The significance of intraluminal crystalloids in benign prostatic glands on needle biopsy.

Based on data from autopsy, radical prostatectomy, and cystoprostatectomy specimens, it has been suggested that the finding of intraluminal crystalloids in benign glands on needle biopsy may indicate a concurrent carcinoma; therefore, repeat biopsy is recommended. We studied data from 56 consecutive needle biopsies from the Johns Hopkins Hospital and Dianon Systems in which the diagnosis of intraluminal crystalloids in benign glands was rendered and follow-up data were subsequently obtained. Cases in which crystalloids were present in glands suspicious for cancer, in glands of high-grade prostatic intraepithelial neoplasia, or in adenosis were excluded from the study. Follow-up data included repeat biopsy results and serum prostatic specific antigen levels. Of the 56 men, 31 (55%) had repeat biopsy (two underwent transurethral resection of the prostate [TURP]); the remaining men were either noncompliant or had medical conditions precluding subsequent biopsy. Of the 31 men who underwent repeat biopsies, 23 (74%) had benign diagnoses, one (3%) had high-grade prostatic intraepithelial neoplasia, and seven (23%) had adenocarcinoma. There was no difference in serum prostate-specific antigen values between those with and without cancer on repeat biopsy. In a control population of men with a benign first biopsy not showing crystalloids, the incidence of cancer on repeat biopsy was 16.2%, which was not statistically significantly different from the incidence found in our study group. We conclude that men with prostate biopsy results showing benign glands with crystalloids are at no significantly higher risk of having cancer on repeat biopsy than if crystalloids were not present.

Transitional cell carcinoma of bladder in children and adolescents.

Transitional cell carcinoma of the bladder is rare in patients under sixteen years of age. A case is described in a ten-year-old boy, and the literature is reviewed. The diagnosis and treatment of this tumor is the same in childhood as in older patients. Recurrence as well as death have been reported in this age group; therefore, these patients warrant careful long-term follow-up.

Modification of Mitrofanoff principle for continent urinary diversion.

In 1980, Mitrofanoff described a method of achieving continent urinary diversion by surgically closing the bladder neck and creating a continent catheterizable stoma from the appendix, which had been implanted in a non-refluxing manner into the bladder, or from a non-refluxing distal ureter. We describe a modification of the Mitrofanoff procedure for continent urinary diversion in 7 children in whom a standard Mitrofanoff procedure was not possible due to either body habitus or appendiceal anatomy. All 7 patients are continent both day and night. Four have required stomal revisions. Renal function has remained stable or improved in all patients. Although the revision rate was high, this modification of the Mitrofanoff principle has provided good long-term results in these patients and may be useful when patient's anatomy does not allow the creation of a standard appendicovesicostomy.

Clinical and pathologic tumor characteristics of prostate cancer as a function of the number of biopsy cores: a retrospective study.

OBJECTIVES: Many men with negative prostate biopsies and persistently elevated serum total prostate-specific antigen (tPSA) values will have cancer detected on a repeated biopsy. An important issue is whether the cancer would have been detected on the initial biopsy had more biopsy samples been obtained. The objective of our study was to retrospectively characterize the clinical and pathologic tumor features associated with men who underwent sextant core biopsies compared with men who needed more than six core biopsies during one or more biopsy sessions to detect prostate cancer. Transrectal ultrasound (TRUS)-estimated prostatic volume was evaluated to determine whether the number of biopsy cores needed for prostate cancer detection was influenced by gland size. METHODS: We retrospectively evaluated the number of biopsy core samples obtained in 185 men (mean age 63+/-6 years) enrolled in our PSA-based screening study for prostate cancer who were found to have prostate cancer and elected radical prostatectomy as treatment. Correlation coefficients were calculated and univariate analyses were performed to evaluate clinical (age, tPSA, TRUS volume, PSA density) and pathologic (Gleason score, pathologic weight, organ confinement, "possibly harmless" cancer) characteristics associated with men who required more biopsy cores to detect the cancer. RESULTS: Of the 185 men, 103 (56%) had 6 or fewer total biopsy cores taken and 82 (44%) had more than 6 cores (44 [24%] of 185 had 7 to 12 cores and 38 [20%] of 185 had 13 or more cores). There was a positive correlation between age, serum tPSA, TRUS-determined prostate volume, and pathologic specimen weight and an increasing number of total cores (all P values < 0.05). The number of biopsy cores was not associated with PSA density, Gleason score, cancer volume, organ confinement, or "possibly harmless" cancers (all P values > 0.05). Men with a TRUS volume 30 cc or less (46%) required a mean of 8 total cores to detect the cancer compared with a mean of 11 cores (P = 0.003) in men with a TRUS volume greater than 30 cc (54%). A greater percentage of men with a TRUS prostate volume greater than 30 cc compared with men whose volume was 30 cc or less would have had their cancer missed with only a six-core biopsy (64% versus 46%, P = 0.01). CONCLUSIONS: Sextant core biopsies may be inadequate to detect prostate cancer in some men. These data support the performance of more than six core biopsies to detect clinical prostate cancer. A prospective trial using TRUS-determined prostate volume to determine the number of cores to take is needed to accurately assess this issue.

