miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215.

BACKGROUND: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Metastatic RCC is difficult to treat. The 5-year survival rate for metastatic RCC is ≤10%. Recently, microRNAs (miRNAs) have been shown to have a role in cancer metastasis and potential as prognostic biomarkers in cancer. METHOD: We performed a miRNA microarray to identify a miRNA signature characteristic of metastatic compared with primary RCCs. We validated our results by quantitative real-time PCR. We performed experimental and bioinformatic analyses to explore the involvement of miR-215 in RCC progression and metastasis. RESULTS: We identified 65 miRNAs that were significantly altered in metastatic compared with primary RCCs. We validated our results by examining the expression of miR-10b, miR-126, miR-196a, miR-204 and miR-215, in two independent cohorts of patients. We showed that overexpression of miR-215 decreased cellular migration and invasion in an RCC cell line model. In addition, through gene expression profiling, we identified direct and indirect targets of miR-215 that can contribute to tumour metastasis. CONCLUSION: Our analysis showed that miRNAs are altered in metastatic RCCs and can contribute to kidney cancer metastasis through different biological processes. Dysregulated miRNAs represent potential prognostic biomarkers and may have therapeutic applications in kidney cancer.

A randomized, double-blind trial to compare shock wave frequencies of 60 and 120 shocks per minute for upper ureteral stones.

PURPOSE: Recent evidence demonstrates that decreasing shock wave frequency from the previous standard of 120 to 60 shocks per minute results in improved fragmentation of stones located within the renal collecting system. We report the first randomized trial to our knowledge to examine the effect of a slower shock wave frequency for shock wave lithotripsy on stones located in the proximal ureter. MATERIALS AND METHODS: A total of 163 patients with a previously untreated radiopaque calculus in the upper ureter measuring at least 5 mm underwent stratified block randomization according to stone size, and shock wave lithotripsy at 60 or 120 shocks per minute. Stone-free status at 3 months was confirmed with noncontrast computerized tomography or a plain abdominal x-ray and ultrasound study. RESULTS: Of the patients 77 were randomized to 60 shocks per minute and 86 were randomized to 120 shocks per minute. The groups were similar in gender, age, body mass index and initial stone area. At 3 months the 60 shocks per minute group had a higher overall stone-free rate (64.9% vs 48.8%, p = 0.039). Significantly fewer shocks were administered to patients treated at 60 shocks per minute (mean 2,680 vs 2,940, p <0.001). However, mean treatment times were longer (44.3 vs 24.5 minutes, p <0.001). Patients treated with 60 shocks per minute required fewer auxiliary procedures (29.9% vs 45.4%) (p = 0.031). CONCLUSIONS: Decreasing the rate of shock wave administration from 120 to 60 shocks per minute results in improved stone-free rates. A slower treatment rate of proximal ureteral stones reduces the need for additional shock wave lithotripsy or more invasive treatments to render patients stone-free, without any increase in morbidity, and with an acceptable increase in treatment time.

Individual patient variation and inter-rater reliability of lower calyceal infundibular width on routine intravenous pyelography.

OBJECTIVE: To standardise infundibular width (IFW) measurement, to determine patient variability, and to determine inter-rater variability on intravenous pyelography (IVP). PATIENTS AND METHODS: Fifty outpatient IVP films were randomly drawn from two hospitals between 1 July 1998 and 31 August 1999, and examined to measure the lower calyceal IFW on the 5, 10 and 20 min films with compression, and after voiding. Kidneys with previous renal surgery, hydronephrosis or renal anatomical anomalies were excluded; in all, 81 kidneys from 50 patients were examined. The IFW was measured at the narrowest point along the infundibulum. All 50 films were then reviewed by two urologists unaware of their origin, to determine the inter-rater reliability of the infundibular measurements. RESULTS: Analysis of variance (anova) with posthoc analysis showed a significant difference in IFW at each phase of the IVP (repeated measures anova, P < 0.001). The mean (95% confidence interval) IFW was greatest on the compression film, at 4.4 (2.6) mm, and least on the postvoid film, at 1.6 (2.1) mm. Overall inter-rater reliability was 0.9780 (intraclass correlation coefficient), and the Pearson correlation between each rater for the IFW at each phase of the IVP was >/= 0.886. CONCLUSIONS: There is wide variability in lower calyceal IFW among the various IVP films in a given study. Thus any predictive value of the IFW must be standardized for the timing and IVP film type (compression, postvoid, etc.). The inter-rater reliability of IFW is high, suggesting that if used correctly it may be more useful in predicting the outcome after shock wave lithotripsy.

Laparoscopic versus open donor nephrectomy.

