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Hidetoshi Yamanaka

Publications and source records attributed to Hidetoshi Yamanaka.

At least 19 recordsLinked to original sources

Preparation of a single prostate needle biopsy specimen for histological diagnosis and RNA analysis.

PURPOSE: When a prostate needle biopsy specimen is used for molecular study, a second specimen from the same area as the first one has previously been required for pathological diagnosis. However, we developed a method for obtaining substances such as RNA and we also made pathological diagnosis possible from a single needle biopsy specimen, improving reliability. MATERIALS AND METHODS: Prostate needle biopsy specimens from 118 patients were frozen in optimal cutting temperature compound. Tissue from the upper part of the frozen specimen was sectioned longitudinally for histopathological examination. The remainder of the specimen was placed in TRIzol reagent to extract total RNA for molecular biological investigation. RESULTS: Pathological diagnosis and total RNA extraction (1.6 to 32.7 microg) could be obtained from 1 needle biopsy specimen. When 2 specimens were obtained from the same area of the prostate, pathological diagnoses were discordant in 19% of the cases. CONCLUSIONS: We established a method for histopathological diagnosis in the prostate needle biopsy specimen used for molecular investigation. This single specimen method may facilitate molecular research in prostate cancer.

Aged↗

The case for androgen deprivation as primary therapy for early stage disease: results from J-CaP and CaPSURE.

PURPOSE: We analyzed the outcome of primary androgen depletion therapy, which has gained more attention as a potential therapeutic option in patients with localized or locally advanced prostate cancer as it has been increasingly implemented despite limited data on its therapeutic impact in Japan and the United States. MATERIALS AND METHODS: We analyzed data from CaPSURE and the Japanese Prostate Cancer study. RESULTS: In Japan primary androgen depletion therapy has long been the treatment of choice for localized and locally advanced prostate cancer. Based on CaPSURE data the frequency of primary androgen depletion therapy being chosen to treat localized and locally advanced disease is also increasing in clinical practice in the United States. A study of the outcomes of endocrine therapy is currently being performed in Japan by the Japanese Prostate Cancer Study Group. CONCLUSIONS: It is important to obtain such information about the role of primary androgen depletion therapy for localized and locally advanced prostate cancer from studies of natural history and clinical trials. It is also important to update practical treatment guidelines.

Androgen Antagonists↗

Prostate-specific antigen changes as a result of chlormadinone acetate administration to patients with benign prostatic hyperplasia: a retrospective multi-institutional study.

BACKGROUND: Antiandrogens used to treat benign prostatic hyperplasia (BPH) may affect the diagnosis of prostate cancer by decreasing serum prostate-specific antigen (PSA) values. We conducted a retrospective survey of BPH patients treated with chlormadinone acetate (CMA) and analysed the effect of CMA on their PSA values. METHODS: A chart-based, retrospective, multi-institutional survey of clinically diagnosed patients with BPH who had been treated with CMA (Prostal; 50 mg/day) was conducted. The patients were divided into three groups according to their baseline PSA values: <4 ng/mL, Group I; >or=4 ng/mL and <10 ng/mL, Group II; and >or=10 ng/mL, Group III. The changes in the PSA values from baseline after 16, 26, and 52 weeks of CMA therapy were predicted using a nonlinear regression model analysis. RESULTS: Data from 192 of the 303 enrolled patients were analysed. The predicted percent changes from baseline among all patients after 16, 26, and 52 weeks of treatment were -49.6%, -49.8%, and -49.9%, respectively. The corresponding values were -42.4%, -43.7% and -43.8% in Group I; -57.4%, -58.4% and -58.5% in Group II; and -50.6%, -50.6% and -50.6% in Group III, respectively. CONCLUSION: The PSA values reached a nadir, approximately -50% of the baseline, after 16 weeks of CMA administration and remained at the same level thereafter. When CMA is used to treat BPH patients, the possibility of abnormal increases in PSA associated with prostate cancer must be considered; if prostate cancer is suspected, prompt testing, including a biopsy, should be performed.

Aged↗

Clinical validity of proliferating cell nuclear antigen as an objective marker for evaluating biologic features in patients with untreated prostate cancer.