Comparison of percent free prostate-specific antigen levels in men with benign prostatic hyperplasia treated with finasteride, terazosin, or watchful waiting.

OBJECTIVES: Finasteride is known to lower total serum prostate-specific antigen (PSA) levels by approximately 50%. Terazosin is thought to have little or no effect on serum PSA concentration. The objective of our study was to determine the effect of finasteride and terazosin on serum total and serum free PSA levels and the ratio of free to total PSA. METHODS: We identified 69 men with symptomatic benign prostatic hyperplasia (BPH) who had been receiving 5 mg/day (n = 33) of finasteride or 2 to 5 mg/day (n = 14) of terazosin or no therapy ("watchful waiting") (n = 22). The three groups were compared with respect to pretreatment total serum PSA levels and post-treatment total, free, and percent free serum PSA levels. RESULTS: Median (+/- semi-interquartile range [SIR]) pretreatment total serum PSA levels (ng/mL) were not significantly different in men taking finasteride (2.8 +/- 1.9), terazosin (2.2 +/- 2.5), or undergoing watchful waiting (5.5 +/- 1.4) (P = 0.12). The median (+/- SIR) post-treatment total serum PSA levels (ng/mL) were significantly lower in the finasteride group (1.1 +/- 1) when compared with the terazosin (2.5 +/- 1.5) or watchful waiting (4.3 +/- 2.8) groups (P = 0.016). Only the finasteride group had significantly lower post-treatment total serum PSA levels compared with pretreatment levels. The median (+/- SIR) post-treatment free PSA levels were significantly lower in the finasteride group (0.26 +/- 0.16) compared with the terazosin (0.54 +/- 0.5) and watchful waiting (0.85 +/- 0.5) groups (P = 0.0015). However, the median (+/- SIR) percent free PSA was not significantly different in the finasteride (23 +/- 6), terazosin (22 +/- 4), and watchful waiting (25 +/- 5) groups (P = 0.66). CONCLUSIONS: Finasteride appears to lower total and free PSA levels equally in men with BPH and does not appear to change the ratio of free to total serum PSA. Terazosin does not appear to alter total or free serum PSA levels in men with BPH. The percent free PSA could potentially be used to screen for prostate cancer in men taking finasteride. Prospective studies are needed to further evaluate this issue.

Percentage of free serum prostate-specific antigen as a predictor of pathologic features of prostate cancer in a screening population.

OBJECTIVES: Measurement of the percentage of free prostate-specific antigen (%FPSA) in serum can improve the specificity of prostate cancer screening. We evaluated the ability of %FPSA to predict pathologic features of screen-detected clinically localized prostate cancer. METHODS: We evaluated the correlation between %FPSA in serum before cancer diagnosis and the pathologic features of the cancers detected in 108 men with clinically localized prostate cancer who were treated with radical prostatectomy and for whom complete embedding of the radical prostatectomy specimen was performed. Ninety-seven men (90%) had a previous negative screening evaluation before prostate cancer was detected. RESULTS: There was a negative correlation of %FPSA with penetration of cancer through the prostatic capsule, cancerous surgical margins, Gleason score, percentage of cancer in the gland, and tumor volume (r = -0.2 to -0.4). After controlling for other preoperative predictors, %FPSA predicted capsular penetration (adjusted odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1 to 2.4, for each 5% decrease in %FPSA) and cancer volume 0.5 cc or greater (adjusted OR 1.6, 95% CI 1.1 to 2.3). Preoperative %FPSA also predicted possibly harmless cancer (OR 1.5, 95% CI 1.1 to 2.2, for each 5% increase in %FPSA). CONCLUSIONS: In a select group of men for whom cancer was detected early via screening, a lower %FPSA in serum suggests a potentially more threatening cancer. This information may aid patients and clinicians in making more informed decisions about the management of prostate cancer, such as selecting patients for watchful waiting. However, more research is needed to determine the performance characteristics of %FPSA in clinical practice.

