Faculty Profiles - NASU Yasutomo

Papers - NASU Yasutomo

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Clinical significance of tumor location for ureteroscopic tumor grading in upper tract urothelial carcinoma. International journal

Satoshi Katayama, Benjamin Pradere, Nico C Grossmann, Aaron M Potretzke, Stephen J Boorjian, Alireza Ghoreifi, Siamak Daneshmand, Hooman Djaladat, John Sfakianos, Andrea Mari, Zine-Eddine Khene, David D'Andrea, Nozomi Hayakawa, Kazutoshi Fujita, Axel Heidenreich, Jay D Raman, Mathieu Roumiguie, Firas Abdollah, Alberto Breda, Matteo Fontana, Morgan Roupret, Vitaly Margulis, Pierre I Karakiewicz, Motoo Araki, Yasutomo Nasu, Shahrokh F Shariat

Journal of endourology 2024.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Although previous literature shows tumor location as a prognostic factor in upper tract urothelial carcinoma (UTUC), there remains uninvestigated regarding the impact of tumor location on grade concordance and discrepancies between ureteroscopic (URS) biopsy and final radical nephroureterectomy(RNU) pathology. METHODS: In this international study, we retrospectively reviewed the records of 1,498 patients with UTUC who underwent diagnostic URS with concomitant biopsy followed by RNU between 2005 and 2020. Tumor location was divided into four sections: the calyceal-pelvic system, proximal ureter, middle ureter, and distal ureter. Patients with multifocal tumors were excluded from the study. We performed multiple comparison tests and logistic regression analyses. RESULTS: Overall, 1,154 patients were included; 54.4% of those with low-grade URS biopsies were upgraded on RNU. In the multiple comparison tests, middle ureter tumors exhibited the highest probability of upgrading, meanwhile pelvicalyceal tumors exhibited the lowest probability of upgrading (73.7% vs 48.5%, p=0.007). Downgrading was comparable across all tumor locations. On multivariable analyses, middle ureteral location was significantly associated with a low probability of grade concordance (OR 0.59; 95%CI, 0.35-1.00; p =0.049) and an increased risk of upgrading (OR 2.80; 95%CI, 1.20-6.52; p =0.017). The discordance did not vary regardless of caliceal location, including the lower calyx. CONCLUSIONS: Middle ureteral tumors diagnosed to be low-grade had a high probability to be undergraded. Our data can inform providers and their patients regarding the likelihood of undergrading according to tumor location, facilitating patient counselling and shared decision making regarding the choice of kidney sparing vs RNU.

DOI： 10.1089/end.2024.0335

The Prognostic Value of Tumor Infiltrating Lymphocytes After Radical Cystectomy for Bladder Cancer: A Systematic Review and Meta-Analysis. International journal

Tatsushi Kawada, Takafumi Yanagisawa, Pawel Rajwa, Reza Sari Motlagh, Hadi Mostafaei, Fahad Quhal, Ekaterina Laukhtina, Maximilian Pallauf, Frederik König, Benjamin Pradere, Motoo Araki, Yasutomo Nasu, Shahrokh F Shariat

Clinical genitourinary cancer 22 ( 2 ) 535 - 543 2024.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: We aimed to assess the prognostic value of tumor infiltrating lymphocytes (TILs) in patients with bladder cancer (BC) after radical cystectomy (RC). MATERIALS AND METHODS: We searched Pubmed, Web of Science and Scopus in April 2022 to identify studies assessing the prognostic value of TILs, including a subset of lymphocytes (eg, CD3, CD8, FOXP3), after RC. The endpoints were overall survival and recurrent free survival. Subgroup analyses were performed based on the evaluation method for TILs (ie, CD3, CD8, FOXP3, HE staining). RESULTS: Overall, 9 studies comprising 1413 patients were included in this meta-analysis. The meta-analysis revealed that elevated expressions of TILs were significantly associated with favorable OS (pooled hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.51-0.83) and RFS (pooled HR: 0.48, 95% CI: 0.35-0.64). In subgroup analyses, high CD8+ TILs were also associated with favorable OS (HR: 0.51, 95% CI: 0.33-0.80) and RFS (pooled HR: 0.53, 95% CI: 0.36-0.76). Among 3 studies comprising 146 patients, high intratumoral TILs were significantly associated with favorable OS (pooled HR: 0.34, 95% CI: 0.19-0.60). CONCLUSION: TILs are useful prognostic markers in patients treated with RC for BC. Although the prognostic value of TILs is varied, depending on the subset and infiltration site, CD8+ TILs and intratumoral TILs are associated with oncologic outcomes. Further studies are warranted to explicate the predictive value of TILs on the response to perioperative systemic therapy to help clinical decision-making in patients with BC.

DOI： 10.1016/j.clgc.2024.01.008

【mRNAワクチンやゲノム編集で注目が集まる遺伝子治療】遺伝子治療技術を用いた疾患治療アデノウイルスベクターを用いた遺伝子治療の最前線

定平卓也, 那須保友

医学のあゆみ 285 ( 5 ) 464 - 468 2023.4

Language：Japanese Publisher：医歯薬出版(株)

難治性癌に対する遺伝子治療を実現するためには,遺伝子とそれを運ぶベクターが必要である.筆者らは,これまでに癌抑制・治療遺伝子REIC(reduced expression in immortalized cell)を発現するアデノウイルスベクター(Ad-REIC)を臨床開発し,難治性前立腺癌に対するin-situ遺伝子治療を実施し,その抗腫瘍効果を実証してきた.また筆者らは最近,きわめて強力な遺伝子発現を実現する超高効率遺伝子発現技術や新規制限増殖型ベクターをREIC遺伝子治療に組み込み,次世代遺伝子治療の可能性を見出している.本稿では,新規Ad-REIC製剤を用いた難治性癌の治療について,最新の研究成果も交えつつ解説する.(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00060&link_issn=&doc_id=20230502010026&doc_link_id=issn%3D0039-2359%26volume%3D285%26issue%3D5%26spage%3D464&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0039-2359%26volume%3D285%26issue%3D5%26spage%3D464&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Significance of UGT1A6, UGT1A9, and UGT2B7 genetic variants and their mRNA expression in the clinical outcome of renal cell carcinoma. International journal

Jun Matsumoto, Anzu Nishimoto, Shogo Watari, Hideo Ueki, Shoya Shiromizu, Naohiro Iwata, Tatsuaki Takeda, Soichiro Ushio, Makoto Kajizono, Masachika Fujiyoshi, Toshihiro Koyama, Motoo Araki, Koichiro Wada, Yoshito Zamami, Yasutomo Nasu, Noritaka Ariyoshi

Molecular and cellular biochemistry 478 ( 8 ) 1779 - 1790 2022.12

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1007/s11010-022-04637-4

Toll-like receptor 4 promotes bladder cancer progression upon S100A8/A9 binding, which requires TIRAP-mediated TPL2 activation

Acosta Gonzalez Herik Rodrigo, Nahoko Tomonobu, Haruka Yoneda, Rie Kinoshita, Yosuke Mitsui, Takuya Sadahira, Shin-ichi Terawaki, Yuma Gohara, Ni Luh Gede Yoni Komalasari, Fan Jiang, Hitoshi Murata, Ken-ichi Yamamoto, Junichiro Futami, Akira Yamauchi, Futoshi Kuribayashi, Yusuke Inoue, Eisaku Kondo, Shinichi Toyooka, Masahiro Nishibori, Masami Watanabe, Yasutomo Nasu, Masakiyo Sakaguchi

Biochemical and Biophysical Research Communications 634 83 - 91 2022.12

Influence of steep Trendelenburg position on postoperative complications: a systematic review and meta-analysis. International journal

Satoshi Katayama, Keiichiro Mori, Benjamin Pradere, Takafumi Yanagisawa, Hadi Mostafaei, Fahad Quhal, Reza Sari Motlagh, Ekaterina Laukhtina, Nico C Grossmann, Pawel Rajwa, Abdulmajeed Aydh, Frederik König, Pierre I Karakiewicz, Motoo Araki, Yasutomo Nasu, Shahrokh F Shariat

Journal of robotic surgery 16 ( 6 ) 1233 - 1247 2022.12

Language：English Publishing type：Research paper (scientific journal)

Intraoperative physiologic changes related to the steep Trendelenburg position have been investigated with the widespread adoption of robot-assisted pelvic surgery (RAPS). However, the impact of the steep Trendelenburg position on postoperative complications remains unclear. We conducted a meta-analysis to compare RAPS to laparoscopic/open pelvic surgery with regards to the rates of venous thromboembolism (VTE), cardiac, and cerebrovascular complications. Meta-regression was performed to evaluate the influence of confounding risk factors. Ten randomized controlled trials (RCTs) and 47 non-randomized controlled studies (NRSs), with a total of 380,125 patients, were included. Although RAPS was associated with a decreased risk of VTE and cardiac complications compared to laparoscopic/open pelvic surgery in NRSs [risk ratio (RR), 0.59; 95% CI 0.51-0.72, p < 0.001 and RR 0.93; 95% CI 0.58-1.50, p = 0.78, respectively], these differences were not confirmed in RCTs (RR 0.92; 95% CI 0.52-1.62, p = 0.77 and RR 0.93; 95% CI 0.58-1.50, p = 0.78, respectively). In subgroup analyses of laparoscopic surgery, there was no significant difference in the risk of VTE and cardiac complications in both RCTs and NRSs. In the meta-regression, none of the risk factors were found to be associated with heterogeneity. Furthermore, no significant difference was observed in cerebrovascular complications between RAPS and laparoscopic/open pelvic surgery. Our meta-analysis suggests that the steep Trendelenburg position does not seem to affect postoperative complications and, therefore, can be considered safe with regard to the risk of VTE, cardiac, and cerebrovascular complications. However, proper individualized preventive measures should still be implemented during all surgeries including RAPS to warrant patient safety.

DOI： 10.1007/s11701-021-01361-x

Prognostic value of hepatocyte growth factor for muscle-invasive bladder cancer. International journal

Satoshi Katayama, Victor M Schuettfort, Benjamin Pradere, Keiichiro Mori, Hadi Mostafaei, Fahad Quhal, Reza Sari Motlagh, Ekaterina Laukhtina, Nico C Grossmann, Abdulmajeed Aydh, Pawel Rajwa, Frederik König, Pierre I Karakiewicz, Martin Haydter, Marco Moschini, Mohammad Abufaraj, Yair Lotan, Richard K Lee, Quoc-Dien Trinh, Eva Compérat, Jeremy Teoh, Yasutomo Nasu, Shahrokh F Shariat

Journal of cancer research and clinical oncology 148 ( 11 ) 3091 - 3102 2022.11

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The HGF/MET pathway is involved in cell motility, angiogenesis, proliferation, and cancer invasion. We assessed the clinical utility of plasma HGF level as a prognostic biomarker in patients with MIBC. METHODS: We retrospectively analyzed 565 patients with MIBC who underwent radical cystectomy. Logistic regression and Cox regression models were used, and predictive accuracies were estimated using the area under the curve and concordance index. To estimate the clinical utility of HGF, DCA and MCID were applied. RESULTS: Plasma HGF level was significantly higher in patients with advanced pathologic stage and LN metastasis (p = 0.01 and p < 0.001, respectively). Higher HGF levels were associated with an increased risk of harboring LN metastasis and non-organ-confined disease (OR1.21, 95%CI 1.12-1.32, p < 0.001, and OR1.35, 95%CI 1.23-1.48, p < 0.001, respectively) on multivariable analyses; the addition of HGF improved the predictive accuracies of a standard preoperative model (+ 7%, p < 0.001 and + 8%, p < 0.001, respectively). According to the DCA and MCID, half of the patients had a net benefit by including HGF, but the absolute magnitude remained limited. In pre- and postoperative predictive models, a higher HGF level was significant prognosticator of worse RFS, OS, and CSS; in the preoperative model, the addition of HGF improved accuracies by 6% and 5% for RFS and CSS, respectively. CONCLUSION: Preoperative HGF identified MIBC patients who harbored features of clinically and biologically aggressive disease. Plasma HGF could serve, as part of a panel, as a biomarker to aid in preoperative treatment planning regarding intensity of treatment in patients with clinical MIBC.

DOI： 10.1007/s00432-021-03887-x

Pacsin 2-dependent N-cadherin internalization regulates the migration behaviour of malignant cancer cells

Haymar Wint, Jianzhen Li, Tadashi Abe, Hiroshi Yamada, Yasutomo Nasu, Masami Watanabe, Kohji Takei, Tetsuya Takeda

2022.8

Diagnostic Performance of Prostate-specific Membrane Antigen Positron Emission Tomography-targeted biopsy for Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis. International journal

Tatsushi Kawada, Takafumi Yanagisawa, Pawel Rajwa, Reza Sari Motlagh, Hadi Mostafaei, Fahad Quhal, Ekaterina Laukhtina, Abdulmajeed Aydh, Frederik König, Maximilian Pallauf, Benjamin Pradere, Francesco Ceci, Pascal A T Baltzer, Marcus Hacker, Sazan Rasul, Pierre I Karakiewicz, Motoo Araki, Yasutomo Nasu, Shahrokh F Shariat

European urology oncology 5 ( 4 ) 390 - 400 2022.8

Language：English Publishing type：Research paper (scientific journal)

CONTEXT: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has gained acceptance as a staging tool for prostate cancer (PCa). Recent reports suggest an association between PSMA PET and detection of clinically significant PCa (csPCa) on prostate biopsy. OBJECTIVE: To assess the diagnostic accuracy of PSMA PET-targeted biopsy (PSMA-PET-TB) for csPCa detection. EVIDENCE ACQUISITION: We searched PubMed, Web of Science, and Scopus in December 2021 to identify studies assessing the accuracy of PSMA-PET-TB for csPCa detection. A diagnostic meta-analysis was performed to calculate pooled sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PSMA-PET-TB alone and in combination with magnetic resonance imaging (MRI)-TB for detecting csPCa. EVIDENCE SYNTHESIS: Overall, five prospective studies involving 497 patients were eligible for this meta-analysis. For csPCa detection, PSMA-PET-TB had pooled sensitivity, specificity, PPV, and NPV of 0.89 (95% confidence interval [CI] 0.85-0.93), 0.56 (95% CI 0.29-0.80), 0.69 (95% CI 0.58-0.79), and 0.78 (95% CI 0.50-0.93), respectively. Among the three studies assessing the PSMA-PET + MRI-TB strategy, the pooled sensitivity, specificity, PPV, and NPV for csPCa detection were 0.91 (95% CI 0.77-0.97), 0.64 (95% CI 0.40-0.82), 0.75 (95% CI 0.56-0.87), and 0.85 (95% CI 0.62-0.95), respectively. For lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3, the sensitivity, specificity, PPV, and NPV were 0.69, 0.73, 0.48, and 0.86, respectively. CONCLUSIONS: PSMA-PET-TB appears to have favorable diagnostic accuracy for csPCa detection and combination with MRI seems to improve this. According to our meta-analysis, PSMA-PET has promising clinical application for detection of csPCa, namely in the case of PI-RADS 3 lesions. Further prospective studies are needed to explore the true clinical utility of a PSMA-PET-based diagnostic pathway. PATIENT SUMMARY: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) is a promising imaging method for detecting clinically significant prostate cancer and seems to have additional value to magnetic resonance imaging (MRI) for detection.

DOI： 10.1016/j.euo.2022.04.006

Adverse Events of Axitinib plus Pembrolizumab Versus Lenvatinib plus Pembrolizumab: A Pharmacovigilance Study in Food and Drug Administration Adverse Event Reporting System. International journal

Jun Matsumoto, Naohiro Iwata, Shogo Watari, Soichiro Ushio, Shoya Shiromizu, Tatsuaki Takeda, Hirofumi Hamano, Makoto Kajizono, Motoo Araki, Yasutomo Nasu, Noritaka Ariyoshi, Yoshito Zamami

European urology focus 9 ( 1 ) 141 - 144 2022.7

Language：English Publishing type：Research paper (scientific journal)

No head-to-head postmarket surveillance study has compared the differences in adverse events (AEs) between two combination therapies, axitinib (AXI) + pembrolizumab (PEMBRO) and lenvatinib (LEN) + PEMBRO, against metastatic renal cell carcinoma. This study aims to highlight the comprehensive differences in AEs between these two therapies based on the real-world big data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. In total, 28 937 records were extracted from the FAERS database, and 139 AEs grouped into the System Organ Class according to the Medical Dictionary for Regulatory Activities were analysed. Logistic regression analyses were performed, and the reporting odds ratio with a 95% confidence interval was determined. We found that the incidences of cardiac and hepatobiliary disorders for AXI + PEMBRO, and blood and lymphatic system, metabolism and nutrition, and vascular disorders for LEN + PEMBRO, all of which were associated with serious AEs, were higher than those for LEN + PEMBRO and AXI + PEMBRO, respectively. The differences in the AEs between AXI + PEMBRO and LEN + PEMBRO were not derived merely from those between AXI and LEN monotherapies. Furthermore, remarkable AE potentiation was observed for AXI + PEMBRO. As FAERS is a spontaneous reporting system comprising partially limited information, analysing more detailed relationships between AEs and patient or treatment characteristics was challenging in this study. The present study is the first to show the overall real-world postmarketing differences in AEs between AXI + PEMBRO and LEN + PEMBRO. Our novel findings will substantially improve clinical practice; we recommend comparing patients' conditions associated with the above AEs when selecting between these two therapies. PATIENT SUMMARY: Herein, we highlight the differences in adverse events (AEs) between axitinib + pembrolizumab and lenvatinib + pembrolizumab therapies using data from the real-world Food and Drug Administration Adverse Event Reporting System database aimed at patients with metastatic renal cell carcinoma. We identified AEs that needed attention in each combination. We recommend the differences in AEs to be considered when selecting these two therapies.

DOI： 10.1016/j.euf.2022.07.003

ステント付着結石により3本尿管ステント留置し2度のECIRSによりstone freeとなった1例

堀井聡, 奥村美紗, 渡部智文, 関戸崇了, 徳永素, 吉永香澄, 丸山雄樹, 山野井友昭, 長尾賢太郎, 富永悠介, 定平卓也, 片山聡, 岩田健宏, 西村慎吾, 佐古智子, 枝村康平, 小林泰之, 荒木元朗, 石井亜矢乃, 渡部昌実, 渡邉豊彦, 那須保友

西日本泌尿器科 84 ( 増刊号2 ) 168 - 168 2022.6

Accuracy and Clinical Utility of a Tumor Grade- and Stage-based Predictive Model in Localized Upper Tract Urothelial Carcinoma. International journal

Satoshi Katayama, Keiichiro Mori, Victor M Schuettfort, Benjamin Pradere, Hadi Mostafaei, Fahad Quhal, Pawel Rajwa, Reza Sari Motlagh, Ekaterina Laukhtina, Marco Moschini, Nico C Grossmann, Motoo Araki, Jeremy Yuen-Chun Teoh, Morgan Rouprêt, Vitaly Margulis, Dmitry Enikeev, Pierre I Karakiewicz, Mohammad Abufaraj, Eva Compérat, Yasutomo Nasu, Shahrokh F Shariat

European urology focus 8 ( 3 ) 761 - 768 2022.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Among various clinicopathologic factors used to identify low-risk upper tract urothelial carcinoma (UTUC), tumor grade and stage are of utmost importance. The clinical value added by inclusion of other risk factors remains unproven. OBJECTIVE: To assess the performance of a tumor grade- and stage-based (GS) model to identify patients with UTUC for whom kidney-sparing surgery (KSS) could be attempted. DESIGN, SETTING, AND PARTICIPANTS: In this international study, we reviewed the medical records of 1240 patients with UTUC who underwent radical nephroureterectomy. Complete data needed for risk stratification according to the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) guidelines were available for 560 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable logistic regression analyses were performed to determine if risk factors were associated with the presence of localized UTUC. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the GS, EAU, and NCCN models in predicting pathologic stage were calculated. RESULTS AND LIMITATIONS: Overall, 198 patients (35%) had clinically low-grade, noninvasive tumors, and 283 (51%) had ≤pT1disease. On multivariable analyses, none of the EAU and NCCN risk factors were associated with the presence of non-muscle-invasive UTUC among patients with low-grade and low-stage UTUC. The GS model exhibited the highest accuracy, sensitivity, and negative predictive value among all three models. According to the GS, EAU, and NCCN models, the proportion of patients eligible for KSS was 35%, 6%, and 4%, respectively. Decision curve analysis revealed that the net benefit of the three models was similar within the clinically reasonable range of probability thresholds. CONCLUSIONS: The GS model showed favorable predictive accuracy and identified a greater number of KSS-eligible patients than the EAU and NCCN models. A decision-making algorithm that weighs the benefits of avoiding unnecessary kidney loss against the risk of undertreatment in case of advanced carcinoma is necessary for individualized treatment for UTUC patients. PATIENT SUMMARY: We assessed the ability of three models to predict low-grade, low-stage disease in patients with cancer of the upper urinary tract. No risk factors other than grade assessed on biopsy and stage assessed from scans were associated with better prediction of localized cancer. A model based on grade and stage may help to identify patients who could benefit from kidney-sparing treatment of their cancer.

DOI： 10.1016/j.euf.2021.05.002

尿から分離されたESBL産生大腸菌株の性状解析を踏まえたFMOXの使用法

榮枝一磨, 定平卓也, 丸山雄樹, 岩田健宏, 荒木元朗, 石井亜矢乃, 渡邉豊彦, 那須保友, 和田耕一郎, 光畑律子

日本化学療法学会雑誌 70 ( Suppl.A ) 289 - 289 2022.5

ロボット支援下前立腺全摘除術中にモノポーラシザースのチップカバーが脱落し、発見が困難であった一例

長尾賢太郎, 岩田健宏, 西村慎吾, 高本篤, 佐古智子, 枝村康平, 荒木元朗, 渡邉豊彦, 那須保友, 小林泰之

Japanese Journal of Endourology and Robotics 35 ( 1 ) 168 - 172 2022.4

Language：Japanese Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会

我々が経験したロボット支援下前立腺全摘除術におけるインシデントを報告する.症例は70歳代男性.手術はda Vinci Xiで行われた.術中,1stポートのインストゥルメントを入れ替えた際に,モノポーラシザースよりチップカバーが外れ,紛失した.腹腔内や術野内外をX線透視も用いて探索するも見つからず,Computed tomographyを施行したところ,1stポート造設部の皮下に迷入していた.その後は手術を再開し,合併症なく終了.チップカバーは画像と同部位の皮下より摘出された.手術映像を見返したところ,チップカバーが適切に装着されておらず,インストゥルメント交換の際にトロッカーが皮下まで抜けていたことが判明した.本件のようなインシデントを予防するためには,チップカバーの適切な装着と,インストゥルメントの正しい手順での交換および交換時の確認が必要である.(著者抄録)

【初心にかえって、TURBTの手技徹底検証!】合併症を回避するTURBTの極意

西村慎吾, 小林泰之, 定平卓也, 岩田健宏, 高本篤, 佐古智子, 枝村康平, 和田耕一郎, 荒木元朗, 渡邉豊彦, 那須保友

Japanese Journal of Endourology and Robotics 35 ( 1 ) 45 - 50 2022.4

Language：Japanese Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会

TURBTは泌尿器科医にとって必須な手技であり,その良し悪しが患者の予後を規定するといっても過言ではない.加えて,TURBTは個体差によるバリエーションに富んでおり,初心者のみならず熟練者であってもその難しさを痛感する手術である.そのため,それぞれの症例に応じた戦略(根治的・姑息的・診断的切除の判断,切除の手順・方法等)をたてることが重要であり,加えて合併症対策をしっかりと行うこと,システム化された指導法を確立することが重要である.今回,初心に立ち返り当院における『合併症を回避するためのポイント』を整理した.術中合併症には穿孔や出血が挙げられる.高齢者,複数回のTUR歴やBCG治療歴などによる膀胱壁菲薄化が術中穿孔リスクとなる.出血は,術中の不十分な止血操作だけでなく,抗血小板薬・抗凝固薬の内服もリスクとなる.これらの薬剤継続による出血のみならず,休薬に伴う血栓症リスクを術前に評価することも重要である.術後合併症には前立腺肥大症などによる尿道カテーテル抜去後尿閉による穿孔がある.これらの合併症対策として,1.術前に画像検査で筋層浸潤の有無を判断し,症例に応じた戦略作成をたてること,2.抗血小板・抗凝固薬の継続,中止の取り扱いを検討すること,3.システム化された指導を行うこと,が重要である.これらのポイントについて,当科で実践している手技,術前戦略が功を奏した症例などを提示しながら解説する.(著者抄録)

Comparison of short-term and long-term neoadjuvant hormone therapy prior to radical prostatectomy: a systematic review and meta-analysis. International journal

Satoshi Katayama, Keiichiro Mori, Benjamin Pradere, Hadi Mostafaei, Victor M Schuettfort, Fahad Quhal, Reza Sari Motlagh, Ekaterina Laukhtina, Nico C Grossmann, Pawel Rajwa, Abdulmajeed Aydh, Frederik König, Romain Mathieu, Peter Nyirady, Pierre I Karakiewicz, Yasutomo Nasu, Shahrokh F Shariat

Scandinavian journal of urology 56 ( 2 ) 85 - 93 2022.4

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: This study aimed to evaluate the efficacy of long-term neoadjuvant androgen-deprivation therapy (ADT) before radical prostatectomy (RP). METHODS: We conducted meta-analyses and network meta-analyses, which included randomized controlled trials that assessed patients with prostate cancer (PC) who received either short-term (<6 months) or long-term (≥6 months) neoadjuvant ADT before RP. RESULTS: Thirteen articles with 2778 patients were eligible for analysis. Short-term neoadjuvant ADT was neither associated with biochemical recurrence (OR 1.19, 95% CI, 0.93-1.51, p = 0.17), metastasis (OR 0.73, 95% CI, 0.45-1.19, p = 0.21), nor overall mortality (OR 0.72, 95% CI 0.43-1.21, p = 0.22); no study investigated survival outcomes in patients on long-term neoadjuvant ADT. In terms of pathologic outcomes, long-term neoadjuvant ADT was significantly associated with a reduced risk of positive surgical margin (SM) and an increased rate of organ-confined disease (OCD) compared to short-term neoadjuvant ADT (OR 0.56, 95% CI 0.39-0.80, p = 0.001, and OR 1.48, 95% CI 1.10-1.99, p = 0.009, respectively). These findings were confirmed in the network meta-analyses. Meanwhile, only a non-significant trend favoring long-term neoadjuvant ADT was observed for pathologic complete response (OR 1.98, 95% Crl 1.00-3.93). CONCLUSION: Long-term neoadjuvant ADT was associated with more favorable pathologic outcomes, but whether these findings translate into favorable survival outcomes still remains unproven due to very limited evidence. Since there are no reliable survival data, long-term neoadjuvant ADT before RP should not be used in clinical practice until more robust evidence arises from ongoing trials.

