Erik T. Goluboff

Semen analyses in 1,283 men from the United States over a 25-year period: no decline in quality

OBJECTIVE To determine whether semen quality has changed in the United States over the last 25 years. DESIGN Retrospective review. SETTING Three U.S. sperm banks, Cryogenic Laboratories, Inc. (Roseville, Minnesota), Idant Laboratories (New York, New York), and California Cryobank, Inc. (Los Angeles, California). INTERVENTION None. MAIN OUTCOME MEASURES Age at sample collection, sperm concentration, volume, motility, and days of abstinence before sample collection were determined for each man. Linear and multiple regression analyses were used to assess changes in these characteristics over time. RESULTS Controlling for the effects of age and duration of abstinence, there was a slight but significant increase in mean sperm concentration but no change in either motility or semen volume over the 25-year period. Both sperm motility and semen volume decreased with increasing age at sample collection. Both sperm concentration and semen volume increased as a function of duration of abstinence. There were significant differences in mean (+/- SEM) sperm concentrations (10(6) sperm/mL) and motilities between the different sperm banks with California lowest (72.7 +/- 3.1, 51.4% +/- 1.1%, respectively), Minnesota higher (100.8 +/- 2.9, 56.0%, respectively), and New York highest (131.5 +/- 3.5, 58.2% +/- 0.5%, respectively). CONCLUSIONS Our data show no decline in sperm counts over a 25-year period in 1,283 men who banked sperm before vasectomy at three distinct geographical sites in the United States.

Exisulind (sulindac sulfone) suppresses growth of human prostate cancer in a nude mouse xenograft model by increasing apoptosis

OBJECTIVES Recent studies have shown that Exisulind, a sulfone metabolite of the nonsteroidal anti-inflammatory drug (NSAID) sulindac, has inhibitory activity in vitro with cultured human prostate cancer cells. To determine whether this effect might be pharmacologically relevant in vivo, we tested whether Exisulind therapy could suppress the growth of human prostate cancer cells in a nude mouse xenograft model. METHODS Thirty athymic nude mice were injected subcutaneously in the flank with 1 x 10(7) LNCaP human prostate tumor cells. All mice received a control diet for 21 days. One group of mice was continued on this control diet for an additional 4 weeks, a second group was switched to a diet supplemented with 0.05% Exisulind (40% of maximal tolerated dose [MTD]), and a third group was switched to a diet supplemented with 0.1% Exisulind (80% MTD) for the additional 4 weeks. Tumor growth was measured through the 4-week test period, and subsequently tissue sections from the various groups were tested for apoptotic and dividing cells by quantified use of the TUNEL assay and a bromodeoxyuridine (BrdU) incorporation immunoassay. RESULTS Tumors grew by 158%, 24%, and 18% for the control and 0.05% and 0.1% Exisulind groups, respectively (P = 0.02) during the 4-week test period. Immunohistochemical studies on excised tumors showed an increased number of apoptotic bodies in the treated groups versus the control group (P<0.0001) but no change in the number of BrdU positive cells. CONCLUSIONS This is the first study to show a direct in vivo effect of an NSAID-derived drug, lacking cyclooxygenase inhibitory activity, in a xenograft model of prostate cancer. Clinical studies to evaluate the effects of Exisulind against prostate cancer in humans are warranted.

Leiomyoma of bladder: Report of case and review of literature

We recently treated a patient with leiomyoma of the bladder and reviewed the 37 most recent cases in the English language literature. Mean patient age was forty-four years. Women made up 76 percent of the patients. Patients presented most commonly with obstructive urinary symptoms (49%), irritative symptoms (38%), hematuria (11%), or flank pain (13%); 19 percent were asymptomatic. Almost all patients had cystoscopy (87%) and intravenous urograms (IVU) (81%), but fewer had masses on bimanual examination (57%), ultrasound (49%), or computed tomography (CT) scan (35%). Most patients were treated with open resection (62%), while 30 percent were treated with transurethral resection (TUR). Almost all patients were cured with a single procedure (89%). Leiomyoma of the bladder is rare and readily cured with excision.

