Prostate specific origin of dipeptidylpeptidase IV (CD-26) in human seminal plasma.

PURPOSE: A number of peptidases which can metabolize certain bioactive peptides and growth factors have been identified in seminal plasma. Our goal in this study was to determine molecular properties and the tissue source(s) for one of these peptidases, dipeptidylpeptidase IV (DPP IV), in human seminal plasma. MATERIALS AND METHODS: We measured the activities of DPP IV with the dipeptide glycylprolyl-p-nitroanalide and its molecular forms using immunoblotting of seminal plasmas of men who were vasectomized or with different sperm concentrations, and in prostatic and seminal vesicle secretions of men undergoing prostatic surgery. RESULTS: DPP IV in seminal plasma of vasectomized men was a membrane associated dimer comprised of subunits of approximately 110 kDa. Its activity did not differ in seminal plasmas of vasectomized, azoospermic, oligozoospermic and normozoospermic men indicating no correlation with the concentration of sperm originally present in the semen. The DPP IV antigen (CD -26) and enzymic activity were present in prostatic secretion, but absent from that of the seminal vesicles. These data indicate that the prostate gland is the primary source of DPP IV activity in seminal plasma. There was little variation in its activities in repeat seminal plasma samples from the same individual, and there was no change in its activity with age to 50 years. CONCLUSIONS: DPP IV in seminal plasma was derived from the prostate gland and it may be useful as a bioindicator of prostate function and/or disease with age in men.

Protein kinase CK2 activities in human prostatic and seminal-vesicle secretions and seminal plasma.

Human prostatic secretion and seminal plasma contain certain protein kinase activities. Protein kinases play important roles in regulating a vast variety of cellular functions. The objective of this study was to determine whether one of these protein kinase activities in human prostatic secretion and seminal plasma is due to CK2, a messenger-independent, serine/threonine protein kinase that has considerable potential as a regulatory enzyme. By employing an anti-CK2 antibody and a CK2-specific peptide substrate, we have established that CK2 is present in these secretions. Approximately 70% of the CK2 activity present in seminal plasma of normozoospermic men (n = 49) is correlated to the number of sperm originally present in the semen. Further, both the prostate gland and the seminal vesicles are sources of CK2 activity in the seminal plasma of vasectomized men (n = 38). Although there was considerable variation between individuals in CK2 activity, the variation in repeat semen samples of the same vasectomized men (n = 6) was within 21%. There was no correlation of CK2 activity in seminal plasma with age for vasectomized (27-48 years, n = 38), oligozoospermic (28-43 years, n = 24), or normozoospermic men (26-48 years, n = 49). These data suggest that the majority of CK2 activity in the seminal plasma of normozoospermic men originates from sperm but that the prostate and seminal vesicles are accessory sex-gland sources of this enzyme.

Inflammatory disease of the ureter.

This article examines how the spectrum of responses of the ureter to inflammation is manifested in conventional radiography and to some extent in newer modalities, such as ultrasound, CT scan, and MR imaging. Common clinical entities are highlighted. The re-emergence of tuberculosis in the urinary tract and current information on infection with organisms are also discussed.

Pseudodiverticulosis: unusual appearance for metastases to the ureter.

A rare pseudodiverticular pattern of metastatic malignancy to the ureter is reported along with pathologic findings at postmortem examination in three patients. There was no clinical or pathological obstruction. This pattern is due to malignancy-induced edema in the subepithelial connective tissues and muscularis propria causing displacement of these layers into the ureteral lumen resulting in an undulating epithelial surface. The epithelium itself is normal. Metastases to the ureter is uncommon in life unless associated with ureteral obstruction. Ureteral pseudodiverticulosis found in vivo in a nonobstructed patient with known metastatic malignancy is likely due to inflammatory causes and usually reversible with antibiotic and medical therapy. A patient with widespread malignancy showing nonreversibility of the ureteral pseudodiverticular pattern, even in the absence of obstruction, should be considered a candidate for impending obstruction and followed closely for ureteral stent placement.

Value of transrectal ultrasound in identifying local disease after radical prostatectomy.

