Fuji Technology Press Ltd. Acta Medica Okayama 1883-8030 17 1 2022 Questionnaire Survey on COVID-19 Vaccination at Okayama University in Japan: Factors Promoting Vaccination Among Young Adults 21 30 EN Chigusa Higuchi Okayama University Health Service Center Naomi Matsumoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshiaki Iwasaki Okayama University Health Service Center Takashi Yorifuji Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junichiro Yamazaki Okayama University Yasutomo Nasu Okayama University Hirofumi Makino Okayama University COVID-19 has been prevalent worldwide since 2019. Increasing COVID-19 vaccination coverage is an important measure to combat the disease. An online survey was conducted with university students and personnel who were vaccinated against COVID-19 at a mass vaccination event to examine the factors promoting vaccination among young adults. The online survey was conducted with persons vaccinated at Okayama University from June 5 to September 27, 2021. Although the number of those who had fever >37.5°C increased after the second vaccination compared to the first, the vaccinated persons got more satisfied after the second shot. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 134 2 2022 吉備中央町が本邦初の革新的事業連携型国家戦略特区指定を受けて―デジタル田園健康特区と規制改革の実現に向けた大学の役割― 115 118 EN Yasutomo Nasu Executive Director for Research, Okayama University Jota Maki Department of Obstetrics and Gynecology, Okayama University Hospital Jun Sakurai Center for Innovative Clinical Medicine, Okayama University Hospital Hisashi Masuyama Department of Obstetrics and Gynecology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshinobu Maeda Executive Director for Hospital, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0300-8177 478 8 2022 Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma 1779 1790 EN Jun Matsumoto Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Anzu Nishimoto Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Watari Department of Urology, National Hospital Organization Okayama Medical Center Hideo Ueki Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Shoya Shiromizu Department of Pharmacy, Okayama University Hospital Naohiro Iwata Department of Pharmacy, Okayama University Hospital Tatsuaki Takeda Department of Pharmacy, Okayama University Hospital Soichiro Ushio Department of Pharmacy, Okayama University Hospital Makoto Kajizono Department of Pharmacy, Okayama University Hospital Masachika Fujiyoshi Department of Pharmacy, Tottori University Hospital Toshihiro Koyama Department of Pharmaceuticals Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Koichiro Wada Department of Urology, Faculty of Medicine, Shimane University Yoshito Zamami Department of Pharmacy, Okayama University Hospital Yasutomo Nasu Department of Urology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Noritaka Ariyoshi Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University UDP-glucuronosyltransferase (UGT) metabolizes a number of endogenous and exogenous substrates. Renal cells express high amounts of UGT; however, the significance of UGT in patients with renal cell carcinoma (RCC) remains unknown. In this study, we profile the mRNA expression of UGT subtypes (UGT1A6, UGT1A9, and UGT2B7) and their genetic variants in the kidney tissue of 125 Japanese patients with RCC (Okayama University Hospital, Japan). In addition, we elucidate the association between the UGT variants and UGT mRNA expression levels and clinical outcomes in these patients. The three representative genetic variants, namely, UGT1A6 541A > G, UGT1A9 i399C > T, and UGT2B7-161C > T, were genotyped, and their mRNA expression levels in each tissue were determined. We found that the mRNA expression of the three UGTs (UGT1A6, UGT1A9, and UGT2B7) are significantly downregulated in RCC tissues. Moreover, in patients with RCC, the UGT2B7-161C > T variant and high UGT2B7 mRNA expression are significantly correlated with preferable cancer-specific survival (CSS) and overall survival (OS), respectively. As such, the UGT2B7-161C > T variant and UGT2B7 mRNA expression level were identified as significant independent prognostic factors of CSS and CSS/OS, respectively. Taken together, these findings indicate that UGT2B7 has a role in RCC progression and may, therefore, represent a potential prognostic biomarker for patients with RCC. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4425 13 2 2022 Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice 285 EN Ruizhi Xue Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Wenfeng Lin Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirofumi Fujita Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jingkai Sun Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Kinoshita Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Ochiai Laboratory of Veterinary Hygiene, Nippon Veterinary and Life Science University Junichiro Futami Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideyo Ohuchi Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Zhengyan Tang Department of Urology, Xiangya Hospital, Central South University Peng Huang Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromi Kumon Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University The role of Dickkopf-3 (Dkk3)/REIC (The Reduced Expression in Immortalized Cells), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of Dkk3/REIC in the male reproductive process, we studied the Dkk3/REIC knock-out (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between Dkk3/REIC-KO and wild-type (WT) male mice. To further explore the underlying molecular mechanism, we performed RNA sequencing (RNA-seq) analysis of testicular tissues. Our results showed that spermiation failure existed in seminiferous tubules of Dkk3/REIC-KO mice, and sperm from Dkk3/REIC-KO mice exhibited inferior motility (44.09 +/- 8.12% vs. 23.26 +/- 10.02%, p < 0.01). The Ultrastructure examination revealed defects in the sperm fibrous sheath of KO mice. Although the average count of Dkk3/REIC-KO epididymal sperm was less than that of the wild-types (9.30 +/- 0.69 vs. 8.27 +/- 0.87, x10(6)), neither the gap (p > 0.05) nor the difference in the sperm vitality rate (72.83 +/- 1.55% vs. 72.50 +/- 0.71%, p > 0.05) were statistically significant. The RNA-seq and GO (Gene Oncology) enrichment results indicated that the differential genes were significantly enriched in the GO terms of cytoskeleton function, cAMP signaling and calcium ion binding. Collectively, our research demonstrates that Dkk3/REIC is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice. No potential conflict of interest relevant to this article was reported.

Ivyspring International Publisher Acta Medica Okayama 1837-9664 13 3 2022 Identification of MICALL2 as a Novel Prognostic Biomarker Correlating with Inflammation and T Cell Exhaustion of Kidney Renal Clear Cell Carcinoma 1214 1228 EN Wenfeng Lin Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Wenwei Chen Department of Urology, Zhujiang Hospital, Southern Medical University Jisheng Zhong School of Medicine, Xiamen University Hideo Ueki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Abai Xu Department of Urology, Zhujiang Hospital, Southern Medical University Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chunxiao Liu Department of Urology, Zhujiang Hospital, Southern Medical University Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Peng Huang Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Purpose: The interplay of inflammation and immunity affects all stages from tumorigenesis to progression, and even tumor response to therapy. A growing interest has been attracted from the biological function of MICALL2 to its effects on tumor progression. This study was designed to verify whether MICALL2 could be a prognostic biomarker to predict kidney renal clear cell carcinoma (KIRC) progression, inflammation, and immune infiltration within tumor microenvironment (TME). Methods: We firstly analyzed MICALL2 expressions across 33 cancer types from the UCSC Xena database and verified its expression in KIRC through GEPIA platform and GEO datasets. The clinicopathological characteristics were further analyzed based on the median expression. Kaplan-Meier method, univariate and multivariate analyses were applied to compare survival outcomes. ESTIMATE and CIBERSORT algorithms were performed to assess immune infiltration, and a co-expression analysis was conducted to evaluate the correlation between MICALL2 and immunoregulatory genes. Enrichment analysis was finally performed to explore the biological significance of MICALL2. Results: MICALL2 was highly expressed in 16 types of cancers compared with normal tissues. MICALL2 expression increased with advanced clinicopathological parameters and was an independent predictor for poor prognosis in KIRC. Moreover, MICALL2 closely correlated with inflammation-promoting signatures and immune infiltration including T cell exhaustion markers. Consistently, MICALL2 involved in the regulation of signaling pathways associated with tumor immunity, tumor progression, and impaired metabolic activities. Conclusion: MICALL2 can function as a prognostic biomarker mediating inflammation, immune infiltration, and T cell exhaustion within the microenvironment of KIRC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Clinical Efficacy and Safety of Sitafloxacin 200 mg Once Daily for Refractory Genitourinary Tract Infections 763 766 EN Takehiro Iwata Department of Urology, Okayama University Hospital Takuya Sadahira Department of Urology, Okayama University Hospital Yuki Maruyama Department of Urology, Okayama University Hospital Takanori Sekito Department of Urology, Okayama University Hospital Kasumi Yoshinaga Department of Urology, Okayama University Hospital Shogo Watari Department of Urology, Okayama University Hospital Kentaro Nagao Department of Urology, Okayama University Hospital Tatsushi Kawada Department of Urology, Okayama University Hospital Yusuke Tominaga Department of Urology, Okayama University Hospital Shingo Nishimura Department of Urology, Okayama University Hospital Atsushi Takamoto Department of Urology, Okayama University Hospital Tomoko Sako Department of Urology, Okayama University Hospital Kohei Edamura Department of Urology, Okayama University Hospital Yasuyuki Kobayashi Department of Urology, Okayama University Hospital Motoo Araki Department of Urology, Okayama University Hospital Ayano Ishii Department of Urology, Okayama University Hospital Masami Watanabe Department of Urology, Okayama University Hospital Toyohiko Watanabe Department of Urology, Okayama University Hospital Yasutomo Nasu Department of Urology, Okayama University Hospital Koichiro Wada Department of Urology, Okayama University Hospital Clinical Study Protocol 10.18926/AMO/62820 The aim of this ongoing trial is to evaluate the clinical efficacy and safety of sitafloxacin (STFX) 200 mg once daily (QD) for 7 days in patients with refractory genitourinary tract infections, which include recurrent or complicated cystitis, complicated pyelonephritis, bacterial prostatitis, and epididymitis. The primary endpoint is the microbiological efficacy at 5-9 days after the last administration of STFX. Recruitment began in February 2021, and the target total sample size is 92 participants. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 6 2021 Testosterone Recovery after Neoadjuvant Gonadotropin-Releasing Hormone Antagonist versus Agonist on Permanent Iodine-125 Seed Brachytherapy in Prostate Cancer Patients: A Propensity Score Analysis 705 711 EN Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tatsushi Kawada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Takamoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Sako Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/62810 Optimal neoadjuvant hormone therapy (NHT) for reducing prostate cancer (PC) patients’ prostate volume pre-brachytherapy is controversial. We evaluated the differential impact of neoadjuvant gonadotropin-releasing hormone (GnRH) antagonist versus agonist on post-brachytherapy testosterone recovery in 112 patients treated pre-brachytherapy with NHT (GnRH antagonist, n=32; GnRH agonists, n=80) (Jan. 2007-June 2019). We assessed the effects of patient characteristics and a GnRH analogue on testosterone recovery with logistic regression and a propensity score analysis (PSA). There was no significant difference in the rate of testosterone recovery to normal levels (> 300 ng/dL) between the GnRH antagonist and agonists (p=0.07). The GnRH agonists induced a significantly more rapid testosterone recovery rate at 3 months post-brachytherapy versus the GnRH antagonist (p<0.0001); there was no difference in testosterone recovery at 12 months between the GnRH antagonist/agonists (p=0.8). In the multivariate analysis, no actor was associated with testosterone recovery. In the PSA, older age and higher body mass index (BMI) were significantly associated with longer testosterone recovery. Post-brachytherapy testosterone recovery was quicker with the neoadjuvant GnRH agonists than the antagonist, and the testosterone recovery rate was significantly associated with older age and higher BMI. Long-term follow-ups are needed to determine any differential effects of GnRH analogues on the quality of life of brachytherapy-treated PC patients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 4 2021 The Cell Cycle Checkpoint Gene, RAD17 rs1045051, Is Associated with Prostate Cancer Risk 415 421 EN Jingkai Sun Department of Urology, Zhujiang Hospital, Southern Medical University Wenfeng Lin Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Qixu Wang Department of Urology, Zhujiang Hospital, Southern Medical University Akiko Sakai Department of Molecular Genetics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ruizhi Xue Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chunxiao Liu Department of Urology, Zhujiang Hospital, Southern Medical University Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Abai Xu Department of Urology, Zhujiang Hospital, Southern Medical University Peng Huang Department of Urology, Zhujiang Hospital, Southern Medical University Original Article 10.18926/AMO/62379 Human RAD17, as an agonist of checkpoint signaling, plays an essential role in mediating DNA damage. This hospital-based case-control study aimed to explore the association between RAD17 rs1045051, a missense sin-gle nucleotide polymorphism (SNP), and prostate cancer risk. Subjects were 358 prostate cancer patients and 314 cancer-free urology patients undergoing treatment at the Zhujiang Hospital of Southern Medical University in China. RAD17 gene polymorphism rs1045051 was evaluated by the SNaPshot method. Compared with the RAD17 gene polymorphism rs1045051 AA genotype, there was a higher risk of prostate cancer for the CC gen-otype (adjusted odds ratio [AOR] = 1.731, 95% confidence interval [95%CI] = 1.031－2.908, p = 0.038). Compared with the A allele, the C allele was significantly associated with the disease status (AOR = 1.302, 95%CI = 1.037－1.634, p = 0.023). All these findings indicate that in the SNP rs1045051, both the CC genotype and C allele may have a substantial influence on the prostate cancer risk. No potential conflict of interest relevant to this article was reported.