URINARY CONTINENCE AFTER RADICAL PROSTATECTOMY: THE COLUMBIA EXPERIENCE

PURPOSE We determine the incidence of urinary incontinence after radical prostatectomy and the factors that may influence this incidence. MATERIALS AND METHODS A total of 615 men who underwent radical retropubic prostatectomy performed by 1 of us (C. A. O. or M. C. B.) at our center between 1988 and 1996 were mailed a questionnaire regarding preoperative and postoperative voiding habits. Data collected included preoperative and postoperative continence status, interval to postoperative continence status, associated urinary symptoms, willingness to undergo radical prostatectomy again if given the chance and additional postoperative procedures. Patient age, date of surgery and duration of followup were also noted. RESULTS Of the 615 patients 480 (78.2%), a mean of 62.6 years old, responded to the questionnaire. Mean followup was 3.3 years (range 1 to 8.8). Continence was defined as no regular use of pads. Of the respondents 91.8% were considered continent, 92% had achieved final continence status by 6 months postoperatively, 10.6% required 1 or more additional procedures related to urinary control and 90% would undergo surgery again if given the chance. Of the patients considered incontinent postoperatively 44% had associated urgency. Age, year of surgery and preoperative urinary leakage or post-void dribbling had no significant impact on postoperative continence status. CONCLUSIONS Using an anonymous self-administered questionnaire we found an 8.2% incontinence rate after radical prostatectomy. This rate was similar to that in large, single institutional studies in which physician interview was used to elicit responses but significantly less than that in a national sample of Medicare patients also given a self-administered questionnaire. With minimal potential for adverse consequences in the hands of experienced surgeons, radical prostatectomy remains well tolerated with excellent patient satisfaction.

Seminal vesicle involvement after radical prostatectomy: predicting risk factors for progression

OBJECTIVES To evaluate and study the factors for progression after radical prostatectomy with seminal vesicle invasion in a cohort of European and American patients. METHODS The data of 137 patients with isolated seminal vesicle invasion who underwent radical retropubic prostatectomy between 1988 and 2001 were analyzed. The Gleason score of the specimen, presence of capsular invasion, and surgical margin status were noted. Follow-up data were obtained through routine serum prostate-specific antigen (PSA) assays and digital rectal examinations. A defining criterion for progression was a postoperative serum PSA level greater than 0.2 ng/mL or any postoperative radiotherapy or hormonal treatment. Kaplan-Meier analysis was used to determine the actuarial biochemical recurrence-free likelihood, and the log-rank test was used to compare these results. Differences were considered statistically significant when the P value was less than 0.05. RESULTS After a mean follow-up of 4.9 years (range 0.9 to 13.4), 70 patients (51.9%) had progression. The biochemical 5-year progression-free survival rate was 33.8%. In univariate and multivariate analyses, only preoperative PSA level (P = 0.001) and Gleason score of the specimen (P = 0.01) were independent predictors of progression. Neither capsular invasion nor positive surgical margins predicted progression. When an analysis was performed according to the major Gleason grade of the radical prostatectomy specimen, Gleason grade 5 was associated with a worse prognosis compared with Gleason grade 3 and 4 (P = 0.01). The mean time to progression was 20.5, 17.1, and 10.1 months for Gleason grade 3, 4, and 5, respectively. CONCLUSIONS Seminal vesicle invasion after radical prostatectomy has historically been associated with a poor prognosis. However, in the present study, seminal vesicle invasion was associated with a 34% rate of freedom from progression at 5 years after surgery alone. Preoperative PSA and Gleason score of the radical prostatectomy specimen were independent factors for progression in the present study, which described the largest patient group to date. The Gleason grade of the radical prostatectomy specimen distinguished among different times to progression.

PRETREATMENT PROSTATE SPECIFIC ANTIGEN DOUBLING TIMES: USE IN PATIENTS BEFORE RADICAL PROSTATECTOMY

PURPOSE We determined whether pre-radical prostatectomy prostate specific antigen (PSA) doubling time could predict pathological stage at radical prostatectomy or PSA failure postoperatively. We also sought to compare PSA doubling times from men with prostate cancer treated with radical prostatectomy to a group treated with radiation therapy. MATERIALS AND METHODS Detailed followup was available for 150 patients with clinically localized prostate cancer who underwent radical prostatectomy from January 1993 to August 1995. PSA doubling time was calculated for all patients with 3 or more pre-radical prostatectomy PSA levels using linear regression. We assessed the association between PSA doubling time and PSA failure, pathologic stage at radical prostatectomy, final PSA before treatment and Gleason score. We compared our PSA doubling time values and distribution to a published series of patients with prostate cancer who had undergone radiation therapy. RESULTS A total of 56 patients had 3 or more PSA values before treatment. Median followup was 17.3 months. PSA doubling time did not correlate with PSA failure, final PSA or Gleason score, but it did with pathological stage at radical prostatectomy (p = 0.0035 for positive margins, p = 0.025 for positive seminal vesicles). Our PSA doubling time and PSA failure rates did not differ from the radiation therapy population with similar followup times. CONCLUSIONS Although studies from the radiation literature have shown PSA doubling time to be useful in predicting PSA failure after treatment for prostate cancer, our results do not confirm this finding. We did find a correlation with pathologic stage at radical prostatectomy, and so longer followup with more patients may confirm this in the future. We also found no significant differences in PSA doubling time between our patients and a group treated with radiation. At least for this parameter, patients with prostate cancer referred for radical prostatectomy and radiation therapy may be similar.

