Prostatic Neoplasms: Ono Y

Tanaka M, Ono Y, Matsuda T, Terachi T, Suzuki K, Baba S, Hara I, Hirao Y, Anonymous00107. · Department of Urology, Fukuoka University Faculty of Medicine, Fukuoka, Japan. ~u.ac.jp · Int J Urol. · Pubmed #19228223 No free full text.

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Kuriyama M, Takahashi Y, Sahashi M, Ono Y, Tanaka T, Shimizu H, Ohshima S. · Tsurumi Nishiguchi Hospital, Yokohama, Kanagawa, Japan. · Jpn J Clin Oncol. · Pubmed #11256836 links to  free full text

Abstract: OBJECTIVE: This prospective and randomized clinical study was initiated to compare the efficacy and safety of combined androgen blockade with combination with UFT in patients with untreated prostate cancer. METHODS: A total of 142 patients were entered in this study between April 1990 and December 1992. All patients received bilateral orchiectomy and 200 mg/day of diethylstilbestrol diphosphate. Of these patients, 70 patients were administered an additional 400 mg/day of UFT after randomization. Either treatment was continued for at least 1 year or until objective progression occurred if the initial response was equal to or better than no change. The endpoints of this study were progression-free survival, cancer-specific survival and change of QOL scores. RESULTS: A total of 136 patients were evaluable and 131 patients (96.3%) could be followed up with a median follow-up period of 1469 days. Both groups showed similar initial treatment response at 12 weeks, adverse effect and change of quality of life score during the first year after initiation of the treatment. There was a significantly longer progression-free survival and better but not significant cancer-specific survival in the endocrine chemotherapy group. The patients with earlier stage and initial serum prostate-specific antigen values <40 ng/ml showed a good indication for this endocrine chemotherapy. CONCLUSION: This endocrine chemotherapy was confirmed to be tolerable and significantly effective in the delay of disease progression, which leads to longer survival in patients with prostate cancer.

Nishimura K, Nonomura N, Ono Y, Nozawa M, Fukui T, Harada Y, Imazu T, Takaha N, Sugao H, Miki T, Okuyama A. · Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan. · Oncology. · Pubmed #11150908 No free full text.

Abstract: OBJECTIVE: To evaluate the clinical usefulness of an oral combination of cyclophosphamide, uracil plus tegafur (UFT) and estramustine in the treatment of patients with hormone-refractory prostate cancer (HRPC). METHODS: Twenty-one patients were treated with oral administration of cyclophosphamide (100 mg/day), UFT (400 mg/day) and estramustine phosphate (560 mg/day). The median age of the patients was 70 years. Twelve patients had symptomatic bone metastasis, 6 had asymptomatic bone metastasis, 5 had lymph node metastasis, while 2 had only biochemical progression evaluated by prostate-specific antigen (PSA). RESULTS: Twelve (57%) out of 21 patients showed a PSA decline of 50% or greater. The median response duration was 7 months (range 2-15 months). Among the 20 patients assessable for bone pain, 2 (10%) improved, 12 (60%) remained stable and 6 (30%) progressed. Among the 10 patients assessable for bone metastasis, 1 (10%) improved, 5 (50%) were stable and 4 (40%) progressed on bone scan. Among 3 patients assessable for measurable disease (lymph node metastasis), 2 (67%) showed partial response and 1 (33%) progression. Most toxicities were mild. CONCLUSIONS: The combination of cyclophosphamide, UFT and estramustine is an active and well-tolerated regimen for HRPC. To evaluate the survival benefit, further randomized studies are required.

Nonomura N, Ono Y, Nozawa M, Fukui T, Harada Y, Nishimura K, Takaha N, Takahara S, Okuyama A. · Department of Urology, Osaka University Medical School, Suita City, Osaka, Japan. · Eur Urol. · Pubmed #11111187 No free full text.

Abstract: OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of intrarenal bacillus Calmette-Guérin (BCG) instillation as a treatment for transitional cell carcinoma in situ (CIS) of the upper urinary tract. METHODS: Diagnostic criteria of upper urinary tract CIS were (1) positive urinary cytology, (2) negative multiple random biopsy of the bladder and prostatic urethra, (3) negative radiographic findings in the upper urinary tract and (4) two serial positive cytologies in selective ipsilateral urine sampling from the pyeloureteral system. Eleven patients diagnosed as having upper urinary tract CIS were enrolled in this study. Thus, 11 renal units were treated with BCG instillation. After placing a 6-french Double-J stent, BCG (80 mg) in 40 ml saline was instilled into the bladder weekly, 6 times in total as one course. RESULTS: At the end of one course, 9 cases showed negative urinary cytology. Among these 9 cases, 2 showed recurrence in the upper urinary tract after 4 months and 8 months of disease-free interval, respectively. These 2 cases have received an additional course of BCG instillation, but the urinary cytology did not normalize. Mean recurrence-free time was 19.6 months. Of the other 7 cases who responded to the first course of instillation, 6 cases were alive with no evidence of the disease. The remaining patient died of rectal cancer with no evidence of transitional cell carcinoma (TCC). Of the 2 cases who showed positive urinary cytology even after the first course, 1 underwent nephroureterectomy. The other case was diagnosed as having malignant lymphoma 3 months after the end of this instillation therapy, and he died of malignant lymphoma. As side effects, 8 cases (72.7%) showed bladder irritability, and 4 presented fever higher than 38 degrees C. However, no patient needed antitubercular treatment. CONCLUSION: As for the short-term response, BCG instillation for the treatment of upper urinary tract CIS is considered to be effective and safe. Longer follow-up and further experience with this treatment are required.

