[Show abstract][Hide abstract] ABSTRACT: Background
High intensity focused ultrasound (HIFU) is a method of delivering acoustic energy to a focal point and is expected to induce tissue thermal ablation. Transrectal HIFU was applied to symptomatic benign prostatic hyperplasia (BPH) for relief of intravesical obstruction without injury to surrounding tissue. The clinical effectiveness and safety of transrectal HlFU were investigated. Methods: Thirty-seven Japanese men with symptomatic BPH were treated with HIFU. The treatment was minimally invasive; operating time was less than 40 minutes, and a post treatment indwelling catheter was left in place for 3–4 days.Results:me maximum urinary flow rate (ml. per second) increased from 7.6 ± 0.6 to 9.3 ± 0.6 at three months in 37 patients (P < c 0.05). During the same period the International Prostatic Symptom Soore and Quality of Life score (points) decreased from 23.6 ± 1.4 to 10.5 ± 0. 5.2 ± 0.3 to 2.6 ± 0.1 (P < 0.001), respectively. Overall response estimated by these three individual parameters were as follows; excellent 18.9 %, good 48.6 %, fair 70.8% and poor 21.6% at three months. Magnetic resonance imaging using an endorectal coil showed coagulative necrosis defined in the therapy zone at one month after treatment. Side effects were transient urinary retention in six patients (16.2%), gross hematuria in four patients (10.8%) and hematospermia in four patients (10.8%). There was almost no intraoperative blood loss.Conclusions:Transrectal HIFU treatment of symptomatic BPH is safe, reduces symptoms significantly. and leads to a slight increase in uroflow.
International Journal of Urology 06/2007; 2(3):176 - 180. DOI:10.1111/j.1442-2042.1995.tb00449.x · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background The prevalence of lower urinary tract symptoms was determined by survey as an initial step in estimating the significance of benign prostatic hyperplasia (BPH) in Asia and Australia.Methods The symptom index (0 to 35) and quality-of-life (QOL) index (0 to 6) of the international prostate symptom score were measured in 7588 men in 9 Asian countries and 146 men in Australia.Results The percentages of Asian men considered to be symptomatic (symptom index ≧ 8) were 18%, 29%, 40%, and 56% in the age groups of 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years, respectively. For Australian men, these figures were 36%, 33%, and 37% in the 50 to 59, 60 to 69, and 70 to 79 year age groups, respectively.Conclusions Our estimates indicate that the prevalences of symptomatic men in Asia and Australia are similar to or greater than those in Europe and America, and suggest BPH is similarly common in these areas.
International Journal of Urology 06/2007; 4(1):40 - 46. DOI:10.1111/j.1442-2042.1997.tb00138.x · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy of primary hormone therapy for localized or locally advanced prostate cancer, by analysing the 10-year survival rates for men with localized or locally advanced prostate cancer treated with primary hormone therapy or prostatectomy.
Between February 1993 and March 1995, men with T1b, T1c or T2-3 N0M0 prostate cancer were enrolled. In all, 176 men who had a prostatectomy were assigned to Study 1 and were given adjuvant luteinizing hormone-releasing hormone (LHRH) agonist; 151 men who did not have a prostatectomy were assigned to Study 2 and had LHRH agonist monotherapy or combined androgen blockade. They were followed until death, loss to follow-up, or until the end of the observation period (31 March 2004). We analysed all cases in each study as a single population, and compared Study 1 with Study 2.
The mean patient ages were 67.2 years in Study 1 and 75.7 years in Study 2. During a median of 10.4 years of follow-up, 20 men in Study 1 and 17 in Study 2 died from prostate cancer, and 21 men in Study 1 and 50 in Study 2 died from other causes. In Study 1, the 10-year overall survival rate was 73% and the 10-year cause-specific survival rate was 86%, vs 41% and 78% in Study 2. Overall survival curves were similar to expected survival curves in both studies. There was no significant difference between studies in cause-specific survival.
The progression of prostate cancer was retarded by primary hormone therapy in men with localized or locally advanced prostate cancer. With primary hormone therapy or prostatectomy, the men had a life-expectancy similar to that of the normal population.
BJU International 10/2006; 98(3):573-9. DOI:10.1111/j.1464-410X.2006.06349.x · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of preoperative androgen deprivation on the outcomes of prostate cancer patients who received radical prostatectomy and subsequent adjuvant endocrine therapy have not yet been fully evaluated.