Transrectal ultrasound was performed on 15 men with clinical suspicion of local disease after radical retropubic prostatectomy. Clinical suspicion was defined as an elevation in serial serum prostate-specific antigen (PSA, above 0.4 ng/mL, Tandem-R + Assay) and/or palpable mass in the rectal vault. Post-radical prostatectomy ultrasound was normal if there was smooth tapering of the bladder neck to the urethra with no foci of variable echogenicity, and suspicious if any hyper- or hypo-echoic foci were present or if a mass was detected. Thirteen of 15 ultrasounds (87%) were described as suspicious while 2 of 15 (13%) were described as normal. Only 6 of 13 patients (46%) with suspicious findings on ultrasound had biopsy-proved carcinoma. Both patients with normal findings on post-radical prostatectomy ultrasound had biopsy-proved cancer. Transrectal ultrasound of the prostatic fossa when used independently is of no value in the diagnosis of local disease after radical prostatectomy. Transrectal ultrasound may help to direct systematic biopsies of the prostatic fossa in those patients in whom local disease is suspected on the basis of elevated serum PSA and/or a mass found on rectal examination.

Use of transrectal ultrasound in follow-up of postradical prostatectomy.

The appearance of the prostatic fossa on transrectal ultrasound following radical retropubic prostatectomy (RRP) is described. Transrectal ultrasonography was performed on 25 patients with normal bone scans and pelvic computed tomography from three to ninety months after RRP using a biplane high frequency probe. The area of the vesicourethral anastomosis (VUA) was identified, its contour characterized, surrounding tissues described, and changes induced by pelvic muscle contraction recorded. In 16 of these patients who had abnormal postoperative serum prostate-specific antigen levels, digital and ultrasound-guided transrectal needle biopsies for local recurrence were done and compared. The VUA was identifiable in all patients as either a smoothly tapered narrowing usually correlating with the presence of continence or distorted or blunted profile which often correlated with absence of urinary continence. The VUA was surrounded almost invariably by hypoechoic soft tissue which was pathologically nonspecific on biopsy. An extrinsic impression on the anterior bladder wall was noted in 80 percent. There was no clear distinguishing ultrasound feature for biopsy-proved local recurrence. The apparent length of the apposed walls of the urethra suggests a urethral high pressure zone (UHPZ). This lengthened significantly with voluntary contraction of the pelvic floor muscles.

Transrectal US in evaluation of patients after radical prostatectomy. Part I. Normal postoperative anatomy.

The appearance of the prostatic fossa on transrectal ultrasound (TRUS) scans obtained after radical retropubic prostatectomy (RRP) was studied in 25 patients believed to have no tumor on the basis of their level of serum prostate-specific antigen (PSA) (< or = 0.4 ng/mL). The profile of the vesicourethral anastomosis (VUA) in the midsagittal plane was tapered in 13 patients (52%) and nontapered in 12 patients (48%). The nontapered profile was associated with incontinence in nine of 11 patients (82%) followed up for less than 12 months but in only four of 14 patients (28%) followed up beyond 1 year. In 20 patients (80%), a hypoechoic soft-tissue lesion (average volume, 1.7 cm3) was seen anterior to the VUA and indented the anterior bladder wall. The length of the urethral high-pressure zone increased with muscular contraction of the pelvic floor. Knowledge of the baseline anatomic structures depicted on TRUS scans obtained after RRP may be useful in selection of tissue for TRUS-guided needle biopsy in patients with elevated levels of PSA. The many post-surgical changes reduced the specificity of the TRUS findings.

Transrectal US in evaluation of patients after radical prostatectomy. Part II. Transrectal US and biopsy findings in the presence of residual and early recurrent prostatic cancer.

