Serum Prostatic Acid Phosphatase Levels Research Articles

Deciphering anti–benign prostatic hyperplasia potential of liangwanoside II based on metabolite profile characterization combined with targeted network pharmacology

Ethnopharmacological relevanceMetapanax delavayi (Franch.) J.Wen & Frodin (Araliaceae), known as “liang wang cha” in China, has been used to treat prostatitis as herbal tea in folk. Recent research suggested that aqueous extract of Metapanax delavayi leaves showed an advantage in anti–benign prostate hyperplasia (BPH) activity, and liangwanoside II was the main component of the active fraction. However, the anti–BPH effect of liangwanosdie II remains to be revealed. Aim of the studyThis study aims to decipher anti–BPH potential of liangwanoside II. Materials and methodsThe anti–BPH effect was evaluated by testosterone propionate–induced BPH rats after oral administration of liangwanoside II at the doses of 30, 60 and 120 mg/kg in vivo. Then, the metabolites of liangwanoside II in rats were identified using ultra–performance liquid chromatography coupled with quadrupole tandem time–of–flight mass spectrometry (UPLC–Q–TOF–MS). Finally, the targeted network pharmacology combined with experimental verification were explored for the mechanism elucidation in vivo. ResultsLiangwanoside II exhibited an anti–BPH effect through reducing the weight of the prostate, prostate index and serum prostatic acid phosphatase level, and improving the prostate tissue morphology in BPH rats. Further, 16 metabolites of liangwanoside II in vivo were identified by UPLC–Q–TOF–MS analysis, in which the prototype compound and 4 metabolites, such as liangwanoside I and serratagenic acid could be absorbed in the plasma and then penetrate the blood–prostate barrier. Then, followed by the targeted network pharmacology and experimental verification, we found that liangwanoside II and its metabolites could jointly involve in the inhibition of the inflammation reaction and hormone imbalance, thus reducing oxidative stress damage, and restoring the balance between cell proliferation and apoptosis, which contributed to the anti–BPH effect of liangwanoside II. ConclusionThe anti–BPH potential of liangwanoside II was revealed using metabolite profile characterization combined with targeted network pharmacology, providing new insight into the development and utilization of liangwanoside II.

Treatment of experimentally induced benign prostatic hyperplasia with Tadalafil and castration in dogs

New methods are being developed for the treatment of benign prostatic hyperplasia (BPH) in dogs. The aim of the present study was to evaluate the effects of Tadalafil on the treatment of experimentally induced BPH in dogs. Twenty-five adult intact male dogs were randomly divided into five groups (n = 5): normal group; dogs induced with BPH and treated with Tadalafil (5 mg/day p.o.); dogs which received Tadalafil (5 mg/day p.o.); dogs induced with BPH and treated with castration; and dogs induced with BPH. For 4 sequential weeks, the hematologic and prostate-specific factors (dihydrotestosterone (DHT), serum prostate-specific antigen (PSA), serum prostatic acid phosphatase (PAP), and canine prostatic specific esterase (CPSE)) were measured. Significant differences were observed in the level of PSA, CPSE, and PAP concentration between the normal vs. BPH-Tadalafil, BPH-castrated, and BPH groups. Treating BPH-induced dogs with Tadalafil or castration significantly declined the serum PSA, CPSE, and PAP levels compared to those of the untreated BPH-induced group. The treatment of normal dogs with Tadalafil did not affect prostate-specific biomarkers in comparison with normal dogs. In conclusion, and according to the prostatic indices, it could be stated that Tadalafil, compared with castration, could be used for the treatment of BPH in dogs.

