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Biomedical subjects

Herbert Lepor

Publications and source records attributed to Herbert Lepor.

At least 19 recordsLinked to original sources
PubMed2006

Proximal prostatic stem cells are programmed to regenerate a proximal-distal ductal axis.

Prostate carcinoma and benign prostatic hypertrophy may both originate in stem cells, highlighting the importance of the characterization of these cells. The prostate gland contains a network of ducts each of which consists of a proximal (adjacent to the urethra), an intermediate, and a distal region. Here, we report that two populations of cells capable of regenerating prostatic tissue in an in vivo prostate reconstitution assay are present in different regions of prostatic ducts. The first population (with considerable growth potential) resides in the proximal region of ducts and in the urethra, and the survival of these cells does not require the presence of androgens. The second population (with more limited growth potential) is found in the remaining ductal regions and requires androgen for survival. In addition, we find that primitive proximal prostate cells that are able to regenerate functional prostatic tissue in vivo are also programmed to re-establish a proximal-distal ductal axis. Similar to their localization in the intact prostate, cells with the highest regenerative capacity are found in the proximal region of prostatic ducts formed in an in vivo prostate reconstitution assay. The primitive proximal cells can be passaged through four generations of subrenal capsule grafts. Together, these novel findings illustrate features of primitive prostate cells that may have implications for the development of therapies for treating proliferative prostatic diseases.

Androgens↗
PubMed2006

Time to return to work and physical activity following open radical retropubic prostatectomy.

PURPOSE: We identified factors that predict return to part-time and full-time work and resumption of unlimited physical activity following open radical retropubic prostatectomy. MATERIALS AND METHODS: Between July 1, 2002 and February 28, 2005, 537 men with clinically localized prostate cancer underwent open radical retropubic prostatectomy, as performed by a single surgeon. Intraoperative, perioperative and postoperative parameters were recorded in real time and entered into a database. An assessment was made 1 and 3 months postoperatively regarding time to return to work and unrestricted physical activity. RESULTS: Of the men 50% returned to part-time and full-time work, and unrestricted activity within 14, 21 and 30 days after discharge home, respectively. Patient age and hematocrit at hospital discharge significantly predicted return to part-time and full-time work, and unlimited physical activity. The number of days that the urinary catheter was indwelling was also associated with return to part-time work. Occupation (blue vs white collar) and marital status were also associated with return to full-time work. In the multivariate model a unit increase in hematocrit decreased the time to return to part-time and full-time work, and unrestricted physical activity by 0.50, 0.60 and 0.59 days, respectively. Men with discharge hematocrit greater than 32% were 1.57 (p = 0.059), 1.65 (p = 0.041) and 2.03 (p = 0.002) times more likely to return to part-time and full-time work, and unlimited activity before 14, 21 and 30 days, respectively. Overall models were developed that accounted for 9.4%, 14.0% and 4.0% of the time to return to part-time work, full-time work and unrestricted physical activity, respectively. CONCLUSIONS: Efforts to increase discharge hematocrit by minimizing intraoperative blood loss or using preoperative blood management strategies and earlier removal of the urinary catheter have a favorable impact on the return to work and physical activity.

Adult↗
PubMed2006

Postoperative blood loss predicts the development of urinary extravasation on cystogram following radical retropubic prostatectomy.

PURPOSE: We determined if the degree of postoperative bleeding predicts the extent of urinary extravasation on initial postoperative cystogram. MATERIALS AND METHODS: Between October 2000 to June 2004, 879 men underwent radical retropubic prostatectomy performed by a single surgeon. Of these men 97% underwent the initial postoperative cystogram 3 to 8 days following radical prostatectomy. Postoperative bleeding was expressed as the absolute change in hematocrit between hematocrit values measured immediately upon arrival into the recovery room and hospital discharge. Three hematocrit points were added to the change in postoperative hematocrit for every unit of blood transfused postoperatively. The relationship between the change in postoperative hematocrit and the extent of extravasation was examined. RESULTS: None, mild, moderate and marked extravasation was observed on the initial cystogram in 82.7%, 7.9%, 8.8% and 0.6% of cases, respectively. A significant relationship was observed between changes in postoperative hematocrit and the extent of extravasation on initial cystography (p <0.001). Postoperative changes in absolute hematocrit points of less than 2, 2 to 6 and greater than 6 identified clinically meaningful risk groups for urinary extravasation. The degree of extravasation was not significantly related to risk of anastomotic stricture or urinary incontinence. CONCLUSIONS: The extent of postoperative bleeding predicts the extent of urinary extravasation on initial cystography. It may be a useful measurement for identifying men who can safely undergo early catheter removal without cystography.

