The potential usefulness of bladder cancer markers.
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Biomarkers, Tumor↗
Biomedical subjects
M M Elhilali
Publications and source records attributed to M M Elhilali.
Alteration of the insulin-like growth factor system of mitogens in hyperplastic bladders of paraplegic rats.
PURPOSE: Smooth muscle cells of the bladder retain the ability to proliferate in response to injury or mechanical stimulation. Insulin-like growth factor (IGF) I is a mitogenic and hypertrophic agent for smooth muscle cells. The purpose of this study is to examine if spinal cord injury could lead to bladder hypertrophy via the IGF system. MATERIALS AND METHODS: The study involved spinal cord transection of female Sprague Dawley rats (approximately 250 to 300 gm.). Six weeks following surgery the urinary bladder was collected. Northern and Western blotting, and IGF-I receptor (IGF-IR) affinity labeling were used to determine the expression of the IGF system, IGFBP levels, and IGF-IR levels respectively. RESULTS: Chronic spinal cord injury leads to an increase in the wet weight of the bladder and in the level of proliferation cell nuclear antigen expression. IGF-I mRNA levels increase, while IGFBP 3 and 5 mRNA and protein levels dramatically decrease. The gene expression of IGFBP 2 and 4 varies from rat to rat, and IGF-IR expression slightly increases. CONCLUSION: Our results suggest that following spinal cord injury, overexpression of IGF-I and underexpression of IGFBP 3 and 5 may lead to hyperplasia of the smooth muscle layer of the bladder.
Animals↗
Reduction of bladder outlet resistance by selective sacral root stimulation using high-frequency blockade in dogs: an acute study.
Detrusor-sphincter dyssynergia is a main problem in supra-sacral spinal cord injured patients. The problem of high pressure voiding is also encountered in most electrically induced micturition because of the mixed somatic and autonomic fiber components of the ventral sacral root. We studied the effect of selective high-frequency blockade at the sacral nerve root in an acute spinalized canine model to prevent the deleterious consequences associated with the elevated bladder outlet resistance. A new functional electrical stimulation system which can generate one signal composed of two independent adjustable current waveforms delivered via a single bipolar electrode was used in 11 dogs. The selectivity resulted from the inhibition of the sphincteric somatic innervation by a high frequency pulse while the low frequency stimuli activated the bladder autonomic fibers. Bladder and urethral pressure as well as electromyograms of external urethral sphincter were recorded to determine whether selective high-frequency blockade occurred. Our experiments showed that we were able to achieve selective blockade of the external urethral sphincter during the simultaneous detrusor stimulation, thus obtaining a more physiologic voiding.
Animals↗
Population-based patterns of radical retropubic prostatectomy use.
OBJECTIVES: To examine the use of radical retropubic prostatectomy (RRP) in a large population-based study. METHODS: Identification of all RRPs performed in the province of Quebec between the years 1988 and 1993 was accomplished by relying on the Quebec Healthcare Plan Database. RESULTS: Overall, 2861 RRPs have been performed during the study period. On average, 80% of surgeries have been performed by urologists using this surgery 12 times or less annually. Of all surgeries, 420 (15%) RRPs have been performed in individuals 71 years of age or older. CONCLUSIONS: Each year, most RRPs (80%) in this population-based study were performed by urologists performing this procedure 12 times or less annually. A substantial proportion (15%) of RRPs have been performed in men 71 years of age or older, in whom the detriments of radical surgery may outweigh its benefits. These findings could potentially contribute to suboptimal outcomes when radical prostatectomy is compared with alternative treatment modalities.
Aged↗
Thirty-day mortality rates and cumulative survival after radical retropubic prostatectomy.
OBJECTIVES: To assess the 30-day mortality rate and overall survival after radical retropubic prostatectomy (RRP). METHODS: Identification of all RRPs performed in the Province of Quebec between January 5, 1988 and January 16, 1996 was accomplished through the Quebec Healthcare Plan Database. RESULTS: Four thousand nine hundred ninety-seven RRPs were performed by 104 urologists. Overall, 451 deaths were recorded: 32 occurred during the first 30 days (0.6% 30-day mortality rate). A significant decrease in the 30-day mortality rate, from 2.45% to 0.5%, was recorded during the span of the study. The year of surgery, patient age, and hospital type were statistically significant short-term mortality variables (life table analysis). Patient age and year of surgery determined the cumulative survival probability (univariate and multivariate Cox analysis). Cumulative survival at 31 months of follow-up increased from 88.2% in 1988 to 98.1% in 1995. Men 75 years old and older were at a clear disadvantage with regard to survival probability compared with their younger counterparts. CONCLUSIONS: In this population-based analysis of RRP outcomes, we demonstrated a significant improvement in short- and long-term outcomes, as evidenced by a decrease in the 30-day mortality rate and an improved cumulative survival, recorded over the span of the study. The recorded outcome trends may be explained by improved patient selection and optimal management. Although we are unable to determine cancer-specific outcomes, the results of this analysis should prove valuable to urologists and patients until there are results from randomized trials.
