Urology

Published by Elsevier
Online ISSN: 0090-4295
Publications
Article
To evaluate the predictive power of the objectivation of the phimosis grade according to the classification defined by Kikiros and Woodward, with regard to the expected efficacy of 0.1% betamethasone cream as a treatment option. From October 2010 to May 2011, a total of 55 boys (aged <10 years) were treated for phimosis at our department. An assessment of the category of phimosis and the retractability of the foreskin, according to the classification of Kikiros and Woodward, was performed. The proposed treatment options included complete circumcision or topical treatment with steroid cream (0.1% betamethasone-17-valerate). Of the 55 patients, 19 (34.5%) underwent conventional circumcision, and 36 (65.5%) were treated with an 8-week course of topical steroid cream. The mean age was 3.9 years (range 0.6-10). Grade 1, 2, 3, 4, and 5 phimosis was seen in 1 (2.8%), 4 (11.1%), 8 (22.2%), 16 (44.4%), and 7 (19.4%) of the cases in the topical steroid cream group, respectively. The success rate for the topical steroid cream was 69.4% and 63.9% at 3 and 8.3 months, respectively. The objectivation of the phimosis grade did not predict the outcome (P > .05). No side effects were associated with the topical steroid treatment. The pretreatment classification of phimosis did not allow the prediction of success with the topical steroid treatment. We believe that topical steroid therapy with foreskin retraction and daily cleansing is a valid therapy modality that should be offered before any surgical intervention, regardless of the degree of phimosis.
 
Article
To compare the efficacy of the doxazosin gastrointestinal therapeutic system (doxazosin-GITS) 4 mg and tamsulosin 0.2 mg on nocturia in Chinese men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Data were analyzed from a prospective, multicenter, randomized, open, parallel study of Chinese men aged 50-84 years with LUTS/BPH. Two hundred patients were randomized to receive daily treatment with 4 mg doxazosin-GITS (n=100) or 0.2 mg tamsulosin (n=100) for 8 weeks. Nocturia was assessed by question 7 of the International Prostate Symptom Score (IPSS-question 7) and a frequency-volume chart (FVC) at weeks 4 and 8. Self-reported quality of sleep and quality of life by the last question of the IPSS questionnaire were also evaluated. A total of 189 patients (94 receiving doxazosin-GITS, 95 tamsulosin) completed the study. The reduction from baseline in mean nocturia was greater with doxazosin-GITS than tamsulosin by the FVC (1.7 vs 1.3 at week 4; 2.1 vs 1.7 at week 8, both P=.001) and by the IPSS-question 7 (1.5 vs 1.1 at 4 weeks, P=.001; 2.0 vs 1.6 at 8 weeks, P<.001). The patients who reported improved quality of sleep was significantly more with doxazosin-GITS than tamsulosin (43.6% vs 27.4% at 4 weeks, P=.020; 81.9% vs 67.4% at 8 weeks, P=.022), and quality of life was better with doxazosin-GITS (2.5 vs 2.8 at 4 weeks, P=.001; 2.1 vs 2.5 at 8 weeks, P<.001). In Chinese patients with LUTS/BPH, doxazosin-GITS is slightly better than tamsulosin in reducing the frequency of nocturia.
 
Article
Most men diagnosed with prostate cancer in 1998 presented with a normal digital rectal examination (DRE) and minimal elevations in serum prostate-specific antigen (PSA) (less than 10 ng/mL). Considerable attention is often given toward identifying small hypoechoic (less than 0.2 cm3) lesions at the time of transrectal ultrasound-guided prostate biopsy. We sought to determine the significance of these lesions and whether an additional biopsy of this area is clinically useful. A prospective data base containing detailed information on 614 biopsies performed by a single urologist was examined. All patients with a hypoechoic lesion underwent sextant prostate biopsy plus a separately labeled core directed through the hypoechoic area. Eighty-one patients who fit the following criteria were assessed: PSA less than 10 ng/mL, normal DRE, and hypoechoic lesion volume less than 0.2 cm3. The mean age of this group was 63.5 years, and the mean PSA was 7.1 ng/mL. Of the 81 patients with small hypoechoic lesions, 20 (24.7%) were positive for cancer in at least one prostatic core. Of the 81 hypoechoic area biopsies (HABs), 14 (17.3%) were positive for cancer; 1 (1.2%) demonstrated high-grade prostatic intraepithelial neoplasia, and 66 (81 .5%) were negative. In 11 of the patients (78.6%) with positive HABs, at least one additional core was positive for cancer. In 3 of the patients (21.4%) with positive HABs, no additional cores were positive for cancer (P<0.05). A significant proportion of small hypoechoic lesions in patients with early T1c prostate cancer are positive for malignancy. Although the overall yield of separate hypoechoic area biopsy is low (3.7%), approximately 15% of cancers would be missed if directed HABs were not performed (P<0.05). Identification and biopsy of small hypoechoic lesions are indicated in this group of patients.
 
Article
The prostate-specific antigen (PSA) definition of disease freedom after radiotherapy for prostate cancer is still in dispute. This report focuses on the PSA nadir achieved in men treated by modern radiotherapy techniques. From 1984 to 1994, 489 consecutive men with clinical Stage T1 -T2 prostate cancer were treated by simultaneous radiation: prostate iodine-125 implant followed by external beam radiation. A transperineal implant was performed on 143 men with Stage T1-T2NX, the focus of this study; 346 men with Stage T1-T2N0 had a retropubic implant. The median pretreatment PSA was 8.3 ng/mL (range 0.3 to 188). A rising PSA was defined as one that rose on three consecutive occasions above whatever nadir was achieved. A minimum 5-year follow-up (range 5 to 15) was reached by 453 men. After a minimum 5-year follow-up, 336 men had a nonrising PSA, and of this group, 107 had undergone simultaneous radiation by the transperineal implant technique. A PSA nadir of 0.2 ng/mL or less was achieved by 97% of the transperineally implanted men, and 3% had a nadir of 0.3 to 1.0 ng/mL. Of the 489 men, those who had a nadir of 0.2 ng/mL or less had a 92% nonrising PSA rate (P = 0.001) 10 years after treatment compared with a 41% rate for men who had a nadir of 0.3 to 1.0 ng/mL. All men whose nadir was greater than 1.0 ng/mL had recurrence. The median time to achieve the PSA nadir of 0.2 ng/mL was 27 months (range 3 to 102). Primarily on the basis of the results from men treated with simultaneous radiation using the transperineal technique, the definition of disease freedom for radiotherapy should be men who achieve and maintain a PSA nadir of 0.2 ng/mL or less.
 