BACKGROUND: As compared with open donor nephrectomy (OpenDN), laparoscopic donor nephrectomy (LapDN) offers donors more rapid recovery and recipients equivalent graft function, but LapDN costs remain greater. This study compared LapDN and OpenDN with cost-utility analysis. METHODS: Utilities were assessed with time trade-off, probabilities derived from systematic review of the literature and the costs derived from 27 OpenDN and 34 LapDN patients treated contemporaneously. A societal perspective was taken. Lost employment costs were included. An incremental cost-effectiveness ratio (ICER) was calculated with best- and worst-case scenarios for confidence intervals. Sensitivity analyses assessed robustness. RESULTS: LapDN costs are lower (11,170.71 dollars vs 12,631.91 dollars), whereas quality of life (QOL) is superior (0.7247 vs 0.6585 quality-adjusted life years [QALY], rendering LapDN a dominant strategy. The model was robust to all variables, and LapDN remained dominant from a payer perspective. In a worst-case scenario, the ICER for LapDN was at most 2,231.61 dollars per QALY. CONCLUSIONS: LapDN offers improved QOL at lower costs, despite the fact that this analysis included patients treated during the learning curve of LapDN at our institution. By potentially increasing organ donor rates, LapDN may be further cost saving by decreasing the number of patients receiving dialysis.

Health-related quality of life after laparoscopic and open nephrectomy.

BACKGROUND: Postoperative recovery often is assessed with parameters (pain and return to work) susceptible to bias. This study sought objectively to compare postoperative health-related quality of life (HRQL) after laparoscopic and open nephrectomy with the Postoperative Recovery (PRS) (a validated questionnaire designed to assess pain), activities of daily living (ADL), and HRQL in postoperative patients. METHODS: Patients undergoing contemporaneous laparoscopic and open nephrectomy received the PRS pre- and postoperatively. The results were analyzed with analysis of covariance (ANCOV) and survival analysis. RESULTS: The 33 open nephrectomy and 38 laparoscopic patients in this study were comparable in age, gender, body mass index (BMI) and employment. Laparoscopic operative time was longer (p = 0.015), and the hospital stay was shorter (p<0.001). Laparoscopic patients had higher HRQL scores from postoperative days 3 to 365 (p<0.001), and they returned to preoperative HRQL faster (p<0.001). CONCLUSIONS: An objective HRQL instrument confirms that laparoscopic nephrectomy patients recover faster and with a higher HRQL than open surgery patients. The PRS can be modified for use after other abdominal procedures, and may prove useful for comparisons of other minimally invasive surgical techniques.

Mechanical percussion, inversion and diuresis for residual lower pole fragments after shock wave lithotripsy: a prospective, single blind, randomized controlled trial.

PURPOSE: We compare the effectiveness of mechanical percussion and inversion with observation for eliminating lower caliceal fragments 3 months after shock wave lithotripsy. MATERIALS AND METHODS: At 3 months after shock wave lithotripsy 69 patients with residual lower caliceal fragments 4 mm. or less were randomized to receive either mechanical percussion and inversion or observation for 1 month. The observation group then received crossover mechanical percussion and inversion if fragments persisted. All patients were followed with plain film of the kidneys, ureters and bladder to assess the stone area and stone-free status, and renal tomography or noncontrast spiral computerized tomography to confirm stone-free status. A blinded radiologist reviewed all films. Patients were treated with a mechanical chest percussor applied to the flank while inverted to greater than 60 degrees after receiving 20 mg. furosemide. RESULTS: A total of 35 patients were randomized to receive immediate mechanical percussion and inversion therapy and 34 observation. Of the patients in the observation group 28 subsequently received mechanical percussion and inversion after completing the observation period. The groups were not different in gender, body mass index, side affected, stone location or renal anatomical features. The mechanical percussion and inversion group had a substantially higher stone-free rate than the observation group (40% versus 3%, respectively, p <0.001). The mechanical percussion and inversion group also had a greater improvement in total stone area than controls (-63.3% versus +2.7%, respectively, p <0.001). No significant adverse effects were noted in the mechanical percussion and inversion group. CONCLUSIONS: Mechanical percussion and inversion is a safe and effective treatment option for residual lower caliceal fragments 3 months after shock wave lithotripsy. Nearly 50% of patients become stone-free, and stone burden is decreased by 50% in the remainder.

A comparison of patient-controlled sedation using either remifentanil or remifentanil-propofol for shock wave lithotripsy.

UNLABELLED: 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 microg or remifentanil 10 microg 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. IMPLICATIONS: The addition of propofol to remifentanil improves patient satisfaction and decreases postoperative nausea and vomiting. However, it causes more respiratory depression than remifentanil alone. When remifentanil-propofol is used with patient-controlled sedation, appropriate monitoring and a minimum 1-2 min lockout interval is required.

Thoracoscopy-assisted high intercostal percutaneous renal access.

