The impact of radical prostatectomy and external beam radiotherapy on the quality of life of patients was compared.
A total of 136 patients underwent radical prostatectomy and 60 underwent external beam radiotherapy for clinically localized prostate cancer. Patients were asked to complete a questionnaire containing The Functional Living Index: Cancer, the Profile of Moods States, and a series of questions evaluating bladder, bowel and sexual function.
The radical prostatectomy group had worse sexual function and urinary incontinence, while the external beam radiotherapy group had worse bowel function. Of the patients 90% from both groups stated that they would undergo the treatment again.
Radical prostatectomy and external beam radiotherapy have comparable impact upon quality of life.
Most surgical interventions have inherent benefits and associated risks. Before implementing a new therapy we should ascertain the benefits and risks of the therapy and assure ourselves that the resources consumed in the intervention will not be exorbitant.
We suggest a 3-step approach to using an article from the urological literature to guide patient care. We recommend asking whether the study can provide valid results, reviewing the results and considering how the results can be applied to patient care.
Key methodological characteristics that have an impact on the validity of a surgical trial include randomization, allocation concealment, stratification, blinding, completeness of followup and intent to treat analysis. To the extent that the quality is poor inferences from this study are weakened. However, if its quality is acceptable, one must determine the range within which the true treatment effect lies (95% CI). One must then consider whether this result can be generalized to a patient and whether the investigators have provided information about all clinically important outcomes. It is then necessary to compare the relative benefits of the intervention with its risks. If one perceives that the benefits outweigh the risks, the intervention may be of use to the patient.
Given the time constraints of busy urological practices and training programs, applying this analysis to every relevant article would be challenging. However, the basics of this process are essentially what we all do hundreds of times each week when treating patients. Making this process explicit with guidelines to assess the strength of the available evidence will serve to improve patient care. It will also allow us to defend therapeutic interventions based on available evidence and not on anecdote.
Properly conducted clinical trials provide essential evidence about the benefits and harms of a therapeutic intervention. To ensure accurate interpretation of study findings urologists should understand measures of effect and their precision. In this segment of the Users' Guide to the Urological Literature series we provide guidance on how measures of effect and precision should be interpreted and used in the evidence-based practice of urology.
Using an example from the urology literature we define commonly used measures of effect and describe how these statistics can be readily generated from the results of a clinical trial. We also highlight the importance of confidence interval interpretations when critically appraising study findings.
The effect of an intervention can be described in absolute or relative terms. Risk of an event, risk difference and number needed to treat are easy to interpret, and allow the patient and urologist to assess the impact of an intervention in absolute terms. Relative measures of effect (relative risk, relative risk reduction) also characterize the treatment effect and can be applied to patients with varying baseline risk. The degree of precision within which the study estimated the actual effect size may be ascertained from the associated confidence interval. Confidence intervals are also useful when interpreting the benefit and harm of an experimental intervention and, therefore, are preferred compared to p values.
Urologists do not need to rely on author interpretations of the effectiveness or harmfulness of a given intervention alone, but may interpret the result of the study themselves. An understanding of measures of effect size and precision is important to the interpretation of the urological literature and facilitates evidence-based clinical practice.
The development of prostate specific antigen (PSA) assays with detection limits of approximately 0.001 microgram./l. is technically feasible. We examined if serum PSA changes of 0.001 to 0.1 microgram./l. for up to 3 years after radical prostatectomy have any clinical value.
We studied 148 patients with a postoperative PSA of less than 0.1 microgram./l. by a conventional PSA assay. At least 3 serial serum samples were collected per patient along with detailed clinicopathological features. Serial serum samples were analyzed for PSA with the ultrasensitive method. Associations between increase in serum PSA and clinicopathological features were analyzed with the unconditional logistic regression model.
After establishing a set of interpretative criteria, we divided the patients into 51 with biochemical relapse, 93 who were free of relapse and 4 with equivocal status. Between the groups with and without relapse there was no difference in year of surgery, age at operation or length of followup. Compared to patients without relapse, those with biochemical relapse were likely to have positive surgical margins (p < 0.01), larger tumor volumes (p < 0.01), greater preoperative PSA (p = 0.03) and disease extending outside the prostate (p = 0.02). The relative risks for biochemical relapse estimated by a univariate logistic regression model were 3.1 (95% confidence interval 1.39 to 6.82, p < 0.01) for positive surgical margin, 3.4 (95% confidence interval 1.46 to 8.13, p < 0.01) for tumor volume, 2.3 (95% confidence interval 1.08 to 5.02, p = 0.03) for high preoperative PSA and 2.7 (95% confidence interval 1.12 to 6.26, p = 0.03) for extraprostatic tumor extension. At multivariate analysis with the same model the associations between positive surgical margins and biochemical relapse (relative risk 2.95, p = 0.04) and tumor volume (relative risk 3.36, p = 0.03) remained significant. These associations were still observed when we analyzed a subset of patients classified as having biochemical relapse based on PSA changes of 0.001 to 0.08 microgram./l.
Increases in postoperative serum PSA at levels of 0.001 to 0.1 microgram./l. after radical prostatectomy are associated with clinicopathological features of poor prognosis. Monitoring postoperative cases with a highly sensitive PSA assay (detection limit 0.001 microgram./l.) could offer a simple and effective means of detecting clinically important biochemical relapse early after radical prostatectomy. These patients may be suitable for early intervention when effective treatments for relapse become available.
Increased urothelial permeability has been proposed as a cause of interstitial cystitis (IC). The potassium sensitivity test assesses bladder discomfort after instillation of 0.4 M KCl for identification of increased urothelial permeability. Since exposure to 0.4 M KCl may be extremely painful for patients with IC we investigated a less traumatic alternative.