Article
To explore whether a "no touch" enhancement to the surgical technique of inflatable penile prosthesis (IPPs) implantaion will further decrease infection rates. A single surgeon performed 2347 IPPs between January 2002 and June 2011. Patients receiving each manufacturer's implants were stratified for age and diabetes. Since 2003, infection retardant-coated IPPs were implanted through the standardized penoscrotal approach. Since 2006, the "no touch" enhancement was added to the surgical procedure. Infection rates in the noncoated IPP, coated IPP with standard technique, and coated IPP implanted with "no touch" enhancement were calculated and subjected to statistical analysis. The two company's implants were scrutinized for their individual infection rates in each group. Patients in all the groups were similar for age and diabetes. 132 noncoated implants had an infection rate of 5.3%. In the years 2003-2005, 704 coated devices had a statistically significant improvement in incidence of infection to 2%. In the years 2006-2010, the "no touch" technique enhanced the standard surgical procedure in 1511 patients. Only 7 infections were seen yielding an infection incidence of 0.46%. There was no difference in the two manufacturer's infection rates. Differentiation between virgin and revision operation displayed no bias in the infection rate. Infection-retardant coatings lower the risk of infection from 5.3% to 2%. The "no touch" enhancement to the surgical procedure further decreases the rate of infection to 0.46%. Neither manufacturer showed statistical superiority in survival from revision for infection.
 
Article
This report describes treatment results of men with prostate cancer staged with a pelvic lymph node dissection. Disease freedom was defined by a prostate-specific antigen (PSA) level nadir of 0.5 ng/mL or less. Since 1984, 363 men with clinical Stage T1 or T2, surgical stage node-negative prostate cancer were simultaneously irradiated with a retropubic iodine 125 prostate implant followed by external-beam radiation. The average pretreatment PSA level was 13.6 ng/mL (median 8.5, range 0.3 to 188). Disease freedom was defined as the achievement and maintenance of a nadir of 0.5 ng/mL or less. Treatment failure was defined as a nadir of more than 0.5 ng/mL or a PSA rise above this level. The median follow-up is 5 years (average 5.5, range 1 to 12.5). For all men, the 5- and 10-year disease-free survival results are 78% and 65%. Of 201 men with a minimum 5-year follow-up, 140 (70%) are disease free. The 5-year disease-free survival rate by pretreatment PSA is 4.0 ng/mL or less, 93%; 4.1 to 10.0 ng/mL, 87%; 10.1 to 20.0 ng/mL, 72%; and greater than 20.0 ng/mL, 45%. The 10-year disease-free survival results of retropubic implantation, a technique considered a failure by many investigators, followed by external-beam radiation appear to be better than either technique given separately and are comparable to the results following radical prostatectomy. These results are valuable because they form a baseline that may be improved upon in the future by simultaneous irradiation using the transperineal implant technique.
 
Article
Currently, approximately 30,000 men die annually of metastatic, hormone-refractory prostate cancer. Androgen blockade is palliative and is generally effective for an average of 2 to 3 years until a patient develops androgen-independent disease. Newer chemotherapeutic regimens can induce remissions in approximately 50% of patients; however, median survival for patients with androgen-independent disease is still 8 to 12 months. The strategy of using chemotherapy regimens after androgen blockade has been proved noncurative, and new approaches are needed to attempt to cure patients with advanced disease. It has been demonstrated in the preclinical setting that androgen withdrawal induces apoptosis in cancer cells in both the Shinogi breast cancer model and the LNCaP prostate cancer model. In both of these models, androgen withdrawal was not curative, and the tumors grew back in a hormone-independent state. It is possible that the addition of chemotherapy at the time of initial androgen ablation will improve cell kill by potentiating apoptosis, thereby killing cells that might otherwise have mutated to the androgen-independent state if allowed to continue to cycle and grow. The rationale behind Radiation Therapy Oncology Group (RTOG) P-0014 is to demonstrate in a randomized phase 3 trial that giving patients chemotherapy at the beginning of androgen blockade may improve patient survival.
 
Article
To evaluate the safety, tolerance, protocol completion rate, tumor response rate, and patient survival of chemoradiotherapy for patients with muscle-invasive operable bladder cancer. After transurethral resection of the tumor in patients with Stage T2-T4a bladder cancer, twice-daily radiotherapy with paclitaxel and cisplatin chemotherapy induction (TCI) was administered. If repeat biopsy showed less than Stage T1 disease, consolidation with TCI was given. If repeat biopsy showed greater than Stage T1 disease, cystectomy was recommended. Adjuvant gemcitabine and cisplatin were given to all patients. A total of 80 patients met protocol eligibility. TCI resulted in 26% developing grade 3-4 acute toxicity, mainly gastrointestinal (25%). During consolidation TCI, grade 3-4 acute toxicity, all transient, was reported in 8%. Four cycles of adjuvant chemotherapy were completed per protocol or with minor deviations in 70% of the patients. Adjuvant treatment was associated with grade 3 toxicity in 46% and grade 4 in 26%. One patient had a fatal hemorrhagic stroke. Late bladder radiation toxicity was evaluated in 53 patients with > or = 2 years of follow-up. Of these 53 patients, 3 experienced self-limited, late grade 3 bladder toxicity. The postinduction complete response rate was 81% (65/80), 36 of the 80 patients died (22 of bladder cancer). At a median follow-up of 49.4 months, the actuarial 5-year overall and disease-specific survival rate was 56% and 71%, respectively. These favorable tumor response rates with possible increased bladder preservation rates suggest that this treatment regimen deserves further study.
 
