Preservation of penile length after radical prostatectomy: early intervention with a vacuum erection device.

Radical prostatectomy has been shown to have a potential negative impact on penile health. Stretched penile length (SPL), which most closely correlates with erect penile length, was significantly reduced in almost half of men undergoing surgery in several studies. The purpose of this study was to test whether early intervention after surgery with a vacuum erection device could prevent the changes in penile health, as defined by SPL, found in prior studies. Forty-two men with good preoperative sexual function undergoing nerve-sparing radical prostatectomy underwent measurement of SPL preoperative and at 3 months postoperative by a single investigator. Daily use of a vacuum erection device (VED) was begun the day after catheter removal, and continued for 90 days. Men kept a log of their compliance with daily VED use. A decrease in SPL of > or = 1.0 cm was considered significant. Out of 42 men, 39 completed the study. In men who used the VED >50% of possible days, only 1/36 (3%) had a decrease in SPL of > or = 1.0 cm. Of the three men with poor VED compliance, two (67%) had a reduction in SPL of > or = 1.0 cm. When compared to prior studies where 48% of men after surgery had a significant reduction in SPL, early intervention with the daily use of a VED resulted in a significantly lower risk of loss of penile length (P<0.0001). For men wishing to preserve penile health/length after surgery, early intervention with the daily use of a VED should be strongly recommended.

Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial.

OBJECTIVE: To present the results (to January 1996, the end of blinded treatment) of the Nutritional Prevention of Cancer (NPC) Trial, a randomized trial of selenium (200 micro g daily) designed to test the hypothesis that selenium supplementation (SS) could reduce the risk of recurrent nonmelanoma skin cancer among 1312 residents of the Eastern USA. MATERIALS AND METHODS: Original secondary analyses of the NPC to 1993 showed striking inverse associations between SS and prostate cancer incidence. A subsequent report revealed that this effect was accentuated among men with the lowest baseline plasma selenium concentrations. The effects of treatment overall and within subgroups of baseline prostate-specific antigen (PSA) and plasma selenium concentrations were examined using incidence rate ratios and Cox proportional hazards models. RESULTS: SS continued to significantly reduce the overall incidence (relative risk and 95% confidence interval) of prostate cancer (0.51, 0.29-0.87). The protective effect of SS appeared to be confined to those with a baseline PSA level of

Culturing precision-cut human prostate slices as an in vitro model of prostate pathobiology.

Due to the complex morphology of the prostate, it was hypothesized that precision-cut tissue slices from human prostate would provide a unique in vitro model. Precision-cut slices were generated from zones of human prostate and their viability was assessed under conditions of different media for up to 120 h. Slices were also exposed to several concentrations of CdCI2, which was used as a model toxicant. Maintenance of both stromal and epithelial cells was noted; however, there was a gradual loss of luminal epithelial cells when the medium was not supplemented with dihydrotestosterone (DHT). Minimal leakage of lactate dehydrogenase occurred throughout the incubation. Prostate-specific antigen (PSA) was detected in the medium at all time points, although the rates of secretion fell over time. There was a loss of PSA-positive cells when the medium was not supplemented with DHT, consistent with a loss of luminal cells, whereas PSA-positive cells were maintained in the DHT-supplemented media. A proliferation of basal cells was observed in the presence of media containing 10% fetal bovine serum. Exposure of slices to CdCl2 demonstrated a dose-response effect ranging from proliferation to complete cellular necrosis. Given the retention of stromal-epithelial interactions and the use of acquired human tissue, prostate slices represent a unique in vitro model for investigating human prostate pathobiology.

Pilot study of changes in stretched penile length 3 months after radical retropubic prostatectomy.