The study comprised 38 controls and 40 patients with IC. In all subjects cystometry was performed with 0.9% NaCl followed by 0.2 M KCl, and filling volume at first urge and maximum bladder capacity (Cmax) were assessed for both solutions.
Controls did not show a significant change in Cmax. KCl decreased Cmax in 37 of 40 (92%) patients with IC with a mean decrease of 30%. The examination was painless in all controls and in 33 of 40 (82%) patients with IC, and was moderately painful in 7.
For demonstration of increased potassium sensitivity and diagnosis of IC, comparative assessment of Cmax is a well tolerated alternative to the 0.4 M potassium sensitivity test. Statistical evaluation of these results suggests that a decrease in Cmax greater than 30% is indicative of IC.
A prostate specific antigen (PSA) cutoff point of 0.2 ng./ml. has been suggested as the standard definition of disease freedom for curative treatment of localized prostate cancer. The time to achieve this goal after irradiation was determined in this study.
From August 1992 to December 1996, 539 consecutive men with clinical stage T1T2NX prostate cancer who had a minimum 5-year PSA followup and achieved a PSA nadir of 0.2 ng./ml. without hormones were evaluated. All patients were treated with simultaneous irradiation with a transperineal prostate iodine implant, followed by external beam irradiation. Time to achieve a PSA of 0.2 ng./ml. was retrospectively calculated from the date of implantation in all men and according to various factors. Recurrence was defined as a subsequent increase above a PSA of 0.2 ng./ml. Minimum followup was 5 years (median 6.5, range 5 to 9).
In all 539 men the median time to a PSA nadir of 0.2 ng./ml. was 27 months, while 534 (99%) achieved this level by 60 months of followup. Median time to achieve this PSA goal was 20 and 39 months in patients without and with a PSA bounce, respectively. Pretreatment PSA, disease status and ultimately PSA bounce, Gleason score and stage had little or no effect on time to a PSA of 0.2 ng./ml.
With rare exceptions to be potentially cured of prostate cancer by simultaneous irradiation men must achieve a PSA nadir of 0.2 ng./ml. within 5 years of implantation. Failure to reach this goal by 60 months of followup almost always indicates persistent disease.
We compared cystometric findings in interstitial cystitis and detrusor overactivity using 0.3 M KCl and 0.9% normal saline.
Female patients with established diagnoses of IC (7 patients according to NIDDK criteria) and urodynamically proven DO (10 patients) underwent consecutive cystometrograms using 0.9% normal saline and 0.3 M KCl, the order of which was randomized for each patient. Individual CMGs were performed by separate investigators, and patients and investigators were blinded to the order in which the solutions were used and to the results of the other CMG. The results were analyzed on a comparative basis using a 2-tailed t test for comparison of the means and a Kolmogorov-Smirnov z test was used for group comparison. A ROC curve was used to plot sensitivity to the false-positive rate.
Irrespective of the diagnosis or the type of infusion used, the volume at FDV was slightly lower with the first CMG compared to the second (mean 76.1 vs 94.2 ml) but did not reach statistical significance (p = 0.20). However, Cmax was similar for first and second CMGs (mean 214 vs 213.2 ml, p = 0.98). Although lower with KCl, there was no significant difference in FDVs obtained with either solution (mean 78.2 vs 92.2 ml for KCl and NS, respectively, p = 0.33). However, KCl produced a significant reduction in Cmax across the whole group (mean 244.5 vs 182.7 ml, p = 0.008). This was most marked in the DO group in which there was a 23% reduction in Cmax with KCl compared to NS, while the IC group showed only a 15% reduction in mean Cmax. The ROC curve, comparing Cmax values for NS with KCl cutoff values of 15% and 30%, resulted in poor positive predictive values (51% and 66%, respectively) for comparative cystometry in distinguishing IC from DO.
The 0.3 M KCl reduces Cmax in IC and DO, the effect being more pronounced in DO. Urothelial hyperpermeability is not specific to IC. Comparative cystometry using NS and 0.3 M KCl does not help to differentiate IC from DO.
We examined the effect of 5α-reductase inhibitor therapy on prostate cancer detection in men with persistently increased or fluctuating prostate specific antigen and prior negative prostate cancer biopsy.
A total of 276 men with prostate specific antigen greater than 4 ng/ml (208) or a prostate specific antigen velocity change of 0.75 ng/ml (68) and a normal digital rectal examination who had previously undergone biopsy a minimum of 2 times with prostate cancer not detected were given 5 mg finasteride (154) or dutasteride (122) daily. In phase 1, 97 patients had prostate specific antigen measured at 6 and 12 months with repeat transrectal ultrasonography and biopsy (12 cores) performed at 1 year. In phase 2, 179 patients underwent biopsy triggered by a change in nadir prostate specific antigen of more than 0.4 ng/ml.
In phase 1 at 1 year prostate specific antigen had decreased by 2.4 ng/ml (-46.7%), and prostate volume had decreased 7.1 ml (-17.9%). Prostate cancer was detected in 27 of 97 (27.8%) patients and the mean minimum prostate specific antigen velocity from a nadir of 0.4 ng/ml was 0.6 ng/ml. In phase 2, 48 of 179 (26.8%) men underwent repeat biopsy at a mean of 14.6 months. Of these 48 men 26 (54.1%) were found to have prostate cancer. Of the 26 men in whom prostate cancer was detected 20 (76.9%) were found to have Gleason score 7 or greater disease.
The magnitude of change in serum prostate specific antigen after 5α-reductase inhibitor therapy may be useful in diagnosing prostate cancer in patients with persistently increased or fluctuating prostate specific antigen and prior negative prostate biopsy.
Recurrent superficial papillary bladder tumors are most commonly treated with transurethral resection with the patient under anesthesia. We report our experience with office fulguration of small, recurrent, low grade papillary tumors using flexible cystodiathermy.
