第二届中日泌尿外科会议抄录

Optimum Approach for Prostate Cancer Detection as an Initial Biopsy: A Prospective Randomized Study Comparing Transperineal versus Transrectal Systematic 12-Core Biopsy.

RYOEI HARA, YOSHIMASA JO, TOMOHIRO FUJII, NORIO KONDO, TERUHIKO YOKOYOMA, YOSHIYUKI MIYAJI AND ATSUSHI NAGAI

Kawasaki Medical School, Japan

OBJECTIVES : Transperineal and transrectal prostate biopsy are both used for prostate cancer detection. However, which approach is superior remains unknown. In this study, we performed a prospective randomized study to compare the efficacy of transperineal versus transrectal 12-core initial prostate biopsy.
METHODS : From May 2003 to October 2005, a prospective randomized study of transperineal versus transrectal 12-core biopsy (126 and 120 patients, respectively) was conducted in 246 patients with a prostate-specific antigen level of 4.0 to 20.0 ng/mL. All procedures were performed with the patient in the lithotomy position, with the transperineal and transrectal approach performed with spinal anesthesia (0.5% bupivacaine) or a caudal block (1% lidocaine), respectively. With both approaches, eight biopsy specimens were obtained systematically from the peripheral zone, including the apex, and four from the transition zone.
RESULTS : The cancer detection rate was 42.1% (53 of 126 patients) with the transperineal approach and 48.3% (58 of 120 patients) with the transrectal approach (P = 0.323). For all patients undergoing transperineal and transrectal biopsy, the cancer core rate (cancer core number/biopsy core number) was 13.7% (207 of 1512 cores) and 14.4% (208 of 1440 cores), respectively (P = 0.566). Apart from headache, presumably related to the spinal anesthesia, no significant differences were found in the complications between the two groups.
CONCLUSIONS : No significant differences were found in the cancer detection rate, cancer core rate, or complications between the two approaches. We believe that the preferred approach as an initial prostate biopsy is the transrectal approach, which does not require spinal anesthesia or another burdensome process.

Nadir PSA predicts androgen-independent progression after endocrine therapy in men with metastatic PCA.

Yang Bo, Sun Yinghao

Department of Urology, Changhai Hospital, Shanghai, China

Beneficial effects of neoadjuvant hormonal therapy prior to radical prostatectomy in patients with clinically localized prostate cancer.

Jun Qiu¹, Yoshihide Higuchi¹, Yusuke Yamada¹, Yasuo Ueda¹, Toru Suzuki¹, Takuo Maruyama¹, Nobuyuki Kondoh¹, Michio Nojima¹, Shingo Yamamoto¹, Mayumi Shincho², Seiichi Hirota², Hiroki Shima¹
1. Department of Urology, Hyogo College of Medicine、2. Department of Surgical Pathology, Hyogo College of Medicine, Japan

PURPOSE : It is well known that the short-term neoadjuvant hormonal therapy (NHT) in patients with clinically localized prostate cancer can significantly decrease the incidence of positive margins and result in a significant downstaging, but it does not reduce prostate-specific antigen (PSA) recurrence rate. The objective of this study was to evaluate PSA recurrence rate effects induced by long-term NHT in patients with clinically localized prostate cancer. 
METHODS : Between January 1999 and January 2005. 40 patients with clinically localized prostate cancer received NHT for 4 to 9 months prior to radical retropubic prostatectomy (RRP). The median age was 67.8 years (range, 54-76 years), the median preoperative PSA value was 20.2 ng/ml (range, 1.3-151 ng/ml), and the median follow-up was 59 months (range, 30-84 months). The clinical stage was T1 in 13 patients and T2 in 27. The Gleason score was < or = 6 in 20 patients and > or = 7 in 20. The pretreatment serum PSA value was < 20 ng/ml in 28 patients. The short-term (4~7 months) hormonal therapy was performed in 16 of 28 patients, while 12 of 28 patients received the long-term (8~9 months) hormonal therapy. Twelve patients with PSA > or = 20 ng/ ml received 4~9 months hormonal therapy.
RESULTS : Positive margin rates were significantly lower in the long-term NHT group than short-term group (0 vs. 12.5%). PSA recurrence rates were also lower in the long-term NHT group than short-term NHT group (8% vs. 56.3 %, p = 0.02) after 3 years. On the other hand, 12 patients (PSA³20 ng/ml) who received NHT for 4 to 9 months prior to RRP, positive margins were found in 3 (25%) patients, and PSA recurrence in 8 (67%) patients after 3 years.