Article
Cryptorchidism has been shown to induce germ cell apoptosis. Nitric oxide (NO), a ubiquitous free radical produced by the nitric oxide synthases (NOSs), has been associated with apoptosis in a number of cell types. We examined the effect of experimental cryptorchidism and subsequent orchidopexy on germ cell apoptosis and endothelial NOS (eNOS) expression. Prepubertal rats were rendered unilaterally cryptorchid, and 14 days later, orchidopexy was performed on a subset of these rats. Forty days after the initial procedure, testes were harvested from experimental and sham-operated rats for immunohistochemical studies. Apoptosis was detected by in situ 3'-end-labeling of DNA with digoxigenin-ddUTP, and eNOS protein was detected using an eNOS monoclonal antibody. Cryptorchid testes were characterized by diffuse hypospermatogenesis and had a 25-fold increase in apoptotic germ cells per cross-sectional area compared with sham-operated testes (P < 0.05). By contrast, the number of apoptotic germ cells per cross-sectional area in orchidopexied testes was not significantly different from that of sham-operated testes. In addition to its known expression in Leydig, Sertoli, and vascular endothelial cells, eNOS was detected in the cytoplasm of degenerating germ cells. Consecutive testis sections stained for eNOS and cellular DNA fragmentation demonstrated co-localization of eNOS protein and germ cell apoptosis. In our experimental model, cryptorchidism induced germ cell apoptosis, and orchidopexy lowered the levels of germ cell apoptosis. Our data also support a role of eNOS in germ cell degeneration.
 
Article
The results of 355 questionnaires are reported, returned one or more years after vasectomy from 1,000 consecutive patients undergoing vasectomies performed by the author from 1959 to 1972. A majority claimed either unchanged or improved health, satisfaction with sexual relations, and frequency of sexual intercourse; 99.5 per cent were satisfied with the operation and in retrospect 96.7 per cent would have the operation again.
 
Article
1,25-Dihydroxyvitamin D can inhibit the proliferation of prostate cancer cells, but its clinical use is limited by hypercalcemia. We examined the effects of a "noncalcemic" vitamin D analogue, 1,25-Dihydroxy-16-ene-23-yne-cholecalciferol (16-23-D3), on the proliferation of human prostate cancer cells in a mouse model. Twenty-four athymic nude mice were inoculated with human prostate carcinoma cells from the PC-3 cell line. Twelve mice (experimental group) received injections of 1.6 micrograms of 16-23-D3 on alternate days over a 22-day period. Twelve mice (control group) received sham injections. Tumor volumes, pathologic findings, and terminal serum calcium levels were compared between groups. The relative increase in tumor volume was significantly lower in the experimental than in the control group in the first interval following treatment (P < 0.01). Mean tumor volumes in the experimental group were approximately 15% smaller than in the control group. Serum calcium levels did not differ between groups. 16-23-D3 showed modest antiproliferative effects on prostate cancer cells in this model without evidence of drug-induced hypercalcemia. These findings support the concept that vitamin D analogues can inhibit the proliferation of human prostate cancer cells in vivo.
 
Article
1,25-dihydroxyvitamin D(3) (calcitriol) inhibits prostate cancer growth in vitro and in vivo. We used a prostate microdialysis technique to better understand the intraprostatic pharmacokinetics of calcitriol, which in turn would facilitate planning for systemic calcitriol therapy in patients with prostate cancer. Male Sprague-Dawley rats were treated with 5 microg of calcitriol intravenously. Animals were either intact (group 1, n = 6) or castrated (group 2, n = 3). Prostate microdialysis was performed by perfusing Krebs solution through a 5-mm linear probe. Effluents were collected hourly from 0 to 20 hours or until death. Serum was collected at baseline and at the end of the experiment. Serum was also obtained from untreated rats at 0, 1, 2, 3, 4, 6, 8, 12, and 24 hours after intraperitoneal injection of calcitriol. Calcitriol levels were measured by radioimmunoassay. The average baseline intraprostatic level of calcitriol in prostate dialysate in intact rats was 21.1 pg/mL (+/-7.5); it was 88 pg/mL (+/-98.4) after calcitriol administration. In castrated animals, the values were 16.6 pg/mL (+/-5.3) and 25.3 pg/mL (+/-10.7). Two peaks in intraprostatic calcitriol levels were observed after intravenous administration: at less than 6 hours after injection and at more than 13 hours after injection. The mean total calcitriol exposure (area under the concentration versus time curve) in the prostate was 297.6 (+/-159) pg/hr/mL (intact) and 272.7 (+/-123.6) pg/hr/mL (castrated). The baseline serum levels were 0.1 to 1 ng/mL and reached a peak of more than 100 ng/mL within 1 hour of intraperitoneal injection. This technique permits real-time measurement of intraprostatic pharmacokinetics of calcitriol. The ratio of the intraprostatic area under the concentration versus time curve to the serum area under the concentration versus time curve of calcitriol was less than 1:100. Hence, within 24 hours of calcitriol administration, only a fraction (less than 1%) of the serum level is detectable in prostatic tissue. A bimodal peak in intraprostatic calcitriol levels is observed. This technique could be used to determine the tissue levels of calcitriol more accurately and to conduct additional studies to better elucidate the effects of castration on the intraprostatic pharmacokinetics of calcitriol.
 
