R. John D'a. Honey

VARIATION IN CLINICAL OUTCOME FOLLOWING SHOCK WAVE LITHOTRIPSY

PURPOSE We measure and compare operator specific success rates of extracorporeal shock wave lithotripsy (ESWL) performed by 12 urologists in 1 unit to determine interoperator variation. MATERIALS AND METHODS From January 1, 1994 to September 1, 1997 a total of 5,769 renal and ureteral stones received 9,607 ESWL treatments by 15 urologists with a Dornier MFL 5000 lithotriptor. The 3-month followup data are available for 4,409 stones. Outcome measures consisted of patient demographics, stone characteristics, technical details of lithotripsy, and stone-free and success rates by treating urologists. RESULTS Treatment results were analyzed for 12 urologists (surgeons A to L) who treated more than 100 stones each, totaling 4,244 with followup information available. Mean stone-free and success rates were 50.6% and 72.3%, respectively. Surgeon A had significantly higher stone-free and success rates of 56.2% and 76.7%, respectively (p<0.05), with treatment results from 877 stones, which was a significantly higher number than others (p<0.05). Significant differences existed in mean number of shocks delivered among urologists (p = 0.0001), with surgeons A and J delivering the highest mean numbers (2,317 and 2,801, respectively). There was no difference in treatment duration (p = 0.75) but variation existed among urologists in terms of mean maximum treatment voltage (p = 0.0001). Mean fluoroscopy time at 4.1 minutes was higher for surgeon A than others (p<0.05). Mean complication rate following ESWL was 4.9% with no difference among urologists (p = 0.175). Re-treatment was required in 21.7% of cases and surgeon A had the lowest rate (15.9%, p<0.05). CONCLUSIONS We demonstrated clinically and statistically significant intra-institutional differences in success rates following ESWL. The best results were obtained by the urologist who treated the greatest number of patients, used a high number of shocks and had the longest fluoroscopy time. Accurate targeting is crucial when using a lithotriptor, such as the Dornier MFL 5000, with a narrow focal zone of 6.5 mm. in diameter. Other centers should be encouraged to develop similar programs of outcome analysis in an attempt to improve performance.

LOW SUCCESS RATE OF REPEAT SHOCK WAVE LITHOTRIPSY FOR URETERAL STONES AFTER FAILED INITIAL TREATMENT

PURPOSE We determined the number of shock wave lithotripsy treatments that should be given for a single ureteral stone before alternate modalities are used. MATERIALS AND METHODS We compared the stone-free rate of initial shock wave lithotripsy for ureteral calculi with that of subsequent treatments. We evaluated 1,593 ureteral stones treated with the Dornier MFL 5000 lithotriptor* from January 1, 1994 to September 1, 1999 using various parameters associated with treatment outcome. RESULTS The stone-free rate after initial treatment was 68% (1,086 of 1,593 stones), which decreased to 46% (126 of 273) after re-treatment 1. We observed a further decrease in the stone-free rate after re-treatment 2 to 31% (19 of 61 stones, p = 0.001). The cumulative stone-free rate increased to 76% (1,212 of 1,593 stones) after 2 treatments and to 77% (1,231 of 1593) after 3. The stone-free rate for stones 10 mm. or less was significantly better than that of stones 11 to 20 mm. initially (64% versus 43%) and after re-treatment (49% versus 37%). A ureteral stent decreased the stone-free rate of initial treatment and re-treatment 1 by 12% and 14%, respectively (p = 0.001). After initial treatment the stone-free rate of the upper and mid ureter was significantly higher than that of the lower ureter. Patient weight had no significant impact on success in either group. CONCLUSIONS The stone-free rate of re-treating ureteral calculi with shock wave lithotripsy decreases significantly after the initial treatment. These findings imply that ureteroscopic management of ureteral stones may be better than shock wave lithotripsy after initial shock wave lithotripsy fails.

Differential protein expressions in renal cell carcinoma: new biomarker discovery by mass spectrometry.

Renal cell carcinoma (RCC) is the most common neoplasm in the adult kidney. Unfortunately, there are currently no biomarkers for the diagnosis of RCC. In addition to early detection, biomarkers have a potential use for prognosis, for monitoring recurrence after treatment, and as predictive markers for treatment efficiency. In this study, we identified proteins that are dysregulated in RCC, utilizing a quantitative mass spectrometry analysis. We compared the protein expression of kidney cancer tissues to their normal counterparts from the same patient using LC-MS/MS. iTRAQ labeling permitted simultaneous quantitative analysis of four samples (cancer, normal, and two controls) by separately tagging the peptides in these samples with four cleavable mass-tags (114, 115, 116, and 117 Da). The samples were then pooled, and the tagged peptides resolved first by strong cation exchange chromatography and then by nanobore reverse phase chromatography coupled online to nanoelectrospray MS/MS. We identified a total of 937 proteins in two runs. There was a statistically significant positive correlation of the proteins identified in both runs (r(p) = 0.695, p < 0.001). Using a cutoff value of 0.67 fold for underexpression and 1.5 fold for overexpression, we identified 168 underexpressed proteins and 156 proteins that were overexpressed in RCC compared to normal tissues. These dysregulated proteins in RCC were statistically significantly different from those of transitional cell carcinoma and end-stage glomerulonephritis. We performed an in silico validation of our results using different tools and databases including Serial Analysis of Gene Expression (SAGE), UniGene EST ProfileViewer, Cancer Genome Anatomy Project, and Gene Ontology consortium analysis.

