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Purpose: We identified and characterized unrecognized testicular secretory proteins that impact human prostate growth., Materials and Methods: Human spermatocele fluid served as a source of testicular epididymal secretions and prostatectomy specimen benign prostatic hyperplasia stromal cells as the in vitro prostate growth promoting effects indicator. RMPI plus medium supplemented with 10% fetal bovine serum MALDI-TOF, MS FBS and ITS+ (Collaborative Research-Becton Dickinson, Bedford, Massachusetts) served as positive and negative controls, respectively. Whole and fractionated spermatocele fluid or specific proteins without and with select polyclonal or monoclonal antibodies were added to routine 6-day cultures. The observation of significantly increased 6-day cell counts compared with appropriate controls (p <0.05) was judged to reflect cell growth. Amino acid microsequencing and MALDI-TOF MS sequence analysis were done on persistent protein bands from active spermatocele fluid fractions., Results: Whole and fractionated human spermatocele fluid increased stromal cell culture numbers significantly. Sequence analysis of 47 and 17 kDa 1-dimensional gel bands in the final active fraction identified a major peptide with sequence homology to human pigment epithelium-derived factor (PEDF). The presence of PEDF was confirmed by Western blot analysis. Addition of recombinant PEDF to incomplete medium significantly increased stromal cell culture number. PEDF antibodies neutralized or markedly decreased the stromal stimulating effect of spermatocele fluid and PEDF., Conclusions: The observations presented provide evidence for human testis/epididymis secretion of PEDF and for a PEDF in vitro growth promoting effect on benign prostatic hyperplasia stroma. The concept that testicular epididymal secretory proteins may influence normal and abnormal prostate growth warrants continued consideration.

Purpose: To present the biochemical cure rates (biochemically no evidence of disease) after external irradiation (RT) in patients with high-risk prostate cancer after radical prostatectomy., Methods and Materials: Seventy-six patients who underwent radical prostatectomy and subsequent RT were included in this analysis. No patient received hormonal therapy. Adjuvant RT was administered in 35 patients (46%), and 41 patients (54%) underwent salvage RT. After prostatectomy, the Gleason score was <7 in 87%, and 24% had seminal vesicle invasion. The median RT dose in the adjuvant RT and salvage RT groups was 60 Gy and 65 Gy, respectively. The biochemical cure rate was defined as a serum prostate-specific antigen of < or =0.2 ng/mL., Results: The overall 5-year Kaplan-Meier biochemical control rate from the end of RT was 70%. The 5-year biochemical cure rate for adjuvant RT was significantly superior to that after salvage RT (86% vs. 57%). The significant predictors of biochemical failure were seminal vesicle invasion in the adjuvant RT group and the presence of Gleason grade 4 or 5 in the salvage RT group. The clinical local control rate in the prostate bed was 100%., Conclusion: This report demonstrates the efficacy of RT in achieving high biochemical cure rates after radical prostatectomy. Additional clinical studies are required to determine the optimal treatment of patients at high risk of biochemical failure after postprostatectomy RT.

Background: Understanding the mechanisms by which diet influences the prostate may eventually lead to novel approaches for preventing prostate cancer. The objective of this research is to examine the impact of dietary fat, vitamin D, and genistein on prostate weight, serum and intraprostatic androgen levels, and the expression of several androgen-response genes., Methods: Sprague-Dawley rats were fed, beginning at 21 days of age, for 1 or 3 months of experimental diets with high saturated fat (32.2% calories from fat), low saturated fat (3.6% calories from fat), genistein plus (20 mg/kg), genistein deficient, vitamin D surplus (4,000 U/kg), or vitamin D deficient. The body weight, food intake, the weights of the ventral prostate and dorsolateral prostate, and the levels of testosterone and dihydrotestosterone (DHT) in the serum and in the prostate were determined. The expression of androgen-response genes was characterized by Northern blot analysis., Results: The pilot experiments showed that high dietary fat appeared to consistently increase the weight of the ventral prostate, while vitamin D or genistein did not have a consistent effect on prostate weight. Further analysis confirmed that the ventral prostate is 15% (P < 0.001) heavier in the rat on a high fat diet as compared to a low fat diet. Dietary fat had no significant influence on the levels of serum and intraprostatic androgens and the expression of androgen-response genes., Conclusions: Our results suggested that the ventral prostate weight of the rat is increased without affecting the androgen axis by feeding the animals with high fat diet beginning at 21 days of age. This observation is potentially important since epidemiological data suggest that saturated fat consumption is a major risk factor associated with prostate cancer incidence rate., (Copyright 2001 Wiley-Liss, Inc.)

Adult Sprague-Dawley male rats, weighing about 350 g, were rendered cryptorchid by suturing the testes to the lateral abdominal wall. Twenty-eight days later, cryptorchidism resulted in a significant decline in testis weight and suppressed spermatogenesis. The ventral prostate was significantly smaller in cryptorchid rats. There was no significant difference in serum testosterone levels between the normal and cryptorchid rats. Charcoal-stripped aqueous extracts of the testis from intact and cryptorchid animals were tested on primary cultures of rat prostatic stromal cells. Cultures treated with extract from the intact testis had a significantly increased cell proliferation as assessed by cell count and by the rate of 3H-thymidine incorporation. Additionally, extracts of seminiferous tubules significantly increased prostate stromal cell proliferation compared to extracts of testicular interstitial components. Furthermore, this proliferative effect of testicular extracts is specific to the prostate as extract of both normal and cryptorchid testis stimulated proliferation of rat footsole fibroblasts in culture, but only extracts from intact testis stimulated proliferation of prostate stromal cells. These observations demonstrate that the testis produces nonandrogenic substances that can promote growth of prostatic stromal cells and that these substances were eliminated in the cryptorchid testis.