Ivyspring International Publisher Acta Medica Okayama 1449-2288 17 12 2021 Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer 3255 3267 EN Wenfeng Lin Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jingkai Sun Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naijin Xu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chunxiao Liu Department of Urology, Zhujiang Hospital, Southern Medical University Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Abai Xu Department of Urology, Zhujiang Hospital, Southern Medical University Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Peng Huang Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Repeated cycles of first-line chemotherapy drugs such as doxorubicin (DOX) and cisplatin (CIS) trigger frequent chemoresistance in recurrent urothelial bladder cancer (UBC). Nitroxoline (NTX), an antibiotic to treat urinary tract infections, has been recently repurposed for cancer treatment. Here we aimed to investigate whether NTX suppresses drug-resistant UBC and its molecular mechanism. The drug-resistant cell lines T24/DOX and T24/CIS were established by continual exposure of parental cell line T24 to DOX and CIS, respectively. T24/DOX and T24/CIS cells were resistant to DOX and CIS, respectively, but they were sensitive to NTX time-and dose-dependently. Overexpressions of STAT3 and P-glycoprotein (P-gp) were identified in T24/DOX and T24/CIS, which could be reversed by NTX. Western blot revealed that NTX downregulated p-STAT3, c-Myc, Cyclin D1, CDK4, CDK6, Bcl-xL, Mcl-1, and Survivin, which were further confirmed by Stattic, a selective STAT3 inhibitor. In vivo, NTX exhibited the significant anti-tumor effect in T24/DOX and T24/CIS tumor-bearing mice. These results suggested that NTX-induced P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC were mediated by inhibition of STAT3 signaling. Our findings repurpose NTX as a novel STAT3 inhibitor to induce P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0041-1345 53 5 2021 ABO Blood Incompatibility Positively Affects Early Graft Function: Single-Center Retrospective Cohort Study 1494 1500 EN Shogo Watari Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Kasumi Yoshinaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Risa Kubota Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Masashi Kitagawa Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hiroshi Morinaga Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hitoshi Sugiyama Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Jun Wada Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Background We investigated the association between ABO-incompatible (ABO-I) kidney transplantation and early graft function. Methods We retrospectively analyzed 95 patients who underwent living donor kidney transplantation between May 2009 and July 2019. It included 61 ABO-compatible (ABO-C) and 34 ABO-I transplantations. We extracted data on immunologic profile, sex, age, cold ischemic time, type of immunosuppression, and graft function. Two definitions were used for slow graft function (SGF) as follows: postoperative day (POD) 3 serum creatinine level >3 mg/dL and estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m2. Logistic regression analysis was performed to analyze the effect of ABO-I on the incidence of SGF. Results The characteristics between the ABO-C and ABO-I were not different. ABO-I received rituximab and plasma exchange. Patients also received tacrolimus and mycophenolate mofetil for 2 weeks and prednisolone for 1 week before transplantation as preconditioning. Of the 95 study patients, 19 (20%) and 21 (22%) were identified with SGF according to POD 3 serum creatinine level or eGFR, respectively. Multivariable analysis revealed that ABO-I significantly reduced the incidence of SGF (odds ratio, 0.15; 95% confidence interval, 0.03-0.7; P = .02), and cold ischemic time >150 min increased the incidence of SGF (odds ratio, 6.5; 95% confidence interval, 1.7-25; P = .006). Similar results were identified in POD 3 eGFR. Inferior graft function in patients with SGF was identified up to 6 months after transplantation. Conclusion ABO-I reduces the incidence of SGF, which is associated with an inferior graft function up to 6 months. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2050-4527 2021 Feasible kidney donation with living marginal donors, including diabetes mellitus EN Kasumi Yoshinaga Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Motoo Araki Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Koichiro Wada Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Takanori Sekito Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Shogo Watari Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Yuki Maruyama Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Yosuke Mitsui Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Takuya Sadahira Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Risa Kubota Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Shingo Nishimura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Kohei Edamura Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Yasuyuki Kobayashi Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Masashi Kitagawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Masami Watanabe Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Toyohiko Watanabe Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Yasutomo Nasu Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Objectives: To compare the donor outcomes of living donor kidney transplantation between standard donors (SDs) and marginal donors (MDs) including diabetic patients (MD + DM). Methods: MDs were defined according to Japanese guideline criteria: (a) age >70-years, (b) blood pressure <= 130/80 mmHg on hypertension medicine, (c) body mass index >25 to <= 32 kg/m(2), (d) 24-h creatinine clearance >= 70 to <80 ml/min/1.73 m(2), and (e) hemoglobin A1c > 6.2 or <= 6.5 with oral diabetic medicine. Fifty-three of 114 donors were MDs. We compared donor kidney functions until 60 months postoperatively. Results: No kidney function parameters were different between SDs and MDs. When comparing SD and MD + DM, MD + DM had a lower postoperative eGFR (48 vs. 41 (1 (month), p = .02), 49 vs. 40 (12, p < .01), 48 vs. 42 (24, p = .04), 47 vs. 38 (36, p = .01)) and the percentage of residual eGFR (SD vs. MD + DM: 63 vs. 57 (1 (month), p < .01), 63 vs. 57 (2, p < .01), 64 vs. 56 (12, p < .01), 63 vs. 57 (24, p < .01), 63 vs. 52 (36, p = .02)). However, when MD with a single risk factor of DM was compared to SD, the difference disappeared. Nine out of 12 (75%) MD + DM had >= 2 risk factors. Conclusions: Although long-term observation of donor kidney function is necessary, careful MD + DM selection had the potential to expand the donor pool. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 133 1 2021 第34回日本泌尿器内視鏡学会総会開催報告 83 84 EN Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 133 1 2021 遠隔治療　泌尿器科編 73 75 EN Yusuke Tominaga Department of Urology, Okayama University Hospital Motoo Araki Department of Urology, Okayama University Hospital Yasutomo Nasu Department of Urology, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2490 21 1 2021 Photodynamic diagnostic ureteroscopy using the VISERA ELITE video system for diagnosis of upper-urinary tract urothelial carcinoma: a prospective cohort pilot study 45 EN Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryuta Tanimoto Department of Urology, Kagawa Prefectural Central Hospital Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shogo Watari Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirochika Nakajima Department of Urology, Fukuyama City Hospital Herik Acosta Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Takamoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Sako Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background The advantages of photodynamic diagnostic technology using 5-aminolevulinic acid (ALA-PDD) have been established. The aim of this prospective cohort study was to evaluate the usefulness of ALA-PDD to diagnose upper tract urothelial carcinoma (UT-UC) using the Olympus VISERA ELITE video system. Methods We carried out a prospective, interventional, non-randomized, non-contrast and open label cohort pilot study that involved patients who underwent ureterorenoscopy (URS) to detect UT-UC. 5-aminolevulinic acid hydrochloride was orally administered before URS. The observational results and pathological diagnosis with ALA-PDD and traditional white light methods were compared, and the proportion of positive subjects and specimens were calculated. Results A total of 20 patients were enrolled and one patient who had multiple bladder tumors did not undergo URS. Fifteen of 19 patients were pathologically diagnosed with UT-UC and of these 11 (73.3%) were ALA-PDD positive. Fourteen of 19 patients were ALA-PDD positive and of these 11 were pathologically diagnosed with UC. For the 92 biopsy specimens that were malignant or benign, the sensitivity for both traditional white light observation and ALA-PDD was the same at 62.5%, whereas the specificities were 73.1% and 67.3%, respectively. Of the 38 specimens that were randomly biopsied without any abnormality under examination by both white light and ALA-PDD, 11 specimens (28.9%) from 5 patients were diagnosed with high grade UC. In contrast, four specimens from 4 patients, which were negative in traditional white light observation but positive in ALA-PDD, were diagnosed with carcinoma in situ (CIS). Conclusions Our results suggest that ALA-PDD using VISERA ELITE is not sufficiently applicable for UT-UC. Nevertheless, it might be better particularly for CIS than white light and superior results would be obtained using VISERA ELITE II video system. Trial registration: The present clinical study was approved by the Okayama University Institutional Review Board prior to study initiation (Application no.: RIN 1803-002) and was registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (Accession no.: UMIN000031205). No potential conflict of interest relevant to this article was reported.

Oxford University Press Acta Medica Okayama 0368-2811 51 1 2020 Long-term ureteroscopic management of upper tract urothelial carcinoma: 28-year single-centre experience 130 137 EN Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Motoo Araki Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Kasumi Yoshinaga Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Manoj Monga Department of Urology, The Cleveland Clinic Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Science Hiromi Kumon Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University Background Long-term survival outcomes of patients who undergo endoscopic management of non-invasive upper tract urothelial carcinoma remain uncertain. The longest mean follow-up period in previous studies was 6.1 years. This study reports the long-term outcomes of patients with upper tract urothelial carcinoma who underwent ureteroscopic ablation at a single institution over a 28-year period. Methods We identified all patients who underwent ureteroscopic management of upper tract urothelial carcinoma as their primary treatment at our institution between January 1991 and April 2011. Survival outcomes, including overall survival, cancer-specific survival, upper-tract recurrence-free survival and renal unit survival, were estimated using Kaplan－Meier methodology. Results A total of 15 patients underwent endoscopic management, with a mean age at diagnosis of 66 years. All patients underwent ureteroscopy, and biopsy-confirmed pathology was obtained. Median (range; mean) follow-up was 11.7 (2.3–20.9, 11.9) years. Upper tract recurrence occurred in 87% (n = 13) of patients. Twenty percent (n = 3) of patients proceeded to nephroureterectomy. The estimated cancer-specific survival rate was 93% at 5, 10, 15 and 20 years. Estimated overall survival rates were 86, 80, 54 and 20% at 5, 10, 15 and 20 years. Only one patient experienced cancer-specific mortality. The estimated mean and median overall survival times were 14.5 and 16.6 years, respectively. The estimated mean cancer-specific survival time was not reached. Conclusions Although upper tract recurrence is common, endoscopic management of non-invasive upper tract urothelial carcinoma provides a 90% cancer-specific survival rate at 20 years in selected patients. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 132 2 2020 序説　人工知能（AI）への期待 91 91 EN Yasutomo Nasu Okayama University Executive Director for Research, Vice President No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Combined Laparoscopic and CT Monitoring of the Ice-Ball Margin during Cryoablation for Renal Cell Carcinoma Associated with von Hippel-Lindau Disease: First Case 443 448 EN Takanori Sekito Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takao Hiraki Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayu Uka Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Komaki Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Matsui Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshihiro Iguchi Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Katayama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kasumi Yoshinaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shogo Watari Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Risa Kubota Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Takamoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Sako Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Kanazawa Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/60806 We report a 47-year-old Japanese female with 10 previous treatments for multiple bilateral renal cell carcinoma (RCC) associated with von Hippel-Lindau disease. The 14-mm right lower pole renal tumor was in contact with the right ureter. Laparoscopic cryoablation was performed to protect the ureter wrapped with gauze. Computed tomography (CT) monitoring was used to confirm the precise ≥ 6 mm ice-ball margin. There was no local progression at 6-months post-surgery. The serum creatinine has been stable. This is apparently the first report of combined laparoscopic and CT monitoring of an ice-ball formation and its margin during cryoablation for RCC. No potential conflict of interest relevant to this article was reported.