Adult↗
Outcome of sextant biopsy according to gland volume.
OBJECTIVES: To reassess positive rate of sextant biopsy according to gland size. METHODS: We evaluated 1974 consecutive men with systematic sextant biopsy, among whom we examined biopsy yield according to gland-volume intervals of 10 cc. RESULTS: Decreasing yield of sextant biopsy is strongly associated with increasing gland volume (P < 0.001). Highest biopsy rate (39.6%) was recorded among men with prostates smaller than 20 cc. The lowest biopsy rate (10.1%) was recorded among men with prostates between 80 and 89.9 cc. Among men with biopsy-proven cancer, age, serum prostate-specific antigen, and Gleason grade were comparable (P > 0.05) throughout the range of gland-volume intervals. CONCLUSIONS: Our findings suggest that gland size represents an important determinant contributing to the yield of sextant biopsy in men at risk of harboring a nonpalpable, isoechoic cancer. Consequently, an individualized sector biopsy approach, based on prostate volume, may warrant consideration because it may ensure superior detection of clinically significant disease among all men at risk, regardless of prostate size.
Adult↗
Morphologic changes induced by neoadjuvant androgen ablation may result in underdetection of positive surgical margins and capsular involvement by prostatic adenocarcinoma.
OBJECTIVE: Neoadjuvant androgen ablation (NAAA) causes significant cytoarchitectural changes in both benign and malignant prostatic epithelial cells that may contribute to underdetection of prostate cancer capsular involvement and positive surgical margins. METHODS: The aim of this study is to determine the ability of cytokeratin immunohistochemistry to enhance the determination of pathologic stage of prostate cancer following NAAA. RESULTS: Cytokeratin AE1/AE3 immunohistochemistry identified 6 (27.3%), 15 (68.2%), 5 (22.7%), and 5 (22.7%) cases of organ-confined disease, capsule penetration, positive surgical margin, and seminal vesicle involvement, respectively, as compared with 10 (45.5%), 10 (45.5%), 3 (13.6%), and 5 (22.7%) cases by hematoxylin-eosin (H&E) staining, respectively. Two cases without detectable tumor by H&E staining had demonstrable residual tumor by cytokeratin immunohistochemical staining. CONCLUSIONS: Cytokeratin immunohistochemistry revealed more extensive intracapsular, capsular, and extracapsular tumor involvement and higher rate of positive surgical margin than did conventional H&E staining. Therefore, the beneficial pathologic effects of NAAA observed may, in part, be attributable to the artifact of observation.
Adenocarcinoma↗
Patient attitudes regarding treatment-related erectile dysfunction at time of early detection of prostate cancer.
OBJECTIVES: To assess potency rate and patient attitudes regarding erectile dysfunction. METHODS: A multiple choice, self-administered questionnaire distributed to 750 men undergoing testing for early detection of prostate cancer was used. RESULTS: Overall, 33.9% of patients reported either partial or complete lack of erections and 31.1% were not sexually active or active less than once per month. Furthermore, 55.4% would be affected or very affected by lack of erections and 73.6% chose definitive treatment despite a 50% chance of erectile dysfunction. Finally, 47.4% found such treatment-induced erectile dysfunction to be an important or very important problem. When asked to ascribe a quantity of life or period of time that they would be willing to sacrifice to preserve sexual function following treatment, only 15.2% of patients were able to do so, but no consensus could be reached regarding its value. CONCLUSIONS: Reported differences in quality-adjusted life expectancy when screening was compared to no screening and definitive therapy was compared to expectant management are marginal. Therefore, close attention to seemingly minor variables such as existing impotence rate, attitude regarding erectile dysfunction, and willingness to undergo therapy despite its inherent morbidity may substantially reduce or even reverse this reported disadvantage.
Adult↗
Early hospital discharge and home care.
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Canada↗
Long-term results of percutaneous endopyelotomy in the treatment of children with failed open pyeloplasty.
