Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma.

Type 2 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) is a multi-functional enzyme that possesses 3alpha-, 17beta- and 20alpha-HSD, as well as prostaglandin (PG) F synthase activities and catalyzes androgen, estrogen, progestin and PG metabolism. Type 2 3alpha-HSD was cloned from human prostate, is a member of the aldo-keto reductase (AKR) superfamily and was named AKR1C3. In androgen target tissues such as the prostate, AKR1C3 catalyzes the conversion of Delta(4)-androstene-3,17-dione to testosterone, 5alpha-dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), and 3alpha-diol to androsterone. Thus AKR1C3 may regulate the balance of androgens and hence trans-activation of the androgen receptor in these tissues. Tissue distribution studies indicate that AKR1C3 transcripts are highly expressed in human prostate. To measure AKR1C3 protein expression and its distribution in the prostate, we raised a monoclonal antibody specifically recognizing AKR1C3. This antibody allowed us to distinguish AKR1C3 from other AKR1C family members in human tissues. Immunoblot analysis showed that this monoclonal antibody binds to one species of protein in primary cultures of prostate epithelial cells and in LNCaP prostate cancer cells. Immunohistochemistry with this antibody on human prostate detected strong nuclear immunoreactivity in normal stromal and smooth muscle cells, perineurial cells, urothelial (transitional) cells, and endothelial cells. Normal prostate epithelial cells were only faintly immunoreactive or negative. Positive immunoreactivity was demonstrated in primary prostatic adenocarcinoma in 9 of 11 cases. Variable increases in immunoreactivity for AKR1C3 was also demonstrated in non-neoplastic changes in the prostate including chronic inflammation, atrophy and urothelial (transitional) cell metaplasia. We conclude that elevated expression of AKR1C3 is highly associated with prostate carcinoma. Although the biological significance of elevated AKR1C3 in prostatic carcinoma is uncertain, AKR1C3 may be responsible for the trophic effects of androgens and/or PGs on prostatic epithelial cells.

Prostate-specific antigen (PSA) and PSA density: racial differences in men without prostate cancer.

BACKGROUND: Many physicians now use serum prostate-specific antigen (PSA) to screen for prostate cancer in asymptomatic men. Whether or not a prostate biopsy should also be performed depends on an accurate definition of what constitutes a normal PSA value. Until recently, studies conducted to establish normal serum PSA values have involved study populations that have included few African-American men. PURPOSE: We sought to compare serum PSA levels and PSA density (i.e., serum PSA level/prostate volume ratio) in African-American and white men without histologic evidence of prostate cancer. METHODS: We reviewed the medical records of 826 consecutive men who underwent one or more prostate biopsies at the Veterans Affairs Medical Center in Shreveport, LA, from January 1993 through December 1995. In this retrospective review, we recorded patient's age, race, serum PSA level, digital rectal examination result, ultrasound-determined prostate volume, indications for biopsy, and biopsy results. Data from a total of 752 consecutive men who were either white or African-American and whose indication for biopsy included a serum PSA of greater than 4.0 ng/mL and/or an abnormal digital rectal examination were analyzed. To examine possible differences in serum PSA level, PSA density, prostate volume, and patient age, the two-sided Student's t test was employed. Multivariate linear regression analysis was used to determine if serum PSA levels were associated with the patient's age, race, or prostate volume in men without prostate cancer. RESULTS: Of the 752 men included in this analysis, 254 had histologic evidence of prostate cancer and 498 did not. Of the 498 men without prostate cancer, 367 (74%) men were white and 131 (26%) were black. There were no racial differences in age or calculated prostate volume. Serum PSA levels and calculated PSA density, however, were significantly (both P < .0001) higher in African-American men that in white men. A multivariate linear regression analysis indicated that race and prostate volume were independent variables associated with serum PSA level. For African-American and white men, serum PSA values of greater than 4 ng/mL were associated with prostate cancer with sensitivities of 89.5% and 81.9%, respectively, and specificities of 38.2% and 52.3%, respectively. CONCLUSION: Among biopsied men without histologic evidence of prostate cancer, African-Americans have a significantly higher PSA level and PSA density than similarly aged white men. IMPLICATIONS: Published criteria for normal PSA level and density have been derived primarily from white men and may not be directly applicable to other populations. Race-specific data are needed to fully optimize PSA as a tumor marker in racial populations that are at high risk for prostate cancer death.