Ivyspring International Publisher Acta Medica Okayama 1837-9664 11 22 2020 Nitroxoline inhibits bladder cancer progression by reversing EMT process and enhancing anti-tumor immunity 6633 6641 EN Naijin Xu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Wenfeng Lin Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jingkai Sun Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Abai Xu Department of Urology, Zhujiang Hospital, Southern Medical University Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kai Guo Department of Urology, Zhujiang Hospital, Southern Medical University Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Gonghui Li Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine Chunxiao Liu Department of Urology, Zhujiang Hospital, Southern Medical University Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Peng Huang Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nitroxoline is considered to be an effective treatment for the urinary tract infections. Recently, it has been found to be effective against several cancers. However, few studies have examined the anti-tumor activity of nitroxoline in bladder cancer. The purpose of the study was to reveal the possible mechanisms how nitroxoline inhibited bladder cancer progression. In vitro assay, we demonstrated that nitroxoline inhibited bladder cancer cell growth and migration in a concentration-related manner. Western blot analysis demonstrated that nitroxoline downregulated the expressions of epithelial mesenchymal transition (EMT)-related proteins. Furthermore, treatment with nitroxoline in the C3H/He mice bladder cancer subcutaneous model resulted in significant inhibition of tumor growth. Moreover, the percentage of myeloid-derived suppressor cells (MDSC) in peripheral blood cells significantly decreased after treatment of nitroxoline. Taken together, our results suggested that nitroxoline may be used as a potential drug for bladder cancer. No potential conflict of interest relevant to this article was reported.

Elsevier B.V. Acta Medica Okayama 22143882 2021 2020 Cytopathic effects and local immune responses in repeated neoadjuvant HSV-tk + ganciclovir gene therapy for prostate cancer 280 288 EN Nobuyuki Yanagisawa Department of Pathology, St. Marianna University School of Medicine Yokohama-City Seibu Hospital, Yokohama Takefumi Satoh Department of Urology, Kitasato University School of Medicine Ken-ichi Tabata Department of Urology, Kitasato University School of Medicine Hideyasu Tsumura Department of Urology, Kitasato University School of Medicine Yasutomo Nasu Department of Urology, Okayama University Masami Watanabe Department of Urology, Okayama University Timothy C. Thompson Department of Genitourinary Medical Oncology - Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center Isao Okayasu Department of Pathology, Kitasato University School of Medicine Yoshiki Murakumo Department of Pathology, Kitasato University School of Medicine Shiro Baba Department of Pathology, Kitasato University School of Medicine Masatsugu Iwamura Department of Urology, Kitasato University School of Medicine ObjectiveCytopathic effects and local immune response were analyzed histologically in prostatic carcinoma (PCa) with in situ herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT). MethodsFour high-risk PCa patients who received HSV-tk/GCV GT were investigated. After two cycles of intraprostatic injection of HSV-tk and administration of GCV, radical prostatectomy was performed. Formalin-fixed, paraffin-embedded sections were evaluated using immunohistochemistry. PCa with hormone therapy (HT, n = 3) or without neoadjuvant therapy (NT, n = 4) that were equivalent in terms of risk were also examined as reference. Immunoreactively-positive cells were counted in at least three areas in cancer tissue. Labeling indices (LI) were calculated as percentage values. ResultsssDNA LI in GT increased, indicating apoptosis, as well as tumor-infiltrating lymphocytes and CD68-positive macrophages, compared with their biopsies. GT cases showed significantly higher numbers of ssDNA LI, CD4/CD8-positive T cells and CD68-positive macrophages including M1/M2 macrophages than HT or NT cases. However, there was no significant difference in CD20-positive B cells among the types of case. There were strong correlations between CD8+ T cells and CD68+ macrophages (ρ = 0.656, p < 0.0001) as well as CD4+ T cells and CD20+ B cells (ρ = 0.644, p < 0.0001) in PCa with GT. ConclusionsEnhanced cytopathic effect and local immune response were might be indicated in PCa patients with HSV-tk/GCV gene therapy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 1 2020 Robotic Renal Autotransplantation: A Feasibility Study in a Porcine Model 53 58 EN Risa Kubota Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kasumi Kawamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuichi Ariyoshi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Iwata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Takamoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Sako Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuzuki Kano Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Kitagawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Sugiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/57953 We investigated the feasibility of robotic renal autotransplantation (RAT) in a porcine model to reduce invasiveness of RAT. Five pigs underwent robotic RAT using the da Vinci® robotic system. A robotic left nephrectomy was performed in all cases. Robotic RAT was performed on the left side in all but one case. Four ports were used. In 3 cases, the kidney was taken out through the GelPort® and irrigated on ice with Ringer’s solution. In 2 cases, a complete intracorporeal robotic RAT was performed. An end-to-side anastomosis was performed between the renal vein and the external iliac vein and between the renal artery and the external iliac artery. Ureteroneocystostomy was also performed in 2 cases. All cases were performed robotically without open conversion. The median (IQR) console time was 3.1 (0.7) h, and the operative time was 3.8 (1.1) h. The estimated blood loss was 30 (0) ml. The warm ischemia time was 4.0 (0.2) min, and the cold ischemia time was 97 (17) min. Intracorporeal transarterial hypothermic renal perfusion was feasible in the 2 complete intracorporeal robotic RAT cases by using a perfusion catheter through a laparoscopic port. Robotic RAT has the potential to be a new minimally invasive substitute for conventional open surgery. No potential conflict of interest relevant to this article was reported.

American Roentgen Ray Society Acta Medica Okayama 0361-803X 2020 Differentiation of Small (≤ 4 cm) Renal Masses on Multiphase Contrast-Enhanced CT by Deep Learning 1 8 EN Takashi Tanaka Department of Radiology, Okayama University Hospital Yong Huang Department of Medical Informatics, Okayama University Hospital Yohei Marukawa Department of Radiology, Okayama University Hospital Yuka Tsuboi Department of Radiology, Okayama University Hospital Yoshihisa Masaoka Department of Radiology, Okayama University Hospital Katsuhide Kojima Department of Radiology, Okayama University Hospital Toshihiro Iguchi Department of Radiology, Okayama University Hospital Takao Hiraki Department of Radiology, Okayama University Hospital Hideo Gobara Department of Radiology, Okayama University Hospital Hiroyuki Yanai Department of Radiology, Okayama University Hospital Yasutomo Nasu Department of Urology, Okayama University Hospital Susumu Kanazawa Department of Radiology, Okayama University Hospital OBJECTIVE. This study evaluated the utility of a deep learning method for determining whether a small (≤ 4 cm) solid renal mass was benign or malignant on multiphase contrast-enhanced CT. MATERIALS AND METHODS. This retrospective study included 1807 image sets from 168 pathologically diagnosed small (≤ 4 cm) solid renal masses with four CT phases (unenhanced, corticomedullary, nephrogenic, and excretory) in 159 patients between 2012 and 2016. Masses were classified as malignant (n = 136) or benign (n = 32). The dataset was randomly divided into five subsets: four were used for augmentation and supervised training (48,832 images), and one was used for testing (281 images). The Inception-v3 architecture convolutional neural network (CNN) model was used. The AUC for malignancy and accuracy at optimal cutoff values of output data were evaluated in six different CNN models. Multivariate logistic regression analysis was also performed. RESULTS. Malignant and benign lesions showed no significant difference of size. The AUC value of corticomedullary phase was higher than that of other phases (corticomedullary vs excretory, p = 0.022). The highest accuracy (88%) was achieved in corticomedullary phase images. Multivariate analysis revealed that the CNN model of corticomedullary phase was a significant predictor for malignancy compared with other CNN models, age, sex, and lesion size. CONCLUSION. A deep learning method with a CNN allowed acceptable differentiation of small (≤ 4 cm) solid renal masses in dynamic CT images, especially in the corticomedullary image model. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 3 2019 Contrast-enhanced Computed Tomography-Guided Percutaneous Cryoablation of Renal Cell Carcinoma in a Renal Allograft: First Case in Asia 269 272 EN Ichiro Tsuboi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Hiroyasu Fujiwara Department of Radiology, Okayama University Hospital Toshihiro Iguchi Department of Radiology, Okayama University Hospital Takao Hiraki Department of Radiology, Okayama University Hospital Naoko Arichi Department of Urology, Shimane University, Faculty of Medicine Kasumi Kawamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Risa Kubota Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Nishimura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoko Sako Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Takamoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Yanai Department of Pathology, Okayama University Hospital Masashi Kitagawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Sugiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroaki Shiina Department of Urology, Shimane University, Faculty of Medicine Susumu Kanazawa Department of Radiology, Okayama University Hospital Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/56871 Nephron-sparing treatment should be offered whenever possible to avoid dialysis in allograph cases. Cryoablation is a new treatment option for treating small-sized renal cell cancer (RCCs). We report a case of RCC arising in a kidney allograft treated by cryoablation. To our knowledge, this is the first case in Asia of RCC in a renal allograft treated using cryoablation. Contrast-enhanced CT-guided percutaneous renal needle biopsy and cryoablation were used to identify the RCC, which could not be identified by other techniques. The postoperative course was uneventful. Contrast-enhanced CT also showed no recurrence or metastases at the 6-month follow-up. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 3 2017 Diagnostic Ureteroscopy for Cases Clinically Suspected of Carcinoma in Situ of the Upper Urinary Tract 227 232 EN Katsumi Sasaki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Morito Sugimoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shin Ebara Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/55205 　We elucidate the fate of cases clinically suspected of carcinoma in situ (Cis) of the upper tract with serial ureteroscopy. Of 143 patients who underwent ureteroscopy for suspected upper tract urothelial carcinoma (UTUC) between January 2008 and February 2016, 12 cases with consistently positive urine cytology and poorly detectable upper-tract malignancies by imaging were reviewed. In these 12 patients, 19 ureteroscopy procedures (25 renal units) were performed. Vesical random biopsy was performed before the 1st ureteroscopy to exclude malignancy of the bladder in all 12 cases. Median follow-up was 42 (13-67) months. Positive biopsy results at the 1st ureteroscopy were obtained in 3 (25%) patients and all were diagnosed wth Cis of the upper tract. Two (17%) of 9 patients who were negative or inconclusive at the 1st ureteroscopy were finally diagnosed as UTUC, but plural ureteroscopy procedures were needed for the diagnoses in both. Carcinoma of the bladder appeared in 5 (42%) patients during follow-up, despite the earlier ruling out of vesical malignancy. Four (33%) of those 5 patients never developed upper-tract urothelial carcinoma during follow-up. Caution is required before undertaking radical surgery for cases clinically suspected of Cis of the upper tract. In our experience, only 42% of such patients developed UTUC; another 33% eventually developed carcinoma of the bladder without UTUC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 2 2017 A Combination Therapy of Partial Nephrectomy and Cryoablation Achieved Good Cancer Control and Renal Function in Bilateral Synchronous Renal Cell Carcinoma 187 190 EN Atsushi Takamoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Morito Sugimoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsumi Sasaki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/54989 We report the case of a 58-year-old Japanese man with bilateral synchronous renal cell carcinoma (RCC). The diameters of the right and left tumors were 56 and 69 mm, respectively. Both tumors were endophytic. Cryoablation with prophylactic