Extravasation of Diagnostic and Therapeutic Materi↗
PubMed2006

Factors predisposing to the development of anastomotic strictures in a single-surgeon series of radical retropubic prostatectomies.

OBJECTIVE: To determine the rate of anastomotic stricture (AS) after radical retropubic prostatectomy (RRP) performed by one experienced surgeon, and to identify factors predisposing to its formation. PATIENTS AND METHODS: In all, 708 men were prospectively monitored for the development of AS after RRP. Potential risk factors for AS were analysed. RESULTS: There were no significant differences in age, Gleason score, nerve-sparing status, intraoperative blood loss, degree of extravasation on initial cystography, or duration of the indwelling urinary catheter between men who developed AS and men who did not. The mean postoperative blood loss was significantly higher in men who developed AS. The incidence of AS was also significantly higher in men whose bladder necks were reconstructed more narrowly. CONCLUSION: The amount of bleeding and the calibre of the reconstructed bladder neck were significantly associated with AS formation after RRP. The development of a haematoma from bleeding might explain the increased likelihood of AS. The mechanism of AS formation is unrelated to the degree of urinary extravasation on cystography, providing that a urinary catheter is left indwelling until extravasation resolves.

Anastomosis, Surgical↗
PubMed2006

Spontaneous retroperitoneal hemorrhage caused by segmental arterial mediolysis.

Spontaneous retroperitoneal hemorrhage is a rare clinical entity; signs and symptoms include pain, hematuria, and shock. Spontaneous retroperitoneal hemorrhage can be caused by tumors, such as renal cell carcinoma and angiomyolipoma; polyarteritis nodosa; and nephritis. The least common cause is segmental arterial mediolysis. Although computed tomography is used for the diagnosis of spontaneous retroperitoneal hemorrhage, it can miss segmental arterial mediolysis as the cause of the hemorrhage. The diagnosis of segmental arterial mediolysis as a cause of spontaneous retroperitoneal hemorrhage requires angiography, with pathologic confirmation for a definitive diagnosis.

Case Reports↗
PubMed2006

The role of gonadotropin-releasing hormone antagonists for the treatment of benign prostatic hyperplasia.

Medical therapy is the preferred first-line approach in the management of lower urinary tract symptoms in men with benign prostatic hyperplasia. The magnitude of the improvement in lower urinary tract symptoms observed in response to combination therapy (alpha-blocker plus 5-alpha reductase inhibitors) does not approach that achieved with prostatectomy. Various drugs have been under consideration, including BXL628, lonidamine, and phosphodiesterase inhibitors, all of which have had unacceptable side effects. The gonadotropin-releasing hormone antagonist cetrorelix is associated with dose-dependent symptom improvement and reduction of prostate volume. Elucidating the mechanism for cetrorelix-mediated improvement in lower urinary tract symptoms will likely contribute to unraveling the pathophysiology of lower urinary tract symptoms in men.

Journal Article↗
PubMed2006

The evolution of alpha-blockers for the treatment of benign prostatic hyperplasia.

Alpha-blockers have been evaluated for the treatment of benign prostatic hyperplasia (BPH) for 30 years, from early trials with the nonselective alpha-inhibitor phenoxybenzamine to short-acting (prazosin) then long-acting (terazosin, doxazosin, tamsulosin, alfuzosin) selective alpha(1)-antagonists. All of the alpha-blockers evaluated have demonstrated comparable effectiveness, and the evolution of alpha-blocker therapy for BPH has therefore focused primarily on improving convenience and tolerability. Although all of the long-acting alpha(1)-blockers are well tolerated, only tamsulosin and alfuzosin SR are administered without the requirement for dose titration. Alfuzosin has the additional advantage over tamsulosin of a lower incidence of ejaculatory dysfunction. Studies of subtype-selective alpha(1)-antagonists have not demonstrated superior efficacy or improved tolerability over the existing long-acting alpha(1)-blockers.