Ono Y, Ohshima S, Takahashi Y, Kuriyama M, Kawada Y, Shimizu H. · Department of Urology, Nagoya University School of Medicine, Japan. · Oncology (Williston Park). · Pubmed #10442379 No free full text.

Abstract: A prospective, randomized clinical trial was conducted to evaluate the efficacy of endocrine chemotherapy with uracil and tegafur (in a molar ratio of 4:1 [UFT]) in patients with prostate cancer. The study included two treatment arms: endocrine plus UFT vs endocrine-only therapy. Of the 136 patients with prostate cancer enrolled in this study from April 1990 to December 1992, 69 received endocrine plus UFT therapy and the remaining 67 received endocrine-only therapy. Among those receiving UFT therapy, eight patients had stage A2 and B prostate cancer, 11 had stage C disease, and 50 had stage D disease. In the endocrine-only group, 10 patients had stage A2 and B disease, seven had stage C disease, and 50 had stage D disease. Tumors were well differentiated in 20 patients, moderately differentiated in 38 patients, and poorly differentiated in 11 patients receiving UFT. The endocrine-only group included 29 patients with differentiated tumors, 26 with moderately differentiated tumors, and 12 with poorly differentiated carcinomas. After a mean follow-up period of 54.9 months for patients receiving endocrine plus UFT therapy and 47.8 months for patients receiving endocrine-only therapy, disease had not progressed in 53.0% of the UFT-treated patients and 43.8% of the endocrine-only-treated patients (P = .114). The 5-year cancer-specific survival rates were 67.4% for the UFT group and 49.5% for the endocrine-only group (P = .273). The 5-year survival rates were 47.4% for the UFT group and 35.4% for the endocrine-only group (P = .177). Adverse effects, such as bone marrow suppression, nausea, vomiting, and anorexia, occurred in 36 patients in the UFT group and 41 patients in the endocrine-only group. However, adverse effects were not specifically related to UFT use. It is concluded that endocrine chemotherapy plus UFT is a tolerable regimen that might be effective for patients with prostate cancer.

Fujii A, Takenaka A, Yuen K, Ono Y, Yamamoto H, Kisaki T, Gohji K, Okamoto M. · Department of Urology, Hyogo Medical Center for Adults. · Nippon Hinyokika Gakkai Zasshi. · Pubmed #10386053 No free full text.

Abstract: PURPOSE: To evaluate the results of radical retropubic prostatectomy in patients treated at a single institution. MATERIALS AND METHODS: Between April 1985 and July 1997, 76 patients with prostate cancer underwent radical retropubic prostatectomy, including 73 receiving pelvic lymphadenectomy. The median age and follow-up time were 68 years old and 44 months, respectively. The pathological stage was pT0 in 6 patients, pT2 in 29, pT3 in 39, pT4 in 2, and pN+ in 22. RESULTS: The surgical margin was positive in 10% of the pT2 patients and 61% of the pT3 patients. Twelve patients had recurrence. Recurrence was shown by biological failure in 4 patients and clinical failure in 8. The disease-free 5-year survival rates (Kaplan-Meier) were 100% in pT0 patients, 87% in pT2, 72% in pT3, 50% in pT4, 77% in pN-, 75% in pN+, 73% for a positive surgical-margin, and 83% for a negative surgical-margin. There were no statistical differences between any of these factors. However, the disease-free survival rate in pT3 patients with poorly differentiated adenocarcinoma (PDA) who received postoperative radiotherapy combined with hormonal therapy was significantly superior to that in patients with the same characteristics who received hormonal therapy (100% vs 27%; p = 0.011). The cause-specific 5-year survival rates were 100% in pT0, 100% in pT2, 92% in pT3, 50% in pT4, 94% in pN-, 93% in pN+, 93% for a positive surgical-margin, 98% for a negative surgical-margin, 100% in the aforementioned pT3 patients with PDA and postoperative radiotherapy combined with hormonal therapy and 86% in pT3 patients with PDA and postoperative hormonal therapy. There were no statistical differences between any of these factors. CONCLUSIONS: Our results suggest that radical prostatectomy is available for both organ-confined and non organ-confined advanced prostate cancer. Postoperative radiotherapy combined with hormonal therapy is especially useful for patients in pT3 with PDA.

Yamazaki H, Nishiyama K, Tanaka E, Maeda O, Meguro N, Kinouchi T, Usami M, Kakimoto K, Ono Y, Nishimura T. · Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajiicho Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. · Anticancer Res. · Pubmed #19192649 No free full text.