Inhibition of the Experimental Induction of Benign Prostatic Hyperplasia: A Possible Role for Fluted Pumpkin (Telfairia occidentalis Hook f.) Seeds

Introduction: Pumpkins are thought to be useful in the management of benign prostatic hyperplasia (BPH). The ability of a 15% Telfairia occidentalis seeds incorporated diet to inhibit hormonal induction of BPH in rats was studied. Materials and Methods: Twenty male Wistar rats were divided into 4 equal groups – one test group and three control groups. The test group was placed on the test diet and was given subcutaneous injections of dihydrotestosterone (DHT) and estradiol valerate (ratio 10:1) every other day for 28 days. One control group, ‘no test diet’ (ND) group, received the hormones, but was placed on a normal diet. The other two control groups, ‘no hormone’ (NH) and ‘no hormone/test diet’ (NHD), received subcutaneous olive oil (vehicle) for the same duration and were placed on the test and normal diets, respectively. Markers of BPH and hormone profile were determined using standard methods. Results: The mean relative prostate weight (×10³) was reduced in the test group (3.6 ± 0.2) relative to the ND group (4.0 ± 0.4). The protein content (mg/tissue) of the rats’ prostates decreased significantly (p < 0.05) from 68.3 ± 2.7 in the ND group to 43.4 ± 3.9 in the test group. Serum prostatic acid phosphatase levels (U/l) decreased significantly (p < 0.05) from 4.8 ± 0.4 in the ND group to 4.0 ± 0.9 in the test group. Histological findings corroborate these data. The testosterone:estradiol ratio (×10³) was significantly (p < 0.05) increased from 7.1 ± 0.1 in the ND group to 8.4 ± 0.4 in the test group. Conclusion: The test diet inhibited the induction of BPH in rats and may act by increasing the testosterone:estradiol ratio.

A phase II trial of an adenovirus/PSA vaccine for prostate cancer

3065 Background: Our phase I adenovirus/PSA vaccine trial has proven the vaccine is safe. We are conducting a phase II clinical trial with two separate protocols for patients with recurrent or hormone-refractory prostate cancer assessing toxicity, immune responses, and change in PSA levels. Methods: In Protocol 1 men with recurrent prostate cancer after definitive initial treatment were randomized to arm A (vaccine injection alone at days 0, 30, and 60) or arm B (vaccine injection 14 days after initiation of androgen deprivation therapy). In Protocol 2 men with hormone-refractory disease receive the vaccine alone at days 0, 30, and 60. Each injection consists of 108 pfu of Ad/PSA vaccine suspended in a collagen matrix. All patients return at regular intervals for physical, chemical, radiologic, and immunologic evaluations. Twenty-five patients will be enrolled in arms A and B in Protocol 1 and 32 in Protocol 2. Results: To date 10 patients have completed 3 monthly injections and have been followed a median of 5 months. Median patient age is 70 years (range 61–84), and median enrollment PSA levels are 0.79 ng/ml (range 0.24–3.93) in Protocol 1 and 5.47 ng/ml (range 0.29–11.17) in Protocol 2. Preliminary results show 86% in both protocols demonstrating anti-PSA T cell responses above preinjection levels. 25% have stable serum PSA levels, 50% have decreased levels, and 25% have increased levels. 11% have stable serum prostatic acid phosphatase (PAP) levels, 56% have decreased levels, and 33% have increased levels. Conclusions: These early results from the first few months of this phase II trial demonstrate the induction of anti-PSA T-cell responses in a high percentage of the vaccinated patients and stabilization or declines in serum PSA and PAP levels. No serious vaccine-related toxicities have been identified. No significant financial relationships to disclose.