We conducted a prospective single institution analysis of 267 consecutive patients with superficial bladder cancer undergoing routine bladder cancer surveillance between January 1998 and December 2001. Cytological and histological recurrences were recorded. Selection criteria for office fulguration were less than 5 low grade appearing papillary tumors, tumor size less than 0.5 cm, negative urine cytology and patient desire. All patients completed initial treatment (transurethral resection, partial cystectomy and/or intravesical therapy) and a minimum of 6 months on surveillance without recurrence (median 11.57 months).
Flexible cystodiathermy for small, low grade, recurrent papillary tumors was efficacious and well tolerated. Of the 123 patients 46% experienced 1 or more tumor recurrences (range 1 to 11) in a median followup of 2.6 years. Of these 123, 74 (60%) underwent office cystodiathermy. No difference was seen in disease specific survival (p = 0.1633) or disease progression (p = 0.860). When stratified by risk of recurrence 202 of 267 patients at high risk (76%) with low grade papillary recurrence had similar rates of progression to patients at low risk (p = 0.9025). Median time from diagnosis was 6.84 years, and time from last tumor was 20.4 months.
Office cystodiathermy of small, low grade papillary recurrence is safe and efficacious in properly selected patients. This change in practice can potentially improve patient quality of life and have a major economic impact on health care.
Few studies have examined the radical prostatectomy followup of a minute focus of adenocarcinoma on prostate needle core biopsy.
We searched the surgical pathology data base (1999 to 2000) for patients with a minute focus of Gleason score 6 adenocarcinoma (defined as a single focus less than or equal to a 40 x microscopic field) who subsequently underwent radical retropubic prostatectomy at our institution. Potentially insignificant tumors were defined as those with a radical prostatectomy tumor volume of less than 0.5 cc, Gleason score 6 or less and organ confined disease.
A total of 54 patients (mean age 58 years, range 45 to 70) were evaluated. The average number of prostate cores per biopsy was 6.3. All had Gleason score 6 by study design. Mean prostate specific antigen (PSA) was 6.0 (range 0.8 to 15). Average tumor volume at radical prostatectomy was 0.39 cc. Of the 54 tumors 24 (44%) were 0.1 cc or less. Two-thirds of the tumors were clinically potentially insignificant. Using a PSA density (PSAD) cutoff of 0.15 we identified 30 of 36 patients (83%) with potentially insignificant tumors. Of those with a PSAD of 0.15 or less with clinically significant tumors, 5 of 6 still had relatively small, organ confined tumors with Gleason score less than 7.
In the era of PSA screening most patients with a minute focus of Gleason score 6 or less adenocarcinoma on needle biopsy had potentially insignificant tumors. However, one-third of patients had clinically significant tumors warranting definitive therapy. The smallest focus of cancer on needle biopsy is not a guarantee of a clinically insignificant tumor. PSAD may have some value within this group in guiding clinicians and patients as to the likelihood of having clinically insignificant tumors.
We performed a prospective randomized trial comparing glycine 1.5% with 2.7% sorbitol-0.5% mannitol irrigating solution. We evaluated blood loss, fluid absorption, temperature change, cardiac effects and postoperative symptoms.
Between April 1998 and July 1999, 205 treated patients were included in the statistical analysis. Intraoperative irrigating fluid absorption was measured with the patient on the operating table. Serum cardiac troponin I was used as a marker of perioperative myocardial damage. Operative details were recorded, including the type of anesthesia, resection time and the weight of resected tissue. Postoperative symptoms were documented prospectively.
Mean patient age was not significantly different in the glycine and sorbitol-mannitol groups. (72.1 versus 73.7 years). American Society of Anesthesiologists grade was also comparable. Median resection time was 27 minutes and resected tissue weighed a mean of 21 gm. The median resection rate was 0.8 gm. per minute. Blood loss and temperature changes during resection were similar in the 2 groups. Overall median blood loss was 216 ml. and irrigant absorption was 140 ml. In the sorbitol-mannitol group significantly less fluid was apparently absorbed during resection (median 88.2 versus 184.4 ml.). Analysis of the incidence of symptoms of the transurethral prostate resection syndrome did not show any differences in the irrigant groups. Cardiac damage measured using troponin I also showed no significant difference in the 2 groups, although there was a high overall incidence of 7.5%.
We noted no significant differences in 1.5% glycine and 2.7% sorbitol-0.5% mannitol as an irrigating solution for transurethral prostate resection.
The detection of low volume and early stage prostate cancer has increased with the widespread use of prostate specific antigen screening for prostatic adenocarcinoma. This increased detection has led to efforts to stratify patient risk and the potential benefits of various treatments based on preoperative clinical and biopsy data. We examined various clinical parameters and prostate biopsy features to determine which variables are most predictive of small volume (less than 0.5 ml) cancer at prostatectomy.
Materials and methods:
We studied 336 patients who underwent prostatectomy for prostate cancer. Radical prostatectomy specimens were completely embedded and whole mounted. Final tumor volume in the radical prostatectomy specimens was determined by the grid method. Clinical data were gathered by a review of patient charts. Various preoperative clinical and biopsy findings were analyzed to determine factors predictive of small volume cancer at prostatectomy.