Background: Although growth factors such as epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, and TGF-beta are important regulators of prostate cell growth in vitro and in animal models, evidence to support their role in human prostate cancer development remains sparse. We previously showed that men without prostate cancer have concentrations of EGF and TGF-alpha in expressed prostatic fluid (EPF) that are individually distinct and stable over time. This study addressed whether growth factor levels in EPF are associated with the presence or progression of prostate cancer., Methods: We measured levels of immunoreactive EGF, TGF-alpha, and TGF-beta1 in stored EPF samples from three age-matched groups: 19 men with untreated, histologically diagnosed prostate cancer (CaP), 38 with benign prostate hyperplasia (BPH), and 19 with normal prostate glands (NPD)., Results: Median TGF-alpha was lower in the BPH group (0.45 ng/ml) than in either CaP (0.63 ng/ml) or NPD (0.58 ng/ml) groups (P = 0.03 and 0.12, respectively). For EGF, the median was lowest in the CaP group and highest in the NPD group (92.5 ng/ml vs. 175.5 ng/ml, P = 0.006). For TGF-beta1, the median level in CaP was 2.7 times higher than the median level among all controls (6.65 ng/ml vs. 2.46 ng/ml, P = 0.002). Growth factor levels were not associated with tumor stage or Gleason score. However, the single case with distant metastases had TGF-beta1 levels 23-fold higher than the CaP median., Conclusions: The results suggest that at the time of CaP diagnosis, EGF levels in EPF are significantly lower, and TGF-beta1 levels significantly higher, than normal. Marked overexpression of TGF-beta1 in advanced CaP might be reflected in extremely high EPF levels., (Copyright 1999 Wiley-Liss, Inc.)

Background: This study was undertaken to attempt to characterize changes in in vitro growth rates and cellular phenotypes of human prostatic stroma associated with aging and/or development of benign prostatic hyperplasia (BPH)., Methods: Prostate stromal cell strains were established from 12 tissue donors of varying age. Culture growth rate was determined by cell counts over a 6-day period. Cell phenotype was assessed by immunocytochemical staining for smooth muscle alpha-actin, smooth muscle myosin, and prolyl-4-hydroxylase., Results: Growth rates of prostate stromal strains in vitro varied. Stromal cells derived from aged males with BPH had significantly slower growth rates than cells from younger donors. A positive reaction for prolyl-4-hydroxylase, a mesenchymal cell marker, was present in all cell cultures regardless of donor age. Expression of smooth muscle-specific actin, a nonspecific smooth muscle cell marker, was present in 48-79% of prostate stromal cultures. Staining for smooth muscle myosin, a specific smooth muscle cell marker, was found to vary significantly with age. The percentage of smooth muscle myosin-positive cells derived from males aged 15, 45, 57, and 72 years were 0.70 +/- 0.14%, 2.12 +/- 0.30%, 4.20 +/- 0.89%, and 26.25 +/- 1.0%, respectively. The shape and size of actin- and/or myosin-positive stromal cells from a 72-year-old donor culture were also usually larger and polygonal in shape as compared to thin and elongated shapes in 15-year-old donor cultures. The shape of actin- and/or myosin-positive cells from a 45-year-old donor culture demonstrated both phenotypes., Conclusions: These results suggest that in human prostate stromal cells cultured as described, the growth rate decreases, the percent of smooth muscle cells increases, and the cellular shape changes with increasing donor age and/or development of BPH.

Purpose: We used expanding observations regarding effects of testicular epididymal plasma and nonandrogenic testis factor(s) (NATF) on prostate growth to propose and evaluate a hypothesis regarding the development of benign prostatic hyperplasia (BPH) in man., Materials and Methods: Current experimental data regarding the presence of NATF were reviewed. The potential for their exposure to the prostate by various routes was assessed. These observations were coupled with recognized anatomical, histological and epidemiological characteristics of BPH to construct a hypothesis regarding its pathogenesis., Results: In vivo observations in man, rats and dogs supported the systemic secretion of NATF. These factors probably are, at least in part, spermatogenesis related. In vitro evaluation of the effect of spermatocele derived testicular epididymal plasma on human prostate stromal cells indicated the presence of androgen independent and androgen synergistic stromal growth promoters. These factors have potential local and systemic access to the prostate. The almost ubiquitous development of a regional, histologically variegated nodular growth occurring in the prostate in the androgen diminished environment of the aging man is compatible with local as well as systemic exposure to an age associated secretion of NATF., Conclusions: We propose that human BPH is an induced phenomenon that is usually initiated by local episodic exposure of periurethral prostate to mitogens secreted by the testis/epididymis. Once initiated, isolated or complex interacting proliferative stimuli from the testis/epididymis and a variety of other sources may achieve exposure to the prostate by several routes and simulate prostate growth.

Purpose: Our goal is to understand human prostate growth phenomena potentially important to BPH development and growth. The objective of the present study is to characterize in vitro prostate stromal proliferative factors in testis epididymal secretions., Materials and Methods: Human spermatocele fluids were used as a source of testicular epididymal plasma (STEP). Primary cultures of human prostate stromal cells were routinely grown in RPMI-1640 with 10% fetal bovine serum. During a 6-day experimental period, cells were cultured in RPMI-1640 in the absence of serum but supplemented with ITS. Whole STEP, ether stripped STEP, or heparin affinity column treated STEP was included in the culture medium with and without the addition of testosterone (T), dihydrotestosterone (DHT), or estradiol (E). Results of these treatments were assessed by cell counts. Antibodies against smooth muscle myosin heavy chain, smooth muscle alpha actin, and prolyl-4-hydroxylase were utilized in immunocytochemical characterization of cultured cells., Results: Whole STEP stimulated prostatic stromal cells derived from prostates of 15, 45, 70 and 72-year-old men. Treatment of STEP by ether stripping or heparin affinity column exposure did not result in a significant reduction in cell counts. With the exception of the 15-year-old specimen, addition of T or DHT to ether stripped STEP resulted in a significant increase in cell counts over that of ether stripped STEP treatment alone. Preliminary immunocytochemical evaluation indicated the presence of variable mixture of fibroblasts, myofibroblasts, and smooth muscle cells in these cultures., Conclusions: These in vitro observations indicate that testis epididymal secretions contain androgen/STEP synergistic and androgen independent STEP factors promoting prostate stromal growth. These factors are not heparin binding. These observations are consistent with the concept that, in addition to the production of steroids, the testis produces non-androgenic factors that act in concert with, as well as independently of, androgen to stimulate prostatic growth.