OBJECTIVES: To evaluate changes in stretched penile length after radical retropubic prostatectomy (RRP) in a prospective penile measurement study because an occasional complaint from patients after RRP is that their penis is shortened. METHODS: Thirty-one patients undergoing RRP by one surgeon were enrolled. The same physician completed measurements with a paper ruler to the nearest 0.5 cm. The stretched penile length was measured from the tip of the glans to the pubopenile skin junction. The measurements were taken in the preoperative holding area before the patient received anesthetic medication for the RRP and again 3 months postoperatively. The reliability and reproducibility of this measurement were confirmed. RESULTS: All 31 patients were measured at 3 months postoperatively. Of the 31 patients, 22 (71%) had a decrease in stretched penile length (range 0.5 to 4.0 cm). Seven were shortened 0.5 cm, 11 were shortened 1.0 to 2.0 cm, and 4 were shortened more than 2.0 cm. Five patients had no change, and in four the penile length was longer (range 0.5 to 1.0 cm). CONCLUSIONS: The results of this pilot study appear to show that the stretched penile length decreases after RRP at 3 months of follow-up in most men; 48% (15 of 31) had considerable shortening greater than 1.0 cm. If confirmed by other investigators, the cause of this change needs to be elucidated.

PEAZ-1: a new human prostate neoplastic epithelial cell line.

BACKGROUND: The generation of prostatic cell lines provides in vitro models for experimental studies of the pathogenesis of prostate carcinoma. Therefore, we established and characterized a new human prostate epithelial cell line, PEAZ-1 (prostate epithelial Arizona-1). METHODS: The PEAZ-1 cells were grown from a primary human prostate carcinoma specimen obtained from radical prostatectomy. The isolated cells were characterized by immunobiochemistry, immunohistochemistry, and tumorigenicity studies. RESULTS: PEAZ-1 cells are near diploid, tumorigenic, and androgen independent for cell growth. PEAZ-1 cells express N-cadherin, alpha- and beta-catenins, and p120 at cell-cell contacts, cytoplasmic laminin 5, vinculin, paxillin, and phosphotyrosine at focal adhesions, vimentin, and cytokeratins 8 and 18. They do not express plakoglobin, E-cadherin, and PSA, and do not form desmosomes and hemidesomomes. PEAZ-1 respond to ocadaic acid, a pro-apoptotic agent, by expression of p53. CONCLUSIONS: PEAZ-1 cells is a human prostate cancer cell line that has a number of mesenchymal characteristics.

Evaluation of cold knife urethrotomy for the treatment of anastomotic stricture after radical retropubic prostatectomy.

PURPOSE: We evaluated the efficacy of cold knife urethrotomy for anastomotic stricture after radical retropubic prostatectomy. MATERIALS AND METHODS: We contacted all patients who underwent cold knife urethrotomy for a symptomatic anastomotic stricture from May 1, 1992 through January 1, 2000 at our institution. A control group of patients who underwent radical retropubic prostatectomy but did not complain of a decreased urine stream was similarly evaluated. Maximum urinary flow rate, post-void residual urine volume, American Urological Association (AUA) symptom index for benign prostatic hyperplasia, and continence status with a questionnaire adapted from the RAND-University of California-Los Angeles Prostate Cancer Index were determined in each study participant. RESULTS: We identified and contacted 61 patients. Complete data were collected on 36 of the 52 patients (59%) who agreed to participate. Mean time after urethrotomy was 31 months (range 1 to 77). In the control group the mean time after prostatectomy was 18.6 months (range 3 to 95). There was no statistically significant difference in the measured urinary parameters of maximum flow rate, post-void residual urine volume, AUA symptom index or continence status in the study and control groups. CONCLUSIONS: Cold knife urethrotomy provides a safe and effective response for the initial treatment of patients with anastomotic stricture after radical retropubic prostatectomy. Maximum urinary flow, post-void residual volume, AUA symptom score and perceptions of continence are similar to those in patients who underwent radical retropubic prostatectomy and had no complaints of a weak urine stream.

Investigation into the mechanism of the loss of laminin 5 (alpha3beta3gamma2) expression in prostate cancer.

Laminin 5 is a pivotal hemidesmosomal protein involved in cell stability, migration, and anchoring filament formation. Protein and gene expression of the alpha3, beta3, and gamma2 chains of laminin 5 were investigated in normal and invasive prostate carcinoma using immunohistochemistry, Northern analysis, and in situ hybridization. Laser capture microdissection of normal and carcinomatous glands, in conjunction with RNA amplification and reverse Northern analysis, were used to confirm the gene expression data. Protein and mRNA expression of all three laminin 5 chains were detected in the basal cells of normal glands. In contrast, invasive prostate carcinoma showed a loss of beta3 and gamma2 protein expression with variable expression of alpha3 chains. Despite the loss of protein expression, there was retention of beta3 and gamma2 mRNA expression as detected by in situ hybridization, Northern and reverse Northern analysis. Our findings imply that an altered mechanism of translation of beta3 or gamma2 mRNAs into functional proteins contributes to failure of anchoring filaments and hemidesmosomal formation. The resultant hemidesmosome instability or loss would suggest a less stable epithelial-stromal junction, increased invasion and migration of malignant cells, and disruption of normal integrin signaling pathways.