A total of 55 patients (16%) were found to have small volume cancer (less than 0.5 ml). On univariate logistic regression certain variables were significant predictors of small volume cancer, namely the highest Gleason score from all positive biopsy sites (p = 0.001), the Gleason score from the biopsy site with the highest percent of adenocarcinoma (p = 0.006), the highest percent of adenocarcinoma at any biopsy site (p <0.0001), the percent of adenocarcinoma at the biopsy site with the highest Gleason score (p <0.0001), the highest percent of cores positive for adenocarcinoma at any biopsy site (p = 0.001), the percent of cores with carcinoma at the site with the highest Gleason score (p = 0.002), the number of positive sites (p <0.0001) and tumor bilaterality (p <0.0001). None of the clinical parameters that we studied, including preoperative prostate specific antigen (p = 0.52), clinical stage (p = 0.62) or patient age (p = 0.94), was predictive of small volume cancer. On multivariate analysis the highest percent of adenocarcinoma at any site (adjusted OR 0.95, 95% CI 0.92 to 0.97, p <0.0001) and the number of positive biopsy sites (adjusted OR 0.97, 95% CI 0.96 to 0.99, p <0.0001) were significant predictors of small volume cancer.
The number of positive biopsy sites and the highest percent of adenocarcinoma at any biopsy site are significant predictors of small volume cancer in radical prostatectomy specimens.
We evaluate results and long-term outcome after partial nephrectomy (PN) for unilateral Wilms tumor (ulWT) in relation to different histological features, performed as initial surgery or after induction chemotherapy (ChT).
Data from patients with ulWT who had undergone PN in the German Study SIOP 93-01/GPOH were analyzed for time of surgery in the treatment schedule, postoperative stage, histological features, surgical radicality and outcome. The results were correlated with overall survival and relapse-free survival, and compared with those of patients who had undergone total tumor nephrectomy (TN).
A total of 770 patients underwent TN and 37 underwent PN, of which 766 (99.5%) and 36 (97.3%), respectively, were radical procedures. A total of 139 TNs and 15 PNs were performed at primary surgery, 630 TNs and 22 PNs after ChT, and 1 TN after irradiation. Two of 15 patients following primary PN and 1 of 22 following delayed PN had local recurrence. Two patients died of metastatic disease. Tumor stage, overall survival of 93% and relapse-free survival of 88% were equal after PN and TN in analysis of the whole group. This was also true for patients with surgery after ChT. One of 2 patients with histologically unfavorable disease had relapse after PN compared to only 3 of 35 patients with histologically low or intermediate risk disease.
PN should be performed only for small, histologically low or intermediate risk tumors after good response to ChT to secure a complete resection.
A total of 100 whole stones was fragmented in vitro at 3-minute intervals with piezoelectric shock waves using the EDAP LT-01 device until all fragments were less than 2 mm. Larger stones and stones with a high computerized tomography attenuation needed longer treatments for fragmentation. Smoothly bulging stones with an even structure according to plain x-ray films were also more resistant to the shock wave treatment. Calcium oxalate monohydrate stones were not more difficult to break than other types of calculi. Stone fragments from 100 patients after extracorporeal shock wave lithotripsy were also analyzed. The average size of the fragments collected was less than 1 mm. Larger stones produced larger fragments and required more treatment sessions.
A total of 433 extracorporeal lithotripsy procedures was performed for renal, ureteral and bladder stones by means of a system of ultrasonographic detection and piezoelectric destruction in 386 patients. The stones were detected easily in 87 per cent of the patients, difficult to detect in 10 per cent and impossible to detect in 3 per cent. Mean duration of treatment was 35 minutes. Mean number of piezoelectric waves was 2,700 at 1.25 per second. With a frequency of 1.25 to 5 per second, extracorporeal lithotripsy was performed without any local, regional or general anesthesia, and without premedication in 210 patients. Of the 217 patients with a renal stone reviewed at 3 months 161 (74 per cent) had successful results and 56 (26 per cent) failed therapy. Thirty patients (14 per cent) underwent 2 or 3 sessions. The morbidity was low: 2 per cent of the patients suffered ureteral obstruction, 1.5 per cent had subcapsular hematoma and 4 per cent had fever. No significant modifications of laboratory tests were necessary and no patient suffered renal failure. Of the stones 31 in the lumbar ureter, 15 in the pelvic ureter and 8 in the bladder were treated, with success rates of 87, 46 and 50 per cent, respectively. A total of 103 patients was treated on an outpatient basis. This outpatient treatment, together with the low cost and minimal maintenance of the apparatus, and the absence of anesthesia constitute a new progress in the treatment of renal stones.
The initial United States cooperative experience with the EDAP LT-01 second generation piezoelectric extracorporeal shock wave lithotriptor using ultrasonic guidance is presented. Particular to the machine are lack of radiation exposure, no need for anesthesia, a purely outpatient procedure, no electrocardiographic problems, a high degree of safety and a paucity of complications. The equipment is described briefly. The same machine currently is being used to destroy renal and biliary stones. The results are encouraging and highly comparable to the initial experience with the earlier machines. Fragmentation rates are approximately 86%, with destruction rates of 63.4% over-all. Ultrasound localization and monitoring proved surprisingly easy to learn and were increasingly less of a problem as experience was gained. No serious complications were observed, and there were no renal losses and no deaths. Only 3 cases of steinstrasse were noted among 461 with 633 stones targeted during 595 treatments.
Piezoelectric second generation lithotriptors are an established means of administering extracorporeal shockwave lithotripsy (ESWL) enabling treatment to be performed without anaesthesia or analgesia, but higher shockwave doses and multiple or staged treatment are frequently required. The bioeffects of this modality of ESWL, therefore, require further assessment. Seven experimental groups of adult male rabbits were treated using the EDAP LT.01 in order to determine the acute and chronic bioeffects of clinical dose, excess dose, divided excess dose, high frequency and multiple treatment (X10) piezoelectric shockwaves (PSW). Renal function was measured before and after treatment using mercaptoacetyltriglycine (MAG 3) scans. Gross and histological morphological changes were assessed at one and 30 days following application of PSW. Application of single clinical dose PSW was not associated with any significant functional or morphological renal injury. Excess dose PSW caused transient gross renal contusion, which resolved in the majority of animals with no persistent microscopic abnormality. Divided excess dose PSW resulted in no gross or microscopic damage. High frequency PSW was associated with mild histological abnormality. Multiple PSW treatments caused small discrete fibrotic lesions in all cases, without any change in renal function.