Prostatic acid phosphatase is a possible tumor marker for intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (LBCL) is a rare and aggressive subtype of diffuse LBCL characterized by disseminated intravascular proliferation of neoplastic lymphocytes. Obstruction of blood flow by tumor cells in a variety of organs can cause an array of clinical changes, including alteration of the neural and spinal system and the respiratory system, as well as skin lesions. It is usually very difficult to diagnose intravascular LBCL in a patient simply from clinical symptoms or laboratory examinations. We here document our findings that serum prostatic acid phosphatase levels in both males and a female (2.2-24.0 microg/L) reflect the presence of intravascular LBCL, changing synchronously in response to chemotherapy. To determine whether prostatic acid phosphatase (PAP) might be a useful tumor marker for early diagnosis, we reviewed five intravascular LBCLs. Immunohistochemically, tumor cells in all cases were positive for anti-PAP antibody. The results were further confirmed in one case by Western-blot analysis and in another by the detection of amplified messenger RNA for PAP in microdissected tumor cells, respectively. PAP has not been detected in 17 lymphomas (diffuse LBCL, 8 cases; follicular lymphoma, 3 cases; T-cell lymphoma, 3 cases; Hodgkin lymphoma, 3 cases) by Western blot analyses. We conclude that serum PAP is a useful tumor marker for intravascular LBCL and that it deserves further investigation in this context.

Elevation of prostate-specific markers after cardiopulmonary resuscitation.

BACKGROUND-Prostate-specific antigen (PSA), acid phosphatase (AP), and prostatic acid phosphatase (PAP) are serum markers for adenocarcinoma of the prostate gland. Previous studies indicated that prostatic ischemia may also produce elevations of PSA. Cardiopulmonary resuscitation (CPR) is frequently associated with profound tissue hypoperfusion. The present study investigated whether PSA, AP, and PAP are influenced by prolonged CPR. METHODS AND RESULTS-PSA, AP, and PAP were assessed immediately, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after prolonged CPR (>5 minutes) in 14 male and 5 female patients. No changes were noted in women. In men, serum levels increased significantly after CPR and gradually decreased to near baseline values after 7 days. PSA, AP, and PAP values above the normal range were observed in 63%, 71%, and 64% of all patients, respectively. Compared with survivors, nonsurvivors exhibited higher peak serum levels of PSA (98.6+/-14.3 versus 1.1+/-2.2 mcg/L; P<0.03), AP (57.0+/-71 versus 8.6+/-8.8 U/L; P<0.05), and PAP (47.0+/-62 versus 5.7+/-8.0 U/L; P=NS). Patients with poor neurological outcome exhibited higher peak serum levels of PSA (86.4+/-135.5 versus 12.0+/-23.8 mcg/L; P<0.05), AP (50.9+/-68.1 versus 8.7+/-9.6 U/L; P=NS), and PAP (41.6+/-59.5 versus 5.8+/-8.8 U/L; P=NS) than patients with good neurological outcome. CONCLUSIONS-Prolonged CPR is frequently associated with increases of PSA, AP, and PAP serum levels. Therefore, PSA cannot be used for diagnosis of adenocarcinoma of the prostate during the first weeks after CPR. Further evaluation of these parameters as additional prognostic markers after CPR is warranted.

The age of the urologist affects the postoperative care of prostate carcinoma patients

Strategies utilized by urologists in managing prostate carcinoma patients after radical prostatectomy vary appreciably. The reason for this is unclear. The authors investigated the effect of practitioner age on management strategies. From among the total of 12,500 American Urological Association (AUA) members, 4467 were randomly selected to receive a custom-designed survey about their care of prostate carcinoma patients after radical prostatectomy. Respondents were asked to describe their follow-up practices for patients treated with curative intent, their motivations regarding postoperative surveillance, their methods of evaluating a postoperative increase in serum prostate specific antigen (PSA) level, and their choices of treatment for patients with recurrent prostate carcinoma. One thousand fifty responses were analyzed. There was a statistically significant influence of practitioner age on the management of at-risk patients, but it was quite small. The typical workup for an elevated postoperative serum PSA level also varied significantly according to practitioner age; older urologists ordered more serum prostatic acid phosphatase levels and computed tomography scans of the abdomen and pelvis, whereas younger urologists ordered more bone scans. The treatment of recurrent prostate carcinoma did not vary significantly according to urologist age. The opinions of older urologists regarding the survival benefits of postoperative surveillance were considerably different from the opinions of their younger colleagues. The results of this study suggest that urologist age accounts for some of the variation in the postoperative management of prostate carcinoma patients. Differences in beliefs regarding the benefits of surveillance may be partially responsible for this. Persuasive clinical research will probably be required to increase the uniformity of practice in this important area.

