Decreased prostatic arachidonic acid in human prostatic carcinoma

OBJECTIVE: To measure prostatic and blood fatty acid composition in a large group of patients undergoing prostatectomy for benign or malignant prostate disease, as there is evidence linking arachidonic acid metabolism and prostate cancer through its role as an eicosanoid precursor, and earlier studies showed lower prostatic arachidonic acid content in a few patients. PATIENTS AND METHODS: Prostatic phospholipid fatty acid composition was determined in prostate tissue from 173 patients undergoing prostate surgery, i.e. radical prostatectomy, cystoprostatectomy or transurethral resection (TURP). Blood fatty acid composition was determined in 99 of these patients and in 85 undergoing prostatic needle biopsy. RESULTS: There was a significantly lower percentage of arachidonic acid in malignant than in benign portions of the prostate (15.2% vs 17%) in all patients assessed. The changes were greatest in those undergoing TURP for known prostate cancer (13.4% vs 17.2%), these patients having the greatest proportion of malignancy in the specimens. There were no consistent changes in blood fatty acid composition. CONCLUSION: This is the first prospective study of arachidonic acids levels involving many consecutive patients undergoing prostate surgery for either benign or malignant disease. The lower prostatic arachidonic acid level is probably a result of the increased use of arachidonic acid for producing prostaglandins and/or leukotrienes. Further understanding of the cause and/or consequence of this finding might lead to a better understanding of prostate cancer.     

Minocycline diffusion into prostatic tissue

We evaluated the concentration of minocycline in human prostatic tissue. Twenty-six patients undergoing transurethral resection of prostate, two patients undergoing open prostatectomy for benign prostatic hyperplasia and two patients undergoing radical cystoprostatectomy for bladder cancer were studied. Prostatic tissue and blood were sampled at 1, 2 or 3 hours after the intravenous administration of 200 mg of minocycline. The concentration of minocycline was 2.95 +/- 1.39 micrograms/ml (mean +/- SD) in serum and 1.97 +/- 0.79 cg/g (mean +/- SD) in the prostatic tissue. The ratio of the prostatic concentration/serum concentration was 0.76 +/- 0.33 (mean +/- SD).     

Surgical outcomes for men undergoing laparoscopic radical prostatectomy after transurethral resection of the prostate

PURPOSE: We reviewed outcomes for men with a history of transurethral prostate resection who underwent laparoscopic radical prostatectomy for prostate cancer. MATERIALS AND METHODS: Between January 26, 1998 and December 2006, 3,061 men underwent laparoscopic radical prostatectomy at our institution. A retrospective review showed that 119 had a history of transurethral prostate resection. These men were compared to randomized matched controls with regard to operative and postoperative outcomes. The matching criteria used to randomly select patients were clinical stage, preoperative prostate specific antigen and biopsy Gleason score. RESULTS: Mean +/- SD age in the groups with and without transurethral prostate resection was 66.2 +/- 5.6 and 60.7 +/- 7.0 years, respectively (p <0.01). Mean estimated blood loss, transfusion rate, pathological prostate volume and reoperation rate were statistically similar between the groups. Mean length of stay for the groups with and without transurethral prostate resection was 6.5 +/- 3.0 and 5.29 +/- 2.3 days, respectively (p <0.01). Mean operative time for the groups with and without transurethral prostate resection was 179 +/- 44 and 171 +/- 38 minutes, respectively (p = 0.02). Positive margins were seen in 21.8% and 12.6% of the patients with and without transurethral prostate resection, respectively (p = 0.02). A total of 64 complications were seen in patients with a history of transurethral prostate resection compared to 34 in those without such a history (p <0.01). CONCLUSIONS: We report that patients with a history of transurethral prostate resection who undergo laparoscopic radical prostatectomy have worse outcomes with respect to operative time, length of stay, positive margin rate and overall complication rate. This subset of patients should be made aware of these potential risks before undergoing laparoscopic radical prostatectomy.     

Determination of norepinephrine levels in the adult human prostate.