During a 2-year period extracorporeal shock wave lithotripsy (ESWL) was done at our institution in 70 patients with the Dornier HM3, 113 with the EDAP LT 01 and 104 with the Sonolith 2000 lithotriptors. The size and location of stones were comparable in all 3 series, and all treatments were done by the same team of urologists. Complete fragmentation occurred in 79% of the patients treated by the Dornier, 82% treated by the EDAP and 79% treated by the Sonolith devices, with 3-month stone-free rates of 66, 67 and 58%, respectively. Auxiliary procedures were needed in 12% of the patients in the Dornier, 13% in the EDAP and 9% in the Sonolith groups. Repeat treatment was necessary in 4% of the Dornier group, 42% of the EDAP group and 26% of the Sonolith group. Therefore, all 3 lithotriptors are effective in stone disintegration and produce satisfactory results when selection criteria for ESWL are observed. The most significant difference among the 3 lithotriptors is the number of repeat treatments, which reflects the power and energy output of the lithotriptors. In conclusion, the Dornier HM3 device has the advantage of low repeat treatment rate and easier stone localization. The EDAP LT 01 unit has the advantage of lower treatment costs and anesthesia-free treatment with no irradiation. The Sonolith 2000 device has features of the other 2 lithotriptors with a superior ultrasound image.
We reviewed 64 cases of upper ureteral stones treated between December 1986 and June 1988. Upper ureteral stones were defined as stones in the ureter distal to the ureteropelvic junction and proximal to the S1 vertebra. All stones were treated in situ with no invasive procedures done before treatment. The over-all success rate in rendering patients free of stones by extracorporeal shock wave lithotripsy monotherapy was 75%. Of the patients 25% required auxiliary procedures, such as percutaneous ultrasonic lithotripsy. The average duration of treatment for each stone was 88 minutes and the average storage energy used was 208 units.
EDAP International (Cambridge, Massachusetts) has developed a new piezoelectric lithotripter (LT.02) that differs from their earlier model (LT.01) in two important respects: method of stone visualization and available power. The LT.02 provides both in-line fluoroscopy as well as real time ultrasound. The maximum energy is 1400 Bar (compared with 1100 Bar in the LT.01). The purpose of this study was to determine whether treatment with the EDAP LT.02 piezoelectric lithotripter would cause significant renal injury in minipigs. Accordingly, 18 minipigs were divided into 3 groups of 6. Each group received a treatment of 20, 40 or 60 minutes; the power level and shock wave frequency were kept at maximal levels throughout the treatment period. Three pigs from each group were sacrificed at 72 hours (acute). The remaining 9 pigs were sacrificed 1 month following LT.02 treatment (chronic). Histopathologic analysis of the treated kidney revealed that 33% of the 9 acute pigs developed a small capsular hematoma, whereas 66% showed only a small parenchymal contusion ( < or = 1% of total renal volume). Among the chronic pigs, 66% had a small cortical scar, whereas 33% had no macroscopic pathology. Despite the differences in the number of shock waves delivered, these changes were evenly distributed among the 3 groups. Histologic acute changes included circumscribed areas of hemorrhagic infarction, vascular thrombosis with recanalization and focal tubular obstruction and damage. At 30 days, however, these acute injuries had completely resolved in 3 pigs and were only notable as minute areas of focal tubular loss in 6 pigs.
The long-term success rate of dilation and/or internal urethrotomy is low in cases of recurrent urethral stricture. We investigated the ability of the Memokath™ 044TW stent to maintain urethral patency after dilation or internal urethrotomy for recurrent urethral stricture.
Materials and methods:
A total of 92 patients with recurrent bulbar urethral strictures (mean length 2.7 cm) were treated with dilation or internal urethrotomy and randomized to short-term urethral catheter diversion (29) or insertion of a Memokath 044TW stent (63). The primary end point was urethral patency, as assessed by passage of a calibrated endoscope. Secondary end points included urinary symptoms and uroflowmetry parameters. Stents were scheduled to remain in situ for 12 months.
The rate of successful stent insertion was 93.6% (59 of 63 patients). In stented patients patency was maintained significantly longer than controls (median 292 vs 84 days, p <0.001). Patency was reflected in significantly improved uroflowmetry and symptom scores. The stent was removed in 100% of patients. The most frequently noted side effects in stented patients were bacteriuria, hematuria and penile pain, which were usually mild and transient. There was no difference in sexual function between stented and control patients. Stent dislocation and occlusion were observed in 8 and 3 patients, respectively.
Patients with recurrent bulbar urethral strictures treated with dilation or urethrotomy and a Memokath 044TW stent maintained urethral patency significantly longer than those treated with dilation or urethrotomy alone. The stent side effect profile was favorable. The stent was straightforward to insert and it was removed without difficulty even after long-term placement.
A marked decrease in renal blood flow (RBF) and glomerular filtration rate (GFR) was found after 24, 48 and 72 hours of total unilateral ureteral obstruction (UUO) in the rabbit. Contralateral GFR showed a modest increase consistent with compensatory hypertrophy. The urinary excretion of thromboxane B2 (TxB2), the stable metabolite of the vasoconstrictor prostaglandin, thromboxane A2 (TxA2) was significantly elevated in the urine obtained following release of the obstructed ureter when compared to the TxB2 level in the urine from the contralateral kidney. Continuous infusion of OKY-046 at 100 micrograms./kg./min. over 24 hours during UUO decreased TxB2 excretion by greater than 80 per cent. However there was no significant preservation of RBF or GFR of the obstructed kidney following ureteral release despite the selective inhibition of TxA2. Moreover the increase in contralateral GFR was also abolished. Taken together with other studies these results strongly suggest that the potent vasoconstrictor TxA2 is not responsible for the rise in renal resistance that follows acute UUO.