Prostate-specific antigen as a screening test for prostate cancer. The United States experience.

Serum PSA-based early detection for prostate cancer has been studied fairly extensively for the past several years. It appears that we can state fairly categorically what the relative performances of total serum PSA, DRE, and TRUS are in detecting early-stage prostate cancer; that initial screening is effective in detecting histologically significant and pathologically organ-confined prostate cancer; that annual, serial, repetitive screening, at least over a 4- to 5-year horizon, does not overdetect prostate cancer, and that the results of early detection will improve as our ability to use certain PSA transformations such as PSA density, PSA slope, age-specific PSA adjustment, and knowledge of free versus total serum PSA is better characterized. These advances in our ability to diagnose early-stage prostate cancer likely will be coupled with an increased ability to predict the behavior, curability, and significance of individual tumors. It is hoped that information soon will be available to allow physicians to categorize an individual tumor as insignificant, significant and surgically curable, or significant and incurable by standard approaches. This ability, coupled with the demonstrated ability to detect prostate cancer, will make an even more compelling argument for widespread PSA-based screening. At present, annual DRE and total serum PSA measurements are recommended for men older than 50 and among younger men at high risk for prostate cancer. All suspicious DRE findings should be evaluated with prostatic biopsy. Among younger men, PSA levels over 2.5 ng/mL should be considered worrisome and further evaluated. For men older than 65, serum PSA levels above 4 ng/mL should be considered abnormal and warrant biopsy. Men with persistent serum PSA elevation and a negative biopsy should undergo repeat biopsy at least once, and perhaps more often if PSA slope exceeds 0.75 per year, if density is greater than 0.10, or if f-PSA is less than 20%.

Cryosurgical ablation of the prostate.

A new surgical procedure, cryosurgical ablation of the prostate, offers patients with organ-confined prostate cancer another treatment option. The advantages of this cryosurgical technique are complete ablation of prostatic cancers without radical prostatectomy procedures, less blood loss, decreased hospital stays, reduced health care costs, and minimal associated morbidity. Some possible complications of cryosurgical ablation of the prostate procedures include incontinence, impotence, rectal freezing from inadequate monitoring of the freezing process, urethrocutaneous and urethrorectal fistula formations, and urethral tissue sloughing. The intraoperative nurse's prime responsibility is to monitor the subfreezing temperatures of the cryoprobes. Postoperatively, patients have only a few perineal incisions covered with sterile dressings and a suprapubic catheter. Most patients have minimal discomfort that is managed easily with opiate analgesics.

Prostatic transition zone biopsies in men with previous negative biopsies and persistently elevated serum prostate specific antigen values.

PURPOSE: In men with persistently elevated serum prostate specific antigen (PSA) concentrations and prostatic biopsies that show no cancer an important question is whether the PSA elevation is caused by undetected cancer in the transition zone of the prostate gland. MATERIALS AND METHODS: To evaluate this issue further we examined 166 men age 50 years of older who participated in a PSA based screening trial for prostate cancer. All men had an initially elevated serum PSA concentration of 4.1 ng./ml. or greater. They had undergone 1 or 2 sets of negative peripheral zone biopsies of the prostate but elevated serum PSA concentrations persisted. They underwent repeat biopsy of the peripheral zone as well as 2 core biopsies from the right and 2 from the left transition zone region of the prostate. RESULTS: Peripheral and transition zone biopsies revealed cancer in 3 of 19 cases (16%). Cancer was present in the peripheral zone only biopsy in 14 of 19 cases (74%). Two of 19 cancers (10%) were detected only in the transition zone. Overall 17 of the 19 cancers (89%) were detected by peripheral zone biopsy. CONCLUSIONS: Transition zone biopsy detects few additional prostate cancers in men with persistent serum PSA elevations and previous negative biopsies.