DOI： 10.1080/21681805.2022.2034941

ロボット支援下前立腺全摘除術中にモノポーラシザースのチップカバーが脱落し、発見が困難であった一例

長尾賢太郎, 岩田健宏, 西村慎吾, 高本篤, 佐古智子, 枝村康平, 荒木元朗, 渡邉豊彦, 那須保友, 小林泰之

Japanese Journal of Endourology and Robotics 35 ( 1 ) 168 - 172 2022.4

Language：Japanese Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会

我々が経験したロボット支援下前立腺全摘除術におけるインシデントを報告する.症例は70歳代男性.手術はda Vinci Xiで行われた.術中,1stポートのインストゥルメントを入れ替えた際に,モノポーラシザースよりチップカバーが外れ,紛失した.腹腔内や術野内外をX線透視も用いて探索するも見つからず,Computed tomographyを施行したところ,1stポート造設部の皮下に迷入していた.その後は手術を再開し,合併症なく終了.チップカバーは画像と同部位の皮下より摘出された.手術映像を見返したところ,チップカバーが適切に装着されておらず,インストゥルメント交換の際にトロッカーが皮下まで抜けていたことが判明した.本件のようなインシデントを予防するためには,チップカバーの適切な装着と,インストゥルメントの正しい手順での交換および交換時の確認が必要である.(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J07650&link_issn=&doc_id=20220531400028&doc_link_id=%2Fcs5robot%2F2022%2F003501%2F032%2F0168-0172%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcs5robot%2F2022%2F003501%2F032%2F0168-0172%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

テキストマイニングによる腎移植に関する症例報告論文の考察

関戸崇了, 荒木元朗, 吉永香澄, 丸山雄樹, 山野井友昭, 定平卓也, 片山聡, 岩田健宏, 西村慎吾, 佐古智子, 枝村康平, 小林泰之, 渡部昌実, 渡邉豊彦, 田邊克幸, 竹内英実, 喜多村真治, 杉山斉, 和田淳, 那須保友

日本臨床腎移植学会プログラム・抄録集 55回 227 - 227 2022.2

Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice. International journal

Ruizhi Xue, Wenfeng Lin, Hirofumi Fujita, Jingkai Sun, Rie Kinoshita, Kazuhiko Ochiai, Junichiro Futami, Masami Watanabe, Hideyo Ohuchi, Masakiyo Sakaguchi, Zhengyan Tang, Peng Huang, Yasutomo Nasu, Hiromi Kumon

Genes 13 ( 2 ) 2022.1

Language：English Publishing type：Research paper (scientific journal)

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, ×106), 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.

DOI： 10.3390/genes13020285

後腹膜リンパ節郭清術後の射精障害の検討

富永悠介, 佐古智子, 奥村美紗, 渡部智文, 近藤崇弘, 関戸崇了, 竹丸紘史, 堀井聡, 吉永香澄, 丸山雄樹, 山野井友昭, 長尾賢太郎, 片山聡, 定平卓也, 岩田健宏, 西村慎吾, 高本篤, 枝村康平, 小林泰之, 荒木元朗, 石井亜矢乃, 渡部昌実, 渡邉豊彦, 那須保友, 松本裕子, 杉本盛人, 和田耕一郎

西日本泌尿器科 84 ( 増刊号1 ) 84 - 84 2022.1

岡山大学病院におけるBioJetシステムを用いたMRI/US融合下経会陰的前立腺生検

高本篤, 河田達志, 長尾賢太郎, 富永悠介, 渡部智文, 三宅修司, 林あずさ, 関戸崇了, 吉永香澄, 和田里章悟, 丸山雄樹, 定平卓也, 岩田健宏, 西村慎吾, 和田耕一郎, 枝村康平, 佐古智子, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

西日本泌尿器科 84 ( 増刊号1 ) 48 - 48 2022.1

岡山大学におけるUTUCに対するURSの成績と課題

和田耕一郎, 丸山雄樹, 荒木元朗, 関戸崇了, 枝村康平, 定平卓也, 林あずさ, 三宅修司, 渡部智文, 吉永香澄, 和田里章悟, 長尾賢太郎, 河田達志, 富永悠介, 大岩裕子, 岩田健宏, 西村慎吾, 高本篤, 佐古智子, 小林泰之, 石井亜矢乃, 渡部昌実, 渡辺豊彦, 那須保友

西日本泌尿器科 84 ( 増刊号1 ) 48 - 49 2022.1

上部尿路上皮癌に対する尿路内視鏡的治療の成績と課題

和田耕一郎, 小川貢平, 坪井一朗, 吉岡彩織, 横山周平, 小林祐介, 中島宏親, 永見太一, 山崎清玄, 小池千明, 椎名浩昭, 荒木元朗, 枝村康平, 岩田健宏, 那須保友

西日本泌尿器科 84 ( 増刊号1 ) 89 - 89 2022.1

待機日数56日で先行的脳死下献腎移植を行った17歳女性の1例

奥村美紗, 吉永香澄, 西村慎吾, 和田耕一郎, 荒木元朗, 渡部智文, 近藤崇弘, 関戸崇了, 堀井聡, 竹丸紘史, 和田里章悟, 丸山雄樹, 山野井友昭, 長尾賢太郎, 河田達志, 富永悠介, 定平卓也, 岩田健宏, 高本篤, 佐古智子, 枝村康平, 小林泰之, 石井亜矢乃, 渡部昌実, 渡辺豊彦, 那須保友

西日本泌尿器科 84 ( 増刊号1 ) 50 - 51 2022.1

全身転移を来たした成人発症の胎児型前立腺横紋筋肉腫の1例

近藤崇弘, 関戸崇了, 定平卓也, 富永悠介, 高本篤, 奥村美紗, 渡部智文, 堀井聡, 竹丸絋史, 和田里章悟, 吉永香澄, 丸山雄樹, 山野井友昭, 長尾賢太郎, 河田達志, 岩田健宏, 西村慎吾, 佐古智子, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 石井亜矢乃, 渡部昌実, 渡邉豊彦, 那須保友, 田端雅弘, 柳井広之

西日本泌尿器科 84 ( 増刊号1 ) 53 - 53 2022.1

岡山大学におけるUTUCに対するURSの成績と課題

和田耕一郎, 丸山雄樹, 荒木元朗, 関戸崇了, 枝村康平, 定平卓也, 林あずさ, 三宅修司, 渡部智文, 吉永香澄, 和田里章悟, 長尾賢太郎, 河田達志, 富永悠介, 大岩裕子, 岩田健宏, 西村慎吾, 高本篤, 佐古智子, 小林泰之, 石井亜矢乃, 渡部昌実, 渡辺豊彦, 那須保友

西日本泌尿器科 84 ( 増刊号1 ) 48 - 49 2022.1

待機日数56日で先行的脳死下献腎移植を行った17歳女性の1例

奥村美紗, 吉永香澄, 西村慎吾, 和田耕一郎, 荒木元朗, 渡部智文, 近藤崇弘, 関戸崇了, 堀井聡, 竹丸紘史, 和田里章悟, 丸山雄樹, 山野井友昭, 長尾賢太郎, 河田達志, 富永悠介, 定平卓也, 岩田健宏, 高本篤, 佐古智子, 枝村康平, 小林泰之, 石井亜矢乃, 渡部昌実, 渡辺豊彦, 那須保友

西日本泌尿器科 84 ( 増刊号1 ) 50 - 51 2022.1

全身転移を来たした成人発症の胎児型前立腺横紋筋肉腫の1例

近藤崇弘, 関戸崇了, 定平卓也, 富永悠介, 高本篤, 奥村美紗, 渡部智文, 堀井聡, 竹丸絋史, 和田里章悟, 吉永香澄, 丸山雄樹, 山野井友昭, 長尾賢太郎, 河田達志, 岩田健宏, 西村慎吾, 佐古智子, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 石井亜矢乃, 渡部昌実, 渡邉豊彦, 那須保友, 田端雅弘, 柳井広之

西日本泌尿器科 84 ( 増刊号1 ) 53 - 53 2022.1

後腹膜リンパ節郭清術後の射精障害の検討

富永悠介, 佐古智子, 奥村美紗, 渡部智文, 近藤崇弘, 関戸崇了, 竹丸紘史, 堀井聡, 吉永香澄, 丸山雄樹, 山野井友昭, 長尾賢太郎, 片山聡, 定平卓也, 岩田健宏, 西村慎吾, 高本篤, 枝村康平, 小林泰之, 荒木元朗, 石井亜矢乃, 渡部昌実, 渡邉豊彦, 那須保友, 松本裕子, 杉本盛人, 和田耕一郎

西日本泌尿器科 84 ( 増刊号1 ) 84 - 84 2022.1

岡山大学病院におけるBioJetシステムを用いたMRI/US融合下経会陰的前立腺生検

高本篤, 河田達志, 長尾賢太郎, 富永悠介, 渡部智文, 三宅修司, 林あずさ, 関戸崇了, 吉永香澄, 和田里章悟, 丸山雄樹, 定平卓也, 岩田健宏, 西村慎吾, 和田耕一郎, 枝村康平, 佐古智子, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

西日本泌尿器科 84 ( 増刊号1 ) 48 - 48 2022.1

p Identification of MICALL2 as a Novel Prognostic Biomarker Correlating with Inflammation and T Cell Exhaustion of Kidney Renal Clear Cell Carcinoma

Wenfeng Lin, Wenwei Chen, Jisheng Zhong, Hideo Ueki, Abai Xu, Masami Watanabe, Motoo Araki, Chunxiao Liu, Yasutomo Nasu, Peng Huang

JOURNAL OF CANCER 13 ( 3 ) 1214 - 1228 2022

Language：English Publishing type：Research paper (scientific journal) Publisher：IVYSPRING INT PUBL

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.

DOI： 10.7150/jca.66922

Presence of decoy cells for 6 months on urine cytology efficiently predicts BK virus nephropathy in renal transplant recipients International journal

Takanori Sekito, Motoo Araki, Kasumi Yoshinaga, Yuki Maruyama, Takuya Sadahira, Shingo Nishimura, Koichiro Wada, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Tanabe, Hidemi Takeuchi, Hiroshi Morinaga, Masashi Kitagawa, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Hiroyuki Yanai, Yasutomo Nasu

International Journal of Urology 28 ( 12 ) 1240 - 1246 2021.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

OBJECTIVES: To investigate the association between duration of consecutive presence of decoy cells on urine cytology and BK virus nephropathy after kidney transplantation. METHODS: In total, 121 kidney transplant recipients were retrospectively evaluated. The best duration of consecutive presence of decoy cells that could be used to predict BK virus nephropathy was analyzed using the area under the curve for each duration, and recipients were divided into two groups based on the best predictive performance. The effectiveness of SV40 immunostaining on urinary cytology was also analyzed. RESULTS: In total, 2534 urine specimens as well as SV40 immunostaining in 2241 urine specimens were analyzed. Six consecutive months of decoy cell positivity had the best predictive performance for BK virus nephropathy (area under the curve = 0.832). The incidence of BK virus nephropathy in recipients with positive decoy cells for 6 months or more consecutive months (5/44) was significantly higher than in those who had positive decoy cells for less than 6 months (0/77; P = 0.005). Decoy cell positivity had a sensitivity, specificity, positive predictive value, and negative predictive value for BK virus nephropathy of 100%, 66%, 11%, and 100% respectively. SV40 immunostaining provided slightly better specificity (68%) and positive predictive value (12%). CONCLUSIONS: The detection of decoy cells at 6 months or more on urine cytology had high predictive value for BK virus nephropathy in kidney transplant recipients. SV40 immunostaining on urine cytology added minimal diagnostic accuracy.

DOI： 10.1111/iju.14679

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/iju.14679

Clinical Efficacy and Safety of Sitafloxacin 200 mg Once Daily for Refractory Genitourinary Tract Infections.

Takehiro Iwata, Takuya Sadahira, Yuki Maruyama, Takanori Sekito, Kasumi Yoshinaga, Shogo Watari, Kentaro Nagao, Tatsushi Kawada, Yusuke Tominaga, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Motoo Araki, Ayano Ishii, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu, Koichiro Wada

Acta medica Okayama 75 ( 6 ) 763 - 766 2021.12

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.18926/AMO/62820

APCCC JAPAN:今こそ日本人泌尿器科医の常識を問う! M0CRPC診療 M0CRPCに対する新規ホルモン剤はどのような症例に有効か?

枝村康平, 河田達志, 定平卓也, 岩田健宏, 西村慎吾, 高本篤, 佐古智子, 小林泰之, 荒木元朗, 石井亜矢乃, 渡部昌実, 渡邉豊彦, 那須保友

日本泌尿器科学会総会 109回 SY31 - 3 2021.12

反復性膀胱炎に対する乳酸菌腟坐剤の予防効果を評価する第II相試験

定平卓也, 和田耕一郎, 石井亜矢乃, 丸山雄樹, 岩田健宏, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器科学会総会 109回 AOP09 - 02 2021.12

腎移植における悪性腫瘍とその治療法:自己腎癌、前立腺癌、PTLDなども含めて腎移植後の前立腺癌・尿路上皮癌

荒木元朗, 吉永香澄, 丸山雄樹, 定平卓也, 山野井友昭, 西村慎吾, 佐古智子, 枝村康平, 小林泰之, 渡辺豊彦, 那須保友

日本泌尿器科学会総会 109回 SY4 - 3 2021.12

Glasgow prognostic scoreは非セミノーマの胚細胞腫瘍患者において治療前にOS・PFSを予測できる

吉永香澄, 定平卓也, 関戸崇了, 和田里章悟, 丸山雄樹, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器科学会総会 109回 OP65 - 04 2021.12

浸潤性膀胱癌に対する開腹膀胱全摘除術(ORC)と比較した腹腔鏡下膀胱全摘除術(LRC)の長期治療成績に関する後方視的検討

和田里章悟, 小林泰之, 河田達志, 定平卓也, 片山聡, 岩田健宏, 西村慎吾, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

西日本泌尿器科 84 ( 2 ) 146 - 153 2021.12

Language：Japanese Publisher：(一社)西日本泌尿器科学会

【目的】腹腔鏡下膀胱全摘除術(LRC)と開腹膀胱全摘除術(ORC)の長期制癌性を検討した本邦からの報告は少数である。当院におけるLRCとORCの周術期成績と長期治療成績を後方視的に比較検討した。【対象】2012年5月から2018年6月までに施行した膀胱全摘症例のうち78例(LRC48例,ORC30例)とした。【結果】観察期間中央値はLRC群30ヵ月,ORC群43.5ヵ月であった。LRC群で男性が多く,回腸導管の割合が高かった。手術時間はLRC群で長く(p=0.038),推定出血量と輸血症例が少なかった(ともにp<0.001)。術後病理結果はLRC群でG2症例が少なかった(p=0.008)が,断端陽性率を含む他の結果に差はなかった。リンパ節郭清領域はORCで内外腸骨動脈分岐部以下,LRCで総腸骨動脈分岐部以下を基本としたが,郭清リンパ節の数とリンパ節陽性症例の割合に差はなかった。LRC群とORC群の5年全生存率,癌特異生存率,無再発生存率は72.2%と54.4%(p=0.249),77.7%と63.4%(p=0.376),71.4%と55.0%(p=0.115)であった。【結語】当院におけるLRC群の周術期成績は出血量,輸血頻度においてORC群より優れていた。制癌性についてもORC群に比しLRC群が優れている傾向を認め,リンパ節郭清領域が制癌性に影響する報告を裏付ける結果となった。(著者抄録)

リアルタイムイメージングを用いた腎虚血再灌流後生体マウス腎における好中球動態のタダラフィル投与による変化

丸山雄樹, 荒木元朗, 城所研吾, 十川裕史, 吉永香澄, 光井洋介, 定平卓也, 和田耕一郎, 渡部昌実, 渡邉豊彦, 柏原直樹, 那須保友

日本泌尿器科学会総会 109回 AOP13 - 06 2021.12

腸骨下腹神経ブロックが鼠径部痛の緩和に有効であった、再発性鼠径ヘルニアを合併したミュラー管遺残症候群の1例

関戸崇了, 丸山雄樹, 定平卓也, 岩田健宏, 西村慎吾, 佐古智子, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 渡部昌実, 渡辺豊彦, 那須保友

日本泌尿器科学会総会 109回 OP05 - 06 2021.12

Testosterone Recovery after Neoadjuvant Gonadotropin-Releasing Hormone Antagonist versus Agonist on Permanent Iodine-125 Seed Brachytherapy in Prostate Cancer Patients: A Propensity Score Analysis.

Takehiro Iwata, Yuki Maruyama, Tatsushi Kawada, Takuya Sadahira, Satoshi Katayama, Atsushi Takamoto, Tomoko Sako, Koichiro Wada, Kohei Edamura, Yasuyuki Kobayashi, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Acta medica Okayama 75 ( 6 ) 705 - 711 2021.12

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.18926/AMO/62810

TVT手術19年後に発症したテープ感染の一例

渡部智文, 富永悠介, 岩田健宏, 西村慎吾, 高本篤, 佐古智子, 枝村康平, 和田耕一郎, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器科学会総会 109回 PP16 - 07 2021.12

限局性上部尿路上皮癌診断における、tumor grade、tumor stageによる予測モデルの臨床的有用性の検討

片山聡, 荒木元朗, 森啓一郎, 岩田健宏, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 小林泰之, 渡部昌実, 渡邉豊彦, Shariat Shahrokh F., 那須保友

日本泌尿器科学会総会 109回 OP19 - 01 2021.12

尿路変向術:私の工夫 RARC ICUD失敗から学んだこと

小林泰之, 岩田健宏, 西村慎吾, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 荒木元朗, 渡邉豊彦, 那須保友

西日本泌尿器科 84 ( 2 ) 122 - 127 2021.12

Language：Japanese Publisher：(一社)西日本泌尿器科学会

ロボット支援膀胱全摘除術(以下:RARC)は,本邦において2019年4月に保険適応され,導入する施設も右肩上がりに増えている。当院においても,腹腔鏡下膀胱全摘除,RARC,体腔外尿路変向(以下:ECUD)を経て2019年6月より体腔内尿路変向(以下:ICUD)を開始した。ICUDは腸管という非常に長い対象物を鏡視下の拡大視野にて扱うため,全容が見えていない状態で手術を行うこととなる。その為に初期症例においては,誰も陥りやすいpit fallがあると考えている。この度,我々が経験した失敗とその対策を提示することで,同様のトラブルが回避できれば幸いと考えている。(著者抄録)

Tumor suppressor REIC/Dkk-3 and its co-chaperone SGTA: Two aspects of a GR inhibitor and AR activator as a modifier of the steroid signaling(和訳中)

岩田健宏, 定平卓也, 片山聡, 枝村康平, 小林泰之, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

西日本泌尿器科学会総会抄録集 73回 175 - 175 2021.11

癌抑制因子REIC/Dkk-3とそのコシャペロンSGTA ステロイドシグナル伝達の調節因子としてのGR阻害剤とAR活性化剤の二つの側面(Tumor suppressor REIC/Dkk-3 and its co-chaperone SGTA: Two aspects of a GR inhibitor and AR activator as a modifier of the steroid signaling)

岩田健宏, 定平卓也, 片山聡, 枝村康平, 小林泰之, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

西日本泌尿器科学会総会抄録集 73回 175 - 175 2021.11

鏡視下手術後の深部静脈血栓症早期発見を目的としたD-dimer測定の有用性

丸山雄樹, 岩田健宏, 吉永香澄, 高本篤, 佐古智子, 枝村康平, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 35回 AP - 6 2021.11

腎移植後リンパ嚢腫の腹腔鏡下開窓術における蛍光尿管カテーテルと軟性尿管鏡の有用性

関戸崇了, 荒木元朗, 和田耕一郎, 吉永香澄, 西村慎吾, 枝村康平, 佐古智子, 小林泰之, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 35回 V - 4 2021.11

ロボット時代の若手への腹腔鏡教育を考える腎副腎メンターの立場から

小林泰之, 富永悠介, 長尾賢太郎, 山野井友昭, 西村慎吾, 岩田健宏, 枝村康平, 荒木元朗, 渡辺豊彦, 那須保友

日本泌尿器内視鏡学会総会 35回 PD - 1 2021.11

腎癌におけるそもそもとまっとう T1a腎癌:別の「まっとう」があるはず腎凍結療法の適応を考える

山野井友昭, 小林泰之, 西村慎吾, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 荒木元朗, 渡邉豊彦, 那須保友, 平木隆夫

西日本泌尿器科学会総会抄録集 73回 126 - 126 2021.11

cT1b腎腫瘍におけるロボット支援腎部分切除術(RAPN)の周術期・中長期成績の検討

山野井友昭, 西村慎吾, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 35回 P - 10 2021.11

腎盂尿管鏡検査における生検組織診断率向上のためのPilot study

岩田健宏, 和田耕一郎, 長尾賢太郎, 富永悠介, 片山聡, 枝村康平, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 35回 P - 9 2021.11

左単腎不完全重複腎盂尿管の合流部狭窄に対するロボット支援下腎盂形成術

小林泰之, 枝村康平, 和田耕一郎, 佐古智子, 西村慎吾, 岩田健宏, 荒木元朗, 渡辺豊彦, 那須保友

日本泌尿器内視鏡学会総会 35回 AV - 2 2021.11

当科で施行した腹腔鏡下仙骨腟固定術とロボット支援下仙骨腟固定術の比較

佐古智子, 岩田健宏, 西村慎吾, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 石井亜矢乃, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 35回 P - 1 2021.11

ロボット支援膀胱全摘除術(RARC)における体腔内・体腔外尿路変更の検討

長尾賢太郎, 岩田健宏, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 35回 P - 1 2021.11

Impact of paclitaxel, cisplatin, and gemcitabine as first-line chemotherapy in cisplatin-fit and -unfit patients with advanced/metastatic urothelial carcinoma. International journal

Satoshi Katayama, Yasuyuki Kobayashi, Atsushi Takamoto, Kohei Edamura, Takuya Sadahira, Takehiro Iwata, Shingo Nishimura, Tomoko Sako, Koichiro Wada, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Urologic oncology 39 ( 10 ) 731.e25-731.e32 2021.10

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: This study aimed to clarify the efficacy and toxicity of first-line combination treatment with paclitaxel, cisplatin, and gemcitabine (PCG) for advanced/metastatic urothelial carcinoma (UC) in cisplatin-unfit patients compared with cisplatin-fit patients. METHODS: We conducted a retrospective study of patients who received first-line PCG. Using international consensus criteria, patients were classified into cisplatin-fit and -unfit groups. Cisplatin-unfit patients received PCG with adjustment of the cisplatin dose after assessing 24-hour urinary creatinine clearance, without modifying the administration interval. RESULTS: From 2008 to 2017, 50 patients received first-line PCG, of whom 30 and 20 were classified into the cisplatin-fit and -unfit groups. After a median follow-up of 15.0 months, the median overall survival (OS) and progression-free survival (PFS) were 15.0 and 9.8 months in all patients, 15.0 and 10.0 months in the cisplatin-fit group, and 13.2 and 9.3 months in the cisplatin-unfit group, respectively. There was no significant difference in OS (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 0.69-2.54) or PFS (HR: 1.38, 95% CI: 0.74-2.55) between the groups. The overall response rate and complete response rate were 58% (95% CI: 43.2-71.8) and 32% (95% CI: 19.5-46.7) in all patients, and 55% (95% CI: 31.5-76.9) and 35% (95% CI: 15.4-59.2) in the cisplatin-unfit group, respectively. The common grade 3 of 4 adverse events experienced were neutropenia (78%), followed by thrombocytopenia (56%), anemia (46%), and febrile neutropenia (16%). The 24-hour urinary creatinine clearance did not differ significantly between the groups after one, two, or three courses of PCG. CONCLUSIONS: We found no significant difference regarding OS and PFS between the cisplatin-fit patients with a full dose of cisplatin and -unfit patients with cisplatin-dose-adjusted chemotherapy. In select cisplatin-unfit patients, PCG with dose adjustment of cisplatin may be useful for treating advanced/metastatic UC without any significant adverse events or impaired renal function compared with cisplatin-fit patients with a full dose of cisplatin.

DOI： 10.1016/j.urolonc.2021.02.029

Impact of Sarcopenia on Erectile Function after Nerve-Sparing Robot-Assisted Radical Prostatectomy. International journal

Yosuke Mitsui, Takuya Sadahira, Yuki Maruyama, Ryota Sato, Acosta Gonzalez Herik Rodrigo, Koichiro Wada, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

The world journal of men's health 39 ( 4 ) 673 - 682 2021.10

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To determine the impact of sarcopenia on erectile functional outcomes after a nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) using patient-reported validated questionnaires. MATERIALS AND METHODS: In this retrospective study, RARP was performed on 841 patients at Okayama University Hospital, of which 132 underwent NS RARP. Erectile functional outcomes were assessed using the 5-item version of the International Index of Erectile Function (IIEF-5) and the Expanded Prostate Cancer Index Composite before and 1, 3, 6, and 12 months after surgery. Automated measurement of skeletal muscle at L3 was achieved using volume analyzer software and normalizing for height (cm²/m²) to calculate skeletal muscle index (SMI). Patients who had an IIEF-5≤4 comprised the group with erectile dysfunction (ED), and those with an IIEF-5≤5 made up the non-ED group. RESULTS: This study enrolled 95 patients of median age 65 years with a preoperative IIEF-5 of 16. There were no significant differences between patients with and without sarcopenia among those with preoperative IIEF-5. Postoperatively, in the ED group, SMI and preoperative IIEF-5 were significantly lower than in the non-ED group. Multiple linear regression analysis revealed that (1) both SMI and preoperative IIEF-5 were independent predictors of ED, and (2) sarcopenia and preoperative IIEF-5 were predictors of ED at 12 months after NS RARP. CONCLUSIONS: Patients with sarcopenia can have worse erectile functional outcomes after NS RARP. Sarcopenia and a lower preoperative IIEF-5 score may be predictive of postoperative ED.