Article
Currently, several prostate cancer rescreening intervals are in use in different countries worldwide, varying from 1 to 4 years. Recently, it has been proposed to determine the rescreening interval relative to the initial prostate-specific antigen (PSA) level and possibly to extend the rescreening interval up to 5 years. We evaluated the screening results of two subsequent screening visits (4-year interval) of 1703 men aged 55 to 65 years with an initial PSA level of 1.0 ng/mL or less within a randomized screening trial. We assessed the PSA values, numbers of men biopsied (biopsy indication: PSA level of 3.0 ng/mL or greater), and numbers of cancers detected at the second and third screening visits. A total of 1327 men (79.3%) attended the second screening visit. Of these men, 13 (0.98%) had a PSA level of 3.0 ng/mL or greater, and three cancers were detected (cancer detection rate 0.23%). At the third screening visit, 1017 men (76.8%) attended, 34 men (3.3%) had a PSA level of 3.0 ng/mL or greater, and five cancers were detected (cancer detection rate 0.49%). The 2344 subsequent PSA determinations in an 8-year period after the initial screening resulted in eight cancers detected, for an overall cancer detection rate of 0.47%. Through linkage of all men with the cancer registry, no additional cancers were found. A strategy of PSA screening every 8 years for men with a PSA level of 1.0 ng/mL or less will lead to a considerable decrease in the number of screening visits (with the associated costs and stress), with a minimal risk of missing aggressive cancer at a curable stage.
 
Article
To study the use of a baseline prostate-specific antigen (PSA) and digital rectal examination in men (aged 40-49 years) in predicting long-term prostate cancer risk in a prospectively followed, representative population cohort. Since 1990, a random sample of men in Olmsted County (aged 40-49 years) has been followed up prospectively (n = 268), with biennial visits, including a urologic questionnaire, PSA screening, and physical examination. The ensuing risk of prostate cancer (CaP) was compared using survival analyses. Median follow-up was 16.3 years (interquartile range 14.0-17.3, max 19.1). For men with a baseline PSA <1.0 ng/mL (n = 195), the risk of subsequent Gleason 6 CaP diagnosis by 55 years was 0.6% (95% confidence interval [CI] 0%-1.7%) and 15.7% (95% CI 6.5%-24.9%) for men with a baseline PSA ≥1.0 ng/mL. No man with a low baseline PSA developed an intermediate or high risk CaP, whereas 2.6% of men with a higher baseline PSA did (95% CI 0.58%-4.6%). Men (aged 40-49 years) can be stratified with a baseline PSA. If it is below 1.0 ng/mL, there is very little risk for developing a lethal CaP, and as many as 75% of men might be able to avoid additional PSA screening until 55 years. Conversely, men aged 40-49 years with a baseline PSA level >1.0 ng/mL had a significant risk of CaP diagnosis and should be monitored more closely.
 
Article
To evaluate our minimum 1.5-year results with "surgeon-tailored" polypropylene mesh (STPM) in stress urinary incontinence treatment and the impact of concomitant pelvic organ prolapse repair on functional outcomes. All patients who were treated for stress urinary incontinence and pelvic organ prolapse using STPM between 2006 and 2010 were reviewed. Fifty-two patients received transobturator midurethral sling alone. Concomitant pelvic organ prolapse repair was performed in 74 (67 cystocele, 14 rectocele). Pre- and postoperative evaluation included subjective assessment of the impact of voiding and prolapse symptoms with International Consultation on Incontinence-Short Form and Prolapse Quality of Life (P-QOL) questionnaires, uroflowmetry, and urodynamic studies when necessary. Surgical outcomes at the last follow-up and complications were compared between the transobturator midurethral sling and transobturator midurethral sling + pelvic organ prolapse repair groups. One-hundred eighteen women were available for analysis. With a mean follow-up of 33.4 and 41.2 months for transobturator midurethral sling and transobturator midurethral sling + pelvic organ prolapse repair groups, stress urinary incontinence was cured in 86.4% and 81.1% of the patients, respectively. Preoperative urge symptoms resolved in 53.8% and 62.5%, and de novo urge symptoms developed in 22% and 15% of patients with respect to study groups. Pelvic organ prolapse was cured in 98.6% patients, with a significant improvement in all domains of the P-QOL questionnaire at the last follow-up. Vaginal mesh erosions were detected in 11 (14.8%) patients with concomitant pelvic organ prolapse repair. STPM may represent a cost-effective option for stress urinary incontinence treatment. Concomitant pelvic organ prolapse repair with STPM does not affect incontinence outcomes and provides high anatomic success and patient satisfaction in the long term. However, mesh-related complications with this approach is a major concern that deserves further investigation of risk factors and better definition of patient selection criteria.
 
Article
To describe an open technique for the cryosurgical ablation of small renal tumors using multiple ultrathin cryoprobes. Renal cryosurgery is an evolving surgical technique, and uncertainties exist regarding the ideal approach to freezing renal tumors. Using an open surgical approach, a 3-cm upper pole renal mass was ablated using five, state-of-the-art, 1.5-mm cryoprobes simultaneously under real-time ultrasound guidance. The technique is described and demonstrated in a multisegment, Internet-based video tutorial. The blood loss was minimal, and no intraoperative or postoperative complications were experienced. Follow-up imaging at 3 months suggested shrunken, nonviable tumor. Cryosurgical ablation of renal tumors using multiple 1.5-mm cryoprobes is a safe, feasible approach that may be associated with a decreased risk of bleeding.
 
Article
To determine whether a rise in the serum prostate-specific antigen (PSA) concentration 24 months or later after completion of external beam radiotherapy (EBRT) for prostate cancer could predict for biochemical failure. We evaluated the records of 1006 patients who had undergone full-dose EBRT alone as primary treatment for T1-T4NxM0 prostate cancer at our institution between April 1987 and January 1998. Patients who had biochemical failure--as determined by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition--prior to 24 months after EBRT were excluded. PSA increases of four different magnitudes (0.5, 0.8, 1.0, and 1.5 ng/mL above the 24-month nadir) were evaluated for their ability to predict ASTRO-defined biochemical failure. A total of 745 patients met the analysis criteria. The rate of ASTRO-defined biochemical failure in patients with a PSA increase of 0.5, 0.8, 1.0, and 1.5 ng/mL above the 24-month nadir was 56%, 64%, 66%, and 71%, respectively. An increase of 1.5 ng/mL or more had a sensitivity of 80% and a specificity of 88% in the prediction of biochemical failure, with an accuracy of 86%. A PSA increase of 1.5 ng/mL or more above the 24-month nadir can be used to predict for ASTRO-defined failure after EBRT and may be used to identify patients at risk early-on.
 