embolization was performed for the left tumor, and 1 month later, a right open partial nephrectomy was performed. No recurrence was observed during a 16-month follow-up, and the serum creatinine level has been stable. The prognosis of bilateral synchronous RCC is better than that of dialysis patients. The novel approach of combining cryoablation and partial nephrectomy can achieve good cancer control and renal function in bilateral RCC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 2 2017 The Downregulation of the Expression of CD147 by Tumor Suppressor REIC/Dkk-3, and Its Implication in Human Prostate Cancer Cell Growth Inhibition 135 142 EN Akihiro Mori Department of Urology, Okayama University, Graduate School of Medicine, Denistry and Pharmacentical Sciences Masami Watanabe Department of Urology, Okayama University, Graduate School of Medicine, Denistry and Pharmacentical Sciences Takuya Sadahira Department of Urology, Okayama University, Graduate School of Medicine, Denistry and Pharmacentical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuichi Ariyoshi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideo Ueki Department of Urology, Okayama University, Graduate School of Medicine, Denistry and Pharmacentical Sciences Koichiro Wada Department of Urology, Okayama University, Graduate School of Medicine, Denistry and Pharmacentical Sciences Kazuhiko Ochiai Department of Veterinary Nursing and Technology, Nippon Veterinary and Life Science University Shun-Ai Li Center for Innovative Clinical Medicine, Okayama University Hospital Yasutomo Nasu Department of Urology, Okayama University, Graduate School of Medicine, Denistry and Pharmacentical Sciences Original Article 10.18926/AMO/54982 The cluster of differentiation 147 (CD147), also known as EMMPRIN, is a key molecule that promotes cancer progression. We previously developed an adenoviral vector encoding a tumor suppressor REIC/Dkk-3 gene (Ad-REIC) for cancer gene therapy. The therapeutic effects are based on suppressing the growth of cancer cells, but, the underlying molecular mechanism has not been fully clarified. To elucidate this mechanism, we investigated the effects of Ad-REIC on the expression of CD147 in LNCaP prostate cancer cells. Western blotting revealed that the expression of CD147 was significantly suppressed by Ad-REIC. Ad-REIC also suppressed the cell growth of LNCaP cells. Since other researchers have demonstrated that phosphorylated mitogen-activated protein kinases (MAPKs) and c-Myc protein positively regulate the expression of CD147, we investigated the correlation between the CD147 level and the activation of MAPK and c-Myc expression. Unexpectedly, no positive correlation was observed between CD147 and its possible regulators, suggesting that another signaling pathway was involved in the downregulation of CD147. This is the first study to show the downregulation of CD147 by Ad-REIC in prostate cancer cells. At least some of the therapeutic effects of Ad-REIC may be due to the downregulation of the cancer-progression factor, CD147. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 2 2017 Evaluation of Urinary Stone Composition and Differentiation between Urinary Stones and Phleboliths Using Single-source Dual-energy Computed Tomography 91 96 EN Nanako Ogawa Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Sato Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ida Department of Radiologic Diagnosis and Interventional Radiology, Fukuyama City Hospital Katsuya Kato Department of Diagnostic Radiology, Kawasaki Hospital Yuichi Ariyoshi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Kanazawa Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/54976 The aim of this study was to investigate the utility of single-source dual-energy computed tomography (SS-DECT) composition analysis in characterizing different types of urinary stones and differentiating them from phleboliths. This study included 29 patients with urinary stones who were scheduled for surgery. All patients were scanned, first using single-energy computed tomography acquisition and then DECT acquisition on SS-DECT. Dual-energy data were archived to a Gemstone spectral imaging (GSI) viewer (GE Healthcare, Milwaukee, WI, USA). Hounsfield units (HU) and effective atomic numbers (Zeff) were estimated using the GSI viewer. The results of dual-energy analysis were compared with the biochemical constitution of the stones. The chemical analysis determined that the stones included 32 calcium-based, 6 cystine and 1 struvite stone. Both HU and Zeff values were helpful in differentiating calcium-based stones from cystine and struvite stones and phleboliths. The Zeff values of phleboliths were significantly higher than those for struvite and cystine stones, whereas it was difficult to distinguish phleboliths from struvite and cystine stones using the HU values. Composition analysis using SS-DECT is helpful for distinguishing urinary stone types and discriminating phleboliths from urinary stones. Zeff values may be more useful than HU values for differentiating urinary stones from phleboliths. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 1 2017 Interfractional Seminal Vesicle Motion Relative to the Prostate Gland for Image-guided Radiotherapy for Prostate Cancer with/without Androgen Deprivation Therapy: A Retrospective Cohort Study 31 39 EN Takahiro Waki Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kuniaki Katsui Department of Radiology, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Takeshi Ogata Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihisa Katayama Department of Radiology, Okayama University Hospital Mitsuhiro Takemoto Department of Radiology, Japanese Red Cross Society Himeji Hospital Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromi Kumon Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Susumu Kanazawa Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/54823 We investigated differences in seminal vesicle (SV) length and interfractional SV motion relative to the prostate gland in prostate cancer patients. We compared 32 patients who received androgen deprivation therapy (ADT) before radiotherapy with 12 patients receiving radiotherapy alone at Okayama University Hospital in August 2008-July 2011. We examined the right and left SVs’ length and motion by computed tomography (CT) to determine the ADT’s effects and analyzed 347 CT scans in a multiple linear regression model. The ADT patients’ SV length was significantly shorter than the non-ADT patients’. The differences in right and left SV lengths between the ADT and non-ADT patients were 6.8 mm (95% CI 2.0-11.7 mm) and 7.2 mm (95% CI 3.1-11.3 mm) respectively in an adjusted regression model. SV motion did not differ between the ADT and non-ADT patients in terms of interfractional motion of the SV tips and the SVs’ center relative to the prostate gland. The ADT patients had significantly shorter SVs compared to the non-ADT patients, but no difference in SV motion was observed. SV interfractional motion should thus be compensated using the same planning margins, regardless of whether ADT is used. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 3 2016 総合診療棟（Ⅱ期）新営工事に伴う臨床研究中核病院（医療法上）に向けた整備について 217 220 EN Yasutomo Nasu The Office for Innovative Medicine, Organization for Research Promotion & Collaboration, Okayama University No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 4 2016 A Phase II Clinical Trial Evaluating the Preventive Effectiveness of Lactobacillus Vaginal Suppositories in Patients with Recurrent Cystitis 299 302 EN Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinya Uehara Department of Urology, Kawasaki Hospital, Kawasaki Medical School Ayano Ishii Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masumi Yamamoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ritsuko Mitsuhata Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Takamoto Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Hotta Center for innovative Clinical Medicine, Okayama University Hospital Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Clinical Study Protocols 10.18926/AMO/54508 Urinary tract infections (UTIs) are the most common bacterial infections in women, and many patients experience frequent recurrence. The aim of this report is to introduce an on-going prospective phase II clinical trial performed to evaluate the preventive effectiveness of Lactobacillus vaginal suppositories for prevention of recurrent cystitis. Patients enrolled in this study are administered vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus every 2 days or 3 times a week for one year. The primary endpoint is recurrence of cystitis and the secondary endpoints are adverse events. Recruitment began in December 2013 and target sample size is 20 participants. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 4 2016 The Efficacy of Rituximab in High-risk Renal Transplant Recipients 295 297 EN Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Mitsui Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Risa Kubota Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Yoshioka Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuichi Ariyoshi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Kitagawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Tanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Sugiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Center for Innovative Clinical Medicine, Okayama University Hospital Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Clinical Study Protocols 10.18926/AMO/54507 Although graft survival following renal transplantation (RTx) has improved, outcomes following highrisk RTx are variable. Preexisting antibodies, including donor-specific antibodies (DSA), play an important role in graft dysfunction and survival. We have designed a study to investigate the safety and efficacy of anti-CD20 monoclonal antibodies (rituximab) in high-risk RTx recipients. Major eligibility criteria include: 1) major and minor ABO blood group mismatch, 2) positive DSA. Thirty-five patients will receive 200 mg/body of rituximab. The primary endpoint is the incidence of B cell depletion. This study will clarify whether rituximab is efficacious in improving graft survival in high-risk RTx recipients. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 3 2016 A Case of Metastatic Urachal Cancer Including a Neuroendocrine Component Treated with Gemcitabine, Cisplatin and Paclitaxel Combination Chemotherapy 223 227 EN Shin Ebara Departments of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuyuki Kobayashi Departments of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsumi Sasaki Departments of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Departments of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Morito Sugimoto Departments of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichirou Wada Departments of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Fujio Departments of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Takamoto Departments of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Departments of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Yanai Departments of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Departments of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Case Report 10.18926/AMO/54423 The present case report describes a case of recurrent and advanced urachal carcinoma including neuroendocrine features with iliac bone metastasis after partial cystectomy and adjuvant chemotherapy consisting of irinotecan and cisplatin in a 32-year-old man. He received gemcitabine/cisplatin/ paclitaxel (GCP) combination chemotherapy, consisting of gemcitabin (1,000mg/m2) on day 1, 8, cisplatin (70mg/m2) on day 1, and paclitaxel (80mg/m2) on day 1 and 8. After three cycles of chemotherapy, PET-CT showed complete regression of the disease. So the patient underwent total cystourethrectomy, and histological examination showed an almost complete pathological response. External beam radiation therapy was also given to the ileac bone metastasis regions. However, PET-CT taken 17 months after the external beam radiation showed multiple lung metastases. He received GCP chemotherapy again, which resulted in a complete response again after three cycles of chemotherapy. This is the first report on GCP chemotherapy used not only as a salvage chemotherapy but also as a rechallenge regimen for metastatic urachal cancer including a neuroendocrine component. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 3 2016 Effectiveness and Safety of Ureteroscopic Holmium Laser Lithotripsy for Upper Urinary Tract Calculi in Elderly Patients 159 166 EN Takashi Yoshioka Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideo Otsuki Department of Urology, Abiko Toho Hospital Shinya Uehara Department of Urology, Abiko Toho Hospital Toshihiro Shimizu Department of Urology, Abiko Toho Hospital Wataru Murao Department of Urology, Abiko Toho Hospital Koji Fujio Department of Urology, Abiko Toho Hospital Kei Fujio Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Wada Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasutomo Nasu Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/54414 Upper urinary tract calculi are common; however, there is no recommended treatment selection for elderly patients. Ureteroscopic holmium laser lithotripsy (URS lithotripsy) is minimally invasive, and it provides a high stone-free rate (SFR) treatment for upper urinary tract calculi. Here, we retrospectively evaluated the surgical outcomes of URS lithotripsy after dividing the 189 cases into 3 groups by patient age: the ʻ＜65 groupʼ (＜65 years old, n＝108), the ʻ65-74 groupʼ (65-74 years old, n＝42), and the ʻ 75 groupʼ ( 75 years old, n＝39). The patientsʼ characteristics, stone status, and perioperative outcomes were assessed. The 65-74 group and the 75 group had a significantly higher prevalence of hypertension compared to the＜65 group. Compared to the＜65 group, the 65-74 group had a significantly higher prevalence of hyperlipidemia, and the 75 group had significantly higher the American Society of Anesthesiologists (ASA) scores. Despite these preoperative risk factors, SFR and postoperative pyelonephritis in the 65-74 group and the 75 group were similar to those of the＜65 group. In conclusion, URS lithotripsy is the preferred treatment for upper urinary tract calculi, even for elderly patients who have multiple preoperative risk factors. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 3 2014 臨床研究中核病院「岡山大学病院」 231 235 EN Yasutomo Nasu No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0918-8959 60 12 2013 Testosterone replacement elevates the serum uric acid levels in patients with female to male gender identity disorder 1321 1327 EN Hiroaki Kurahashi Masami Watanabe Morito Sugimoto Yuichi Ariyoshi Sabina Mahmood Motoo Araki Kazushi Ishii Yasutomo Nasu Atsushi Nagai Hiromi Kumon Gender identity disorder (GID) results from a disagreement between a person's biological sex and the gender to which he or she identifies. With respect to the treatment of female to male GID, testosterone replacement therapy (TRT) is available. The uric acid (UA) level can be influenced by testosterone; however, the early effects and dose-dependency of TRT on the serum UA concentration have not been evaluated in this population. We herein conducted a dose-response analysis of TRT in 160 patients with female to male GID. The TRT consisted of three treatment groups who received intramuscular injections of testosterone enanthate: 125 mg every two weeks, 250 mg every three weeks and 250 mg every two weeks. Consequently, serum UA elevation was observed after three months of TRT and there was a tendency toward testosterone dose-dependency. The onset of hyperuricemia was more prevalent in the group who received the higher dose. We also demonstrated a positive correlation between increased levels of serum UA and serum creatinine. Since the level of serum creatinine represents an individual's muscle volume and the muscle is a major source of purine, which induces UA upregulation, the serum UA elevation observed during TRT is at least partially attributed to an increase in muscle mass. This is the first study showing an association between serum UA elevation and a TRT-induced increase in muscle mass. The current study provides important information regarding TRT for the follow-up and management of the serum UA levels in GID patients. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0171-5216 138 5 2012 DNA methylation status of REIC/Dkk-3 gene in human malignancies 799 809 EN Tatsuro Hayashi Hiroaki Asano Shinichi Toyooka Kazunori Tsukuda Junichi Soh Tadahiko Shien Naruto Taira Yuho Maki Norimitsu Tanaka Hiroyoshi Doihara Yasutomo Nasu Nam-ho Huh Shinichiro Miyoshi The REIC (reduced expression in immortalized cells)/Dkk-3 is down-regulated in various cancers and considered to be a tumor suppressor gene. REIC/Dkk-3 mRNA has two isoforms (type-a,b). REIC type-a mRNA has shown to be a major transcript in various cancer cells, and its promoter activity was much stronger than that of type-b. In this study, we examined the methylation status of REIC/Dkk-3 type-a in a broad range of human malignancies. We examined REIC/Dkk-3 type-a methylation in breast cancers, non-small-cell lung cancers, gastric cancers, colorectal cancers, and malignant pleural mesotheliomas using a quantitative combined bisulfite restriction analysis assay and bisulfate sequencing. REIC/Dkk-3 type-a and type-b expression was examined using reverse transcriptional PCR. The relationships between the methylation and clinicopathological factors were analyzed. The rate of REIC/Dkk-3 type-a methylation ranged from 26.2 to 50.0% in the various primary tumors that were examined. REIC/Dkk-3 type-a methylation in breast cancer cells was significantly heavier than that in the other cell lines that we tested. REIC/Dkk-3 type-a methylation was inversely correlated with REIC/Dkk-3 type-a expression. There was a correlation between REIC/Dkk-3 type-a and type-b mRNA expression. REIC/Dkk-3 type-a expression was restored in MDA-MB-231 cells using 5-aza-2'-deoxycytidine treatment. We found that estrogen receptor-positive breast cancers were significantly more common among the methylated group than among the non-methylated group. REIC/Dkk-3 type-a methylation was frequently detected in a broad range of cancers and appeared to play a key role in silencing REIC/Dkk-3 type-a expression in these malignancies. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 68 1 2014 A Rare Complication:Misdirection of an Indwelling Urethral Catheter into the Ureter 47 51 EN Tsutomu Ishikawa Motoo Araki Takeshi Hirata Masami Watanabe Shin Ebara Toyohiko Watanabe Yasutomo Nasu Hiromi Kumon Case Report 10.18926/AMO/52144 We report 3 patients with the rare complication of an indwelling urethral catheter misdirected into the ureter. This is the largest series to date. Patients were referred to us for a variety of reasons following exchange of their chronic indwelling urinary catheters. CT in all cases demonstrated the urinary catheters residing in the left ureter. The ages of the patients were 37, 67 and 81 years old. All patients suffered from neurogenic bladder. Two patients were female, one was male, and 2 of the 3 had a sensory disorder inhibiting their pain response. The catheters were replaced with open-end Foley catheters. Extensive follow-up CT scans were obtained in one case, demonstrating improvement of hydronephrosis and no evidence of ureteral stenosis. Cystoscopy in this patient demonstrated normally positioned and functioning ureteral orifices. Although the placement of an indwelling urethral catheter is a comparatively safe procedure, one must keep in mind that this complication can occur, particularly in female patients with neurogenic bladder. CT without contrast is a noninvasive, definitive diagnostic tool. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 68 1 2014 Robot-Assisted Radical Prostatectomy:Modified Ultradissection Reduces pT2 Positive Surgical Margins on the Bladder Neck 35 41 EN Motoo Araki Wooju Jeong Sung Yul Park Young Hoon Lee Yasutomo Nasu Hiromi Kumon Sung Joon Hong Koon Ho Rha Original Article 10.18926/AMO/52142 The purpose of this study was to compare the positive surgical margin (PSM) rates of 2 techniques of robot-assisted radical prostatectomy (RARP) for pT2 (localized) prostate cancer. A retrospective analysis was conducted of 361 RARP cases, performed from May 2005 to September 2008 by a single surgeon (KHR) at our institution (Yonsei University College of Medicine). In the conventional technique, the bladder neck was transected first. In the modified ultradissection, the lateral border of the bladder neck was dissected and then the bladder neck was transected while the detrusor muscle of the bladder was well visualized. Perioperative characteristics and outcomes and PSM rates were analyzed retrospectively for pT2 patients (n＝217), focusing on a comparison of those undergoing conventional (n＝113) and modified ultradissection (n＝104) techniques. There was no difference between the conventional and modified ultradissection group in mean age, BMI, PSA, prostate volume, biopsy Gleason score, and DʼAmico prognostic criteria distributions. The mean operative time was shorter (p＜0.001) and the estimated blood loss was less (p＜0.01) in the modified ultradissection group. The PSM rate for the bladder neck was significantly reduced by modified ultradissection, from 6.2% to 0% (p＜0.05). In conclusion, modified ultradissection reduces the PSM rate for the bladder neck. No potential conflict of interest relevant to this article was reported.

Springer Japan KK Acta Medica Okayama 1341-9625 18 1 2013 Could salvage surgery after chemotherapy have clinical impact on cancer survival of patients with metastatic urothelial carcinoma? 110 115 EN Kensuke Bekku Takashi Saika Yasuyuki Kobayashi Ryo Kioshimoto Taiki Kanbara Yasutomo Nasu Hiromi Kumon The clinical impact of salvage surgery after chemotherapy on cancer survival of patients with metastatic urothelial carcinoma is controversial. We aimed to verify the clinical role of salvage surgery by analyzing the long-term outcome in patients with urothelial carcinoma treated by chemotherapy. Between 2003 and 2010 at a single institution, 31 of 47 patients (66%) with metastatic urothelial carcinoma showed objective responses (CR in 4, PR in 27) after multiple courses of cisplatin/gemcitabine/paclitaxel-based chemotherapy, and a cohort of patients with partial response (PR) were retrospectively enrolled. Twelve (10 male and 2 female, median age 64.0 years) of 27 patients with PR underwent salvage surgeries after the chemotherapy: metastatectomy of residual lesions (10 retroperitoneal lymph nodes, 2 lung), and 6 radical surgeries for primary lesions as well. Progression-free survival and overall patient survival rates were analyzed retrospectively and compared with those of patients without salvage surgery. All 12 patients achieved surgical CR. Pathological findings of metastatic lesions showed viable cancer cells in 3 patients. In univariate analysis, sole salvage surgery affected overall survival in 27 patients with PR to the chemotherapy (P = 0.0037). Progression-free survival and overall survival rates in patients with salvage surgery were better than those in 15 PR patients without the surgery (39.8 vs. 0%, and 71.6 vs. 12.1% at 3 years, P = 0.01032 and 0.01048; log-rank test). Salvage surgery for patients with residual tumor who achieve partial response to chemotherapy could have a possible impact on cancer survival. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0020-7136 126 7 2010 Down-regulation of BiP/GRP78 sensitizes resistant prostate cancer cells to gene-therapeutic overexpression of REIC/Dkk-3 1562 1569 EN Ryuta Tanimoto Masakiyo Sakaguchi Fernando Abarzua Ken Kataoka Kaoru Kurose Hitoshi Murata Yasutomo Nasu Hiromi Kumon Nam-Ho Huh We have recently shown that an adenovirus carrying REIC/Dkk-3 (Ad-REIC) exhibits a potent tumor-specific cell-killing function for various human cancers. It has also become evident that some human cancers are resistant to Ad-REIC-induced apoptosis. The aim of the present study was to determine the molecular mechanisms of resistance to Ad-REIC. First, we isolated resistant clones from a human prostate cancer cell line, PC3, after repeated exposure to Ad-REIC. Infection efficiency of the adenovirus vector and expression level of REIC/Dkk-3 in the resistant clones were similar to those in the parental PC3 cells. By screening for alteration in levels and functional status of proteins involved in Ad-REIC-induced apoptosis, we found that BiP/GRP78, an ER-residing chaperone protein, was expressed at higher levels consistently among resistant cells. Expression levels of BiP and rates of apoptosis induced by Ad-REIC were inversely correlated. Down-regulation of BiP with siRNA sensitized the resistant cells to Ad-REIC in vivo as well as in culture. These results indicate that BiP is a major determinant of resistance to Ad-REIC-induced apoptosis. Thus BiP is useful for diagnosis of inherent and acquired resistance of cancers and also as a target molecule to overcome resistance to the gene therapeutic Ad-REIC. No potential conflict of interest relevant to this article was reported.

Nature Publishing Group Acta Medica Okayama 0929-1903 17 7 2010 Potent antitumor effects of combined therapy with a telomerase-specific, replication-competent adenovirus (OBP-301) and IL-2 in a mouse model of renal cell carcinoma 484 491 EN P Huang H Kaku J Chen Y Kashiwakura T Saika Y Nasu Y Urata T Fujiwara M Watanabe H Kumon OBP-301 (a telomerase-specific, replication-competent adenovirus with hTERT promoter) was constructed in a previous study and it showed a strong anticancer effect by inducing cell lysis in human lung and prostate cancer cells. This study investigated the effectiveness of a combination therapy of OBP-301 and interleukin-2 (IL-2) in a mouse model of renal cell carcinoma (RCC). The cell-killing effect of OBP-301 was confirmed in vitro in the RENCA cancer cells. In in vivo experiment, luciferase-expressing RENCA cells were implanted in the left kidney and lung of BALB/c mice to prepare the RCC metastatic model. The animals were randomly divided into four treatment groups: PBS, IL-2 alone, OBP-301 alone and the combination. The analyses of orthotopic tumor weight, lung metastasis and luciferin-stained tumor images 14 days after each treatment showed significant tumor growth inhibition in the combination group in comparison with that in the OBP-301- or IL-2-treated groups. In addition, the percentage of regulatory T-cells (Tregs) in the combination group was significantly suppressed in comparison with that in the PBS and single-agent treatment groups. The outcomes of this study suggest that tumor-specific oncolytic immunovirotherapy may become an attractive strategy for the treatment of human RCC. No potential conflict of interest relevant to this article was reported.

