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.

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.

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.

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.

Venogenic impotence following dermal graft repair for Peyronie's disease.

Peyronie's plaque excision with dermal grafting generally offers good cosmetic results for patients who require surgical intervention for Peyronie's disease. However, postoperative impotence has been reported in 12 to 100% of such patients. The mechanism of impotence in this setting is not well defined. We present 3 men who had venogenic impotence after plaque excision and dermal grafting for Peyronie's disease. One patient has subsequently responded well to dorsal vein ligation, 1 has chosen an effective nonoperative method of management and 1 continues to consider the options. We report venous leak as an organic cause of impotence after plaque excision and dermal grafting for Peyronie's disease, and its successful management by dorsal vein ligation. The implications of these findings in the surgical management of Peyronie's disease are discussed.

Rhabdomyosarcoma of the penis in children.

A rare case of a young boy with embryonal rhabdomyosarcoma of the penis is presented and the literature is reviewed.

Prostate specific antigen levels in men older than 50 years without clinical evidence of prostatic carcinoma.

In their derivation of normal prostate specific antigen (PSA) levels (0 to 4.0 ng./ml.) Hybritech used almost exclusively men less than 60 years old. The purpose of this study was to define PSA levels by age decade in men older than 50 years without clinical evidence of prostatic carcinoma or so-called cancer-free. We define the cancer-free population as men with a PSA less than or equal to 4.0 ng./ml. and nonsuspicious digital rectal examination, and those with an abnormality in either parameter with a nonmalignant prostate biopsy. A total of 755 men was recruited for a prostate cancer detection study using serum PSA and digital rectal examination, of whom 728 fulfilled our criteria of cancer-free. Newly derived mean and standard deviation were 1.32 +/- 1.10 ng./ml. in the 50 to 59-year group, 1.91 +/- 1.72 ng./ml. in the 60 to 69-year group and 2.36 +/- 1.98 ng./ml. in the 70 to 79-year group. The upper limits for PSA (mean+2 standard deviations) by age were 3.5 ng./ml. in the 50 to 59-year group, 5.4 ng./ml. in the 60 to 69-year group and 6.3 ng./ml. in the 70 to 79-year group. The apparent accuracy of these new limits is strong in the 60 to 69-year group but it declines in the next decade. The data support further attempts at using PSA, age and digital rectal examination to establish selection criteria for prostate biopsy with adequate sensitivity and specificity.

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.

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.

Dithiothreitol effects on human sperm quality.

Human semen normally coagulates immediately after ejaculation and then undergoes liquefaction during the next 15 to 60 minutes. Incomplete seminal liquefaction can result in impaired sperm motility and make clinical evaluation and manipulation difficult. Dithiothreitol, a mucolytic agent that reduces the mucoprotein disulfide bonds in sputum, has been found to induce liquefaction of incompletely liquefied semen in vitro. We studied the effects of dithiothreitol on sperm motility, viability, acrosomal integrity and morphology. A semen sample was provided by 45 healthy, young men at the University of Arizona. Of the specimens 10 (22%) demonstrated incomplete liquefaction. Sperm motility and motion characteristics of untreated (control) semen and semen treated with dithiothreitol were objectively evaluated using computer assisted semen analysis. Sperm cell membrane integrity and mitochondrial integrity were measured by fluorescence microscopy using the deoxyribonucleic acid specific fluorochrome propidium iodide and the mitochondria specific fluorochrome rhodamine-123, respectively. Acrosomal integrity was determined using the fluorescent stain chlortetracycline. Sperm morphology was evaluated using bright field microscopy. For completely liquefied semen (35 cases) dithiothreitol reduced sperm motility (59.1 +/- 1.2% untreated versus 53.2 +/- 1.2% treated, p < 0.01) and motion characteristics. However, dithiothreitol had no statistically significant effect on motility on sperm in the group with incompletely liquefied semen (10 cases). Sperm cell membrane, mitochondrial and acrosomal integrity was unaffected by dithiothreitol regardless of liquefaction status. Dithiothreitol caused a significant increase in abnormally large sperm head morphology in the group with completely liquefied semen. The minimal effects of dithiothreitol on sperm motility traits and viability support its use as a possible aid in the evaluation and manipulation of incompletely liquefied semen.