DOI： 10.5534/wjmh.200036

Blood concentrations of tacrolimus upon conversion from rabeprazole to vonoprazan in renal transplant recipients: Correlation with cytochrome P450 gene polymorphisms. International journal

Shogo Watari, Motoo Araki, Jun Matsumoto, Kasumi Yoshinaga, Takanori Sekito, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Koichiro Wada, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Shinji Kitamura, Hitoshi Sugiyama, Noritaka Ariyoshi, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Drug metabolism and pharmacokinetics 40 100407 - 100407 2021.10

Language：English Publishing type：Research paper (scientific journal)

We evaluated the impact of vonoprazan on blood concentrations of tacrolimus via a retrospective analysis of 52 renal transplant recipients who took tacrolimus and converted from rabeprazole to vonoprazan between August 2018 and September 2019. We compared tacrolimus trough levels upon conversion among groups that were classified based on cytochrome P450 (CYP) gene polymorphisms. CYP3A5 groups were heterozygous or homozygous for CYP3A5∗1 and CYP3A5∗3 alleles. CYP2C19 genotypes were classified as extensive (∗1/∗1), intermediate (∗1/∗2 and ∗1/∗3) or poor metabolizers (∗2/∗2, ∗2/∗3 and ∗3/∗3). Tacrolimus trough levels increased only 0.3 ng/mL upon conversion in the CYP3A5∗3/∗3 group: 5.8 [3.4-7.2] vs 6.1 [3.8-7.9]; p = 0.06. No statistically significance changes in tacrolimus levels also occurred in the CYP3A5∗1/∗1 or CYP3A5∗1/∗3 groups. Subgroup analyses of CYP3A5∗3/∗3 demonstrated low changes for all three CYP2C19 subgroups: 5.2 [4.3-6.5] vs 6.2 [4.3-7.9]; p = 0.07, 6.1 [3.4-7.2] vs 6.7 [4.6-7.9]; p = 0.12 and 5.4 [3.6-6.5] vs 4.7 [3.8-6.3]; p = 1.00, respectively. Conversion to vonoprazan thus resulted in little increase of tacrolimus trough levels, even in the group predicted to be most susceptible (CYP3A5∗3/∗3 and 2C19∗1/∗1), thus supporting the safety of concomitant use of vonoprazan with tacrolimus.

DOI： 10.1016/j.dmpk.2021.100407

A Clinical Trial Evaluating the Usefulness of Tailored Antimicrobial Prophylaxis Using Rectal-culture Screening Media Prior to Transrectal Prostate Biopsy: A Multicenter, Randomized Controlled Trial.

Takuya Sadahira, Yuki Maruyama, Yoshiki Hiyama, Hiroyuki Kitano, Hiroki Yamada, Takayuki Goto, Tsubasa Kondo, Katsumi Shigemura, Yosuke Mitsui, Takehiro Iwata, Kohei Edamura, Motoo Araki, Masami Watanabe, Tadasu Takenaka, Jun Teishima, Yasuyoshi Miyata, Kiyohito Ishikawa, Ei-Ichiro Takaoka, Jun Miyazaki, Satoshi Takahashi, Naoya Masumori, Hiroshi Kiyota, Masato Fujisawa, Shingo Yamamoto, Takafumi Sakuma, Norihiro Kusumi, Takaharu Ichikawa, Toyohiko Watanabe, Yoshitsugu Nasu, Masaya Tsugawa, Yasutomo Nasu, Koichiro Wada

Acta medica Okayama 75 ( 5 ) 663 - 667 2021.10

Language：English Publishing type：Research paper (scientific journal)

The aim of this report is to introduce an on-going, multicenter, randomized controlled trial to evaluate whether tailored antimicrobial prophylaxis guided by rectal culture screening prevents acute bacterial prostatitis following transrectal prostate biopsy (TRPB). Patients will be randomized into an intervention or non-intervention group; tazobactam-piperacillin or levofloxacin will be prophylactically administered according to the results of rectal culture prior to TRPB in the intervention group whereas levofloxacin will be routinely given in the non-intervention group. The primary endpoint is the occurrence rate of acute bacterial prostatitis after TRPB. Recruitment begins in April, 2021 and the target total sample size is 5,100 participants.

DOI： 10.18926/AMO/62782

Intraluminal diamond-like carbon coating with anti-adhesion and anti-biofilm effects for uropathogens: A novel technology applicable to urinary catheters. International journal

Shogo Watari, Koichiro Wada, Motoo Araki, Takuya Sadahira, Daiki Ousaka, Susumu Oozawa, Tatsuyuki Nakatani, Yuichi Imai, Junichi Kato, Reiko Kariyama, Toyohiko Watanabe, Yasutomo Nasu

International journal of urology : official journal of the Japanese Urological Association 28 ( 12 ) 1282 - 1289 2021.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To examine anti-adhesion and anti-biofilm effects of a diamond-like carbon coating deposited via a novel technique on the inner surface of a thin silicon tube. METHODS: Diamond-like carbon coatings were deposited into the lumen of a silicon tube with inner diameters of 2 mm. The surface of the diamond-like carbon was evaluated using physicochemical methods. We used three clinical isolates including green fluorescent protein-expressing Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. We employed a continuous flow system for evaluation of both bacterial adhesion and biofilm formation. Bacterial adhesion assays consisted of counting the number of colony-forming units and visualization of adhered bacterial cells by scanning electron microscope to evaluate the diamond-like carbon-coated/uncoated samples. The biofilm structure was analyzed by confocal laser scanning microscopy on days 3, 5, 7 and 14 for green fluorescent protein-expressing Pseudomonas aeruginosa. RESULTS: The smooth and carbon-rich structure of the intraluminal diamond-like carbon film remained unchanged after the experiments. The numbers of colony-forming units suggested lower adherence of green fluorescent protein-expressing Pseudomonas aeruginosa and Escherichia coli in the diamond-like carbon-coated samples compared with the uncoated samples. The scanning electron microscope images showed adhered green fluorescent protein-expressing Pseudomonas aeruginosa cells without formation of microcolonies on the diamond-like carbon-coated samples. Finally, biofilm formation on the diamond-like carbon-coated samples was lower until at least day 14 compared with the uncoated samples. CONCLUSIONS: Intraluminal diamond-like carbon coating on a silicone tube has anti-adhesion and anti-biofilm effects. This technology can be applied to urinary catheters made from various materials.

DOI： 10.1111/iju.14675

Comparison of inflammation-based prognostic scores as predictors of survival outcomes in patients with germ cell tumors

Yoshinaga K, Sadahira T, Maruyama Y, Mitsui Y, Iwata T, Wada K, Araki M, Watanabe T, Nasu Y

Investing Cline Urol 62 ( 1 ) 47 - 55 2021.9

ABO血液型不適合生体腎移植後の細菌感染症が急性抗体関連拒絶反応に与える影響についての検討

西村慎吾, 荒木元朗, 和田耕一郎, 関戸崇了, 吉永香澄, 和田里章悟, 丸山雄樹, 山野井友昭, 山下里美, 佐古智子, 枝村康平, 小林泰之, 渡邉豊彦, 那須保友

移植 56 ( 総会臨時 ) O11 - 1 2021.9

【RARC ICUDを行う際のpit fall】RARCにおけるECUDとICUD(回腸導管)の比較検討

小林泰之, 枝村康平, 岩田健宏, 西村慎吾, 和田耕一郎, 荒木元朗, 渡辺豊彦, 那須保友

Japanese Journal of Endourology 34 ( 2 ) 182 - 185 2021.9

Language：Japanese Publisher：(一社)日本泌尿器内視鏡学会

岡山大学病院にて2018年1月より2020年9月までの期間に単一術者にて連続的に行われたロボット支援膀胱全摘(以下:RARC)46症例体腔外尿路変更(以下:ECUD)(23例),体腔内尿路変更(以下:ICUD)(23例)の比較検討を行った.検討項目は手術時間,推定出血量,輸血率,リンパ節郭清個数,入院日数,血液生化学データ,術後合併症とした.尿路変更に要した時間はICUD群の方が有意に長かったが,入院期間はICUD群が有意に短かった.他の周術期成績はECUDと同等であった.術者の視点では良好な拡大視野,尿管導管吻合の精緻性,同一視野で手術の流れが途切れることなく継続できることがICUDのメリットではないかと考える.(著者抄録)

【これから始めるロボット支援下仙骨腟固定術】ロボット支援下仙骨腟固定術の導入に向けて

佐古智子, 岩田健宏, 西村慎吾, 高本篤, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 石井亜矢乃, 渡邉豊彦, 那須保友

Japanese Journal of Endourology 34 ( 2 ) 221 - 225 2021.9

Language：Japanese Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会

骨盤臓器脱に対する治療として,2010年に経腟メッシュ手術が,2014年に腹腔鏡下仙骨腟固定術が保険収載され,泌尿器科医が骨盤臓器脱に対する治療を行うことも一般的になってきている.2020年4月の診療報酬改定により,新たにロボット支援腹腔鏡下仙骨腟固定術が保険収載された.腹腔鏡下仙骨腟固定術は,正確な剥離操作を要し,深部での縫合結紮操作を多用する手術であることなど,良性疾患に対する手術でありながら手技の難易度が比較的高い術式であると考えられる.これに対して手術支援ロボットを用いることで,手術の難易度が低減されること,手術成績が向上することが期待される.当院でも2020年8月よりロボット支援下仙骨腟固定術を導入した.ロボット支援下仙骨腟固定術のメリットやデメリット,導入の意義などについて,手術導入に向けた取り組みについて述べる.(著者抄録)

Nationwide surveillance of bacterial pathogens isolated from patients with acute uncomplicated cystitis in 2018: Conducted by the Japanese Research Group for Urinary Tract Infections (JRGU)

Wada K, Yokoyama T, Uno S, Araki M, Sadahira T, Maruyama Y, Acosta H, Nakajima H, Hiyama Y, Kunishima Y, Togo Y, Nukaya T, Yamada H, Shigemura K, Ito S, Tanimura M, Kobayashi K, Kitano H, Teishima J, Yasuda M, Uehara S, Hamasuna R, Watanabe T, Nakagawa T, Hayami H, Miyazaki J, Takahashi S, Masumori N, Ishikawa K, Kiyota H, Fujisawa M, Arakawa S, Nasu Y, Yamamoto S

J Infect Chemother 1169 ( 1180 ) 2021.8

The Cell Cycle Checkpoint Gene, RAD17 rs1045051, Is Associated with Prostate Cancer Risk.

Jingkai Sun, Wenfeng Lin, Qixu Wang, Akiko Sakai, Ruizhi Xue, Masami Watanabe, Chunxiao Liu, Takuya Sadahira, Yasutomo Nasu, Abai Xu, Peng Huang

Acta medica Okayama 75 ( 4 ) 415 - 421 2021.8

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.18926/AMO/62379

腎部分切除術を施行した巨大類上皮型腎血管筋脂肪腫の1例

横山周平, 富永悠介, 高本篤, 定平卓也, 関戸崇了, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 渡部昌実, 渡邉豊彦, 柳井広之, 那須保友

西日本泌尿器科 83 ( 3 ) 175 - 180 2021.8

Language：Japanese Publisher：(一社)西日本泌尿器科学会

症例は41歳,女性。2008年に結節性硬化症,両側腎血管筋脂肪腫およびIgA腎症と診断され,経過観察されていた。2015年に右腎血管筋脂肪腫より出血を認め緊急経カテーテル的動脈塞栓術を施行し,左腎血管筋脂肪腫に対しても待機的に経カテーテル的動脈塞栓術を施行した。2017年にCTで右腎尾側に新たに腫瘤を指摘され,2年の経過で12cmから20cm大に急速に増大したため2019年3月にCTガイド下針生検を実施し類上皮型腎血管筋脂肪腫と診断された。2019年5月に術前TAE後に開腹右腎部分切除術を施行した。2019年9月よりエベロリムスを開始したが,腎機能障害とHbA1cの上昇を認めたため中止した。その後,術後12ヵ月まで再発および転移を認めず経過している。(著者抄録)

ハイリスク腎移植 game changers DSA陽性ハイリスク腎移植

西村慎吾, 荒木元朗, 関戸崇了, 坪井一朗, 吉永香澄, 和田里章悟, 丸山雄樹, 光井洋介, 窪田理沙, 定平卓也, 岩田健宏, 高本篤, 佐古智子, 枝村康平, 和田耕一郎, 小林泰之, 渡邉豊彦, 那須保友

西日本泌尿器科 83 ( 3 ) 152 - 160 2021.8

Language：Japanese Publisher：(一社)西日本泌尿器科学会

腎移植は末期腎不全に対する腎代替療法として理想的な治療である。生体で約94%,献腎で約88%という高い5年生着率が得られており,抗ドナー抗体(Donor-Specific Antibody:DSA)陽性のハイリスク症例に対する移植も積極的に行われつつある。2019年12月にDSA陽性腎移植における術前脱感作として免疫グロブリン大量静注療法(Intravenous Immunoglobulins:IVIG)が保険適応となった。IVIGは海外ではその有効性について多くの報告があり,日本でもGame changerとなりうる。今回,当科でDSA陽性に対し術前IVIGを行った2例を含めその有用性について文献的に検討する。症例1は69歳,3次移植の男性。原疾患不明の腎不全に対し,外国にて献腎移植を施行するも,術中に超急性拒絶反応を認め即座に移植腎を摘出,2つ目の腎が移植された。移植後約12年で当科に紹介受診。移植後約20年でgraft lossに至り,妻をドナーとしたA型(Rh+)→AB型(Rh+)の血液型不一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-DQ強陽性であった(nMFI=23,230)。TAC,PSLに加え術前6週前より中止していたMMFを再開し,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。症例2は71歳,女性。IgA腎症を原疾患とする腎不全に対して,HD導入前に当科受診。妊娠・出産歴3回,夫をドナーとしたAB型(Rh+)→AB型(Rh+)の血液型一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-C,DR,DQ陽性であった(nMFI=〜5,000)。術前脱感作はTAC,MMF,PSL,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。2症例とも術後現在まで一度も拒絶反応を起こすことなく良好な腎機能で経過している。(著者抄録)

去勢抵抗性前立腺癌 game changers mCRPC治療におけるPARP阻害剤、IOの役割

枝村康平, 那須保友

西日本泌尿器科 83 ( 3 ) 132 - 137 2021.8

Language：Japanese Publisher：(一社)西日本泌尿器科学会

近年,去勢抵抗性前立腺癌(castration-resistant prostate cancer:CRPC)に対する治療の選択肢は増えてきているが,分子標的薬の一種であるPoly ADP-ribose polymerase(PARP)阻害剤や免疫治療剤(Immuno-oncology drug:IO剤)もその有用性が報告され始めている。PARP阻害剤は,本邦でも2020年12月にBRCA遺伝子変異陽性の遠隔転移を有する去勢抵抗性前立腺癌に対するオラパリブの使用が承認された。これはPROfound試験の結果に基づくもので,BRCA1/2またはATM遺伝子変異陽性のmCRPC症例に対して,オラパリブ群とエンザルタミドまたはアビラテロン群を比較した結果,無増悪生存期間の有意な延長が確認されたものである。IO剤に関する試験も多数行われており,抗PD-1抗体であるペムブロリズマブは,がん化学療法後に増悪した進行・再発の高頻度マイクロサテライト不安定性(MSI-high)を有する固形癌への適応が承認された。さらに米国では腫瘍変異量の多い(TMB-h)進行固形癌に対する適応が追加承認された。遺伝子レベルで患者個別の特性に合わせた加療を行うプレシジョンメディシンとしてのPARP阻害剤やIO剤は今後のmCRPC治療において重要な役割を担うと考えられる。(著者抄録)

腎部分切除術を施行した巨大類上皮型腎血管筋脂肪腫の1例

横山周平, 富永悠介, 高本篤, 定平卓也, 関戸崇了, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 渡部昌実, 渡邉豊彦, 柳井広之, 那須保友

西日本泌尿器科 83 ( 3 ) 175 - 180 2021.8

Language：Japanese Publisher：(一社)西日本泌尿器科学会

症例は41歳,女性。2008年に結節性硬化症,両側腎血管筋脂肪腫およびIgA腎症と診断され,経過観察されていた。2015年に右腎血管筋脂肪腫より出血を認め緊急経カテーテル的動脈塞栓術を施行し,左腎血管筋脂肪腫に対しても待機的に経カテーテル的動脈塞栓術を施行した。2017年にCTで右腎尾側に新たに腫瘤を指摘され,2年の経過で12cmから20cm大に急速に増大したため2019年3月にCTガイド下針生検を実施し類上皮型腎血管筋脂肪腫と診断された。2019年5月に術前TAE後に開腹右腎部分切除術を施行した。2019年9月よりエベロリムスを開始したが,腎機能障害とHbA1cの上昇を認めたため中止した。その後,術後12ヵ月まで再発および転移を認めず経過している。(著者抄録)

ハイリスク腎移植 game changers DSA陽性ハイリスク腎移植

西村慎吾, 荒木元朗, 関戸崇了, 坪井一朗, 吉永香澄, 和田里章悟, 丸山雄樹, 光井洋介, 窪田理沙, 定平卓也, 岩田健宏, 高本篤, 佐古智子, 枝村康平, 和田耕一郎, 小林泰之, 渡邉豊彦, 那須保友

西日本泌尿器科 83 ( 3 ) 152 - 160 2021.8

Language：Japanese Publisher：(一社)西日本泌尿器科学会

腎移植は末期腎不全に対する腎代替療法として理想的な治療である。生体で約94%,献腎で約88%という高い5年生着率が得られており,抗ドナー抗体(Donor-Specific Antibody:DSA)陽性のハイリスク症例に対する移植も積極的に行われつつある。2019年12月にDSA陽性腎移植における術前脱感作として免疫グロブリン大量静注療法(Intravenous Immunoglobulins:IVIG)が保険適応となった。IVIGは海外ではその有効性について多くの報告があり,日本でもGame changerとなりうる。今回,当科でDSA陽性に対し術前IVIGを行った2例を含めその有用性について文献的に検討する。症例1は69歳,3次移植の男性。原疾患不明の腎不全に対し,外国にて献腎移植を施行するも,術中に超急性拒絶反応を認め即座に移植腎を摘出,2つ目の腎が移植された。移植後約12年で当科に紹介受診。移植後約20年でgraft lossに至り,妻をドナーとしたA型(Rh+)→AB型(Rh+)の血液型不一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-DQ強陽性であった(nMFI=23,230)。TAC,PSLに加え術前6週前より中止していたMMFを再開し,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。症例2は71歳,女性。IgA腎症を原疾患とする腎不全に対して,HD導入前に当科受診。妊娠・出産歴3回,夫をドナーとしたAB型(Rh+)→AB型(Rh+)の血液型一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-C,DR,DQ陽性であった(nMFI=〜5,000)。術前脱感作はTAC,MMF,PSL,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。2症例とも術後現在まで一度も拒絶反応を起こすことなく良好な腎機能で経過している。(著者抄録)

Successful deceased donor kidney transplantation to a recipient with a history of COVID-19 treatment. International journal

Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Kou Hasegawa, Takanori Sekito, Shuji Miyake, Shogo Watari, Yuki Maruyama, Takuya Sadahira, Shingo Nishimura, Katsuyuki Tanabe, Hidemi Takeuchi, Yuri Nakashima, Masaru Kinomura, Herik Acosta, Yosuke Mitsui, Risa Kubota, Hirochika Nakajima, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Fumio Otsuka, Jun Wada, Yasutomo Nasu

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 7 ) 1097 - 1101 2021.7

Language：English Publishing type：Research paper (scientific journal)

CASE PRESENTATION: A 49-year-old Asian male, who had undergone hemodialysis for >16 years, complained of a fever, dysgeusia and dysosmia, and was diagnosed with COVID-19 pneumonia based on severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (SARS-CoV-2 PCR) and computed tomography (CT). Treatment was started with oral favipiravir and ciclesonide inhalation. On the 10th day of treatment, the patient had a persistent high fever and a chest CT showed exacerbation of pneumonia, so dexamethasone was intravenously started. He was discharged after confirming two consecutive negative SARS-CoV-2 PCR tests. Three months after COVID-19 treatment, a SARS-CoV-2 PCR test was negative and he underwent a deceased donor kidney transplantation. Basiliximab induction with triple drug immunosuppression consisting of extended-release tacrolimus, mycophenolate mofetil and prednisolone, which is our regular immunosuppression protocol, was used. He was discharged on postoperative day 18 without the need for postoperative hemodialysis or any complications. The serum creatinine level was 1.72 mg/dL 95 days postoperatively and he had a favorable clinical course that was similar to deceased donor kidney recipients without a history of SARS-CoV-2 infection. CONCLUSION: We report the first case of a kidney transplantation after COVID-19 treatment in Japan and the fourth case globally. We would like to provide information about our successful case due to the anticipated increase in similar candidates in the near future.

DOI： 10.1016/j.jiac.2021.03.018

A Cace of Metastatic Fumarate Hydratase-Deficient-like Renal Cell Carcinoma Successfully Managed by Ipilimumab plus Nivolumab (Ipi/Nivo)

Sekito T, Takamoto A, Kobayashi Y, Mitsui M, Watari S, Kubota R, Sadahira T, Iwata T, Nishimura S, Edamura K, Sako T, Araki M, Watanabe M, Watanabe T, Shibata R, Ennishi D, Nasu Y

Acta Med. Okayama 75 ( 3 ) 397 - 402 2021.6

A second opinion pathology review improves the diagnostic concordance between prostate cancer biopsy and radical prostatectomy specimens

Maehara T, Sadahira T, Maruyama Y, Wada K, Araki M, Watanabe M, Watanabe T, Yanai H, Nasu Y

UROLOGY ANNALS 13 ( 2 ) 119 - 124 2021.6

ABO Blood Incompatibility Positively Affects Early Graft Function: Single-Center Retrospective Cohort Study. International journal

Shogo Watari, Motoo Araki, Koichiro Wada, Kasumi Yoshinaga, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Transplantation proceedings 53 ( 5 ) 1494 - 1500 2021.6

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.transproceed.2021.03.043

"Intracorporeal versus extracorporeal urinary diversion in robot‑assisted radical cystectomy: a systematic review and meta‑analysis"

Katayama S, Mori K, Pradere B, Mostafaei H, Schuettfort VM, Quhal F, Motlagh RS, Laukhtina E, Moschini M, Grossmann NC, Nasu Y, Shariat SF, Fajkovic H

Int J Clin Oncol 26 ( 9 ) 1587 - 1599 2021.6

抗TFE3抗体による免疫染色陽性所見からXp11.2転座型腎癌と考えられた3例

井上陽介, 関戸崇了, 定平卓也, 高本篤, 杉本盛人, 和田耕一郎, 荒木元郎, 那須保友

西日本泌尿器科 83 ( 1 ) 10 - 10 2021.6

腎門部に発生した粘液嚢胞腺癌の1例

三宅修司, 岩田健宏, 長尾賢太郎, 河田達志, 富永悠介, 定平卓也, 西村慎吾, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 渡部昌実, 渡邉豊彦, 久保寿夫, 柳井広之, 那須保友

西日本泌尿器科 83 ( 1 ) 14 - 14 2021.6

若年発症の前立腺炎症性偽腫瘍の1例

佐久間貴文, 丸山雄樹, 定平卓也, 高本篤, 和田耕一郎, 小林泰之, 荒木元朗, 渡部昌実, 渡辺豊彦, 那須保友

西日本泌尿器科 83 ( 1 ) 11 - 11 2021.6

遺伝性平滑筋腫症-腎細胞癌症候群関連腎細胞癌の術後骨転移に対してイピリムマブ・ニボルマブ併用療法が有効であった1例

渡部智文, 榮枝一磨, 津川昌也, 関戸崇了, 富永悠介, 高本篤, 定平卓也, 小林泰之, 荒木元朗, 渡邉豊彦, 小田和歌子, 黒田直人, 十川麗美, 山本英喜, 平沢晃, 那須保友

西日本泌尿器科 83 ( 1 ) 9 - 9 2021.6

Efficacy of holmium laser enucleation in patients with a small (less than 30 mL) prostate volume. International journal

Ichiro Tsuboi, Yuki Maruyama, Takuya Sadahira, Nobuyoshi Ando, Yasuhiro Nishiyama, Motoo Araki, Takushi Kurashige, Takaharu Ichikawa, Ryoji Arata, Noriaki Ono, Toyohiko Watanabe, Syunji Hayata, Hiroaki Shiina, Yasutomo Nasu

Investigative and clinical urology 62 ( 3 ) 298 - 304 2021.5

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To evaluate the efficacy of holmium laser enucleation of the prostate (HoLEP) in patients with a small prostate volume (≤30 mL). MATERIALS AND METHODS: We retrospectively evaluated 1,135 patients who underwent HoLEP at two institutions between July 2007 and March 2020. Patients who were not evaluated for the International Prostate Symptom Score (IPSS) before or after HoLEP were excluded. We divided patients into two groups according to estimated prostate volume (ePV): ≤30 (n=198) and >30 mL (n=539). The patient characteristics, IPSS, peak urinary flow rate (Qmax), postvoid residual urine volume (PVR), and other data were compared before and after surgery in each group and between the two groups. Multivariate analysis was performed to identify the factors associated with the efficacy of HoLEP in the group with ePV ≤30 mL. RESULTS: A total of 737 patients were included in this retrospective study. ePV (23.4 mL vs. 50 mL; p<0.001) and PVR differed significantly between the two groups. The IPSS, IPSS-quality of life, PVR, and Qmax significantly improved after HoLEP in both groups. Improvements in the IPSS, IPSS-quality of life, Qmax, and PVR were greater in the >30 mL group (p<0.001), whereas operation time and morcellation time were significantly shorter in the ≤30 mL group. In the multivariate analysis, age <70 years was independently associated with improvement by HoLEP. CONCLUSIONS: HoLEP is an effective treatment for patients with a small prostate, even though the extent of improvement after HoLEP was greater in those with a larger prostate.

DOI： 10.4111/icu.20200450

Relevance of CYP3A5 Expression on the Clinical Outcome of Patients With Renal Cell Carcinoma. International journal

Jun Matsumoto, Yumi Kotera, Shogo Watari, Koichi Takeuchi, Hideo Ueki, Toshihiro Koyama, Koichiro Wada, Masachika Fujiyoshi, Yasutomo Nasu, Noritaka Ariyoshi

Anticancer research 41 ( 5 ) 2511 - 2521 2021.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/AIM: This study aimed to elucidate the detailed characteristics of CYP3A5 expression and the association between CYP3A5 expression and clinical outcomes in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: This study retrospectively enrolled 124 Japanese patients with RCC treated at the Okayama University Hospital. The commonest CYP3A5 gene polymorphism, CYP3A5*3, and expression levels of CYP3A5 mRNA and protein in each tissue were examined. RESULTS: Expression of CYP3A5 mRNA and protein in RCC tissues was significantly down-regulated compared to that in adjacent normal tissues. High level of CYP3A5 mRNA expression significantly extended cancer-specific survival (p=0.004) and overall survival (p=0.002). The CYP3A5 mRNA expression level was identified as a significant independent prognostic factor for both cancer-specific survival and overall survival. CONCLUSION: CYP3A5 could serve as a potential marker for prognostication and treatment planning for patients with RCC.