Objective: To obtain evidence of metabolic changes in the human prostate associated with prostate pathology, in particular carcinoma of the prostate, by identifying and evaluating associated changes in prostatic secretory products., Methods: Expressed prostatic fluid (EPF) from 36 patients with carcinoma, 128 with BPH histologically confirmed, and 148 with clinical BPH was subjected to determination of protein (Lowry; UV 280 nm absorption), enzymatic (DMA modified Row procedure) acid phosphatase (AcP), and immunologically identified (Tandem-PAP immunoenzymatic assay) prostatic acid phosphatase (PAP) concentration., Results: The important EPF findings are the following: (1) Protein concentrations (Lowry and UV determinations) are significantly increased in carcinoma as compared to histologic BPH, (2) AcP and PAP secretions remain stable in carcinoma versus BPH, and (3) AcP and PAP/Lowry protein ratios are significantly lower with carcinoma., Conclusions: These findings of increased protein and the decreased relative secretions of AcP and PAP to total protein (ratio) in EPF from patients with carcinoma compared to BPH support and help to characterize the diffuse metabolic alteration in the prostate associated with prostate carcinoma. EPF observations identify potential metabolic changes occurring in prostate carcinoma that may have potential clinical and investigative relevance.

Purpose: We sought to determine the efficacy of radical retropubic prostatectomy in men with high grade adenocarcinoma of the prostate in a population that had not been screened for prostate specific antigen (PSA)., Materials and Methods: An inception cohort of 116 men surgically treated for prostate cancer between 1980 and 1991 was created in April 1992 and prospectively followed thereafter. Median followup was 7 years (range 2.2 to 14.6)., Results: The major cause of death in this group of men was prostate cancer, not competing causes. Ten-year disease specific survival was 96% for organ confined (stage pT2c or less) and 78% for unconfined (stage pT3a or greater) disease. Five and 10-year PSA progression-free survival by pathological stage was 83 and 53% for organ confined disease, and 34 and 22% for unconfined disease with negative pelvic lymph node dissection (p = 0.001). Five and 10-year metastasis-free survival was 96% for organ confined disease, and 81 and 62% for unconfined disease (p = 0.011). Men with pelvic lymph node metastasis had 70 and 30% 5 and 10-year metastasis-free survival, and 75 and 55% disease specific survival, respectively. PSA progression-free survival was 33% at 5 years. A significantly decreased risk of PSA progression was observed in men with unconfined carcinoma who received adjuvant external beam radiotherapy., Conclusions: In men with high grade prostate cancer the major cause of death was prostate cancer, not competing causes. Pathologically confined carcinoma had a significantly decreased rate of metastatic progression. These observations support the bias that early detection in these men at high risk for cause specific death may favorably impact survival.

Background: Prostatic fluid (PF) provides a unique medium for noninvasive evaluation of critical growth and differentiation signals in the prostatic microenvironment. The purpose of this study was to establish the feasibility of measuring two prostatic mitogens, epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) in PF, and specifically to quantify extraneous variability attributable to the assay itself, sample handling, or biological variation within an individual over time., Methods: PF was collected by transrectal massage from consecutive patients attending a urology clinic. Pooled PF and individual samples from 25 men with stable benign prostatic hyperplasia (BPH) were analyzed for EGF and TGF-alpha by radioimmunoassay and for total protein., Results: Reproducibility was adequate at dilutions as low as 1:50 (2-microliter pooled sample) and 1:5 (20 microliters) for EGF and TGF-alpha, respectively. Results were not affected by freeze-thaw cycles, time in storage, or protease inhibition in fresh PF. EGF and TGF-alpha were detectable in 100% and 92% of individual men, with respective means of 152 and 0.2 ng/ml. Correlations between two samples obtained from the same man within 12 months were highly significant (EGF r = 0.89, TGF-alpha r = 0.71). Protein concentrations were consistent over time; expression of either peptide per weight of protein rather than per volume did not improve within-man correlation. Between-man variability far exceeded within-man variability for both peptides, and was estimated to account for 84% and 61% of the total variability in EGF and TGF-alpha, respectively. There was no correlation between EGF and TGF-alpha in the same samples., Conclusions: We conclude that men with BPH secrete consistent and distinct levels of EGF-related peptides in PF, and that these levels can be detected with acceptable sensitivity and precision by radioimmunoassay (RIA). Measurement of TGF-alpha, which has not been reported previously, requires a relatively larger sample.

This review will present a new concept on the etiology of the development of benign prostatic hyperplasia (BPH). Conventionally, two known etiological factors for the development of BPH have been aging and the presence of functional testes. Assignment of these two factors, although reasonable, has not been conducive to aid the research community to identify and isolate the patho-physiological agents that are directly responsible for the development of this disease. In the present review, we proposed a broadened concept of intrinsic and extrinsic factors for BPH. This concept offers identifiable research opportunities that will facilitate our quest in search for etiological agents for BPH. A brief description of various intrinsic and extrinsic factors and justifications for their selection will be discussed.

Background: This study was performed to evaluate the efficacy of radical prostatectomy for men with clinically localized, poorly differentiated (Gleason score > or = 7) prostate cancer and to characterize further the prognostic significance of traditional pathologic variables. The effectiveness of adjuvant radiotherapy was assessed in a subpopulation of men for whom the pathologic assessment suggested a high risk of persistent disease., Methods: Two hundred thirty-eight consecutive men, 74 of whom had clinically localized, poorly differentiated carcinoma, were followed for a median of 6.2 and 5.1 years, respectively. The disease specific outcomes were derived from a non-prostate specific antigen (PSA) screened population., Results: The 5-year disease specific survival (DSS) for 52 men with a clinically localized Gleason score of 7 and for 22 men with a Gleason score greater than or equal to 8 carcinoma was 92% and 79%, respectively. The 5-year likelihood of having an undetectable PSA level was 50% for those with a Gleason score of 7 and 38% for those with a Gleason score greater than or equal to 8. Gleason score was the most powerful pathologic predictor of disease progression and survival. Pathologic stage was significantly associated with disease progression for carcinomas with Gleason scores less than 7 but was found to be less predictive of progression for carcinomas with Gleason scores greater than or equal to 7. Adjuvant radiotherapy provided a significantly reduced risk of PSA-detectable progression (P = 0.02, relative risk = 0.56, 95% CI: 0.34, 0.92); however, radiotherapy had no significant impact on DSS., Conclusions: Long term DSS is possible in a non-PSA screened series of men with poorly differentiated prostate cancer treated by radical prostatectomy. These results compare favorably with alternative treatment strategies, although they do illustrate a continued need to develop more effective adjuvant therapies for men with poorly differentiated prostate cancer.

