treated by an expert. RESULTS: For mean stone sizes of 22.3 ± 12.9, 22.7 ± 14.9, and 31.1 ± 25.5 mm, the OR-time was 124 ± 35, 106 ± 37, and 99 ± 31 min for the novice groups 1, 2, and 3, respectively. In contrast, the expert required an OR-time of 85 ± 28 min for a mean stone size of 19.7 ± 4.2 mm (p < 0.001; p < 0.01; n.s.). Stone free rates were 100, 96, and 100%; however, second-look procedures were necessary in 24, 16, and 20% of cases, whereas the expert needed only 8% second-look procedures. No complications Clavien IIIb-V occurred. 16, 4, and 8% of patients required a double-J placement (Clavien IIIa) due to hydronephrosis or urine leakage. One patient in the novice group 2 needed transfusion (Clavien II). Other minor complications (Clavien I) occurred in 28, 20 and 12% in the novice groups 1, 2 and 3, respectively, in comparison with 22% in the expert group. CONCLUSIONS: Percutaneous stone treatment under combined sonographic/fluoroscopic guided puncture can be performed safe and efficiently during the learning curve. The lower expertise causes longer operation times and a higher re-intervention rate without compromising the patients' safety.

Decreased levels of discomfort in repeatedly handled mice during experimental procedures, assessed by facial expressions.

Mice are the most commonly used laboratory animal, yet there are limited studies which investigate the effects of repeated handling on their welfare and scientific outcomes. Furthermore, simple methods to evaluate distress in mice are lacking, and specialized behavioral or biochemical tests are often required. Here, two groups of CD1 mice were exposed to either traditional laboratory handling methods or a training protocol with cup lifting for 3 and 5 weeks. The training protocol was designed to habituate the mice to the procedures involved in subcutaneous injection, e.g., removal from the cage, skin pinch. This protocol was followed by two common research procedures: subcutaneous injection and tail vein blood sampling. Two training sessions and the procedures (subcutaneous injection and blood sampling) were video recorded. The mouse facial expressions were then scored, focusing on the ear and eye categories of the mouse grimace scale. Using this assessment method, trained mice expressed less distress than the control mice during subcutaneous injection. Mice trained for subcutaneous injection also had reduced facial scores during blood sampling. We found a clear sex difference as female mice responded to training faster than the male mice, they also had lower facial scores than the male mice when trained. The ear score appeared to be a more sensitive measure of distress than the eye score, which may be more indicative of pain. In conclusion, training is an important refinement method to reduce distress in mice during common laboratory procedures and this can best be assessed using the ear score of the mouse grimace scale.

Urolithiasis through the ages: data on more than 200,000 urinary stone analyses.

PURPOSE: The incidence and prevalence of urolithiasis are increasing but clinicians also have the impression that gender and age distributions of stone formers are changing. Moreover, regional differences in stone occurrence and composition have been observed. We analyzed such trends based on a large series of urinary stone analyses. MATERIALS AND METHODS: A total of 224,085 urinary stone analyses from 22 German centers were evaluated to determine the incidence of stone composition and identify age and gender distributions from 1977 to 2006. A subset of 58,682 stone analyses from 1993 to 2006 was available to identify regional differences in stone composition in Germany. RESULTS: Calcium containing calculi were most common in each gender. The overall male-to-female ratio of 2.4:1 increased from 1977 (1.86:1) to 2006 (2.7:1). The predominance of male calcium stone formers was even higher among elderly patients with a 3.13:1 ratio at ages 60 to 69. Since 1997, we observed a tendency toward an increasing incidence in middle-aged patients at ages 40 to 49 years. While the rate of infection stones constantly decreased, the incidence of uric acid calculi remained stable with an overall rate of 11.7% in males and 7.0% in females with a peak at higher ages. Cystine stones remained rare at 0.4% in males and 0.7% in females. In terms of regional analyses we noted great variation in stone composition in the 2 genders. Uric acid stones were more common in the eastern and southern regions but infection stones were mostly seen in eastern regions. CONCLUSIONS: In what is to our knowledge the largest series of stone analysis reported to date we identified an age and gender relationship of stone formation and composition. Regional variations are common and underline the influence of living habits, diet and standard of medical care on urinary stone formation.