The American Society for Biochemistry and Molecular Biology, Inc. Acta Medica Okayama 0021-9258 284 21 2009 Overexpression of REIC/Dkk-3 in Normal Fibroblasts Suppresses Tumor Growth via Induction of Interleukin-7 14236 14244 EN Masakiyo Sakaguchi Ken Kataoka Fernando Abarzua Ryuta Tanimoto Masami Watanabe Hitoshi Murata Swe Swe Than Kaoru Kurose Yuji Kashiwakura Kazuhiko Ochiai Yasutomo Nasu Hiromi Kumon Nam-ho Huh We previously showed that the tumor suppressor gene REIC/Dkk-3, when overexpressed by an adenovirus (Ad-REIC), exhibited a dramatic therapeutic effect on human cancers through a mechanism triggered by endoplasmic reticulum stress. Adenovirus vectors show no target cell specificity and thus may elicit unfavorable side effects through infection of normal cells even upon intra-tumoral injection. In this study, we examined possible effects of Ad-REIC on normal cells. We found that infection of normal human fibroblasts (NHF) did not cause apoptosis but induced production of interleukin (IL)-7. The induction was triggered by endoplasmic reticulum stress and mediated through IRE1 alpha, ASK1, p38, and IRF-1. When Ad-REIC-infected NHF were transplanted in a mixture with untreated human prostate cancer cells, the growth of the cancer cells was significantly suppressed. Injection of an IL-7 antibody partially abrogated the suppressive effect of Ad-REIC-infected NHF. These results indicate that Ad-REIC has another arm against human cancer, an indirect host-mediated effect because of overproduction of IL-7 by mis-targeted NHF, in addition to its direct effect on cancer cells. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 66 1 2012 Preclinical Safety and Efficacy of in Situ REIC/Dkk-3 Gene Therapy for Prostate Cancer 7 16 EN Keiichiro Kawauchi Masami Watanabe Haruki Kaku Peng Huang Kasumi Sasaki Masakiyo Sakaguchi Kazuhiko Ochiai Nam-ho Huh Yasutomo Nasu Hiromi Kumon Original Article 10.18926/AMO/48076 The preclinical safety and therapeutic efficacy of adenoviral vectors that express the REIC/Dkk-3 tumor suppressor gene (Ad-REIC) was examined for use in prostate cancer gene therapy. The Ad-human (h) and mouse (m) REIC were previously demonstrated to induce strong anti-cancer effects in vitro and in vivo, and we herein report the results of two in vivo studies. First, intra-tumor Ad-hREIC administration was examined for toxicity and therapeutic effects in a subcutaneous tumor model using the PC3 prostate cancer cell line. Second, intra-prostatic Ad-mREIC administration was tested for toxicity in normal mice. The whole-body and spleen weights, hematological and serum chemistry parameters, and histological evaluation of tissues from throughout the body were analyzed. Both experiments indicated that there was no significant difference in the examined parameters between the Ad-REIC-treated group and the control (PBS- or Ad-LacZ-treated) group. In the in vitro analysis using PC3 cells, a significant apoptotic effect was observed after Ad-hREIC treatment. Confirming this observation, the robust anti-tumor efficacy of Ad-hREIC was demonstrated in the in vivo subcutaneous prostate cancer model. Based on the results of these preclinical experiments, we consider the adenovirus-mediated REIC/Dkk-3 in situ gene therapy to be safe and useful for the clinical treatment of prostate cancer. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 5 2011 Single Nucleotide Polymorphism WRN Leu1074Phe Is Associated with Prostate Cancer Susceptibility in Chinese Subjects 315 323 EN Lei Wang Haruki Kaku Peng Huang Kexin Xu Kai Yang Jiheng Zhang Ming Li Liping Xie Xiaofeng Wang Akiko Sakai Masami Watanabe Yasutomo Nasu Kenji Shimizu Hiromi Kumon Yanqun Na Original Article 10.18926/AMO/47013 Deficiencies in the human DNA repair gene WRN are the cause of Werner syndrome, a rare autosomal recessive disorder characterized by premature aging and a predisposition to cancer. This study evaluated the association of WRN Leu1074Phe (rs1801195), a common missense single nucleotide polymorphism in WRN, with prostate cancer susceptibility in Chinese subjects. One hundred and forty-seven prostate cancer patients and 111 male cancer-free control subjects from 3 university hospitals in China were included. Blood samples were obtained from each subject, and the single nucleotide polymorphism WRN Leu1074Phe was genotyped by using a Snapshot assay. The results showed that WRN Leu1074Phe was associated with the risk of prostate cancer in Chinese men and that the TG/GG genotype displayed a decreased prevalence of prostate cancer compared with the TT genotype (OR＝0.58, 95%CI:0.35-0.97, p＝0.039). Through stratified analysis, more significant associations were revealed for the TG/GG genotype in the subgroup with diagnosis age <_ 72 yr (OR＝0.27, 95%CI:0.12-0.61, p＝0.002) and in patients with localized diseases (OR＝0.36, 95%CI:0.19-0.70, p＝0.003). However, no statistically significant difference was found in the subgroup with age ＞72 yr or in patients with advanced diseases. We concluded that the genetic variant Leu1074Phe in the DNA repair gene WRN might play a role in the risk of prostate cancer in Chinese subjects. No potential conflict of interest relevant to this article was reported.

Academic Press Inc Elsevier Science Acta Medica Okayama 0006-291X 412 2 2011 Tumor suppressor REIC/Dkk-3 interacts with the dynein light chain, Tctex-1 391 395 EN Kazuhiko Ochiai Masami Watanabe Hideo Ueki Peng Huang Yasuyuki Fujii Yasutomo Nasu Hirofumi Noguchi Takeshi Hirata Masakiyo Sakaguchi Nam-ho Huh Yuji Kashiwakura Haruki Kaku Hiromi Kumon Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. HuH-7 hepatoma-derived cells are widely used as the only cell-based HCV replication system for HCV research, including drug assays. Recently, using different hepatoma Li23-derived cells, we developed an HCV drug assay system (ORL8), in which the genome-length HCV RNA (O strain of genotype 1b) encoding renilla luciferase replicates efficiently. In this study, using the HuH-7-derived OR6 assay system that we developed previously and the ORL8 assay system, we evaluated 26 anti-HCV reagents, which other groups had reported as anti-HCV candidates using HuH-7-derived assay systems other than ORB. The results revealed that more than half of the reagents showed different anti-HCV activities from those in the previous studies, and that anti-HCV activities evaluated by the ORB and ORL8 assays were also frequently different. In further evaluation using the HuH-7-derived AH1R assay system, which was developed using the AH1 strain of genotype 1b, several reagents showed different anti-HCV activities in comparison with those evaluated by the OR6 and ORL8 assays. These results suggest that the different activities of anti-HCV reagents are caused by the differences in cell lines or HCV strains used for the development of assay systems. Therefore, we conclude that plural HCV assay systems developed using different cell lines or HCV strains are required for the objective evaluation of anti-HCV reagents. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 123 2 2011 泌尿器科領域における低侵襲治療 111 117 EN Yasutomo Nasu No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 2 2011 For Vol. 64, No. 1 pp 27-31 Prognostic Factors Influencing Survival after ephroureterectomy for Transitional Cell Carcinoma of the Upper Urinary Tract 143 149 EN Yasuyuki Kobayashi Takashi Saika Daisuke Manabe Yasutomo Nasu Hiromi Kumon Corrected and Republished Article 10.18926/AMO/45274 We analyzed the prognostic factors influencing survival after surgeries for upper urinary tract urothelial carcinoma (UUT-UC) with longer follow-up periods than in previous studies. Between January 2000 and December 2004, 386 patients underwent nephroureterectomy for UUT-UC. The data for the 221 patients with UUT-UC were retrospectively reviewed. Nine variables were evaluated for association with the survival outcomes of cause-specific survival. The prognostic significance was tested univariately with the log-rank test. The simultaneous effects of multiple prognostic factors were estimated by multiple regression analysis using the Cox proportional hazards model. The median follow-up was 38.4 months. The 5-year over all survival was 62.3%. Significant prognostic factors for disease-specific survival rate on univariate analysis were pathological stage (p0.0001), tumor grade (p0.0324), and venous invasion (p0.0001). Multivariate analysis revealed that only venous invasion was significant for disease-specific survival rate (p0.0205). Venous invasion was the only independent prognostic factor in pathologically localized UUT-UC. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 14 7 2007 Natural course of lower urinary tract symptoms following discontinuation of alpha-1-adrenergic blockers in patients with benign prostatic hyperplasia 598 601 EN Teruhiko Yokoyama Toyohiko Watanabe Takashi Saika Yasutomo Nasu Hiromi Kumon Yoshiyuki Miyaji Atsushi Nagai alpha 1-adrenergic blockers (alpha b) remain the first-line therapy in men with lower urinary tract symptoms (LUTS). The current published work advocates continued use of alpha b for their effect to be maintained. However, some patients decide to discontinue use of the medication after their symptoms are relieved and can keep good conditions. In this study, we investigated the natural course of LUTS after the discontinuation of successful treatment of alpha b. Methods: Among 75 patients with LUTS who stopped alpha b medication once their symptoms improved, 60 patients (age, 50-87 years; median, 70) who could be followed for at least 12 months after discontinuation of alpha b were analyzed in this study. Evaluations included a clinical determination of the International Prostate Symptom Score (IPSS), peak flow rate (Qmax) and postvoid residual urine volume (PVR). Upon patient request or in cases of PVR more than 100 mL, administration of alpha b was resumed. Results: Eighteen out of the 60 patients (30%) asked for re-treatment within 12 months after discontinuation (re-treatment group). The other 42 patents were able to maintain good condition without medication (discontinuation group). The IPSS was 15.9, 8.7, 10.1, 10.2, 9.7, 8.8 and 9.0, on the first visit, just before discontinuation, and 1, 3, 6, 9 and 12 months after stopping treatment among the discontinuation group, respectively. Similarly, Qmax was 10.6, 14.8, 14.2, 14.3, 14.7, 13.2 and 13.6 mL/ s, respectively. Treatment periods, prostatic volume and peak flow rates just before discontinuation of medication differed significantly between the re-treatment and discontinuation group. Conclusions: In spite of the short follow-up periods, these results suggest that selected patients with relatively small prostatic volume and good flow rates after therapy can discontinue alpha b medication after their symptoms improve. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 61 6 2007 Routine Transurethral Biopsy of the Bladder is not Necessary to Evaluate the Response to Bacillus Calmette-guerin Therapy 341 344 EN Takanori Murakami Shin Ebara Takashi Saika Shin Irie Katsuji Takeda Yoshio Maki Sadayuki Miyaji Daisuke Manabe Haruki Kaku Yasutomo Nasu Tomoyasu Tsushima Hiromi Kumon Original Article 10.18926/AMO/32881 We evaluated the need for transurethral biopsy at first follow-up after intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder cancer. The records of 84 patients with superficial bladder cancer who received a 6- or 8-week course of BCG were reviewed. Pathological results before BCG, cystoscopic findings, urinary cytology, and biopsy results for evaluation of BCG therapy were reviewed. All 19 patients with positive urinary cytology had evidence of positive bladder biopsy results. Fifty-three of 54 patients (98.1%) with no visible recurrent tumor and negative urinary cytology demonstrated negative pathological results on bladder biopsy. When not found in conjunction with positive urinary cytology, erythematous mucosa on cystoscopy was not an indicator of tumor recurrence or residual cancer. In conclusion, routine transurethral biopsy of the bladder for evaluating the response to BCG intravesical therapy is not necessary in patients who have no visible tumor on cystoscopy and negative urinary cytology./ No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 61 6 2007 The Efficacy of Neoadjuvant Androgen Deprivation Therapy as a Prostate Volume Reduction before Brachytherapy for Clinically Localized Prostate Cancer 335 340 EN Shin Ebara Daisuke Manabe Yasuyuki Kobayashi Ryuta Tanimoto Takashi Saika Yasutomo Nasu Shirou Saito Takefumi Satoh Kenta Miki Katsuyoshi Hashine Hiromi Kumon Original Article 10.18926/AMO/32878 From September 2003 to December 2005, 188 patients who visited our hospital and allied institutions for the purpose of prostate brachytherapy were administrated hormonal therapy for volume reductions before brachytherapy. The pretreatment and posttreatment of prostate volume using a transrectal ultrasound volumetric study and the types and duration of hormonal therapy were analyzed. We administered 91 patients with Luteinizing hormone-releasing hormone (LH-RH) agonist, 49 patients with anti-androgen (bicaltamide/flutamide), and 48 patients with maximum androgen blockade (MAB). The duration of the hormonal therapy was 1-3 months for 49 patients, 4-6 months for 59 patients, 7-9 months for 40 patients, 10-12 months for 32 patients, and over 13 months for 8 patients. Before the initiation of hormonal therapy, the mean prostate volume was 35.12 ml (11.04-78.71 ml), and the average of prostate volume before and after hormonal therapy was 36.79 ml and 24.79 ml, respectively (a 32.4% reduction). The prostate volume reduction rate was 32.0% for the LH-RH agonist only, 18.1% for the anti-androgen only and 41.2% for the MAB. No statistically significant difference was observed for the duration of hormonal therapy between 3 groups. A three-month course of the neoadjuvant LH-RH agonist indicated a sufficient volume reduction effectiveness for a large prostate volume. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 61 6 2007 Vaginoplasty with an M-Shaped Perineo- Scrotal Flap in a Male-to-female Transsexual 355 360 EN Yuzaburo Namba Narushi Sugiyama Shuji Yamashita Kenjiro Hasegawa Yoshihiro Kimata Kazushi Ishii Yasutomo Nasu Original Article 10.18926/AMO/32875 To date, many techniques have been reported for vaginoplasty in male-to-female trans-sexual (MTFTS) patients, such as the use of a rectum transfer, a penile-scrotal flap and a reversed penile flap. However, none of these procedures is without its disadvantages. We developed a newly kind of flap for vaginoplasty, the M-shaped perineo-scrotal flap (M-shaped flap), using skin from both sides of the scrotum, shorn of hair by preoperative laser treatment. We applied this new type of flap in 7 MTFTS patients between January 2006 and January 2007. None of the flaps developed necrosis, and the patients could engage in sexual activity within 3 months of the operation. The M-shaped flap has numerous advantages: it can be elevated safely while retaining good vascularity, it provides for the construction of a sufficient deep vagina without a skin graft, the size of the flap is not influenced entirely by the length of the penis, and it utilizes skin from both sides of the scrotal area, which is usually excised. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 61 4 2007 Orthotopic ileal neobladder versus sigmoidal neobladder: a "quality of life" (QOL) survey 229 234 EN Ryoji Arata Takashi Saika Tomoyasu Tsushima Fernando Abarzua Yasutomo Nasu Hiromi Kumon Original Article 10.18926/AMO/32868 To compare the quality of life (QOL) in patients with ileal neobladder and sigmoidal neobladder, a retrospective survey was conducted using a formulated questionnaire. Between January and March 1999, a QOL survey was conducted using self-administered questionnaires (EORTC QLQ-C30, IPSS, supplemented with detailed questionnaires about continence, sexual function, and patient’s satisfaction with the selected urinary diversion method) for 78 patients with orthotopic urinary reservoir (OUR) who were followed-up for more than 3 months after cystectomy. Among 78 patients, 63 had OUR using an ileal segment (male/female＝59/4, median age: 70.8 years old, median follow-up: 1.7 years). Fifteen patients had OUR using a sigmoidal segment (male/female＝13/2, median age: 71.9, median follow-up: 3.9). The QLQ-C30 functional evaluation and the items in relation to sexual function showed no diff erences between the 2 groups. Concerning the voiding condition, bladder emptying, frequency, and urgency, scores in the sigmoidal OUR group were signifi cantly higher. The QOL score concerning voiding conditions, daytime, and nighttime continence and quantity of pad showed a better score in the ileal OUR group. Concerning the satisfaction with methods of urinary diversion, patients in the sigmoidal OUR group expressed less satisfaction than their preoperative expectations. Considering several postoperative voiding conditions, ileal OUR seems superior to sigmoidal OUR. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 64 1 2010 Prognostic Factors Influencing Survival after ephroureterectomy for Transitional Cell Carcinoma of the Upper Urinary Tract 27 31 EN Yasuyuki Kobayashi Takashi Saika Daisuke Manabe Yasutomo Nasu Hiromi Kumon Original Article 10.18926/AMO/32862 We analyzed the prognostic factors influencing survival after surgeries for upper urinary tract urothelial carcinoma (UUT-UC) with longer follow-up periods than in previous studies. Between January 2000 and December 2004, 386 patients underwent nephroureterectomy for UUT-UC. The data for the 221 patients with UUT-UC were retrospectively reviewed. Nine variables were evaluated for association with the survival outcomes of cause-specific survival. The prognostic significance was tested univariately with the log-rank test. The simultaneous effects of multiple prognostic factors were estimated by multiple regression analysis using the Cox proportional hazards model. The median follow-up was 38.4 months. The 5-year over all survival was 62.3%. Significant prognostic factors for disease-specific survival rate on univariate analysis were pathological stage (p0.0001), tumor grade (p0.0324), and venous invasion (p0.0001). Multivariate analysis revealed that only venous invasion was significant for disease-specific survival rate (p0.0205). Venous invasion was the only independent prognostic factor in pathologically localized UUT-UC. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 57 6 2003 Anterior urethral recurrence of superficial bladder cancer: its clinical significance. 293 297 EN Takashi Saika Tomoyasu Tsushima Yasutomo Nasu Ryoji Arata Haruki Kaku Naoki Akebi Nobuyuki Kusaka Hiromi Kumon Article 10.18926/AMO/32815 The aim of this study was to reveal the clinical features of anterior urethral recurrence in patients with superficial bladder cancer, and to determine the appropriate treatment. Three hundred and three patients with superficial bladder cancer, who were newly diagnosed and initially treated conservatively in our hospital between 1965 and 1990, were followed for at least 5 years and their clinical outcomes were analyzed. Clinical factors, including anterior urethral recurrence, were evaluated statistically regarding tumor progression. Eight patients (2.6%) had anterior urethral recurrence following superficial bladder cancer. Twenty-four patients (7.9%) had tumor progression and 149 (49.2%) had tumor recurrence. In a multivariate analysis using a logistic model, anterior urethral recurrence was the most important factor, followed by histological grade. Four of 5 patients who were treated for anterior urethral recurrent tumors by transurethral resection showed progression and died of the cancer within one year. Two of the remaining three patients who underwent radical cysto-urethrectomy at the time of anterior urethral recurrence survived. Anterior urethral recurrence following superficial bladder cancer is a predictor for rapid subsequent malignant progression. Once there is anterior urethral recurrence, radical intensive therapy, including radical cysto-urethrectomy, should be carried out immediately. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 58 4 2004 Ureteroscopy using a detachable access sheath. 215 216 EN Fernando Abarzua Koichi Monden Atsushi Nagai Yasutomo Nasu Hiromi Kumon Article 10.18926/AMO/32084 Ureteroscopy has evolved in many aspects, particularly in the flexibility and size of ureteroscopes. We have developed a new detachable access sheath to make ureteroscopic procedures more straight-forward and to reduce possible damage to delicate instruments used in the procedure. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 59 5 2005 Sex reassignment surgery for male to female transsexuals: initial experience in Okayama university hospital. 231 233 EN Atsushi Nagai Eijirou Tokuyama Yuzaburo Nanba Tetsuya Tsutsui Yoshihiro Kimata Mikiya Nakatsuka Isao Koshima Takashi Saika Yasutomo Nasu Hiromi Kumon Article 10.18926/AMO/31976 The first case of sex reassignment surgery (SRS) in our hospital was performed in January 2001; as of February, 2005, 4 cases of MTF-SRS had been performed. In the 2 most recent cases, we used penile and scrotal skin flaps to avoid complications. The depth and width of the new vagina was made to be adequate for sexual intercourse. Future attention should be focused on devising a surgical technique that will help prevent the complications of partial necrosis of the epidermal skin and wound dehiscence. Although ours is only an initial experience, we describe our surgical technique herein. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 59 5 2005 Long-term clinical outcomes of 420 consecutive prostate cancer patients in a single institute. 195 199 EN Kohei Edamura Takashi Saika Takashi Senoh Fumihito Koizumi Daisuke Manabe Shin Ebara Haruki Kaku Teruhiko Yokoyama Fernando Abarzua Atsushi Nagai Yasutomo Nasu Tomoyasu Tsushima Hiromi Kumon Article 10.18926/AMO/31973 This study was undertaken to reveal the trends of prostate cancer and the outcome of treatment modalities for each disease stage in patients in a single institute over a 10-year period. From January 1994 through December 2003, 420 consecutive patients with previously untreated and histologically confirmed prostate cancer were analyzed for annual distributions of disease stages and treatment modalities and for long-term clinical progression-free survival, prostate cancer-specific survival, and prostate-specific antigen (PSA) failure-free survival rates for each stage and treatment modality. Annual trends showed that the number of patients, especially those with clinically localized cancer, increased dramatically. The 5-year disease-specific survival rates for patients with clinically localized disease were 100 percent for all treatment modalities, including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml showed an 81 percent 5-year PSA failure-free survival rate with radical prostatectomy. Stage C patients treated by surgery or radiation-based therapy with concomitant hormonal therapy obtained 93 percent and 100 percent cause-specific survival rates, respectively, and those treated by hormonal therapy alone showed a 79 percent rate. The number of patients with localized prostate cancer was increasing in this decade. While long-term hormonal therapy alone was highly efficient in controlling localized prostate cancer, radical therapies in conjunction with neo-adjuvant hormonal therapy produced better survival rates in cases of locally advanced disease. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 59 2 2005 Clinical results of one-stage urethroplasty with parameatal foreskin flap for hypospadias. 