Prognosis of Patients with Prostate Carcinoma Presenting as Nonregional Lymph Node Metastases

Objective: The mode of progression in patients with prostate cancer with metastasis to nonregional lymph nodes was examined in order to know whether the site of metastasis effects the prognosis of prostate cancer. Methods: From 1986 to 1995 at the Chiba University Hospital, 205 cases of prostatic cancer with distant metastases were experienced. In 17 of them, nonregional lymph node metastases were observed at the diagnosis, of whom 10 also had bone metastases. Results: There was no statistical difference in prognosis between 17 patients with nonregional lymph node metastases and remaining 188 patients with metastatic prostate cancer. In all patients metastasized to nonregional lymph nodes, serum prostate-specific antigen and/or prostatic acid phosphatase levels were elevated. Anti-androgen therapy was effective in 15 cases and 5-year survival rate was 45.8%. Patients without bone metastases at the initial diagnosis could survive longer than those with metastases to bone (p < 0.05). Conclusions: From these observations, endocrine therapy was effective even in patients with distant lymph node metastases.

Prostatic hyperplasia: an unknown feature of acromegaly.

This study was designed to investigate whether GH and insulin-like growth factor I (IGF-I) excess could lead to the development of benign prostatic hyperplasia and/or prostatic carcinoma. Prostatic diameters and volume as well as the occurrence of prostatic diseases were studied by ultrasonography in 10 untreated acromegalic patients less than 40 yr of age and 10 age- and body mass index-matched healthy males. Serum GH, IGF-I, PRL, testosterone, dihydrotestosterone, prostate-specific antigen, and prostatic acid phosphatase levels were assessed. All patients had secondary hypogonadism, as diagnosed by low testosterone levels, and 4 of 10 patients had hyperprolactinemia. After 1 yr of treatment with octreotide (0.3-0.6 mg/day), ultrasound scan and hormone parameters were repeated. The 4 hyperprolactinemic acromegalics were treated with octreotide and cabergoline (1-2 mg/week) to suppress PRL levels. Symptoms due to prostatic, seminal vesicle, and/or urethral disorders or obstruction were experienced by neither acromegalics nor controls. Digital rectal examination revealed no occurrence of prostatic nodules or other abnormalities. Compared to healthy subjects, a remarkable increase in transversal prostatic diameter and volume was observed in acromegalics. In healthy subjects, prostate volume ranged from 15.1-21.8 mL, whereas in acromegalics it ranged from 21.8-41.8 mL. Similarly, an increased median lobe was observed. In fact, the transitional zone diameter was just detectable in 5 of 10 controls, whereas it was measurable in all acromegalics (18 +/- 1.2 vs. 2.8 +/- 0.3 mm; P < 0.001). The prevalence of periurethral calcifications was more than doubled in acromegalics (50%) compared to that in controls (20%). Treatment with octreotide for 1 yr produced normalization of circulating GH and IGF-I levels in 7 of 10 patients. In these 7 patients, ultrasound evaluation showed a significant reduction of the antero-posterior diameter (26.1 +/- 1 vs. 28.9 +/- 1.6 mm; P < 0.01), the transversal diameter (44.9 +/- 2 vs. 48 +/- 2 mm; P < 0.01), and the cranio-caudal diameter (36.5 +/- 1 vs. 41.3 +/- 1.5 mm; P < 0.001), whereas the transitional zone diameter was unchanged (16.4 +/- 1.5 vs. 17.4 +/- 1.7 mm). As a consequence, a significant decrease in prostate volume was recorded (22.1 +/- 1.1 vs. 29.8 +/- 2.5 mL; P < 0.001). Prostate volume increased in 2 of the 3 patients who did not achieve normalization of GH and IGF-I after octreotide treatment. Finally, after treatment, serum testosterone levels were significantly increased (from 1.5 +/- 0.3 to 3.5 +/- 0.3 microg/L), whereas dihydrotestosterone, dehydroepiandrosterone sulfate, delta4-androstenedione, 17beta-estradiol, prostate-specific antigen, and prostatic acid phosphatase were unchanged. Serum PRL levels were suppressed after cabergoline treatment in all 4 hyperprolactinemic patients throughout the study period. In conclusion, prostate enlargement occurs in young acromegalics with a higher than expected prevalence of micro- and macrocalcifications. This suggests that a careful prostate screening should be included in the work-up and follow-up of acromegalic males.