Journal Article↗
PubMed2005

Prostate-specific antigen velocity accurately predicts response to salvage radiotherapy in men with biochemical relapse after radical prostatectomy.

OBJECTIVES: To determine whether prostate-specific antigen (PSA) velocity (PSAV), used as a selection criterion for salvage radiotherapy (RT) after radical prostatectomy (RP), predicts the likelihood of response to RT in men with biochemical relapse. METHODS: We retrospectively reviewed the records of 48 patients who had undergone salvage RT for biochemical relapse after RP. All men were followed up with serial PSA measurements for a minimum of 6 months from their initial PSA recurrence, and RT was only offered to those patients with a serum PSA level remaining at less than 1.0 ng/mL. The response to RT was defined as maintenance of a PSA level of less than 0.1 ng/mL. The pathologic and clinical parameters, including PSAV, were examined to determine their individual ability to predict the response to RT. RESULTS: Of the 48 patients, 30 had maintained a PSA level of less than 0.1 ng/mL at a median follow-up of 16 months. The PSAV was strongly predictive of the likelihood of a response to salvage RT. The median relapse-free survival time for patients with a PSAV of less than 0.035 ng/mL/mo was 28 months compared with 16 months for patients with a PSAV greater than 0.035 ng/mL/mo. All other parameters tested, including Gleason score, seminal vesicle invasion, extracapsular extension, and margin status, were not predictive of the likelihood of a response to RT. CONCLUSIONS: In the present study, PSAV accurately predicted the likelihood of response to salvage RT in men with biochemical relapse after RP. No other pathologic parameters predicted the likelihood of response to RT. Using PSAV as a sole selection criterion for salvage RT after RP may allow improvement in the historically low rates of durable response.

Disease-Free Survival↗
PubMed2005

Outcomes for men younger than 50 years undergoing radical prostatectomy.

OBJECTIVES: To compare the surgical outcomes after radical prostatectomy between men younger than 50 years and men 50 years old or older. METHODS: Between October 1, 2000 and December 31, 2003, 790 men underwent open radical retropubic prostatectomy by a single surgeon. The intraoperative, perioperative, and postoperative parameters were recorded in real time and entered into a database. The outcomes were compared for 66 men younger than 50 years of age (group 1) versus 724 men who were 50 years old or older (group 2). RESULTS: The pathologic stage, percentage of cancer in the surgical specimen, positive surgical margin rate, and Gleason score were not significantly different among the two age groups. No significant difference was found in the risk factors for prostate cancer between groups 1 and 2 (33.3% versus 28.9%, respectively; P = 0.63). The operative complications were exceedingly low in both groups. Of the men in groups 1 and 2, 93.3% and 97.1% achieved continence, respectively (P = 0.26). Of the potent men at baseline who underwent bilateral nerve-sparing prostatectomy, 100% of men in group 1 versus 81.4% in group 2 (P = 0.02) were having erections adequate for intercourse with or without phosphodiesterase-5 inhibitors or intracavernous injection therapy, as determined by direct patient interview. Of the men who underwent bilateral nerve-sparing radical retropubic prostatectomy, 78.3% of group 1 versus 62.6% of group 2 (P = 0.14) were potent with or without phosphodiesterase-5 inhibitors. CONCLUSIONS: The preoperative and pathologic predictors of organ-confined disease and biochemical recurrence were similar in both age groups. The results of this study have demonstrated that radical retropubic prostatectomy can be performed with good results and low complication rates in men with localized prostate cancer who are younger than 50 years of age.

Adult↗
PubMed2005

Reoperation versus observation in men with major bleeding after radical retropubic prostatectomy.