A Comparison of Patient-controlled Sedation Using Either Remifentanil or Remifentanil-propofol for Shock Wave Lithotripsy

Patient-controlled sedation (PCS) has been used for extracorporeal shock wave lithotripsy (SWL) because it allows for rapid individualized titration of anesthetics. Because of its sedating effects, the addition of propofol to remifentanil may improve patient tolerance of SWL with PCS. One hundred twenty patients were randomly assigned to receive remifentanil 10 &mgr;g or remifentanil 10 &mgr;g plus propofol 5 mg for PCS with zero-lockout interval. Nine patients in the Remifentanil group and three patients in the Remifentanil-Propofol group required additional sedatives to complete their SWL (P = 0.128). Compared with the Remifentanil group, the Remifentanil-Propofol group required less remifentanil, had a decreased incidence of postoperative nausea and vomiting, and had a better overall satisfaction level. However, they had an increased incidence of transient apnea and oxygen desaturation. The incidence of apnea was 15% in the Remifentanil group and 52% in the Remifentanil-Propofol group (P < 0.001). All patients were able to move themselves to the stretcher at the end of SWL, and median time to home discharge was <70 min in both groups. Both remifentanil and remifentanil-propofol were useful for PCS during SWL.

Shockwave Frequency Affects Fragmentation in a Kidney Stone Model

PURPOSE To study the effect of altering shockwave frequency on the efficiency of stone fragmentation using the MFL 5000 spark-gap lithotripter. MATERIALS AND METHODS Standardized solid plaster stones, 12.0 +/- 0.5 mm in diameter, were fragmented at an energy setting of 20 kV. The shockwave frequencies tested were 60, 80, and 117 per minute. Stones were fragmented throughout the entire lifespan of the electrode, from 0 to >100% consumption, at each frequency tested. Electrode pressure output was studied for each frequency. RESULTS A greater number of shocks was required to fragment the plaster balls at higher frequencies (regression coefficient 1.93; p < 0.003). An inverse relation was found between the number of shocks necessary to break the stones and electrode consumption (regression coefficient -2.16; p < 0.001). The analysis of delivered pressure from the electrode failed to demonstrate a linear relation with frequency (regression coefficient -0.40; p < 0.728) or consumption (regression coefficient -1.11; p < 0.158). CONCLUSIONS The number of shocks required to fragment a stone is influenced in part by the frequency at which the shockwaves are delivered. Increasing the shockwave frequency from 60 to 117 per minute in this study caused a significant rise in the number of shocks required to break the stone. The pressure output of the electrode was similar at the frequencies tested, thus making the difference in stone fragmentation secondary to the mechanism of stone disintegration and not the function of the electrode.

Dysregulation of kallikrein-related peptidases in renal cell carcinoma: potential targets of miRNAs

Abstract Renal cell carcinoma (RCC) accounts for 3% of all adult malignancies and currently no diagnostic marker exists. Kallikrein-related peptidases (KLKs) have been implicated in numerous cancers including ovarian, prostate, and breast carcinoma. KLKs 5, 6, 10, and 11 have decreased expression in RCC when compared to normal kidney tissue. Our bioinformatic analysis indicated that the KLK 1, 6, and 7 genes have decreased expression in RCC. We experimentally verified these results and found that decreased expression of KLKs 1 and 3 were significantly associated with the clear cell RCC subtype (p<0.001). An analysis of miRNAs differentially expressed in RCC showed that 61 of the 117 miRNAs that were reported to be dysregulated in RCC were predicted to target KLKs. We experimentally validated two targets using two independent approaches. Transfection of miR-224 into HEK-293 cells resulted in decreased KLK1 protein levels. A luciferase assay demonstrated that hsa-let-7f can target KLK10 in the RCC cell line ACHN. Our results, showing differential expression of KLKs in RCC, suggest that KLKs could be novel diagnostic markers for RCC and that their dysregulation could be under miRNA control. The observation that KLKs could represent targets for miRNAs suggests a post-transcriptional regulatory mechanism with possible future therapeutic applications.

Virtual reality ureteroscopy simulator as a valid tool for assessing endourological skills

Aim:  Virtual reality (VR) simulators are now commercially available for various surgical skills training. The Uro Mentor VR Ureteroscopy Simulator by Symbionix is one system that may revolutionize the way we assess and teach surgical residents. Surgical educators may no longer have to depend on the operating room as the sole venue for teaching residents technical skills. We validated performance on this new system with previously developed assessment tools and compared it to performance on a high fidelity ureteroscopy bench model.