Tissue levels of norepinephrine were measured in prostate tissue from 24 men ranging in age between 41 and 83 years. Prostatic tissue was obtained from men with subtle palpable prostate nodules undergoing transperineal needle biopsy. None of the patients were shown to have histologic evidence of adenocarcinoma. The severity of the symptoms of prostatism was evaluated prospectively using a standardized micturition symptom score questionnaire. Norepinephrine levels were quantified using a sensitive radioenzymatic assay (REA). Overall, the prostates contained relatively high levels of norepinephrine (1666 +/- 124 ng./gm.). Inverse correlations were observed between tissue norepinephrine levels and severity of symptoms of prostatism (r = -0.58; p = 0.003); age (r = -0.53; p = .008); and prostate size (r = -0.48; p = .02). Norepinephrine levels were also measured in tissue specimens obtained from men undergoing enucleation prostatectomy and transurethral resection of the prostate (TURP). The level of norepinephrine in these prostatectomy specimens (115 ng./gm.) was only 14% the level of the prostate biopsy specimens. The relatively low level of norepinephrine in the specimens obtained from patients with symptoms necessitating prostatectomy provides further evidence that norepinephrine levels are inversely related to the degree of symptomatic bladder outlet obstruction.     

The relationship of prostate specific antigen levels and residual tumor volume in stage A prostate cancer.

Preoperative serum prostate specific antigen correlates well with morphometrically determined prostate tumor volume in prostatectomy specimens. However, since prostate specific antigen is produced by hyperplastic as well as malignant prostatic epithelium, the contribution of hyperplastic epithelium (benign prostatic hyperplasia) to serum prostate specific antigen interferes with the ability of serum prostate specific antigen to predict tumor volume in individual patients. We wondered if the removal of benign prostatic hyperplasia tissue would increase the correlation between prostate specific antigen and tumor volume, and, thus, make prostate specific antigen a more accurate predictor of residual cancer volume after transurethral resection of the prostate. A total of 67 patients with clinical stage A cancer underwent radical retropubic prostatectomy (22, or 33%, with stage A1 and 45, or 67%, with stage A2 disease), and had pre-radical prostatectomy measurement of serum prostate specific antigen and morphometric determination of residual cancer volume in the radical prostatectomy specimen. The correlation between serum prostate specific antigen and residual cancer volume for all 67 patients was 0.66, and for stages A1 and A2 disease it was 0.64 and 0.70, respectively. All stage A1 cancer patients with a serum prostate specific antigen value of 1 ng./ml. or less had residual tumor volumes of less than 0.5 cc and all stage A cancer patients with a serum prostate specific antigen value of more than 10 ng./ml. had residual tumor volumes of greater than 0.5 cc. Of the patients 51% had levels of 1 to 10 ng./ml. and serum prostate specific antigen was not useful to predict residual tumor volume in this group. Serum prostate specific antigen measurements may be helpful in stage A1 cancer patients with levels of 1 ng./ml. or less, or greater than 10 ng./ml. in choosing the most appropriate therapy.     

Autonomic receptors in human prostate adenomas.

Radioligand receptor binding techniques were used to characterize alpha 1 adrenergic, alpha 2 adrenergic and muscarinic cholinergic (MCh) binding sites in human prostate adenomas obtained from men with symptomatic and asymptomatic benign prostatic hyperplasia (BPH). Prostate adenoma specimens were obtained from nine men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). A quantitative symptoms score analysis and urinary flow rate determinations documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The mean equilibrium dissociation constants (Kd) and the mean densities of 125I-Heat (alpha 1 adrenergic) and 3H-NMS (MCh) binding sites were similar in tissue homogenates obtained from men with asymptomatic and symptomatic BPH. The mean Kd of 3H-Rauwolscine (3H-Ra) was significantly greater in the prostatectomy specimens obtained from men with symptomatic BPH compared to the specimens obtained from men with asymptomatic BPH (p less than 0.05). The density of 3H-Ra (alpha 2 adrenergic) binding sites was significantly greater in the prostate adenomas obtained from men with symptomatic BPH compared to the prostate adenomas obtained from men with asymptomatic BPH (p less than 0.05). The difference in alpha 2 adrenoceptor density was accounted for by an increased receptor density in the open prostatectomy specimens. There was no significant correlation between alpha 2 adrenergic, alpha 1 adrenergic, and MCh receptor densities and prostate weight or patient age. This study indicates that the development of infravesical obstruction in men with BPH is not related to upregulation or altered binding affinity of alpha 1 adrenergic or MCh receptor binding sites. The significance of the observed upregulation of alpha 2 adrenoreceptors in the prostate adenomas obtained from men undergoing open prostatectomy is unknown, and requires further investigation.     