We have recently demonstrated that computer assisted image analysis of paraffin embedded testicular tissue based on deoxyribonucleic acid content and morphology characteristics is an effective method for the quantitative assessment of spermatogenesis. We assess the use of testicular touch preparation image analysis as a technique for quantification of spermatogenesis.
Air dried, touch imprints of testicular tissue from obstructed azoospermic and severely oligozoospermic patients were obtained at the time of biopsy. Image analysis using a filter based on deoxyribonucleic acid content and cellular morphological characteristics was performed on Feulgen stained touch preparation imprints as well as paraffin embedded sections.
Image analysis of 52 testicular touch preparations from 48 azoospermic or severely oligozoospermic men revealed significant differences (p < 0.05) in the percentages of spermatid and spermatozoa, and 2N and 4N cells among seminiferous tubules exhibiting the 5 diagnostic categories of obstruction with normal spermatogenesis, maturation arrest at the spermatocyte stage, maturation arrest at spermatid stage, hypospermatogenesis and Sertoli cell only. Similar differences were observed in the image analysis data of the corresponding paraffin embedded testicular sections.
Computer assisted image analysis of testicular touch preparation is an effective quantitative method of spermatogenesis evaluation.
We present our 4-year experience with the thermo-expandable shape memory alloy Memokath 051 stent (Engineers and Doctors of Copenhagen, Copenhagen, Denmark) for managing long-term ureteral obstruction.
We used a nickel-titanium shape memory alloy ureteral stent to treat 28 patients 29 to 86 years old (mean age 59.2). Ureteral obstruction was caused by malignancy in 18 cases and by recurrent benign disease in 10. A total of 37 stents were inserted from November 1996 to November 2000 using general anesthesia. Mean followup was 19.3 months (range 3 to 35).
Upper tract decompression was achieved in all cases. Currently 15 stents are functional in 13 patients, while 8 patients died with a total of 13 functioning stents in place. In 7 patients 9 stents were removed for various reasons. There has been no radiological evidence of encrustation to date. No patient has been rehospitalized with stent related sepsis pain or hematuria, resulting in improved quality of life.
This stent seems to provide a significant benefit over conventional Double-J (Medical Engineering Corp., New York, New York) and other metallic stents. Its remarkable thermal memory permits removal, a feature that until recently was not available in any other metallic ureteral stent. Durable and complication-free decompression of the upper tract can be achieved with the Memokath 051.
Epidemiological studies in women have revealed an association between caffeine intake and urinary incontinence, although evidence among men is limited. Therefore, we evaluated the association between caffeine intake and urinary incontinence in United States men.
Materials and methods:
Data were used from male NHANES (National Health and Nutrition Examination Surveys) 2005-2006 and 2007-2008 participants. Urinary incontinence was defined using a standard questionnaire with Incontinence Severity Index scores 3 or greater categorized as moderate to severe. Structured dietary recall was used to determine caffeine consumption (mg per day), water intake (gm per day) and total dietary moisture (gm per day). Stepwise multivariable logistic regression models were used to assess the association between caffeine intake at or above the 75th and 90th percentiles and moderate to severe urinary incontinence, controlling for potential confounders, urinary incontinence risk factors and prostate conditions in men age 40 years or older.
Of the 5,297 men 3,960 (75%) were 20 years old or older with complete data. Among these men the prevalence of any urinary incontinence was 12.9% and moderate to severe urinary incontinence was 4.4%. Mean caffeine intake was 169 mg per day. Caffeine intake at the upper 75th percentile (234 mg or more daily) and 90th percentile (392 mg or more per day) was significantly associated with having moderate to severe urinary incontinence (1.72, 95% 1.18-2.49 and 2.08, 95% 1.15-3.77, respectively). In addition, after adjusting for prostate conditions, the effect size for the association between caffeine intake and moderate to severe urinary incontinence remained.
Caffeine consumption equivalent to approximately 2 cups of coffee daily (250 mg) is significantly associated with moderate to severe urinary incontinence in United States men. Our findings support the further study of caffeine modification in men with urinary incontinence.
Oxalate, a metabolic end product, is a major constituent of majority of renal stones. Previous studies with LLC-PK1 cells, a line of proximal renal epithelial cells of porcine origin, have shown that oxalate produces time and concentration dependent effects on the growth and viability of these cells. We assessed the possibility that oxalate may be toxic to HK-2 cells, a line of human proximal renal epithelial cells.
HK-2 cells were maintained in Dulbecco's modified Eagle's medium supplemented with fetal bovine serum and antibiotics. Cells were exposed to oxalate for various intervals. Trypan blue exclusion criteria were used to assess membrane integrity, cell morphology was assessed by hematoxylin and eosin staining and crystal violet staining was used to measure cell density. DNA synthesis was measured by [3H]-thymidine incorporation and superoxide production was measured by the nitroblue tetrazolium reduction method.
Exposure of HK-2 cells to oxalate produced time and concentration dependent increase in the membrane permeability to trypan blue and changes in the light microscopic appearance of the cells. Long-term exposure to oxalate resulted in an increase in DNA synthesis and alterations in cell viability with net cell loss after exposure to high oxalate concentrations.
To our knowledge the results provide the first direct demonstration of the toxic effects of oxalate in HK-2 cells, a line of human renal epithelial cells, and suggest that hyperoxaluria may contribute to renal tubular damage associated with calcium oxalate stone disease.