Article
Improved discrimination between prostate cancer (PC) and benign prostatic hyperplasia (BPH) is clearly needed. Our aim in this study was to evaluate whether the free to total prostate-specific antigen (PSA) ratio would be useful in the gray zone of 1.8-10 ng/mL total PSA range. In a consecutive series of 435 clinic patients referred for prostate evaluation, 308 had a total PSA < 10 ng/mL (92 had PC and 216 BPH). Free and total PSA were measured, and the free to total PSA ratio calculated. Total PSA values were significantly different between the two groups. For the 200 patients with a total PSA < 6 ng/mL, no significant difference in total PSA values were seen (P = 0.411), whereas free to total PSA ratios remained statistically different (P < 0.001). Receiver operating characteristic (ROC) curve analysis comparing the performances of total PSA over the ratio of free to total PSA showed a clear advantage for the ratio at all sensitivity levels. These data demonstrate that in a significant number (n = 308) of prostatic patients in the diagnostic gray zone of 1.8-10 ng/mL total PSA, the routine use of free to total PSA might be advantageous in discriminating between cancer and benign hyperplasia. This advantage remained for total PSA < 4 ng/mL. Further study is warranted to confirm these findings in an unselected population.
 
Article
To prospectively evaluate the Stage T1c prostate cancer detection rate and pathologic characteristics of patients with a serum prostate-specific antigen (PSA) level of 3.0 to 4.0 ng/mL and compare this with the rate of patients who had a PSA level of 4.1 to 10.0 ng/mL. We analyzed the data of patients who had PSA levels of 3.0 to 10.0 ng/mL, benign findings on digital rectal examination, and no specific lesion identified on transrectal ultrasonography. The clinical characteristics, cancer detection rate, and pathologic findings of the biopsy and prostatectomy specimen were compared between the low (3.0 to 4.0 ng/mL) and intermediate (4.1 to 10.0 ng/mL) PSA groups. A total of 450 patients met our criteria. Of these 450 patients, 85 and 365 had a low or an intermediate PSA level, respectively. Prostate cancer was diagnosed in 26% of the low and 19% of the intermediate PSA group. No significant difference was found between the two groups in the pathologic biopsy findings, including the mean Gleason score and percentage of patients with a Gleason score of 7 or more. The pathologic findings of the prostatectomy specimens also showed no significant differences between the two groups, including the mean Gleason score, pathologic stage, and percentage of insignificant prostate cancer. No statistically significant difference was found in the incidence of Stage T1c prostate cancer or pathologic characteristics in comparison between the low and intermediate PSA groups. These results suggest that a lower PSA cutoff should be considered as an indication for prostate biopsy in the Korean population.
 
Article
To determine the ability of complexed prostate-specific antigen (cPSA) levels to diagnose prostate cancer. Between September 1998 and March 1999, cPSA levels in 182 consecutive patients with an abnormal digital rectal examination (DRE) or a total PSA (tPSA; Tandem-R assay) level greater than 4.1 ng/mL were examined. Levels of cPSA were measured by the Markit-M PSA-ACT (alpha(1)-antichymotrypsin) assay (cPSA-MM) and Bayer Immuno 1 complexed PSA assay (cPSA-BI). Free PSA (fPSA) was measured by the Tandem-R free PSA assay. Of the 140 patients with tPSA between 4.1 and 10.0 ng/mL, 116 were histologically confirmed as having benign tissue; the remaining 24 were diagnosed with prostate cancer. To ensure a 92% sensitivity of cancer detection, a cutoff value for the tPSA, cPSA-MM, and cPSA-BI assays of 4.8 ng/mL, 2.7 ng/mL, and 4.6 ng/mL, respectively, was determined. The percentage of negative biopsies prevented at these cutoff (ie, specificity) values was 14%, 23%, and 24%. No significant differences among these three assays were found. At 92% sensitivity, the cutoff value for the fPSA/tPSA, fPSA/cPSA-MM, and fPSA/cPSA-BI ratios was 18%, 27%, and 18%, respectively. The specificity was 35%, 49%, and 51%. No significant differences were found among these three fPSA ratios. Significant differences were noted between tPSA and the fPSA/cPSA-MM ratio and between tPSA and the fPSA/cPSA-BI ratio. No differences were seen among the other PSA parameters. No difference in the ability of cPSA levels to distinguish prostate cancer and noncancer was observed between cPSA-MM and cPSA-BI or between their fPSA ratios. Only the fPSA/cPSA-MM and fPSA/cPSA-BI ratios provided significantly enhanced diagnostic performance compared with tPSA.
 
Article
To analyze prospectively whether prostate cancer (CaP) incidence differs between Japanese men with a prostate-specific antigen (PSA) level of 2.0 to 4.0 ng/mL and those with a PSA level of 4.1 to 10.0 ng/mL. Men 79 years old or younger who were referred to our clinic were screened for CaP. Individuals with PSA levels of 2.0 ng/mL or greater were recommended for transrectal prostate biopsy. The prebiopsy clinical characteristics, cancer detection rate, and pathologic findings from the needle biopsy and prostatectomy specimen were compared between the low (2.0 to 4.0 ng/mL) and intermediate (4.1 to 10.0 ng/mL) PSA groups. Of 858 patients screened for CaP, 440 with benign findings on digital rectal examination met the criteria, and 274 (62.3%) underwent biopsy. Of those undergoing biopsy, 110 and 123 patients had a low or an intermediate PSA level, respectively. Men in the low PSA group had a higher free/total PSA ratio, smaller prostate volume, and lower PSA density compared with those in the intermediate PSA group. CaP was diagnosed in 26 (23.6%) of 110 in the low and 29 (23.6%) of 123 in the intermediate PSA group. No statistically significant difference was found between the two groups in the pathologic findings of needle biopsy, including Gleason score, number of cores per biopsy, percentage of positive cores, and cancer length in the positive cores. No statistically significant difference was found in the incidence of CaP (23.6%) between men with low and intermediate PSA levels in a Japanese population. The diagnostic yield was comparable to that reported for both white and black men.
 