Prostatic acid phosphatase and prostate specific antigen in liver disease

Serum concentrations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) were measured in 51 liver cirrhosis, 37 chronic active hepatitis (CAH) patients and 26 healthy individuals. Elevated PSA levels have been found in 2 of cirrhotic patients while no increase has been detected in CAH and controls. Serum PAP levels have been observed slightly increased in 2 patients with cirrhosis, 2 patients with CAH and 1 control case. Mean PSA and mean PAP values showed no significant difference between groups (p > 0.05). Serum PSA and PAP levels are reliable in diagnosing and monitoring prostate cancer in chronic liver patients and maintain their specificity in this situation.

Differential suppression of serum prostatic acid phosphatase and prostate‐specific antigen by 5‐alpha‐reductase inhibitor

To evaluate the effect of finasteride (Proscar) on the serum levels of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH). Thirty patients on finasteride therapy for BPH formed the study group. Serum PSA and PAP levels were monitored for 2 years while the patients were receiving finasteride. During 12 months of finasteride therapy the serum PSA was suppressed but serum PAP was unaffected. The baseline mean PAP value was 1.303 ng/mL prior to finasteride therapy; this changed to 1.510 ng/mL (P = 0.195) at 6 months and 1.166 ng/mL (P = 0.383) at 12 months. The serum PSA was 2.630 ng/mL at baseline, 1.757 ng/mL (P < 0.001) at 6 months and 1.545 ng/mL (P = 0.001) at 12 months. Further studies are warranted to determine if PAP has a role as a tumour marker in patients whose PSA is suppressed as a result of finasteride therapy.

Radiation therapy for T1 and T2 prostate cancer: Prostate-specific antigen and disease outcome

Objectives To evaluate disease outcome using serum prostate-specific antigen (PSA) as an outcome measure in patients with T1 or T2 prostate cancer treated with radiation therapy in the PSA era. Methods We reviewed the outcome for 461 patients with T1 (n = 205) or T2 (n = 256) prostate cancer followed for a median of 31 months after radiation therapy as the sole initial treatment. Univariate and multivariate analyses were used to delineate significant prognostic factors. Results The freedom from relapse or rising PSA rate was 70% at 6 years and the survival rate was 83%. Although T stage, Gleason grade, serum prostatic acid phosphatase level, and serum PSA level were each significant determinants of outcome in univariate analysis, pretreatment PSA level was the only clearly independent covariate ( P <0.0001) in multivariate analysis. The 5-year actuarial freedom from relapse or from rising PSA levels is shown according to the pretreatment PSA level: 4 ng/mL or less (117 patients), 91%; more than 4 but 10 ng/mL or less (169 patients), 69%; more than 10 but 20 ng/mL or less (118 patients), 62%; and more than 20 ng/mL (57 patients), 38%. PSA doubling times in 75 patients with rising post-treatment profiles ranged from 1.3 to 78.2 months (mean, 14.4; median 11.3). Faster doubling times correlated significantly with adverse pretreatment prognostic factors (high-grade, high pretreatment PSA, and aneuploidy). To date, the survival rate of patients with rising PSA profiles was not depressed below the expected. Conclusions Radiation therapy is an acceptable modality for treating T1 or T2 disease and produces results comparable to those following radical prostatectomy when patients are stratified according to their pretreatment PSA value. The rapid PSA doubling times observed in patients with relapsing disease are more consistent with a “selective” rather than an “aggravation” mechanism.