Purpose: We tested the hypothesis that the histochemically demonstrated prostate specific antigen (PSA) content of prostate carcinoma cells does not necessarily reflect PSA production and secretion by evaluating expressed prostatic fluid., Materials and Methods: Expressed prostatic fluid and serum from 152 men with clinical benign prostatic hypertrophy (BPH), 132 with histologically proved BPH and 46 with prostate carcinoma were analyzed with the Hybritech PSA assay., Results: Expressed prostatic fluid PSA levels from carcinoma patients (median 1.70 mg./ml., mean 2.25) were significantly higher than in the histologically proved BPH group (median 1.28 mg./ml., mean 1.42, p < 0.05)., Conclusions: PSA concentration is increased in the expressed prostatic fluid of prostates of men with carcinoma compared to those with histological BPH. This finding may be a functional manifestation of a field change or paracrine effects within the prostate.

Benign Prostatic Hyperplasia (BPH) is the most common neoplastic condition that afflicts men, and it constitutes a major factor impacting the health of the American male. This article reviews voiding dysfunction and the role of aging, the testis, and androgen in the development of BPH. Emphasis is placed on new concepts in the basic aspects of BPH etiology as a result of recent investigations.

Reversed seromuscular flaps of ileum and standard bowel replacement procedures were performed in 16 dogs to evaluate their potential to decrease the likelihood of recognized complications in cases of standard bowel replacement. Of 12 dogs augmentation cystoplasty was done in 6 and ureteral replacement was done in 6. In each group 4 procedures were performed using reversed seromuscular flap, while the remaining 2 were done in the conventional manner (controls). All flap animals had partial to full re-epithelialization with transitional cells but they also had gross and microscopic evidence of flap contraction at the end of 6 months. In the flap augmentation group intravesical pressure measured preoperatively at bladder volumes of 30 cc and 60 cc averaged 25.8 and 45.8 mm. Hg compared to sacrifice pressures of 56.7 and 80.8 mm. Hg. Monthly serum blood urea nitrogen measurements were lower in reversed seromuscular flap animals compared to controls. An additional 4 dogs were studied to help elucidate the etiology of graft contraction, of which 2 underwent reversed seromuscular flap enterocystoplasty with no mucosal stripping while 2 had a procedure exposing intact intestinal serosa to the lumen of the bladder and urine. All of these animals demonstrated good re-epithelialization of the serosal surface with transitional cells as well as little or no evidence of flap fibrosis or contraction. Our results demonstrate that the use of reversed seromuscular flaps in the urinary tract in dogs results in good re-epithelialization of the serosal surface with transitional cells but also flap contraction. This fibrosis and scarring process is largely due to the trauma of mucosal stripping and not urine contact.

Flow cytometry was performed on bladder cells from patients with interstitial cystitis and control patients. Cells were processed in standard fashion for flow cytometry with propidium iodide staining and analysis was restricted to samples with sufficient cells for cytokeratin gating and acceptable coefficients of variation. Of 14 interstitial cystitis patients 4 (29%) demonstrated aneuploid deoxyribonucleic acid (DNA) profiles as evidenced by a discrete peak with a DNA index of 1.2 or greater in the cytokeratin positive population. The aneuploid peak accounted for up to 54% of the cytokeratin positive population in these samples. No such aneuploid DNA profiles were evident in specimens obtained from control patients. A significant DNA tetraploid population, as evidenced by a 4C (G2) peak greater than 20%, was observed in 6 of 14 interstitial cystitis patients (43%) and 8 of 11 controls (72%). Manual counting of the per cent of binucleated cytokeratin positive cells in the cytokeratin stained population and nuclear preparations of several samples for flow analysis indicate that apparent DNA tetraploidy in the interstitial cystitis and control patients is due to an abundance of binucleated cells. Aneuploid DNA profiles on barbotage specimens from interstitial cystitis patients may reflect a real karyotypic abnormality or altered chromosome complement (true aneuploidy), abnormal chromatin structure or abnormal cytoplasmic binding of the propidium iodide stain. This finding may signal an underlying abnormality of the epithelial cell population in some patients with the clinical diagnosis of interstitial cystitis.

We studied expressed prostatic secretions from 106 patients with prostatitis to determine the longitudinal course of prostatic fluid inflammation. Prostatic fluid specimens were collected from 14 patients with acute bacterial, 13 with chronic bacterial and 79 with abacterial prostatitis. White blood cells per high power microscopic field of the expressed prostatic secretion were counted under a cover slip. Inflammation in the expressed prostatic secretion was considered to be consistent with prostatitis if there were 10 or more white blood cells per high power field. The 14 patients with acute bacterial prostatitis had a mean of 10 visits with a mean followup of 59 months. Inflammation resolved within 1 month in 9 patients with acute bacterial prostatitis but it recurred in 5 other patients in association with urinary tract infection. The 13 patients with chronic bacterial prostatitis had a mean of 10 visits with a mean followup of 58 months. Episodic inflammation in the expressed prostatic secretion associated with urinary tract infection was seen in all patients during followup. The 79 patients with abacterial prostatitis had a mean of 7 visits with a mean followup of 40 months. Resolution of inflammation in the expressed prostatic secretion occurred in 9 patients (11%). Inflammation in the expressed prostatic secretion at followup was seen in 70 patients (89%), and 27 of the 79 patients (34%) had 10 or more white blood cells per high power field of expressed prostatic secretion in all subsequent specimens. In cases of abacterial prostatitis, neither the initial expressed prostatic secretion white blood count nor the presence of symptoms reliably predicted subsequent inflammation. The data suggest that prostatic inflammation resolves in most patients with acute bacterial prostatitis and is episodic in patients with chronic bacterial or abacterial prostatitis.

In this preliminary study, we report that an enzyme-linked immunofluorescence assay (EFLA) was developed for the determination of PR92 antigen in prostatic fluid, utilizing anti-PR92 monoclonal antibody. Fluid samples from 64 patients were assayed. PR92 antigen was expressed as unit per microgram (U/microgram) of prostatic fluid proteins. One hundred percent of men (7 out of 7) less than 50 years of age demonstrated concentrations less than 25 U/micrograms; 91% of men (10 out of 11) with documented carcinoma, and only 9.5% of men (2 out of 21) with benign prostatic hyperplasia, demonstrated concentrations above 230 U/micrograms. The mean concentration of PR92 antigen in prostatic fluid of a group of patients suspected of having prostate cancer (high-risk group; 227 +/- 42 U/micrograms) was significantly greater than that of those with benign prostatic hyperplasia (87 +/- 23 U/micrograms; P = 0.05). Further evaluation of this potential marker and of other antigens within the prostatic fluid is warranted.