Abstract: BACKGROUND: As hormonal therapy has an influence not only on outcome but also on toxicities, we compare the efficacy of three-dimensional radiotherapy planning (3D-RTP) and of conventional radiotherapy (Conv-RT) in association with long-term hormonal therapy in reducing toxicity of treatment. PATIENTS AND METHODS: A retrospective case-control study was performed comparing the frequency of radiation toxicity between 63 Conv-RT and 52 3D-RTP patients with locally advanced prostate cancer (intermediate to high risk) treated with combined hormonal therapy. The average duration of neoadjuvant treatment was 7 months (1-38 months) and that of adjuvant treatment was 38 months (4-94 months). Patients were treated with 70 Gy of box field radiotherapy for the same clinical target volume (60 Gy prostate + seminal vesicle and 10 Gy boost to prostate). RESULTS: Treatment volumes (= X(RL) x Y(SI) x X(AP), where X(RL) = right left length of anterior-posterior portals, X(AP) = anterior posterior length of lateral portals and Y(SI) = superior inferior length of anterior-posterior portals) were significantly smaller in the 3D-RTP group (630 +/- 130 cm3) than in the Conv-RT group (1036 +/- 223 cm3) (p < 0.0001). Acute side-effects in urological tracts (GU) were associated with XRL (p = 0.02), Y(SI) (p = 0.008) and treatment technique (Conv-RT vs. 3D-RTP: p = 0.01). The frequency of acute gastrointestinal tract (GI) toxicity was associated with X(RL) (p = 0.02), X(AP) (p = 0.03). Late GU toxicities were associated with YAP (p = 0.02) and X(RL) (p = 0.03). Treatment technique was the determinant of late GI toxicities (p = 0.03). Frequency of late GI toxicities of G2 or more was reduced from 35% in the Conv-RT group to 15% in the 3D-RTP group (p = 0.03, odds ratio = 0.43). Patients with late GI toxicity received longer periods (39 +/- 19 months) of adjuvant hormonal therapy than the patients without (31 +/- 18 months, p = 0.04). Prostate-specific antigen (PSA) failure-free survival rates at 3 years were 92% for the 3D-RTP group and 90% for the Conv-RT group (73% at 5 years, 67% at 10 years). Overall survival rates were 97% (3-year), 91% (5-year), and 91% (10-year) in the Conv-RT group, compared to 100% at 3 years in the 3D-RTP group. CONCLUSION: Long-term hormonal therapy has the potential to improve outcome but induce late GI toxicity. 3D-RTP simultaneously reduced treatment volume and frequency of acute urinary and late GI toxicities even with long-term hormonal therapy.

Ono Y, Chiba K, Tanaka H. · The Department of Urology, Hyogo Prefectural Kakogawa Hospital. · Hinyokika Kiyo. · Pubmed #16285616 No free full text.

Abstract: Fifteen out of 140 men (median age 67 years, range 62-75) had a serum prostate-specific antigen (PSA) level of < or = 4 ng/ml before radical prostatectomy which was performed without preoperative neoadjuvant hormonal therapy between 2001 January and 2004 September. Demographic and clinical data were analyzed. Pathological specimens were evaluated by routine hematoxylin and eosine staining and immunohistochemistry with anti-PSA antibody, for both pathological staging and grading, and for the presence of PSA production. Pathological data were compared between patients with PSA < or = 4 ng/ml and those with 4 < PSA < or = 10 ng/ml. Clinically insignificant cancer was defined as a cancer volume of < 0.5 ml and the Gleason score < or = 6. The median PSA level was 3.0 ng/ml (range 1.4-3.9). Thirteen tumors (87%) were pT2. One tumor had a Gleason score of 7 and 14 tumors had a final Gleason score of < or = 6. Nine (60%) tumors were clinically insignificant. Comparison of pathological variables, PSA < or = 4 ng/ml cancer had a significantly lower Gleason score (p = 0.0029), and a smaller cancer volume (p = 0.0451) than 4 < PSA < or = 10 ng/ml cancer. All tumors were stained strongly for PSA. During a median follow-up of 24 (9-36) months, no patient showed elevated PSA (PSA > or = 0.1 ng/ml). Most prostate cancers in men with a PSA level of < or = 4 ng/ml were pT2, and about half of them were clinically insignificant. All cancers produced PSA.

Nakano Y, Okamura K, Takamura S, Okamoto N, Narishima M, Yoshino Y, Hattori R, Ono Y, Ohshima S, Nagasaka T. · Tosei General Hospital, Seto, Japan. · Int J Urol. · Pubmed #16174045 No free full text.

Abstract: AIM: To investigate whether measuring prostate specific antigen complexed to alpha1-Antichymotrypsin (PSA-ACT) can increase sensitivity and specificity in detecting prostate cancer. METHODS: In this prospective study, we measured serum total PSA, PSA-ACT, free PSA, prostate volume and transition zone volume on 210 patients with total PSA level of 4-20 ng/mL. From fitted curves between positive predictive values for prostate cancer and age, prostate volume, transition zone volume, total PSA, PSA-ACT or F/T ratio, each function predicting prostate cancer was determined. Relative probabilities for prostate cancer (RPpca) which were defined by combined functions of age, F/T ratio, prostate volume or transition zone volume, and total PSA or PSA-ACT were calculated. Furthermore, using logistic regression, analysis was performed to determine the probability of prostate cancer. Receiver-operating characteristic analysis was performed to clarify the areas under the curve (AUC) for conventional single parameters, RPpca and logistic regression probability. RESULTS: F/T ratio showed the largest AUC among conventional parameters. The AUC of RPpca was larger than those of F/T ratio and logistic regression probability. RPpca using the functions of age, transition zone volume, PSA-ACT and F/T ratio showed the largest AUC and highest specificity at sensitivity 95% level, however, specificities at sensitivity 90% and 85% were identical to those of RPpca using the functions of age, prostate volume, total PSA and F/T ratio. CONCLUSIONS: RPpca using the functions of age, transition zone volume, PSA-ACT and F/T ratio was the best way to detect prostate cancer, however, the usefulness of PSA-ACT appears limited, considering the cost.

Maeda O, Kakimoto K, Ono Y, Meguro N, Kinouchi T, Usami M. · The Department of Urology, Osaka Medical Centerfor Cancer and Cardiovascular Diseases. · Hinyokika Kiyo. · Pubmed #16164273 No free full text.