45 48 EN Atsushi Nagai Yasutomo Nasu Masami Watanabe Norihiro Kusumi Hiromu Tsuboi Hiromi Kumon Article 10.18926/AMO/31964 We investigated the usefulness of one-stage urethroplasty by the parameatal foreskin flap method (OUPF procedure), which is useful for repairing all types of hypospadias. Between June 1992 and March 2001, the OUPF procedure was performed on 18 patients with hypospadias: 10 patients with distal and 8 with proximal hypospadias. The follow-up periods ranged from 33-75 months, with an average of 52 months. The duration of surgery, the catheter indwelling period, and the postoperative complications of each patient were analyzed. The median age of the patients at the time of surgery was 3 years and 8 months. The length of surgery for OUPF II ranged from 150-230 min (average 186 min), and from 190-365 min (average 267 min) for OUPF IV. Postoperative complications were confirmed in 3 of the 18 patients (16.6%). Two patients had fistulas, and one had a meatal regression. The fistulas were successfully closed by the simple multilayered closure method. After adopting DuoDerm dressings instead of elastic bandages for protection of the wound, no fistulization occurred. DuoDerm dressings are useful in the healing of wounds without complications. To date, the longest follow-up period has been 75 months, and during that time there have been no late complications such as urethral stenosis or penile curvature. OUPF is a useful method in the treatment of hypospadias with a low incidence of early and late complications. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 59 6 2005 Intracavernous injection of prostaglandin E1 is effective in patients with erectile dysfunction not responding to phosphodiseterase 5 inhibitors. 279 280 EN Atsushi Nagai Norihiro Kusumi Hiromu Tsuboi Kazushi Ishii Takashi Saika Yasutomo Nasu Hiromi Kumon Short Communication 10.18926/AMO/31956 We report on 64 patients who did not achieve erections adequate for satisfactory sexual intercourse from among a total of 243 patients who were prescribed PDE5 inhibitors for erectile dysfunction (ED). Intracavernous injection (ICI) of PGE was performed in this non-responder group. An ICI of 20 or 40 mcg of PGE1 in 1 ml saline was performed and the responses evaluated. Forty-nine out of 64 (77 percent ) cases responded to 20 mcg of PGE1. Forty mcg of PGE was injected into the 15 non-responding cases, and 9 patients responded favorably. The overall effective rate was 58/64 (91 percent ). No major adverse effects were observed. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 63 3 2009 Prospective longitudinal comparative study of health-related quality of life in patients treated with radical prostatectomy or permanent brachytherapy for prostate cancer 129 135 EN Makoto Kobuke Takashi Saika Yoshiko Nakanishi Shin Ebara Daisuke Manabe Tatsuya Uesugi Hiroyuki Nose Ryoji Arata Tomoyasu Tsushima Yasutomo Nasu Hiromi Kumon Original Article 10.18926/AMO/31847 To determine health-related quality of life (HRQOL) after radical retropubic prostatectomy (RRP) or permanent prostate brachytherapy (BT), third party-conducted QOL surveys were prospectively compared. Between 2004 and 2005, 37 patients underwent RRP and 36 were treated with BT. A QOL survey consisting of the Medical Outcomes Study 36-Item Short Form (SF-36), the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and the International Prostate Symptoms Score (IPSS) was completed prospectively by a research coordinator at baseline, and at 1, 3, 6 and 12 months after treatment. The RRP patients scored well in general QOL except at 1 month after surgery, with their mental health better than at baseline by 6 months after surgery. Disease-specific QOL in RRP patients received a low score at 1 month for both urinary and sexual function, though urinary function rapidly recovered to baseline levels. BT patient QOL was not affected by the therapy except in the IPSS score. However, general and mental health scores in BT patients were inferior to those in RRP patients. This prospective study revealed differences in QOL after RRP and BT. These results will be helpful in making treatment decisions. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 56 1 2002 Laparoscopic radical prostatectomy: initial cases at Okayama University Hospital. 51 52 EN Atsushi Nagai Yasutomo Nasu Yoshinori Shirasaki Hiroki Iguchi Ryouji Arata Masaya Tsugawa Tomoyasu Tsushima Hiromi Kumon Article 10.18926/AMO/31722 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. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 47 3 1993 Hyperthermotherapy added to the multidisciplinary therapy for penile cancer. 169 174 EN Masahiro Kuroda Tomoyasu Tsushima Yasutomo Nasu Junichi Asaumi Koji Nishikawa Xian Shu Gao Ikuo Joja Yoshihiro Takeda Izumi Togami Eiichi Makihata Shoji Kawasaki Hiroyuki Ohmori Yoshio Hiraki Article 10.18926/AMO/31599 We performed a long-term follow-up of 4 patients with penile cancer who underwent hyperthermotherapy from August 1985 until August 1992. Hyperthermia was applied using a frequency of 350 MHz with a waveguide applicator twice a week for 60 min each for an average of 9.5 times (varying from 6 to 13 times). The total heating time that the temperature of urethra could be kept above 42 degrees C, was 166 min on the average (ranging from 0 to 463 min). Two patients classified as stage I according to the Jackson classification and 1 patient classified as stage IV underwent combined radiotherapy and received an average radiation dose of 53 Gy (range, 40-70 Gy). Among these patients 2 underwent combined chemotherapy with bleomycin or peplomycin. Malignant cells disappeared posttherapeutically and in August 1992, after an average of 5 years and 9 months (varying from 4 years 6 months to 6 years 10 months), the patients were free of recurrences. The one patient on stage IV had extensive invasion of the abdominal wall, but still recovered completely. One patient on stage III underwent combined chemotherapy and hyperthermotherapy, but heating had obviously been insufficient. There was a residue of malignant cells after the treatment and we performed a penectomy. Regarding functional preservation of the penis a multidisciplinary therapy incorporating hyperthermotherapy can be expected to increase the curativity. This indicates that it could induce in an advanced case, where an operation would be difficult, complete remission. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 62 1 2008 Iodine-125 Seed Implantation (Permanent Brachytherapy) for Clinically Localized Prostate Cancer 9 13 EN Shin Ebara Yoshihisa Katayama Ryuta Tanimoto Kohei Edamura Hiroyuki Nose Daisuke Manabe Tomoko Kobayashi Yasuyuki Kobayashi Makoto Kobuke Mitsuhiro Takemoto Takeshi Saika Yasutomo Nasu Susumu Kanazawa Hiromi Kumon Original Article 10.18926/AMO/30986 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. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 62 6 2008 Initial Report of Hybrid Radical Prostatectomy for Prostate Cancer:Reduced Bleeding, Clear Vision, and Secure Surgical Margins 379 384 EN Takashi Saika Yasuyuki Kobayashi Toyohiko Watanabe Daisuke Manabe Shin Ebara Shinya Uehara Yasutomo Nasu Hiromi Kumon Original Article 10.18926/AMO/30950 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. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 62 6 2008 Mechanistic Analysis of Resistance to REIC/Dkk-3-induced Apoptosis in Human Bladder Cancer Cells 393 401 EN Tomoko Kobayashi Masakiyo Sakaguchi Ryuta Tanimoto Fernando Abarzua Mikiro Takaishi Haruki Kaku Ken Kataoka Takashi Saika Yasutomo Nasu Masahiro Miyazaki Hiromi Kumon Nam-ho Huh Original Article 10.18926/AMO/30945 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. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 62 4 2008 The Benefits of Clamping the Renal Artery in Laparoscopic Partial Nephrectomy 269 273 EN Yasuyuki Kobayashi Takashi Saika Daisuke Manabe Yasutomo Nasu Hiromi Kumon Original Article 10.18926/AMO/30939 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. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 60 1 2006 Combination chemotherapy with estramustine phosphate, ifosfamide and cisplatin for hormone-refractory prostate cancer. 43 49 EN Haruki Kaku Takashi Saika Tomoyasu Tsushima Atsushi Nagai Teruhiko Yokoyama Fernando Abarzua Shin Ebara Daisuke Manabe Yasutomo Nasu Hiromi Kumon Article 10.18926/AMO/30759 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. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 60 2 2006 Effects of radiofrequency ablation on individual renal function: assessment by technetium-99m mercaptoacetyltriglycine renal scintigraphy. 85 91 EN Takashi Mukai Shuhei Sato Toshihiro Iguchi Hidefumi Mimura Kotaro Yasui Hideo Gobara Takashi Saika Yasutomo Nasu Hiromi Kumon Susumu Kanazawa Article 10.18926/AMO/30731 We quantitatively evaluated total and individual renal function by technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) renal scintigraphy before and after radiofrequency ablation (RFA) of renal tumors. Eleven patients who underwent Tc-99m MAG3 renal scintigraphy 1 week before and after RFA were evaluated (7 men and 4 women ; age range : 23-83 years ; mean age : 60.6 years). Five patients had solitary kidneys, and five had normally or minimally functioning contralateral kidneys. One patient had a renal cell carcinoma in the contralateral kidney. One patient with a solitary kidney underwent RFA a second time for a residual tumor. In patients with a solitary kidney, MAG3 clearance decreased after 5 of 6 RFAs, and in patients with a normally functioning contralateral kidney, MAG3 clearance decreased after 4 of 5 RFAs, but no significant differences were observed between before and after treatments. In addition to the total MAG3 clearance, the split MAG3 clearance was evaluated in patients with a normally functioning contralateral kidney. MAG3 clearance decreased in 4 of 5 treated kidneys, while it adversely increased in the contralateral kidneys after 4 of 5 RFAs. No significant differences, however, were observed between before and after treatments. The results of our study revealed no significant differences in sCr, BUN, CCr, or MAG3 clearance between pre- and post-RFA values. These results support data regarding the functional impact and safety of renal RFA in published reports. We evaluated total and individual renal function quantitatively using Tc-99m MAG3 renal scintigraphy before and after treatment. This scintigraphy was very useful in assessing the effects of RFA on renal function. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 114 2 2002 前立腺癌遺伝子治療の現状と展望 173 177 EN No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 00301558 120 2 2008 XIII 泌尿器科がんにおける標準的治療 207 213 EN Makoto Kobuke Yasutomo Nasu Hiromi Kumon No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 00301558 120 2 2008 内分泌療法再燃前立腺癌に対する HSV-tk 遺伝子発現アデノウイルスベクター及びガンシクロビルを用いた自殺遺伝子治療臨床研究 149 152 EN Yasutomo Nasu 「前立腺癌に対する herpes simplex virus-thymidine kinase遺伝子発現アデノウイルスベクター及びガンシクロビルを用いた遺伝子治療臨床研究」を実施した．対象となる被験者は内分泌療法中に再燃してきた臨床的に遠隔転移を認めない局所再燃前立腺癌とした．まず herpes simplex virus-thymidine kinase（HSV-tk）遺伝子発現アデノウイルスベクターを単独で腫瘍内に直接投与し，その後ガンシクロビル（ganciclovir：GCV）を全身投与した．　本研究は2001年3月より第1例目の被験者の治療を開始し，平成17年7月に最終登録例である9例目の被験者の治療を実施し，6ヶ月以上観察し，臨床試験を終了とした（8名のべ9症例）．　9症例すべてにおいて有意な副作用を認めなかった．また，ウイルスベクター投与後の抗アデノウイルス中和抗体価の上昇は軽度でかつ一過性であった．ウイルスベクター投与後，48時間において採取した組織においてｍRNA レベルでの HSV-tk 遺伝子の発現が確認された．治療効果の指標として腫瘍マーカーである PSA は9例中6例において低下した．　結論として局所再燃前立腺癌に対し，HSV-tk 遺伝子発現アデノウイルスベクターを単独で局所内投与し，その後ガンシクロビルを全身投与することの安全性および治療効果が確認された． No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1986 膀胱腫瘍における malignant potential の指標としての ABH-isoantigen PAP 法による染色パターンに基づく判定基準の作成ならびに CEA, Fib-ronectin との関連性 EN No potential conflict of interest relevant to this article was reported.