Hormonal therapy combined with surgery in the management of prostate cancer.

Ming Cai, Haige Chen, Wei Xue, Yiran Huang

Department of Urology, Shanghai Renji Hospital, Shanghai, China

Prostate cancer mortality and the predictive value of PSA: a prospective cohort study of 231,937 adult male in Taiwan.

Fang-shun Lin and CP Wen

Department of Urology, pathology Mennonite Christian Hospital & Center for health policy Research and Development, National Health Research Institutes  Tai Wan

OBJECTIVES : Factors associated with prostate cancer mortality and the predictive value of PSA will be assessed.
Methods: The cohort consisted of 231,937 male individuals aged older than 20 years who participated in a standard medical screening program since 1994, including 46,951 subjects with one PSA test and 21,786 subjects with two or more tests. As of 2006, among 8914 deaths identified, there were 123 deaths listed as prostate cancer. Cox proportionate hazard model was used for calculation of hazard ratio (HR).

Results: Age was a major risk factor for prostate cancer deaths, doubling the risk every 5 years from age 50 on, and being 74 at age 70-74, 171 at age 75-79 and 300 at age 80+. Lower educated (2.84), smokers (1.21), physically inactive (1.30), obesity (1.34) and increasing height (above 164 cm) were associated with increased risks of prostate cancer deaths, but because of sample size limitation, most of them did not reach statistical significance. PSA also increased with age, with 0.2% above 10 at age 50-54, but 2.9% at age 70-74 and 5.0% at age 75+. PSA tended to decrease with BMI. The mortality risk (HR) increased exponentially when PSA increased from <3: 9.7 (PSA3-6.9), 64.8 (PSA 7-9.9), 177.8 (PSA 10-14.9) 396 (PSA 15-19.9), 494 (PSA> 20).   Because prostate cancer death is a rare event, 0.2% of all deaths at age 50-54, 0.8% at age 60-64, 1.0% at age 65-69, 1.8% at age 70-74 and 2% after age 75, even with such power of PSA in predicting prostate cancer mortality, say PSA>10, the false positive rates were extremely high: only one cancer death actually occurred in 235 positives (age 50-54), 127 positives (age 55-59), 147 positives (age 60-64), 128 (65-69), 57 positives (age 70-74) and 49 positives (age 75+).

CONCLUSION : PSA is a powerful predictor of prostate cancer deaths, but because the disease was so rare in Taiwan, there were just too many false positives for PSA to be an effective screening tool.

Clinical outcome in patients with locally and locally advanced prostate cancer treated with high-dose-rate brachytherapy.

Yoshimasa Jo, Ryoei Hara, Norio Kondo, Tomohiro Fujii, Teruhiko Yokoyama, Yoshiyuki Miyaji and Atsushi Nagai

Kawasaki Medical School, Japan

PURPOSE : To report the long-term results of treatment with locally and locally advanced prostate cancer using irridium-192 (Ir-192) high　dose rate brachytherapy (HDR-BT) and external beam radiotherapy (EBRT).
MATERIALS AND METHODS : 376 patients with T1c-T3bN0M0 prostate cancer diagnosed between October 1997 and March 2006 underwent HDR-BT with EBRT and were followed for at least 2 years. Treatment consisted of external irradiation (4-port irradiation) of the prostate at 36.8-39.0 Gy (13-16fraction) and HDR-BT at 18-24 Gy (2-4 fraction). No patient received adjuvant hormonal therapy after radiotherapy.
RESULTS : The most recent PSA level was 0.01 to 5.5ng/mL (median, 0.31ng/mL). The overall biochemical disease-free survival (BDFS) rate was 91 % at 8 years. The BDFS rate by risk category was 98% at 8 years for low risk, 91% for intermediate risk, and 82% for high risk. The BDFS rate was better in patients when initial PSA level was<20 ng/ml compared with≧20 ng/ml ( 93% and 79%, respectively, P<0.001). The treatment was well tolerated in all patients, with no grade 4 (RTOG) acute complications. However, urethral stricture was observed as the late complication in 50 patients (13.3%) mainly in 4 fractions HDR-BT group.
CONCLUSIONS : With a low complication rate and satisfactory BDFS rates, this combination therapy is considered to be an alternative method for locally and locally advanced prostate cancer and is expected to improve the QOL of patients.