We analyzed the long-term complications (greater than 90 days postoperatively) in a large, single center series of patients who underwent cystectomy and substitution with an ileal neobladder.
A total of 1,540 radical cystectomies were performed at our center between January 1986 and September 2008. Of the patients 1,013 received an ileal neobladder. Only the 923 patients with followup longer than 90 days (median 72 months, range 3 to 267) were included in analysis. All long-term complications were identified. The complication rate was calculated using the Kaplan-Meier method.
The overall survival rate was 65.5%, 49.8% and 28.3% at 5, 10 and 20 years, respectively. The overall long-term complication rate was 40.8% with 3 neobladder related deaths. Hydronephrosis, incisional hernia, ileus or small bowel obstruction and feverish urinary tract infection were observed in 16.9%, 6.4%, 3.6% and 5.7% of patients, respectively, 20 years postoperatively. Subneovesical obstruction in 3.1% of cases was due to local tumor recurrence in 1.1%, neovesicourethral anastomotic stricture in 1.2% and urethral stricture in 0.9%. Chronic diarrhea was noted in 9 patients. Vitamin B12 was substituted in 2 patients. Episodes of severe metabolic acidosis occurred in 11 patients and 307 of 923 required long-term bicarbonate substitution. Rare complications included cutaneous neobladder fistulas in 2 cases, and intestinal neobladder fistulas, iatrogenic neobladder perforation, spontaneous perforation and necrotizing pyocystis in 1 each.
Even in experienced hands the long-term complication rate of radical cystectomy and neobladder formation are not negligible. Most complications are diversion related. The challenge of optimum care for these elderly patients with comorbidities is best mastered at high volume hospitals by high volume surgeons.
We first described the meatal advancement and glanuloplasty (MAGPI) procedure in 1981 as a technique to repair distal hypospadias. During the last 10 years our experience has increased to more than 1,000 cases. Case selection is critical to surgical outcome. Excessively thin or rigid ventral parameatal skin, or a meatus that is too proximal or too wide must be avoided. To prevent the ventral meatal wall from falling back and leaving a retrusive meatus, the glans wrap to support the advanced ventral urethral wall requires a solid approximation of glans tissue in 2 layers. Meatal stenosis may be avoided by an adequately deep dorsal Heineke-Mikulicz tissue rearrangement, making the incision from within the urethral meatus distally into the glanular urethral groove. The MAGPI procedure is routinely performed on an outpatient basis without urinary diversion. A review of our experience with 1,111 cases during a 12-year period reveals that a secondary procedure was required in only 1.2%. The overall success rate with the MAGPI procedure suggests that it should continue to be an important operation in the reconstruction of distal hypospadias.
We performed a prospective oncological evaluation of laparoscopic radical prostatectomy in regard to local tumor control and biochemical recurrence.
Between January 1998 and March 2002, 1,000 consecutive patients with a mean age +/- SD of 63 +/- 6.2 years and clinically localized prostate cancer underwent laparoscopic radical prostatectomy at 1 institution. Preoperative 1997 TNM clinical stage was T1a in 6 patients (0.6%), T1b in 3 (0.3%), T1c in 660 (66.5%), T2a in 304 (30.4%) and T2b in 27 (2.7%). Mean preoperative prostate specific antigen (PSA) +/- SD was 10 +/- 6.1 ng./ml. (range 1.5 to 55). Postoperatively, surgical specimens were assessed and positive surgical margins recorded. Factors that could influence the surgical margins status were evaluated. Irrespective of pathological stage or surgical margin status, no adjuvant treatment was proposed before an increasing PSA. PSA recurrence was defined as PSA greater than 0.1 ng./ml. and was confirmed by a second increase. Recurrence time was defined as the time of the first increase in PSA.
Postoperative pathological stage was pT2aN0/Nx in 203 patients (20.3%), pT2bN0/Nx in 572 (57.2%), pT3aN0/Nx in 142 (14.2%), pT3bN0/Nx in 77 (7.7%) and pT1-3 N1 in 6 (0.6%). Positive surgical margin rate was 6.9%, 18.6%, 30% and 34% for pathological stages pT2a, pT2b, pT3a and pT3b, respectively (p <0.001). The main predictors of a positive surgical margin were preoperative PSA (p <0.001), clinical stage (p = 0.001), pathological stage (p <0.001) and Gleason score (p = 0.003). The overall actuarial biochemical progression-free survival rate was 90.5% at 3 years. According to the pathological stage, the progression-free survival rate was 91.8% for pT2aN0/Nx, 88% for pT2bN0/Nx, 77% for pT3aN0/Nx, 44% for pT3bN0/Nx and 50% for pT1-3N1 (p <0.001). Of the patients 94% with negative surgical margins and 80% with positive margins had progression-free survival (p <0.001). Preservation of the neurovascular bundles in patients with localized tumors had no significant effect on the subsequent risk of positive surgical margins or progression-free survival.
Based on followup, our evaluation confirms that laparoscopic radical prostatectomy provides satisfactory results in regard to local tumor control and biochemical recurrence.
We report the results of 1,000 consecutive patients who underwent percutaneous removal of renal and ureteral stones. Removal was successful for 98.3 per cent of the targeted renal stones and 88.2 per cent of the ureteral stones. Complications, evolution and technique are discussed. Percutaneous techniques are an effective way to handle the majority of renal calculi and these techniques will continue to be important as shock wave lithotripsy becomes more widespread in the United States.