OBJECTIVES: To compare the postoperative and quality-of-life outcomes for men experiencing major bleeding after radical retropubic prostatectomy that was managed with reoperation or observation. METHODS: A total of 916 men underwent radical retropubic prostatectomy by a single surgeon between October 2000 and August 2004. Of the 916 men, 15 (1.6%) experienced major bleeding, defined as the transfusion of 3 U or more of allogeneic blood within the first 36 hours after radical prostatectomy. The outcomes were compared between the 5 men undergoing reoperation (group 1) and the 10 men whose bleeding was managed with observation (group 2). RESULTS: The mean total number of allogeneic blood units transfused was significantly greater in group 1 (7.4 U) than in group 2 (4.1 U; P = 0.002). Group 1 also experienced a significantly longer hospital stay (4.6 versus 2.6 days). Those men undergoing reoperation had a significantly lower probability of moderate to severe extravasation on initial cystogram compared with group 2 (0% versus 70%). In addition, the urinary catheter was indwelling for a shorter interval (9.6 versus 23.5 days). We also found a suggestion of better continence in group 1. CONCLUSIONS: Reoperation for major bleeding after radical retropubic prostatectomy facilitates both healing of the vesicourethral anastomosis and removal of the urinary catheter.

Humans↗
PubMed2005

Ultrasensitive serum prostate specific antigen nadir accurately predicts the risk of early relapse after radical prostatectomy.

PURPOSE: Ultrasensitive prostate specific antigen (PSA) assays allow a lower limit of detection (less than 0.01 ng/ml) than standard PSA assays. In this study we examined the ability of ultrasensitive PSA nadir to predict relapse after radical prostatectomy (RP). MATERIALS AND METHODS: A total of 906 men treated with RP were followed with PSA measurements at 3, 6 and 12 months, and yearly thereafter. Of the 906 men 545 (60%) with a PSA nadir of less than 0.01 ng/ml or at least 3 followup ultrasensitive PSA measurements underwent analysis and stratification by PSA nadir. Biochemical relapse was defined as 2 consecutive increasing post-nadir PSA measurements of 0.1 ng/ml or greater. The ability of ultrasensitive PSA nadir to predict relapse was assessed by univariate and multivariate analysis. RESULTS: At a mean followup of 3.1 years 54 of 545 men (9.9%) experienced biochemical relapse with a mean time to relapse of 25.2 months. Relapse rates in men with a PSA nadir of less than 0.01 (423), 0.01 (75), 0.02 (19) and 0.04 or greater ng/ml (28) were 4%, 12%, 16% and 89%, respectively. Men with a nadir of less than 0.01 ng/ml had a significantly lower relapse rate than men with a nadir of 0.01 (p <0.01), 0.02 (p <0.025) or 0.04 or greater ng/ml (p <0.01). Multivariate logistic regression analysis showed that a nadir of 0.01 (p <0.05), 0.02 (p <0.05) and 0.04 or greater ng/ml (p <0.01) independently predicted an increased risk of biochemical relapse compared to a nadir of less than 0.01 ng/ml. CONCLUSIONS: Ultrasensitive PSA nadir accurately predicts the risk of early biochemical relapse following RP. Men who achieve a nadir of less than 0.01 ng/ml have a low likelihood of early relapse. Higher nadir points may identify candidates for early adjuvant or salvage therapies.

Follow-Up Studies↗
PubMed2005

An artificial somatic-autonomic reflex pathway procedure for bladder control in children with spina bifida.