Article
To evaluate the usefulness of measuring the free/total prostate-specific antigen (PSA) ratio (%fPSA) in men with initial PSA levels of 4.1 to 10.0 ng/mL as a predictor of the future risk of developing prostate cancer. Between 1989 and 2001, 201 subjects with an initial PSA level of 4.1 to 10.0 ng/mL, who had free PSA measured at initial screening using frozen serum and underwent consecutive screening at least once, were enrolled in this study. All participants were followed up by consecutive PSA measurements. Biopsies were performed for those with PSA levels greater than 10.0 ng/mL or with a PSA velocity of 1.0 ng/mL or greater in consecutive screening. The follow-up period was 1 to 12 years, and the mean number of screenings was 3.8. The usefulness of %fPSA, age, and total PSA as predictive factors of future prostate cancer morbidity was investigated. The cumulative non-prostate cancer rate was evaluated using Kaplan-Meier analysis relative to various %fPSA cutoffs. A total of 142 patients (71%) underwent prostate biopsy at least once during observation according to the biopsy criteria. The detection rate of prostate cancer was 26% (53 of 201) in consecutive screening. The most recent PSA velocity and serum PSA levels at last follow-up in patients with prostate cancer were significantly higher than in those without prostate cancer. The cumulative non-prostate cancer rate was significantly greater in subjects with %fPSA less than the cutoff than in those with %fPSA at the cutoff point or greater in the %fPSA cutoffs of 16% to 25%. Men with PSA levels of 4.1 to 10 ng/mL who are not suspected of having prostate cancer by whatever means should undergo %fPSA measurement and be carefully monitored at short intervals over the long-term if they have lower %fPSA levels.
 
Article
To determine whether granulocyte colony-stimulating factor receptor (G-CSFR) autocrine signaling promotes endothelial cell adhesion and invasion of bladder cancer cells through a beta1-integrin-mediated pathway. A significant fraction of invasive bladder carcinomas express both G-CSF and G-CSFR. Bladder carcinoma cell line 5637 constitutively secretes G-CSF but lacks G-CSFR expression. Thus, we studied the effects of G-CSFR expression on cell adhesion and invasion in this unique model system. Flow cytometry and adhesion assay were performed to detect expression of beta1-integrin in G-CSFR-expressing 5637 cells and adhesion of these cells to human umbilical vein endothelial cell, respectively. Furthermore, an invasion chamber assay was done with the 5637 cells. Next, we used the G-CSF-specific antibody, siRNA, and a truncated version of G-CSFR (GR19) to block G-CSFR autocrine loop in these cells. We also used a beta1-integrin-specific neutralizing antibody in the adhesion and invasion assays with the 5637 cells. G-CSFR-mediated increased expression (approximately threefold) of beta1-integrin is significantly abrogated by G-CSF specific antibody or siRNA in 5637 cells. GR19 also completely blocked beta1-integrin expression. G-CSFR signaling increased adhesion (approximately 2.5-fold) of 5637 cells to human umbilical vein endothelial cells, which are potently blocked by beta1-integrin-specific antibody. G-CSF/G-CSFR autocrine signaling significantly increased the invasiveness of 5637 cells (approximately 10-fold), which was reduced by either attenuating G-CSF production (G-CSF-specific antibody and siRNA) or interfering with G-CSFR signaling (GR19). Furthermore, beta1-integrin-specific antibody completely blocked G-CSFR-mediated invasion of 5637 cells. Autocrine G-CSF/G-CSFR signaling in bladder cancer can significantly contribute to cancer cell adhesion and invasion in a beta1-integrin-dependent manner.
 
Article
Since the publication of the Southwest Oncology Group (SWOG) 99-16 and TAX 327 studies, which demonstrated a survival benefit for docetaxel-based therapy, clinicians for the first time have a therapy to offer men with metastatic prostate cancer that is not merely palliative in its effects. Phase 2 and phase 3 trials are now building on the findings of SWOG 99-16 and TAX 327 by evaluating the potential of combination taxane-based therapies, such as docetaxel plus high-dose calcitriol, docetaxel-estramustine-bevacizumab, and docetaxel-thalidomide. The optimal timing of docetaxel-based chemotherapy is still unknown, as there are no prospective clinical trial data to indicate whether earlier treatment (eg, at the time of prostate-specific antigen failure) is more or less effective than later treatment (eg, in metastatic and/or symptomatic disease).
 
Article
To investigate whether testosterone surges occur on repeat injections of 3.6 or 10.8 mg goserelin (Zoladex) depot and, if so, their extent. Men with prostate cancer for whom hormonal therapy was indicated were randomized to open-label goserelin 3.6 mg every 28 days (n = 129) or 10.8 mg every 84 days (n = 118) for 48 weeks. Serum testosterone and luteinizing hormone levels were measured before repeat injection on day 1 of each treatment cycle and then on days 4 and 8. Surges were defined in three ways: type 1, simultaneous increase in both testosterone and luteinizing hormone to within the age-specific normal range; type 2, increase in testosterone to within the age-specific normal range; and type 3, elevation in testosterone from less than to greater than the castrate level (greater than 18.5 ng/dL). Most patients did not experience a testosterone surge. Two patients (1.8%) in the 10.8-mg group had a type 1 surge after one repeat injection and two (1.6%) in the 3.6-mg group had a type 2 surge after one repeat injection. Type 3 surges occurred after one or more repeat injections in 34 (27.0%) and 20 (17.7%) patients in the 3.6-mg and 10.8-mg groups, respectively (P = 0.065); the mean surge (+/- standard deviation) was 11.2 ng/dL (+/-13.5) and 17.3 ng/dL (+/-24.6), respectively. No patient with a testosterone surge had clinical symptoms of a tumor flare reaction. The testosterone levels were consistently maintained within the castrate range (18.5 ng/dL or less) in most (77.4%) patients receiving long-term 3.6 mg or 10.8 mg goserelin.
 