SALVAGE HIGH-INTENSITY FOCUSED ULTRASOUND IN PATIENTS WITH RECURRENCE AFTER RADIATION THERAPY.

Toyoaki Uchida, Mayura Nakano, Masahiro Nitta, Sunao Shoji, Yoshihiro Nagata.

Tokai University Hachioji Hospital, Japan

OBJECTIVES : Men who have external beam radiation　therapy (EBRT) or interstitial　 brachytherapy　for clinically localized prostate cancer　have a 20–30% chance of having prostate specific antigen (PSA) failure. Salvage therapy is indicated when men treated with　radiotherapy, brachytherapy, or a　 combination　of these for presumed localized prostate　cancer have a recurrence. Prostatectomy, cryosurgery, brachytherapy and high-intensity focused ultrasound (HIFU) have　been used in the salvage setting.
To investigate the use of minimally invasive HIFU as a salvage therapy　 To investigate the use of minimally invasive HIFU as a salvage therapy.
PATIENTS AND METHODS : A review of 20 cases treated using the Sonablate® 500 HIFU device, between　June 2002 and May 2008, was carried out. All men had presumed organ-confined, recurrent prostate adenocarcinoma following radiation therapy. Treatment failure was defined by the revised ASTRO criteria (more than 2 ng/ ml elevation from nadir PSA or positive biopsy).
 RESULTS : The mean (range) age was 69 (59–85) years　with a mean pre- radiation PSA level of　12 (5.7–118) ng/mL. Mean duration after radiation therapy was 54 (24-120) months. The patients were followed for a mean (range) of 12 (2–50) months. Side-effects included urethral stricture in 2 of the 20 patients (10%), urinary tract infection or dysuria syndrome in five (25%), and urinary incontinence (grade I) in one (5%). Recto-urethral fistula occurred in two men (10%). Six (55%) of 11 patients who were followed more than 12 months were categorized biochemical disease-free. Among them, five of 6 patients were classified in low or intermediate risk group by D'Amico's　classification system.
CONCLUSIONS : Salvage HIFU can achieve good cancer control in patients with low and intermediate risk groups. Technological advances may provide　further therapeutic advantages and lower complication rates.

Clinicopathological study of prostate cancer in Mennonite Christian Hospital: statistical analysis of 97 cases in the past 9 years – preliminary report.