Positive bethanechol supersensitivity test in neurologically normal patients.

A positive bethanechol supersensitivity test (BST) usually indicates neuropathic detrusor areflexia and warrants neurologic correlation. Seven females, average age thirty-three years, with straining to void and high residual urines, had detrusor areflexia, with a borderline or positive BST, ranging from 19 cm water to 55 cm H2O change in intravesical pressure after 5 mg of subcutaneous bethanechol. However, all patients had a normal neurologic workup, even though 2 patients had insignificant spina bifida occulta. Two of the patients also had prior pelvic surgery, 1 of whom was azotemic, and 4 of the patients had psychosocial problems; factors reported to be associated with a false positive BST. The positive BST is not diagnostic of neurogenic detrusor areflexia because of the many variables that can influence the test. Therefore, the bethanechol supersensitivity test should be interrupted in light of the complete neurourologic evaluation.

Distal ureteral obstruction complicating percutaneous nephrolithotomy.

Endourologic techniques for the treatment of surgical stone disease have proved cost-effective and safe with results comparable to open surgical procedures. Because these are new procedures, unexpected complications are going to occur. We have had 3 cases of complete distal ureteral obstruction unrelated to a ureteral calculus following a percutaneous nephrolithotomy. The obstruction resolved after extended nephrostomy tube drainage. These 3 cases and their treatment and pathogenesis are presented.

Fournier's gangrene in children.

Necrotizing fasciitis of the genitalia is a rare urologic emergency that is especially uncommon in children. We report a case of Fournier's gangrene in a four-year-old boy and analyze the data from 55 previously reported cases. Pediatric cases have been successfully managed with a more conservative surgical approach and have had a significantly lower mortality rate than adult cases.

Treatment of renal calculus in inferior crossed renal ectopia.

Percutaneous nephrolithotomy is still the treatment of choice for selected cases of "surgical" stone disease. This is a case report of the surgical treatment for a renal calculus located in the inferior moiety of right-to-left inferior crossed renal ectopia. After a failed attempt at extracorporeal shock-wave lithotripsy, a successful percutaneous nephrolithotomy was done without complication.

Acute urinary retention in a child with appendiceal abscess: diagnostic dilemma.

Rarely do children with appendiceal abscess present with acute urinary retention as the only sign or symptom. This presentation may delay diagnosis and definitive therapy, thereby causing additional morbidity and possible mortality. We report the eighth case of acute urinary retention in a child associated with an appendiceal abscess.

Acquired immunodeficiency syndrome manifesting as prostate nodule secondary to cryptococcal infection.

We report the first case of acquired immunodeficiency syndrome (AIDS) presenting as prostate nodularity secondary to mycotic granulomatous prostatitis which mimicked prostatic cancer on digital rectal examination. Transrectal ultrasonography revealed hypoechoic areas in the peripheral zone, which on biopsy specimen were found to represent cryptococcal infection. Subsequent serologic evaluation of the patient confirmed human immunodeficiency virus (HIV) positivity and later AIDS developed in the patient.

Ureteral injury in abdominal vascular reconstructive surgery.

Iatrogenic ureteral injuries in vascular reconstructive surgery are rarely reported. We present a case of ureteral transection during repair of an aortic aneurysm in a patient with a previously placed aortobifemoral graft. In reported series of surgical ureteral injuries, 17 of 381 injuries occurred during vascular procedures. A review of the literature and management scheme for ureteral complications in the presence of prosthetic vascular grafts is presented in light of current endourologic materials and techniques.