Contractile properties of human prostate adenomas and the development of infravesical obstruction

The contractile response of human prostate adenomas to KCl, phenylephrine (alpha 1 adrenergic agonist), UK 14304 (alpha 2 adrenergic agonist), and carbachol (muscarinic cholinergic agonist) was evaluated in tissue specimens obtained from men with symptomatic and asymptomatic BPH. Prostate specimens were obtained from 5 men with asymptomatic BPH undergoing cystoprostatectomy, 11 men with symptomatic BPH undergoing open prostatectomy, and 11 men with symptomatic BPH undergoing transurethral resection of the prostate (TURP). Quantitative symptom score analysis and urinary flow rate determination documented the absence of bladder outlet obstruction in men undergoing cystoprostatectomy and confirmed the presence of bladder outlet obstruction in men undergoing prostatectomy. The magnitude of the contractile response (Emax) and the potency of phenylephrine-induced contractions (EC50) in prostatic preparations obtained from men with symptomatic and asymptomatic BPH were similar. The IC50 for the inhibition of phenylephrine-induced contractions by prazosin was 3.2 nM, confirming that phenylephrine-induced contraction in the human prostate is mediated by the alpha 1 adrenoceptor. The contractile responses of prostate adenomas to muscarinic cholinergic and alpha 2 agonists were negligible. This study demonstrates that the development of bladder outlet obstruction in men with BPH is not related to alterations in the functional response of the smooth muscle component of the prostate adenoma.     

Can stage A1 tumor extent be predicted by transurethral resection tumor volume, per cent or grade? A study of 64 stage A1 radical prostatectomies with comparison to prostates removed for stages A2 and B disease

We studied 64 totally embedded radical prostatectomy specimens of stage A1 prostate cancer. The transurethral resection specimens were studied and compared to previously studied stages A2 and B cancer in which tumor volumes also were calculated. At radical prostatectomy 6% of the specimens had no residual cancer, 74% had minimal cancer and 20% had substantial cancer. Although most stages A2 and B tumors were larger, there was overlap among all stages. Transurethral resection tumor volume, per cent and grade were not statistically correlated with either radical prostatectomy residual tumor volume, or whether tumor was classified as minimal or substantial. Gleason sum 2 to 4 versus 5 to 7 tumor on transurethral resection showed no difference in predicting radical prostatectomy residual tumor or minimal versus substantial tumor status. Because 20% of all stage A1 cancers have substantial tumor at radical prostatectomy unpredictable by transurethral resection, radical prostatectomy remains an option for young men with stage A1 prostate cancer.     

Should prostate cancer status be determined in patients undergoing radical cystoprostatectomy?

INTRODUCTION: We estimate the frequency of prostate cancers detected incidentally in radical cystoprostatectomy specimens and discuss whether the prostate cancer status should be determined in patients undergoing radical cystoprostatectomy. MATERIALS AND METHODS: A total of 97 radical cystoprostatectomies without evidence of prostate cancer on digital rectal examination were performed for transitional cell carcinomas of the bladder between January 2001 and May 2004. The mean patient age at the time of surgery was 66.9 +/- 9.52 (range 49-75) years. RESULTS: The overall incidence of prostate cancer detected in radical cystoprostatectomy specimens was 21.6% (21/97 specimens). The mean tumor volume was found to be 0.93 +/- 0.81 ml. The tumor volume was >0.5 ml in 12 cases (57.1%). The surgical margin was negative in all cases, and the disease was organ confined in 20 patients (95.2%). Capsular invasion was evident in 2 patients (9.5%), 1 of whom had lymph-node-positive disease. CONCLUSIONS: Despite the high prevalence of incidental prostate carcinomas among patients with bladder cancer undergoing cystoprostatectomy, the vast majority of the cancers are organ confined. However, the prostate cancer status should be determined on the basis of digital rectal examination and prostate-specific antigen in patients undergoing radical cystoprostatectomy - especially if prostate-sparing cystectomy is planned.     