BACKGROUND: Although Gleason grading may be the most useful system for evaluating biological activity of untreated prostate cancer, lack of interobserver validity with Gleason scores (GS) is an unsolved issue. In this study, the proliferating cell nuclear antigen labeling index (PCNA LI) in untreated prostate cancer was investigated in order to clarify the usefulness of supplemental and objective markers for evaluating the biologic features of prostate cancer. METHODS: Sixty cases of prostate cancer were randomly selected from the cancer registry in Gunma University Hospital for this study. PCNA LI were evaluated using paraffin-embedded biopsy cores taken at diagnosis. Correlation of PCNA LI with the Gleason grading system, clinical stage, serum prostate-specific antigen (PSA) levels and age were evaluated. Cumulative rates of freedom from cause-specific death were also evaluated stratified by various clinicopathologic features, including PCNA LI using Kaplan-Meier analysis. RESULTS: Proliferating cell nuclear antigen labeling index was significantly higher in patients with PSA levels over 100 ng/mL, advanced clinical stage (>T4, N1 or M1 disease), higher Gleason grade or with a higher GS than in those with other clinicopathologic features. The 5-year cumulative rate of death from prostate cancer was significantly higher at 62% in patients with a PCNA LI of 20 or more than those with PCNA LI of less than 20, who accounted for 4%. CONCLUSIONS: Proliferating cell nuclear antigen labeling index in combination with Gleason grading system may be of clinical value in evaluating biologic features and also in predicting cause specific survival of prostate cancer in an objective, reliable and reproducible manner.

Aged↗

Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer.

PURPOSE: To clarify the optimal duration and methods for adjuvant endocrine therapy after external beam radiation therapy (EBRT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Between 2001 and 2003, 215 patients with locally advanced prostate cancer were enrolled in the study. Patients were registered as primary candidates of the study and were treated with 6 months of LHRH agonist, with short-term of antiandrogen treatment for flare-up prevention. Patients with PSA levels below 10 ng/ml after the 6-month endocrine treatment were randomly divided into two arms. Then, a total dose of 72 Gy was given to the prostate. After 14 months of the protocol treatment, patients were treated with continuous androgen ablation (arm 1) or intermittent androgen ablation (arm 2). RESULTS: A total of 188 cases (87%) remained in the protocol. The median PSA level at entry was 25.3 ng/ml. The Gleason score was 2-6 in 32 cases (16%), 7 in 94 cases (48%), and 8-10 in 68 cases (35%). The median PSA level showed a remarkable decrease to 1.1, 0.2, and 0.1 ng/ml, after 6, 8, and 14 months of the protocol treatment, respectively. Of the 157 cases treated with EBRT, 153 cases (97.5%) had no biochemical failure in the mean follow-up of 17.3 months. CONCLUSIONS: The present study may reveal the possibilities of intermittent endocrine therapy after EBRT. However, the follow-up interval is short and little can be said about the results observed so far, exception of acute tolerance and patient acceptance of the protocol.

Adenocarcinoma↗

Prostate carcinoma detection and increased prostate-specific antigen levels after 4 years in Dutch and Japanese males who had no evidence of disease at initial screening.

BACKGROUND: In the current study, the authors set out to investigate the possibility that increased prostate-specific antigen (PSA) levels in Dutch and Japanese men without suspicious findings at initial prostate cancer screening were indicative of the risk of newly developing clinical malignancy in the Netherlands and Japan. METHODS: Between 1992 and 2000, 2650 men ages 55-74 years who had PSA levels < 4.0 ng/mL and no suspicious findings on digital rectal examination were entered into the current study from a population-based prostate cancer screening cohort in Gunma Prefecture, Japan. In addition, between 1994 and 1997, 3163 men with the same clinical background were entered into the current study from the Rotterdam (Netherlands) Section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Prostate carcinoma incidence and the cumulative probability of freedom from PSA increases to levels > 2.0, 3.0, and 4.0 ng/mL, respectively, after 4 years of observation were compared between the Japanese and Dutch populations. The predictive value of initial PSA level, age at study entry, and geographic location also were investigated using Cox proportional hazards models. RESULTS: The overall risk of developing prostate carcinoma during the 4-year observation period was significantly higher for the ERSPC Rotterdam cohort (5.2%) compared with the Gunma cohort (1.6%). The cumulative probability of freedom from prostate carcinoma detection and freedom from an increase in PSA levels to >/= 4.0 ng/mL (PSA progression) decreased significantly with increasing initial PSA level and did not differ significantly between Japanese and Dutch patients whose initial PSA levels fell within the same range (0.0-0.9, 1.0-1.9, 2.0-2.9, or 3.0-3.9 ng/mL). Multivariate analysis also revealed that after controlling for age and initial PSA level, the probability of PSA progression was the same for Japanese and Dutch men. Initial PSA level was the only variable found to be significantly predictive of PSA progression on multivariate analysis (P < 0.0001). CONCLUSIONS: The risk of developing prostate carcinoma within a given 4-year period is greater for Dutch males ages 55-69 years compared with their Japanese counterparts, because the former have higher PSA levels. Nonetheless, there appears to be no significant difference in prostate carcinoma risk between Dutch and Japanese males whose baseline PSA levels fall within the same range.