PURPOSE: We reviewed our experience with the safety and long-term efficacy of percutaneous endopyelotomy in children with secondary ureteropelvic junction obstruction who previously underwent open pyeloplasty. MATERIALS AND METHODS: Nine patients a median of 7 years old underwent endopyelotomy between June 1985 and July 1995. Anderson-Hynes pyeloplasty had previously been performed in all children. Antegrade endopyelotomy was done with a cold knife in conjunction with balloon dilation in some cases. Postoperative stenting lasted 6 weeks. RESULTS: The median interval between pyeloplasty and endopyelotomy was 7.5 months. Mean operative time was 240 minutes. Percutaneous endopyelotomy was successful in 8 of the 9 patients. One patient who required repeat endopyelotomy after 4 years is presently well at 5 years of followup. Average followup was 5.6 years (range 2 to 10). There was a low morbidity rate, including 1 case of urinary tract infection, 1 of pneumonia and 1 that required blood transfusion. CONCLUSIONS: Percutaneous antegrade endopyelotomy is a safe, effective and durable alternative for children who previously underwent unsuccessful pyeloplasty.
Adolescent↗
Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study.
OBJECTIVE: To evaluate the efficacy and safety of 2 years' treatment of moderate benign prostatic hyperplasia (BPH) with finasteride. DESIGN: Double-blind, parallel-group, placebo-controlled, multicentre, prospective randomized study. SETTING: Outpatient care in 28 centres across Canada. PARTICIPANTS: Men aged 45 to 80, in good health, with moderate BPH and no evidence of prostate cancer. A total of 613 men were entered into the study; 472 completed the 2 years of treatment. INTERVENTION: After 1 month of receiving a placebo (run-in period), patients were given either finasteride (5 mg/d) or a placebo for 2 years. OUTCOME MEASURES EFFICACY: changes from baseline in BPH symptom scores, maximum urinary flow rates and prostate volume. SAFETY: onset, course and resolution of all adverse events during the treatment period. RESULTS: In the efficacy analyses the mean BPH symptom scores decreased 2.1 points (from 15.8 to 13.7) in the finasteride group, as compared with a decrease of 0.7 points (from 16.6 to 15.9) in the placebo group (P < or = 0.01). The maximum urinary flow rate increased by a mean of 1.4 mL/s (from 11.1 to 12.5 mL/s) in the finasteride group, as compared with an increase of 0.3 mL/s (from 10.9 to 11.2 mL/s) in the placebo group (p < or = 0.01). The mean prostate volume decreased by 21% (from a mean volume of 44.1 cm3 at baseline) in the treatment group; it increased by 8.4% (from a mean volume of 45.8 cm3 at baseline) in the placebo group (p < or = 0.01). In the safety analysis, the proportion of patients who experienced any adverse event was similar in the two groups (81.0% in the treatment group and 81.2% in the placebo group). However, the incidence of adverse events related to sexual dysfunction were significantly higher in the finasteride group than in the placebo group (ejaculation disorder 7.7% v. 1.7% and impotence 15.8% v. 6.3%; p < or = 0.01 for both parameters). CONCLUSION: Finasteride is a well-tolerated and effective alternative to watchful waiting in the treatment of moderate BPH.
Aged↗
Reassessment of nonplanimetric transrectal ultrasound prostate volume estimates.
OBJECTIVES: To assess the accuracy and reproducibility of nonplanimetric transrectal ultrasound (TRUS) volume estimates because inaccurate volume estimates may potentially undermine the value of serum prostate-specific antigen density (PSAD) in early prostate cancer detection. METHODS: We prospectively evaluated 535 consecutive male patients with two consecutive volume determinations performed by the same ultrasonographer at the time of the same visit. RESULTS: Pearson correlation coefficients between two consecutive gland volume estimates ranged from 0.82 to 0.85 depending on the formula used; however, these correlation coefficients corresponded to an average 25% difference between the first and second gland volume estimates. CONCLUSIONS: Although two consecutive nonplanimetric TRUS volume estimates show statistically good correlation, clinically up to a 25% volume difference should be expected between two such volume estimates. In consequence, nonplanimetric TRUS volume estimates should be interpreted with caution, especially when used for PSAD calculation, in the early detection of prostate cancer.
Adult↗
A multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of terazosin in the treatment of benign prostatic hyperplasia.