DOI： 10.21873/anticanres.15029

Evaluation of Neutrophil Dynamics Change by Protective Effect of Tadalafil After Renal Ischemia/Reperfusion Using In Vivo Real-time Imaging. International journal

Yuki Maruyama, Motoo Araki, Kengo Kidokoro, Yuji Sogawa, Kasumi Yoshinaga, Yosuke Mitsui, Takuya Sadahira, Koichiro Wada, Masami Watanabe, Toyohiko Watanabe, Naoki Kashihara, Yasutomo Nasu

Transplantation 106 ( 2 ) 280 - 288 2021.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Neutrophils play a major role in ischemia/reperfusion injury (IRI) in renal transplantation and acute kidney injury. However, it has been difficult to observe changes in neutrophil dynamics over time in living mice kidney. We investigate neutrophil dynamics in IRI in living mice using novel in vivo multiphoton microscope imaging techniques and characterize the renoprotective effects of a selective phosphodiesterase (PDE) 5 inhibitor, tadalafil. METHODS: Wild-type (WT) and eNOS knockout (eNOS-KO) mice, a model of endothelial dysfunction, were used to establish in vivo real-time imaging in living mouse kidneys. Neutrophils were labeled green with Ly-6G monoclonal antibody, and plasma flow was labeled red with bovine serum albumin. Tadalafil was administered orally 1 h before surgery. Both kidney pedicles were reperfused after 37° warm ischemia for 45 min. RESULTS: Our novel approach revealed that neutrophils were trapped in glomerulus within a few minutes after reperfusion. They gradually increased over time and Infiltrated neutrophils were observed in the tubular lumen and peritubular capillary. The neutrophils were clearly visualized rolling on peritubular capillary plexus at 3 μm/min. The administration of tadalafil significantly reduced neutrophil influx into the glomerulus in both WT and eNOS-KO mice. Reduced neutrophil infiltration in tadalafil groups, which was confirmed by flow cytometry, resulted in histopathologically decreased tubular injury. The expression of VCAM-1 and KIM-1 was partially prevented by tadalafil. CONCLUSIONS: Use of a novel technique contributed to elucidation of neutrophil dynamics after reperfusion. Tadalafil has a potential for inhibiting neutrophil infiltration in renal IRI.Supplemental Visual Abstract; http://links.lww.com/TP/C223.

DOI： 10.1097/TP.0000000000003803

Robot-assisted partial nephrectomy versus standard laparoscopic partial nephrectomy for renal hilar tumor: A prospective multi-institutional study. International journal

Nobuyuki Hinata, Ryoichi Shiroki, Kazunari Tanabe, Masatoshi Eto, Atsushi Takenaka, Mutsushi Kawakita, Isao Hara, Fumiya Hongo, Naokazu Ibuki, Yasutomo Nasu, Jun Teishima, Noriyasu Kawai, Akihiro Kawauchi, Tsunenori Kondo, Naoki Kawamorita, Chikara Oyama, Shigeo Horie, Masaki Shimbo, Masashi Kato, Hiroomi Kanayama, Yuya Koito, Masato Fujisawa

International journal of urology : official journal of the Japanese Urological Association 28 ( 4 ) 382 - 389 2021.4

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To investigate whether robot-assisted partial nephrectomy compared with laparoscopic partial nephrectomy is effective for renal hilar tumor removal. METHODS: This was a prospective, multicenter, single-arm, open-label trial with a 2-year enrollment period. A total of 22 academic hospitals in Japan participated in the present study. Comparison with historical control values from reported studies of laparoscopic partial nephrectomy was carried out. The warm ischemia time and positive surgical margin rate were set as primary perioperative and oncological outcomes. In the historical control group, these were 27.7 min and 13%, respectively. RESULTS: The analysis population included 105 participants. The mean warm ischemia time was 20.2 (95% confidence interval 16.7-21.8; P < 0.0001 vs 27.7). Two of 103 participants (1.9%) had a positive surgical margin (95% confidence interval 0.5-6.8%). Both results satisfy the prespecified decision criteria for the superiority of robot-assisted partial nephrectomy over the historical control of laparoscopic partial nephrectomy. Resected weight and preoperative estimated glomerular filtration rate were predictive factors of functional loss of the partially nephrectomized kidney after robot-assisted partial nephrectomy. CONCLUSION: Robot-assisted partial nephrectomy for clinical T1 renal hilar tumors results in shorter warm ischemia time than and comparable positive surgical margin rate to those reported for laparoscopic partial nephrectomy.

DOI： 10.1111/iju.14469

Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment. International journal

Wenfeng Lin, Chaoming Li, Naijin Xu, Masami Watanabe, Ruizhi Xue, Abai Xu, Motoo Araki, Ruifen Sun, Chunxiao Liu, Yasutomo Nasu, Peng Huang

International journal of nanomedicine 16 2775 - 2787 2021.4

Language：English Publishing type：Research paper (scientific journal)

Purpose: With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men's health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment. Methods: By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation. Results: With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9±1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96±1.88)% compared with (0.99±0.10)% in PBS group, revealing the enhanced immune response against PCa. Conclusion: The dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy.

DOI： 10.2147/IJN.S301552

若年発症の前立腺炎症性偽腫瘍の1例

佐久間貴文, 丸山雄樹, 定平卓也, 高本篤, 和田耕一郎, 小林泰之, 荒木元朗, 渡部昌実, 渡辺豊彦, 那須保友

西日本泌尿器科 83 ( 1 ) 54 - 58 2021.4

Language：Japanese Publisher：(一社)西日本泌尿器科学会

症例は19歳,男性。抗菌薬投与で改善しない排尿障害,排尿時痛を主訴に前医を受診。MRIで前立腺のT1強調像,T2強調像ともに低信号で,造影効果を伴う膀胱内に突出する腫瘤を指摘され当院紹介となった。血液,尿検査では特記事項なく,尿培養,尿細胞診は陰性であった。PSAを含め腫瘍マーカーの有意な上昇を認めなかった。膀胱鏡検査では前立腺部尿道に約35mmの非乳頭状広基性腫瘍を認めた。造影CTでは前立腺部にMRI同様の所見を認め,リンパ節腫大及び遠隔転移は認めなかった。排尿障害改善及び組織検査目的に経尿道的前立腺切除術(TUR-P)を施行した。切除組織は長紡錘形細胞の束状の増殖とリンパ球,形質細胞浸潤を認め,免疫染色でALK(anaplastic lymphoma kinase)陽性,α-smooth muscle actinが少数の細胞で陽性であり,前立腺炎症性偽腫瘍(inflammatory pseudtumor:IPT)と診断した。局所再発の可能性はあるものの,遠隔転移の可能性は低く,排尿状態の改善を得られたため経過観察の方針とした。術後10ヵ月現在で腫瘍の再燃を認めていない。(著者抄録)

遺伝性平滑筋腫症-腎細胞癌症候群関連腎細胞癌の術後骨転移に対してイピリムマブ・ニボルマブ併用療法が有効であった1例

渡部智文, 榮枝一磨, 津川昌也, 関戸崇了, 富永悠介, 高本篤, 定平卓也, 小林泰之, 荒木元朗, 渡邉豊彦, 小田和歌子, 黒田直人, 十川麗美, 山本英喜, 平沢晃, 那須保友

西日本泌尿器科 83 ( 1 ) 31 - 36 2021.4

Language：Japanese Publisher：(一社)西日本泌尿器科学会

症例は45歳,男性。X-1年9月に肉眼的血尿と右腰痛を主訴に当院を受診し,単純CTで右腎上極に長径5cm大の腫瘤を認めた。腹部造影CTでは動脈相で早期濃染,後期相でwashout patternを伴う内部不整な腫瘤を同部位に認めたが,明らかなリンパ節・他臓器転移を認めなかった。右腎癌cT1bN0M0 Stage Iと診断し,同年10月に腹腔鏡下右腎摘除術を施行した。病理所見は,腫瘍細胞は淡明細胞や好酸性細胞が乳頭状・管状の構造を取り,細胞質に好酸性の核小体および核周囲明庭を認めた。Fumarate hydratase(FH)免疫染色陰性でFH欠損腎細胞癌と診断した。術後2ヵ月で多発骨転移を認め,International Metastatic RCC Database Consortium(IMDC) intermediate riskと判断し,イピリムマブ・ニボルマブ併用療法を開始した。4コース施行後,CT上新規の転移巣や転移巣の増大を認めなかった。遺伝学的検査でFH遺伝子の病的バリアントを認め,腎細胞癌の家族歴と合わせ,遺伝性平滑筋腫症-腎細胞癌症候群(hereditary leiomyomatosis and renal cell carcinoma syndrome;HLRCC)関連腎細胞癌と診断した。現在ニボルマブ単剤投与を継続中で,骨転移増悪や新規遠隔転移は認めていない。(著者抄録)

抗TFE3抗体による免疫染色陽性所見からXp11.2転座型腎癌と考えられた3例

井上陽介, 関戸崇了, 定平卓也, 高本篤, 杉本盛人, 和田耕一郎, 荒木元郎, 那須保友

西日本泌尿器科 83 ( 1 ) 42 - 47 2021.4

Language：Japanese Publisher：(一社)西日本泌尿器科学会

1例目は27歳,女性。CTで8cm大の左腎腫瘍を認め,左腎癌cT2aN0M0と診断し,腹腔鏡下左腎摘除術を施行した。病理所見でTFE3免疫染色陽性で,Xp11.2転座型腎癌と考えられた。術後24ヵ月で傍大動脈リンパ節転移をきたし,sunitinib,axitinib投与後,現在nivolumabを投与中である。2例目は32歳,女性。CTで2cm大の緩徐に造影される左腎腫瘍を認めた。腹腔鏡下左腎部分切除術を施行し,病理所見でTFE3免疫染色陽性,Xp11.2転座型腎細胞癌と考えられた。術後50ヵ月で,再発転移を認めていない。3例目は31歳,女性。CTで右嚢胞性腎腫瘍と転移性肝腫瘍を指摘された。PET-CTで肝臓,骨,子宮に多発転移を認め,肝転移巣を生検し,未分化の尿路上皮癌と診断された。Gemcitabine+Cisplatin+Paclitaxelによる抗癌化学療法を2コース施行後,転移巣の増大,新たな転移巣(頭蓋骨,乳腺)の出現を認めた。新規転移巣を摘出し,病理所見でTFE3免疫染色陽性,最終的にXp11.2転座型腎細胞癌と考えられた。Temsirolimus投与するも,病状悪化し,第221病日に死亡した。Xp11.2転座型腎癌は若年者に多いとされる。確定診断には遺伝子検査またはFISHが求められるが,今回の3症例では施行していない。TFE3免疫染色はXp11.2転座型腎癌が疑われる際に有用である。(著者抄録)

Photodynamic diagnostic ureteroscopy using the VISERA ELITE video system for diagnosis of upper-urinary tract urothelial carcinoma: a prospective cohort pilot study. International journal

Koichiro Wada, Motoo Araki, Ryuta Tanimoto, Takuya Sadahira, Shogo Watari, Yuki Maruyama, Yosuke Mitsui, Hirochika Nakajima, Herik Acosta, Satoshi Katayama, Takehiro Iwata, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

BMC urology 21 ( 1 ) 45 - 45 2021.3

Language：English Publishing type：Research paper (scientific journal)

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).

DOI： 10.1186/s12894-021-00819-2

RAPNの周術期合併症の予防と対策

小林泰之, 荒木元朗, 枝村康平, 渡辺豊彦, 那須保友

泌尿器科 13 ( 3 ) 323 - 325 2021.3

神経線維腫症1型に合併した後腹膜悪性末梢神経鞘腫瘍の1例

宗田大二郎, 岩田健宏, 定平卓也, 富永悠介, 片山聡, 西村慎吾, 高本篤, 佐古智子, 枝村康平, 小林泰之, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友, 中田英二, 柳井広之

西日本泌尿器科 82 ( 6 ) 596 - 600 2021.2

Language：Japanese Publisher：(一社)西日本泌尿器科学会

症例は30代,女性。過去に左腋窩皮膚生検で神経線維腫と診断され,特徴的な皮膚所見や家族歴などから神経線維腫症1型(NF-1;von Recklinghausen病)を疑われていたが放置していた。20XX年2月に右大腿部痛,背部痛を主訴に近医を受診しMRI,造影CTで約13cm大の後腹膜腫瘤を指摘され,L2神経根からの発生と脊柱管内の浸潤も疑われ,神経線維腫の疑いとして手術目的に当科紹介された。合同での手術が必要と考えられたため,整形外科に紹介しMRIガイド下生検で悪性末梢神経鞘腫瘍の可能性を示唆された。同年6月に腫瘍の動脈塞栓術施行後に右後腹膜腫瘍摘出術を施行し,病理結果から悪性末梢神経鞘腫瘍と診断された。術後10ヵ月現在再発認めず,外来通院中である。後腹膜原発腫瘍において悪性末梢神経鞘腫瘍は極めて稀な症例であり,有効な治療法は確立されていない。今回,後腹膜原発の悪性末梢神経鞘腫瘍の1例を経験したので,若干の文献的考察を加えて報告する。(著者抄録)

岡山大学病院における去勢抵抗性前立腺癌に対するドセタキセルの長期治療成績

河田達志, 高本篤, 横山周平, 宗田大二郎, 坪井一馬, 長尾賢太郎, 富永悠介, 岩田健宏, 西村慎吾, 佐古智子, 枝村康平, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

西日本泌尿器科 82 ( 6 ) 605 - 605 2021.2

The role of Wnt signaling in male reproductive physiology and pathology. Reviewed International journal

Ruizhi Xue, Wenfeng Lin, Jingkai Sun, Masami Watanabe, Abai Xu, Motoo Araki, Yasutomo Nasu, Zhengyan Tang, Peng Huang

Molecular human reproduction 27 ( 1 ) 2021.1

Language：English Publishing type：Research paper (scientific journal)

Accumulating evidence has shown that Wnt signaling is deeply involved in male reproductive physiology, and malfunction of the signal path can cause pathological changes in genital organs and sperm cells. These abnormalities are diverse in manifestation and have been constantly found in the knockout models of Wnt studies. Nevertheless, most of the research solely focused on a certain factor in the Wnt pathway, and there are few reports on the overall relation between Wnt signals and male reproductive physiology. In our review, Wnt findings relating to the reproductive system were sought and summarized in terms of Wnt ligands, Wnt receptors, Wnt intracellular signals and Wnt regulators. By sorting out and integrating relevant functions, as well as underlining the controversies among different reports, our review aims to offer an overview of Wnt signaling in male reproductive physiology and pathology for further mechanistic studies.

DOI： 10.1093/molehr/gaaa085

The role of Wnt signaling in male reproductive physiology and pathology. International journal

Ruizhi Xue, Wenfeng Lin, Jingkai Sun, Masami Watanabe, Abai Xu, Motto Akira, Yasutomo Nasu, Zhengyan Tang, Peng Huang

Molecular human reproduction 2021.1

Language：English Publishing type：Research paper (scientific journal)

Accumulating evidence has shown that Wnt signaling is deeply involved in male reproductive physiology, and malfunction of the signal path can cause pathological changes in genital organs and sperm cells. These abnormalities are diverse in manifestation and have been constantly found in the knockout models of Wnt studies. Nevertheless, most of the research solely focused on a certain factor in the Wnt pathway, and there are few reports on the overall relation between Wnt signals and male reproductive physiology. In our review, Wnt findings relating to the reproductive system were sought and summarized in terms of Wnt ligands, Wnt receptors, Wnt intracellular signals and Wnt regulators. By sorting out and integrating relevant functions, as well as underlining the controversies among different reports, our review aims to offer an overview of Wnt signaling in male reproductive physiology and pathology for further mechanistic studies.

DOI： 10.1093/molehr/gaaa085

Long-term ureteroscopic management of upper tract urothelial carcinoma: 28-year single-centre experience. International journal

Yuki Maruyama, Motoo Araki, Koichiro Wada, Kasumi Yoshinaga, Yosuke Mitsui, Takuya Sadahira, Shingo Nishimura, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Manoj Monga, Yasutomo Nasu, Hiromi Kumon

Japanese journal of clinical oncology 51 ( 1 ) 130 - 137 2021.1

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1093/jjco/hyaa132

Comparison of inflammation-based prognostic scores as predictors of survival outcomes in patients with germ cell tumors. International journal

Kasumi Yoshinaga, Takuya Sadahira, Yuki Maruyama, Yosuke Mitsui, Takehiro Iwata, Koichiro Wada, Motoo Araki, Toyohiko Watanabe, Yasutomo Nasu

Investigative and clinical urology 62 ( 1 ) 47 - 55 2021.1

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The aim of this study was to compare the prognostic value of pretreatment inflammation-based scoring systems in terms of overall survival (OS) and progression-free survival (PFS) in patients with germ cell tumors (GCTs) receiving bleomycin, etoposide, and cisplatin (BEP) chemotherapy. MATERIALS AND METHODS: We evaluated 63 patients with GCTs retrospectively. The Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio, prognostic index, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index, and albumin-to-globulin ratio (AGR) were measured in all patients before chemotherapy. To assess the predictive ability of each scoring system, areas under the receiver operating characteristic curve were calculated, and multivariate analysis was performed to identify associations between the predictive scores and OS. RESULTS: Of all the inflammation-based scoring systems, the GPS had the greatest area under the curve (0.847) for predicting OS, followed by the PNI (0.829) and AGR (0.810). Kaplan-Meier analyses revealed that the GPS, PNI, and AGR were significantly associated with OS, whereas the GPS, PLR, and PNI were significantly associated with PFS. In the multivariate analysis, the GPS was an independent predictor of OS and PFS. CONCLUSIONS: We demonstrated that the GPS was the most valuable biomarker of OS and PFS in patients with GCTs.

DOI： 10.4111/icu.20200103

The role of Wnt signaling in male reproductive physiology and pathology

Xue R, Lin W, Sun J, Watanabe M, Xu A, Araki M, Nasu Y, Tang Z, Huang P

molecular human reproduction 27 ( 1 ) 2021

Feasible kidney donation with living marginal donors, including diabetes mellitus. International journal

Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Takanori Sekito, Shogo Watari, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Kohei Edamura, Yasuyuki Kobayashi, Katsuyuki Tanabe, Hidemi Takeuchi, Masashi Kitagawa, Shinji Kitamura, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Immunity, inflammation and disease 9 ( 3 ) 1061 - 1068 2021

Language：English Publishing type：Research paper (scientific journal)

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/m2 , (d) 24-h creatinine clearance ≥70 to <80 ml/min/1.73 m2 , 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.

DOI： 10.1002/iid3.470

Prognostic value of the systemic immune‑infammation index in non‑muscle invasive bladder cance

Katayama S, Mori K, Pradere B, Laukhtina E, SchuettfortQuhal F, Motlagh RS, Mostafaei H, Grossmann NC, Rajwa P, Moschini M, Mathieu R, Abufaraj M, D'Andrea D, Comperat E, Haydter M, Egawa S, Nasu Y, Shariat SF

World Journal of Urology 2021

Discovery and Validation of Nitroxoline as a Novel STAT3 Inhibitor in Drug-resistant Urothelial Bladder Cancer. International journal

Wenfeng Lin, Jingkai Sun, Takuya Sadahira, Naijin Xu, Koichiro Wada, Chunxiao Liu, Motoo Araki, Abai Xu, Masami Watanabe, Yasutomo Nasu, Peng Huang

International journal of biological sciences 17 ( 12 ) 3255 - 3267 2021

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.7150/ijbs.63125

Efficacy of Lactobacillus vaginal suppositories for the prevention of recurrent cystitis: A phase II clinical trial

Sadahira T, Wada K, Araki M, Mitsuhata R, Yamamoto M, Maruyama Y, Iwata T, Watanabe M, Watanabe T, Kariyama R, Nasu Y, Ishii A

INTERNATIONAL JOURNAL OF UROLOGY 2021

Comparison of intracorporeal versus extracorporeal urinary diversion after robot-assisted radical cystectomy at a medium-sized facility

Iwata T, Kobayashi Y, Maruyama Y, Kawad T, Sadahira T, Oiwa Y, Katayama S, Nishimura S, Takamoto A, SakoT, Wada K, Edamura K, Araki M, Watanabe M, Watanabe T, Nasu Y

Int J Clin Oncol 2021

Management of Groin Pain Using an Iliohypogastric Nerve Block in a Patient with Inguinal Hernia due to Persistent Müllerian Duct Syndrome. International journal

Takanori Sekito, Takuya Sadahira, Masahiro Sugihara, Kohei Edamura, Motoo Araki, Yasutomo Nasu

Case reports in urology 2021 7577632 - 7577632 2021

Language：English

Persistent Müllerian duct syndrome can cause an inguinal hernia, although this is a rare occurrence; recurrent inguinal hernias can, in turn, cause ongoing groin pain. Management of groin pain plays an important role in patients' quality of life. We present our experience with a 43-year-old man who had a 2-week history of left-sided groin pain. The patient underwent laparoscopic surgery for a left inguinal hernia via the transabdominal preperitoneal approach. Right-sided cryptorchidism was noted during surgery, with a solid structure-thought to be a uterus-extending into the left inguinal canal. The diagnosis was persistent Müllerian duct syndrome, and the groin pain was relieved after a laparoscopic right orchiectomy with a bilateral preperitoneal hernia repair using a mesh. Four years later, magnetic resonance imaging performed for new-onset left groin pain showed a left inguinal hernia caused by the uterine structure. We diagnosed the recurrent hernia as the cause of his pain. Prior to performing any invasive surgical procedures, an iliohypogastric nerve block was performed using 1% lidocaine. Short-term analgesia was provided by the block, improving his quality of life. He has been followed since then and has declined surgical neurectomy. An iliohypogastric nerve block can be an effective method of controlling groin pain caused by an inguinal hernia resulting from persistent Müllerian duct syndrome; the effectiveness of the nerve block will help determine whether surgical neurectomy is indicated for permanent pain control.

DOI： 10.1155/2021/7577632

【地方の腎移植の継続と継承-組織・指導医の取り組みと今後の展望-】岡山大学における腎移植継承の取り組み

荒木元朗, 西村慎吾, 吉永香澄, 丸山雄樹, 山野井友昭, 定平卓也, 富永悠介, 岩田健宏, 片山聡, 佐古智子, 枝村康平, 小林泰之, 那須保友

腎移植・血管外科 33 ( 2 ) 67 - 71 2021

【地方の腎移植の継続と継承-組織・指導医の取り組みと今後の展望-】岡山大学における腎移植継承の取り組み

荒木元朗, 西村慎吾, 吉永香澄, 丸山雄樹, 山野井友昭, 定平卓也, 富永悠介, 岩田健宏, 片山聡, 佐古智子, 枝村康平, 小林泰之, 那須保友

腎移植・血管外科 33 ( 2 ) 67 - 71 2021

Language：Japanese Publisher：腎移植・血管外科研究会

1.岡山大学の腎移植の背景・歴史岡山大学泌尿器科は2009年に新しい腎移植プログラムを立ち上げ総計144例となった.成績も1年生存・生着率100%を維持している.2.人材確保医局員の確保から始まる.3.育成腎移植は幅広いテクニックが要求される.血管縫合糸は若手医師でも縫いやすく結紮もし易いGore-tex sutureを用いている.いい雰囲気でやることを心がけている.4.腎臓内科との連携術前術後連携を取るため腎移植カンファレンスを月一回行い情報共有している.5.教室内での他の領域の医師との関係腎移植チームのメンバーも腫瘍の手術やロボット手術を担当することによって腎移植のみに偏らない配慮をしている.6.働き方改革移植前後の管理の簡略化に努めている.(著者抄録)

Surgical treatment for a periurethral diverticulum with dysuria: A case reports

Satoko Matsuo, Ryuta Tanimoto, Morito Sugimoto, Tomoyasu Tsushima, Aya Nakamura, Takuya Sadahira, Shogo Watari, Yasuyuki Kobayashi, Motoo Araki, Toyohiko Watanabe, Yasutomo Nasu

Nishinihon Journal of Urology 82 ( 5 ) 514 - 517 2020.12

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The West Japan Urological Association

A 46-year-old woman visited a urological clinic with the chief complaint of urinary frequency and dysuria. She had been examined with regular follow-up MRI following excision of a uterine fibroid, which had revealed a cystic lesion around the urethra. Her symptoms did not improve under medical treatment, so she was then referred to our hospital for further treatment. Abdominal ultrasound revealed no post-void residual urine but a cystic lesion around the urethra. Internal examination indicated an elastic soft mass below the anterior vaginal wall. Communication between the cystic lesion and the urethra was observed with cystourethroscopy when the cystic lesion was punctured in a transvaginal way and injected with indigo carmine. Her symptoms improved for a while, however, nine months later, the cystitis symptoms recurred, and MRI showed an enlarged cystic lesion. Transvaginal urethral diverticulectomy was then performed. The communication of diverticulum with the urethra was closed, and the mucosal lining within the diverticulum was removed as much as possible. The periurethral fascia and vaginal wall were closed, respectively. The patient had no perioperative complications and no recurrent urinary symptoms.

腎門部腫瘍に対するロボット支援腎部分切除術の有効性を評価する多施設共同臨床試験

日向信之, 白木良一, 田邉一成, 江藤正俊, 武中篤, 川喜田睦司, 原勲, 本郷文弥, 伊夫貴直和, 那須保友, 松原昭郎, 河合憲康, 河内明宏, 近藤恒徳, 川守田直樹, 大山力, 堀江重郎, 新保正貴, 後藤百万, 金山博臣, 小糸悠也, 藤澤正人, ROBOHIT Study Group

日本泌尿器科学会総会 108回 1760 - 1760 2020.12

UTUCに対するKidney-sparing surgeryの現状と課題岡山大学の手技と成績

和田耕一郎, 丸山雄樹, 荒木元朗, 小林泰之, 定平卓也, 高本篤, 佐古智子, 枝村康平, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 34回 SY - 1 2020.11

RALP術中にモノポーラーシザースのチップカバーが脱落し、発見が困難であった一例

長尾賢太郎, 宗田大二郎, 岩田健宏, 佐古智子, 枝村康平, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 34回 O - 2 2020.11

初心者向けの新術式一筆書きHoLEPの提案と教育効果について

富永悠介, 宗田大二郎, 坪井一馬, 岩田健宏, 佐古智子, 枝村康平, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 34回 O - 4 2020.11

岡山大学病院におけるBioJetシステムを用いたMRI/US融合下経会陰的前立腺生検の初期

高本篤, 河田達志, 小林泰之, 岩田健宏, 西村慎吾, 佐古智子, 枝村康平, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 34回 O - 1 2020.11

これから始めるロボット支援下仙骨腟固定術ロボット支援腹腔鏡下仙骨腟固定術の導入に向けて

佐古智子, 岩田健宏, 西村慎吾, 高本篤, 枝村康平, 小林泰之, 荒木元朗, 石井亜矢乃, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 34回 SY - 1 2020.11

腹腔鏡技術認定医実際の教育現場を紹介します! 岡山大学泌尿器科における腹腔鏡教育

小林泰之, 富永悠介, 枝村康平, 岩田健宏, 西村慎吾, 高本篤, 佐古智子, 荒木元朗, 渡辺豊彦, 那須保友

日本泌尿器内視鏡学会総会 34回 SY - 1 2020.11

当院におけるロボット支援腹腔鏡下腎部分切除術後再発症例の検討

河田達志, 坪井一馬, 西村慎吾, 高本篤, 佐古智子, 枝村康平, 小林泰之, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 34回 P - 2 2020.11

Combined Laparoscopic and CT Monitoring of the Ice-Ball Margin during Cryoablation for Renal Cell Carcinoma Associated with von Hippel-Lindau Disease: First Case.