直腸診, 画像診断では検出できない前立腺癌 (T1c癌) の臨床病理学的検討

Clinical and pathologic characteristics of stage T1c disease (nonpalpable and nonvisible cancer) was studied retrospectively in men who underwent radical prostatectomy in order to better understand this disease entity. Findings in stage T1c disease (16 patients) were directly compared with those in stage T2b disease (11 patients). No significant difference was observed between these groups with regard to age, preoperative serum prostatic acid phosphatase level, prostatic weight, numbers of tumor foci, total tumor volume, volume of index cancer and tumor grade (p > 0.05). Preoperative prostate specific antigen concentration was significantly lower in stage T1c group (p < 0.05). Substantially larger number of patients with stage T1c disease had pathologically organ confined disease when compared with T2b group (86.7% versus 45.5%, p < 0.05). Seventy-five percent (12/16) of stage T1c and 90.9% (10/11) of stage T2b disease were considered clinically significant. Most of stage T1c disease is organ confined and clinically significant. Clinical and pathologic features of these tumors are similar to those in T2b disease. Twenty-five percent of stage T1c disease, however, are small and thus may potentially be overtreated. Enhanced detection of prostate cancer achieved with modern technology can lead to undesirable treatment of clinically insignificant tumors. Preoperative diagnostic modalities which can reliably distinguish groups of tumor with different biological potential are needed to overcome this contradiction.

Prostate Specific Antigen as an Outcome Variable for T1 and T2 Prostate Cancer Treated by Radiation Therapy

Between 1987 and 1991, 269 patients with clinical stage T1 or T2, NO or Nx adenocarcinoma of the prostate underwent external beam radiation therapy as the sole initial treatment and were followed with serial prostate specific antigen (PSA) levels for 9 to 73 months (mean 33, median 30). Of the patients 26 had clinical evidence of disease relapse, 58 had an increasing PSA profile and 62 had either relapse or an increasing PSA. The actuarial incidence of increasing PSA was 30% at 5 years and the incidence of relapse or increasing PSA was 36% at the same time. With relapse or increasing PSA level as an end point, pretreatment PSA level, Gleason grade and serum prostatic acid phosphatase level were individually significant covariates. However, in multivariate analysis only pretreatment PSA level was significant. The 5-year actuarial rates of relapse or increasing PSA according to pretreatment PSA level were 4 ng./ml. or less—14%, greater than 4 to 10 ng./ml.—33%, greater than 10 to 30 ng./ml.—55% and greater than 30 ng./ml.—greater than 80%. Post-irradiation PSA levels at 3 and 6 months provided prognostic information additional to that inherent before treatment. However, the nadir PSA value, achieved typically at 6 to 12 months, was the most significant aspect of posttreatment PSA. Patients with a nadir PSA level of less than 1 ng./ml. fared well, with a 12% incidence of relapse or increasing PSA at 5 years. Nadir values exceeding 1 ng./ml. were associated with an increasing relapse rate as the nadir value increased, and nearly two-thirds of the cases in which the nadir exceeded 4 ng./ml. failed by 2 years. When increasing PSA was used as an end point additional to relapse, the outcome in this series was significantly worse than in an earlier series evaluated without PSA. Comparing these 2 series resulted in an estimate that PSA begins to increase approximately 4 to 5 years before the appearance of clinically overt disease.These results reveal the high significance of pretreatment PSA levels, significance of nadir PSA values after treatment, earlier detection of persistent disease by the increasing PSA profile, and the fact that total and permanent eradication of localized prostate cancer is considerably more difficult than traditionally believed. The therapeutic implications of this series, and the implications on the quantity and quality of patient lives await prospective study.