A Comparison of Treatment Modalities for Renal Calculi Between 100 and 300 mm2: Are Shockwave Lithotripsy, Ureteroscopy, and Percutaneous Nephrolithotomy Equivalent?

BACKGROUND AND PURPOSE Shockwave lithotripsy (SWL) is considered a standard treatment for patients with upper-tract stones that are less than 10 mm in diameter, whereas stones that are larger than 20 mm are best managed by percutaneous nephrolithotomy (PCNL). The management of stones between these sizes remains controversial. Our purpose was to review our contemporary series of SWL, ureteroscopy (URS), and PCNL outcomes for intermediate-sized upper tract calculi (100-300 mm(2)). PATIENTS AND METHODS Analysis was restricted to those patients who were treated for a renal calculus that measured between 100 and 300 mm(2) during a 4-year span. Demographic, stone, patient, treatment, and follow-up data were collected from a prospectively maintained database. RESULTS A total of 137 patients were referred with nonstaghorn calculi with an area between 100 and 300 mm(2). Fifty-three (38.7%) patients were treated with SWL, while 41 (29.9%) and 43 (31.4%) underwent ureteroscopy and PCNL, respectively. Mean stone area was higher in the PCNL group (P < 0.001), whereas stone density was higher for patients undergoing SWL (P = 0.002). Single treatment success rates were better for PCNL at 95.3%,vs 87.8% for ureteroscopy and 60.4% for SWL, P < 0.001. When allowing for two SWL treatments, the success rate improved to 79.2%, thus equalizing the success of the three treatment modalities (P = 0.66). Auxiliary treatments were more common after SWL (42.3%; P < 0.01). CONCLUSIONS For intermediate-sized upper-tract stones, when allowing for up to two SWL treatments, there was no significant difference between treatment modalities. Thus, SWL is a reasonably successful treatment alternative for patients who are not fit for a general anesthetic or who prefer SWL over competing treatments, provided they accept a potentially higher number of treatments.

Percutaneous Nephrolithotomy in the Prone and Prone-Flexed Positions: Anatomic Considerations

OBJECTIVES Percutaneous nephrolithotomy is commonly performed in the prone position. Knowledge of renal anatomy and the relationship of adjacent organs is essential to minimize patient morbidity and iatrogenic organ injury. We present the anatomical basis for a prone-flexed modification to patient positioning and review the advantages and disadvantages of alternate positions. METHODS Triphasic computed tomography was conducted with the patient in supine, prone, and prone-flexed positions, and an anatomical survey was conducted. A 30 degrees angle was used to approximate the plane of nephrostomy access and the risk of organ injury. RESULTS For upper pole punctures, the liver and spleen were more medially situated, and thus more likely to be injured with supine positioning, compared with either prone or prone-flexed positioning (p < 0.001). In contrast, for lower pole punctures, the colon was more medially situated in the prone and prone-flexed positions compared to supine (p < 0.001). With prone-flexed positioning, the left kidney was displaced lower than the right in 92.3% of cases. The prone-flexed modification increased the distance from the posterior iliac crest to the 12th and 11th ribs by 2.9 and 3.0 cm, respectively (p < 0.001). If access was performed in the most superior calyx, this would have converted an upper pole access above the 11th rib to one above the 12th rib in 5 of 11 patients (45.5%). CONCLUSIONS Prone-flexed positioning is a simple modification that provides improved access to the upper pole and more mobility for lower pole percutaneous nephrolithotomy. This position is well tolerated and has several advantages over other patient positions, including the supine position.

Urinary Potassium Is a Clinically Useful Test to Detect a Poor Quality Diet

Poor eating habits, a strong predictor of health outcomes, are not objectively assessed in routine clinical practice. In this study, we evaluated the use of urinary potassium (K(+)) as a means to identify people consuming a poor quality diet. Consecutive patients with kidney stones (n = 220), aged 18-50 y, from a population-based lithotripsy unit, collected a single 24-h urine sample to assess urinary K(+). They also completed a FFQ to derive the recommended foods score (RFS), an index of overall diet quality, and had their blood pressure, heart rate, weight, and height measured. Urinary K(+) was related positively with the intake of recommended food items, including vegetables, fruit, whole grains, low-fat dairy products, fish and poultry, and wine and negatively to those not recommended by current dietary guidelines, including red meat, fast food, and high-energy drinks. Urinary K(+) was also correlated with the RFS (r = 0.226; P < 0.001). Using a receiver operating characteristic curve, K(+) excretion values below the gender-specific median (men, 60 mmol/d; women, 41 mmol/d) were identified as the optimal cutoff values for a poor quality diet, indicated by the RFS. Higher urinary K(+) was inversely related to adjusted BMI (P-trend = 0.03), diastolic blood pressure (P-trend = 0.04) and heart rate (P-trend = 0.006), after controlling for potential confounders. Urinary K(+) provides a summary measure of diet quality, is significantly related to BMI, blood pressure, and heart rate, and may be useful clinically to detect poor dietary habits and monitor response to dietary interventions.