Percutaneous nephrostomy for palliation of metastatic ureteral obstruction.

Urinary diversion for palliation of metastatic ureteral obstruction has been associated with high rates of morbidity and mortality, especially with open surgical nephrostomies. An evaluation of percutaneous nephrostomy drainage for the palliation of metastatic ureteral obstruction in 27 patients revealed an increase in survival with decreased morbidity, and a follow-up ranging from three to twenty-five months. The mean survival of all patients was 6.63 months (N = 19), with 8 patients still alive. The histology was the main determinant of length of survival, with prostate, rectal, and cervical cancer patients surviving the longest. The perioperative mortality was 11.1 per cent (3/27), and the postoperative complications consisted of hemorrhage requiring transfusion 29.6 per cent (8/27), gastrointestinal bleeding 3.7 per cent (1/27), and dislodged nephrostomy tubes 44.4 per cent (12/27). Percutaneous nephrostomy drainage is a less morbid procedure than open surgical procedures, and the main determinant of length of survival is the histology of the primary tumor in patients with metastatic ureteral obstruction.

Female urinary retention.

The urodynamic results in 68 females with urinary retention were reviewed. There were two groups: 39 patients with neurologic causes for retention, and 29 patients in whom possible causes for retention included: psychological history (15 patients), gynecologic pathology, and urinary tract infection. Nine patients in the neurogenic group and 13 patients in the non-neurogenic group had undergone urethral dilatation with no improvement. Upper urinary tract evaluation was unremarkable. Detrusor failure was the prominent bladder pattern in both groups. In the neurogenic group, low pressure detrusor activity was also present in 10 patients, 3 of whom had sphincter dyssynergia. Flow rate, surface electromyography, and bethanechol supersensitivity test could not help differentiate neurogenic from non-neurogenic detrusor failure. The notation of abnormal bladder sensation did significantly differ between the groups, but was of limited accuracy as an indicator of neurogenic retention. Self-intermittent catheterization was the most effective treatment for both groups, with some patients voiding adequately in follow-up. Although no one test can accurately differentiate neurogenic from nonneurogenic female urinary retention, careful neurourologic evaluation will help guide us to more appropriate management.

Ureteral stump carcinoma incidentally found at cystectomy for bladder cancer.

We report on a sixty-five-year-old man with hematuria secondary to superficial bladder cancer. Because of previous urethral trauma, a complete transurethral resection of his bladder tumor could not be done. He, therefore, underwent cystectomy, at which time we incidentally found a transitional cell carcinoma of the left ureteral stump that had been left from a previous left nephrectomy for a World War II-related injury. This case underscores the importance of a thorough investigation of the complete urinary tract in a patient with hematuria or other urinary tract symptoms even if an obvious cause is found for his symptoms.

Anatomic, functional, and pathologic changes from internal ureteral stent placement.

The anatomic, hydrodynamic, functional, and pathologic changes associated with unilateral internal ureteral stenting were evaluated in 20 female canines. Selective glomerular filtration rates (GFR) were measured with technetium 99m diethylenetriamine pentaacetic acid (DTPA) renal scans (N = 14) prior to and several weeks after unilateral internal stent placement. Cystometry and cystography were done at weekly intervals to determine if reflux occurred and to measure the intravesical pressure to produce this reflux (N = 16). Ureteral lumenal capacities of mid 6-cm ureteral segments of stented and unstented ureters were compared. The mid-ureteral lumenal volumes were three times greater in the stented ureters (p < 0.002). There were no significant differences in the selective GFR before and after stenting. Low-pressure vesicoureteral reflux occurred at a mean intravesical pressure of 13.7 cm of water and was present in 84.6 percent (11/13) of the canines whose stents did not migrate or obstruct from encrustation. There were no significant alterations in serum chemistries or blood counts. Fluoroscopic imaging also showed ineffective ureteral peristalsis. This study confirms that internal ureteral stents cause vesicoureteral reflux and significant lumenal dilation without altering renal function.