The failure of current histological techniques to predict local failure and disease progression after radical prostatectomy is supported by substantial evidence. Moreover, the characterization of histological findings is hampered by the lack of uniform interpretation. We report a prospective study of 92 patients undergoing radical prostatectomy for clinical stages A and B prostate cancer in which the technique of touch preparation cytological analysis of surgical margins is compared to the standard histological approach. We evaluated 47 pathological stage B, 43 stage C and 2 stage D specimens. Specimens initially assigned to pathological stage B were upstaged to stage C on review by 1 blinded pathologist in 19 of 65 cases (29%). Overall, 15 of 47 histological stage B specimens (32%), 20 of 43 histological stage C specimens (47%) and 2 of 2 histological stage D specimens (100%) had malignant cells identified on the margins by touch preparation cytology. Postoperative mean followup of 7 months (range 0.4 to 26) revealed that 7 of 14 nonstage D cancer patients (50%) with elevated serum prostate specific antigen levels had positive cytology results, including 1 with histologically confirmed organ-confined disease. Among the stage C specimens cytology was more likely to be positive if there was concomitant seminal vesicle invasion. Correlation of this information with eventual patient course during the long term will be necessary to assess its role in patient management.

Objective: To determine if selective renal papillectomy would impair urinary concentrating ability, thereby decreasing urinary calcium concentration., Methods: Left papillectomy was performed in dogs using either incisional (n = 6) or Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (n = 5) techniques. Split renal function studies were then performed four months postoperatively to determine the effect on multiple parameters including inulin and para-aminohippurate (PAH) clearance, free water reabsorption, and calcium concentrations. Partially infarcted kidneys (n = 6) were evaluated in a similar fashion to determine the role of impaired glomerular filtration rate (GFR) in the observed concentrating defect occurring after papillectomy., Results: Papillectomized kidneys demonstrated impaired free water reabsorption, resulting in a decreased urinary osmolality and an increased fractional excretion of water. Osmolar clearance [Na+] and Na+ excretion were unaffected by papillectomy, whereas [Ca++] was significantly reduced. While a slight defect in free water reabsorption existed following partial infarction, urinary osmolality was only minimally decreased, fractional excretion of water was unchanged, and Na+ excretion was decreased., Conclusions: The concentrating defect induced by papillectomy via either sharp excision or laser ablation is due to loss of medullary tissue and is greater than the defect resulting from impaired GFR, which is presumably due to decreased medullary solute delivery and increased flow of water in remaining nephrons. Since the physiologic consequences of papillectomy (formation of less concentrated urine with decreased [Ca++]) have potential clinical applicability, further study of this concept is warranted.

The present study was carried out to investigate whether testicular fluid derived from a spermatocele contains substance(s) that promote the growth of human prostatic cells in culture. Human spermatocele fluid was centrifuged to sediment spermatozoa. The supernatant was then added to cultures of human prostatic stromal or epithelial cells that were isolated from surgical specimens of benign prostatic hyperplasia. Addition of spermatocele fluid in quantities of 1 microgram/ml of protein resulted in a significant increase in the number of both prostatic stromal and epithelial cells at the end of a 6-day culture period. Human serum at equivalent protein concentrations in the culture medium had no stimulatory effect. At least two separate growth-promoting factors were found in spermatocele fluid, one for stromal cells and one for epithelial cells. The mitogen for stromal cells was heat labile and persisted after treatment with activated charcoal. The factor for epithelial cells was heat stable but was removed by charcoal treatment. These observations are consistent with the concept that the human testis secretes nonandrogenic substances that can promote prostatic growth.

Nephrogenic adenoma is a metaplastic condition which usually involves the bladder urothelium within the clinical setting of chronic inflammation. Its presentation/endoscopic appearance may mimic bladder cancer and a premalignant potential has been speculated. DNA flow cytometry performed on involved bladder tissue revealed a diploid phenotype exhibiting low proliferative activity. These findings are most suggestive of a benign process.

A widely held view is that the role of testis in prostatic growth is through its ability to secrete androgen. Our earlier observation suggested a non-androgenic role for the testis, and perhaps the epididymis, in promoting growth of the ventral prostate in rats. The present study was conducted to evaluate the separate role of the testis and the epididymis in this phenomenon. In the first study, increasing quantities of silastic tubing filled with crystalline testosterone were implanted into adult Sprague-Dawley rats at the time of bilateral epididymo-orchiectomy or sham-operation. Twenty-eight days later, growth of the ventral prostate, as determined by fresh weight, DNA, and protein content, was significantly greater in sham-operated rats than in those receiving combined epididymo-orchiectomy, confirming our previous observation using dihydrotestosterone. In the second and third studies, rats were subjected to selective surgical procedures to evaluate the independent role of the testis and the epididymis. At the same time, 12 cm silastic tubing filled with testosterone or dihydrotestosterone were implanted subcutaneously into each of these animals for 28 days. Results indicated that the ventral prostate was significantly smaller in rats receiving the combined epididymo-orchiectomy than that of sham-operated controls. Simple orchiectomy or simple epididymectomy resulted in an increased weight of the ventral prostate between the two values obtained from the above two groups. Ligation of either the efferent duct or the vas deferens yielded ventral prostatic weights comparable to the androgen-treated, sham-operated controls. These results indicated that in order to achieve a maximal effect on androgen-supported growth of the ventral prostate, the presence of both the testis and the epididymis is required.

Background: The prevalence and incidence of clinical problems secondary to and associated with benign prostatic hyperplasia (BPH) are of increasing concern as the population ages., Methods: Selected published reports using anatomical and clinical criteria to identify BPH and its clinical sequelae were reviewed., Results: The following observations seem to reflect the current state of knowledge: (1) BPH develops with increasing frequency as men age; (2) BPH causes significant pathologic changes in the urinary tract of some patients and symptoms in others; and (3) other identifiable or cryptic etiologic factors may be the predominant cause of identical voiding dysfunction in patients with BPH., Conclusion: Essential information about factors initiating and promoting development of BPH, the exact mechanisms by which BPH alters voiding mechanisms, and definitive diagnostic criteria to establish the role of BPH in clinical changes are lacking. Progress in these problem areas is essential to guide appropriate clinical management.