Morbidity of radical perineal prostatectomy following transurethral resection of the prostate

Radical prostatectomy in patients who have had prior transurethral resection of the prostate has been reported to result in significant morbidity. From 1974 to 1982, 30 patients who had had previous transurethral resection of the prostate underwent radical perineal prostatectomy for localized prostatic cancer. Operative time and blood loss were similar to a group of patients who had not had prior transurethral resection of the prostate. Over-all, 3 patients (10 per cent) had total incontinence and 3 (10 per cent) had stress incontinence requiring a pad or device. No patient undergoing radical prostatectomy less than 4 weeks or more than 4 months after transurethral resection of the prostate had postoperative incontinence. When radical perineal prostatectomy was performed between 4 weeks and 4 months after transurethral resection of the prostate the incidence of incontinence was 50 per cent. Five patients experienced prolonged perineal urinary drainage, all but 1 of whom healed spontaneously. Of the 6 patients with incontinence 3 had prolonged drainage. No patient had a rectal injury and there was no operative mortality. Two patients died without cancer and 1 has evidence of disease recurrence. We conclude that radical prostatectomy may be performed safely with acceptable morbidity following transurethral resection of the prostate and that if 4 weeks has elapsed since resection it might be advantageous to wait 4 months before performing radical surgery to lessen the risk of incontinence.     

Malignant Cytological Washings from Radical Prostatectomy Specimens: A Possible Mechanism for Local Recurrence of Prostate Cancer Following Surgical Treatment of Organ Confined Disease

Purpose

Local recurrence of prostate cancer following complete and successful resection of organ confined disease has been variably reported in men. We hypothesized that observed secretions from the cut distal urethra during radical prostatectomy may contain malignant prostatic epithelial cells and contribute to this problem.

Materials and Methods

A prospective study was done of prostate cytology specimens from 50 consecutive men with clinically organ confined adenocarcinoma of the prostate undergoing radical retropubic or radical perineal prostatectomy. Direct cytological evaluation by 1 examiner was used to identify malignant or benign cells in these washings.

Results

Of 33 radical perineal and 17 radical retropubic prostatectomy specimens organ confinement was confirmed in 58 percent. Malignant prostatic epithelial cells were observed in 24 percent of all cytology specimens. Of cytological washings from prostates with pathologically confirmed organ confined cancers 17 percent showed malignant cells. While perineural invasion was noted in a majority of tumors with positive washings, only Gleason grade was a statistically significant predictor of recurrence (p = 0.009). Surgical approach did not alter the rate of positive cytology.

Conclusions

Malignant prostatic epithelial cells can be identified in the prostatic washings from men with pathologically organ confined prostate cancer. Surgical approach did not change the cytological findings. Gleason grade is a statistically significant predictor of cytological malignancy. These cells may represent a mechanism of failure following successful radical prostatectomy.     

Utility of tissue microarrays for profiling prognostic biomarkers in clinically localized prostate cancer： the expression of BCL-2, E-cadherin, Ki-67 and p53 as predictors of biochemical failure after radical prostatectomy with nested control for clinical and pathological risk factors

A cure cannot be assured for all men with clinically localized prostate cancer undergoing radical treatment. Molecular markers would be invaluable if they could improve the prediction of occult metastatic disease. This study was carried out to investigate the expression of BCL-2, Ki-67, p53 and E-cadherin in radical prostatectomy specimens. We sought to assess their ability to predict early biochemical relapse in a specific therapeutic setting. Eighty-two patients comprising 41 case pairs were matched for pathological stage, Gleason grade and preoperative prostate-specific antigen （PSA） concentration. One patient in each pair had biochemical recurrence （defined as PSA ≥ 0.2 ng mL^-1 within 2 years of surgery） and the other remained biochemically free of disease （defined as undetectable PSA at least 3 years after surgery）. Immunohistochemical analysis was performed to assess marker expression on four replicate tissue microarrays constructed with benign and malignant tissue from each radical prostatectomy specimen. Ki-67, p53 and BCL-2, but not E-cadherin, were significantly upregulated in prostate adenocarcinoma compared with benign prostate tissue （P 〈 0.01）. However, no significant differences in expression of any of the markers were observed when comparing patients who developed early biochemical relapse with patients who had no biochemical recurrence. This study showed that expression of p53, BCL-2 and Ki-67 was upregulated in clinically localized prostate cancer compared with benign prostate tissue, with no alteration in E-cadherin expression. Biomarker upregulation had no prognostic value for biochemical recurrence after radical prostatectomy, even after considering pathological stage, whole tumour Gleason grade and preoperative serum PSA level.     