Flexible ureterorenoscopy versus miniaturized PNL for solitary renal calculi of 10-30 mm size.

INTRODUCTION: The value of flexible ureterorenoscopy (fURS) and miniaturized PNL (mPNL) for larger renal calculi is under discussion. This non-randomized prospective study aimed to evaluate fURS and mPNL for solitary renal stones of 10-30 mm size. MATERIALS AND METHODS: fURS was carried out in 21 patients with last generation 7.5F endoscopes. Ureteral access sheaths were used in 19 patients. For mPNL, an 18F modified Amplatz sheath with a 14F nephroscope were used (n = 25). The procedure was performed either tubeless with an antegrade stent or a nephrostomy. Outcome and complications of both procedures were assessed. RESULTS: Patients' demographics and stone sizes were comparable (18 ± 5 vs. 19 ± 4 mm, P = 0.08). Patients in the fURS group had a higher mean BMI (31 vs. 27, P < 0.05). Total OR time was significantly longer for fURS (106 ± 51 vs. 59 ± 19 min., P < 0.001). More patients were stone-free after one single percutaneous treatment, while 2nd-stage treatments with fURS were common (total procedures 1.04 vs. 1.52, P < 0.001; immediate stone-free rate (SFR) 96% vs. 71.5%, P < 0.001). SFR after 4 weeks was 100% (mPNL) and 85.8% (fURS) (P < 0.01). Minor complications as classified by Clavien I or II occurred in 16 and 23.8%, mPNL and fURS, respectively, P = 0.13). No major complications (Clavien III-V) occured in both groups. CONCLUSIONS: Our series supports both the concept of either percutaneous or retrograde endoscopic treatment for renal calculi with both modalities offering excellent safety. However, while for fURS, a significantly higher rate of 2nd-stage procedures was necessary, and mPNL led to faster and higher SFR without increasing complication rate.

Do new generation flexible ureterorenoscopes offer a higher treatment success than their predecessors?

New generation flexible ureterorenoscopes offer an improved deflection mechanism and a stiffer sheath compared to their predecessors. We aimed to determine if these improvements in design lead to a higher efficacy in the treatment of nephrolithiasis. Ninety patients with upper urinary tract calculi were included into a retrospective analysis. Twenty-nine cases were treated with the conventional flexible ureterorenoscope (11274 AA, Karl Storz Endoscopy, Germany) and 61 cases were treated with the new generation device (Flex-X, Karl Storz Endoscopy). Patients' and stone characteristics, intraoperative data, treatment success and complications were retrieved from the charts and compared between the two groups. Preoperative data were comparable in both groups. Whereas stone access was also comparable (97 vs. 100%; n.s.), immediate treatment success was significantly higher for the new flexible scope (70 vs. 38%; p = 0.003). For the subgroup of lower pole stones, stone access was possible in 94 versus 100% (n.s.) and treatment success was 31 versus 69% (p = 0.0004) for the conventional and the new generation device, respectively. No major complications were observed, minor complications were comparable in both groups. Our study suggests an advantage of the new generation flexible ureterorenoscopes compared to their predecessors. They offer an increased stone free rate especially in the treatment of lower pole stones. It seems therefore advisable to switch to the latest generation flexible devices.

New alternatives for laser vaporization of the prostate: experimental evaluation of a 980-, 1,318- and 1,470-nm diode laser device.