Article
To assess the short-term efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) with the standard Dornier Lithotripter S 220 F EMSE in the treatment of a large population of 736 patients with renal and ureteral stones. This is the only report with more than 1000 treatments performed with this device. Between January 2003 and July 2006, a total of 479 renal and 257 ureteral stones were treated with 1168 ESWL sessions. ESWL was performed on an outpatient basis. Patients were evaluated after 1 and 3 months. Stone size and location, total number of shockwaves, stone-free rate, and complications were investigated. The stone-free rate for renal calculi was 60.5% at 1 month and 82.5% at 3 months. The stone-free rate for ureteral stones was 58% at 1 month and 82.9% at 3 months. The overall stone-free rate was 59.6% at 1 month and 82.5% at 3 months. Anesthesia was not needed in any case. Analgesia with hospital admission was necessary in 15 patients (2.0%). The major complications observed were renal hematoma in only 1 patient (0.1%), obstruction with sepsis in 3 patients (0.4%), and steinstrasse development in 5 patients (0.7%). The Dornier Lithotripter S 220 F EMSE is a safe and effective tool in the treatment of urolithiasis; the lack of invasiveness and absence of anesthesia confirm its worthy role as an alternative to ureterorenoscopy and percutaneous nephrolitotomy.
 
Article
To determine the incidence and spectrum of significant alternative or additional diagnoses established or suggested on unenhanced helical computed tomography (CT) in a large series of patients with suspected renal colic. One thousand consecutive unenhanced helical CT examinations were performed for suspected renal colic. All official CT reports were retrospectively reviewed, which was followed by review of all available relevant follow-up radiology reports. A selected image and chart review was also performed. Ureteral calculi were identified on 557 examinations, findings consistent with a recently passed stone were discovered on 67 examinations, and 275 CT examinations were unremarkable. An alternative or additional diagnosis was established or suggested on 101 examinations, including in 26 patients with concurrent ureteral calculi. There were 62 genitourinary and 39 nongenitourinary tract diagnoses. Eighty-seven of the diagnoses could be confirmed on retrospective image review combined with patient follow-up. There were two false-positive diagnoses for significant, alternative pathologic findings. A wide spectrum of significant, alternative, and additional genitourinary and nongenitourinary diagnoses can be reliably established or suggested on unenhanced helical CT performed for suspected renal colic. These abnormalities were identified in 10% of cases in this series of 1000 consecutive CT examinations.
 
Article
Elevated circulating levels of interleukin 6 (IL-6) have been associated with cancer metastasis. IL-6 binds either to membrane or to soluble IL-6 receptor (IL-6sR), which then induces homodimerization of gp130 that activates downstream signaling. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels are associated with prostate cancer stage, progression, and metastasis after radical prostatectomy. Plasma levels of IL-6 and IL-6sR were measured in 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer, 44 healthy men without any cancer, 19 men with prostate cancer metastatic to the regional lymph nodes, and 10 men with prostate cancer metastatic to bone. Plasma IL-6 and IL-6sR levels were highest in patients with bone metastases (P <0.001). The preoperative IL-6 and IL-6sR levels were associated with the preoperative prostate-specific antigen (PSA) level (P </=0.041), prostatectomy tumor volume (P </=0.048), and final Gleason sum (P </=0.042). The preoperative IL-6 and IL-6sR levels and biopsy Gleason sum were independent predictors of PSA progression (P </=0.029). However, in a model that included both IL-6 and IL-6sR, only IL-6sR and the biopsy Gleason sum predicted progression (P </=0.040). In patients whose disease progressed, the preoperative IL-6 and IL-6sR levels were highest in those with presumed aggressive failure (P </=0.042). Plasma IL-6 and IL-6sR levels were dramatically elevated in the men with prostate cancer metastatic to bone. In patients with clinically localized prostate cancer, the preoperative plasma IL-6 and IL-6sR levels independently predicted biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.
 
Article
To evaluate microstaging by means of quantifying the depth of invasion of the subepithelial connective tissue in pT1 transitional cell carcinoma (TCC) of the bladder for its additional prognostic value with respect to disease recurrence and progression. We reviewed the pathologic findings of a consecutive series of 124 patients with pT1 tumors entered in a prospective randomized multicenter trial comparing mitomycin C and bacillus Calmette-Guérin treatment, with at least 3 years of follow-up and clinical outcome hidden from reviewers. The depth of invasion was established by identifying submucosal tumor invasion up to, in, or beyond the muscularis mucosae or vascular plexus and classified as pT1a, pT1b, or pT1c, respectively. In addition to tumor grade, the presence of carcinoma in situ (CIS) near the primary tumor or in biopsy specimens taken from abnormal looking mucosa was taken into account. The risks of recurrence and progression were calculated using Kaplan-Meier curves and modeled with proportional hazard models. pT1 subclassification was possible in more than 90% of the specimens. The 3-year risk of recurrence was not different in any of the subgroups. By contrast, the Kaplan-Meier 3-year risk for progression was 6%, 33%, and 55% for pT1a, pT1b (hazard ratio [HR] 5.51), and pT1c (HR 12.35) tumors, respectively (log-rank test P < 0.001). The Kaplan-Meier 3-year risk of progression was 9% versus 39% (HR 5.62) for the absence or presence of CIS in the tumor (P=0.001) and 8% versus 49% (HR 6.72) for CIS in biopsy specimens (P < 0.001). Tumor grade had no statistically significant prognostic value with respect to progression, nor had tumor volume or multifocality. The combination of the parameters (pT1c and CIS) increased the risk of progression by a factor of 27 (P < 0.0001) compared with the absence of pT1c and CIS. These data show that the extent of lamina propria invasion (pT1a, pT1b, pT1c) is a clinically relevant prognostic factor for progression of pT1 TCC of the bladder. With the combination of this pT1 subclassification and the presence of CIS subgroups, distinct risks of progression can be identified that may give additional information for follow-up and treatment policies.
 