The anatomic appearance of the prostatic fossa on transrectal ultrasound (TRUS) scans obtained after radical retropubic prostatectomy (RRP) for carcinoma was studied in 16 patients in whom local recurrence was suspected on the basis of rising serum prostate-specific antigen (PSA) levels above 0.4 ng/mL, negative pelvic computed tomographic scans, and negative bone scans. Findings in samples obtained with ultrasound (US)-guided biopsy were compared with those in samples obtained with digitally guided biopsy (DGB); each patient was his own control. When the postoperative anatomic appearance on TRUS scans was compared with that in patients without suspected recurrence of cancer, no significant difference was seen. Needle biopsy was positive for carcinoma in eight patients (50%): US-guided biopsy, in seven patients; DGB, in five patients; and both US-guided biopsy and DGB, in four patients. US-guided biopsy has limited usefulness over DGB in patients with rising PSA levels after RRP, but use of both DGB and US-guided biopsy may maximize sensitivity. The main value of TRUS may be in accurate positioning of the biopsy needle about the vesicourethral anastomosis.

Preoperative assessment of prostatic carcinoma by computerized tomography. Weaknesses and new perspectives.

A retrospective study of five years' experience with fourth-generation computerized tomography (CT) scan was undertaken to assess the frequency of understaging in prostate cancer. A total of 160 patients with preoperative scans were surgically staged. In 10 patients, the operation was aborted after pelvic node dissection had revealed unsuspected metastatic involvement. Based on the histopathologic evidence of local tumor invasion, extension into seminal vesicles or pelvic lymph nodes, restaging was required in 78 percent of cases. Accuracy was 24 percent for capsular extension, 69 percent for seminal vesicle invasion, and 72 percent for lymphadenopathy. The poor yield of CT scan as a preoperative staging modality is demonstrated. Recent advances in the understanding and management of prostatic cancer require reassessing patient benefit and cost effectiveness of available imaging techniques, focusing on the problem of detecting nodal metastases, and predicting tumor spread to regional lymph nodes by accurately evaluating the primary neoplasm. We conclude that CT scan fails to demonstrate the required precision needed to evaluate local tumor spread; therefore, this goal must be pursued with newer imaging modalities.

Early detection of local disease progression from stage A1 prostate carcinoma by transrectal ultrasonography.

Fifty-two patients with Stage A1 prostate cancer diagnosed by transurethral resection performed between 1975 and 1989 were re-examined by transrectal ultrasonography and ultrasonographically guided biopsies. Follow-up after the initial diagnosis ranged from 1 to 15 years (mean, 5.8 years). For eight patients, results of digital rectal examination were abnormal. For 44 patients, results were normal or indicated a low probability of cancer. Serum prostate-specific antigen (PSA) levels (4.6 to 14.6 ng/ml) were elevated in ten patients. Ultrasonography showed from one to three hypoechoic areas in 29 patients. Locally progressive disease, defined as moderately to poorly differentiated cancer, was detected in five (10%) patients, three of whom underwent radical prostatectomy. Histopathologic examination of the specimens revealed localized disease (no capsular invasion). The remaining two patients had radiation therapy. In three patients, results of digital rectal examination and the serum PSA level were normal, but focal, well-differentiated cancer, identical to that initially diagnosed, was detected after a follow-up of 5 to 10 years. Because the clinical significance of this finding is unknown, these three patients were not considered to have progressive disease and did not have additional treatment. Our data suggest that transrectal ultrasonography is valuable in early detection of local disease progression and should be used in the follow-up program for patients with Stage A1 prostate cancer.

Transurethral balloon dilatation of the prostatic urethra: effectiveness in highly selected patients with prostatism.

Transurethral balloon dilatation of the prostate has been shown to be a safe and potentially effective alternative to surgery in the treatment of benign prostatic hyperplasia, with a 66% success rate in relatively unselected patients. This study hypothesized that more careful patient selection might result in a significantly better rate of improvement. Ninety-one subjects with symptoms and signs of prostatism attributable to benign prostatic hyperplasia were studied. Group 1 comprised 42 patients with an initial mean symptom score of 16.8, residual urine of 249 ml, maximal flow rate of 7.9 ml/sec, and nomogram of maximal flow rate of -1.5. Group 2 comprised 49 less symptomatic patients with an initial mean symptom score of 14.5, residual urine of 105 ml, maximal flow rate of 10.7 ml/sec, and nomogram of maximal flow rate of -0.8. The difference in mean age and prostate size between groups was not statistically significant, but differences in baseline symptom score, residual urine, maximal flow rate, and nomogram of maximal flow rate were significant (p less than .04). Transurethral balloon dilatation of the prostate was performed under local anesthesia or IV sedation and analgesia with single-or double-balloon catheters with maximal diameters of 25-30 mm inflated to 2.5-4.0 atmospheres pressure for 10 min. Patients were followed up with repeat symptom scoring, uroflometry, and measurement of residual urine. After a mean follow-up of 22 months (range, 6-48 months), an improvement in symptom score was seen in 80% of group 2 patients compared with 43% in group 1. Improvement in symptom scores was statistically significant in both groups (p less than .04). We conclude that transurethral balloon dilatation of the prostate is more effective in patients with more moderate symptoms and with less marked signs of obstruction than in patients with more marked prostatism.