Abstract: Watchful-waiting policy is an important treatment option for some patients with localized prostate cancer and it is widely recognized in Western countries in which the prostate cancer mortality rate is 510 fold higher than that in Japan. Most men with well and perhaps moderately differentiated prostate cancer who have a life expectancy of less than 10 years will die of other causes and it is not clear whether early primary hormone therapy improves survival and the quality of life compared to androgen suppression deferred until signs and symptoms of clinical progression. There is one major question as to whether patients who do not need radical treatment should undergo early primary hormone therapy in Japan in spite of high cost and treatment-related adverse effects of hormone therapy.

Okamura K, Takaba H, Kamihira O, Kinukawa T, Ono Y, Ohshima S, Nagasaka T. · Depatment of Urology, National Center for Geriatrics and Gerontology, Obu, Japan. · Int J Urol. · Pubmed #15948720 No free full text.

Abstract: BACKGROUND: To investigate whether using a new concept of relative probability for prostate cancer (RPpca) can increase sensitivity and specificity in detecting prostate cancer. METHODS: For 217 patients with total prostate-specific antigen (PSA) level of 4-20 ng/mL, prostate volume and free to total PSA (F/T) ratio were measured. From the fitted curves between positive predictive values for prostate cancer and age, prostate volume, total PSA or the F/T ratio, each function predicting prostate cancer was determined. RPpca defined by the combined functions of age, prostate volume, total PSA and F/T ratio was calculated for each individual patient. The probability of prostate cancer was also calculated, using logistic regression analysis (LRPpca). Receiver-operating characteristic analysis was performed to elucidate the areas under the curve (AUC), sensitivities and specificities and cutoff values of the conventional and new parameters. Finally, we investigated the applicability of the above parameters in the other patient group using a different PSA assay kit (AxSYM). RESULTS: Although RPpca had the largest AUC in the total PSA range of 4-20 ng/mL, it did not reach statistical significance between RPpca and F/T ratio or LRPpca. The cutoff values of F/T ratio, LRPpca and RPpca were determined as 0.15, 0.12 and 0.20, respectively. Using these cutoff values in AxSYM data, RPpca had the highest sensitivity (91%) and specificity (57%). CONCLUSIONS: RPpca can provide more precise information to avoid unnecessary biopsy than LRPpca or F/T ratio. RPpca could be valuable to decide whether to perform prostate biopsy when using various PSA kits.

Arai Y, Egawa S, Terachi T, Suzuki K, Gotoh M, Kawakita M, Tanaka M, Terada N, Baba S, Okumura K, Hayami S, Ono Y, Matsuda T, Naito S. · Department of Urology, Kurashiki Central Hospital, Kurashiki, Japan. · Int J Urol. · Pubmed #12887364 No free full text.

Abstract: AIM: Laparoscopic radical prostatectomy is being evaluated throughout the world. The aim of the present study is to report early multi-institutional experience of the procedure in Japan. METHODS: A total of 148 men who were diagnosed with clinically localized prostate cancer underwent laparoscopic radical prostatectomy at seven different institutions in Japan. Early complications (within 30 days postoperatively) and postoperative convalescence were reviewed retrospectively. The median age of patients was 68.0 years (range, 51-80). RESULTS: The median operative time was 403 minutes (range, 167-925; average, 427). Blood loss ranged from 50 to 5000 mL (median, 540; average, 856). A total of 66 complications were reported in 55 patients (37.2%). Intraoperative complications were noted in 25 of 148 patients (16.9%): 10 rectal injuries (6.8%); five bladder injuries (3.4%); five cases of subcutaneous emphysema (3.4%); two intestinal injuries (1.4%); one major vessel injury (0.7%); one ureteral injury (0.7%); and one obturator nerve injury (0.7%). Overall, 16 of 148 patients (10.8%) required open conversion or postoperative open surgical repair. The most common postoperative complications were anastomotic leakage (6.8%), wound-related complications (4.7%) and perineal pain (4.7%). The bladder catheter was removed on day 7 or earlier in 73 cases (49.3%). The median time to ambulation was 1 day (mean 1.4, range 1-5). Oral intake was started on postoperative day 1 in 67 patients (45.2%) and on postoperative day 2 in 65 (43.9%). CONCLUSION: Although laparoscopic radical prostatectomy is technically demanding, reduced blood loss and shorter convalescence periods can be expected from the procedure. Surgeons should be aware of the disturbingly high morbidity rate related to early experience. By mastering laparoscopic skills and sharing knowledge, surgeons could reduce the impact of the learning curve required to complete this procedure competently.

Suzuki K, Matsui H, Ohtake N, Nakata S, Takei T, Nakazato H, Okugi H, Koike H, Ono Y, Ito K, Kurokawa K, Yamanaka H. · Department of Urology, Gunma University School of Medicine, Maebashi, Gunma, Japan. · J Biomed Sci. · Pubmed #12824702 No free full text.