Patients with stage A(2), B or C prostate cancers were randomized to one of two groups: group I (n = 90), who received androgen deprivation (leuprolide and chlormadinone acetate) for 3 months followed by radical prostatectomy and subsequent adjuvant endocrine therapy (leuprolide alone), and group II (n = 86), who underwent the surgery followed by 3-month androgen deprivation (leuprolide and chlormadinone acetate) and subsequent adjuvant endocrine therapy (leuprolide alone). The effects of preoperative androgen deprivation on survival, clinical relapse (serum prostate specific antigen, PSA, above the normal level, local recurrence, or distant metastases), and PSA relapse (PSA above the detectable level) were evaluated at 5 years or later after treatment.
There were no significant differences in overall, cause-specific, clinical relapse-free, or PSA relapse-free survival rates between the two groups. In a subanalysis, no prostate cancer deaths or clinical relapses were noted in 29 patients with organ-confined disease (OCD: negativity of capsular invasion, seminal vesicle invasion, surgical margins or nodal involvement). The odds ratio for OCD depending on group assignment was 2.44 (95% confidence interval, CI 1.04-5.72), for group I, demonstrating a higher probability of having OCD. This ratio was increased to 4.00 (95% CI 1.06-15.16) if the analysis was conducted in a subpopulation with prostate specific antigen levels less than 35.6 ng/mL and with clinical stage B or C cancers.
Preoperative androgen deprivation has no demonstrable benefit in 5-year outcomes for patients undergoing radical prostatectomy and adjuvant endocrine therapy. However, it did increase the probability of OCD, which was associated with no clinical relapse during the follow-up. A longer observation is needed to clarify the exact extent of the benefits in terms of survival.
International Journal of Urology 06/2004; 11(5):295-303. DOI:10.1111/j.1442-2042.2004.00795.x · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We retrospectively compared the 5-year survival rates of T1b-T3N0M0 prostate cancer patients treated either by endocrine therapy plus radical prostatectomy or endocrine therapy alone.
Clinical T1b-T3N0M0 prostate cancer patients were enrolled at 104 institutions in Japan. They were assigned to study 1 (n = 176), if they were indicated to prostatectomy, if not indicated, they were assigned to study 2 (n = 151). The indication of prostatectomy was based on the clinical judgement of physicians and/or patients. Those assigned to study 1 underwent prostatectomy and adjuvant endocrine therapy with or without preoperative androgen deprivation. Those assigned to study 2 were treated with leuprorelin acetate with or without chlormadinone acetate. They were followed-up every 3 months until death or for 5 years and over.
Those assigned to study 1 were younger (mean age 67.2 vs 75.7 years), less advanced in clinical stage, and had lower prostate specific antigen levels (mean 43.8 vs 103.6 ng/mL). Death for any reason was observed less frequently in study 1 (n = 29, 16%) than study 2 (n = 50, 33%), and the 5-year overall survival rate was higher in study 1 (87 vs. 68%). However, prostate cancer deaths were comparatively seldom (9% in study 1 and 7% in study 2), resulting in the identical 5-year cause specific survival rate in both study groups (91%). In both study groups the overall survival was almost equal to the natural survival of age-matched men.
Endocrine therapy offers a reasonable survival rate in T1b-T3 prostate cancer patients within a 5-year follow-up. Observation will be extended to determine 10-year outcomes.
International Journal of Urology 05/2004; 11(4):218-24. DOI:10.1111/j.1442-2042.2003.00781.x · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of primary hormonal therapy for patients with localized and locally advanced prostate cancer.
Patients with stage T1b-T3 prostate cancer who were not scheduled for radical prostatectomy were allocated into two groups: group 1 (73 men) received luteinizing hormone-releasing hormone (LHRH) agonist monotherapy and group 2 (78 men) received LHRH agonist and chlormadinone acetate. Patients were followed using serum prostate specific antigen levels, prostate size and the detection of distant metastasis for 5 years.
The median (range) follow-up was 78 (63-87) months. The 5-year progression-free survival rate was significantly higher in group 2 (68%) than in group 1 (47%). However, the overall and cause-specific survival rate at 5 years were similar in both groups, at 72% and 93% in group 1, and 64% and 89% in group 2, respectively.