Unique expression pattern of the alpha6beta4 integrin and laminin-5 in human prostate carcinoma.

BACKGROUND: The alpha6beta4 integrin and its ligand, laminin-5, are essential gene products for the maintenance and remodeling of a stratified epithelium. Apparent loss of polarized alpha6beta4 integrin and laminin-5 protein expression in invasive prostate cancer as compared to normal prostate glands is known to occur. It is unknown whether these alterations occur in prostatic intraepithelial neoplasia (PIN) lesions and whether this combined defect occurs in other epithelial cancers. METHODS: Human prostate tissues containing both normal, PIN, and cancerous regions and normal and cancer tissue from breast and colon were obtained at surgery and examined for beta4 integrin and laminin-5 using standard immunofluorescence staining methods. RESULTS: Both normal prostate glands and PIN lesions contain beta4 integrin and laminin-5. Prostate carcinoma was unique in that both beta4 integrin and laminin-5 expression was uniformly absent. In contrast, the beta4 integrin and its ligand, laminin-5 were detected in all of the colon carcinoma cases and in 60% of the breast carcinomas. CONCLUSIONS: The beta4 integrin and its ligand, laminin-5 are altered during the transition of PIN lesions to invasive prostate carcinoma. These data suggest the loss of these proteins during cancer progression. In both prostate and breast carcinoma, the normal expression pattern of the beta4 integrin and laminin-5 is interrupted, in contrast to the persistent beta4 integrin and laminin-5 expression detected in colon carcinoma.

Differences in sexual function and quality of life after nerve sparing and nonnerve sparing radical retropubic prostatectomy.

PURPOSE: We determine the impact of nerve sparing techniques on quality of life after radical retropubic prostatectomy for prostate cancer. MATERIALS AND METHODS: The RAND/UCLA Prostate Cancer Index and several questions about surgical outcomes, including sexual function, were sent to 170 consecutive patients at least 1 year after radical retropubic prostatectomy. Statistical analysis was performed on data for the entire group as well as subgroups of patients after nerve sparing and nonnerve sparing surgery. RESULTS: Nonnerve sparing surgery was performed in 83 of 129 responders (nonnerve sparing group) and the remaining 46 were treated with unilateral nerve sparing surgery (nerve sparing group). Scores for sexual function, sexual bother, physical function and physical limitation domains were significantly better in the nerve sparing group. Spontaneous erectile activity was reported by 50% of nerve sparing group patients. Nerve sparing status did not affect urinary function, bowel function or disease outcome. CONCLUSIONS: Nerve sparing techniques have positive effects on quality of life and sexual function for patients undergoing radical retropubic prostatectomy.

Accuracy of prostate needle biopsy in predicting extracapsular tumor extension at radical retropubic prostatectomy: application in selecting patients for nerve-sparing surgery.

OBJECTIVES: To evaluate prostate biopsy outcomes along with other clinical parameters in an effort to define the cancer-specific safety of nerve-sparing surgery. METHODS: Sixty-six consecutive men underwent radical retropubic prostatectomy for clinically localized prostate cancer (T1c = 36, T2 = 30). Preoperative prostate needle biopsies were performed on all patients, and radical prostatectomy specimens were processed in their entirety. Our pathologic end point was capsular perforation extending entirely through the prostatic capsule. Each prostatic side was analyzed individually, for a total of 132 specimens. The specimens were further divided into four categories on the basis of biopsy grade (no cancer = 44, low = 20, moderate = 60, high = 8). Additional study variables included preoperative prostate-specific antigen (PSA) and number of positive biopsy cores. RESULTS: Overall, 40 of the 132 specimens had evidence of capsular perforation. Of the 40 capsular perforations, 39 were observed in specimens (sides) that had cancer identified on biopsy. The one specimen with capsular perforation and a negative biopsy result occurred in the setting of high-grade contralateral cancer. PSA, digital rectal examination, and number of positive biopsy cores did not reliably predict capsular perforation. CONCLUSIONS: Our findings suggest that in patients with low- and moderate-grade tumors, the neurovascular bundle can be safely preserved on the side without evidence of cancer having obtained at least three biopsy cores. No safe parameters for considering nerve-sparing surgery were observed in the small number of patients with high-grade tumors, or in any specimen with cancer present on biopsy. Other clinical parameters, such as PSA or number of positive cores, did not aid in identifying candidates for nerve-sparing surgery.