Prolactin and testosterone are synergistic in stimulating growth of the rat prostate. The lateral lobe is more sensitive to this synergism than the ventral and dorsal lobes. To investigate whether prolactin acts directly in the rat prostate or indirectly through another systemic mediator, anterior pituitary grafts (1 mm3) were implanted in the lateral prostate of castrated Sprague-Dawley rats in whom a 0.5 cm or 1.0 cm testosterone-filled silastic tubing was implanted subcutaneously at the same time. Rats were randomly assigned to receive either the pituitary or a muscle chip of similar size grafted beneath the fascia lateral to the lateral prostate. Twenty-one days later, serum prolactin levels were not elevated in pituitary-grafted animals and were not significantly different from those in muscle-grafted rats. The mean lateral prostate weight on the grafted side in pituitary-implanted rats with 1.0 cm testosterone tubing was 43% heavier than either that of the contralateral side or the corresponding weights in muscle-implanted rats. In pituitary-implanted rats with 0.5 cm testosterone tubing, the mean lateral prostate weight on the grafted side was 60% heavier than either that of the contralateral side or that of the corresponding weights in muscle-implanted rats. The weight of the ventral and dorsal lobes of the prostate was not significantly affected by the presence of pituitary grafts in one of the lateral lobes. The local effect of prolactin on the lateral prostate was further demonstrated by an overall decline in tissue concentrations of dihydrotestosterone in the grafted side. These results provided evidence to indicate that there was a direct effect of prolactin on growth of the lateral prostate in rats.

Since the landmark observations of Huggins and Hodges in 1941, androgen deprivation has been the mainstay of treatment for advanced-stage prostate cancer. Although early, poorly controlled studies suggested enhanced survival with hormonal therapy, this view fell into disfavor as a result of the observations of the first and second VACURG studies. Recently, there has been a proliferation of experimental and clinical data supporting early androgen deprivation, including a reanalysis of the VACURG data, which suggests a survival advantage for younger patients with stage D disease and high-grade tumors who undergo androgen-ablative therapy at the time of diagnosis. The risk-benefit analysis presented in this review is strongly supportive of early hormonal therapy. Finally, long-term survival of patients with metastatic prostate cancer will require the development of novel treatment strategies effective against androgen-resistant tumor cells and their use in concert with early androgen deprivation.

Transferrin receptors (TfR) were measured in benign and malignant prostatic cells by performing Scatchard analysis following the administration of 125I-transferrin. Established human prostate cancer cell lines (PC-3 and DU-145) as well as biologically aggressive variants (PC-3 ASC and PC-3 DES) were shown to possess significant levels of high affinity TfR when assessed in vitro. In contrast, TfR content was negligible in cultured stromal cell fractions derived from human benign prostatic hyperplasia (BPH) specimens. Scatchard analysis was also performed on in vivo derived prostatic tissues: tumors resulting from the subcutaneous xenografting of PC-3 ASC cells into athymic, nude mice and fresh BPH surgical specimens. These tissues were dissociated and their stromal and epithelial components separated. TfR were only detected in the epithelial component of both malignant and benign epithelial cells. PC-3 ASC tumor cells exhibited TfR levels comparable to their in vitro expression and these levels were 10-fold greater than in the BPH cells. These findings suggest that elevated TfRs may serve as another useful marker of the transformed phenotype within human prostate tumor systems.

This study was conducted to investigate whether the testis, aside from its ability to secrete androgen, is able to promote prostatic growth in rats. Increasing quantities of silastic capsules filled with crystalline dihydrotestosterone (DHT) were implanted subcutaneously into adult Sprague-Dawley rats at the time of bilateral epididymo-orchiectomy or sham operation on the testes. Control animals received empty capsules. Twenty-eight days later, the growth of the ventral prostate as measured by wet weight, DNA, and protein content per prostate was significantly greater in rats with intact testes than in orchiectomized rats. An overall increased growth was noted at all doses of exogenous DHT administered. Serum levels of luteinizing hormone in animals treated with DHT were undetectable. Serum levels of testosterone in intact rats treated with DHT were not significantly different from those in castrated rats. These observations suggest a non-androgenic role for the testis and, perhaps, epididymis in promoting prostatic growth in rats, and are consistent with the concept that a non-androgenic substance, produced from the testis and/or epididymis, is able to enhance prostate growth induced by androgen stimulation. The possibility that this phenomenon may play a role in the benign growth of the prostate observed in aging human males with decreased blood levels of androgen warrants consideration.

This review presents the current status of attempts to identify individuals with a high risk of carcinoma of the prostate by using biochemical, immunochemical, and immunologic studies of body fluids. Blood, urine, and prostatic fluid have been subjected to a variety of analyses in attempts to find alterations that are sufficiently specific and sensitive enough to be useful in the early recognition of patients with a high probability of localized or disseminated carcinoma of the prostate. A variety of immunologic and immunochemical techniques to identify and quantify acid phosphatase of prostatic origin in the serum are currently being explored for this purpose; as yet, none has achieved the specificity-sensitivity relationship necessary for widespread clinical application. Biochemical studies of prostatic fluid have disclosed a reversal of the lactic dehydrogenase (LDH) isoenzyme pattern with a predominance of LDH-V and increased levels of transferrin, complement C 3 and possibly complement C 4 in association with carcinoma of the prostate. The value of these non-specific changes is increased by the probable direct relationship between prostatic epithelial cell metabolism and changes in prostatic fluid composition. These approaches to identify individuals with a high risk of carcinoma of the prostate hold promise; they should be continued and expanded., (Copyright © 1980 American Cancer Society.)

Our original series of patients with prostatic carcinoma treated with irradiation as the initial modality has been updated. The over-all 5-year survival rate for patients with stage III carcinoma of the prostate was 55 per cent--26 per cent were alive with residual disease and have had post-irradiation hormone manipulation, while 29 per cent were alive without metastases at 5 years.