Medical therapy for benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common clinical entity in elderly men. We review the epidemiology of BPH and the mechanisms by which it causes bladder outlet obstruction. The currently available medical therapies are examined with respect to mechanism of action, effectiveness, side effects, and cost. They are briefly compared with the more traditional treatment options of watchful waiting and transurethral prostatectomy. A logical approach to the treatment of symptomatic BPH is discussed.

A clinical-care pathway for decreasing hospital stay after radical prostatectomy.

OBJECTIVES: To evaluate the use of a clinical-care pathway that decreased the stay in hospital after radical retropubic prostatectomy from 3 to 2 days, assessing the costs and quality of care. PATIENTS AND METHODS: Forty-four consecutive men who underwent radical retropubic prostatectomy were evaluated prospectively. The first 22 men were hospitalized under the standard 3-day clinical-care pathway in use at our institution. This pathway was evaluated, shortened to construct a 2-day pathway, and a second group of 22 consecutive men hospitalized under the new pathway. Both groups were evaluated and compared 6 weeks post-operatively. RESULTS: The mean (SD) hospital stay was 2.1 (0.3) days for men in the 2-day and 2.9 (0.4) days for men in the 3-day pathway (P < 0.001). The mean (SD) hospital cost was $8468 (801) in the 2-day and $8806 (630) in the 3-day pathway (P=0.13). None of the men in the 2-day and one of 22 men in the 3-day pathway experienced a major complication (P=0.31). Two of 22 men in the 2-day and one of 22 in the 3-day pathway exceeded the expected stay by one day (P=0.55). CONCLUSION: The hospital stay after radical retropubic prostatectomy can be safely shortened from 3 to 2 days for most men. However, the shorter hospital stay does not result in significant cost savings. The shorter stay does not appear to compromise quality of care. Proper patient education and careful pre- and post-operative supervision are necessary for a successful outcome.

Serial prostatic biopsies in men with persistently elevated serum prostate specific antigen values.

The objective of this study was to determine the need for repeat prostatic biopsies in men whose initial biopsy results revealed no evidence of cancer or atypia. We evaluated 1,136 men who underwent 1 or more prostatic biopsies in a longitudinal prostate specific antigen (PSA) based prostate cancer screening study that called for biopsy if the serum PSA level was greater than 4.0 ng./ml. (Hybritech assay) and findings on rectal examination or ultrasonography were abnormal or suspicious for cancer. Of the 1,136 men who underwent prostatic biopsy 391 (34%) had prostate cancer on the initial biopsy. Of 427 men who had negative initial biopsy results, a persistent serum PSA level of greater than 4.0 ng./ml. and abnormal rectal or ultrasound examination findings 82 (19%) had cancer on biopsy 2. Of 203 men with persistent abnormalities 16 (8%) had cancer on biopsy 3 and 6 of 91 (7%) had cancer on biopsy 4 or later. Thus, 96% of the cancers were detected through either biopsy 1 or 2. The median initial PSA level, followup PSA levels and the yearly rate of change in PSA were significantly greater in men whose cancer was detected compared with those of men whose cancer was not detected (6.4 versus 5.4 ng./ml., 7.4 versus 6.6 ng./ml. and 1.1 versus 0.7 ng./ml. per year, respectively). There was a trend for a higher percentage of tumors detected through serial screening to be pathologically organ confined with those detected through initial screening (73% versus 62%, p = 0.07). We conclude that men with a persistently elevated serum PSA value after an initial negative prostatic biopsy should routinely undergo at least 1 repeat biopsy to exclude adequately the presence of detectable prostate cancer.

Development of a mouse model for nonbacterial prostatitis.

Nonbacterial prostatitis is a common clinical entity which is often difficult to diagnose and treat. Little is known with regard to the etiology and pathogenesis of this disease process. To develop an animal model and characterize the immune parameters of nonbacterial prostatitis, we harvested the prostates from SJL, AJ, Balb/c, C57bl/6 and C57bl/6 lpr mice. These prostates were homogenized and injected into syngeneic mice. Controls were injected with Freund's complete adjuvant only. Mice from each group were sacrificed 30 days after injection, and the prostates were harvested. Prostatic tissue was examined histologically for degree of inflammation. None of the Balb/c mice exhibited prostatic inflammation. The SJL and AJ mice exhibited varying degrees of prostatic inflammation. All of the C57bl/6 mice were found to have lymphocytic infiltration of the stroma and periglandular region. The C57bl/6 lpr mice did not appear to be more susceptible than the parental strain. Adoptive transfer studies demonstrated the prostatic inflammation to be at least in part immune mediated. We conclude that injection of syngenic prostate antigen induces prostatic inflammation similar to clinical nonbacterial prostatitis. Nonbacterial prostatitis may be an autoimmune process.