Prostatic asymmetry as a risk factor for prostatic carcinoma: serial prostate-specific antigen monitoring and cancer detection.

OBJECTIVE: To compare the rates of cancer detection in men with a normal, asymmetric, or suspicious prostate on digital rectal examination (DRE) initially and after 3 years of serial monitoring of prostate specific antigen (PSA) level. PATIENTS AND METHODS: Prostatic 'asymmetry' was defined as asymmetric growth of the lateral lobes of the prostate without induration or nodules, as assessed by a DRE. The study included 963 men with no clinical evidence of prostate cancer and whose serum PSA levels were monitored at 4 month intervals. Prostatic biopsy was recommended if the PSA level became persistently abnormal (> 4ng/mL) or increased by > 20% after having been initially abnormal. Cancer detection rates were compared among groups categorized by the initial DRE findings and serum PSA level. RESULTS: On comparing groups with suspicious and normal DREs, and abnormal with normal PSA levels both, as expected, were associated with a statistically significant increase in cancer detection. However, an asymmetric prostate did not carry an increased risk of detecting prostate cancer when compared with a normal prostate, regardless of PSA level. CONCLUSIONS: An asymmetric prostate does not appear to be an independent risk factor for detecting prostate cancer. Therefore, an asymmetric prostate with no abnormality in PSA level should not mandate prostatic biopsy, or even an increase in monitoring frequency above the presently recommended annual interval.

Prospective longitudinal evaluation of men with initial prostate specific antigen levels of 4.0 ng./ml. or less.

PURPOSE: We evaluated the 3-year longitudinal changes in serial serum prostate specific antigen (PSA) levels in men with an initial PSA of 4.0 ng./ml. or less and no suspicion of prostate cancer. MATERIALS AND METHODS: A total of 760 men with an initial PSA of 4.0 ng./ml. or less plus a normal or suspicious digital rectal examination and a benign prostate biopsy was enrolled into an every 4-month PSA monitoring study. RESULTS: Of the 559 men with an initial PSA of 2.0 ng./ml. or less only 3 (0.5%) had a persistently abnormal PSA for 3 years and 1 cancer (0.2%) was detected, and 48 men had a PSA velocity of 0.8 ng./ml. per year or more at year 1 but only 1 (2%) had a persistent rate of increase (2.4 ng./ml. per year) at 3 years. Of the 201 men with a PSA of 2.1 to 4.0 ng./ml. 85 had an abnormal PSA but only 37 (43%) met the criteria for biopsy. Only 8 of 23 biopsies (35%) revealed cancer. Of the 201 men 24 had a PSA velocity of 0.8 ng./ml. per year or more at year 1 but only 4 had persistence for 3 years. All 4 men had cancer but they were identified as at high risk by PSA criteria. CONCLUSIONS: Men with a PSA of 2.0 ng./ml. or less are at low risk for an abnormal PSA or cancer within 3 years and annual monitoring may not be necessary. However, annual monitoring is clinically useful in men with an initial PSA of 2.1 to 4.0 ng./ml. Also, serial monitoring with interval testing in men whose PSA becomes greater than 4.0 ng./ml. is beneficial in identifying a high risk group requiring biopsy. Finally, PSA velocity did not add further to cancer detection in this population.

Ketoconazole-induced adrenal crisis in a patient with metastatic prostatic adenocarcinoma: case report and review of the literature.