Age Distribution↗

Effect of androgen concentration on seminal vesicle blood flow in rats-establishment of new highly sensitive simultaneous androgen measurement method.

OBJECTIVES: To clarify the effect of androgen concentration on blood flow regulation in seminal vesicles and to identify the androgen most responsible for this effect. METHODS: The androgen concentrations in the seminal vesicles and the seminal vesicle blood flow were measured at 0, 3, 6, 12, 24, 48, and 72 hours after castration. The androgen concentration was measured with a newly developed highly sensitive simultaneous androgen quantification method that uses liquid chromatography-tandem mass spectrometry. The blood flow was measured with the radioactive microsphere injection method. The change in seminal vesicle blood flow in 6-hour castrated rats after administration of 3 mg/kg testosterone, 3 mg/kg dihydrotestosterone (DHT), 3 mg/kg dehydroepiandrosterone, or 3 mg/kg testosterone plus 20 mg/kg finasteride was evaluated. RESULTS: A correlation was observed between the DHT concentration and blood flow in the rat seminal vesicle after castration. The DHT concentration and blood flow decreased after castration to 31.6% and 37.9%, respectively, of the normal level at 6 hours. The decline in DHT concentration and blood flow decreased further thereafter to 2.2% and 18.1%, respectively, of the normal level at 72 hours. Both testosterone and DHT fully restored the organ blood flow in castrated rat seminal vesicles. However, the blood-flow-increasing effect of testosterone was attenuated by more than 50% when administered in combination with finasteride. Dehydroepiandrosterone did not increase seminal vesicle blood flow. CONCLUSIONS: The results of our study showed a strong correlation between the organ DHT concentration and blood flow in rat seminal vesicles. Of the various androgens, the most active androgen in the regulation of seminal vesicle blood flow was DHT.

Androgens↗

[Cancer screening].

The purpose of cancer screening is to widen the difference between morbidity and mortality of the target cancer. Since 1983 cancer screening has been supported by the Japanese government. Initially it covered gastric and cervical cancer with lung, breast and endometrial cancers supported from 1987 and colorectal cancer in 1992. Since 1998 support for cancer screening has been transferred to local government. It is generally accepted that the uptake of screening services is too low. Estimates for Japan suggest that at best 30% of the eligible population accept the services. In other parts of the world screening is more widely accepted, for example, 67% for breast cancer and 79% for cervical screening in the USA. Barriers within Japan for increasing screening are complex and include, legal, ethical, financial, technical infrastructure, data related matters and the level of understanding and education of the general public. In 2000 the MHLW conducted an evaluation of cancer screening in terms of usefulness and effectiveness. It concluded that fair or better evidence for reduction in mortality existed for cervical cancer (cytology), breast cancer (mammography with clinical examination for women aged > or = 50 years), colorectal cancer (faecal occult blood test), gastric cancer, lung cancer and liver cancer. As a step towards improving screening services and their uptake by the general public a new Research Centre for Cancer Prevention and Screening was established at the National Cancer Centre in October 2003. This and other initiatives will build on the progress of the past 20 years but it is generally agreed that there is still have a long way to go.