A recombinant defective adenoviral agent expressing anti-bcl-2 ribozyme promotes apoptosis of bcl-2-expressing human prostate cancer cells.

Over‐expression of bcl‐2, a potent anti‐apoptosis protein, is likely to be one of the genetic mechanisms through which human prostate cancer cells develop resistance to hormonal and other forms of therapy. To develop a therapeutic agent for hormone‐resistant prostate cancer based on suppression of bcl‐2 expression, we had previously designed and synthesized a dual‐hammerhead ribozyme capable of recognizing and specifically cleaving human bcl‐2 mRNA in vitro as well as in vivo. To increase the efficiency by which the anti‐bcl‐2 ribozyme can be delivered to target cells, we have created a recombinant replication‐deficient (defective) adenoviral agent capable of expressing the anti‐bcl‐2 ribozyme upon infection. This viral agent effectively reduces intracellular levels of bcl‐2 mRNA and protein in cultured LNCaP prostate cancer cells following standard infection procedures. Likewise, the defective adenovirus‐anti‐bcl‐2 ribozyme induces extensive apoptosis in several androgen‐sensitive (LNCaP) and androgen‐insensitive (LNCaP/bcl‐2 and PC‐3) human prostate cancer cell lines that express differing amounts of bcl‐2 protein. One androgen‐insensitive prostate cancer cell line, DU‐145, lacking in bcl‐2 expression, was found to be completely refractory to the effects of the virus ribozyme, supporting the concept that the cytotoxic effects of the ribozyme are based solely on its effects on bcl‐2 expression. Our results support further development of this adenovirus/anti‐bcl‐2 ribozyme for potential gene therapeutic purposes in certain forms of hormone‐resistant prostate cancer where over‐expression of bcl‐2 proto‐oncogene is indicated. Int. J. Cancer 82:846–852, 1999.

Accuracy of semen counting chambers as determined by the use of latex beads

OBJECTIVE To assess the accuracy of the Hemacytometer (Hausser Scientific, Horsham, PA), Makler (Sefi-Medical Instrument, Haifa, Israel), Cell-VU (Millennium Sciences Inc., New York, NY), and Micro-Cell chambers (Conception Technologies, San Diego, CA) counting chambers. DESIGN A solution containing a known concentration of latex beads was used as the standard to perform counts on the four different counting chambers. MAIN OUTCOME MEASURES Bead counts for the four different chambers were compared with the bead counts of the standard solution. Variability within chambers also was determined. RESULTS Mean bead concentrations for both the Cell-VU and Micro-Cell chambers were consistently similar to the bead concentration of the standard solution. Both the hemacytometer and the Makler chambers overestimated the actual bead concentration of the standard solution by as much as 50% and revealed significant interchamber variability. CONCLUSIONS Our data revealed marked differences in the accuracy and reliability of the different counting chambers tested and emphasized the need for standardization and quality control of laboratory procedures.

Management of ejaculatory duct obstruction: etiology, diagnosis, and treatment

Abnormalities of the distal ejaculatory ducts related to infertility have been well-documented. Although there are no specific findings associated with ejaculatory duct obstruction, several clinical findings are highly suggestive. A diagnosis of ejaculatory duct obstruction is suggested in an infertile male with oligospermia or azoospermia with low ejaculate volume, normal secondary sex characteristics, testes, and hormonal profile, and dilated seminal vesicles, midline cyst, or calcifications on TRUS. Other causes of infertility may be concomitantly present and need to be evaluated and treated. Trans urethral resection of ejaculatory ducts (TURED) has resulted in marked improvement in semen parameters, and pregnancies have been achieved. Proper patient selection and surgical experience are necessary to obtain optimal results. In case of testicular dysfunction, chances of success are minimal. Extended follow-up periods are needed after TURED to examine the long-term effects of this procedure. Better understanding of the anatomy and pathology of the ejaculatory ducts will continue to refine diagnostic and therapeutic procedures for this disorder.

Transurethral resection of the ejaculatory ducts for treating ejaculatory symptoms

To report our experience with transurethral resection of the ejaculatory ducts (TURED) in infertile men with symptomatic ejaculatory duct obstruction (EDO).