Takanori Sekito, Motoo Araki, Takao Hiraki, Mayu Uka, Toshiyuki Komaki, Yusuke Matsui, Toshihiro Iguchi, Satoshi Katayama, Kasumi Yoshinaga, Shogo Watari, Yuki Maruyama, Yosuke Mitsui, Risa Kubota, Takuya Sadahira, Shingo Nishimura, Koichiro Wada, Atsushi Takamoto, Kohei Edamura, Tomoko Sako, Yasuyuki Kobayashi, Toyohiko Watanabe, Susumu Kanazawa, Yasutomo Nasu

Acta medica Okayama 74 ( 5 ) 443 - 448 2020.10

Language：English

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.

DOI： 10.18926/AMO/60806

Low-dose rituximab induction therapy is effective in immunological high-risk renal transplantation without increasing cytomegalovirus infection. International journal

Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Haruhito Adam Uchida, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

International journal of urology : official journal of the Japanese Urological Association 27 ( 12 ) 1136 - 1142 2020.10

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To analyze the effect and impact of low-dose rituximab induction therapy on cytomegalovirus infection in living-donor renal transplantation. METHODS: A total of 92 recipients undergoing living-donor renal transplantation at Okayama University Hospital from May 2009 to August 2018 were evaluated retrospectively. Indications for preoperative rituximab (200 mg/body) were the following: (i) ABO major mismatch; (ii) ABO minor mismatch; (iii) donor-specific anti-human leukocyte antigen antibody-positive; and (iv) focal segmental glomerulosclerosis. We excluded four recipients who were followed <3 months, five who received >200 mg/body rituximab and seven who received prophylactic therapy for cytomegalovirus. RESULTS: There were 59 patients in the rituximab group and 17 in the non-rituximab group. Groups differed significantly in age (median age 53 vs 37 years, respectively; P = 0.04), but not in sex (male 64% vs 65%, P = 1.00), focal segmental glomerulosclerosis (3% vs 0%, P = 1.00) or percentage of cytomegalovirus-seronegative recipients of renal allografts from cytomegalovirus-seropositive donors (12% vs 18%, P = 0.68). The estimated glomerular filtration rate did not differ significantly between groups until 24 months after transplantation. Cytomegalovirus clinical symptoms (10% vs 24%, P = 0.22), including fever ≥38°C (5% vs 12%, P = 0.31) and gastrointestinal symptoms (5% vs 12%, P = 0.31), and the 5-year survival rates of death-censored graft loss (90% vs 83%, P = 0.43) did not differ significantly between groups. CONCLUSIONS: Low-dose rituximab induction therapy is effective in immunological high-risk recipients without increasing cytomegalovirus infection in the absence of valganciclovir prophylaxis.

DOI： 10.1111/iju.14382

Aspects of Gene Therapy Products Using Current Genome-Editing Technology in Japan. International journal

Teruhide Yamaguchi, Eriko Uchida, Takashi Okada, Keiya Ozawa, Masafumi Onodera, Akihiro Kume, Takashi Shimada, Satoru Takahashi, Kenzaburo Tani, Yasutomo Nasu, Tomoji Mashimo, Hiroyuki Mizuguchi, Kohnosuke Mitani, Kazushige Maki

Human gene therapy 31 ( 19and20 ) 1043 - 1053 2020.10

Language：English Publishing type：Research paper (scientific journal)

The development of genome-editing technology could lead to breakthrough gene therapy. Genome editing has made it possible to easily knock out or modify a target gene, while current gene therapy using a virus vector or plasmid hampering modification with respect to gene replacement therapies. Clinical development using these genome-editing tools is progressing rapidly. However, it is also becoming clear that there is a possibility of unintended gene sequence modification or deletion, or the insertion of undesired genes, or the selection of cells with abnormalities in the cancer suppressor gene p53; these unwanted actions are not possible with current gene therapy. The Science Board of the Pharmaceuticals and Medical Devices Agency of Japan has compiled a report on the expected aspects of such genome-editing technology and the risks associated with it. This article summarizes the history of that discussion and compares the key concepts with information provided by other regulatory authorities.

DOI： 10.1089/hum.2020.156

Correlation between lumbar skeletal muscle size and urinary incontinence after radical prostatectomy. International journal

Yosuke Mitsui, Takuya Sadahira, Toyohiko Watanabe, Motoo Araki, Yuki Maruyama, Ryota Sato, Acosta Gonzalez Herik Rodrigo, Koichiro Wada, Masami Watanabe, Michael B Chancellor, Yasutomo Nasu

Lower urinary tract symptoms 12 ( 3 ) 245 - 252 2020.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Urinary incontinence is a major concern after radical prostatectomy because it can decrease quality of life. The aim of the present study was to explore the effect of preoperative skeletal muscle on urinary quality of life after robot-assisted radical prostatectomy. METHODS: A total of 762 patients underwent robot-assisted radical prostatectomy. Longitudinal health-related quality of life was evaluated using the Expanded Prostate Cancer Index Composite instrument. The skeletal muscle area at the level of the third lumbar vertebra was assessed preoperatively by computed tomography and was standardized to height to obtain the skeletal muscle index. Reduced skeletal muscle size (RSMS) was defined as a skeletal muscle index ≤ 53 or ≤ 43 cm2 /m2 in patients with a body mass index (BMI) ≥25 or < 25, respectively. RESULTS: A total of 301 patients were included in this study, of whom 91 were classified as having RSMS (30.2%). Non-RSMS patients exhibited better urinary function at 12 months (P = .012) and better urinary continence recovery at 2 weeks and 12 months (P = .033 and P = .014, respectively) after prostatectomy compared with RSMS patients. Univariate and multivariate analyses identified preoperative RSMS as a significant and independent predictor of urinary incontinence (odds ratio = 1.77, P = .028). CONCLUSIONS: Patients with RSMS had a lower urinary quality of life compared with non-RSMS patients after robot-assisted radical prostatectomy, and RSMS, independent of age or BMI, was predictive of postoperative urinary incontinence.

DOI： 10.1111/luts.12312

Tumor suppressor REIC/Dkk-3 and its interacting protein SGTA inhibit glucocorticoid receptor to nuclear transport

Iwata T, Sadahira T, Ochiai K, Ueki H, Sasaki T, Haung P, Araki M, Watanabe T, Nasu Y, Watanabe M

20 ( 2 ) 1739 - 1745 2020.8

性同一性障害における泌尿器科の役割

富永悠介, 佐古智子, 松本裕子, 杉本盛人, 那須保友

泌尿器科 12 ( 2 ) 191 - 196 2020.8

Nitroxoline inhibits bladder cancer progression by reversing EMT process and enhancing anti-tumor immunity. International journal

Naijin Xu, Wenfeng Lin, Jingkai Sun, Takuya Sadahira, Abai Xu, Masami Watanabe, Kai Guo, Motoo Araki, Gonghui Li, Chunxiao Liu, Yasutomo Nasu, Peng Huang

Journal of Cancer 11 ( 22 ) 6633 - 6641 2020.7

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.7150/jca.47025

Impact of sarcopenia on longitudinal erectile functional outcomes after nerve-sparing robot assisted radical prostatectomy

Mitsui Y, Sadahira T, Maruyama Y, Araki M, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

Eur Urol Open Sci 19 ( Suppl 2 ) e1112 2020.7

The second opinion pathology review improves concordance between prostate biopsy and radical prostatectomy specimens

Maruyama Y, Sadahira T, Araki M, Mitsui Y, Wada K, Edamura K, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

Eur Urol Open Sci 19 ( Suppl 2 ) e1556 2020.7

Preventive efficacy and safety of lactobacillus vaginal suppositories in women with recurrent cystitis: A phase 2 study

Sadahira T, Wada K, Ishii A, Maruyama Y, Iwata T, Araki M, Watanabe M, Watanabe T, Nasu Y

Eur Urol Open Sci 19 ( Suppl 2 ) e2036 2020.7

Mixed 20-peptide cancer vaccine in combination with docetaxel and dexamethasone for castration-resistant prostate cancer: a randomized phase II trial. International journal

Masanori Noguchi, Gaku Arai, Shin Egawa, Chikara Ohyama, Seiji Naito, Kazumasa Matsumoto, Hirotsugu Uemura, Masayuki Nakagawa, Yasutomo Nasu, Masatoshi Eto, Shigetaka Suekane, Tetsuro Sasada, Shigeki Shichijo, Akira Yamada, Tatsuyuki Kakuma, Kyogo Itoh

Cancer immunology, immunotherapy : CII 69 ( 5 ) 847 - 857 2020.5

Language：English Publishing type：Research paper (scientific journal)

A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase II trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances the antitumor effects in patients with castration-resistant prostate cancer (CRPC). In this double-blind, placebo-controlled, randomized phase II study, we enrolled chemotherapy-naïve patients with CRPC from ten medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to receive either KRM-20 combined with docetaxel and dexamethasone (n = 25) or placebo with docetaxel and dexamethasone (n = 26). The primary endpoint was the difference in prostate-specific antigen (PSA) decline between each treatment. The rates of > 50% PSA decline in the two arms were similar (56.5% versus 53.8%; P = 0.851). Human leukocyte antigen (HLA)-matched peptide-specific immunoglobulin G (P = 0.018) and CTL (P = 0.007) responses in the KRM-20 arm significantly increased after treatment. The addition of KRM-20 did not increase toxicity. There were no between-group differences in progression-free or overall survival (OS). The addition of KRM-20 was safe, and similar PSA decline and HLA-matched peptide-specific CTL and IgG responses increased in combination with docetaxel and dexamethasone in CRPC patients. Subgroup analysis suggested that this treatment is favorable for CRPC patients with ≥ 26% lymphocytes or PSA levels of < 11.2 ng/ml, but further clinical trials comparing OS are required.

DOI： 10.1007/s00262-020-02498-8

Clinical Practice Guidelines for Bladder Cancer 2019 edition by the Japanese Urological Association: Revision working position paper

Hiroaki Matsumoto, Koji Shiraishi, Haruhito Azuma, Keiji Inoue, Hirotsugu Uemura, Masatoshi Eto, Chikara Ohyama, Osamu Ogawa, Eiji Kikuchi, Hiroshi Kitamura, Nobuo Shinohara, Satoru Takahashi, Toyonori Tsuzuki, Masayuki Nakagawa, Yoshifumi Narumi, Hiroyuki Nishiyama, Tomonori Habuchi, Shiro Hinotsu, Yasuhisa Fujii, Kiyohide Fujimoto, Hiroyuki Fujimoto, Takashi Mizowaki, Hideyasu Matsuyama, Nobuyuki Sekita, Hiroshi Juri, Yuki Inada, Takashige Abe, Hideo Fukuhara, Yukio Naya, Satoshi Mutoh, Shigehisa Kitano, Takashi Kobayashi, Teruo Inamoto, Makito Miyake, Junichi Inokuchi, Tetsutaro Hayashi, Takahiro Kojima, Katsuyoshi Hashine, Toshiki Kijima, Yoshiyuki Matsui, Tomohiko Hara, Shingo Hatakeyama, Yoshiaki Yamamoto, Shintaro Narita, Tomoyasu Tsushima, Takafumi Miura, Takeru Shiroiwa, Mototsugu Oya, Momokazu Gotoh, Haruki Kume, Yasutomo Nasu, Katsuyuki Tsunemune

International Journal of Urology 27 ( 5 ) 362 - 368 2020.5

Clinical experience with pembrolizumab in the treatment of advanced urothelial cancer

Yusuke Tominaga, Atsushi Takamoto, Takanori Sekito, Syogo Watari, Yuko Oiwa, Risa Kubota, Satoshi Katayama, Takehiro Iwata, Shingo Nishimura, Tomoko Sako, Koichiro Wada, Kohei Edamura, Yasuyuki Kobayashi, Motoo Araki, Toyohiko Watanabe, Yasutomo Nasu

Nishinihon Journal of Urology 82 ( 1 ) 106 - 110 2020.4

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The West Japan Urological Association

[Introduction and objective) Pembrolizumab, a programmed death one checkpoint inhibitor, was approved as second-line treatment of advanced urothelial cancer (UC). We performed a pilot study to investigate the effect of pembrolizumab. [Methods and patients) 19 patients who were treated with pembrolizumab from April 2018 to July 2019 were retrospectively reviewed and analyzed to evaluate efficacy and safety. Pembrolizumab was administered after platinum-based chemotherapy. [Results) The median age was 68 years old
male-to-female ratio was 14:5
primary lesions were upper urinary tract, bladder and others (10, 7 and 2, respectively)
recurrence lesions were lymph nodes, lung, bone and liver (14, 9, 4 and 2, respectively). The median number of cycles was three courses (range, 1-16). The objective response rate, median progression-free survival period (PFS), and median overall survival period (OS) were 24%, 2.7 months and 9.1 months, respectively. Pembrolizumab showed a long-term effect for all responsive cases until the end of the follow-up period. Immune-related adverse events (irAE) were observed in four patients. Neutrophil-to-lymphocyte ratio was negatively correlated with PFS, but not significantly correlated with OS. [Conclusion) Pembrolizumab demonstrated a comparable efficacy and safety profile in the treatment of advanced UC. In particular, responsive cases showed a durable response. Further investigation is required to identify predictive markers that can be routinely used in clinical practice.

Factors predicting pathological upgrading after prostatectomy in patients with Gleason grade group 1 prostate cancer based on opinion-matched biopsy specimens. Reviewed International journal

Yuki Maruyama, Takuya Sadahira, Motoo Araki, Yosuke Mitsui, Koichiro Wada, Acosta Gonzalez Herik Rodrigo, Kazuaki Munetomo, Yasuyuki Kobayashi, Masami Watanabe, Hiroyuki Yanai, Toyohiko Watanabe, Yasutomo Nasu

Molecular and clinical oncology 12 ( 4 ) 384 - 389 2020.4

Language：English Publishing type：Research paper (scientific journal)

The present study investigated the concordance between Gleason scores assigned to prostate biopsy specimens by outside pathologists and a urological pathology expert, and determined the risk of upgrading between opinion-matched Gleason grade group (GGG) 1 biopsy specimens and radical prostatectomy specimens. Between January 2012 and May 2018, 733 patients underwent robot-assisted radical prostatectomy. Patients whose original biopsy specimens from outside hospitals were reviewed by a urological pathology expert Okayama University Hospital were included. Patients who had received neoadjuvant hormonal therapy were excluded. Logistic regression analysis was used to identify predictors of upgrading among GGG 1 diagnoses. A total of 403 patients were included in the present study. Agreement in GGG between initial and second-opinion diagnoses was present in 256 cases (63.5%). Although opinion-matched cases improved concordance between biopsy and prostatectomy specimen GGG compared with single-opinion cases (initial, 35.2%; second-opinion, 36.5%; matched, 41.4%), 71% (56/79) of cases classified as GGG 1 were upgraded after prostatectomy. Multivariate analysis revealed that prostate-specific antigen density and Prostate Imaging Reporting and Data System version 2 score were significant predictors of upgrading (odds ratio, 1.10; P=0.01; and odds ratio, 1.88; P=0.03, respectively). In conclusion, the GGG concordance rate between needle-core biopsy and radical prostatectomy specimens was higher in opinion-matched cases; however, 71% of opinion-matched GGG1 cases were upgraded after robot-assisted radical prostatectomy. Urologists should propose treatment strategies or further biopsy rather than active surveillance for patients with GGG1 and a high PSAD and/or PI-RADS score.

DOI： 10.3892/mco.2020.1996

Quality of Life and Mental Satisfaction Improve Slowly in Preemptive Kidney Transplantation Compared With Nonpreemptive Kidney Transplantation. Reviewed International journal

Yosuke Mitsui, Motoo Araki, Yuki Maruyama, Kasumi Yoshinaga, Takuya Sadahira, Koichiro Wada, Katsuyuki Tanabe, Masashi Kitagawa, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Transplantation proceedings 52 ( 3 ) 740 - 747 2020.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIMS: Preemptive kidney transplantation (PEKT) is recognized as the best therapy to avoid dialysis. However, it is not clear whether PEKT recipients experience an improvement in quality of life (QoL) after kidney transplantation (KT) that exceeds that of non-PEKT recipients, since PEKT recipients have not experienced the heavy burden of dialysis. The aim of this study was to compare the changes in QoL for PEKT and non-PEKT recipients following transplantation. METHODS: Patients included in this study underwent living donor KT in our hospital. We excluded patients with incomplete SF-36 scores and with factors that could affect QoL, such as complications or rejection. QoL was assessed by the Short Form 36-Item Health Survey version 2.0 preoperatively and 3 and 12 months postoperatively. RESULTS: Eighty-eight patients underwent living donor KT in our hospital. Twelve PEKT and 20 non-PEKT recipients were enrolled in this retrospective study. In the non-PEKT group, both the physical and mental domain scores dramatically improved from baseline at 3 months, and remained at a similar level at 12 months. In contrast, in the PEKT group, only 1 domain of the physical and mental score improved at 3 months, and the social functioning score gradually improved at 12 months. Although the mental component score showed significant improvement in the non-PEKT group, it did not change in the PEKT group. CONCLUSIONS: The improvement of QoL after transplantation is more evident in the non-PEKT group. PEKT recipients have less mental satisfaction than non-PEKT recipients.

DOI： 10.1016/j.transproceed.2020.01.042

Administration of sitafloxacin (200 mg/day) for | non-gonococcal urethritis

Koichiro Wadal, Takuya Sadahira, Motoo Arakf, I Toyohiko Watanabe, Yasutomo Nasu

Japanese Journal of Chemotherapy 68 ( 2 ) 181 - 185 2020.3

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Society of Chemotherapy

Male urethritis is a common disease encountered by clinicians, and at the initial visit to an outpatient clinic, male urethritis is diagnosed as gonococcal urethritis or non-gonococcal urethritis (NGU) and treated with antimicrobial agents. In patients with NGU. Chlamydia trachomatis is the most common pathogen: However, examination for pathogens other than Neisseria gonorrhoeae and C. trachomatis is not approved by insurance providers in Japan In general, diagnosis of chlamydial/non-chlamydial urethritis is made after first-line antimicrobial administration to patients with NGU. Clinicians should administer second-line treatment for non-gonococcal or treatment-refractory urethritis cases in which Mycoplasma genitalium or other drug-resistant pathogens are likely. According to Japanese guidelines, sitafloxacin (STFX) is recommended as the first-line drug for chlamydial urethritis and as the second-line regimen for oon-chlamydial NGU. Randomized controlled trials in Japan have reported superior outcomes with STFX as compared to azithromycin (AZM) in patients with NGU. Thus, although AZM is the first-line therapy of choice for NGU. including non-chlamydial NGU. STFX should be used not only for treatment-refractory patients, but also as first-line therapy for selected cases of NGU.

Differentiation of Small (≤ 4 cm) Renal Masses on Multiphase Contrast-Enhanced CT by Deep Learning. International journal

Takashi Tanaka, Yong Huang, Yohei Marukawa, Yuka Tsuboi, Yoshihisa Masaoka, Katsuhide Kojima, Toshihiro Iguchi, Takao Hiraki, Hideo Gobara, Hiroyuki Yanai, Yasutomo Nasu, Susumu Kanazawa

AJR. American journal of roentgenology 214 ( 3 ) 605 - 612 2020.3

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.2214/AJR.19.22074

Robotic Renal Autotransplantation: A Feasibility Study in a Porcine Model. Reviewed

Risa Kubota, Motoo Araki, Koichiro Wada, Kasumi Kawamura, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Yuichi Ariyoshi, Takehiro Iwata, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Yuzuki Kano, Masashi Kitagawa, Katsuyuki Tanabe, Hitoshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Acta medica Okayama 74 ( 1 ) 53 - 58 2020.2

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.18926/AMO/57953

ハイドロゲルスペーサーを併用した前立腺癌密封小線源永久挿入療法の1例

田邊新, 片山敬久, 福間省吾, 三道幹大, 大野凌, 大川広, 渡邉謙太, 金澤右, 勝井邦彰, 大岩裕子, 高本篤, 那須保友

Japanese Journal of Radiology 38 ( Suppl. ) 75 - 75 2020.2

Post-ablation syndrome after percutaneous cryoablation of small renal tumors: A prospective study of incidence, severity, duration, and effect on lifestyle

Kawabata T, Hiraki T, Iguchi T, Matsui Y. Uka M, Masaoka Y, Komaki T, Sakurai J, Gobara H, Araki M, Nasu Y, Kanazawa S

Eur J Radiol 2020

Comparison of longitudinal health-related quality-of-life outcomes between anterior and posterior surgical approaches to robot-assisted radical prostatectomy. International journal

Yuki Maruyama, Takuya Sadahira, Motoo Araki, Yosuke Mitsui, Koichiro Wada, Ryuta Tanimoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Journal of robotic surgery 14 ( 2 ) 255 - 260 2020

Language：English Publishing type：Research paper (scientific journal)

Increasingly, studies have explored health-related quality-of-life (HRQOL) outcomes after robot-assisted radical prostatectomy (RARP). Nevertheless, no study has compared differences between anterior and posterior surgical approaches. The aim of this study is to assess differences of HRQOL following these two surgical approaches. From January 2012 to September 2017, 653 patients underwent RARP at our institution. We included patients who underwent operations by three experienced surgeons with interchangeability of role as console operator, and who could evaluate preoperatively the Expanded Prostate Cancer Index Composite (EPIC) score. Patients treated with neoadjuvant hormonal therapy were excluded. HRQOL was assessed using the EPIC score, and the questionnaire was administered at 6 timepoints: the baseline survey was conducted within 3 months before the surgery, and follow-up surveys were conducted at 2 weeks, 1, 3, 6, and 12 months after surgery. We defined the minimal clinically important difference (MCID) as half the standard deviation of the baseline score for each domain. A total of 201 patients were included in this retrospective study. Of these, 146 patients underwent RARP using an anterior surgical approach and 55 patients underwent a posterior approach. The clinical characteristics had no significant differences except for median prostate volume between the anterior and posterior groups (27 ml vs 29 ml, p = 0.049). There were no significant differences between the two groups in score decline beyond the MCID in any domain at any timepoint. Our study demonstrates no significant differences in HRQOL between anterior and posterior surgical approaches to RARP.

DOI： 10.1007/s11701-019-00975-6

生体腎移植後に急性浸潤性の再燃を呈した副鼻腔真菌症の1例

西村慎吾, 和田耕一郎, 小林泰之, 渡邉豊彦, 村井綾, 檜垣貴哉, 那須保友, 荒木元朗, 関戸崇了, 吉永香澄, 和田里章悟, 丸山雄樹, 光井洋介, 窪田理沙, 山下美里

移植 55 387_3 - 387_3 2020

Language：Japanese Publisher：一般社団法人日本移植学会

<p>症例は65歳男性。糖尿病性腎症による末期腎不全に対する腎移植術前CTにて右蝶形骨洞に真菌を疑う軟部影を認めたが、無症候性であった。しかしながら、移植後の免疫抑制状態で劇症型になる可能性を考慮し、移植3カ月前に内視鏡下副鼻腔手術ESSにて糸状菌塊を除去（粘膜への真菌浸潤なし）、追加治療することなく経過は安定していた。生体腎移植については妻をドナーとしたABO不適合（術前減感作療法としてRituximab 200mg/body×1、DFPP×2、PE×1を実施、免疫抑制剤はTac-ER、MMF、PSL、Basiliximabを使用）、経過は良好でPOD18に退院となった（ Cr 1.28mg/dl ）。移植後2カ月が経過し、右顔面痛・頭痛が出現、近医で副鼻腔洗浄や抗菌薬投与を受けるも改善せず。β-Dグルカン 53pg/mlと異常高値、副鼻腔MRIでは一部骨への浸潤を疑う軟部影を認め、再度ESSを施行、紙様板は腐骨化を認めたが真菌塊を可及的に除去した。VRCZも併用・継続し、術後1カ月でβ-Dグルカンも正常化、現在、再燃を認めていない。浸潤性副鼻腔真菌症は副鼻腔から眼窩，海綿状静脈洞，頭蓋内へ浸潤し致死的となり、全生存率は概ね50%と、予後不良とされる。今回、予防的にESSを先行したが、腎移植後、急性浸潤性に再燃した症例を経験したので、若干の文献的考察を加えて報告する。 </p>

DOI： 10.11386/jst.55.Supplement_387_3

Preventive efficacy and safety of lactobacillus vaginal suppositories in women with recurrent cystitis: A phase 2 study Reviewed

Sadahira T, Wada K, Ishii A, Maruyama Y, Iwata T, Araki M, Watanabe M, Watanabe T, Nasu Y

Eur Urol Open Sci 19 ( 2 ) 2036 - 2037 2020

ロボット支援下腎動脈瘤修復術のfeasibility study

荒木元朗, 和田耕一郎, 西村慎吾, 枝村康平, 小林泰之, 渡辺豊彦, 那須保友

日本内視鏡外科学会雑誌 24 ( 7 ) MO336 - 7 2019.12

Percutaneous thermal ablation for renal cell carcinoma in patients with Birt–Hogg–Dubé syndrome

Y. Matsui, T. Hiraki, H. Gobara, T. Iguchi, K. Tomita, M. Uka, M. Araki, Y. Nasu, M. Furuya, S. Kanazawa

Diagnostic and Interventional Imaging 100 ( 11 ) 671 - 677 2019.11

Publishing type：Research paper (scientific journal)

Purpose: The purpose of this study was to analyze the outcome of patients with Birt–Hogg–Dubé (BHD) syndrome who underwent percutaneous thermal ablation of renal cell carcinoma (RCC). Materials and methods: Six patients with genetically proven BHD syndrome who underwent one or more sessions of percutaneous thermal ablation for the treatment of RCC were included. There were 4 men and 2 women, with a mean age of 57.3 ± 7.5 [SD] years (range: 44–67 years). A total of 29 RCCs (1–16 tumors per patient) were treated during 20 thermal ablation sessions (7 with radiofrequency ablation and 13 with cryoablation). Outcomes of thermal ablation therapy were assessed, including technical success, adverse events, local tumor progression, development of metastases, survival after thermal ablation, and changes in renal function. Results: Technical success was achieved in all ablation sessions (success rate, 100%). No grade 4 or 5 adverse events were observed. All patients were alive with no distant metastasis during a median follow-up period of 54 months (range: 6–173 months). No local tumor progression was found. The mean decrease in estimated glomerular filtration rate during follow-up was 10.7 mL/min/1.73 m2. No patients required dialysis or renal transplantation. Conclusion: Radiofrequency ablation and cryoablation show promising results for the treatment of RCCs associated with BHD syndrome. Percutaneous thermal ablation may be a useful treatment option for this rare hereditary condition.