Adult↗

Rectal bleeding after hypofractionated radiotherapy for prostate cancer: correlation between clinical and dosimetric parameters and the incidence of grade 2 or worse rectal bleeding.

PURPOSE: To investigate the incidence and severity of rectal bleeding after high-dose hypofractionated radiotherapy (RT) for prostate cancer, and to explore the factors affecting the incidence of Grade 2 or worse rectal bleeding. METHODS AND MATERIALS: The data of 52 patients who had been treated by external beam RT for localized prostate cancer between 1999 and 2002 were analyzed. All the patients had received hypofractionated external beam RT to a total dose of 69 Gy in 3-Gy fractions, three fractions weekly. The clinical and dosimetric factors affecting the incidence of Grade 2 or worse late rectal bleeding were analyzed by univariate and multivariate analyses. The effect of the percentage of the whole rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose (V(30), V(50), V(80), and V(90), respectively) on the incidence of rectal bleeding was evaluated. RESULTS: Of the 52 patients, 13 (25%) developed Grade 2 or worse rectal bleeding. One patient who needed laser coagulation and blood transfusion for the treatment of rectal bleeding was classified as having Grade 3 rectal bleeding. The median time to the development of Grade 2 or worse rectal bleeding was 11 months. The results of the univariate analysis revealed that the presence of a history of diabetes mellitus (p < 0.001), and V(30) >/= 60%, V(50) >/= 40% (p < 0.05), V(80) >/= 25%, and V(90) >/= 15% (p < 0.001) were statistically significant risk factors for the occurrence of Grade 2 or worse rectal bleeding. The results of the multivariate analysis revealed that a history of diabetes mellitus was the most statistically significant risk factor for the occurrence of rectal bleeding after hypofractionated RT for prostate cancer (p < 0.05). CONCLUSION: A history of diabetes mellitus was the most statistically significant risk factor for the occurrence of Grade 2 or worse rectal bleeding after high-dose hypofractionated RT, although dosimetric factors were also closely associated with the risk of rectal bleeding.

Aged↗

Direct regulation of prostate blood flow by vascular endothelial growth factor and its participation in the androgenic regulation of prostate blood flow in vivo.

Previous studies on prostate blood flow regulation have indicated that androgen regulates prostate blood flow. However, the mechanism responsible for this regulation is unknown. In the present study, we focused on the effects of vascular endothelial growth factor (VEGF), a key factor responsible for angiogenesis and androgenic blood flow regulation. We examined in vivo the effect of VEGF on prostate blood flow and its participation in the androgenic regulation of this blood flow using a castrated rat model following subcapsular intraprostatic injection method. We found that VEGF is involved in blood flow regulation with an activity equal to that of dihydrotestosterone (DHT). The effect of VEGF on prostate blood flow was already seen at 30 min after the administration. The elevating effect of DHT on castrated rat prostate blood flow was abolished by coadministration of DHT with neutralizing anti-VEGF antibody. The change in VEGF-A mRNA expression in response to androgen stimulation was examined by double-fluorescent probe quantitative PCR (Taqman PCR). The results showed that androgenic regulation of VEGF gene expression occurred shortly after androgen stimulation. VEGF gene up-regulation was abolished or down-regulated by coadministration of neutralizing anti-VEGF antibody. This is the first report on the importance of VEGF in the androgenic regulation signaling pathway that affects prostate blood flow. Alternative treatment targeted toward anti-VEGF activity as a substitute for ordinary antiandrogenic therapy may be effective against prostate diseases, especially those with androgen-independent and hyperhemorrhagic status.

Androgens↗

External beam radiotherapy for clinically node-negative, localized hormone-refractory prostate cancer: impact of pretreatment PSA value on radiotherapeutic outcomes.