Fang-shu Lin，Yung-chen Tsai，Hui-ming Chung，Fuh-Jinn Luo*

Department of Urology, pathology*, Mennonite Christian Hospital, Taiwan

A SURVEY OF PROSTATIC CANCER
BACKGROUND : INCREASING LIFE EXPECTANCY, WESTERNIZATION OF ENVIRONMENT AND EATING HABIT RESULT IN INCREASING TENDENCY OF PROSTATIC CANCER. THROUGH THE HIGH RESOLUTION OF TRANSRECTAL ULTRASONOGRAPHY, AND HIGH SENSITIVITY OF PROSTATE SPECIFIC ANTIGEN (PSA) MAKE THE EARLY DIAGNOSIS OF PROSTATIC CA POSSIBLE.AT FIRST, WE USED ENDOCRINE THERAPY FOR THOSE PATIENTS, WHOM WE COLLECTED AT UROLOGY OPD AND THEN, AGGRESSIVE COMBINATION TREATMENT WITH RADIOTHERAPY WAS APPLIED laterLY. THROUGH THESE 97 CASES OF PRIMARY PROSTATIC CA., WE TREATED AT MENONITE HOSP; WE TRIED TO ANALYSIS THE INTERRELATION BETWEEN THE TREATMENT STRTEGY AND PROGNOSIS FROM CLINICOPATHOLOGIAL VIEWPOINT.
METHODS : SINCE 1996 TO 2004,WE COMPLIED THE CLINICAL DATAS INCLUDING DIAGNOSTIC DATE P’T 'S AGE, SYMTOMS, DIAGNOTIC METHODS, TREATMENTS, AND CLINICAL STAGING OF 97 CASES OF PRIMARY PROSTATIC CA. EITHER THROUGH TRANSRECTAL ULTRASOUND GUIDING PUNTCH NEEDLE BIOPSY OR TRANSURETHRAL RESECTION OF THE PROSTATE (TUR-P), WE APPLIED GLEASON SCORE FOR GRADING AND TISSUE SAMPLES EXAMIMED AND DIAGNOSISED BY ONE PATHOLOGY SPECIALIST.FROM THE STARTING DATE OF THE P'T'S EXAIMINATION, WE FOLLOWED UP (LOST RATE 6%) AND CACULATED THE SURVIVAL RATE PRECISELY UNTIL THE CLOSURE DATE OF DEC.31 OF 2004.
IN DATA ANALYSIS, WE USED STATA 7.0 EDITION (STATA CORPORATION, TEXAS), TO ANALYSIS THE PROBABILITY   AND SURVIVAL RELATED VARIABLES, BY KAPLAN-MEIER CURVE AND LONG-RANK TEST OF EQUALITY OR COX PROPORTIONAL HAZARD MODEL REPECTIVELY.
RESULTS : THE INCIDENCE WAS INCREASED ABRUPTLY IN 1998 ON YEARLY BASE.
THE AGE DISTRIBUTION OF OUR POOL WAS FROM 53 TO 90,74.65 IN AVERAGE, THE RANGE OF 70-79Y/O PREDOMINATE (53 cases, 55%). ABNORMAL PSA  (>4.0 ng/ml) WAS NOTED IN 93 CASES (ONLY 4 CASES ARE IN NROMAL RANGE). 85 CASES (89%) RECEIVED TRANSRECTAL PUNCH BIOPSY, WHILE 10 CASES TUR-P PERFORMED, THE REMAINED 2 CASES REFERED FROM OTHER HOSP.CLINICAL STAGEING WAS DONE WITH 79 PATIENTS (18 CASES WITHOUT RECORD) BY BONE SCAN, CT SCAN OR MRI, TO HAVE 23 CASES OF T1c.
PATHOLOGICAL GRADING BY GLEASON SCORE FOR 97 CASES OF ADENOCARCINOMA, SCORE <5,6,7,8,9 AND 10, EACH HOLD 6,31,32,14,10 AND 2 CASES RESPECTIVELY.TREATMENT START WITH ENDOCRINOLOGICAL THERAPY, 5 CASES (OUT OF 97) COMBINE WITH RADIOTHERAPY AT LATER PERIOD.
CONCLUSION : TREATMENT OF PROSTATIC CA IN OUR DEPARTMENT, WE CHOOSE THE ENDOCRINE THERAPY
AS STARTING MANAGEMENT, FOR LATER CLINICOPATHOLOGICAL STAGING PATIENTS, COMBINATION OF R/T BECOME INEVITABLE.

Natural history of lower urinary tract symptoms after radical retropubic prostatectomy: A comparison with the urination status of elderly women.

Xiu-Xian Wu, Rikiya Taoka, Hiroyuki Tsunemori, Masashi Inui, Mikio Sugimoto, and Yoshiyuki Kakehi

