公文 裕巳

We evaluated the efficiency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cisplatin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no effective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m2 IFM on days 1 to 5 and 70 mg/m2 CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50% reduction in prostate-specific antigen was observed in 9 of 18 patients (50%), and a more than 50% reduction in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29%). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC. However, in comparison with our previous chemotherapy regimen of IFM and CDDP, no additional long-lasting effects resulting from the inclusion of ECT could be affirmed.

The purpose of this study is to compare the performance of laparoscopic partial nephrectomy (LPN) with and without clamping of the renal artery and to evaluate the impact of clamping on postoperative renal function. A total of 20 patients underwent LPN, 13 without and 7 with clamping of the renal artery. The 2 groups were compared with respect to complications, blood loss, operative time, mean tumor size, and incidence of positive margins. Renal function was evaluated by pre- and postoperative renal scintigraphy using ^99mTechnetium-mercaptoacetyltriglycine (^99mTc-MAG3). Intraoperative blood loss was significantly higher in the group without clamping than in the group with clamping (p0.04). In the group with clamping, the median warm ischemic time was 35min (range 25-40min). The serum creatinine values and the renal scintigraphy showed no influence on postoperative renal function with or without clamping. In the group without clamping, 2 cases were showed positive surgical margins. The procedure performed with clamping of the renal artery is superior to the procedure performed without clamping as it provides the advantages of controlling hemorrhaging without injury to renal function and prolonging the surgical time and allowing for more accurate resection of renal tumors.

We have recently shown that a new therapeutic modality using the REIC/Dkk-3 gene (Ad-REIC) is effective against various human cancers, including those of prostate, testis and breast origins. The aim of the present study was to examine the sensitivity of bladder cancers to Ad-REIC and to clarify the molecular mechanisms that determine sensitivity/resistance. We found that 2 human bladder cancer cell lines, T24 and J82, are resistant to Ad-REIC. In T24 and J82 cells, the ER stress response and activation of JNK were observed in a manner similar to that in the sensitive PC3 cells. Translocation of Bax to mitochondria occurred in PC3 cells but not in T24 and J82 cells. Bcl-2 was remarkably overexpressed in T24 and J82 compared with the expression levels in sensitive cell lines. Treatment of T24 and J82 cells with a Bcl-2 inhibitor sensitized the cells to Ad-REIC-induced apoptosis. The results indicate that some human bladder cancers are resistant to apoptosis induced by overexpression of REIC/Dkk-3, which is at least in part due to up-regulation of Bcl-2. These results provide a basis for possible use of Bcl-2 as a marker of sensitive cancers and to try to sensitize resistant cancers to Ad-REIC by down-regulation of Bcl-2.

To evaluate morbidity in Hybrid Radical Prostatectomy (HRP, hybridized laparoscopic and open retropubic radical prostatectomy). The operative and pathological outcomes obtained in 25 consecutive patients who underwent HRP were reviewed. The median operating time was 220min, median blood loss was 550ml, and no patient required an allogenic blood transfusion. No severe postoperative complications were observed. The surgical margin was positive in 12% of all patients, and in 1 patient with pT2 or less (4.5%). These results indicate that HRP is safe and may be able to combine the benefits of both laparoscopic and open procedures.

From January 2004 to March 2007, 308 patients with clinically localized prostate cancer were treated using iodine-125 (125I) seed implantation (permanent brachytherapy) at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. We evaluated the treatment’s effi cacy and morbidity in 300 prostate cancer patients who were followed up for more than 1 month after brachytherapy. Based on the National Comprehensive Cancer Network (NCCN) guidelines, patients with a prostate volume of less than 40 ml in transrectal ultrasound imaging were classifi ed as low or intermediate risk. The median patient age was 67 years (range 50 to 79 years), the median prostate-specific antigen (PSA) value before biopsy was 6.95 ng/ml (range 1.13 to 24.7 ng/ml), and the median prostate volume was 24.33 ml (range 9.3 to 41.76 ml). The median follow-up was 18 months (range 1 to 36 months) and the PSA levels decreased in almost all patients after brachytherapy. Although 194 of 300 patients (64.7%) complained of diffi culty in urination, pollakisuria/urgency, miction pain, and/or urinary incontinence, all of which might be associated with radiation prostatitis during the fi rst month after brachytherapy, these symptoms gradually improved. 125I seed implantation brachytherapy is safe and eff ective for localized prostate cancer within short-term follow up.

Dynamin is a protein essential to endocytosis. Dynamin 2, a dynamin isoform, is expressed most intensely in testicular tissue; however, precise localization has never been studied. Therefore, we investigated the expression of dynamin 2 in rat testicular tissue using immunohistochemical methods, and discuss here the physiological function of this protein. Testicular tissues were obtained from Wistar rats at 10, 21 and 63 days of age. Immunohistochemistrical examination and Western blot analysis were conducted using dynamin 2 specific antibody. Western blot analysis showed that expression in 21- and 63-day-old rats was more intense than that in 10-day-old rats. Dynamin 2 expression was observed using immunohistochemical method in the seminiferous tubules of all rats. In the 63-day-old rats, the expression was intense, especially in spermatids in the earlier maturation stages and in spermatocytes, and was observed in Sertoli cells. However, in spermatids, the expression gradually declined as spermatids matured to spermatozoa. In the 21-day-old rats, the expression was evident in spermatocytes and Sertoli cells, but that in the 10-day-old rats was weak. Intense expression of dynamin 2 during spermatogenesis suggests that this protein plays an important role in this process.

Tremendous excitement has been generated by the use of botulinum toxin for the treatment of various types of urethral and bladder dysfunction over the past several years. Botulinum toxin is the most lethal naturally occurring toxin known to mankind. Why, then, would an urologist want to use this agent to poison the bladder or urethral sphincter? In this review article we will examine the mechanisms underlying the effects of botulinum toxin treatment. We will discuss the current use of this agent within the urologic community and will provide perspectives on future targets of botulinum toxin.

We performed laparoscopic prostatectomy in seven cases with organ-confined prostate cancer. In 6 cases, the surgery was completed successfully and the mean operative time was 424 min. Volume of blood loss was 200 to 3,200 ml and catheterization lasted 6 to 37 days. No major complications were observed in 6 of the cases. In one case, open surgical conversion was necessary mainly due to a bladder injury. Although these were the first cases of laparoscopic prostatectomy in our institution, the technical difficulty and complexity of the surgery were moderate. We believe that laparoscopic radical prostatectomy will become a standard option for the treatment of organ-confined prostate cancer.