The overall survival rates of the both groups were no different from that of the normal Japanese population of the same age group. Although this study did not include an untreated group, i.e. watchful waiting, these results might indicate the usefulness of primary hormonal therapy in controlling localized and locally advanced prostate cancer. The 5-year observation period is still short and the study is continuing to determine the 10-year survival.
BJU International 02/2003; 91(1):33-6. DOI:10.1046/j.1464-410X.2003.04014.x · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 65-year-old man presented with the complaint of gross hematuria. Cystoscopy revealed a sessile tumor on the left bladder wall. It was diagnosed as primary signet ring cell carcinoma of the bladder (T3bN0M0). The patient did not want surgical treatment. Therefore, three courses of arterial infusion of carboplatin were administered at 3-week intervals. Complete remission was obtained and has been maintained for 44 months. Our case appears to be the first report of successful treatment with chemotherapy alone of an infiltrating signet ring cell carcinoma of the bladder.
[Show abstract][Hide abstract] ABSTRACT: A kind of lactic acid bacteria, Lactobacillus casei strain Shirota, shows antitumor activity in experimental animals. One clinical trial using L. casei showed a significant decrease in the recurrence of superficial bladder cancer. So, to assess the preventive effect of the intake of L. casei, widely taken as fermented milk products in Japan, against bladder cancer, we conducted a case-control study.
A total of 180 cases (mean age: 67 years, SD 10) were selected from 7 hospitals, and 445 population-based controls matched by gender and age were also selected. Interviewers asked them 81 items. The conditional logistic regression was used to estimate adjusted odds ratios (OR).
The OR of smoking was 1.61 (95% confidence interval: 1.10-2.36). Those of previous (10-15 years ago) intake of fermented milk products were 0.46 (0.27-0.79) for 1-2 times/week and 0.61 (0.38-0.99) for 3-4 or more times/week, respectively.
It was strongly suggested that the habitual intake of lactic acid bacteria reduces the risk of bladder cancer.
Urologia Internationalis 02/2002; 68(4):273-80. DOI:10.1159/000058450 · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background : The majority of patients with localized and some cases of locally advanced prostate cancer undergo radical prostatectomy. However, radical prostatectomy cannot always be selected for those patients. In this situation, primary hormone therapy is an alternative treatment option. We have designed a prospective randomized study of the effects of primary hormone therapy for such patients. Methods : A total of 151 patients with T1b, T1c, T2a, T2b or T3a prostate cancer who were not scheduled for radical prostatectomy were enrolled into this study. Patients were randomly allocated into two groups; Group I received luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy (leuprorelin acetate depot, 3.75 mg monthly) and Group II received LH-RH agonist in combination with chlormadinone acetate (100 mg/day). Effects on serum prostate-specific antigen level, progression-free survival and survival were observed for 2 years. Results : The reasons why radical prostatectomy was not scheduled were poor risk for surgery (38%), patient’s wish (32%) and physician’s recommendation (30%). After 12 weeks of treatment, 49% of the patients in both groups showed a complete response (CR). Of the patients showing a partial response (PR) after 12 weeks of treatment, 25% in Group I and 52% in Group II improved to CR 1 year later ( p < 0.05). Group II showed a longer progression-free survival ( p < 0.05). Progression-free survival rates were 62% (Group I) and 91% (Group II) in T2b patients and 43% (Group I) and 73% (Group II) in T3 patients. Only one patient in each group died from prostate cancer. Conclusions : Early primary hormone therapy is a reasonable treatment option for localized or locally advanced prostate cancer patients if radical prostatectomy was not scheduled. Chlormadinone acetate showed an additive effect with LH-RH agonist, at least in 2 years’ observation.
Japanese Journal of Clinical Oncology 03/2000; 30. DOI:10.1093/jjco/hyd035 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade.
Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate).
There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone.
Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.
Japanese Journal of Clinical Oncology 12/1999; 29(11):562-70. DOI:10.1093/jjco/29.11.562 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of preoperative androgen deprivation were explored in the patients who received radical prostatectomy and subsequent adjuvant endocrine therapy for prostate cancer.
Stage A2, B or C prostate cancers were randomized to one of two groups: (i) group I (n=90), who received androgen deprivation (leuploride and chlormadinone acetate) for 3 months preoperatively followed by radical prostatectomy and adjuvant endocrine therapy (leuploride only); and (ii) group II (n=86), who underwent the surgery followed by 3 month androgen deprivation and subsequent adjuvant endocrine therapy. The effects of preoperative androgen deprivation on clinical relapse (serum prostate specific antigen (PSA) > 1.98 ng/mL, local recurrence or distant metastasis) and PSA relapse (PSA >0.2ng/mL) were evaluated at 2 years after randomization.