Ketoconazole has been used with success to treat disseminated intravascular coagulation and acute spinal cord compression syndromes associated with metastatic prostatic adenocarcinoma. It effects prompt, reversible medical castration, making it especially useful as empiric therapy when histologic diagnosis is delayed but prostate cancer is suspected. Side effects are usually limited to asthenia, nausea, diarrhea, and gynecomastia, but a theoretical risk of adrenal suppression exists. We report a case of fulminant adrenal crisis precipitated by ketoconazole given on a 6-hour dosing schedule in a patient with nerve root compression secondary to prostatic metastases. Through a review of the literature, we attempt to provide a better understanding of the use and potential dangers associated with ketoconazole therapy.

Differential expression of laminin 5 (alpha 3 beta 3 gamma 2) by human malignant and normal prostate.

Laminin 5 is an extracellular matrix protein integral to the formation of the hemidesmosomes that attach normal basal cells to the underlying basal lamina. We have shown that these hemidesmosomal complexes are lost in prostate carcinoma, possibly allowing malignant cells to detach from the anchoring structures and then to invade and migrate through the adjacent tissue. Our previous immunohistochemical studies of normal and malignant human prostate tissue demonstrated that the laminin subchains alpha 1, alpha 2, beta 1, beta 2, gamma 1, and gamma 2 were all expressed as normal components of the basal lamina surrounding prostate glands. Although most of these subchains were also expressed by the de novo basal lamina synthesized by prostate carcinoma, the gamma 2 subchain of laminin 5 was not detected. In an effort to investigate the role laminin 5 plays in the tumorigenesis of prostate carcinoma, the protein expression of the three subchains of laminin 5 (alpha 3, beta 3, and gamma 2) was compared in normal prostate, prostatic intraepithelial neoplasia, and invasive carcinoma using immunohistochemistry. The results showed that the protein for the alpha 3 subchain of laminin 5 is retained by both normal prostate epithelium and prostate carcinoma, but the beta 3 and the gamma 2 subchains were not detected in invasive carcinoma. Despite the absence of the gamma 2 protein, however, the carcinoma cells continued to express substantial amounts of the gamma 2 mRNA. Although it is unclear how the gene for the gamma 2 subchain of laminin 5 is regulated, results of this study suggest that there is a post-transcriptional defect in the expression of the gamma 2 subchain that occurs during the progression from a premalignant lesion to invasive carcinoma. As laminin 5 is a component of the anchoring filaments, the failure to express the gamma 2 subchain may contribute to the failure to form anchoring filaments and hemidesmosomes. This failure of hemidesmosome formation results in a less stable epithelial-stromal junction, which may allow malignant cells more potential to invade and spread through adjacent structures.

Randomized study of neoadjuvant testicular androgen ablation therapy before radical prostatectomy in men with clinically localized prostate cancer.

PURPOSE: We determined whether 12 weeks of neoadjuvant testicular androgen ablation therapy using a luteinizing hormone-releasing hormone agonist could improve pathological outcomes in men undergoing radical retropubic prostatectomy for clinically localized (stages T1C, T2A and T2B) prostatic carcinoma. MATERIALS AND METHODS: A total of 56 participants was randomized to receive either monthly injections of a luteinizing hormone-releasing hormone agonist at 4-week intervals followed by radical retropubic prostatectomy (28) or to undergo immediate radical retropubic prostatectomy alone (28). Operations were performed via similar technique and all prostatic specimens were processed histologically in their entirety. RESULTS: There was no improvement in pathological outcome using luteinizing hormone-releasing hormone agonist preoperatively compared to surgery alone. Of 28 men undergoing immediate radical retropubic prostatectomy 23 had organ-confined (17) or specimen-confined (6) disease versus 22 of 28 who received luteinizing hormone-releasing hormone neoadjuvant therapy for 12 weeks preoperatively (16 with organ-confined and 6 with specimen-confined disease, p = 1.00). In addition, when the study population was analyzed by pretreatment prostate specific antigen (PSA) levels (10 ng./ml. or less, or greater than 10 ng./ml/) there was also no difference in pathological outcome (p = 0.65 for PSA greater than 10 and p = 0.32 for PSA less than 10). CONCLUSIONS: Neoadjuvant androgen ablation therapy for 12 weeks before radical prostatectomy in patients with clinically localized adenocarcinoma of the prostate does not result in improved pathological outcomes.

Endoscopic evaluation and treatment of anastomotic strictures after radical retropubic prostatectomy.