PURPOSE: To analyze the results of clinically node-negative, localized hormone-refractory prostate cancer treated with external beam radiotherapy (EBRT) and to investigate the potential prognostic factors that influenced the therapeutic outcome. METHODS AND MATERIALS: Fifty-three patients who had developed localized hormone-refractory prostate cancer were treated with EBRT between 1994 and 2001. According to the 1992 American Joint Committee on Cancer clinical stage, 4 patients had T2 and 49 had T3 at the start of RT, and 14 patients had a Gleason score <7, 14 had a Gleason score of 7, and 23 had a Gleason score of 8-10. All patients were treated with EBRT using the unblocked oblique four-field technique, with a total dose of 69 Gy. The fraction dose was 3 Gy three times weekly. The median follow-up after RT was 35 months (range, 8-96 months) and after androgen ablation was 73 months (range, 42-156 months). RESULTS: Of 53 patients, 15 patients subsequently developed clinical relapse, including locoregional and/or distant metastases. The site of first relapse was bone metastasis in 10, lymph nodes in 3, and local failure in 2 patients; 3 patients died of prostate cancer during the analysis period. The 3-year and 5-year cause-specific survival rate was 94% and 87%, respectively, and the 3-year and 5-year clinical relapse-free survival rate was 78% and 56%, respectively. The univariate analysis revealed that a short prostate-specific antigen (PSA) doubling time and high PSA value at the start of RT and a high Gleason score were statistically significant factors for the risk of clinical relapse. Multivariate analysis demonstrated that the PSA value (PSA or=15 ng/mL) at the start of RT was an independent prognostic factor. CONCLUSION: EBRT could be a treatment of choice for clinically node-negative, localized, hormone-refractory prostate cancer.

Aged↗

Cumulative probability of PSA increase above 4.0 NG/ML in population-based screening for prostate cancer.

Routine screening for prostate cancer remains controversial. However, it is very important to show how the optimal rescreening interval should be set for men who want to be screened after informed consent. To solve this issue, the risk of prostate-specific antigen (PSA) increase above 4.0 ng/ml relative to baseline PSA levels and age was investigated. Between 1988 and 2000, 7,757 subjects screened twice or more and also with baseline PSA levels of 4.0 ng/ml or lower were enrolled in our study. All serum PSA levels were measured by E-test Tosoh II PA assay at one center. Interval PSA levels for men undergoing screening with a greater than 1 year interval were calculated on the assumption that PSA levels changed over time in a simple exponential fashion. Then, the cumulative rate of freedom from PSA increase above 4.0 ng/ml was estimated using the Kaplan-Meier technique stratified by baseline PSA ranges of 0.0 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 ng/ml and every 10 years of age ranges. Of the 7,757 subjects, 559 (7.2%) were expected to have had PSA levels increase above 4.0 ng/ml within 5 years after the baseline PSA measurements. The cumulative rate of freedom from the PSA increase above 4.0 ng/ml at 5 years was 98.7%, 92.9%, 70.3% and 38.5% in cases of baseline PSA levels of 1.0 ng/ml or lower, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml and 3.1 to 4.0 ng/ml, respectively. The cumulative rates of freedom from the PSA increase were significantly decreased with the baseline PSA ranges being higher regardless of age range. Re-screening interval should be set stratified by baseline PSA levels, regardless of age and race. Rescreening interval should be set at 1, 1 to 2 and 3 to 5 years for men with baseline PSA ranges of 2.1 to 4.0 ng/ml, 1.1 to 2.0 ng/ml and 0.0 to 1.0 ng/ml, respectively, in individual-based screening. In mass screening system using PSA alone, rescreening interval should be set in the same manner as in individual-based screening, except for men with baseline PSA levels of 1.1 to 2.0 ng/ml, which should be set at 1 year to avoid developing incurable prostate cancer.

Aged↗

Expression of bone morphogenetic protein-7 (BMP-7) in human prostate.