PURPOSE: Several diode laser systems were introduced in recent years for the minimal-invasive surgical therapy of benign prostate enlargement. We investigated the ablation capacities, hemostatic properties and extend of tissue necrosis of different diode lasers at wavelengths of 980, 1,318 and 1,470 nm and compared the results to the 120 W GreenLight HPS laser. METHODS: The laser devices were evaluated in an ex vivo model using isolated porcine kidneys. The weight difference of the porcine kidneys after 10 min of laser vaporization defined the amount of ablated tissue. Blood loss was measured in blood-perfused kidneys following laser vaporization. Histological examination was performed to assess the tissue effects. RESULTS: The side-firing 980 and 1,470 nm diode lasers displayed similar ablative capacities compared to the GreenLight HPS laser (n.s.). The 1,318-nm laser, equipped with a bare-ended fiber, reached a higher ablation rate compared to the other laser devices (each P < 0.05). A calculated 'output power efficiency per watt' revealed that the 1,318-nm laser with a bare-ended fiber reached the highest rate compared to the side-firing devices (each P < 0.0001). All three diode lasers showed superior hemostatic properties compared to the GreenLight HPS laser (each P < 0.01). The extend of morphological tissue necrosis was 4.62 mm (1,318 nm), 1.30 mm (1,470 nm), 4.18 mm (980 nm) and 0.84 mm (GreenLight HPS laser), respectively. CONCLUSION: The diode lasers offered similar ablative capacities and improved hemostatic properties compared to the 120 W GreenLight HPS laser in this experimental ex vivo setting. The higher tissue penetration of the diode lasers compared to the GreenLight HPS laser may explain improved hemostasis.

Outcome of sigmoid compared to ileal orthotopic bladder substitution in terms of micturition and defecation parameters in an 8-year long-term follow-up.

INTRODUCTION: Various techniques have been described for orthotopic bladder substitution. Bladder substitution with sigma is rather classed as a useful alternative standby. We report the long-term results of sigmoid neobladder in comparison to ileal neobladder with respect to urodynamic and defecation parameters. PATIENTS AND METHODS: We matched 10 patients with sigmoid neobladder (mean age 62.6 +/- 10.9) and 10 patients with ileal neobladder (mean age 66.4 +/- 10.2). Mean follow-up for sigmoid neobladder was 8.1 +/- 2.1 years and 7.2 +/- 1.9 years for the ileal neobladder. Each patient was evaluated by medical history, the SF-36 questionnaire, physical examination and urodynamics. RESULTS: Bladder capacity differed significantly between both groups (sigmoid neobladder 619 ml, ileal neobladder 422 ml). Pressure showed a slight statistical difference (sigmoid neobladder 15 +/- 3 cm H(2)O, ileal neobladder 18 +/- 4 cm H(2)O). The defecation frequency varied significantly between the two groups (sigmoid neobladder 1.1/day, ileal neobladder 3.1/day, p < 0.0001). The SF-36 questionnaire showed no significant difference. CONCLUSION: Orthotopic bladder substitution with sigmoid segments has shown equivalent results compared to orthotopic ileal bladder substitution. The sigmoid neobladder is a useful alternative to the ileal neobladder.

In-vitro comparison of different slice thicknesses and kernel settings for measurement of urinary stone size by computed tomography.

Non-contrast enhanced computed tomography (NCCT) is widely used measuring stone size in patients with urolithiasis. We performed an evaluation of the accuracy of stone size measuring via NCCT. In an in-vitro study, we analyzed a total of 38 uric acid and 38 phantom stones. Within NCCT, we used different slice thicknesses (1.5 mm, 2.0 mm, and 3.0 mm) and kernel settings (bone and soft-tissue window). Maximal height, maximal length, and maximal width of each stone were measured on a picture archiving and communication system workstation. Blinded to these results, a second physician measured stone size in the same way using a caliper (real stone size). We used the Bland-Altman method for the analysis of agreement between the two measuring methods. The limit of agreement that was deemed clinical insignificant was ± 1.0 mm. All measurements via NCCT correlated significantly with the real stone size (p < 0.001). This was more pronounced for bone window and smaller slice thickness. Bland-Altman plots showed limits of agreement that exceeded the a priori defined level for all types of measurement with bone window and small slice thickness (1.5 mm) being better than soft-tissue window and large slice thickness (3.0 mm). We conclude that stone size measurement by NCCT with established settings is not exact. Stone size can easily be over- or underestimated by several millimeters. Using bone window and small slice thickness leads to more accurate results.

Systematic evaluation of a recently introduced 2-microm 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.