DOI： 10.1016/j.diii.2019.06.009

岡山大学病院におけるロボット支援腹腔鏡下腎部分切除術の検討

窪田理沙, 小林泰之, 西村慎吾, 高本篤, 佐古智子, 枝村康平, 和田耕一郎, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 33回 O - 4 2019.11

ロボット支援下腎動脈瘤修復術のfeasibility study

荒木元朗, 和田耕一郎, 河村香澄, 丸山雄樹, 光井洋介, 窪田理沙, 西村慎吾, 小林泰之, 渡辺豊彦, 那須保友

日本泌尿器内視鏡学会総会 33回 AV - 2 2019.11

岡山大学病院におけるロボット支援根治的膀胱摘除術(RARC)の検討

大岩裕子, 小林泰之, 西村慎吾, 高本篤, 佐古智子, 枝村康平, 和田耕一郎, 荒木元郎, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 33回 P - 5 2019.11

技術認定医取得における腹腔鏡下腎摘術-こうすればよくなる- 技術認定医取得における腹腔鏡下腎摘除術剥離層、出血への対応

小林泰之, 和田耕一郎, 枝村康平, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 33回 SY - 4 2019.11

部尿路上皮癌に対する尿管鏡治療の長期成績 28年にわたる単施設の検討

丸山雄樹, 荒木元朗, 和田耕一郎, 西村慎吾, 高本篤, 佐古智子, 枝村康平, 小林泰之, 渡辺豊彦, 那須保友

日本泌尿器内視鏡学会総会 33回 O - 3 2019.11

Low risk上部尿路上皮癌に対する尿管鏡下生検の有用性についての検討

片山聡, 小林泰之, 西村慎吾, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 荒木元朗, 渡邉豊彦, 那須保友

日本泌尿器内視鏡学会総会 33回 O - 1 2019.11

Prognostic role of the urokinase plasminogen activator (uPA) system in patients with nonmuscle invasive bladder cancer. International journal

Takehiro Iwata, Shoji Kimura, Mohammad Abufaraj, Florian Janisch, Mehdi Kardoust Parizi, Andrea Haitel, Micheal Rink, Morgan Rouprêt, Harun Fajkovic, Veronica Seebacher, Peter Nyirady, Pierre I Karakiewicz, Dmitry Enikeev, Leonid M Rapoport, Yasutomo Nasu, Shahrokh F Shariat

Urologic oncology 37 ( 10 ) 774 - 783 2019.10

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To assess the role of the urokinase plasminogen activator (uPA) system as a prognostic biomarker in patients with nonmuscle invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB) with or without adjuvant intravesical therapy. MATERIAL AND METHODS: We stained TURB tissue from 827 NMIBC patients with uPA, its receptor (uPAR) and its inhibitor (PAI-1). The status of these markers was categorized as normal vs. overexpressed using the cutoffs of 30% for uPA, 50% for uPAR, and 30% for PAI-1. Multivariable Cox regression analyses were performed to evaluate the prognostic value of these markers. RESULTS: uPA was overexpressed in 37.7% of patients, uPAR in 44.7% and PAI-1 in 44.6%. Overexpression of these markers was associated with high tumor grade. Within a median follow-up was 60 months (interquartile range: 22-109), uPA (hazard ratio [HR]: 1.40; P = 0.006), uPAR (HR: 1.70; P < 0.001), PAI-1 (HR: 1.35; P = 0.014), and the combination of all 3 markers (HR: 3.38; P < 0.001) were associated with recurrence-free survival (RFS); uPA (HR: 1.68; P = 0.035) and the combination of all 3 markers (HR: 8.79; P = 0.005) were associated with progression-free survival (PFS). The addition of the uPA system to a base model improved the discrimination by 1.3% for RFS and 2.1% for PFS. In subgroup analyses, uPA (HR: 2.19; P = 0.018) was associated with PFS in T1G3 patients and its addition to a base model improved the discrimination by 2.5%. uPA (HR: 1.44; P = 0.019), uPAR (HR: 1.54; P = 0.006), PAI-1 (HR: 1.46; P = 0.013) and the combination of all 3 markers (HR: 3.48; P < 0.001) were associated with RFS in TaG1-2 patients and their addition to a base model improved the discrimination by 2.1%. CONCLUSION: uPA, uPAR, and PAI-1 are overexpressed in one-third to half of patients with NMIBC. Their overexpression is an independent prognosticator of RFS and PFS which improved the predictive accuracy of current clinicopathological characteristics. Biomarkers that capture the biological and clinical behavior of individual tumors may help personalize clinical decision-making in patients with NMIBC.

DOI： 10.1016/j.urolonc.2019.05.019

Fumarate hydratase(FH)欠損腎細胞癌によるリンパ節転移に対して、イピリムマブ+ニボルマブ併用療法が奏功した一例

関戸崇了, 高本篤, 小林泰之, 三井將雄, 和田里章吾, 窪田理沙, 岩田健宏, 枝村康平, 佐古智子, 荒木元朗, 渡邉豊彦, 柳井広之, 那須保友

西日本泌尿器科 81 ( 増刊 ) 151 - 151 2019.10

岡山大学病院における進行性尿路上皮腫瘍に対するpembrolizumabの治療経験

高本篤, 小林泰之, 大岩裕子, 片山聡, 枝村康平, 窪田理沙, 岩田健宏, 西村慎吾, 佐古智子, 和田耕一郎, 荒木元朗, 渡邉豊彦, 那須保友

西日本泌尿器科 81 ( 増刊 ) 183 - 183 2019.10

Clinical pharmacokinetics of oral azithromycin in epididymal tissue. Reviewed International journal

Takuya Sadahira, Koichiro Wada, Kazuro Ikawa, Norifumi Morikawa, Masao Mitsui, Motoo Araki, Masachika Fujiyoshi, Ayano Ishii, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 25 ( 10 ) 832 - 834 2019.10

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Chlamydia trachomatis is one of the major pathogens causing acute epididymitis. Azithromycin (AZM) has a good efficacy against C. trachomatis; however, the ability of AZM to penetrate into human epididymal tissue has not yet been fully elucidated. Here, we examined the appropriate dosage of oral AZM for human epididymal tissue by site-specific pharmacokinetic/pharmacodynamic (PK/PD) analysis. METHODS: Patients with prostate cancer who underwent orchiectomy were included in this study. All patients received a 1-g dose of AZM before orchiectomy. Both epididymal tissue and blood samples were collected during surgery, and the drug concentrations were measured by high-performance liquid chromatography. All concentration-time data were analyzed with a three-compartment model with first-order absorption and elimination processes to simulate AZM concentrations in serum and epididymal tissue. RESULTS: A total of 10 patients were enrolled in the current study. For the observed values, the ratio of the epididymal concentration to the serum concentration was 5.13 ± 3.71 (mean ± standard deviation). For the simulated values, the maximum concentrations were 0.64 μg/mL at 2.42 h in serum and 1.96 μg/g at 4.10 h in epididymal tissue. The 24-h concentrations were 0.239 μg/mL in serum and 0.795 μg/g in epididymal tissue. CONCLUSIONS: The penetration of oral AZM into human epididymal tissue was examined to assess the potential application of AZM for the treatment of acute epididymitis. Based on the previous reports mentioning drug-susceptibility of C. trachomatis, multiple doses of oral AZM 1 g would be recommended for epididymitis based on the site-specific PK/PD.

DOI： 10.1016/j.jiac.2019.05.011

The role of adjuvant radiotherapy after surgery for upper and lower urinary tract urothelial carcinoma: A systematic review. International journal

Takehiro Iwata, Shoji Kimura, Mohammad Abufaraj, Florian Janisch, Pierre I Karakiewicz, Veronika Seebacher, Morgan Rouprêt, Yasutomo Nasu, Shahrokh F Shariat

Urologic oncology 37 ( 10 ) 659 - 671 2019.10

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: The role of adjuvant radiotherapy (ART) in patients with bladder cancer (BCa) and upper tract urothelial carcinoma (UTUC) is controversial. We systematically evaluated the oncologic efficacy of ART and its associated toxicity in patients treated with surgery and ART for BCa and UTUC. MATERIALS AND METHOD: We performed a literature search on December 2018 using MEDLINE, Web of Science, Cochrane databases and Scopus according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Fourteen BCa studies and 14 UTUC studies were included in this systematic review. The data were too scarce and heterogeneous for meta-analytical analysis. RESULTS: The quality and quantity of the data on ART in BCa and UTUC patients are limited. The combination of ART and chemotherapy appears to be beneficial in patients with locally advanced BCa or UTUC. The early and late adverse effects of ART are decreasing reflecting the progress in radiation technology. CONCLUSIONS: According to the currently available literature, there is no clear benefit of ART after radical surgery in BCa and UTUC. Future efforts should focus on evaluating multimodal approach using ART with chemotherapy. Until that time comes, ART should be used carefully in patients with BCa and UTUC on a case-by-case basis.

DOI： 10.1016/j.urolonc.2019.05.021

Upregulation of Mobility in Pancreatic Cancer Cells by Secreted S100A11 Through Activation of Surrounding Fibroblasts. Reviewed International journal

Yosuke Mitsui, Nahoko Tomonobu, Masami Watanabe, Rie Kinoshita, I Wayan Sumardika, Chen Youyi, Hitoshi Murata, Ken-Ichi Yamamoto, Takuya Sadahira, Acosta Gonzalez Herik Rodrigo, Hitoshi Takamatsu, Kota Araki, Akira Yamauchi, Masahiro Yamamura, Hideyo Fujiwara, Yusuke Inoue, Junichiro Futami, Ken Saito, Hidekazu Iioka, Eisaku Kondo, Masahiro Nishibori, Shinichi Toyooka, Yasuhiko Yamamoto, Yasutomo Nasu, Masakiyo Sakaguchi

Oncology research 27 ( 8 ) 945 - 956 2019.8

Language：English Publishing type：Research paper (scientific journal)

S100A11, a member of the S100 family of proteins, is actively secreted from pancreatic ductal adenocarcinoma (PDAC) cells. However, the role of the extracellular S100A11 in PDAC progression remains unclear. In the present study, we investigated the extracellular role of S100A11 in crosstalking between PDAC cells and surrounding fibroblasts in PDAC progression. An abundant S100A11 secreted from pancreatic cancer cells stimulated neighboring fibroblasts through receptor for advanced glycation end products (RAGE) upon S100A11 binding and was followed by not only an enhanced cancer cell motility in vitro but also an increased number of the PDAC-derived circulating tumor cells (CTCs) in vivo. Mechanistic investigation of RAGE downstream in fibroblasts revealed a novel contribution of a mitogen-activated protein kinase kinase kinase (MAPKKK), tumor progression locus 2 (TPL2), which is required for positive regulation of PDAC cell motility through induction of cyclooxygenase 2 (COX2) and its catalyzed production of prostaglandin E2 (PGE2), a strong chemoattractive fatty acid. The extracellularly released PGE2 from fibroblasts was required for the rise in cellular migration as well as infiltration of their adjacent PDAC cells in a coculture setting. Taken together, our data reveal a novel role of the secretory S100A11 in PDAC disseminative progression through activation of surrounding fibroblasts triggered by the S100A11-RAGE-TPL2-COX2 pathway. The findings of this study will contribute to the establishment of a novel therapeutic antidote to PDACs that are difficult to treat by regulating cancer-associated fibroblasts (CAFs) through targeting the identified pathway.

DOI： 10.3727/096504019X15555408784978

Metastatic ureteral tumor arising from gastrointestinal cancer: A report of two cases

Kasumi Kawamura, Motoo Araki, Takuya Sadahira, Yuki Maruyama, Yosuke Mitsui, Shingo Nishimura, Atsushi Takamoto, Koichiro Wada, Ryuta Tanimoto, Morito Sugimoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu, Hiroyuki Yanai

Nishinihon Journal of Urology 81 ( 4 ) 461 - 466 2019.8

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The West Japan Urological Association

We report two cases where gastrointestinal cancer gave rise to a metastatic ureteral tumor. Case one was a 64-year-old man who was operated on for descending colon cancer in September, 2007. In 2014, he was referred to our hospital because computed tomography (CT) scan showed a tumor of the right ureter. Ureteroscopic biopsy showed a metastatic ureteral tumor arising from descending colon cancer. The patient underwent open tumor resection. Transurethral resection of a bladder tumor (TUR- BT) was required three times for treatment of tumor recurrence from the ureteral stump in an effort to control gross hematuria Case two was a 62-year-old man who underwent pylorus-preserving gastrectomy for gastric cancer in December, 2014. Follow-up CT showed right hydronephrosis and thickening of the right ureteral wall in 2017. Selective urine cytology of the right ureter revealed urothelial carcinoma, class V. Ureteroscopic biopsy of the right ureter revealed invasive urothelial carcinoma. The patient underwent retroperitoneal laparoscopic nephroureterectomy. Histological examination revealed the right ureteral tumor to be metastasis of gastric cancer.

Oncologic outcomes after robot-assisted versus open radical cystectomy: a systematic review and meta-analysis. International journal

Takehiro Iwata, Shoji Kimura, Beat Foerster, Nicola Fossati, Alberto Briganti, Pierre I Karakiewicz, Kilian M Gust, Shin Egawa, Yasutomo Nasu, Mohammad Abufaraj, Shahrokh F Shariat

World journal of urology 37 ( 8 ) 1557 - 1570 2019.8

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The efficacy of RARC in oncologic outcomes compared ORC is controversial. We assess potential differences in oncologic outcomes between robot-assisted radical cystectomy (RARC) and open radical cystectomy (ORC). METHODS: We performed the literature search systematically according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. A pooled meta-analysis was performed to assess the difference in oncologic outcomes between RARC and ORC, separately in randomized controlled trials (RCTs) and non-randomized studies (NRCTs). RESULTS: Five RCTs and 28 NRCTs were included in this systematic review and meta-analysis. There was no difference in the rate of overall positive surgical margin (PSM) in RCTs, while NRCTs showed a lower rate for RARC. There was no difference in the soft tissue PSM rate between RARC and ORC in both RCTs and NRCTs. There was no difference in the lymph node yield by standard and extended lymph node dissection between RARC and ORC in both RCTs and NRCTs. There was no significant difference in survival outcomes between RARC and ORC in both RCTs and NRCTs. CONCLUSIONS: Based on the current evidence, there is no difference in the rate of PSMs, lymph node yield, recurrence rate and location as well as short-term survival outcomes between RARC and ORC in RCTs. In NRCTs, only PSM rates were better for RARC compared to ORC, but this was likely due to selection and reporting bias which are inherent to retrospective study designs.

DOI： 10.1007/s00345-019-02708-8

Comparison of the predictive value among inflammation-based scoring systems for bleomycin pulmonary toxicity in patients with germ cell tumors. International journal

Yuki Maruyama, Takuya Sadahira, Motoo Araki, Yosuke Mitsui, Koichiro Wada, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

International journal of urology : official journal of the Japanese Urological Association 26 ( 8 ) 813 - 819 2019.8

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To compare the predictive value of pretreatment inflammation-based scoring systems in patients with germ cell tumors receiving first-line bleomycin-based chemotherapy. METHODS: Retrospectively, we evaluated 57 patients with germ cell tumors. Bleomycin pulmonary toxicity was defined as the presence of asymptomatic decline in pulmonary function tests, pulmonary symptoms or interstitial pneumonia on computed tomography in the absence of infection. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, albumin-to-globulin ratio, Prognostic Nutritional Index, Glasgow Prognostic Score and C-reactive protein were measured in all patients. To assess the predictive ability of each scoring system, the area under the receiver operating characteristic curve was calculated, and multivariate analysis was carried out to identify the predictive scores associated with bleomycin pulmonary toxicity. RESULTS: Of the 57 patients, 15 patients developed bleomycin pulmonary toxicity. The neutrophil-to-lymphocyte ratio had the highest area under the curve value (0.763) of all inflammation-based scoring systems, followed by the Prognostic Nutritional Index (0.749). In multivariate analysis, the neutrophil-to-lymphocyte ratio (odds ratio 11.5; P = 0.009) and Prognostic Nutritional Index (odds ratio 9.07; P = 0.013) were independently associated with development of bleomycin pulmonary toxicity. As these two independent markers were combined, the area under the curve achieved the highest value (0.822). CONCLUSIONS: The present study shows that the neutrophil-to-lymphocyte ratio and Prognostic Nutritional Index are independent risk factors for development of bleomycin pulmonary toxicity. The combination of the neutrophil-to-lymphocyte ratio and Prognostic Nutritional Index seems to have superior predictive value compared with other inflammation-based scoring systems.

DOI： 10.1111/iju.14017

Comparison of perioperative complications and health-related quality of life between robot-assisted and open radical cystectomy:A systematic review and meta-anasis

Kimura S, Iwata T, Foerster B, Fossati N, Briganti A, Nasu Y, Egawa S, Abufaraj M, Shariat S.F

Int J Urol 26 ( 8 ) 760 - 774 2019.8

Interobserver variability of 3.0-tesla and 1.5-tesla magnetic resonance imaging/computed tomography fusion image-based post-implant dosimetry of prostate brachytherapy. International journal

Kenta Watanabe, Norihisa Katayama, Kuniaki Katsui, Toshi Matsushita, Atsushi Takamoto, Hiroki Ihara, Yasutomo Nasu, Mitsuhiro Takemoto, Masahiro Kuroda, Susumu Kanazawa

Journal of radiation research 60 ( 4 ) 483 - 489 2019.7

Language：English Publishing type：Research paper (scientific journal)

This study aimed to compare the interobserver variabilities in magnetic resonance imaging (MRI)/computed tomography (CT) fusion image-based post-implant dosimetry of permanent prostate brachytherapy (PPB) between 1.5-T and 3.0-T MRI. The study included 60 patients. Of these patients, 30 underwent 1.5-T MRI and CT 30 days after seed implantation (1.5-T group), and 30 underwent 3.0-T MRI and CT 30 days after seed implantation (3.0-T group). All patients received PPB alone. Two radiation oncologists performed MRI/CT fusion image-based post-implant dosimetry, and the interobserver variabilities of dose-volume histogram (DVH) parameters [dose (Gy) received by 90% of the prostate volume (prostate D90)], percentage of the prostate volume receiving at least the full prescribed dose (prostate V100), percentage of the prostate volume receiving at least 150% of the prescribed dose (prostate V150), dose (Gy) received by 5% of the urethral volume (urethral D5) and the urethral volume receiving at least 150% of the prescribed dose (urethral V150)] were retrospectively estimated using the paired Student's t test and Pearson's correlation coefficient. The Pearson's correlation coefficients of all DVH parameters were higher in the 3.0-T group than in the 1.5-T group (1.5-T vs 3.0-T: prostate D90, 0.65 vs 0.93; prostate V100, 0.62 vs 0.82; prostate V150, 0.97 vs 0.98; urethral D5, 0.92 vs 0.93; and urethral V150, 0.88 vs 0.93). In the paired Student's t test, no significant differences were observed in any of the DVH parameters between the two radiation oncologists in the 3.0-T group (0.068 ≤ P ≤ 0.842); however, significant differences were observed in prostate D90 (P = 0.004), prostate V100 (P = 0.011) and prostate V150 (P = 0.002) between the oncologists in the 1.5-T group. The interobserver variability of DVH parameters in the MRI/CT fusion image-based post-implant dosimetry analysis of brachytherapy was lower with 3.0-T MRI than with 1.5-T MRI.

DOI： 10.1093/jrr/rrz012

Inflammatory myofibroblastic bladder tumor with divergent behavior in a patient with spinal cord injury. International journal

Ichiro Tsuboi, Yuki Maruyama, Takuya Sadahira, Koichiro Wada, Nobuyoshi Ando, Yosuke Mitsui, Yasuhiro Nishiyama, Ryoji Arata, Motoo Araki, Yasutomo Nasu, Noriaki Ono

IJU case reports 2 ( 4 ) 212 - 214 2019.7

Language：English

Introduction: An inflammatory myofibroblastic tumor of the bladder is rare. Some urothelial carcinoma with sarcomatoid changes may mimic an inflammatory myofibroblastic tumor. Case presentation: A 76-year-old man with indwelling urinary catheters because of a spinal cord injury presented with gross hematuria. Transurethral electrocoagulation and a resection were performed. A T2-weighted magnetic resonance imaging showed a tumor and hematoma in the bladder diverticulum that pathologically resembled an inflammatory myofibroblastic tumor. This lesion was then removed en bloc by partial cystectomy. Histology showed a squamous cell carcinoma with sarcomatoid changes. After 4 months, a computed tomography showed the lesion had expanded outside the skin adjacent to the bladder. Conclusion: Some cases of inflammatory myofibroblastic tumors have a malignant course. Urologists therefore need to be aware of the possibility of rare cases of malignant bladder myofibroblasts.

DOI： 10.1002/iju5.12085

ロボット支援腹腔鏡下腎部分切除術後に再発した3症例の検討

小林泰之, 荒木元朗, 枝村康平, 西村慎吾, 高本篤, 渡辺豊彦, 那須保友

腎癌研究会会報 ( 49 ) 40 - 40 2019.7

Robotic renal auto transplantation

Motoo Araki, Koichiro Wada, Shingo Nishimura, Risa Kubota, Kasumi Kawamura, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Atsushi Takamoto, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Ayano Ishii, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Nishinihon Journal of Urology 81 ( 3 ) 314 - 320 2019.6

Language：Japanese Publishing type：Research paper (international conference proceedings) Publisher：The West Japan Urological Association

Renal autotransplantation (RAT) is a great surgical procedure for renal preservation, however it is underutilized due to its invasiveness. Robotic RATx has been in use since 2014. We conducted robotic RATx following a feasibility study using a porcine model. A 38-year-old woman with left ureteral stenosis was referred to us for urinary tract reconstruction. She had undergone an emergency Caesarean section for intraperitoneal bleeding secondary to left ovarian rupture four years earlier. After the surgery, she developed hypovolemic shock and disseminated intravascular coagulation (DIC) due to postoperative bleeding. Left internal iliac artery embolization saved her life. However, it resulted in a left ureteral stenosis measuring 2.7 cm that was located 5 cm from the left ureteral orifice, which required chronic ureteral stent exchange. Neither balloon dilation nor laser incision was successful. In addition, retrograde pyelography showed a possible left ureteropelvic junction obstruction. The patient was hesitant about the surgery because of its invasiveness. However, four years later, the patient elected to undergo robotic RATx. To date, only four cases of robotic RATx have been reported, including the current case. The indication of all four cases was extensive ureteral stenosis. Ileal ureter is frequently used for the treatment of extensive ureteral stenosis, but it can entail many problems including urine reabsorption resulting in metabolic acidosis. Ileal ureter is contraindicated for patients with a serum creatinine (sCr) level greater than 2 mg/dl. Even if sCr is less than 2 mg/dl, it is questionable whether sCr will remain less than 2 mg/ dl for the remainder of someone's life. Boari flap can give rise to vesicoureteral reflux causing urinary tract infection. RATx does not have those problems. Robotic RATx is a new, minimally invasive approach to renal preservation.

The role of adjuvant radiotherapy after surgery for upper and lower urinary tract urothelialcarcinoma: A systematic review

Iwata T, Kimura S, Abufaraj M, Janisch F, Karakiewicz P.I, Seebacher V, Roupre't M, Nasu Y, Shariat S.F

Urol Oncol 37 ( 10 ) 659 - 671 2019.6

Clinical phamacokinetics of oral azithromycin in epididymal tissue

Sadahira T, Wada K, Ikawa K, Morikawa N, Mitsui M, Araki M, Fujiyoshi M, Ishii A, Watanabe M, Watanabe T, Nasu Y

J Infect Chemother 25 ( 10 ) 832 - 834 2019.6

Rituximab induction therapy is effective without increasing adverse events in immunological high risk recipients

Kawamura K, Araki M, Maruyama Y, Mitsui Y, Sadahira T, Kubota T, Nishimura S, Wada K, Kobayashi Y, Watanabe T, Nasu Y

The Journal of Urology 201(Supplement 4) ( 4S ) e1124 - e1125 2019.5

Pelvic magnetic resonance imaging parameters predict urinary incontinence after robot-assisted radical prostatectomy. International journal

Takuya Sadahira, Yosuke Mitsui, Motoo Araki, Yuki Maruyama, Koichiro Wada, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Lower urinary tract symptoms 11 ( 3 ) 122 - 126 2019.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Urinary incontinence (UI) is a major prostate cancer (PCa) treatment-related morbidity. It has been reported that post-prostatectomy UI is related to the width of the pelvic floor muscles (PFM) and the length of the urethra. However, the details of these anatomical parameters are unknown. The aim of this study was to investigate whether preoperative pelvic parameters or anatomical parameters of the urethra, as measured by magnetic resonance imaging (MRI), are correlated with UI. METHODS: Between 2010 and 2017, 571 patients with localized PCa underwent robot-assisted radical prostatectomy (RARP) at Okayama University Hospital. Patients treated by a single experienced surgeon were included in the study. Preoperative prostate volume, obturator internal muscle, anal sphincter muscle, levator ani muscle (LAM), urethra wall thickness (UWT), and membranous urethral length (MUL) were measured by MRI. Patients were divided into two groups depending on leakage status 1 year after RARP using Expanded Prostate Index Composite Item 1. RESULTS: Seventy patients were included in this retrospective study. Based on leakage status, 37 and 33 patients were allocated to the no-leakage and leakage groups, respectively. There were significant differences between the two groups in age (P = 0.03), MUL (P < 0.001), UWT (P = 0.03), and LAM (P = 0.001). Multivariate logistic regression analyses revealed that MUL and LAM predicted UI 1 year after RARP. CONCLUSIONS: Pelvic parameters measured by MRI before RARP may be useful in the prediction of UI. In particular, MUL and LAM can predict postoperative UI by strict definition.

DOI： 10.1111/luts.12245

Three-year follow-up of a phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer and bone metastases

Hirotsugu Uemura, Hiroji Uemura, Satsohi Nagamori, Yoshiaki Wakumoto, Go Kimura, Hiroaki Kikukawa, Akira Yokomizo, Atsushi Mizokami, Takeo Kosaka, Naoya Masumori, Yoshihide Kawasaki, Junji Yonese, Yasutomo Nasu, Satoshi Fukasawa, Takayuki Sugiyama, Seigo Kinuya, Makoto Hosono, Iku Yamaguchi, Takashi Akagawa, Nobuaki Matsubara

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 24 ( 5 ) 557 - 566 2019.5

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

Background Radium-223 is a first-in-class targeted alpha therapy to prolong overall survival (OS) in castration-resistant prostate cancer with bone metastases (mCRPC). The aim of the present analysis was to assess the long-term safety with radium-223 in Japanese patients with mCRPC.Methods Patients with symptomatic mCRPC, >= 2 bone metastases and no known visceral metastases received up to 6 injections of radium-223 (55 kBq/kg), one every 4 weeks. Adverse events (AEs) considered to be related to radium-223 were reported until 3 years after the first injection. Pre-specified conditions, such as acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or other primary malignancies, were reported regardless of causality.Results Of the 49 patients enrolled in the study, 44 (89.8%) entered the survival follow-up period and 33 (67.3%) died. Throughout the entire study, there were no reports of second primary malignancy or other pre-specified conditions. Eight patients (16.3%) experienced post-treatment drug-related AEs, which were all hematological (anemia and decreased lymphocyte, platelet, and white blood cell counts). No serious post-treatment drug-related AEs were reported. Updated median OS was 19.3 months (95% CI: 14.2, 28.5).Conclusions In Japanese patients with symptomatic mCRPC and bone metastases, radium-223 had a favorable long-term safety profile with no second primary malignancies reported. Taken together with median OS, which was comparable to that in the pivotal phase III ALSYMPCA study, these results support continued benefit from radium-223 in Japanese patients with mCRPC.