Abstract: An association between the Pro/Pro genotype of p53 codon 72 and a lower risk of prostate cancer in Caucasians was recently reported. However, the association of this polymorphism with prostate cancer risk in a Japanese population has not been clarified. We performed a case-control study consisting of 114 prostate cancer patients and 105 noncancer controls. Sixty-nine percent (79 of 114) of the patients had a positive family history. The genotypic frequencies in the controls were 39.0% for Arg/Arg, 54.3% for Arg/Pro and 6.7% for Pro/Pro; they were in Hardy-Weinberg equilibrium. When a comparison of the distribution of the p53 codon 72 polymorphism was made between patients with a first-degree family history and all control subjects, the adjusted odds ratios (ORs) for prostate cancer associated with the Arg/Arg, Arg/Pro and Pro/Pro genotypes were 1.00, 0.99 [95% confidence interval (CI) 0.53-1.88] and 2.80 (95% CI 1.04-7.53), respectively. When stratification of cases was performed based on clinical stage (localized or metastatic cancer) and pathological grade (a Gleason score of <7 or > or =7), there tended to be a greater number of patients with localized cancers among those patients with the Arg/Pro genotype than among those with the Arg/Arg genotype (overall cases: age-adjusted OR 0.36, 95% CI 0.13-1.00, p = 0.049; positive family history cases: age-adjusted OR 0.25, 95% CI 0.075-0.84, p = 0.025). In addition, there tended to be a greater number of patients with low-grade cancers among those with the Pro/Pro genotype than among those with other genotypes (overall cases: age-adjusted OR 0.41, 95% CI 0.13-1.30, p = 0.13; positive family history cases: age-adjusted OR 0.20, 95% CI 0.004-0.89, p = 0.035). The present findings suggest that the Pro/Pro genotype of p53 codon 72 played a role in prostate cancer susceptibility in a Japanese population. However, the Pro allele did not appear to worsen such clinical parameters as clinical stage or pathological grade.

Miyake H, Ono Y, Park SJ, Hara I, Eto H. · Department of Urology, Hyogo Medical Center for Adults, Akashi, Japan. · Int J Urol. · Pubmed #12823693 No free full text.

Abstract: BACKGROUND: The objective of the present study was to analyze the pathological findings of radical prostatectomy specimens diagnosed on single core positive prostate biopsy in eight systematic transrectal ultrasonography (TRUS)-guided biopsies with a Gleason score </= 4. METHODS: Between January 1993 and March 2001, 975 patients underwent TRUS-guided prostate biopsy, and 32 patients were diagnosed as having prostate cancer based only on one positive core with a Gleason score </= 4. In this study, 14 of the 32 patients who underwent radical prostatectomy without any neoadjuvant therapies were enrolled, and the pathological findings of their radical prostatectomy specimens were evaluated. RESULTS: The clinical stage of the 14 patients was T1c in 10 and T2 in four. Cancer was detected in the prostate apex in seven patients, the middle in two, the base of the peripheral zone (PZ) in three, the lateral horn of the PZ in one and the transitional zone (TZ) one. Pathological stage of the 14 patients was pT2a in four, pT2b in six, pT3a in three and pT3b one. Gleason score of the radical prostatectomy specimens in 11 patients was also </= 4. Of the 10 patients diagnosed with cT1c, extraprostatic disease was found in only one radical prostatectomy specimen. All three patients whose cancer was detected from the base of the PZ showed pT3 disease. During the median follow-up period of 47.5 months, all patients were alive with no evidence of disease. CONCLUSION: The prognosis of patients who were diagnosed with one core positive prostate biopsy with a Gleason score </= 4 is generally favorable; however, advanced disease tended to be observed in patients who were diagnosed with cT2a and/or whose cancer was detected from the base of PZ.

Egawa S, Arai Y, Kawakita M, Matsuda T, Tanaka M, Naito S, Okumura K, Terachi T, Hayami S, Suzuki K, Gotoh M, Ono Y, Baba S. · Department of Urology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. · Int J Clin Oncol. · Pubmed #12720102 No free full text.

Abstract: BACKGROUND: Because laparoscopic radical prostatectomy requires significant laparoscopic expertise, it needs to be evaluated critically before being accepted as a standard therapeutic option for localized prostate cancer. METHODS: A total of 148 men diagnosed as having clinically resectable prostate cancer underwent laparoscopic radical prostatectomy at seven different institutions in Japan. Early biochemical and oncological outcomes were investigated. RESULTS: Policies underlying the selection of laparoscopic radical prostatectomy did not appear to be consistent among the participating institutions. Pathologically organ-confined disease was found in 64.0% of the patients who had undergone neoadjuvant therapy and in 77.2% of those who had not. Positive surgical margins were found in 36.0% and 34.1%, respectively, of the specimens. The most common site was the apex, which accounted for 77.8% of positive margins in patients who had undergone neoadjuvant therapy and 50.0% in those who had not. Seven patients have experienced biochemical failure at a median follow-up of 9.0 months. No clinical progression has been reported. CONCLUSIONS: Continuing improvements in each step of laparoscopic radical prostatectomy, especially apical dissection, should be sought as we pursue the goal of still better oncological outcomes. A systematic approach and therapeutic guidelines should help to reduce the learning curve for competent performance of this procedure.

Fukatsu A, Ono Y, Ito M, Yoshino Y, Hattori R, Gotoh M, Ohshima S. · Department of Urology, Nagoya University Graduate School of Medicine, Nagoya-shi, Japan. · Urology. · Pubmed #12597950 No free full text.