Specimens of pooled prostatic fluid, collected by rectal massage from men under 50 years of age with no apparent prostatic disorders, were subjected to two-dimensional gel electrophoresis to study the composition of its proteins. In a preliminary study, a total of 57 major protein groups were detected. In the present study, we attempted to identify, in the two-dimensional gels, those that are related to prostate-associated proteins, i.e., prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), and prostate binding protein (PBP). Individual proteins were recognized by the procedure of Western Blot using specific antisera with peroxidase-antiperoxidase as the staining reagent. Each protein spot in the two-dimensional gel was expressed, along the abscissa, by its isoelectric point (pI) and, along the ordinate, by the molecular weight (MW). PAP consisted of a train of more than ten protein spots that occupied an area in the gel from pI 7.0, MW 45,000 to pI 6.0, MW 50,000. Four protein spots with a MW of 34,000 and a pI range of 8.2-8.8 were identified as PSA. PBP was observed as having three protein spots that were located at pI 5.6-6.6 with a single MW of 15,000. For PAP and PSA, additional protein spots with lower MWs also stained positively with the specific antisera, suggestive of the presence of degradative products of these proteins. Following the removal of the serum-related proteins by an extensive absorption with anti-human serum antibody by affinity chromatography, the prostatic fluid contained 27 major groups of non-serum proteins. These non-serum proteins in the prostatic fluid included PAP, PSA, PBP, and their related smaller molecular species. These results indicate that the prostatic fluid contains PAP, PSA, PBP and that their presence and the patterns of their distribution in the two-dimensional gels should be considered as the characteristic property of the prostatic secretions.

The attempt to identify changes in the biochemical composition of prostatic fluid that might accompany and characterize disease states in the prostate was stimulated by two assumptions based on observations. First, the composition of prostatic fluid was judged to be likely to reflect the metabolic status of at least the epithelial cells accurately. Secondly, the metabolic changes preceding or associated with the development of carcinoma in the prostate seemed likely to be diffuse rather than limited to the histologically abnormal prostatic cells. As a consequence of these assumptions, prostatic fluid obtained from the urethra by digital massage of the prostate was evaluated microscopically and subjected to numerous analytical procedures. Differences in lactate dehydrogenase (LDH) isoenzymes, complement C3, and transferrin concentrations in the prostatic fluid of men with histologically identified carcinoma (Ca) and benign prostatic hyperplasia (BPH) have been observed. The ratio of LDH-5/ LDH-1 was found to have a mean value of 5.94 +/- 0.25(S.E.) in 98 determinations on 83 patients with Ca, and 1.84 +/- 0.14 in 212 determinations on 142 patients with BPH with 10 or less white blood cells per high power field (WBC/hpf) on microscopic examination of the prostatic fluid. Fluid from 52 patients with BPH with greater than 10 WBC/hpf (84 determinations) had a mean ratio of 5.85 +/- 0.88 and from 286 patients with greater than 10 WBC/hpf without an established histologic diagnosis (460 determinations) of 3.12 +/- 0.21. Two hundred twenty-two men under 45 years of age (255 determinations) judged to have a normal prostate clinically had a mean ratio of 0.67 +/- 0.05. The mean transferrin concentration in 44 patients (51 determinations) with Ca was 47.03 +/- 3.76mg/100 ml, in 59 patients with BPH (90 determinations) was 12.97 +/- 1.20, in 23 patients with BPH with > 10 WBC/hpf in the prostatic fluid (38 determinations) was 14.93 +/- 2.19, in 87 patients with > 10 WBC/hpf (92 determinations) was 13.42 +/- 1.41, and in 33 patients less than 45 years of age with clinically normal prostates (33 determinations) was 7.45 +/- 1.08. The mean complement C3 concentration in 46 patients with Ca (57 determinations) was 17.48 +/- 1.60, in 58 patients with BPH (85 determinations) was 3.83 +/- 0.55, in 24 patients with BPH with > 10 WBC/hpf (39 determinations) was 5.87 +/- 0.68, in 93 patients with > 10 WBC/hpf (98 determinations) was 4.47 +/- 0.53, and in 34 patients less than 45 years of age (34 determinations) was 2.06 +/- 0.43. The mean ratio of LDH-5/LDH-1 was significantly greater for Ca than BPH with 10 or less WBC/hpf in the prostatic fluid. The mean concentrations of transferrin and complement C3 were significantly greater in Ca than in all other groups studied. No obvious relationship between stage of disease and these findings was observed. These observations support the suggestion that determination of prostatic fluid composition assists in identifying men with a high risk of cancer of the prostate.

Available English language articles relating the grade, stage, and grade-stage of carcinoma of the prostate to evidence of tumor progression and survival in untreated and treated patients have been reviewed. Observations of the extremes of the spectrum of biological behavior of carcinoma of the prostate have been emphasized; for example, tumor progression, never or always; survival, never or always. The reported experiences indicated the following; namely, 1) reproducible biologically meaningful grading is achievable; however, grade cannot be utilized as a reliable indicator of stage; 2) accurate staging provides information that correlates with tumor progression and survival in groups of patients. However, unexpectedly prolonged or abbreviated progression-free survivals occur frequently enough in every stage, except perhaps patients with clinically unsuspected focal carcinoma, to indicate that the natural history and treatment response of individuals grouped by stage is far from homogeneous; 3) appropriate use of carefully obtained grade and stage information together maximizes the accuracy of prognostic attempts and is necessary to evaluate treatment results. At the present time, assessment and consideration of the grade and stage of carcinoma of the prostate is essential to formulate prognosis and advise and evaluate treatment in patients with this disease.

Hyperprolactinemia, achieved by grafting pituitaries under the renal capsule, has been shown to cause a delay in the rate of castration-induced prostatic regression in rats. The mechanism of this prolactin action is not established, although it has been suggested that the action of prolactin in the rat prostate is mediated through the action of androgen. To explore the possibility that a small amount of residual endogenous androgen present in the prostate at the time of castration acts synergistically with prolactin to cause this delay in prostatic regression, Flutamide has been used in the present study in an attempt to inhibit this residual androgen effect by blocking its interaction with androgen receptors. Two experiments were conducted. In experiment 1, daily sc injections of Flutamide (25 mg/kg) for 7 days to castrated rats supplemented with dihydrotestosterone-filled silastic tubing either 1 or 4 cm long completely suppressed both prostatic weight and protein content to the level that was normally observed in castrated rats receiving empty tubings. Furthermore, treatment of Flutamide to castrated rats did not cause an increase in prostatic weight and protein content over those of castrated rats treated with the vehicle only. These results indicate that Flutamide, at this dosage, is a potent antiandrogen and that the compound itself does not have any androgenic activity in the rat prostate. In experiment 2, adult male rats were castrated and received two female pituitaries grafted under the renal capsule. One week later, their serum prolactin levels increased from 20 +/- 3 ng/ml to 102 +/- 8 ng ml. This elevated level of serum prolactin was associated with a delay in the rate of prostatic regression. Administration of Flutamide, at a dose (25 mg/kg) which completely suppressed prostatic growth, failed to inhibit the delay in prostatic regression in castrated rats bearing the pituitary grafts. Since Flutamide inhibits the androgen action in the prostate by blocking the binding of intracellular dihydrotestosterone to androgen receptors, the failure of Flutamide to block the effect of prolactin suggests that the prolactin action in regressing prostates is not mediated by androgen receptors.