PURPOSE: We describe endoscopic findings and treatment outcome in 17 men who presented with a symptomatic anastomotic stricture after radical prostatectomy. MATERIALS AND METHODS: Endoscopic evaluation revealed an immature stricture in 6 men, which was treated by initial dilation and subsequent cold-knife urethrotomy. The 11 men with a mature anastomotic stricture were treated by initial cold-knife urethrotomy (10) or dilation followed by urethrotomy (1). RESULTS: There were no long-term complications from treatment, which was successful in 15 of the 17 men (88%). CONCLUSIONS: Initial dilation with subsequent urethrotomy for immature or initial urethrotomy for mature anastomotic strictures is a safe and effective treatment plan.

Derivation and application of upper limits for prostate specific antigen in men aged 50-74 years with no clinical evidence of prostatic carcinoma.

OBJECTIVE: To derive age-specific upper limits for prostate specific antigen (PSA) level in men 50-74 years of age with no clinical evidence of prostatic carcinoma, and to test the sensitivity and specificity for cancer detection of these upper limits. SUBJECTS AND METHODS: A total of 6166 men were recruited for a multicentre study of prostate cancer detection and underwent a serum PSA determination and digital rectal examination (DRE). Men considered to be clinically free of prostatic carcinoma were those with a normal DRE and a PSA level < or = 4.0 ng/mL, and men with an abnormality in either parameter who underwent ultrasonography-guided prostate biopsy that revealed no evidence of carcinoma. By these criteria, 5469 men had no evidence of prostatic carcinoma. Dividing the population into 5-year age increments, three statistical methods were assessed to derive upper limits for serum PSA level by age; the mean +2 SD, the 99th percentile, and a 97.5% prediction interval based on linear regression. RESULTS: Newly-derived upper limits calculated by each method in the 50-54 and the 70-74 age group were 3.9 ng/mL and 7.6 ng/mL (mean +2 SD), 5.2 ng/mL and 14.0 ng/mL (99th percentile), and 4.7 ng/mL and 8.2 ng/mL (97.5% prediction interval). The sensitivity of the newly-derived upper limits was tested using receiver operating characteristic curves derived from men with no suspicious findings on DRE and a serum PSA concentration > 4.0 ng/mL. Although the specificity of the test increased with increasing PSA upper limits, no upper limits derived from these three methods yielded adequate sensitivity to detect cancer; sensitivities by age range were from 53 to 94%, using mean +2 SD, from 25 to 50% with the 99th percentile, and from 47 to 64% with the 97.5% prediction interval. CONCLUSION: We do not recommend age-referenced adjustments in upper limits for serum PSA concentration, but recommend that an upper limit of 4.0 ng/mL be used in all men 50-74 years of age.

Expression of hemidesmosomal and extracellular matrix proteins by normal and malignant human prostate tissue.

The progression of prostate carcinoma may be influenced by the biochemical nature of the basal lamina surrounding the primary carcinoma cells. As a first step toward understanding this process, the composition and structure of the basal lamina in normal prostate, prostatic intraepithelial neoplasia, and human carcinoma were determined. In addition, a comparison was made between the attachments of the normal basal cell to its underlying basal lamina and those made by primary prostate carcinoma. The normal basal cells form both focal adhesions and hemidesmosomal-like structures as observed by transmission electron microscopy. The normal basal cells exhibited a polarized distribution of hemidesmosomal associated proteins including BP180, BP230, HD1, plectin, laminin-gamma 2(B2t), collagen VII, and the corresponding integrin laminin receptors alpha 6 beta 1 and alpha 6 beta 4. The expression and distribution pattern of these proteins were retained in the prostate intraepithelial neoplasia lesions. In contrast, the carcinoma cells uniformly lacked hemidesmosomal structures, the integrin alpha 6 beta 4, BP180, laminin-gamma 2 (B2t), and collagen VII but did express BP230 (30%), plectin, HD1 (15%), and the integrin laminin receptors alpha 3 beta 1 and alpha 6 beta 1. These results suggest that, although a detectable basal lamina structure is present in carcinoma, its composition and cellular attachments are abnormal. The loss of critical cellular attachments may play a role in influencing the progression potential of prostate carcinoma.