There was no significant difference in clinical or PSA relapse-free survival and quality of life measures between the two groups, although relapses occurred significantly more frequently in patients who had more advanced stages, higher pretreatment PSA values or lower histologic differentiation in either group. Subgroup analysis indicated that clinical relapse-free survival in stage C cancer tended to be better in patients with preoperative androgen deprivation than in those patients without it (P< 0.1).
Preoperative androgen deprivation may be beneficial for stage C prostate cancer patients receiving radical prostatectomy and adjuvant endocrine therapy over the 2 year observation period. A longer follow up is needed to clarify the exact extent of benefit in terms of survival and quality of life.
International Journal of Urology 06/1999; 6(5):229-37; discussion 238-9. DOI:10.1046/j.1442-2042.1999.00050.x · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nicotine-induced adrenal medullary hypertrophy in rats has been suggested to be a model for pheochromocytoma. Study conditions for proving such an assertion, however, have not been optimized.
Studies on strain difference, dose dependency, and the time course of catecholamine metabolism in response to nicotine treatment were conducted. Under the putative optimal experimental conditions, metabolic and histologic changes in the adrenal medulla were investigated.
Male Wistar rats treated with a maximum dose of 4 mg/kg per day of nicotine for 9 weeks, including a 2-week lead-in period, developed highly consistent changes in the adrenal medulla. Concerning metabolic indices, the norepinephrine content of the adrenal and the urinary excretion of epinephrine and metanephrine were significantly elevated. Hyperplastic and hyperactive states of the adrenal medulla were also indicated by a morphometric analysis on electron microscopic figures. These showed an enlarged cytoplasmic area, the development of a rough-surfaced endoplasmic reticulum, and an increased number and density of intracellular catecholamine granules. The metabolic changes were found to reverse 3 weeks after the cessation of nicotine administration.
These results provide better-defined experimental conditions for an animal model of pheochromocytoma.
International Journal of Urology 12/1998; 5(6):575-81. DOI:10.1111/j.1442-2042.1998.tb00415.x · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transurethral resection of the prostate (TUR-P) is the gold standard for treating symptomatic benign prostatic hyperplasia (BPH) despite some perioperative morbidity. As a minimally-invasive alternative to TUR-P, a neodymium:YAG laser, and more recently a holmium:YAG laser, have been used in transurethral surgery for BPH. In order to assess the safety and efficacy of various BPH treatments, the outcome in patients treated with transurethral ultrasound-guided laser induced prostatectomy (TULIP), visual laser ablation of the prostate (VLAP) and holmium:YAG laser resection of the prostate (HoLRP) were retrospectively compared.
From May 1995 to August 1996, 60 patients with symptomatic BPH underwent TULIP (n=20), VLAP (n=20), and HoLRP (n=20). All patients were evaluated preoperatively and at 1 and 3 months postoperatively by the International Prostate Symptom Score (IPSS), the IPSS quality-of-life score (QOL), maximum flow rate (MFR), prostate volume, and residual urine volume.
The preoperative mean IPSS was 18.5, 19.3, and 19.6 and the mean MFR was 6.3, 6.9, and 6.1 mL/sec in the TULIP, VLAP, and HoLRP groups, respectively. At 1 month after surgery, the mean IPSS was 10.2, 9.5, and 4.7 and the mean MFR was 9.6, 13.4, and 18.7 mL/sec while at 3 months the mean IPSS was 6.2, 6.1, and 3.6 and the mean MFR was 14.1, 16.0, and 21.5 mL/sec in patients treated with TULIP, VLAP, and HoLRP, respectively. No serious complication occurred in any patient.
Although HoLRP requires expertise, it appears to be a promising treatment modality for BPH.
International Journal of Urology 04/1998; 5(2):152-6. DOI:10.1111/j.1442-2042.1998.tb00266.x · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the usefulness of serum immuno-suppressive acidic protein (IAP) as a predictor for staging renal cell carcinoma (RCC), using receiver-operator characteristic (ROC) analysis, and to compare IAP with other tumour markers.