Polyglycolic acid (PGA) tube stented, silastic stented and non-stented anastomoses were compared in 18 ureteroureterostomies performed in 13 dogs. Urinalysis, urine culture, BUN and serum creatinine and intravenous pyelograms were done periodically from 1 day to 6 months postoperatively and ureteral dynamics were performed at 6 months. Normal intravenous pyelograms were observed following 10 of 11 PGA stented, 3 of 4 silastic stented and 2 of 3 unstented anastomoses. PGA stents prevented extravasation and dissolved within 7 days without stone formation. Urodynamic and histopathologic studies revealed no significant differences among the 3 groups. The data suggest that PGA stents are as effective as silastic stents and do not require additional procedures for removal.

A retrospective review of 100 patients undergoing pelvic lymphadenectomy alone or with additional surgery was done to assess the morbidity and to help identify factors contributing to a high wound morbidity. Major wound morbidity occurred in 8 per cent of patients, while 16 per cent had minor wound problems. Factors contributing to wound morbidity included urinary tract infection, altered metabolic states, and the use of wound drains. Other morbid events are tabulated.

The status of the biochemical markers explored for use in patients with carcinoma of the prostate is reviewed. No unique marker has been identified. However, a variety of substances, primarily enzymes and specific proteins, found in the serum, urine, and prostatic fluid, have been evaluated. Their main value remains in the staging of disease and the monitoring of response to therapy.

Two children with priapism are presented; one case was secondary to trauma and the other was idiopathic in nature. Both boys were effectively treated by bilateral corporosaphenous shunts. The mechanism of normal erection and the pathophysiology of priapism are discussed.

A corpora cavernosa-glans penis shunt was carried out to control priapism in eight patients in the past two years. Four of the five patients treated by sertion of a biopsy needle through the glans into the corpora and three patients treated by creation of a window in the tunica albugenia of the corpora through a glans penis incision experienced prompt detumescence and maintained potency. These observations support the efficacy of a venous shunt to achieve rapid detumescence and support the concept that potency is likely to be preserved if venous stasis is relieved promptly and its recurrence prevented. Surgical incision of the glans penis to permit creation of a shunt from each corpora cavernosum under direct vision is simple, safe and effective. This procedure warrants primary consideration as the initial treatment of priapism.

We reviewed the tissue histology of 115 patients with clinically localized carcinoma to determine the correlation between tumor grades in the biopsy and the prostatectomy specimen. Gleason's primary and secondary pattern score systems were used, and each specimen was graded on a scale of 2 to 10 by a referee pathologist in a blind fashion. If the difference in the summed primary and secondary grades in the 2 specimens was no more than 1 grade, the discrepancy was regarded as insignificant. In all but 32 cases initial diagnostic biopsy specimens predicted accurately the final prostatectomy specimen score. The discrepancy was 3 grades in 7 cases and 2 grades in 25 cases. As a result, the lesions in 19 cases were changed from a well differentiated (2 to 4), a moderately differentiated (5 to 7) or a poorly differentiated (8 to 10) lesion to another of these categories. The lesions were upgraded from a well differentiated to a moderately differentiated category in 9 cases and from a moderately to a poorly differentiated category in 4 cases. The lesions were downgraded from a moderately differentiated to a well differentiated category in 6 cases. In 13 other cases the discrepancy was 2 but the lesion remained within the moderately differentiated group. Although in 19 cases the cancerous tissue occupied less than 10 per cent of the biopsy specimen, accurate prediction could be made in 16. The results indicate that diagnostic biopsy specimens will predict the grade of the primary tumor in a majority (72 per cent) but not all of the cases.

Based on reports of regression of superficial bladder tumors after urinary diversion, a study was designed to measure the effects of urine and continued exposure to carcinogen on the incidence of progression of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced early urinary bladder lesions to invasive tumor. After being fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide diet for 14 weeks, one-half of the male Fischer rats had urinary diversion by ureterosigmoidostomy, and the remainder were sham operated. One-half of each of these two groups was continued on the N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide diet while the remaining animals were fed regular chow postoperatively. One-half of each of the four groups was sacrificed at 3 months, and the remainder were sacrificed at 6 months after ureterosigmoidostomy or sham-operation. The incidence and mean number of tumors as well as the incidence of invasive tumor were tabulated. The combined 3- and 6-month data indicate that excreted carcinogen in the urine influences progression of the preinvasive lesions more than urine alone or systemic carcinogen alone. However, urine alone had a significant effect (p < 0.025) on tumor incidence (8 of 19 sham-operated animals with tumor versus 1 of 18 diverted animals with tumor). Urine acts as a promoter in this experimental system. These findings may have clinical applications in the treatment of early transitional cell carcinoma.

In an attempt to identify an indicator(s) specifically associated with prostatic cancer prostatic fluid was collected by rectal massage from patients with prostatic cancer, prostatitis, benign prostatic hyperplasia and from those without recognized prostatic lesions in order to measure various immunoproteins. The proteins examined were IgG, IgA, IgM, complements C3 and C4, and transferrin. Prostatic fluid samples were subjected first to immunoelectrophoresis. Distinct differences in C3, C4 and transferrin concentrations were noted between patients with prostatic cancer and other patients. These proteins were stained heavily in the electrophoresis gels of fluid from cancer patients but were either missing or lightly stained in all other groups. These qualitative determinations were replaced subsequently by a quantitative measurement using the radial immunodiffusion technique. Results of the latter study confirmed the aforementioned observations and indicated that the levels of C3, C4 and transferrin in the prostatic fluid of cancer patients were elevated significantly when compared to all other patient groups. These observations indicate that the measurement of complements C3 and C4, and transferrin in the prostatic fluid may assist in the identification of patients with a high risk of prostatic cancer.

The current studies of expressed prostatic fluid tend to confirm our previous reported pilot observations of a shift in lactic dehydrogenase (LDH) isoenzymes to a predominance of LDHV in patients with prostatic malignancy. They also suggest a decrease in concentration of acid phosphatase and an increase in concentration of protein in the presence of carcinoma of the prostate. These observations suggest a diffuse metabolic alteration of the prostate in the presence of prostatic carcinoma.