PURPOSE: Neurogenic bladder is a major problem for children with spina bifida. Despite rigorous pharmacological and surgical treatment, incontinence, urinary tract infections and upper tract deterioration remain problematic. We have previously demonstrated the ability to establish surgically a skin-central nervous system-bladder reflex pathway in patients with spinal cord injury with restoration of bladder storage and emptying. We report our experience with this procedure in 20 children with spina bifida. MATERIALS AND METHODS: All children with spina bifida and neurogenic bladder underwent limited laminectomy and a lumbar ventral root (VR) to S3 VR microanastomosis. The L5 dorsal root was left intact as the afferent branch of the somatic-autonomic reflex pathway after axonal regeneration. All patients underwent urodynamic evaluation before and after surgery. RESULTS: Preoperative urodynamic studies revealed 2 types of bladder dysfunction- areflexic bladder (14 patients) and hyperreflexic bladder with detrusor external sphincter dyssynergia (6). All children were incontinent. Of the 20 patients 17 gained satisfactory bladder control and continence within 8 to 12 months after VR microanastomosis. Of the 14 patients with areflexic bladder 12 (86%) showed improvement. In these cases bladder capacity increased from 117.28 to 208.71 ml, and mean maximum detrusor pressure increased from 18.35 to 32.57 cm H2O. Five of the 6 patients with hyperreflexic bladder demonstrated improvement, with resolution of incontinence. Urodynamic studies in these cases revealed a change from detrusor hyperreflexia with detrusor external sphincter dyssynergia and high detrusor pressure to nearly normal storage and synergic voiding. In these cases mean bladder capacity increased from 94.33 to 177.83 ml, and post-void residual urine decreased from 70.17 to 23.67 ml. Overall, 3 patients failed to exhibit any improvement. CONCLUSIONS: The artificial somatic-autonomic reflex arc procedure is an effective and safe treatment to restore bladder continence and reverse bladder dysfunction for patients with spina bifida.

Adolescent↗
PubMed2005

Open versus laparoscopic radical prostatectomy.

Expert laparoscopic surgeons have demonstrated that laparoscopic radical prostatectomy with or without robotic assistance can be performed with excellent results. There is no evidence that laparoscopic radical prostatectomy with or without robotic assistance offers any clinically relevant advantage over open radical prostatectomy. Laparoscopic radical prostatectomy with or without robotic assistance requires a significant learning curve, is a longer surgical procedure, carries greater costs, and requires an expanded operating room team. The literature suggests that laparoscopic radical prostatectomy is associated with more intraoperative complications and higher positive surgical margins. The lesser amount of postoperative bleeding associated with laparoscopic radical prostatectomy is not clinically relevant. Laparoscopic radical prostatectomy is not associated with less pain and does not facilitate earlier urinary catheter removal. The best way to improve overall outcomes after radical prostatectomy is to direct patients to expert open or laparoscopic surgeons.

Journal Article↗
PubMed2005

Comparison of single-agent androgen suppression for advanced prostate cancer.

Gonadotropin-releasing hormone (GnRH) agonists are the agents of choice for achieving androgen suppression in men with advanced prostate cancer. The GnRH agonists that have been developed and marketed for prostate cancer are leuprolide, goserelin, triptorelin, and histrelin. So far, there have been few randomized studies directly comparing these single-agent therapies; however, the literature and the data on file with the Food and Drug Administration suggest that triptorelin may be more reliable than leuprolide in maintaining castration levels of serum testosterone. The clinical significance of this benefit remains to be proven.

Journal Article↗
PubMed2005

Managing and preventing acute urinary retention.

Acute urinary retention (AUR), an uncomfortable and potentially dangerous condition, often occurs in men who have benign prostatic hyperplasia. Although the reported incidence of AUR varies in the literature, there are a number of events that are known to precipitate episodes of AUR, including ingestion of certain agents, infection, general anesthesia, and performance of various diagnostic genitourinary procedures. Because it is preferable to avoid the need for catheterization (and the associated risks) in men at high risk for AUR, certain measures have been studied as means to prevent AUR episodes. Specifically, alpha-blockers and 5-alpha-reductase inhibitors have been shown to reduce the incidence of initial and subsequent AUR episodes in certain at-risk men.

Journal Article↗
PubMed2005

A review of surgical techniques for radical prostatectomy.

Since the early 20th century, radical prostatectomy has been used in the treatment of prostate cancer. However, before the widespread acceptance of prostate-specific antigen screening, the majority of cancers were clinically advanced and not amenable to cure, so relatively few men were candidates for this procedure. Modern advances have contributed dramatically to the reduction of complications and morbidity associated with radical prostatectomy. As a result, the procedure has become the most common treatment selected by men with localized prostate cancer. This article reviews several issues regarding radical prostatectomy, including surgical techniques, cancer control, intraoperative localization of the cavernous nerves, patient selection, and laparoscopic versus robotic approaches.

Journal Article↗