BACKGROUND: It is known that BMP is a factor that strongly induces bone formation in muscle tissue. However, the expression of BMP-7 is not detected in normal bone tissues. Recently, we reported that the level of BMP-7 expression was significantly higher in metastatic bone lesions than in normal bone and that the high expression of BMP-7 in metastatic bone lesions was related to osteoblastic metastasis. The aim of this study was to investigate the level of BMP-7 gene expression in normal prostate glandular tissues, newly diagnosed prostate cancer tissues, and local recurrent prostate cancer tissues. METHODS: Total RNA was extracted from 23 samples of normal prostate glandular tissues, 28 samples of newly diagnosed prostate cancer tissues, and 23 samples of local recurrent prostate cancer tissues. We also examined the expression of BMP-7 in human prostatic epithelial cells (HPECs) under conditions of androgen replacement. After reverse transcription of the RNA samples, the expression of BMP-7 was measured by real-time quantitative polymerase chain reaction (PCR). Glyceraldehyde phosphate dehydrogenase (GAPDH) was used as an internal standard. RESULTS: The level of BMP-7 expression was highest in the normal prostate glandular tissue (P < 0.05). The expression of BMP-7 tended to be lower during the development and progression of prostate cancer. The expression of BMP-7 in prostate epithelial cells treated with 10(-7) M dihydrotestosterone (DHT) was significantly higher than in the DHT-free control (P = 0.0285). CONCLUSIONS: It has been reported that the BMP-7 mRNA level is androgen-dependent in the mouse prostate. The present results suggest that the BMP-7 mRNA level is androgen-dependent in the human prostate, since the expression of BMP-7 was decreased in local recurrent prostate cancer tissues after hormonal therapy and was increased by DHT.

Aged↗

Diagnostic significance of PSA density adjusted by transition zone volume in males with PSA levels between 2 and 4ng/ml.

OBJECTIVE: To investigate the diagnostic significance of prostate-specific antigen (PSA), density (PSAD), and PSAD adjusted by transition zone volume (PSATZD) in men with PSA levels between 2.1 and 4.0ng/ml. METHODS: Between 1993 and 2000, 69 men with PSA levels between 2.1 and 4.0ng/ml underwent transrectal ultrasonography (TRUS) and 8-core prostate biopsy. Diagnostic accuracies for various cut-offs of PSAD and PSATZD were investigated according to subdivided PSA levels of 2.1 to 3.0ng/ml and 3.1 to 4.0ng/ml. RESULTS: The detection rate of prostate cancer was 21.7% (15/69). The percentage of patients with extracapsular disease was 33.3% (5/15) and primary Gleason grade 4 or 5 was obtained in 4 (26.7%) patients. The transition zone volume and PSATZD in cancer cases were significantly different in comparison with those in non-cancer cases. The area under the receiver operating characteristic curve for PSATZD was significantly higher in comparison with that for PSAD in the same subdivided PSA ranges. The diagnostic efficiency for PSATZD was higher than that for PSAD. The diagnostic efficiency showed the highest value at the cut-off level for PSATZD of 0.23 and 0.28 in men with PSA levels of 2.1 to 3.0ng/ml and 3.1 to 4.0ng/ml, respectively. CONCLUSIONS: The use of PSATZD cut-offs as a biopsy indication may reduce many unnecessary biopsies without missing most prostate cancer cases in the PSA range of 2.1 to 4.0ng/ml.

Adult↗

Comparative study on the prevalence of clinically detectable prostate cancer in patients with and without bladder cancer.

OBJECTIVES: To investigate the prevalence of prostate cancer in patients with a past or present history of bladder cancer compared with age-matched control subjects in population-based screening for prostate cancer. METHODS: Between 1998 and 2000, 106 patients who were followed up in the outpatient clinic for bladder cancer (case cohort) and 1060 age-matched men who participated in screening for prostate cancer (control cohort) were enrolled in this study. Serum prostate-specific antigen (PSA) levels were measured for all participants, and all participants underwent digital rectal examination (DRE). The PSA distribution and prevalence rate of prostate cancer were compared between these two cohorts. RESULTS: The serum PSA levels were significantly greater in the case cohort than in the control cohort. The detection rate of prostate cancer was 12.3% (13 of 106) and 1.5% (16 of 1060) in the case and control cohorts, respectively. The biopsy compliance for those with abnormal PSA and/or DRE findings was significantly lower (31%) in the control cohort than in the case cohort (84%). If all those in the control cohort with abnormal PSA and/or DRE findings had undergone prostate biopsies, another 26 cases of prostate cancer might have been detected. The expected detection rate of prostate cancer in the control cohort was high at 4.0% (42 of 1060); however, this was still significantly lower than that in the case cohort. CONCLUSIONS: Patients with a present or past history of bladder cancer could be a high-risk group for developing or having prostate cancer. Additional studies should be conducted to confirm this.

Adenocarcinoma↗

Androgen-dependent blood flow control and morphological changes of the capillaries in rat prostate.