Long-term followup results after expectant management of stage A1 prostatic cancer.

A total of 132 patients with stage A1 adenocarcinoma of the prostate was followed for 5 to 23 years (mean 8.2 years). Of these patients 52 underwent a second staging transurethral resection of the prostate between 1977 and 1986. Progressive disease developed in 3 of the 12 patients (25%) in whom residual foci of well differentiated cancer were detected by the second transurethral resection and who did not undergo further treatment. Of the 38 patients in whom the second transurethral resection did not detect residual cancer 3 (8%) also had progressive disease. From April 1989 to December 1989, 44 patients were re-evaluated by transrectal ultrasonography and ultrasonographically guided biopsies. Of these patients 3 had locally progressive disease. Progressive disease also developed in 4 more patients. Thus, 13 of the 132 patients (10%) had either locally or systemically progressive disease after long-term followup. The interval from diagnosis of stage A1 disease to detection of progression ranged from 6 months to 20 years (mean 7 years). Ten patients underwent definitive treatment for what was believed to be locally progressive disease, 2 underwent palliative therapy and 1 had no therapy due to poor physical condition. Of the 10 patients who underwent definitive therapy 6 are alive without evidence of disease, 2 died of unrelated causes without evidence of disease and 2 are alive with stage D1 disease. These data suggest that patients in whom a second staging transurethral resection of the prostate detects residual cancer have a high probability of progressive disease. Also, negative findings from a second staging transurethral resection may not exclude the possibility of disease progression. Expectant management of stage A1 disease is warranted but regular and long-term followup is mandatory.

Ureteral pseudodiverticula: frequent association with uroepithelial malignancy.

Ureteral pseudodiverticula are tiny outpouchings usually seen as incidental findings on retrograde urography during routine work-up for common urinary tract disorders. We report 37 patients with ureteral pseudodiverticula, of whom 17 (46%) had associated uroepithelial malignancy. Ureteral pseudodiverticula were diagnosed in all patients on excretory or retrograde urography as an incidental finding during evaluation for a variety of urologic symptoms and signs. All patients were assessed with urinalysis, urine culture, cystoscopy, and when indicated, ureteroscopy. Diagnosis of transitional cell carcinoma was made by surgery or endoscopic biopsy in 16 patients and squamous cell carcinoma in one. In nine patients with radiographs showing ureteral pseudodiverticula and a urinary tract filling defect (usually in the bladder), 78% of the cases were proved malignant. In six patients with ureteral pseudodiverticula and a stricture in the ureter or renal collecting system, 67% of the cases were proved malignant. Of the patients with tumor, 53% had a single ureteral pseudodiverticulum. In two cases, the pseudodiverticula antedated the diagnosis of malignancy by 2 and 4 years, respectively. Our experience suggests that the association between ureteral pseudodiverticula and uroepithelial malignancy may be more common than previously assumed, approaching 50%. Even a single ureteral pseudodiverticulum should be regarded as a serious marker for potential malignancy, antedating cancer by 2-10 years, and such patients should be closely followed up. The coexistence of ureteral pseudodiverticula and a stricture or filling defect in the urinary tract is highly suggestive that a tumor is present.

Experimental treatment of benign prostatic hyperplasia with transurethral balloon dilation of the prostate: preliminary study in 73 humans.