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.

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.

Site-specific positive margins at radical prostatectomy: assessing cancer-control benefits of wide excision of the neurovascular bundle on a side with cancer on biopsy.

OBJECTIVE: To determine the potential risk of biopsy-selected nerve-sparing surgery based on the findings of site-specific extracapsular extension (ECE) and positive surgical margins (PSMs) in the area of the neurovascular bundle in radical prostatectomy specimens. PATIENTS AND METHODS: Controlling for surgical technique and pathological interpretation, 221 consecutive patients had their neurovascular bundles removed on the side with a positive biopsy. The surgical specimens were reviewed for ECE and PSM status, specifically in the area of the neurovascular bundle, from apex to base. RESULTS: Of the 221 patients, 38% had ECE and 43 (20%) had a PSM in the area of the neurovascular bundle. This equates to a ratio of 51% for PSM/ECE. An additional 42 men (18%) had ECE with negative margins, but would have been at potential risk for PSMs if the neurovascular bundle had been preserved. CONCLUSION: Preserving the neurovascular bundle on the side with a positive biopsy could result in a significantly greater incidence of PSM than with wide excision. Optimizing cancer control may require excision of the neurovascular bundle on a side known to have cancer on biopsy. In future site-specific analyses, the PSM/ECE ratio could be used as a marker comparing cancer-control outcomes from studies with differing technical approaches and indications for nerve-sparing surgery.

Contrast-induced central nervous system toxicity after radiographic evaluation of the lower urinary tract in myelodysplastic patients with ventriculoperitoneal shunts.

Routine urological evaluation of children with myelomeningocele helps to identify those at risk for upper urinary tract deterioration. We report on 2 patients with ventriculoperitoneal shunts who had intraperitoneal rupture of the bladder. Reflux of contrast media via or around the ventriculoperitoneal shunt into the cerebral ventricles occurred in both patients, resulting in severe neurological insult.

Differential expression of cytokeratin mRNA and protein in normal prostate, prostatic intraepithelial neoplasia, and invasive carcinoma.

The expression of cytokeratin (CK) mRNA for CK5, -8, -14, -16, and -19 was investigated in normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and invasive carcinoma using in situ hybridization. Protein localization was carried out in adjacent sections using immunohistochemistry and correlated with mRNA expression. Snap-frozen human prostate samples including 22 examples of normal glands, 20 cases of PIN lesions, and 12 cases of invasive carcinoma were examined. CK5 and -14 mRNA and protein were prominently expressed only in the basal cells of normal glands and PIN lesions. CK14 mRNA was absent in the luminal cells of the most of the PIN lesions but was seen at a low level in some PIN lesions. CK14 protein was not detected in any PIN lesion, suggesting that, if the cell that makes up the PIN lesions is derived from a basal cell, CK14 translation is depressed although a low level of CK14 mRNA may persist. CK8 mRNA and protein were constitutively expressed in all epithelia of normal and abnormal prostate tissues. CK19 mRNA and protein were persistently expressed in both basal and luminal cells of the tubular portion of normal glands as well as PIN lesions, but were expressed heterogeneously in both basal and luminal cells of normal alveoli. CK16 mRNA was expressed in a similar pattern as CK19, but CK16 protein was not detected either in normal or in abnormal prostate tissues. In conclusion, the expression of CK19 in PIN lesions is similar to its tubular expression and would support an origin of PIN lesions from this structure rather than the alveolar portion of the glands. The similar cytokeratin expression between PIN lesions and invasive carcinoma further supports the concept that PIN is a precursor lesion of invasive carcinoma.

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.

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.