Late decompensation of neobladder.

We report on 6 patients in whom we constructed detubularized ileocolonic neobladders in conjunction with cystectomy to treat invasive transitional cell carcinoma of the bladder. The patients had delayed complete or partial decompensation of the neobladder after an initial interval of normal voiding. Two patients experienced complete decompensation with inability to empty in the absence of urodynamic, cystoscopic or radiographic evidence of outlet obstruction. The other 4 patients had greater than 400 cc residual urine without evidence of outlet obstruction. The mean interval to decompensation after the initial period of normal voiding was 12.8 months (range 4 to 21). All 6 patients had a reservoir capacity of greater than 800 cc. We also constructed neobladders in 3 other patients for similar indications. These 3 patients have a neobladder capacity of less than 800 cc and all are voiding to completion with followup of 19 to 32 months. We hypothesize that neobladder decompensation is due either to creation of an excessively large pouch alone or in combination with a poor Valsalva ability. Until we know the neobladder capacity required for continence that will simultaneously allow for complete emptying, all patients should be advised of the possible need for intermittent self-catheterization. Urological followup should include monitoring of post-void residual urine volume to detect failure to empty early before irreversible decompensation occurs.

Predicting the pathology results of radical prostatectomy from preoperative information: a validation study.

BACKGROUND: There are now over 13 published models for predicting the outcomes of radical prostatectomy using preoperative information. Because their ability to predict the pathology of the prostatectomy is key in deciding who benefits the most from this surgery, it is important to know how well these models work for new data. METHODS: The patients in this study were 100 men diagnosed with prostate carcinoma in the prostate specific antigen (PSA)-based screening program at Washington University Medical Center. To test the models, the authors used preoperative information and the published algorithms to predict postoperative pathology outcomes. Statistical methods included plots of predicted probability against observed probability, boxplots of predicted probability against observed outcomes, logistic regression, and linear regression. RESULTS: Although none of the published models predicted the outcomes of radical prostatectomy perfectly, those that predicted tumor volume performed best, and in general those that were multivariate also performed best. Nevertheless, the ability of any of these models to discriminate binary outcomes was not very great. CONCLUSIONS: The results of this study suggest that preoperative variables based on serum PSA and the results of needle biopsies can be used in multivariate models to predict tumor volume, but these models need to be improved. Predicting locally advanced tumor stage is likely to be more difficult and may require information beyond what needle biopsies can provide.

Repeat biopsy strategy in men with isolated prostatic intraepithelial neoplasia on prostate needle biopsy.

PURPOSE: Isolated high grade prostatic intraepithelial neoplasia on needle biopsy of the prostate is a strong predictor of malignancy on repeat biopsy. However, the optimal repeat biopsy technique for these patients has not been defined. MATERIALS AND METHODS: We reviewed the records of 66 men in whom isolated prostatic intraepithelial neoplasia was found on needle biopsy of the prostate. We evaluated the side and/or quadrant and grade of prostatic intraepithelial neoplasia on initial biopsy, and compared the findings to the location of cancer on repeat biopsy. RESULTS: Of 66 men 31 (47%) had cancer on repeat biopsy, with disease on the same side of the prostate as prostatic intraepithelial neoplasia in 20 (64%). The quadrant locations of prostatic intraepithelial neoplasia and cancer matched in 6 of 12 cases (50%). Low and high grade prostatic intraepithelial neoplasia predicted the side of cancer on repeat biopsy in 3 of 5 (60%) and 17 of 26 (65%) cases, respectively. CONCLUSIONS: Directing repeat biopsy solely to the side with prostatic intraepithelial neoplasia will miss cancer in approximately 35% of cases. The optimal repeat biopsy technique for patients with high grade prostatic intraepithelial neoplasia should include systematic biopsy of the prostate.

Cystic dysplasia of the testis. Sonographic features with pathologic correlation.

Testicular cysts are an uncommon in the pediatric population unlike adults where they occur frequently. We describe a case of cystic dysplasia of the testis in a prepubertal boy. The known literature is reviewed and the sonographic appearance of the lesion is correlated with pathologic findings.