Abstract: OBJECTIVES: To estimate the relationship between serum prostate-specific antigen (PSA) and prostatic epithelial volume, a new simple method for measuring epithelial volume was developed and its efficacy evaluated in patients with benign prostatic hyperplasia. METHODS: Between March 1998 and June 2001, 122 patients without prostate cancer in the transurethral resected specimen were enrolled in this study. Of the 122 patients, 55 had a serum PSA level of 4.0 ng/mL or greater and negative sextant biopsies before surgery. First, we measured the epithelium/glandular lumen ratio by computer image analysis in 20 specimens. Second, we measured the percentage of glandular lumen in all 122 patients. The prostatic epithelial volume was then calculated as follows: calculated epithelium volume (in cubic centimeters) = epithelium/glandular lumen ratio percentage of glandularlumen x total prostate volume (in cubic centimeters). RESULTS: The epithelium/glandular lumen ratio was 1.01 in the 20 specimens. In the 122 patients with benign prostatic hyperplasia, the calculated epithelial volume correlated more strongly with the serum PSA level than did the total prostate volume, transition zone volume, or percentage of epithelium (gamma = 0.672, P <0.0001). The mean PSA level per calculated epithelial volume was 1.27 ng/mL/cm(3). The calculated epithelial volumes from the biopsy specimens correlated significantly with those from transurethral resection specimens (gamma = 0.956, P <0.0001). CONCLUSIONS: Serum PSA levels correlated significantly with prostatic epithelial volumes in patients with benign prostatic hyperplasia. The method of measuring prostatic epithelial volume used in this study is very convenient for clinical practice.

Suzuki K, Ohtake N, Nakata S, Takei T, Matsui H, Ono Y, Nakazato H, Hasumi M, Koike H, Ito K, Fukabori Y, Kurokawa K, Yamanaka H. · Department of Urology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, Japan 371-8511. · Anticancer Res. · Pubmed #12552947 No free full text.

Abstract: BACKGROUND: To investigate the relationship between two common variants (Ser217 and Ala541) of the HPC2/ELAC2 gene and prostate cancer risk in a Japanese population, we performed a case-control study. MATERIALS AND METHODS: Cases and controls consisted of 81 prostate cancer patients with a family history and 106 controls. Ser217 and Ala541 polymorphisms were analyzed by the restriction fragment length polymorphism method. RESULTS: In controls, 94.5% and 100.0% had wild-type Ser217Ser and Ala541Ala genotypes, respectively. 5.7% of the controls had the Leu217 genotype. No Thr541 genotype was observed in the controls. 92.6% and 97.5% of the cases had the Ser217Ser and Ala541Ala genotypes. No significant differences were observed in the genotypic frequencies between controls and cases. We stratified prostate cancer cases according to the pathological grade (low- or high-grade) or the clinical stage (localized or metastatic). There was no statistical difference between the genotypic frequencies between the groups. CONCLUSION: The present study suggested that the common variants in the HPC2/ELAC2 gene play a limited role in the risk of prostate cancer in the Japanese population.

Kurokawa K, Ito K, Suzuki K, Ono Y, Yamamoto T, Akimoto T, Yamanaka H. · Department of Urology and Radiology, Gunma University School of Medicine, Maebashi, Japan. · Jpn J Clin Oncol. · Pubmed #12499419 links to  free full text

Abstract: BACKGROUND: We attempted to identify factors that predict the outcomes of salvage external beam radiotherapy (sEBRT) in patients who showed local recurrence without systemic progression or isolated prostate specific antigen (PSA) recurrence after initial hormonal therapy. METHODS: The subjects were 33 patients who were diagnosed as having local recurrence without systemic progression (30 cases) or isolated PSA recurrence (three cases). Of these patients, those with continuously decreasing PSA levels, which were 1.0 ng/ml or less 1-1.5 years after sEBRT, were regarded as good responders (GR) whereas the remaining patients were regarded as poor responders (nGR). Survival rates in these patients and factors that distinguish GR from nGR were evaluated retrospectively. RESULTS: The cancer-specific 10-year survival rate was 82.4% in the 33 patients, 100% in the 21 GR patients and 55% in the 12 nGR patients (P < 0.0001). Stepwise variable selection to discriminate between GR and nGR revealed that the time from sEBRT initiation to the nadir PSA was the most significant factor (P = 0.000097). Before sEBRT, GR can be predicted in patients with pre-sEBRT PSA <30.0 ng/ml and PSA doubling time (PSADT) >7.0 months, with a sensitivity of 95.2% (20/21), a specificity of 100% and an accuracy of 97.0%. CONCLUSION: Good responses to sEBRT can be expected in patients with local recurrence without systemic progression or isolated PSA recurrence after initial hormonal therapy when the patients show both pre-sEBRT PSA <30.0 ng/ml and PSADT >7.0 months.

Suzuki K, Koike H, Matsui H, Ono Y, Hasumi M, Nakazato H, Okugi H, Sekine Y, Oki K, Ito K, Yamamoto T, Fukabori Y, Kurokawa K, Yamanaka H. · Department of Urology, Gunma University School of Medicine, Maebashi, Japan. · Int J Cancer. · Pubmed #12115487 No free full text.

Abstract: Genistein is a major component of soybean isoflavone and has multiple functions resulting in antitumor effects. Prostate cancer is 1 of the targets for the preventive role of genistein. We examined the effect of genistein on human prostate cancer (LNCaP and PC-3) cells. Proliferation of both cell lines was inhibited by genistein treatment in a dose-dependent manner. To obtain the gene expression profile of genistein in LNCaP cells, we performed cDNA microarray analysis. The expression of many genes, including apoptosis inhibitor (survivin), DNA topoisomerase II, cell division cycle 6 (CDC6) and mitogen-activated protein kinase 6 (MAPK 6), was downregulated. Expression levels were increased more than 2-fold in only 4 genes. The glutathione peroxidase (GPx)-1 gene expression level was the most upregulated. Quantitative real-time polymerase chain reaction revealed significant elevation of transcript levels of GPx-1 in both LNCaP and PC-3 cells. Upregulation of gene expression levels accompanied elevation of GPx enzyme activities. In contrast, no significant changes were observed in the gene expression levels and enzyme activities of the other antioxidant enzymes, superoxide dismutase and catalase. GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells.