From September 1983 to December 1995, serum IAP was measured in 133 untreated patients with RCC (mean age 60.1 years, SD 11.4. range 31-84). The erythrocyte sedimentation rate (ESR), the levels of fibrinogen, C-reactive protein (CRP), and alpha 2-globulin were also measured. To compare these markers as predictors of local involvement of the renal capsule, lymph node and distant metastasis, the area under the corresponding ROC curve was calculated. Tumour size at the time of resection was added in this analysis for comparison with the levels of these tumour markers.
The final pathological stage was T1 or T2 in 101 patients and T3 or T4 in 32, while it was N0 in 122 patients, N1-3 in seven, M0 in 114 patients and M1 in 19. The area of the ROC curve for tumour size was greatest (0.843) for staging of the local extent (T1/T2 versus T3/T4) and that for IAP was 0.714, similar to the values for fibrinogen, ESR and CRP. For predicting lymph node metastasis, IAP and fibrinogen were the most important (0.864). However, IAP alone (0.894) was the most important predictor of distant metastasis. Using an IAP threshold of 600 micrograms/mL gave a high sensitivity and specificity for detecting lymph node and distant metastasis.
IAP is a valuable predictor of lymph node and distant metastasis in patients with RCC, although it is inferior to tumour size in predicting local involvement of the renal capsule. The appropriate threshold value of IAP for detecting lymph node and distant metastasis is 600 micrograms/mL.
British Journal of Urology 08/1997; 80(1):25-9. DOI:10.1046/j.1464-410X.1997.00244.x
[Show abstract][Hide abstract] ABSTRACT: Preoperative endocrine therapy has been suggested to improve surgical radicality and/or patient prognosis in prostate cancer.
Patients with clinical stage A2, B, and C prostate cancer were randomized to either group I (n = 113) or group II (n = 111). Group I patients were to receive preoperative endocrine therapy consisting of leuprolide and chlormadinone for 3 months, followed by radical prostatectomy with lymph node dissection. Group II patients were to undergo the surgery before endocrine therapy.
Group I patients showed a remarkable decrease in prostate-specific antigen (PSA) (mean +/- SE: 41.8 +/- 8.6 ng/mL to 2.7 +/- 0.7 ng/mL) and prostate volume (29.8 +/- 1.7 mL to 21.2 +/- 1.6 mL) during the preoperative therapy. Histopathologic analysis showed a significant difference in the rates of down-staging (19.1% in group I versus 3.3% in group II), positive surgical margins (63.8% versus 81.3%) and positive lymph node metastasis (20.7% versus 36.5%). No significant difference was detected in operating features. Subgroup analyses indicated that beneficial effects were correlated positively with degree of histologic differentiation and negatively with the basal PSA level.
Preoperative endocrine therapy reduced local extension of prostate cancer, and the effects depended on histologic differentiation and PSA level. Long-term follow-up data are needed to determine the effects on the patient prognosis.
International Journal of Urology 04/1997; 4(2):144-51. DOI:10.1111/j.1442-2042.1997.tb00161.x · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prevalence of lower urinary tract symptoms was determined by survey as an initial step in estimating the significance of benign prostatic hyperplasia (BPH) in Asia and Australia.
The symptom index (0 to 35) and quality-of-life (QOL) index (0 to 6) of the international prostate symptom score were measured in 7588 men in 9 Asian countries and 146 men in Australia.
The percentages of Asian men considered to be symptomatic (symptom index > or = 8) were 18%, 29%, 40%, and 56% in the age groups of 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years, respectively. For Australian men, these figures were 36%, 33%, and 37% in the 50 to 59, 60 to 69, and 70 to 79 year age groups, respectively.
Our estimates indicate that the prevalences of symptomatic men in Asia and Australia are similar to or greater than those in Europe and America, and suggest BPH is similarly common in these areas.
International Journal of Urology 01/1997; 4(1):40-6. · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a recent study by the Casodex Combination Study Group, USA, patients in a flutamide (750 mg/day) plus LH-RH agonist group showed a high treatment failure rate, mainly due to flutamide-induced diarrhea and hepatotoxicity. Our current study was conducted to determine the optimal dose of flutamide for use in this type of combination therapy.
In a randomized, multicenter study, 30 patients (hormone untreated; stage C or D) were divided into 2 groups: flutamide 250 mg (125 mg x 2; 14 patients) and flutamide 375 mg (125 mg x 3; 16 patients, and each dose combined with either goserelin acetate (3.6 mg every 4 weeks) or leuprolide acetate (3.75 mg every 4 weeks). Goserelin and leuprolide were administered to patients in a 1:1 ratio. Flutamide monotherapy at a daily dose of 375 mg was determined to be the optimal dose in Japan in our previous phase II study. The endpoints of this pilot study were the objective response and adverse events during the 12-week treatment.