PURPOSE: We describe a technique for safely accessing an upper pole calix through a 9th or 10th intercostal puncture. PATIENTS AND METHODS: A 9th or 10th intercostal access was used for percutaneous nephrolithotomy (PCNL) in nine patients. Thoracoscopy via the 5th or 6th intercostal space was used to ensure safe passage of the nephrostomy needle. RESULTS: Access was obtained in all patients without visceral injury. Seven patients were stone free after PCNL; the initial two required sandwich therapy to become so. Chest tubes were inserted routinely in the first eight cases. They were removed on postoperative day three and did not affect the length of hospital stay. CONCLUSIONS: Access through the 9th or 10th intercostal space is occasionally necessary and is ideal in certain circumstances. Thoracoscopy-assisted percutaneous renal access allows access under direct vision, thus preventing pulmonary injury.

Electrode performance beyond the manufacturer's recommended lifespan using the Dornier MFL 5000 lithotripter.

BACKGROUND AND PURPOSE: Electrodes used by the Dornier MFL 500 lithotripter have a specified lifespan, after which, the manufacturer recommends replacing the electrode before continuing the treatment. The aim of this study was to investigate whether electrodes continue to function effectively beyond 100% consumption by measuring the pressure output of electrodes up to 300% consumption or until electrode failure. MATERIALS AND METHODS: We assessed new, refurbished, and twice-refurbished electrodes to compare their respective performances. RESULTS: Rather than a decrease, there was a trend toward increased pressure output beyond 100% electrode consumption, with no drop in pressure prior to 300% consumption or electrode failure. All three types of electrodes functioned adequately above 100% consumption. CONCLUSION: These observations suggest that discarding the electrode before the completion of the treatment or electrode failure is not warranted. Using a single electrode rather than multiple electrodes to complete a treatment has the potential to save both time and cost.

A prospective randomized controlled trial comparing nonstented versus stented ureteroscopic lithotripsy.

PURPOSE: A prospective randomized controlled trial was performed to determine whether stents may be eliminated after uncomplicated ureteroscopic lithotripsy for ureteral stones. MATERIALS AND METHODS: A total of 58 patients underwent uncomplicated ureteroscopic intracorporeal lithotripsy. After stone fragmentation patients were randomized to a nonstented (29) or a stented (29) treatment group. Intracorporeal lithotripsy was performed with the holmium laser in 57 cases and by electrohydraulic lithotripsy in 1 without balloon dilation or the extraction of stone fragments. Patients were followed 1, 6 and 12 weeks postoperatively. In stented cases the stent was removed at 1 week. Outcome measures included postoperative symptoms assessed with a visual analog scale, postoperative analgesic requirements, complications and the stone-free rate. RESULTS: At 1 week the symptoms of flank pain, abdominal pain, dysuria and frequency were significantly greater in the stented group (p <0.005). There were no differences in symptoms in the groups at subsequent followup visits. There was no difference in treatment groups in terms of the amount of analgesic required in the recovery room or during 1 week after ureteroscopy. Similarly there was no difference in the number of patients requiring antiemetics. One patient in the stented group required hospitalization for genitourinary sepsis and 1 patient in the nonstented group visited the emergency room for postoperative vomiting. The stone-free rate was 100% in each group. CONCLUSIONS: These results demonstrate that after ureteroscopic intracorporeal lithotripsy with the holmium laser patients with a stent have significantly greater irritative and painful symptoms than those without a stent in the early postoperative period. There was no difference in nonstented and stented ureteroscopy with respect to complications or stone-free status. Therefore, we believe that routine stenting after ureteroscopic intracorporeal lithotripsy with the holmium laser is not required as long as the procedure is uncomplicated and performed without balloon dilation of the ureteral orifice.

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.

Higher urinary potassium is associated with decreased stone growth after shock wave lithotripsy.

PURPOSE: We correlated serum and urinary biochemical parameters with radiological evidence of stone growth after shock wave lithotripsy. MATERIALS AND METHODS: Biochemical parameters in serum and 24-hour urine collections of 359 patients were correlated with stone growth for 2 years after shock wave lithotripsy. Each patient underwent a minimum of 2 radiological studies at 3 and 12 months and plain abdominal x-ray at 24 months. The presence and size of stones were documented by a radiologist in blinded fashion. Stone growth was defined as measurable growth of a preexisting stone or new stone formation. RESULTS: A total of 209 patients remained stone-free or had no existing stone growth, while stone size decreased in 30. Of the remaining 120 patients with stone growth 72 had new growth and 48 had growth of preexisting stones. Urinary excretion of potassium was significantly higher in those without than with stone growth (mean 24-hour urine collection plus or minus standard deviation 62 +/- 27 versus 54 +/- 23 mmol., p = 0.009). The only parameter significantly associated with stone growth was urinary potassium. Linear regression revealed that for each 10 unit increase in urinary potassium there was a corresponding 2 mm. decrease in stone growth (p = 0.013). CONCLUSIONS: Our results indicate that increased urinary potassium excretion correlates with a decreased risk of stone growth up to 2 years after shock wave lithotripsy, implying that a high potassium diet may be beneficial for preventing stone growth. The effect of potassium supplementation on stone formation and growth must be investigated further.