OBJECTIVES: This study was designed to evaluate the safety and efficacy of the selective alpha 1-adrenoceptor blocker terazosin in the treatment of benign prostatic hyperplasia (BPH). METHODS: Two hundred twenty-four patients aged 50 to 80 years, who had a diagnosis of BPH based on medical history, physical examination, and digital palpation, were recruited from 11 different sites between January 1992 and January 1994. The study consisted of a screening phase, a placebo phase, a double-blind dose-titration phase, and a double-blind maintenance phase. RESULTS: Of the patients recruited, 164 entered the double-blind phase and of these 134 were evaluable. Only 11 patients withdrew because of an adverse event, 7 in the terazosin and 4 in the placebo group. Compared to placebo, terazosin significantly increased peak and mean urine flow rates without significantly affecting voided volume or postvoid residual volume. It significantly improved both the obstructive and irritative symptoms associated with BPH. Fifty-one patients from the terazosin group reported a total of 120 adverse events compared with 83 reported by 42 patients in the placebo group. The majority of these events were mild to moderate. Seventeen terazosin-treated patients reported hypotension-related adverse events and 4 withdrew from the study. However, concurrent treatment with antihypertensive agents did not affect the blood pressure response of the terazosin group. CONCLUSIONS: Overall, this study showed terazosin to be safe and effective in relieving the signs and symptoms of BPH and should be considered as a treatment alternative.
Adrenergic alpha-Antagonists↗
Vasoactive intestinal peptide and impotence in experimental diabetes mellitus.
OBJECTIVE: To determine whether a defect in vasoactive intestinal peptide (VIP)-mediated vasodilatation underlies diabetic impotence. MATERIALS AND METHODS: Rats treated with streptozotocin for 8 weeks developed diabetes, as shown by hyperglycaemia and glycosuria, and had significant impairment of sexual function, as determined by tests of sexual behavior. The VIP content of the penis and major pelvic ganglion, the VIP release by the penis in vitro and the responsiveness of the vasculature of the penis in vivo to intracavernous VIP injection were determined. RESULTS: In diabetic rats, the VIP content of the major pelvic ganglion and penis was markedly increased, while the acetylcholine content of the penis was normal. The amount of VIP released in vitro by high potassium concentration or veratridine was similar for penile tissue slices of normal and diabetic rats. Intracavernous injection of VIP induced erection in the control rats but not in diabetic rats, whereas intracavernous injection of the adenylate-cyclase activator forskolin produced erection in both control and diabetic rats. CONCLUSION: Because VIP induces vasodilatation by activating adenylate cyclase, and forskolin produced erection in the diabetic rats, the failure of VIP to produce erection in these rats is unlikely to be due to a defect in the second-messenger mechanism or in the properties of vascular smooth muscle. Thus, a defect at the level of the VIP receptor or of the associated G-protein possibly explains the failure of intracavernous VIP to produce erection in the diabetic rats. Hence, an abnormality in VIP is a component of sexual dysfunction in the diabetic rat and the defect is at the level of the VIP receptor or associated G-protein.
Acetylcholine↗
Stimulator design and subsequent stimulation parameter optimization for controlling micturition and reducing urethral resistance.
An implantable computerized electrical stimulation system designed to induce bladder evacuation in animal models (dogs) after spinal cord transection has been realized and evaluated. This fully programmable system is based on a handheld device and generates a wide range of stimuli through multichannel implantable miniaturized stimulator. Using the new bladder stimulator and inducing reversible fatigue to the external sphincter via the pudendal nerve enables us to reduce the bladder outlet resistance, resulting in the proper emptying of the bladder during stimulation without the need for sacral nerve rhizotomies and the pudendal nerve neurectomies. Four chronically affected dogs were studied to determine the optimal stimulation parameters for inducing a sphincter fatigue that would reliably empty the bladder for the duration of the experiment. These parameters were: maximum amplitude of 1.5 mA +/- 0.5 SD, stimuli composed of a high frequency signal of 200 Hz +/- 50 SD modulated by a low frequency signal of 10 Hz +/- 5 SD, pulse width controlled by a duty-cycle of 20% +/- 10 SD, sacral nerve stimulation of 50 s +/- 25 SD and fatiguing duration of 20 s +/- 5 SD.
Animals↗
Value of systematic transition zone biopsies in the early detection of prostate cancer.