DOI： 10.1007/s10147-018-01389-4

Experience of robot-assisted radical cystectomy in Okayama University Hospital

Yasuyuki Kobayashi, Masao Mitsui, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Koichiro Wada, Kohei Edamura, Motoo Araki, Toyohiko Watanabe, Yasutomo Nasu

Nishinihon Journal of Urology 81 ( 2 ) 122 - 127 2019.4

Language：Japanese Publishing type：Research paper (international conference proceedings) Publisher：The West Japan Urological Association

Robot-assisted radical cystectomy became listed as being covered by insurance in 2018 and accordingly, it is expected to become a popular surgical method in Japan in the future. In this study, we examined the findings of 102 patients who underwent total cystectomy (ORC, 35 cases), laparoscopic radical cystectomy (LRC, 52 cases), and robot-assisted radical cystectomy (RARC, 15 cases). The examined items were operative time, bleeding volume, postoperative complications, length of hospital stay, postoperative walking start date, postoperative pain and postoperative fever. Operative time was the shortest for RARC and bleeding volume was the lowest for RARC. Postoperative complications comprised approximately 33% (all grades) in any group. LRC and RARC were superior to ORC regarding both the period until walking start day and the period of postoperative persistent fever. Compared to ORC, patients undergoing RARC can expect an earlier recovery after surgery. In addition, patients undergoing RARC can expect stable surgical results with little difference in the postoperative course of each case.

Perioperative blood transfusion affects oncologic outcomes after nephrectomy for renal cell carcinoma: A systematic review and meta-analysis. International journal

Takehiro Iwata, Shoji Kimura, Beat Foerster, Mohammad Abufaraj, Pierre I Karakiewicz, Felix Preisser, Yasutomo Nasu, Shahrokh F Shariat

Urologic oncology 37 ( 4 ) 273 - 281 2019.4

Language：English Publishing type：Research paper (scientific journal)

AIM: To investigate the association of perioperative blood transfusion (PBT) with oncologic outcomes in patients with renal cell carcinoma (RCC), we conducted a systematic review and meta-analysis of the literature to clarify the long-term oncologic effect of PBT in patients undergoing nephrectomy for RCC. MATERIALS AND METHODS: We searched the MEDLINE, Web of Science, Cochrane Library and Scopus on 15th April 2018 to identify studies that compared patients who received PBT undergoing radical or partial nephrectomy for RCC to patients who did not with the aim of evaluating its impact on overall mortality (OM), cancer-specific mortality (CSM) and disease recurrence using multivariable cox regression analysis. RESULTS: A total of 19,681 patients in 7 studies matched the selection criteria for the systematic review and meta-analysis. All 7 studies were retrospective design and published between 1994 and 2018. Our study included low quality of eligible studies due to their retrospective design and showed a significant heterogeneity. PBT was associated with OM (pooled hazard ratio [HR], 1.49, 1.24-1.78), CSM (pooled HR, 1.46, 1.20-1.77), and disease recurrence (pooled HR, 1.80, 1.03-3.12). In a subgroup analysis of 3,664 patients with nonmetastatic RCC, PBT was remained associated with OM (pooled HR, 1.91; 1.06-3.41), but not anymore with CSM (pooled HR, 1.92, 0.94-3.91) or disease recurrence (pooled HR, 2.18, 0.86-5.55). CONCLUSIONS: PBT in patients undergoing nephrectomy for RCC is associated with worse overall survival. While PBT may be reflective of the underlying aggressiveness of the disease, it could be that its detrimental effect on outcomes is caused by its negative effect on the host's resilience.

DOI： 10.1016/j.urolonc.2019.01.018

Contrast-enhanced Computed Tomography-Guided Percutaneous Cryoablation of Renal Cell Carcinoma in a Renal Allograft: First Case in Asia

Ichiro Tsuboi, Motoo Arakio, Hiroyasu Fujiwara, Toshihiro Iguchi, Takao Hiraki, Naoko Arichi, Kasumi Kawamura, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Tomoko Sako, Atsushi Takamoto, Koichiro Wada, Yasuyuki Kobayashi, Toyohiko Watanabe, Hiroyuki Yanai, Masashi Kitagawa, Katsuyuki Tanabe, Hitoshi Sugiyama, Jun Wada, Hiroaki Shiina, Susumu Kanazawa, Yasutomo Nasu

ACTA MEDICA OKAYAMA 73 ( 3 ) 269 - 272 2019.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

Use of single-dose perioperative antimicrobial therapy is acceptable in recipients of living-donor renal transplants in the rituximab era. International journal

Shingo Nishimura, Koichiro Wada, Motoo Araki, Takuya Sadahira, Yuki Maruyama, Yosuke Mitsui, Ryuta Tanimoto, Yasuyuki Kobayashi, Toyohiko Watanabe, Yasutomo Nasu

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 25 ( 4 ) 247 - 252 2019.4

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The aim of this study was to evaluate the efficacy of single-dose perioperative antimicrobial therapy as infection prophylaxis in recipients of living-donor renal transplants in the rituximab era. PATIENTS AND METHODS: Between 2009 and 2017, 84 recipients underwent living-donor renal transplantation (LDRT) at Okayama University Hospital; 3 with vascular/urinary complications requiring additional surgery were excluded from this analysis. Data including recipient characteristics, antimicrobial prophylaxis and administration of rituximab were retrospectively examined for an association with perioperative infections. Prophylactic antimicrobial agents, selected according to the Results of preoperative urine cultures, were administered just before incision. Perioperative infections, which consisted of surgical site infections, remote infections, and urinary tract infections, were defined as a positive culture indicating required administration of additional antimicrobial agents. RESULTS: Among the 81 recipients, prophylactic cefazolin, ampicillin/sulbactam, and others were administered to 66 (82%), 13 (16%), and 2 (3%) recipients, respectively. Twenty-one (26%) received single-dose antimicrobial prophylaxis, while 60 (74%) received multiple doses up to 7 days. Rituximab was used in 59 (72.8%) recipients. The incidence of urinary tract infection, surgical site infection and remote infection was 13 (16%), 1 (1%), and 0, respectively. Univariate analysis could not demonstrate any significant risk factors for postoperative urinary tract infections, including a single dose vs multiple doses of antimicrobial therapy (P = 0.069) and administration of rituximab (P = 0.717). CONCLUSIONS: Our data suggest that the use of single-dose perioperative antimicrobial therapy is acceptable for prophylaxis of infections in patients undergoing LDRT, even in the rituximab era.

DOI： 10.1016/j.jiac.2018.11.013

Comparison of longitudinal health-related quality of life outcomes between the anterior and posterior surgical approach to robot-assisted radical prostatectomy.

Maruyama Y, Sadahira T, Araki M, Tanimoto R, Kawamura K, Mitsui Y, Wada K, Edamura K, Kobayashi Y, Watanabe M, Nasu Y

European Urology Supplements 18 ( 1 ) e1186 - e1187 2019.3

Editorial Comment from Dr Sadahira et al. to Use of fosfomycin as targeted antibiotic prophylaxis before prostate biopsy: A prospective randomized study. International journal

Takuya Sadahira, Koichiro Wada, Yasutomo Nasu

International journal of urology : official journal of the Japanese Urological Association 26 ( 3 ) 399 - 399 2019.3

Clinical impact of abdominal fat distribution measured by 3-D computed tomography volumetry on post-transplant renal function in recipients after living kidney transplantation: a retrospective study.

Yosuke Mitsui, Takuya Sadahira, Motoo Araki, Yuki Maruyama, Koichiro Wada, Ryuta Tanimoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Clinical and experimental nephrology 23 ( 3 ) 415 - 424 2019.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Excessive visceral fat may decrease renal function because of metabolic derangements. The aim of this study was to evaluate the impact of abdominal fat distribution on renal function of recipients after kidney transplantation using the visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) ratio. METHODS: Seventy-nine patients underwent living kidney transplantation from 2009 to 2017. Patients without a correct measurement of VAT and SAT, follow-up of < 6 months, or with kidney transplant rejection or a virus infection were excluded. VAT and SAT were calculated automatically by 3-D volume analyzer software in recipients prior to living kidney transplantation. Our primary aim was to identify abdominal fat distribution measured by CT associated with renal dysfunction (estimate glomerular filtration rate; eGFR < 45) at 6 month post renal transplantation in recipient. RESULTS: Fifty-eight living kidney recipients were included in this retrospective study: 30 for the high VAT/SAT ratio group; 28 for the VAT/SAT low group. Multiple logistic regression analysis showed the VAT/SAT ratio and pre-donor eGFR were associated with eGFR < 45 ml/min/1.73 m2. An increase in VAT/SAT ratio was associated independently with the incidence of decreased renal function. CONCLUSION: This finding indicates that adipose tissue distribution is an important predictor of the outcome of living kidney transplantation in recipients.

DOI： 10.1007/s10157-018-1643-6

The 3-D Volumetric Measurement Including Resected Specimen for Predicting Renal Function AfterRobot-assisted Partial Nephrectomy. International journal

Yosuke Mitsui, Takuya Sadahira, Motoo Araki, Yuki Maruyama, Shingo Nishimura, Koichiro Wada, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Urology 125 104 - 110 2019.3

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: To investigate the relationship between postoperative renal function and resected cortex margin volume calculated by a 3-dimensional reconstruction technique based on the resected specimen, and to determine predictors of renal function after robot-assisted partial nephrectomy. METHODS: A total of 114 patients underwent robot-assisted partial nephrectomy from 2014 to 2018. Patients without a 1 mm slice computed tomography or renal scintigraphy were excluded. We identified the margins of the tumor from each resected specimen with 2 mm margin being added as the ischemic margin. The volume of the renal cortex was calculated automatically using 3-dimensional volume analyzer software. The total margin volume was excluded from the ipsilateral cortex volume to calculate the cortex volume split. Predicted estimated glomerular filtration rate (eGFR) was calculated using the change in cortex volume and then compared with the actual eGFR. RESULTS: Eighty-two patients were included in this retrospective study. Sixty-six patients (80%) were cT1a. A strong correlation was observed between renal scintigraphy split and pre- and postoperative cortex volume split (Pearson correlation coefficient r = 0.9330 and 0.8742, respectively). The predicted eGFR correlated strongly with post 1, 3, 6, and 12 months eGFR (r = 0.8929, 0.9294, 0.9320, and 0.8952, respectively). Preoperative relative renal function and total cortex margin volume were independent risk factors for decreasing postoperative renal function. CONCLUSION: This precise volumetric assessment that includes the resected margin is an alternative to renal scintigraphy for predicting postoperative relative renal function. The healthy cortex margin volume calculated by the reconstruction technique is an independent risk factor of decreasing postoperative renal function.

DOI： 10.1016/j.urology.2018.12.020

Sarcopenia patients are clinically dissatisfied with postoperative urinary function compared with non-sarcopenia patients in robot-assisted radical prostatectomy

Mitsui Y, Araki M, Maruyama Y, Sadahira T, Wada K, Edamura K, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

European Urology Supplements 18 ( 1 ) e1194 - e1195 2019.3

The level of QOL improves slower in preemptive kidney transplantation than the one in non-preemptive kidney transplantation

Mitsui Y, Araki M, Maruyama Y, Sadahira T, Wada K, Edamura K, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

European Urology Supplements 18 ( 1 ) e1651 - e1652 2019.3

Tumor suppressor REIC/Dkk-3 and its co-chaperone SGTA: Their interaction and role to control castration-resistant prostate cancer by the release from androgen independence and malignancy

Sadahira T, Maruyama Y, Mitsui Y, Wada K, Edamura K, Kobayashi Y, Araki M, Watanabe M, Nasu Y

European Urology Supplements 18 ( 1 ) e68 2019.3

Gosha-jinki-gan, a herbal medicine, is effective for the treatment of female patients with overactive bladder and sensitivity to the cold

Yuko Matsumoto, Ayano Ishii, Masumi Yamamoto, Satoko Matsuo, Tomoko Sako, Motoo Araki, Toyohiko Watanabe, Yasutomo Nasu, Miyabi Inoue, Shinako Araki, Noritaka Ishito, Hitoshi Takamoto

Nishinihon Journal of Urology 81 ( 1 ) 12 - 16 2019.2

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The West Japan Urological Association

The herbal medicine "gosha-jinki-gan" is effective for the treatment of patients with overactive bladder and an increase in peripheral blood flow. We prospectively assessed the relationship between the effectiveness of gosha-jinki-gan for female patients with overactive bladder and an improvement in their sensitivity to the cold. Between December 2012 and March 2016, gosha-jinki-gan 2.5 g t.i.d. was administered to a total of 56 adult female patients with overactive bladder for a period of 4 weeks. Their symptoms were assessed using the Overactive Bladder Symptom Score (OABSS), and their sensitivity to the cold was assessed using a questionnaire about the cold, based on Terasawa's diagnostic criteria. Skin temperature (at the palmar, suprapubic and plantar locations), OABSS and answers to the questionnaire about the cold were obtained at baseline and again at 4 weeks after treatment. Average age was 64 ± 13.8 years. Total OABSS improved significantly at 4 weeks (7.57 ± 3.36 vs. 6.73 ± 3.50), however skin temperature did not increase significantly. In a subgroup analysis, total OABSS was found to have improved significantly at 4 weeks (7.94 ± 3.65 vs. 6.86 ± 3.61) in the 36 women with sensitivity to the cold. However, although it showed a trend for improvement, that improvement was not statistically significant in the 20 women without sensitivity to the cold. Our findings indicated that gosha-jinki-gan improved overactive bladder symptoms more in patients with sensitivity to the cold than in patients without sensitivity to the cold.

Loss of psoas major muscle volume during systemic chemotherapy is related to worse prognosis in testicular cancer. International journal

Yosuke Mitsui, Takuya Sadahira, Motoo Araki, Yuki Maruyama, Koichiro Wada, Ryuta Tanimoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Japanese journal of clinical oncology 49 ( 2 ) 183 - 189 2019.2

Language：English Publishing type：Research paper (scientific journal)

Objective: In several cancers, the loss of skeletal muscle is well associated with oncological outcome. However, its effect is unknown in testicular cancer. This study evaluated the prognostic impact of psoas major muscle volume loss during systemic chemotherapy. Methods: This was a retrospective study of patients who underwent chemotherapy from 2008 to 2017. Psoas major muscle volume was calculated by volume analyzer software, and its loss was calculated during systemic chemotherapy. The patients were divided according to muscle volume loss: Group 1 (<20%) and Group 2 (≥20%). The losses were compared with Kaplan-Meier curves, and a Cox proportional hazard model was applied to test predictors of poor prognosis. Results: Fifty patients were included. Seventeen were classified into Group 1, and 33 into Group 2. The Kaplan-Meier curves revealed that the progression-free and the overall survival of Group 1 were significantly better than those of Group 2 (P = 0.002, P = 0.03, respectively). A multivariate analysis identified psoas major muscle volume loss as a significant and independent predictor of poor prognosis. Conclusions: Patients with psoas major muscle volume loss during chemotherapy had a significantly worse prognosis than those without loss.

DOI： 10.1093/jjco/hyy166

Clitoral Blood Flow Changes after Surgery with Tension-Free Vaginal Mesh for Pelvic Organ Prolapse.

Yuko Oiwa, Toyohiko Watanabe, Takuya Sadahira, Ayano Ishii, Tomoko Sako, Miyabi Inoue, Koichiro Wada, Yasuyuki Kobayashi, Motoo Araki, Yasutomo Nasu

Acta medica Okayama 73 ( 1 ) 21 - 27 2019.2

Language：English Publishing type：Research paper (scientific journal)

We measured basal clitoral blood flow by Doppler sonography to determine whether tension-free vaginal mesh(TVM) affects the clitoral blood flow and sexual function in women with pelvic organ prolapse (POP). We performed a prospective study of 22 patients who underwent TVM for POP. Clitoral blood flow was measured by Doppler ultrasound. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) of the clitoral arteries were measured preoperatively and at 1, 3, and 6 months postoperatively. Female sexual function was also investigated with the Female Sexual Function Index (FSFI). The mean PI and RI were increased at 1 month and significantly decreased at 6 months postoperatively (p<0.05). In contrast, the mean PSV and EDV decreased at 1 month postoperatively and increased at 6 months postoperatively. These four parameters recovered to baseline levels at 6 months following surgery. Total FSFI scores improved significantly from 10.2±7.9 at baseline to 18.2±8.9 at 6 months postoperatively. Color Doppler ultrasonography is potentially useful in measuring clitoral blood flow in patients treated with TVM for POP. Prospective long-term studies are needed to evaluate the utility of this modality as a diagnostic and prognostic tool for female sexual dysfunction.

DOI： 10.18926/AMO/56455

高位精巣摘除術後14年後に再発をきたしたStage I期セミノーマの1例(VERY LATE RELAPSE AND MANAGEMENT OF CLINICAL STAGE I SEMINOMA AFTER ORCHIECTOMY: A CASE REPORT) Reviewed

和田里章悟, 定平卓也, 高本篤, 丸山雄樹, 光井洋介, 和田耕一郎, 谷本竜太, 杉本盛人, 小林泰之, 荒木元朗, 渡邉昌実, 渡邉豊彦, 那須保友, 柳井広之

西日本泌尿器科 81 ( 1 ) 45 - 48 2019.2

Language：English Publisher：西日本泌尿器科学会

Stage I期セミノーマの手術後には補助治療を行わず経過観察とするsurveillanceが現在の主流となっており、再発率は13〜20%と言われている。補助治療の有無によらず、再発の大半は手術後2年以内が占める。以降の再発は晩期再発と呼ばれ区別されているが、そのリスク因子は明確になっていない。手術後5年以降の再発は0.8%〜2.5%と報告されており、術後10年を超えての再発はさらに稀である。今回、我々は高位精巣摘除術14年後に発生したセミノーマ晩期再発を経験したので、若干の文献的考察を加え報告する。症例は40代、男性。右下腿浮腫、総腸骨リンパ節の腫大、骨盤内腫瘤を指摘され当科紹介受診した。患者は前医受診の14年前に右精巣腫瘍に対し高位精巣摘除術を行われており、セミノーマpT2N0M0 Stage IBとして術後6年間のフォローの後に終診となっていた。当科受診時にはLDH 667 U/l(120〜240U/l)、β-hCG 17.5mIU/l(<0.5mIU/l)と高値を認め、骨盤内腫瘤生検によりセミノーマの再発と診断、救済化学療法としてBEP3コース、VeIP療法を3コース施行した。VeIP療法施行後、骨盤内残存腫瘤の切除を行った。摘出標本は壊死組織のみでviable cellは認めず、術後7ヵ月時点では局所再発、転移は認めていない。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01004&link_issn=&doc_id=20190222240009&doc_link_id=%2Fer9niuro%2F2019%2F008101%2F009%2F0045-0048%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fer9niuro%2F2019%2F008101%2F009%2F0045-0048%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Robotic-assisted renal autotransplantation: Preliminary studies and future directions

Motoo Araki, Koichiro Wada, Kasumi Kawamura, Yuuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Takashi Yoshioka, Yuichi Ariyoshi, Kei Fujio, Atsushi Takamoto, Morito Sugimoto, Katsumi Sasaki, Yasuyuki Kobayashi, Shin Ebara, Amano Hiroyuki, Masashi Inui, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Endourology Progress: Technique, Technology and training 143 - 148 2019.1

Language：English Publishing type：Part of collection (book) Publisher：Springer Singapore

The indications for renal autotransplantation (RATx) include renal vascular trauma, thrombosis, stenosis, aneurysm, complex ureteral injuries, renal cell carcinoma, urolithiasis, retroperitoneal fibrosis, and loin pain-hematuria syndrome. Unfortunately, RATx is underutilized because of its invasiveness. The current gold standard approach to RATx is laparoscopic nephrectomy and open autotransplantation, which requires a large pelvic incision. Robotic-assisted renal autotransplantation (robotic RATx) is a new, minimally invasive approach that has been used since 2014. The first completely intracorporeal robotic RATx, used to repair a ureteral injury, was reported in 2014. Since then, only three cases have been reported, all from North America. After an initial porcine study, we conducted the fourth robotic RATx procedure. Robotic surgery has multiple advantages, such as providing a three-dimensional magnified view, navigating in narrow spaces, and fine suturing and dissection, which are particularly helpful in cases with desmoplastic changes. Most robotic RATx procedures have been used to repair ureteral injuries. These cases tend to have desmoplastic changes due to previous surgeries. Nephrectomy and RATx are technically challenging, hence robotic surgery may be the best option in patients with complex and severe desmoplastic changes. The disadvantages of robotic RATx include the length of surgery and cost. However, with continued use, both the operative time and the cost should decrease. In conclusion, robotic RATx is a new, minimally invasive approach to renal preservation.

DOI： 10.1007/978-981-13-3465-8_18

The Novel Combination of Nitroxoline and PD-1 Blockade, Exerts a Potent Antitumor Effect in a Mouse Model of Prostate Cancer. Reviewed International journal

Naijin Xu, Linglong Huang, Xiezhao Li, Masami Watanabe, Chaoming Li, Abai Xu, Chunxiao Liu, Qiang Li, Motoo Araki, Koichiro Wada, Yasutomo Nasu, Peng Huang

International journal of biological sciences 15 ( 5 ) 919 - 928 2019

Language：English Publishing type：Research paper (scientific journal)

Programmed cell death protein 1 (PD-1) blockade is a promising therapeutic strategy against prostate cancer. Nitroxoline has been found to have effective anticancer properties in several cancer types. We investigated the efficacy of a combination therapy involving nitroxoline and PD-1 blockade in a prostate cancer mouse model. In our in vitro analysis, we found that nitroxoline inhibited the viability and proliferation of the mouse prostate cancer cell line RM9-Luc-PSA. Additionally, nitroxoline downregulated the expressions of phospho-PI3 kinase, phospho-Akt (Thr308), phospho-Akt (Ser473), phospho-GSK-3β, Bcl-2, and Bcl-xL. Nitroxoline also downregulated programmed death-ligand 1 (PD-L1) expression levels in prostate cancer cell line and tumor tissue. In our murine prostate cancer orthotopic model, nitroxoline plus PD-1 blockade synergistically suppressed tumor growth when compared with nitroxoline or PD-1 blockade alone, leading to reductions in tumor weight, bioluminescence tumor signals, and serum prostate-specific antigen levels. Furthermore, fluorescence-activated cell sorting analysis showed that the combination strategy significantly enhanced antitumor immunity by increasing CD44+CD62L+CD8+ memory T cell numbers and reducing myeloid-derived suppressor cell numbers in peripheral blood. In conclusion, our findings suggest that nitroxoline plus PD-1 blockade may be a promising treatment strategy in patients with prostate cancer.

DOI： 10.7150/ijbs.32259

Favorable long-term oncological and urinary outcomes of incidental prostate cancer following holmium laser enucleation of the prostate. International journal

Yusuke Tominaga, Takuya Sadahira, Yosuke Mitsui, Yuki Maruyama, Ryuta Tanimoto, Koichiro Wada, Shuhei Munemasa, Nobuyuki Kusaka, Yasuhiro Nishiyama, Takushi Kurashige, Yasutomo Nasu, Shunji Hayata

Molecular and clinical oncology 10 ( 6 ) 605 - 609 2019

Language：English Publishing type：Research paper (scientific journal)

The aim of the present study was to investigate the impact of incidental prostate cancer (IPCa), which was diagnosed by holmium laser enucleation of the prostate (HoLEP), on long-term oncological and functional outcomes. A total of 482 patients who underwent HoLEP for benign prostatic hyperplasia (BPH) between 2008 and 2016 at our institution were retrospectively reviewed. We defined IPCa as prostate cancer (PCa) according to the enucleated tissue of transitional zone. Therefore, 64 patients were excluded for the following reasons: Prostate-specific antigen (PSA) ≥4.0 ng/ml and no prostate biopsy (n=46); and PSA ≥4.0 ng/ml and diagnosed with PCa by prostate biopsy performed during HoLEP (n=18). Notably, 418 patients were included in the study and divided into two groups: The BPH group and the IPCa group. For 5 years, postoperative PSA and functional outcomes were evaluated. Of 418 patients, 25 (6%) were diagnosed with IPCa by HoLEP, 21 patients (84%) had a Gleason score ≤6 and 5 patients (20%) received adjuvant therapy for PCa following HoLEP. No significant differences were observed between groups for preoperative PSA, PSA density, or urinary and sexual function outcomes; however, age at the time of HoLEP significantly differed between groups (71.7 vs. 75.5 years, P=0.026). Long-term (5-year) urinary outcomes demonstrated sustained improvement. Postoperative PSA increased gradually in the IPCa group (3-year, P=0.033; 4-year, P=0.037); International Index of Erectile Function 5 conversely decreased (5-year, P=0.068). According to the present results, if standard PSA screening and prostate biopsy are performed, watchful waiting for IPCa is feasible, and IPCa does not impact on 5-year urinary outcomes.

DOI： 10.3892/mco.2019.1839

Burned-out Prostate Cancer ? Primary Metastatic Cancer Not Detected on Repeat Biopsy. Reviewed

Mitsui Y, Sadahira T, Maruyama Y, Wada K, Tanimoto R, Sugimoto M, Araki M, Watanabe M, Yanai H, Watanabe T, Nasu Y

Acta medica Okayama 72 ( 6 ) 605 - 609 2018.12

Language：English Publishing type：Research paper (scientific journal)

Metastatic prostate cancer (PCa) cases that cannot be detected on repeat prostate biopsy are extremely rare. Our patient was a 51-year-old Japanese man diagnosed as metastatic PCa by histopathological examination of lesions obtained bone biopsy and lymph node dissection. The primary tumor was not detected after repeated prostate biopsy. Metastatic PCa was diagnosed based on immunohistochemical staining: PSA, AR, P504S, and NKX3.1 of bone and lymph node with metastasis. We speculate that the primary PCa was "burned-out," demonstrating remote metastases with no apparent primary tumor in the prostate. Burned-out PCa may be difficult to diagnose and treat due to its rarity.