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.

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.

Mechanical percussion inversion can result in relocation of lower pole stone fragments after shock wave lithotripsy.

OBJECTIVES: To determine whether mechanical percussion combined with inversion (MPI) therapy and forced diuresis can move stone fragments out of the lower pole of the kidney. METHODS: Twelve patients with lower pole residual stone fragments at least 2 weeks after shock wave lithotripsy were treated using the following protocol. Eleven patients received 20 mg of furosemide before MPI therapy. Patients were treated in the prone Trendelenberg position on a pivoting stretcher and given 10 minutes of percussion over the flank using a mechanical chest physiotherapy percussor. Stone location was documented with plain abdominal radiographs before, immediately after, and 2 weeks following MPI therapy. Voided urine was strained immediately after MPI therapy and throughout the study period. RESULTS: Abdominal radiographs before and after treatment demonstrated movement of fragments out of the lower pole in 11 patients. In 8 patients, the lower pole appeared entirely clear of fragments on the immediate post-treatment film. Four patients passed stone fragments in their first voided urine. Ten patients passed stone fragments during the 2-week follow-up period. CONCLUSIONS: MPI therapy combined with diuresis can effectively mobilize stone fragments out of the lower pole calyces and appears to aid in the passage of fragments.

A randomized controlled trial to assess the incidence of new onset hypertension in patients after shock wave lithotripsy for asymptomatic renal calculi.

PURPOSE: To answer the question of whether extracorporeal shock wave lithotripsy (ESWL*) induces hypertension, a prospective, randomized controlled trial of normotensive patients with asymptomatic renal calculi was designed. MATERIALS AND METHODS: Patients were randomized to receive immediate ESWL versus observation, reserving ESWL for the onset of symptoms. The rates of new onset hypertension were evaluated for both groups. RESULTS: There was no observed difference in the incidence of hypertension between the treatment and observation groups. CONCLUSIONS: The risk of hypertension in patients undergoing ESWL therapy is similar to that of a control cohort of initially observed asymptomatic patients.

Assessment of a new tipless nitinol stone basket and comparison with an existing flat-wire basket.

Flexible nephroscopes and ureteroscopes make it possible to see calculi in remote calices, but it is often impossible to remove these with existing technology. Flat-wire baskets impede deflection and can traumatize the papilla. This study compares the performance of a new 3.2F tipless nickel-titanium (Nitinol) basket with that of an existing 3.0F flat-wire basket. Specifications were compared using a 15F nephroscope and a 7.5F flexible ureteroscope in a pig kidney model. A calculus was placed in a calix, and the author and two residents were timed while using both baskets to retrieve the stone. To open fully, the flat-wire basket needed to protrude 1.2 cm further than the tipless basket. The tipless basket did not restrict deflection of the nephroscope, whereas the flat-wire basket limited flexion by 24 degrees and extension by 28 degrees. The tipless basket did not restrict extension of the 7.5F ureteroscope but limited flexion by 10 degrees. The flat-wire basket limited flexion by 79 degrees and extension by 72 degrees. Using the pig kidney model, the three operators took a mean of 5.3, 11.8, and 6.4 seconds to catch the stone with the tipless basket. Using the flat-wire basket, the mean times were 15.3, 34.5, and 28.9 seconds (combined data: 8.2 seconds for the tipless basket and 27.8 seconds with the flat-wire basket; P = 0.0001). Only the flat-wire basket was seen to traumatize the papilla. The Nitinol tipless basket has significant advantages over the flat-wire basket.

Diagnosis and management of urethral sarcoidosis.

We report on a woman with urethral sarcoidosis with obstructive urinary symptoms and previously known systemic sarcoidosis. The diagnosis of this rare lesion and management are discussed, and the genitourinary manifestations of sarcoidosis are reviewed.

Testicular seminoma presenting with features of androgen excess.

A 32-year-old white man presented with worsening acne and noticeable increase in muscle bulk. On examination, a firmer area with a granular consistency was noted in the right testis. A right radical orchiectomy was performed and the histologic findings were those of a typical seminoma associated with marked Leydig cell hyperplasia. A solitary right iliac lymph node metastasis, but not the primary seminoma, contained human chorionic gonadotrophin- (HCG) producing syncytiotrophoblast, which was regarded as the hormonal stimulus for Leydig cell hyperplasia and elevated serum testosterone. This seems to be the first report of testicular seminoma presenting with symptoms of androgen excess.