Kinouchi T, Maeda O, Ono Y, Meguro N, Kuroda M, Usami M. · Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Nakamichi, Higashinari-ku, Japan. · Int J Urol. · Pubmed #12110102 No free full text.

Abstract: A 75-year-old man with metastatic prostate cancer had been treated with goserelin acetate, and prostate specific antigen (PSA) had decreased, but 11/2 years after beginning the treatment of goserelin acetate, PSA was markedly elevated and serum testosterone was at normal level. After castration the serum testosterone was at castrate level and PSA decreased. In the present case, leuprorelin acetate 1-month depot suppressed the luteinizing hormone level in 1 month, even after the patient underwent castration.

Miyake H, Hara S, Yamanaka N, Ono Y, Eto H, Yamada Y, Takechi Y, Arakawa S, Kamidono S, Hara I. · Department of Urology, Kobe University School of Medicine, Kobe, Japan. · Urol Int. · Pubmed #12053023 No free full text.

Abstract: OBJECTIVE: The objective of the present study was to evaluate the usefulness of the combined systematic biopsy with serum prostate-specific antigen-alpha(1)-antichymotrypsin complex (PSA-ACT) level to predict the extent of prostate cancer. MATERIALS AND METHODS: Sixty-two patients with clinically organ-confined disease who underwent radical prostatectomy were evaluated for serum PSA and PSA-ACT levels, systematic biopsy, and the pathological stage. RESULTS: The incidence of extraprostatic disease in patients with more than half the biopsy cores positive or > or = 8 ng/ml PSA-ACT was significantly higher than those with less than half positive or <8 ng/ml PSA-ACT, respectively, whereas cancer in bilateral lobes or > or = 10 ng/ml PSA could not be used as a predictor of extraprostatic disease. Furthermore, in those with more than half the biopsy cores positive and > or = 8 ng/ml PSA-ACT or those with more than half the biopsy cores positive and > or = 10 ng/ml PSA, extraprostatic disease was significantly more common than in those with less than half positive and <8 ng/ml PSA-ACT or those with less than half positive and <10 ng/ml PSA, respectively. However, the incidence of extraprostatic disease predicted by these three variables was not significantly better than those by the two variables (percentage positive biopsy cores plus serum PSA-ACT or PSA). CONCLUSIONS: The combined systematic biopsy with serum PSA-ACT or PSA could be used as a useful predictor for the extent of prostate cancer. Patients with more than half the biopsy cores positive and > or = 8 ng/ml PSA-ACT or > or = 10 ng/ml PSA could avoid a prostatectomy because there is a high probability that they have extraprostatic disease.

Nishimura K, Nonomura N, Satoh E, Harada Y, Nakayama M, Tokizane T, Fukui T, Ono Y, Inoue H, Shin M, Tsujimoto Y, Takayama H, Aozasa K, Okuyama A. · Department of Urology, Graduate School of Medicine, Osaka University, Suita-City, Japan. · J Natl Cancer Inst. · Pubmed #11717335 links to  free full text

Abstract: BACKGROUND: Dexamethasone, a synthetic glucocorticoid, has clinical benefit in patients with hormone-refractory prostate cancer (HRPC), but the mechanisms responsible for its effects are unknown. The nuclear factor-kappaB (NF-kappaB)-dependent cytokine interleukin (IL) 6 (IL-6) is thought to stimulate growth of HRPC. Because dexamethasone interferes with NF-kappaB activation, we determined whether dexamethasone inhibits prostate cancer growth by working through the glucocorticoid receptor (GR) to interfere with NF-kappaB-IL-6 pathway. METHODS: Three human prostate cancer cell lines (DU145, PC-3, and LNCaP) were assessed for GR expression and responsiveness to dexamethasone. Levels of GR, NF-kappaB, and the cytoplasmic NF-kappB inhibitor IkappaBalpha were determined by western blotting and of IL-6 by enzyme immunoassay. The subcellular localization of NF-kappaB was analyzed by immunofluorescence. The effects of dexamethasone (thrice weekly injections of 1 microg/mouse) on DU145 xenografts in nude and severe combined immunodeficient (SCID) mice were evaluated. GR expression in human prostate cancers was assessed by immunohistochemistry. All statistical tests were two-sided. RESULTS: Dexamethasone dose dependently decreased GR levels and inhibited the growth of DU145 and PC-3 but not LNCaP cells (DU145 cells, P< .001; PC-3 cells, P = .009). Dexamethasone increased IkappaBalpha protein levels and the cytosolic accumulation of NF-kappaB in DU145 cells and decreased secreted IL-6 levels to 37 pg/mL (95% confidence interval [CI] = 33 pg/mL to 41 pg/mL), compared with 164 pg/mL (95% CI = 162 pg/mL to 166 pg/mL) secreted by ethanol-treated control cells. Dexamethasone inhibited the growth of DU145 xenografts in nude (P = .006) and SCID (P = .026) mice without affecting GR levels. Eight of 16 human prostate cancers expressed GR at high levels (>or=30% GR-positive cells). CONCLUSION: Dexamethasone inhibited the growth of GR-positive cancers, possibly through the disruption of the NF-kappaB-IL-6 pathway.