PURPOSE: A prospective study was done to determine the value of performing 2 systematic transition zone biopsies in addition to systematic sextant peripheral zone biopsies for early detection of prostate cancer. MATERIALS AND METHODS: From January 1 to August 31, 1994 we evaluated 847 consecutive patients referred to us for a suspicious lesion on digital rectal examination or an elevated serum prostate specific antigen level. All patients underwent 2 systematic transition zone biopsies in addition to systematic sextant biopsies of the peripheral zone. RESULTS: Of the transition zone biopsies 68 (24.4%) contained malignancy, including only 8 (2.9%) with cancer found exclusively in the transition zone. The remaining 271 cases (97.1%) had 1 or more positive peripheral zone biopsies and would have been detected with or without additional systematic transition zone biopsies. The same analysis of 552 patients with a negative digital rectal examination yielded 6 (4.1%) exclusively transition zone tumors among 145 cancers detected in this group. CONCLUSIONS: The low additional yield of transition zone biopsies (2.9 to 4.1%) does not warrant their systematic use for the early detection of prostate cancer.
Adult↗
Effectiveness and safety of the Dornier compact lithotriptor: an evaluative multicenter study.
PURPOSE: We evaluated the efficacy and safety of the Dornier compact lithotriptor for management of renal stones. MATERIALS AND METHODS: We administered 191 treatments to 169 patients with renal stones on 176 occasions with the patient under combined parental sedation and analgesia. The Dornier Compact lithotriptor is mobile and ultrasound guided, and uses an electromagnetic energy source. RESULTS: A total of 22 patients required a second treatment (13%), 123 (72.8%) were stone-free, 26 (15.4%) had fragments less than 4 mm. large, 16 (9.5%) had stone fragments larger than 4 mm, and 4 (2.4%) required auxiliary therapy (treatment failures). The side effects were mostly mild to moderate, with nausea and/or vomiting reported in 26 patients (14%), colic or pain in 66 (39%), ureteral obstruction in 2, steinstrasse in 7 (4%) and fever in 1. Our clinical results indicate that extracorporeal shock wave lithotripsy was effective for treatment of stones in the kidney, with a low incidence of complications and adverse effects. The lithotriptor used is much smaller, less expensive and user friendly with no installation requirements, rendering it mobile. CONCLUSIONS: The success rate with newer generation devices compares well with results obtained using other stationary and larger versions.
Adult↗
Role of prostate-specific antigen density after applying age-specific prostate-specific antigen reference ranges.
OBJECTIVES: To determine the potential role of prostate-specific antigen (PSA) density (PSAD) in the early detection of prostate carcinoma if we apply age-specific PSA reference ranges (2.5 ng/mL or less for ages 40 to 49 years, 3.5 or less for ages 50 to 59, 4.5 or less for ages 60 to 69, and 6.5 or less for ages 70 to 79. METHODS: We retrospectively reviewed 3234 cases referred to us by urologists for transrectal ultrasound (TRUS) between January 1, 1991, and September 28, 1993. We included 2429 patients in the study, ages 40 to 79 years, with Hybritech or Abbott IMx serum PSA determinations and without previously diagnosed prostate cancer. We performed digital rectal examination (DRE) and TRUS in all cases, and TRUS-guided biopsies when indicated. We used stringent criteria to define 736 cases without clinical evidence of malignancy that were designated as a "benign group." RESULTS: In the benign group, we found serum PSA to increase with age in parallel with the increase in prostate volume with age (r = 0.25 and r = 0.26, respectively). The association between serum PSA and prostate volume was stronger (r = 0.46). Using multiple regression analysis, prostate volume accounted for 18% of the variation in serum PSA, whereas age accounted for only an additional 2%. PSAD, which directly relates serum PSA to prostate volume, showed a weak association with age (r = 0.1). In the entire study population of 2429 cases, 555 patients had negative DRE and TRUS results and a serum PSA level between the age-specific upper limit of normal and 10.0 ng/mL. According to the proposed age-specific algorithm, these patients would have required automatic biopsies. Of these, 315 cases (56.8%) still had a PSAD of less than 0.15. We performed biopsies in 108 of these 315 and detected only two cancers, for a positive biopsy rate (PBR) of 1.9%. The remaining 240 cases had a PSAD of 0.15 or higher, and we performed biopsies in 217 of these cases and detected 59 cancers, for a PBR of 27.2%. CONCLUSIONS: The use of age-specific PSA reference ranges does not totally account for the effect of prostate volume on serum PSA. Therefore PSAD can still be used to reduce safely the number of biopsies performed in patients with negative DRE and TRUS results and a serum PSA level 10.0 ng/mL or less and above the age-specific upper limit of normal.
Adult↗