Wilms' tumor with renal cell carcinoma overgrowth in a 3-year-old child.

Wilms' tumors that contain features of both renal cell carcinoma and classic Wilms' tumor histology are rare. Even though nine such cases have been previously reported in the literature, we report the first case of a Wilms' tumor with an overwhelmingly renal cell carcinoma histologic pattern.

Idiopathic anejaculation treated by vibratory stimulation.

Idiopathic anejaculation is a rare cause of infertility usually treated by psychotherapy. However, electrovibration may be a simple, noninvasive adjunct to the treatment of this disorder. In our two cases, we obtained ejaculate adequate for insemination in one patient and noted some gain in orgasmic sensation in the other. The success in these two infertile patients who had already undergone lengthy psychotherapy is promising. Nevertheless, psychotherapy will continue to be the standard of therapy until we have more experience with penile electrovibration.

5alpha-Androstane-3alpha,17beta-diol activates pathway that resembles the epidermal growth factor responsive pathways in stimulating human prostate cancer LNCaP cell proliferation.

5alpha-Androstane-3alpha,17beta-diol (3alpha-diol) is considered to have no androgenic effects in androgen target organs unless it is oxidized to 5alpha-dihydrotestosterone (5alpha-DHT). We used microarray and bioinformatics to identify and compare 3alpha-diol and 5alpha-DHT responsive gene in human prostate LNCaP cells. Through a procedure called 'hypervariable determination', a similar set of 30 responsive genes involving signal transduction, transcription regulation, and cell proliferation were selected in 5alpha-DHT-, 3alpha-diol-, and epidermal growth factor (EGF)-treated samples. F-means cluster and networking procedures showed that the responsive pattern of these genes was more closely related between 3alpha-diol and EGF than between 5alpha-DHT and 3alpha-diol treatments. We conclude that 3alpha-diol is capable of stimulating prostate cell proliferation by eliciting EGF-like pathway in conjunction with androgen receptor pathway.

The impact of 5-alpha-reductase inhibitors on the number of prostatectomies for benign prostatic hyperplasia.

To determine the impact of a 5-alpha-reductase inhibitor on the need for surgical treatment of symptomatic benign prostatic hyperplasia (BPH) in clinical urologic practice, we retrospectively reviewed records of 794 patients treated with pharmacotherapy or surgery (or both). The number of transurethral resections of the prostate (TURPs) performed during the 30 months since introduction of finasteride was compared with the number performed during the 30 months before finasteride became available. The alpha-blockers doxazosin and prazosin were used during both times for the treatment of BPH. Of the 619 patients treated with drugs, 88.5% received finasteride for a mean of 249.6 days. The alpha-blockers, either alone or combined with finasteride, were prescribed for 11.5% of patients for a mean of 179 days. In the 30 months after the introduction of finasteride, 65 patients underwent TURP: 28 of these men had initially received drug therapy. In contrast, 138 TURPs were performed in the 30 months prior to the availability of finasteride. The use of a 5-alpha-reductase inhibitor as primary medical therapy for symptomatic BPH decreased the number of prostatectomies by 52.9% (65 vs 138). This observation warrants corroboration through additional prospective studies.

Endourologic management of ureteroscopic complications.

Ureteroscopic injuries can be treated with endourologic techniques avoiding the morbidity of open operation. We report two cases of ureteral injury following ureteroscopy: one with extravasation, and the other, diagnosed one month postoperatively, with fistula and retroperitoneal urinoma. Both cases were successfully treated by percutaneous approaches. Possible etiology, preventive measures, and treatments are discussed.

Incidental ileal carcinoid associated with multiple urologic malignancies.

Although associated primary neoplasms frequently occur with carcinoid tumors, associated nonendocrine urologic malignancies are uncommonly encountered. We report the first case of an incidental ileal carcinoid associated with bilateral renal cell carcinoma and prostatic adenocarcinoma.