Hattori R, Ono Y, Gotho M, Yoshikawa Y, Hirabayashi S, Yamada S, Ohshima S. · Department of Urology, Nagoya University School of Medicine. · Nippon Hinyokika Gakkai Zasshi. · Pubmed #11593701 No free full text.

Abstract: PURPOSE: We report the clinical results and efficacy of laparoscopic radical prostatectomy for localized prostate cancer. PATIENTS AND METHODS: Between December, 1999 and June, 2000 we performed transperitoneal laparoscopic radial prostatectomy on 10 patients with T1 or T2 organ confined prostate cancer according to the techniques as described by Guillonneau et al. Different points were as follows: 1) We placed double J catheters during surgery to prevent ureteral injury. 2) We treated dorsal vein complex using an Endo-GIA-stapler. 3) We dissected the bladder neck from the prostate using an ultrasound scalpel in the manner to preserve the bladder neck. RESULT: We could not completed laparoscopic prostatectomy on two patients because of massive bleeding from dorsal vein and consuming too much time to suture urethra-bladder anastomosis. The average operating time in all cases was 8.1 hours including 1.8 hours in laparoscopic pelvic lymphadenectomy. The average estimated blood loss in all cases was 859 ml. There were 2 surgical complications with bladder injury and port site hernia. The histological examination revealed prostate cancer; pT2pNO in 8, pT3pNO in 2. The surgical margin and lymph nodes were negative in all patients. The duration of an indwelling catheter ranged from 5 to 40 days mean 17 days. The duration to recovery of normal micturition was 6 to 90 days, mean 40 days. CONCLUSION: Long-term follow-up and extensive studies are necessary to evaluate the efficacy of this procedure. It might provide shorter duration of an indwelling catheter and earlier recovery of normal micturition as compared with the conventional open surgery.

Hara I, Miyake H, Hara S, Yamanaka N, Ono Y, Eto H, Takechi Y, Arakawa S, Kamidono S. · Department of Urology, Kobe University School of Medicine, Kobe, Japan. · BJU Int. · Pubmed #11446846 No free full text.

Abstract: OBJECTIVE: To determine whether serum levels of the prostate-specific antigen-alpha1-antichymotrypsin complex (PSA-ACT) and its density (ACTD) in patients scheduled to undergo radical prostatectomy for clinically localized prostate cancer can predict organ-confined vs extraprostatic disease. PATIENTS AND METHODS: Serum samples were obtained from 62 patients with clinically localized prostate cancer before they underwent radical prostatectomy. PSA and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT, respectively. Furthermore, the PSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) were calculated. The relationships of serum PSA, PSA-ACT, PSAD, ACTD and the pathological stage of the prostatectomy specimens were analysed. RESULTS: The disease was organ-confined or extraprostatic in 30 and 32 men, respectively. In men with organ-confined cancer, the mean PSA and PSA-ACT levels were significantly lower than in those with extraprostatic disease. Furthermore, there were significantly higher mean PSAD and ACTD levels in men with extraprostatic than with organ-confined disease. There were also significant differences in PSA, PSA-ACT, PSAD and ACTD levels at each pathological stage, whereas there was no significant association between these variables and the Gleason score. Receiver-operating characteristic curve analysis for detecting organ-confined disease showed that PSA-ACT and ACTD had a larger area under the curve than PSA and PSAD, respectively, but these differences were not significant. Furthermore, PSA-ACT and ACTD provided significantly better sensitivity for detecting organ-confined disease than PSA and PSAD, respectively. CONCLUSIONS: Measuring PSA-ACT and ACTD may improve the preoperative evaluation of patients scheduled to undergo radical prostatectomy, because these factors better differentiate extraprostatic from organ-confined disease than PSA and PSAD.

Uchida K, Takeshima H, Akaza H, Ono Y. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. · Jpn J Clin Oncol. · Pubmed #10768873 links to  free full text

Abstract: BACKGROUND: The incidence of prostate cancer in Japan is not very high but it is the most increasing malignant tumor form. To decrease the mortality from cancer, detection of early cancer and early treatment are most effective. As a primary screening for prostate cancer, measurement of serum prostate-specific antigen(PSA) added to the health checkup system has not been assessed. METHODS: Among males who received a health checkup during a 30-month period, serum PSA levels were measured in males who desired prostate cancer screening. The cut-off value for PSA was 4.0 ng/ml. Males with serum PSA levels exceeding this value were referred for further screening by digital rectal examination (DRE) and transrectal ultrasonography (TRUS). In secondary screening, in all males with PSA levels of 10.0 ng/ml or more and in males in whom PSA levels were within the gray zone (4.0-10.0 ng/ml) and either DRE or TRUS showed abnormal findings, systematic prostate sextant needle biopsy was performed. RESULTS: Of 24528 males who received a health checkup, 1125 (4.6%) underwent prostate cancer screening. In 60 (5.3%) of these males, PSA levels exceeded the cut-off value. In 34 of 50 males who received further screening, prostate biopsy was performed. Seventeen males were diagnosed as having prostate cancer. Detection rates of prostate cancer were 1.53% (17/1125) in males overall and 2.1% (17/819) in males > or =50 years old. In 16 of 17 males, clinically localized cancer was suggested. In 12 of these patients, radical prostatectomy was performed. No lymph node metastasis was detected in any patient. CONCLUSIONS: These results suggest that prostate cancer screening using PSA as a primary screening parameter during general health checkups is very useful for efficiently detecting early-stage prostate cancer.