In situ hybridization of prostate-specific antigen mRNA in human prostate.

Prostate-specific antigen (PSA) mRNA was detected by in situ hybridization utilizing a 428 base pair [35S]-labelled cDNA probe from the 3' noncoding region of the PSA gene. Thirty six fresh surgical specimens were collected from patients undergoing radical retropubic prostatectomy for carcinoma of the prostate. Quantitative analysis of the levels of PSA mRNA in both the benign and malignant tissues was performed using an IBAS 2000 Image Analysis System. The results of this study demonstrated that there is a significant decrease in the expression of PSA mRNA in the carcinoma tissue when compared to the benign epithelium. The average binding (number of silver grains/1 x 10(4) microns. 2) for 20 specimens of malignant epithelium was 475 +/- 161 and 586 +/- 140 for 16 specimens of benign epithelium (p less than 0.05). Eleven patients had both benign and malignant tissue from the same surgical specimen available for study. From these paired specimens, the PSA mRNA expression was also significantly reduced in the malignant epithelium when compared to the benign epithelium, 445 +/- 162 and 588 +/- 135 respectively (p less than 0.005). The PSA protein was detected using a monoclonal antibody to PSA with an immunohistochemical staining technique. The PSA protein expression paralleled the expression of the PSA mRNA in the majority of the tissue sections. Many of the tumor specimens showed a heterogeneous expression of PSA, whereas all of the benign epithelium had a uniform high level of PSA expression. In conclusion, PSA mRNA and protein are located only within the glandular epithelial tissue, the expression of PSA protein parallels that of the PSA mRNA, and both the PSA protein and PSA mRNA are significantly decreased in the malignant epithelium when compared to benign prostatic epithelium.     

Malignant cytological washings from prostate specimens: an independent predictor of biochemical progression after radical prostatectomy

PURPOSE: Malignant cells have previously been identified in the cytological washings of prostate specimens obtained at radical prostatectomy for clinically localized prostate cancer. We investigated whether malignant cells in the cytological washings of radical prostatectomy specimens predict biochemical progression. The affect of total androgen blockade on cytological washings was also examined. MATERIALS AND METHODS: Cytological washings were obtained from radical prostatectomy specimens in 147 consecutive patients undergoing the procedure for clinically localized prostate cancer between November 1993 and April 1998. Of the 147 patients 54 were randomly selected to receive 1 month of total androgen blockade immediately before prostatectomy. To obtain the cytological specimen the extirpated prostate was subjected to a normal saline bath, as previously described. The cytology specimen was examined by a single cytopathologist blinded to preoperative and pathological findings. Biochemical progression, defined as prostate specific antigen 0.15 ng./ml. or greater, was determined using the Kaplan-Meier method. We also performed multivariate analysis of factors related to progression, including prostate specific antigen, pathological stage, margin status, Gleason grade and cytology status. Median followup was 37 months (range 13 to 66). RESULTS: Followup was available in 146 of 147 cases. Cytological washings were malignant in 14 of 92 patients (15%) who did not receive total androgen blockade preoperatively. In this group without androgen blockade the biochemical progression rate was significantly higher in those with positive cytology (p < 0.001). Positive cytology was an independent predictor of progression on multivariate analysis and a stronger predictor of progression than Gleason grade. No malignant cells were observed in cases of preoperative total androgen blockade (p < 0.001). However, biochemical progression was similar in the groups with and without androgen blockade (p = 0.355). CONCLUSIONS: Malignant cells may be identified in the cytological washings of radical prostatectomy specimens and they are an independent predictor of biochemical progression. One month of total androgen blockade preoperatively significantly decreases the rate of positive cytology but does not appear to change the rate of early biochemical failure.     

The relative proportion of stromal and epithelial hyperplasia is related to the development of symptomatic benign prostate hyperplasia.