Hemostatic properties of four devices for partial nephrectomy: a comparative ex vivo study.

PURPOSE: Laparoscopic partial nephrectomy (LPN) is a common minimally-invasive treatment modality for renal tumors, and achieving hemostasis during excision is a major challenge. The aim of our study was to investigate the hemostatic potential of four different devices for realizing this under standardized conditions. MATERIALS AND METHODS: LPN was performed on a standardized model of blood-perfused ex-vivo porcine kidneys. Each of the four devices (Greenlight KTP laser, Habib Sealer, LigaSure, and SonoSurg) as well as a scalpel (for comparison) were used to perform 10 excisions with the renal artery and vein clamped, and another 10 were performed with no clamping. Treatment time (TT), blood loss (BL), and the ease of handling of the device were measured and histologic examination of the margins was carried out. RESULTS: In general, TT was faster and there was less BL with clamping than without in all cases. TT was shortest for the KTP laser (6.07+/-1.2 minutes; P<0.0001), followed by the LigaSure (8.78+/-0.42 minutes), the SonoSurg (15.9+/-1.28 minutes), and the Habib (21.7+/-3.4 min). The SonoSurg showed a significantly higher BL without clamping (66+/-6 ml, p<0.0001) but there were no significant differences between the other devices. With clamping, BL four all four devices was comparable (13+/-2 ml) and without statistical significance (p=0.5). TT was shortest for the KTP laser (3.27+/-0.55 min, p<0.0001) followed by the LigaSure (6.47+/-0.38 s), the SonoSurg (8.35+/-3 min) and the Habib (9.71+/-1.18 minutes). The excised surface was completely coagulated for all of the devices except for the SonoSurg. CONCLUSION: Our ex-vivo study suggests that hemostatic potential and the coagulative effect of all four devices is inadequate. Furthermore, none of the devices produced clean and sharp resection margins, which is a prerequisite for negative surgical margins.

Prospective evaluation of acute endocrine pancreatic injury as collateral damage of shock-wave lithotripsy for upper urinary tract stones.

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.

Ureteroscopy for stone treatment using new 270 degrees 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.

A biological model to teach percutaneous nephrolithotomy technique with ultrasound- and fluoroscopy-guided access.

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.

Improvement in mortality and morbidity in transurethral resection of the prostate over 17 years in a single center.

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.

Microstructures of Randall's plaques and their interfaces with calcium oxalate monohydrate kidney stones reflect underlying mineral precipitation mechanisms.

Randall's plaques (RP) are preferred sites for the formation of calcium oxalate monohydrate (COM) kidney stones. However, although processes of interstitial calcium phosphate (CaP) plaque formation are not well understood, the potential of plaque microstructures as indicators of CaP precipitation conditions received only limited attention. We investigated RP-associated COM stones for structural details of the calcified tissues and microstructural features of plaque-stone interfaces as indicators of the initial processes of stone formation. Significantly increased CaP supersaturation can be expected for interstitial fluid, if reabsorbed ions from the tubular system continuously diffuse into the collagenous connective tissue. Densely packed, fine-grained CaP particles were found in dense textures of basement membranes while larger, laminated particles were scattered in coarse-meshed interstitial tissue, which we propose to be due to differential spatial confinements and restrictions of ion diffusion. Particle morphologies suggest an initial precipitation as metastable amorphous calcium phosphate (ACP). Morphologies and arrangements of first COM crystals at the RP-stone interface ranged from stacked euhedral platelets to skeletal morphologies and even porous, dendritic structures, indicating, in this order, increasing levels of COM supersaturation. Furthermore, these first COM crystals were often coated with CaP. On this basis, we propose that ions from CaP-supersaturated interstitial fluid may diffuse through porous RP into the urine, where a resulting local increase in COM supersaturation could trigger crystal nucleation and, hence, initiate stone formation. Ion-depleted fluid in persistent pores of initial COM layers may get replenished from interstitial fluid, leading to CaP precipitation in porous COM.

Risk of collateral damage to endourologic tools by holmium:YAG laser energy.

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.