To clarify the effect of androgens on the microcirculation of the prostate, organ blood flow and ultrastructural features of the capillaries were investigated. In the ventral prostate (VP) of adult Wistar rats, organ blood flow was measured using a laser Doppler flowmetry, and the morphological features of the subepithelial capillaries were investigated and their luminal area was measured using transmission electron microscopy and a computed image analyzer at 1, 2, 3, and 7 days after castration, and 2 days after castration and gradational testosterone supplementation. The capillaries of the VP were classified into three types; oval opened (type 1), intermediate (type 2) and collapsed (type 3). Organ blood flow reduced from 40.5 to 27.7 mL/min/100 g (p < 0.0001) and the luminal area of the capillaries reduced from 13.5 to 4.5 microm2 (p < 0.0001) 2 days after castration. These reductions of the blood flow and the luminal area were gradationally prevented by testosterone supplementation. In the morphological features of the capillary, type 1 had rapidly shifted to types 2 and 3 after castration, and the shift of the capillary type was significantly prevented by the testosterone supplementation. These results clearly demonstrated that the androgen-dependent ultrastructural and morphological features in subepithelial capillaries revealed local microcirculatory conditions correlating the organ blood flow changes in VP.

Animals↗

Characteristics of patients with prostate cancer who have initially been treated by hormone therapy in Japan: J-CaP surveillance.

OBJECTIVE: Hormone therapy for prostate cancer has empirically prevailed in Japan. We planned to evaluate the trends and outcome of hormone therapy for establishing an adequate guideline. METHODS: Patients with prostate cancer who were initially treated by hormone therapy were registered through the J-CaP registration system. This report summarizes the background factors. RESULTS: From January 2001 to October 2003, 17,872 patients were registered from 395 institutes throughout Japan. The background factors of 17,312 patients were analyzed. The 17,872 patients were estimated as composing more than half of newly diagnosed prostate cancer patients in Japan. Of these, 22.9, 35.1, 32.9 and 8.6% belonged to T1, T2, T3 and T4, respectively. For the purposes of hormone therapy, 77.5% was primary hormone therapy. Neoadjuvant setting and adjuvant setting were 18.1 and 4.3%, respectively. About 60% of the hormone therapy was combined hormone therapy with LH-RHa plus anti-androgens. CONCLUSION: Irrespective of patients' age, TNM, stage of illness, or histological background, the majority of prostate cancer patients in Japan are receiving hormone therapy. It is necessary to evaluate whether this trend is merely a continuation of past experience of Japanese urologists or if there is a difference in the profile of effect and side-effect in the case of Japanese patients compared to therapy given in Westerners.

Aged↗

The risk of rapid prostate specific antigen increase in men with baseline prostate specific antigen 2.0 ng/ml or less.

PURPOSE: We estimated the risk of a rapid prostate specific antigen (PSA) increase in men with a low baseline PSA range of 0.0 to 2.0 ng/ml to investigate the validity of setting a re-screening interval of more than 1 year. MATERIALS AND METHODS: Between 1988 and 1999, 6,252 men with baseline PSA 2.0 ng/ml or less without suspicious findings on digital rectal examination (DRE) and 7,304 with the same baseline PSA who did not undergo DRE at the time of baseline PSA measurement were re-screened. The risks of a PSA increase to 4.1 to 10.0, 10.1 to 20.0 and greater than 20.0 ng/ml were investigated and stratified by re-screening interval, baseline DRE status, and subdivided baseline PSA ranges of 0.0 to 1.0 and 1.1 to 2.0 ng/ml. RESULTS: A total of 28 cases (0.2% of 13,556) of prostate cancer were detected after an average re-screening interval of 3.6 years. High PSA above 10 ng/ml at diagnosis was noted in 5 patients (18%), including 2 with a great PSA increase to 1,928 and 298 ng/ml at re-screening intervals of 4 and 6 years, respectively. CONCLUSIONS: Setting 4 to 5-year re-screening intervals for PSA measurements in men with PSA 1.0 ng/ml or less can decrease the cost of PSA tests without lowering sensitivity. A re-screening interval for PSA measurement should be set annually for men with PSA 1.1 to 2.0 ng/ml to minimize the risk of missing aggressive cancer.

Aged↗