Faculty of Medicine, Kagawa University, Japan

OBJECTIVE : Anatomic modification of lower urinary tract in men who underwent radical retropubic prostatectomy (RRP) resembles that in women. The aim of this study is to clarify the natural history of lower urinary tract symptoms in men after RRP and to compare it with the urination status of elderly women.
MATERIALS AND METHODS : Self-administered questionnaires were mailed to 112 patients who underwent RRP for localized prostate cancer, and the response was obtained from 102 (91%) patients. The mean perioperative age of our patients with response was 65.9 ± 5.3 years. The questionnaires were conducted between 2 months and 6 years post-operatively (median: 44 months). Urination status was assessed using a self-administered questionnaire of the International Prostate Symptom Score (IPSS), QOL score, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Overactive Bladder Symptom Score (OABSS). Urinary status of 40 elderly women (mean age ± SD: 59.5 ± 6.9 years) who consulted in our outpatient clinic for unrelated conditions without lower urinary tract symptoms (e.g. microhematuria, simple renal cyst, etc.) were evaluated with the IPSS.
RESULTS : In men, total IPSS and QOL score showed statistically significant postoperative improvement (P = 0.0004, P = 0.0015, respectively). In particular, the voiding symptom subscore of IPSS also significantly improved (P < 0.0001). Moreover, ICIQ-SF score revealed an improvement of incontinence in the prostatectomy patients within one year postoperatively (P = 0.06). In contrast, the storage symptom subscore of IPSS was not different with time after RRP. Furthermore, the urinary urgency score of OABSS showed a progressive increase after RRP (P = 0.08). On the other hand, in elderly women, storage symptom subscore of IPSS was significantly higher than voiding symptom subscore (P < 0.0019).
CONCLUSIONS : Prostate cancer patients showed significant improvement in their voiding symptoms and continence status post-operatively. However, their storage symptoms did not improve following RRP, rather they progressively worsened. Consequently, careful follow-up and appropriate medical intervention are needed for men after RRP, as is the case in aging women.

The Diagnosis and Surgical Treatment of Primary Bladder Neck Obstruction in Women.

Kexin XU, Guoxi ZHANG, Xiaofeng W ANG

Department of Urology, Peking University People’s Hospital, China

Percutaneous Nephrolithotomy in Semisupine Position.

Kewei Xu, Jian Huang

Department of Urology, The Second Affiliated Hospital, Sun Yat-sen University, China

Direct and distant antitumor effects of a telomerase-selective oncolytic adenoviral agent, OBP-301, in a mouse prostate cancer model.

P Huang¹, H Kaku^1,3,  Watanabe^1,2, J Chen¹, T Saika¹, Y Nasu¹,and H Kumon^1,2,3

1. Department of Urology, 2. Innovation Center Okayama for Nanobio-Targeted Therapy, 3. Center for Gene and Cell Therapy, Okayama University, Japan.

We previously constructed OBP-301 (Telomelysin, a tumor- or telomerase-specific replication-competent adenovirus with human telomerase reverse transcriptase (hTERT) promoter), which showed a strong anticancer effect by inducing cell lysis of human non-small cell lung cancer and colorectal cancer cells. In order to investigate the utility of OBP-301 for prostate cancer treatment, we herein evaluate the cell killing and antitumor effects. First, in vitro hTERT-specific adenovirus transduction in human prostate cancer cells (LNCaP, PC3, DU145) was confirmed using the OBP-401 {Telomelysin-green fluorescent protein (GFP)}. There was no detectable transduction in human prostate normal cells (PrEC, PrSC). Consistently, the cell killing effect of OBP-301 was observed only in the cancer cells. Second, using an in vivo subcutaneous LNCaP tumor model in nude mice, we demonstrated that 3 intratumoral OBP-301 injections (107 PFU/tumor X 3days) were sufficient to eradicate the detectable LNCaP prostate tumor. We also demonstrated that the ispilateral treatment with OBP-301 significantly suppressed contralateral LNCaP tumor grown in both sides of the tumor model. Histological and immunohistochemical analyses revealed diffuse oncolytic degeneration and adenoviral E1A protein expression in both sides of the tumor.  Therefore, in situ OBP-301 administration could be a promising therapeutic strategy against prostate cancer and its metastatic lesions.

ER stress caused by immunosuppressant is involved in inflammatory reaction-a novel mechanism for immunosuppression？

Shuqi Du, Chuize Kong

Department of Urology, The First Affiliated Hospital, China Medical University，China

Aberrant methylation of the tumor suppressor gene DLC1 in the early pathogenic stage of renal cell carcinoma.

Qian Zhang

Department of Urology, Peking University First Hospital, China

The prognostic study of T1G3 bladder cancer and the establishment of prognostic evaluation system.

Xiaoqiang Liu，Guang Sun

Department of Urology, The Second Affiliated Hospital, Tianjin Medical University, China