The specific features of the prostate adenoma predisposing to the development of symptomatic benign prostatic hyperplasia (BPH) are unknown. Our objective was to determine whether the histological composition of the prostate adenoma is related to the development of symptomatic BPH. Prostate adenomas were obtained from men with asymptomatic BPH undergoing cystoprostatectomy for invasive transitional cell carcinoma, and from men with symptomatic BPH undergoing open prostatectomy, transurethral resection of the prostate and pharmacotherapy. The severity of bladder outlet obstruction was evaluated with the Boyarsky symptom score and uroflowmetry. The percentages of stroma, epithelium and glandular lumen were determined in the prostate adenomas via quantitative image analysis on a computer-assisted morphometry system. The prostate adenomas from the 33 men with symptomatic BPH contained 62 +/- 1%, 15 +/- 1% and 23 +/- 1 of stroma, epithelium and glandular lumen, respectively. The prostate adenomas from 6 men with asymptomatic disease contained 54 +/- 1%, 21 +/- 1% and 25 +/- 1% of stroma, epithelium and glandular lumen, respectively. The ratios of stromal-to-epithelial hyperplasia in the prostate adenomas from men with symptomatic and asymptomatic disease were 4.6 +/- 0.3 and 2.7 +/- 0.1, respectively. The differences in percentage of stroma and epithelium, and the stromal-to-epithelial ratio in the prostate adenomas from men with symptomatic and asymptomatic BPH were statistically significant. Our study suggests that the histological composition of the prostate adenoma is related to the development of symptomatic BPH.     

Racial differences in androgen receptor protein expression in men with clinically localized prostate cancer

PURPOSE: Black American men experience disproportionate mortality from prostate cancer (CaP) compared with white American men. Differences in outcome may stem from differences within the androgen axis. Since serum testosterone levels appear to be similar by race in men with CaP, we measured and compared androgen receptor (AR) protein expression in malignant and benign prostate tissue from black and white men who underwent radical prostatectomy for clinically localized CaP. MATERIALS AND METHODS: Archived radical prostatectomy specimens obtained from 25 white and 25 black men had AR protein antigen retrieved and immunostained. AR protein expression from CaP and benign tissue was assessed by 2 methods. Automated digital color video image analysis was used to measure the percent area immunostained for AR protein and the intensity of expression (mean optical density). Visual scoring was performed to compare results with automated values. RESULTS: In black compared with white men malignant nuclei were 27% more likely to immunostain for AR (p = 0.005) and in immunopositive nuclei AR protein expression was 81% greater (p = 0.002). Visual scoring of malignant nuclei revealed that AR immunostaining was significantly increased in black vs white men (171 +/- 40 vs 149 +/- 37, p = 0.048). In immunopositive benign nuclei AR protein expression was 22% greater in black than in white men (p = 0.027). Visual scoring of benign nuclei revealed 20% increased immunostaining in black vs white men, although this difference did not attain statistical significance (p = 0.065). Racial differences in AR protein expression were not explained by age, pathological grade or stage, although serum prostate specific antigen levels were higher in black men (9.7 +/- 7.5 vs 15.5 +/- 12.2 ng/ml, p = 0.049). CONCLUSIONS: AR protein expression was 22% higher in the benign prostate and 81% higher in the CaP of black African compared with white men. CaP may occur at a younger age and progress more rapidly in black than in white men due to racial differences in androgenic stimulation of the prostate.     

Evaluation of a new tumor marker for localized prostate cancer.

Adenocarcinoma associated antigen (ACAA) is a large molecular weight protein that is normally found in low serum levels. Recent data have revealed elevations in patients with adenocarcinomas, including prostate cancer. To evaluate the relationship of ACAA levels with prostate cancer, we measured the cytosol content in malignant and nonmalignant prostate tissue and compared these results to those of the standard markers, prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA). Enzyme solid phase immunoassay was used to quantitate PSA and ACAA levels, and the enzymatic method was used to measure PAP. Wedge resection from the right and left posterior lobes of 50 fresh radical retropubic prostatectomy specimens were used for cytosol analysis. All foci of within each prostate gland were carefully mapped by a single pathologist. When all malignant wedges (N = 74) were compared to all the benign wedges (N = 21), only the PSA levels showed significant elevation (p less than 0.02). However, when benign and malignant tissue from the same prostate were available for comparison, both PSA (N = 17) and ACAA (N = 16) showed significant elevations in the cytosol of the malignant tissue (p less than 0.002 and p less than 0.03, respectively). Although not statistically significant, the cytosol PAP did show a consistent trend to be greater in malignant tissue. It appears that there is an association of increased cytosol ACAA and PSA with prostate cancer.     