The objective response rate was 83.3% in the flutamide 250 mg group and 85.7% in the flutamide 175 mg group according to the Japanese response criteria for prostate cancer. Elevated PSA levels fell to within the normal range in 83.3% of the patients in the former group and in 93.3% of the patients in the latter group. One patient administered 250 mg of flutamide experienced diarrhea, while the serum GOT and/or GPT were elevated in 3 patients administered 250 mg of flutamide and 4 patients administered 375 mg of flutamide.
Based on the findings of this pilot study of maximal androgen-depletion therapy for advanced prostate cancer, 375 mg/day of flutamide is recommended in combination with an LH-RH agonist. Assessment of the effects of our recommended regimen on longer term survival, quality of life and antiandrogen withdrawal syndrome of patients treated requires additional patients and time for follow-up.
International Journal of Urology 12/1996; 3(6):468-71. DOI:10.1111/j.1442-2042.1996.tb00578.x · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mechanisms of relative potency in direct action of antiandrogens have not been fully elucidated. Using castrated rats, the effects of antiandrogens on the prostatic weight gain induced by exogenous testosterone (T), and on T uptake into prostatic cells were examined. Tested antiandrogens were cyproterone acetate, chlormadinone acetate, a new steroidal antiandrogen, 17acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione (TZP-4238), and one nonsteroidal type, flutamide (FL). Suppression of prostatic weight gain, T uptake and serum concentrations of compounds, correlated well each other among steroidal antiandrogens, while FL was five times more active in suppressing weight gain than TZP-4238, associated with a lower nuclear distribution of androgen. The results suggest that 1) suppression of T uptake is a major and common mechanism of steroidal antiandrogens and the relative potency is attributable to pharmacokinetic characteristics in vivo, and 2) FL suppress s nuclear T uptake more specifically than steroidal antiandrogens.
The Prostate 09/1996; 29(3):146-52. DOI:10.1002/(SICI)1097-0045(199609)29:3<146::AID-PROS1>3.0.CO;2-C · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Various treatment modalities for benign prostatic hyperplasia (BPH) have emerged and are now in use or await evaluation of clinical usefulness. It is difficult, however, to compare their efficacies on a single scale, because standardized criteria for therapeutic efficacy of BPH treatments have not been established.
A total of 692 BPH patients from 8 institutions in Japan received various treatments, and were judged by specialized physicians for overall efficacy, and for efficacy in 4 domains: symptom, function, anatomy, and quality of life (QOL). Efficacy of treatment was graded as excellent, good, fair or poor, and assessed using items based on conventional clinical measurements. These items included 1) the difference (post-pretreatment value), 2) relative ratio (post/pre) and, 3) the individual values of pre- or posttreatment measurements. The cut off levels for each grade were heuristically selected by Spearman's rank correlation and multiple regression analysis so that the results accurately predicted physicians' judgement, while the feasibility was maintained.
The results for each efficacy grade (range of excellent, range of good, range of fair, range of poor) were summarized as follows: Symptom: (post/pre treatment ratio of I-PSS) < or = 0.25, < or = 0.5, < or = 0.75, > 0.75. Function: (post-pre of Qmax) > or = 10 mL/s, > or = 5 mL/s, > or = 0.25 mL/s, < 0.25 mL/s. Anatomy: (post/pre ratio of prostate volume) < or = 0.5, < or = 0.75, < or = 0.9, > 0.9. QOL: (pre-post of QOL index) > or = 4, 3, 2 and 1, < or = 0. The overall efficacy grade was defined as the median of efficacy grades of 3 domains: symptom, function and QOL. The agreement rates between the criteria and physicians' judgement on the dichotomous efficacy (either excellent plus good, or fair plus poor) were approximately 80% in individual domains and overall estimate, and consistent among various treatments.
The proposed criteria are fairly accurate, simple, and practical, and thus may be useful as a standard method for assessing the clinical efficacy of BPH treatments.
International Journal of Urology 07/1996; 3(4):267-73. DOI:10.1111/j.1442-2042.1996.tb00532.x · 1.80 Impact Factor