Between May 10, 1982 and September 1, 1990, 1,000 kidney transplant recipients underwent parallel incision extravesical ureteroneocystostomy for urinary tract reconstruction. Complications attributed to this surgical technique that required reoperation occurred in 2.1% of the recipients. These complications included urinary extravasation in 9 patients, ureteral necrosis in 3, ureteral obstruction in 3, ureteral bleeding in 3, ureteral implantation into thickened folds of peritoneum in 2 on chronic ambulatory peritoneal dialysis and ureteral implantation into an ovarian cyst in 1. Vesicoureteral reflux occurred in 0.4% of the ureteroneocystostomies, none of which was revised. No allografts were lost as a result of these complications. The principles of the technique are sound. One should be careful if the patient has a small, defunctionalized or scarred bladder, has undergone multiple pelvic operations or has had pelvic inflammatory disease.
We critically examined the intraoperative and postoperative complications associated with radical retropubic prostatectomy in the modern era.
Between April 18, 1994 and July 13, 2000, 1,000 men underwent radical retropubic prostatectomy performed by a single surgeon. The whole inpatient hospital medical record of 909 patients, the outpatient charts of 955 and a self-administered patient survey completed by 679 were reviewed by 2 data managers not involved in surgical management or followup care. In all 1,000 cases at least 1 of the 3 data sources was reviewed.
Mean patient age was 60.3 years. In 73%, 99.8% and 95.7% of cases serum prostate specific antigen was 10 ng./ml. or less, disease was clinical stage T1 or T2 and Gleason score was 7 or less, respectively, while 19.9% of pathological specimens showed positive margins. There were 8 intraoperative complications (0.8%). All 5 rectal injuries and the single ureteral injury were detected during the initial surgical procedure and repaired without sequelae. Only 14 men (1.4%) had any other complications during hospitalization. Until postoperative day 30, 4 pulmonary emboli (0.4%) with or without deep vein thrombosis and 5 myocardial infarctions (0.5%) developed. There were no intraoperative or in-hospital postoperative deaths and only 1 postoperative death secondary to myocardial infarction during the initial 30 days. Reexploration was done for hemorrhage and a disrupted anastomosis in 3 and 2 cases, respectively. Mean hospitalization was 2.3 days, 9.7% of patients required allogenic blood transfusion and 15 (1.5%) were rehospitalized.
Our series represents a rigorous assessment of the complications associated with radical retropubic prostatectomy. It shows that in the hands of an experienced urological surgeon, this procedure is associated with minimal intraoperative and postoperative morbidity. Of the patients 98% had no intraoperative or postoperative complications. Our series enables appropriate contemporary comparisons to be made with laparoscopic prostatectomy and radiation therapy. This outcomes analysis implies that radical retropubic prostatectomy cannot be assumed to have greater morbidity than radiation therapy and it sets a high standard for those advocating laparoscopic radical prostatectomy.
Holmium laser prostate enucleation is a contemporary treatment for benign prostatic hyperplasia. We report our experience with more than 1,000 procedures.
From June 1998 to March 2009 we performed 1,065 holmium laser prostate enucleations. After receiving institutional review board approval we retrospectively reviewed the database. Reported short-term, intermediate term and long-term results are 0 to 6, 6 to 12 and greater than 12 months, respectively.
Bladder stones were present in 50 patients (4.7%) and 87 of the 717 (12.1%) with laboratory studies available had renal insufficiency. Preoperative urinary retention was present in 411 cases (38.7%). Significant preoperative stress and urge incontinence was noted in 8 and 16 patients, respectively. Mean transrectal ultrasound prostate volume was 99.3 gm (range 9 to 391). Mean preoperative American Urological Association symptom score was 20.3 (range 1 to 35) and maximum urinary flow was 8.4 cc per second (range 1.1 to 39.3). Intraoperative or postoperative complications occurred in 24 cases (2.3%). Mean followup was 287 days (range 6 to 3,571). At short-term, intermediate term and long-term followup the mean symptom score was 8.7, 5.9 and 5.3, and maximum urinary flow was 17.9, 19.5 and 22.7 cc per second, respectively. At the most recent followup 3 patients (0.3%) were in urinary retention. One patient with maximum urinary flow 20 cc per second required a second procedure for bleeding prostatic regrowth. Urethral stricture was noted in 9 (0.9%), 11 (1.3%), 4 (1.3%) and 0 patients, and bladder neck contracture was found in 0, 7 (0.8%), 4 (1.3%) and 5 (6.0%) at short-term, intermediate term, long-term and greater than 5-year followup, respectively. At the most recent followup significant stress and urge incontinence was noted in 9 and 6 patients, respectively.
Holmium laser prostate enucleation is safe and effective for benign prostatic hyperplasia. The complication rate is low, and incontinence and the need for ancillary procedures are rare for holmium laser prostate enucleation with durable long-term results.
We determined the incidence of positive pelvic lymph nodes in men undergoing radical retropubic prostatectomy and describe the correlation with prostate specific antigen, histological grade and stage. We examined whether tumor cells are localized in the sentinel nodes only or also in other nonsentinel lymph nodes.
A total of 1,055 men with prostate cancer underwent radio guided pelvic lymph node dissection and radical retropubic prostatectomy. In men with prostate specific antigen 20 ng/ml or less and biopsy Gleason score 7 or less only sentinel nodes were removed. In men with prostate specific antigen more than 20 ng/ml or Gleason score greater than 7 extended pelvic lymph node dissection was also performed.
Positive lymph nodes were found in 207 men (19.6%). In 63.3% of the men these lymph nodes were detected outside of the region of standard lymphadenectomy. The percent of patients with positive nodes was greater than predicted by currently used nomograms. The higher the preoperative prostate specific antigen, pathological stage and grade, the greater the percent of men with positive sentinel and nonsentinel lymph nodes (p<0.001).
When deciding on pelvic lymph node dissection, sentinel or extended lymphadenectomy should be performed since more than half of patients have positive nodes outside of the region of standard lymphadenectomy. In cases of positive sentinel nodes extended lymph node dissection should be performed since tumor cells are also detectable in nonsentinel lymph nodes.