Studies on 5-FU concentration in serum and prostate cancer tissue after oral administration of UFT

The serum, urine and tissue concentrations of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT), 5-fluorouracil (5-FU) and uracil were estimated in 11 patients with prostate cancer (4 cases treated by total prostatectomy and 7 cases by transurethral resection (TUR-P) after oral administration of UFT. The concentration of FT, 5-FU and uracil in the tumor tissue (micrograms/g) were 5.920 +/- 5.902, 0.018 +/- 0.012 (T/S; 2.20) and 7.785 +/- 4.151 in 4 patients treated by total prostatectomy and 1.943 +/- 1.355, 0.024 +/- 0.010 (T/S; 1.46) and 4.616 +/- 2.848 in 7 patients treated by transurethral resection of prostate. The concentrations of FT, 5-FU and uracil in the tumor tissue did not increase as compared with those in normal tissue in 4 cases treated by total prostatectomy.     

Evaluation of the prostate peripheral zone/capsule in patients undergoing radical cystoprostatectomy: defining risk with prostate capsule sparing cystectomy

OBJECTIVES: Prostate capsule sparing cystectomy has been performed in conjunction with orthotopic diversion to preserve sexual function and improve urinary control. Because concerns remain regarding incomplete surgical resection, we evaluated the risk of urothelial and prostate cancer in a series of patients undergoing radical cystoprostatectomy. METHODS: A total of 35 men undergoing radical cystoprostatectomy (August 2003-August 2005) had separate submission of the prostate peripheral zone/capsule from the prostate adenoma and bladder after surgery. These specimens were evaluated for bladder and prostate cancer grade, stage, and largest diameter of prostate cancer. Patient records were reviewed for demographic and medical information. Clinical variables were compared between patients with and without carcinoma involving the prostate using standard statistical software. RESULTS: Of patients, 57% had cancer involving the prostate at radical cystoprostatectomy. There were 9 patients (26%) who had urothelial carcinoma involving the prostate; only prostatic urethral biopsy identified these patients before radical cystoprostatectomy. Prostate adenocarcinoma was evident in 16 of 35 (47%) patients, with a majority involving the prostate peripheral zone/capsule (43%). There were 4 patients (11%) who had clinically significant prostate cancer (Gleason sum >6 or tumor volume >0.5 cm(3)). Patients with prostate cancer were significantly older than patients without prostate cancer (P = 0.01). CONCLUSIONS: No clinical variable can confidently predict patients with prostate cancer involving the prostate. Because a majority of patients undergoing radical cystoprostatectomy have cancer involving their prostate, preoperative evaluation with prostatic urethral and prostate biopsy may be useful to guide patient selection for prostate capsule sparing cystectomy.     

Autocrine expression of neurotrophins and their receptors in prostate cancer

Previously, it has been demonstrated that the neurotrophins and their receptors are present in human prostate tissue, but neither their functional role nor localization is clearly understood. We studied the expression of neurotrophins and their receptors in prostate cancer. Between 1990 and 1999, 48 prostate cancer specimens were obtained from patients undergoing radical prostatectomy, of whom 25 received neoadjuvant hormonal therapy (NHT) and 23 were untreated. The specimens were analyzed immunohistochemically for neurotrophins (nerve growth factor, brain derived neurotrophic factor, neurotrophin 3, neurotrophin 4/5) and their receptors (TrkA, TrkB, TrkC, p75NTR). Immunohistochemical studies revealed that both benign and malignant prostate gland epithelial cells expressed the neurotrophins and their receptors to various degrees, but no obvious immunopositive reaction was observed in stromal cells. In benign epithelial cells, the neurotrophins were localized to secretory cells and the receptors were localized to basal cells. The neurotrophins, TrkA and TrkC were expressed to a similar extent in prostate cancer specimens obtained from patients both with and without NHT. In contrast, the expression of TrkB was down-regulated and the expression of p75NTR was up-regulated in prostate cancer after hormonal therapy. These findings suggest that neurotrophins are secreted by prostate cancer cells in an autocrine fashion. Neurotrophins may be involved, through their receptors, in the escape mechanism from cell death after androgen depletion found in prostate cancer.