Article
To assess the operative morbidity, we reviewed retrospectively 101 groin dissections performed in 67 patients for management of squamous cell carcinoma of the penis. No patients died, but only 18 per cent experienced no postoperative complications. Early complications included flap necrosis in 50 per cent, seroma in 16 per cent, wound infection in 14 per cent, lymphocele in 9 per cent, and thrombophlebitis in 6 per cent. Leg edema developed in 50 per cent of those operated on and remained severe in about one third of these. The frequency of complications has changed little over the thirty-five-year time span of the study and is not related to the extent of the surgical procedure. In view of the high operative morbidity, caution should be exercised against using the surgical procedure injudiciously.
 
Article
Bilateral renal cell carcinomas (bRCC) account for <4% of all renal tumors. We report on the management, histopathologic results, and long-term follow-up of 101 patients with bRCC. A total of 101 patients with bRCC who had undergone surgery from 1975 to 2005 at our institution were identified from our kidney tumor database and included in this retrospective analysis. Cancer-specific survival was assessed using the Kaplan-Meier method. Subgroups were compared using the log-rank test. Statistical analysis was performed with the Statistical Package for Social Sciences for Windows. Of 3097 kidney tumor patients, 101 (3.3%) had bRCC on final histopathologic examination. Synchronous tumors were found in 43 patients (42.6%) and metachronous tumors in 58 (57.4%). The cancer-specific survival rate of the entire cohort was 91.9%, 79.1%, and 56.7% after 5, 10, and 20 years, respectively. The survival of patients with synchronous or metachronous bRCCs did not differ significantly. Patients with metachronous bRCC were significantly younger at first diagnosis than those with synchronous bRCCs (median age 53.6 vs 58.7 years, P < .05). The histopathologic results revealed significantly greater rates of papillary bRCCs in synchronous tumors (P < .05). Standardized techniques of nephron-sparing surgery can achieve excellent survival rates in bRCC. Among other arguments for nephron-sparing surgery, kidney-preserving strategies are of particular importance in younger patients with unilateral RCC against the background of an increasing risk of developing a contralateral neoplasm with older age.
 
Article
The initial encouraging results using 5-aminolevulinic acid (5-ALA) induced fluorescence endoscopy (AFE) have promised a procedure with an outstanding sensitivity for the detection of early stage bladder cancer. Summarized here is our clinical experience and data comprising 1012 fluorescence endoscopies. Two hours, 30 minutes before endoscopy, 1.5 g 5-ALA dissolved in 50 mL of 5.7% sodium monohydrogen phosphate was instilled in patients intravesically. Before AFE, all patients underwent white light endoscopy, and a bladder washing cytologic specimen was obtained. A special light source provided blue light (375 to 440 nm) for fluorescence excitation. Suspicious sites were identified by their red fluorescence contrasting against backscattered blue light when observed through the long pass filter (445 nm) integrated into the telescope eyepiece. Two thousand four hundred seventy-five specimens were obtained (2.4 biopsies per AFE). In 552 AFEs (54.5%), neoplastic urothelial lesions were detected, in 34.2% only because of their positive fluorescence; 38.7% of these additionally detected neoplastic foci had poorly differentiated histologic features. AFE has proved to be a clinically feasible procedure with an outstanding detection rate for flat, urothelial, high-risk lesions.
 
Article
To identify the rates of decline in health-related quality of life during the year before death in men with prostate cancer. We studied men in a subset analysis within a longitudinal, observational cohort of patients with metastatic prostate cancer at the University of California, Los Angeles, Center for Health Sciences. The analysis included 23 patients who died and had submitted at least two health-related quality-of-life surveys in the final months before death. The outcomes were measured with the RAND 36-Item Health Survey, an established, validated instrument that includes physical and emotional domains. To gauge the effect of marital status, education, and income, we dichotomized these demographic variables. Most domains showed declines, many of them substantial. Patients who had a slower rate of decline in the physical domains tended to be married, better educated, and more affluent. We noted a trend toward a slower deterioration in the mental composite scores among patients who had less than a college degree and an annual household income of $30,000 or less. Patients dying of metastatic prostate cancer appear to experience declines in health-related quality of life during their final year of life. Further investigation may help identify specific patient characteristics associated with more rapid declines; this will help focus attention on enhancing patients' quality of life as death approaches.
 
Article
To evaluate the early morbidity of palladium 103 (103Pd) prostate brachytherapy. Thirty-two patients with Stage A or B prostate carcinoma were implanted transperineally with 103Pd using transrectal ultrasound and fluoroscopy between May 1990 and December 1992. Patients were subsequently followed to evaluate for morbidity and possibility of migration of the implanted seeds into the lungs. The median follow-up time was 20 months (range, 2 to 45 months). The major acute toxicity of the procedure, dysuria, was seen in 88% of the patients. Although this was generally grade 1 or 2 and transient, grade 3 or 4 toxicity occurred in 18% of patients. Mild rectal symptoms (transient diarrhea, rectal bleeding) occurred in 19% of patients. Sexual functions could not be evaluated. Seven of the 3213 total seeds implanted (0.2%) were found to have migrated to the lung in 6 of 30 (20%) patients having a postoperative chest radiograph. This did not cause any clinical problems. 103Pd prostate brachytherapy is generally associated with only mild or moderate urinary and rectal symptoms, and the incidence of severe complications is low. Further follow-up is required to evaluate the efficacy.
 
Top-cited authors
Ian Osterloh
Alan Riley
Claus G Roehrborn
  • University of Texas Southwestern Medical Center
David G Bostwick
Alan W Partin
  • Johns Hopkins Medicine