A prospective noncontrolled study of the safety and potential efficacy of transurethral balloon catheter dilation of the prostate (TUDP) in the treatment of benign prostatic hyperplasia (BPH) was performed in 73 subjects with moderate to severe symptoms and signs of prostatism who were selected on the basis of a quantitative symptom score (SS), uroflowmetry measurements, and residual urine volume. Seven patients had urinary retention. Mean age was 69.6 years (range, 59-95 years). TUDP was successfully accomplished in 70 patients (96%). There were no significant complications. Mean follow-up was 16.2 months (range, 6-36 months). Forty-six patients (66%) showed improved SS at the most recent follow-up. In 24 patients (34%) SS was unimproved, necessitating prostatectomy in 17 subjects (24%). Reduction in mean residual urine volume was not statistically significant. Only 38% of patients with median lobe enlargement showed improvement in SS, compared with 74% for the others. The authors conclude that TUDP is safe and shows promising effectiveness and that the ultimate demonstration of effectiveness requires a controlled clinical trial.

Routine quality control tests for film-screen mammographic systems with automatic exposure control.

Quality control of the contrast and density of mammograms is of extreme importance not only because of patient dose considerations but also because of the need to monitor changes in the breast over extended periods of time. A phantom and test technique has been developed and used at two institutions for monitoring the ability of mammographic generators and phototiming systems to provide consistent contrast and density. The phantom consists of a solid acrylic block and an embedded aluminum step wedge designed specially for low kVp use. Optical densities of various portions of the phantom are used to determine constancy of density and contrast. By minimizing fluctuations due to processing and film handling, normal variations were reduced enough to determine changes in contrast and density due to generator and phototimer changes equivalent to those monitored in processor quality control programs. The data have been correlated with changes in processor function. Changes in density and contrast values have also been related to phototimer malfunction and reduced image quality.

The pathology of ureteral pseudodiverticulosis.

We studied 200 postmortem ureters from 100 adult men to test the hypotheses that ureteral pseudodiverticula (UPD) are more prevalent than clinically recognized, that UPD are secondary to chronic inflammations, and that they are associated with uroepithelial neoplasm. The ureters were inflated with 10% formaldehyde and fixed for 24 hours. One hundred sixteen ureters were drained and refilled with 25% diatrizoate sodium meglumine and radiographed before gross and microscopic pathologic examination. No radiographs of the remaining 84 ureters were obtained. UPD were identified pathologically in 11%. None of these patients had a history of upper urinary tract disease. UPD were smaller than those reported clinically and invariably were associated with focal microscopic ureteritis cystica and glandularis in ureters otherwise free of histologic abnormality. UPD displayed mild benign mucosal hyperplasia with invagination in the subepithelial connective tissue as well as impression and sometimes thinning of the muscularis propria but without penetration. No mucosal atypia or malignancy was seen. We postulate that UPD represent a proliferative response to focal inflammation resulting in intramural invasion producing elevation and thinning of the ureteral wall. Continued focal inflammation may be sustained by local urine stasis. Enlargement to clinically detectable size may be enhanced by more generalized disease such as clinical infection, stone, or obstruction.

Assessment of prostatism: role of intravenous urography.

A prospective study of 502 patients referred for assessment of symptoms of bladder outlet obstruction was performed to determine the value of routine intravenous urography (IVU). The purpose was to establish the rate at which significant occult abnormality in the upper urinary tract is detected with IVU alone; to determine to what extent these abnormalities can be predicted from routine clinical and laboratory evaluation, thus allowing better patient selection for IVU; and to recommend alternative imaging modalities. History, physical examination, and routine laboratory studies constituted the preliminary examination. Abnormalities were found in 23% of patients but significant conditions in only 10%. Occult significant abnormalities that would have been missed without IVU occurred in only 1.5% of patients. Most of these could be detected on an abdominal radiograph. Only one malignancy would have been missed without routine IVU. The authors conclude that IVU in the assessment of prostatism should be limited to patients with positive findings in the clinical work-up. An abdominal radiograph is recommended in the others. Significant cost savings can thus be achieved.