Changes in immunohistochemical staining of PSA, PAP, and TURP-27 following irradiation therapy for clinically localized prostate cancer

Objectives. To determine if tissue expression of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and a prostate-associated monoclonal antibody (TURP-27) is retained after irradiation therapy and to compare these results with serum levels. Methods. Immunohistochemical tests were performed on prostatic tissue obtained byneedle biopsy or transurethral resection prior to and following definitive irradiation therapy for clinically localized prostatic carcinoma. PSA, PAP, and TURP-27 were studied. Results were compared with serum PSA and PAP values. Results. All 20 preirradiation specimens stained positively for PSA and PAP; 19 of 20stained for TURP-27. All 5 of the initial post-treatment biopsy specimens that showed recurrent tumor stained for all 3 markers. In 2 cases, staining for the 3 markers was greatly diminished. Only 8 of 15 post-treatment biopsy-negative specimens stained for all 3 markers. Six of 15 demonstrated loss of tissue expression for all 3 antigens. One specimen stained for PAP and TURP-27 but failed to stain for PSA. Serum PSA levels paralleled tissue expression in recurrent tumor specimens. However, 3 of the post-treatment biopsy-positive cases with PAP expressing tissue had normal serum PAP levels. Conclusions. No cases of recurrent tumor with marker-negative tissue were identified.However, benign epithelial prostate cells appear to sustain sufficient damage from irradiation to lose the capacity to produce certain proteins. Diminished contribution of benign glands to circulating PSA, in addition to decreased expression in malignant tissues, may explain the lower than anticipated serum PSA levels in patients who progress after irradiation therapy.

Characteristics of prostatc infarcts and their effect on serum prostate-specific antigen and prostatc acid phosphatase

Objectives. To determine how prostatic infarcts affect serum prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels. Methods. Two hundred eighteen clinically benign, whole prostates were obtained atautopsy, completely sectioned, and examined histologically. PSA and PAP levels were determined from premortem serum. Results. Six of the 218 (2.8%) prostates had infarcts. The infarcts were usually multipleand usually located in the central and/or middle concentric zones of the middle third of the prostate without a preference for a particular lobe. Serum PSA by immunoradiometric assay were elevated in all 6 cases. Serum PAP by both enzymatic assay (ACA), and immunoradiometric assay were available for 5 cases and were elevated by both methods in 2 cases, approached elevated levels by both methods in 1 case, and were normal by both methods in 2 cases. The PSA and PAP levels appeared to be affected more by the age than by the size of the infarct. Conclusions. Prostatic infarcts elevate PSA levels more frequently than PAP levels, andprostatic infarcts may be responsible for some unexplained elevations of serum PSA and PAP levels.

Relationship between diurnal rhythm of serum testosterone and two prostatic markers (PSA and PAP) in untreated prostate cancer

Objective. To clarify the relation between diurnal rhythm of serum levels of testosterone and two prostatic markers, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP). Methods. Blood was obtained every four hours during a thirty-two-hour period from fourteen men with untreated prostate cancer. Results. Serum levels of PSA and PAP showed circadian rhythm in 4 and 5 patients, respectively. About half of the remaining patients, the highest or nearly highest peaks of serum levels of PSA or PAP were ob served in the afternoon rather than the morning. In 3 patients, circadian rhythms were not observed in serum levels of PAP, but the fluctuation patterns were the same as those of testosterone and showed synchronous movement. In 7 patients, serum testosterone levels were followed by the same fluctuation pattern for either PSA or PAP after some time delay. Little change in serum levels of PSA was seen throughout the thirty-two-hour period despite large fluctuations of testosterone and PAP levels in 5 patients. Conclusions. Close relation between the fluctuation in serum levels of PSA and PAP, and that in serum levels of testosterone during diurnal periods could be considered. However, the relationship between serum testosterone levels and those of PSA and PAP was ambiguous because of both the difference in the time delay of PSA and PAP in relation to testosterone and the small fluctuation in PSA despite obvious fluctuations in testosterone and PAP in some cases.

Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Investigate the Effect of Finasteride (MK-906) on Stage D Prostate Cancer

A total of 28 untreated patients with asymptomatic, stage D prostate cancer was randomized in a double-blinded fashion to receive finasteride (10mg. per day), a 5α-reductase inhibitor or placebo. Patients were evaluated at 3-week intervals by rectal examination, and serum prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) levels, and at 6-week intervals by bone scan and transrectal ultrasound determinations of prostatic volume. Patients stopped the medication at week 6 at the discretion of the investigator when PSA levels increased from baseline. After 12 weeks all patients were reevaluated.Of the patients 13 received finasteride and 15 received placebo. The 2 groups did not differ statistically with respect to patient age, initial PSA and PAP level, or the extent of metastases on initial bone scan. A statistically significant decrease in the median percentage change from baseline in PSA at weeks 3 and 6 occurred in the finasteride group compared to the placebo group (−22.9% versus −2.9% and −15.1% versus +11.7%, respectively, p <0.05). Finasteride had no effect upon PAP, serum testosterone, prostatic volume or appearance of bone scans.A decrease in serum PSA in the finasteride treatment group suggests that finasteride exerts a minor effect in patients with prostate cancer. This effect does not approach that seen with medical or surgical castration yet because of the potency preserving feature and the lack of toxicity finasteride may warrant further study in the treatment of prostate cancer.

The Risk of Dying of Prostate Cancer in Patients with Clinically Localized Disease

From 1966 to 1979, 360 patients with clinical stages A2, B and Cl prostate cancer underwent staging pelvic lymphadenectomy, and completed a course of combined interstitial radioactive gold seeds and external beam radiotherapy. All patients had a normal serum prostatic acid phosphatase level and a bone scan negative for metastases. All patients were followed until death or for a mean of 7.3 years (range 1.2 to 18.25 years) for those alive at analysis. To determine the risk of dying of prostate cancer we reviewed the records of the 142 patients (39%) who died. At analysis 21% of the patients had died of prostate cancer and 17% of other known causes. The cause of death could not be determined in 4 patients (1%). Cardiovascular disease accounted for a fifth of all deaths.The actuarial risk of death of prostate cancer for all patients was 8 ± 3% (± 2 standard errors) at 5 years and 30 ± 7% at 10 years. The risk of death of all causes was 16 ± 4% at 5 years and 46 ± 7% at 10 years. An increased risk of cancer death was associated with established risk factors, including advanced local disease, poorly differentiated histology, pelvic nodal metastases and distant recurrence. We also noted a substantial risk of cancer death in patients who had local tumor recurrence.While previous studies have reported a relatively low incidence of cancer deaths (4 to 17%) in patients initially diagnosed with localized disease, our data suggest that prostate cancer is the major cause of mortality in such patients. Aggressive curative therapy, regardless of treatment modality, should be considered for localized prostate cancer in men with a life expectancy of 10 or more years.

Prostate irradiation does not affect the serum prostatic acid phosphatase level

Twenty-nine consecutive patients with localized prostatic carcinoma were studied prospectively to assess the effect of radical pelvic irradiation on the serum prostatic acid phosphatase level (SPAPL). The doses of radiation given ranged from 64.00 to 66.00 Gy. SPAPLs were taken before, during and shortly after their treatment. No significant individual variations in SPAPLs were found. When patients with prostatic carcinoma show rises in serum prostatic acid phosphatase during or after pelvic irradiation, these are unlikely to be due to their treatment and occult pelvic nodal or bony disease should be considered.