DOI： 10.18926/AMO/56380

経腹的到達法による根治的腎摘除術

小林泰之, 西村慎吾, 高本篤, 佐古智子, 和田耕一郎, 枝村康平, 荒木元朗, 渡辺豊彦, 那須保友

日本泌尿器内視鏡学会総会 32回 SEP - 2 2018.11

ロボット支援下腎部分切除におけるearly unclamp法の術後腎機能に対する有用性の検討

和田里章悟, 谷本竜太, 丸山雄樹, 光井洋介, 前原貴典, 西村慎吾, 高本篤, 杉本盛人, 和田耕一郎, 小林泰之, 荒木元朗, 渡辺豊彦, 那須保友

西日本泌尿器科 80 ( 増刊 ) 189 - 189 2018.10

当院で経験した前立腺炎症性偽腫瘍の1例

佐久間貴文, 高本篤, 河村香澄, 岩田健宏, 和田耕一郎, 谷本竜太, 杉本盛人, 小林泰之, 荒木元朗, 渡邊豊彦, 柳井広之, 那須保友

西日本泌尿器科 80 ( 増刊 ) 176 - 176 2018.10

QOL向上をめざした泌尿器がん治療ロボット支援下膀胱全摘除術

小林泰之, 三井將雄, 佐古智子, 高本篤, 西村慎悟, 和田耕一郎, 荒木元朗, 渡邉豊彦, 那須保友

西日本泌尿器科 80 ( 増刊 ) 95 - 95 2018.10

THE PROMISING USE OF PROBIOTICS AGAINST RECURRENT URINARY TRACT INFECTIONS Reviewed

定平卓也, 和田耕一郎, 三井將雄, 石井亜矢乃, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

西日本泌尿器科 = The Nishinihon journal of urology 80 ( 10 ) 505 - 509 2018.10

Language：Japanese Publisher：西日本泌尿器科学会

尿路感染症に対する治療として中心的な役割を果たしてきた抗菌化学療法は大きな転機を迎えている。世界的な時流として耐性菌の問題や医療経済的にも抗菌薬の使用量を減少させる方向に移行している。尿路感染症においても例外ではなく、そのマネジメントに関して治療法の見直しだけでなく予防の重要性についての議論がなされている。そのうち、これまでに様々な臨床研究において有効性が確認されつつあるプロバイオティクスが抗菌薬とは異なる尿路感染症対策として注目されている。健常な閉経前の女性の腟内においては、基本的に乳酸菌が細菌叢(フローラ)を形成しているが、月経中や閉経後は乳酸菌が減少して腸内細菌が腟内に定着することとなる。その腟がリザーバーとなって細菌を供給し、頻繁に尿路の逆行性感染を引き起こすと考えられている。すなわち、腟内を乳酸菌中心のフローラに保つことで尿路感染症の再発(反復)リスクが低くなることが期待でき、実際にプロバイオティクスを用いた多くの研究が行われている。我々が現在行っている乳酸菌製剤のほか、プロバイオティクスの経口摂取が腟内フローラに与える影響に関しても検証が進んでおり、プロバイオティクスが尿路感染症の予防や治療に寄与することが期待されている。(著者抄録)

鰓耳腎症候群の小児に対する生体腎移植の1例

窪田理沙, 荒木元朗, 和田耕一郎, 河村香澄, 丸山雄樹, 光井洋介, 西村慎吾, 小林泰之, 渡邉豊彦, 那須保友, 宮井貴之, 北川正史, 田邊克幸, 和田淳

移植 53 ( 総会臨時 ) 434 - 434 2018.9

生体腎移植におけるリツキシマブ投与の効果と有害事象

河村香澄, 荒木元朗, 丸山雄樹, 坪井一朗, 光井洋介, 窪田理沙, 西村真吾, 和田耕一郎, 小林泰之, 渡邉豊彦, 那須保友, 山下里美, 北川正史, 田邉克幸, 杉山斉, 和田淳

移植 53 ( 総会臨時 ) 481 - 481 2018.9

腎移植患者における24時間蓄尿から見る1日塩分・蛋白摂取量の意義

光井洋介, 荒木元朗, 丸山雄樹, 坪井一朗, 河村香澄, 窪田理沙, 西村慎吾, 和田耕一郎, 小林泰之, 渡辺豊彦, 北川正史, 田邊克之, 杉山斉, 和田淳, 那須保友

移植 53 ( 総会臨時 ) 475 - 475 2018.9

リツキシマブは腎移植レシピエントの周術期細菌感染症のリスクになるか

西村慎吾, 和田耕一郎, 荒木元朗, 山下里美, 坪井一朗, 河村香澄, 丸山雄樹, 光井洋介, 窪田理沙, 定平卓也, 谷本竜太, 小林泰之, 渡邉豊彦, 那須保友

移植 53 ( 総会臨時 ) 436 - 436 2018.9

Prospective randomized controlled trial of postoperative early intravesical chemotherapy with pirarubicin (THP) for solitary non-muscle invasive bladder cancer comparing single and two-time instillation Reviewed

Ryuta Tanimoto, Takashi Saika, Shin Ebara, Yasuyuki Kobayashi, Ryoji Nasu, Daisuke Yamada, Hitoshi Takamoto, Yoshiyuki Miyaji, Yasutomo Nasu, Tomoyasu Tsushima, Hiromi Kumon

World Journal of Urology 36 ( 6 ) 889 - 895 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Verlag

Purpose: Single immediate intravesical instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) has been the gold standard treatment for patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Herein, we conducted a multicenter prospective randomized controlled trial in Japan, comparing recurrence-free survival between single and two-time instillation of pirarubicin (THP) for solitary NMIBC. Methods: Between 2005 and 2009, 257 patients with solitary NMIBC were enrolled and randomized to single instillation of THP (30 mg/50 mL) immediately after TURBT (Group A) or two-time instillation of THP immediately after and 1 day after TURBT (Group B). The primary endpoint was recurrence-free survival. Secondary endpoints included rates of recurrence and adverse effects, including hematuria, micturition pain, difficult urination, pollakiuria, systemic symptoms, and other complications. This study was registered as UMIN C000000266. Results: Of 257 patients, 99 in Group A and 102 in Group B could be evaluated for recurrence. Median follow-up was 71 months. The overall recurrence rate was 39 and 31%, respectively (p = 0.2704). Although the 5-year recurrence-free survival rates were 55.9% and 67.7% in groups A and B, respectively, the difference between groups was not significant (p = 0.2031). No significant differences in adverse effects were observed between groups, except for pollakiuria (7 vs 22%, p = 0.0031). Multivariate analyses did not show that the treatment group was a significant risk factor for bladder cancer recurrence. Conclusions: Postoperative two-time intravesical instillation of THP was not superior to single immediate instillation for preventing recurrence after complete resection of a solitary NMIBC.

DOI： 10.1007/s00345-018-2196-8

Renal Function after Nephrectomy Influences the Risk of Cardiovascular Events.

Taiki Kambara, Ryuta Tanimoto, Motoo Araki, Takashi Saika, Hideaki Hashimoto, Tadashi Oeda, Tomoyasu Tsushima, Shunji Hayata, Yasutomo Nasu, Yasuyuki Kobayashi

Acta medica Okayama 72 ( 3 ) 241 - 247 2018.6

Language：English Publishing type：Research paper (bulletin of university, research institution)

We retrospectively analyzed the factors related to postoperative cardiovascular (CV) events in patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for clinical T1 renal cell carcinoma (RCC). We identified 570 patients who underwent PN or RN for T1 renal cell carcinoma between January 1998 and December 2009 at our institution and related hospitals. We determined the cumulative incidence rate of CV events and overall survival (OS) using Kaplan-Meier survival curves with a log-rank test, and we evaluated the risk for an increase in CV events and OS using Cox proportional hazard regression. Of the 570 patients, 171 underwent PN and 399 underwent RN. The type of surgery was not significantly related with CV events. The only factor that significantly increased the risk of CV events in both the univariate (HR 2.67, p=0.006) and multivariate analyses (HR 2.14, p=0.044) was a postoperative estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2. Postoperative eGFR was also a significant risk factor for OS in the univariate analysis (HR 2.38, p=0.0104), but not in the multivariate model. Postoperative renal function was a significant independent predictor of the incidence of subsequent CV events.

DOI： 10.18926/AMO/56069

Gene therapy for prostate cancer: Current status and future prospects

Yasutomo Nasu, Masami Watanabe

Hormone Therapy and Castration Resistance of Prostate Cancer 397 - 406 2018.5

Language：English Publishing type：Part of collection (book) Publisher：Springer Singapore

Prostate is an ideal target organ for gene therapy as a translational research. It has some advantages as follows: prostate is not a life keeping organ, can be approached easily by ultrasound as a routine clinical practice and PSA is a sensitive and useful tumor marker for the evaluation of clinical response. Intraprostatic therapeutic gene transduction (in situ gene therapy) is one of the potent therapeutic options for prostate cancer gene therapy aiming at antimetastatic benefits through the generation of immune cell-mediated cytotoxic activities that affect not only the primary tumor but also metastatic lesion. In this chapter, current outcome and future prospect of prostate cancer gene therapy are discussed.

DOI： 10.1007/978-981-10-7013-6_40

Prognostic impact of bleomycin pulmonary toxicity on the outcomes of patients with testicular cancer

Maruyama Y, Sadahira T, Mitsui Y, Takamoto A, Wada K, Tanimoto R, Kobayashi Y, Araki M, Watanabe M, Watanabe T, Nasu Y

The Journal of Urology 199 ( 4S ) e1131 - e1132 2018.5

Oncological impact of neoadjuvant hormonal therapy on permanent iodine-125 seed brachytherapy in patients with low- and intermediate-risk prostate cancer. International journal

Atsushi Takamoto, Ryuta Tanimoto, Kensuke Bekku, Motoo Araki, Takuya Sadahira, Koichiro Wada, Shin Ebara, Norihisa Katayama, Hiroyuki Yanai, Yasutomo Nasu

International journal of urology : official journal of the Japanese Urological Association 25 ( 5 ) 507 - 512 2018.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy. METHODS: Between January 2004 and November 2014, 564 patients underwent transperineal ultrasonography-guided permanent iodine-125 seed brachytherapy. We retrospectively analyzed low- or intermediate-risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence-free survival, progression-free survival, cancer-specific survival and overall survival. RESULTS: A total of 484 patients with low-risk (259 patients) or intermediate-risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5-year actuarial biochemical recurrence-free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence-free survival outcomes in low- (P = 0.8949) or intermediate-risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate-specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence-free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression-free survival, cancer-specific survival or overall survival. CONCLUSIONS: In patients with low- or intermediate-risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.

DOI： 10.1111/iju.13555

Prognostic impact of bleomycin pulmonary toxicity on the outcomes of patients with germ cell tumors. Reviewed International journal

Yuki Maruyama, Takuya Sadahira, Yosuke Mitsui, Motoo Araki, Koichiro Wada, Ryuta Tanimoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Medical oncology (Northwood, London, England) 35 ( 6 ) 80 - 80 2018.4

Language：English Publishing type：Research paper (scientific journal)

Bleomycin pulmonary toxicity (BPT) has been well described in patients with germ cell tumors treated with bleomycin etoposide and cisplatin chemotherapy (BEP). To assess the prognostic impact of BPT, we retrospectively identified 52 patients who underwent bleomycin etoposide and cisplatin chemotherapy from 2008 to 2017 in our institution, and evaluated the risk factors of BPT and its effect on prognosis. Patients who had received chemotherapy at another institution were excluded. BPT was defined as bleomycin discontinuation in response to pulmonary function test decline, pulmonary symptoms, or interstitial pneumonia on computed tomography without infection. We divided the patients into two groups according to this definition: BPT and non-BPT. Their median age was 34.2 years, and their median body mass index was 22.8 kg/m2. Twenty patients had a smoking history, 37 were diagnosed with non-seminoma, and 20 had lung metastasis. The median cumulative bleomycin dose was 270 mg/body. Fifteen patients were classified into the BPT group and 37 into the non-BPT group. Only body mass index < 22 was identified as a predictor of BPT in multivariable logistic models. Age or use of granulocyte-colony stimulating factor did not have a significant impact. Kaplan-Meier analysis revealed that the presence of BPT had no significant impact on either 5-year overall survival or progression-free survival. Lower body mass index can increase the risk of BPT in patients with germ cell tumors undergoing BEP. However, discontinuation of bleomycin with BPT does not adversely influence the survival outcomes.

DOI： 10.1007/s12032-018-1140-5

Clinical impact of abdominal fat distribution using 3-D computed tomography volumetry on renal function after renal transplantation

Mitsui Y, Sadahira T, Maruyama Y, Takamoto A, Wada K, Tanimoto R, Kobayashi Y, Araki M, Watanabe M, Watanabe T, Nasu Y

The Journal of Urology 199 ( 4S ) e831 2018.4

Prognostic impact of bleomycin pulmonary toxicity on the outcomes of patients with germ cell tumors

Maruyama Y, Sadahira T, Mitsui Y, Araki M, Wada K, Tanimoto R, Kobayashi Y, Watanabe M, Watanabe T, Nasu Y

Med Oncol 35 ( 6 ) 453 - 458 2018.4

Acute Inflammatory Syndrome Paradoxically Induced by de novo Purine Inhibitors Synthesis before Renal Transplantation: A Case Report and Review of the Literature

Maruyama Y, Sadahira T, Mitsui Y, Wada K, Tanimoto R, Nishimura S, Kobayashi Y, Watanabe T, Nasu Y, Araki M

Transplant Proc 50 ( 3 ) 895 - 897 2018.4

SINGLE OR TWO-TIME INTRAVESICAL INSTILLATION OF PIRARUBICIN AFTER TRANSURETHRAL RESECTION OF A SOLITARY NON-MUSCLE INVASIVE BLADDER CANCER: A PROSPECTIVE RANDOMIZED CONTROL STUDY Reviewed

Tanimoto Ryuta, Takashi Saika, Ebara Shin, Kobayashi Yasuyuki, Nasu Ryoji, Daisuke Yamada, Takamoto Hitoshi, Miyaji Yoshiyuki, Nasu Yasutomo, Tsushima Tomoyasu, Kumon Hiromi

JOURNAL OF UROLOGY 199 ( 4 ) E1120 2018.4

Phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer

Nobuaki Matsubara, Satsohi Nagamori, Yoshiaki Wakumoto, Hirotsugu Uemura, Go Kimura, Akira Yokomizo, Hiroaki Kikukawa, Atsushi Mizokami, Takeo Kosaka, Naoya Masumori, Yoshihide Kawasaki, Junji Yonese, Yasutomo Nasu, Satoshi Fukasawa, Takayuki Sugiyama, Seigo Kinuya, Makoto Hosono, Iku Yamaguchi, Hirokazu Tsutsui, Hiroji Uemura

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 23 ( 1 ) 173 - 180 2018.2

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

Radium-223 dichloride (radium-223) is the first targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with bone metastases. This study investigated the efficacy and safety of radium-223 in Japanese patients with symptomatic CRPC and bone metastases.In this open-label, multicenter, phase II study, patients with progressive, symptomatic CRPC and bone metastases were treated with radium-223 (55 kBq/kg, intravenously) in a 4-week cycle for six cycles. The primary endpoint was the percent change in total alkaline phosphatase (ALP) from baseline at 12 weeks. Secondary endpoints included the percent ALP change from baseline to end of treatment (EOT), ALP response rates, percent change in prostate-specific antigen (PSA) from baseline to 12 weeks and EOT, PSA response rates, overall survival (OS), and time to symptomatic skeletal events (SSEs). Adverse events were monitored throughout the study period.Of the 49 Japanese patients (median age 74 years), 28 completed all infusions. Mean percent change in total ALP and PSA from baseline to 12 weeks was -19.3 and +97.4%, respectively. One-year OS and SSE-free rate at the end of active follow-up were 78 and 89%, respectively. The ALP response rate was 31%, while the PSA response rate was 6%. Grade 3/4 treatment-emergent adverse events observed in >= 10% of patients included decreased lymphocyte count (14%), anemia (14%), anorexia (10%), and bone pain (10%).Radium-223 is effective and well tolerated in Japanese patients with CRPC and bone metastases. Results were comparable with the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial.ClinicalTrials.gov NCT01929655.

DOI： 10.1007/s10147-017-1176-0

Mixed 20-peptide cancer vaccine in combination with docetaxel and dexamethasone for castration-resistant prostate cancer: A randomized, double-blind, placebo-controlled, phase 2 trial.

Masanori Noguchi, Gaku Arai, Shin Egawa, Chikara Ohyama, Seiji Naito, Kazumasa Matsumoto, Hirotsugu Uemura, Masayuki Nakagawa, Yasutomo Nasu, Masatoshi Eto, Shigetaka Suekane, Tetsuro Sasada, Shigeki Shichijo, Akira Yamada, Tatsuyuki Kakuma, Kyogo Itoh

JOURNAL OF CLINICAL ONCOLOGY 36 ( 6 ) 2018.2

Induction of cells with prostate cancer stem-like properties from mouse induced pluripotent stem cells via conditioned medium. Reviewed International journal

Naijin Xu, Xiezhao Li, Masami Watanabe, Hideo Ueki, Hao Hu, Na Li, Motoo Araki, Koichiro Wada, Abai Xu, Chunxiao Liu, Yasutomo Nasu, Peng Huang

American journal of cancer research 8 ( 8 ) 1624 - 1632 2018

Language：English Publishing type：Research paper (scientific journal)

Cancer stem cells (CSCs) that closely correlated with tumor growth, metastasis, provide a plausible explanation for chemoresistance and cancer relapse. CSCs are usually isolated and enriched from carcinoma cells, which is inconvenient, low-efficient, and even unreliable. Here, we converted mouse induced pluripotent stem cells (miPSCs) into prostate cancer stem-like cells with carcinoma microenvironment following exposure to conditioned medium (CM) derived from RM9, a mouse prostate cancer cell line. These transformed cells, termed as miPS-RM9CM, displayed CSCs properties, including spheroids morphology and expression of both stemness genes and cancer stem cells surface markers, such as Oct3/4, Sox2, Nanog, Klf-4, c-Myc, CD44, and CD133. In addition, in vivo transplantation experiment was performed to confirm the tumorigenicity. Furthermore, we used the model to assess conventional chemotherapeutic agent, docetaxel. The results showed that miPS-RM9CM cells exhibited increased resistance to docetaxel, however, high susceptibility to the cancer cell stemness inhibitor I (BBI-608). Our current study demonstrates that CM from cultured RM9 cells play a crucial role in the determination of cell fate from miPSCs to cancer stem-like cells and provide a potentially valuable system for the study of CSCs.

Sarcopenia in patients with testicular cancer undergoing chemotherapy :Prognostic impact of psoas major muscle loss

Mitsui Y, Sadahira T, Maruyama Y, Takanoto A, Wada K, Tanimoto R, Kobayashi Y, Araki M, Watanabe M, Watanabe T, Nasu Y

European Urology Supplements 17 ( 2 ) e1137 - e1138 2018

Red nodular melanoma of the penile foreskin: A case report and literature review. International journal

Yuki Maruyama, Takuya Sadahira, Yosuke Mitsui, Koichiro Wada, Ryuta Tanimoto, Yasuyuki Kobayashi, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Molecular and clinical oncology 9 ( 4 ) 449 - 452 2018

Language：English Publishing type：Research paper (scientific journal)

The penis is an extremely rare primary site for malignant melanomas, and the clinical presentation may vary greatly. We herein present the case of a 71-year-old male patient who presented with a 6-year history of two slow growing, asymptomatic red macules on the penile foreskin. On physical examination, the mobility of the foreskin was good, and there was no metastasis on computed tomography and magnetic resonance imaging. The patient underwent segmental circumcision for treatment and histological diagnosis, and the histological examination revealed a malignant melanoma. As cancer cells were identified at the edge of the tissue specimen and computed tomography-positron emission tomography revealed increased uptake of 18F-fluorodeoxyglucose in the penis, wider resection and a right sentinel lymph node biopsy were performed; both specimens came back negative. Two years after the surgery, there has been no evidence of locoregional recurrence or distant metastases. The aim of this report is to alert physicians to include melanoma in the differential diagnosis of red-pigmented lesions of the penile foreskin.

DOI： 10.3892/mco.2018.1697

Impact of selective media for detecting fluoroquinolone-insusceptible/extended-spectrum beta-lactamase-producing Escherichia coli before transrectal prostate biopsy Reviewed

Takuya Sadahira, Koichiro Wada, Motoo Araki, Ayano Ishii, Toyohiko Watanabe, Yoshitsugu Nasu, Masaya Tsugawa, Tadasu Takenaka, Yasutomo Nasu, Hiromi Kumon

INTERNATIONAL JOURNAL OF UROLOGY 24 ( 12 ) 842 - 847 2017.12

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

ObjectivesTo investigate the prevalence of fluoroquinolone-insusceptible and/or extended-spectrum beta-lactamase-producing Escherichia coli colonizing in the male rectum before transrectal prostate biopsy.
MethodsWe carried out a prospective cohort study of men undergoing transrectal prostate biopsy. CHROMagar Orientation originally supplemented with levofloxacin and CHROMagar Orientation/extended-spectrum beta-lactamase were used for detecting fluoroquinolone-insusceptible and extended-spectrum beta-lactamase-producing Escherichia coli. Rectal specimens were collected before prostate biopsy, and the results of cultures in the selective medium were compared with drug susceptibility measured by standard methods. Targeted prophylactic antimicrobials were administered to patients with drug-resistant Escherichia coli and the incidence of postoperative prostatitis was investigated. In the case of prostatitis, pathogens preoperatively isolated from the rectum and those from urine were compared using pulsed-field gel electrophoresis.
ResultsRectal colonization of fluoroquinolone-insusceptible or extended-spectrum beta-lactamase-producing Escherichia coli was detected in 217 of 694 (31.3%) and 85 of 640 (13.3%) participants, respectively. The sensitivity and specificity of fluoroquinolone-insusceptible selective media were 96.8% and 88.2%, respectively. A total of 618 participants underwent transrectal prostate biopsy, and postoperative acute prostatitis was observed in four of 618 (0.6%) participants. Escherichia coli strains isolated preoperatively from the rectum and postoperatively from urine were found to be identical.
ConclusionsThe present findings showed accuracy and performance of the selective media. Screening cultures before transrectal prostate biopsy using selective media seems to be helpful for guiding antibiotic prophylaxis and thus decreasing the rate of post-biopsy acute prostatitis.

DOI： 10.1111/iju.13447

Exogenous DKK-3/REIC inhibits Wnt/beta-catenin signaling and cell proliferation in human kidney cancer KPK1 Reviewed

Jiaqi Xu, Takuya Sadahira, Rie Kinoshita, Shun-Ai Li, Peng Huang, Koichiro Wada, Motoo Araki, Kazuhiko Ochiai, Hirofumi Noguchi, Masakiyo Sakaguchi, Yasutomo Nasu, Masami Watanabe

ONCOLOGY LETTERS 14 ( 5 ) 5638 - 5642 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

The third member of the Dickkopf family (DKK-3), also known as reduced expression in immortalized cells (REIC), is a tumor suppressor present in a variety of tumor cells. Regarding the regulation of the Wnt/beta-catenin signaling pathway, exogenous DKK-1 and DKK-2 are reported to inhibit Wnt signaling by binding the associated effectors. However, whether exogenous DKK-3 inhibits Wnt signaling remains unclear. A recombinant protein of human full-length DKK-3 was used to investigate the exogenous effects of the protein in vitro in KPK1 human renal cell carcinoma cells. It was demonstrated that the expression of phosphorylated (p-)beta-catenin (inactive form as the transcriptional factor) was increased in KPK1 cells treated with the exogenous DKK-3 protein. The levels of non-p-beta-catenin (activated form of beta- catenin) were consistently decreased. It was revealed that the expression of transcription factor (TCF) 1 and c-Myc, the downstream transcription factors of the Wnt/beta-catenin signaling pathway, was inhibited following treatment with DKK-3. A cancer cell viability assay confirmed the anti-proliferative effects of exogenous DKK-3 protein, which was consistent with a suppressed Wnt/beta-catenin signaling cascade. In addition, as low-density lipoprotein receptor-related protein 6 (LRP6) is a receptor of DKK-1 and DKK-2 and their interaction on the cell surface inhibits Wnt/beta-catenin signaling, it was examined whether the exogenous DKK-3 protein affects LRP6-mediated Wnt/beta-catenin signaling. The LRP6 gene was silenced and the effects of DKK-3 on the time course of the upregulation of p-beta-catenin expression were subsequently analyzed. Notably, LRP6 depletion elevated the base level of p-beta-catenin; however, there was no significant effect on its upregulation course or expression pattern. These findings indicate that exogenous DKK-3 upregulates p-beta-catenin and inhibits Wnt/beta-catenin signaling in an LRP6-independent manner. Therefore, exogenous DKK-3 protein may inhibit the proliferation of KPK1 cells via inactivating Wnt/beta-catenin signaling.

DOI： 10.3892/ol.2017.6833

岡山大学病院における鏡視下ドナー腎採取術の検討

西村慎吾, 荒木元朗, 小林泰之, 山下里美, 河村香澄, 光井洋介, 吉岡貴史, 有吉勇一, 和田耕一郎, 渡辺豊彦, 那須保友

移植 52 ( 4-5 ) 478 - 478 2017.11

岡山大学病院における腹腔鏡下膀胱全摘除術の検討

大岩裕子, 小林泰之, 杉本盛人, 高本篤, 和田耕一郎, 荒木元朗, 渡邉豊彦, 那須保友, 佃和憲, 佐々木克己

Japanese Journal of Endourology 30 ( 3 ) 258 - 258 2017.11

腹腔鏡手術〜初心者に何をどう教えるべきか〜ロボット支援腹腔鏡下手術時代における腹腔鏡教育

小林泰之, 和田耕一郎, 谷本竜太, 杉本盛人, 荒木元朗, 渡辺豊彦, 那須保友

Japanese Journal of Endourology 30 ( 3 ) 126 - 126 2017.11

Ureterolithotripsy for a Ureteral Calculus at the Ureteroureterostomy of a Renal-transplant Recipient Reviewed

Yosuke Mitsui, Koichiro Wada, Motoo Araki, Takashi Yoshioka, Yuichi Ariyoshi, Shingo Nishimura, Yasuyuki Kobayashi, Katsumi Sasaki, Toyohiko Watanabe, Yasutomo Nasu

ACTA MEDICA OKAYAMA 71 ( 5 ) 449 - 452 2017.10

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

We describe a 40-year-old living-donor renal-transplant recipient who underwent successful ureterolithotripsy. He had been on hemodialysis for >15 years pre-transplant and underwent ureteroureterostomy along with the surgery. One year post-transplant, ultrasound examination demonstrated hydronephrosis, and CT showed a 6-mm ureteral calculus at the ureteroureterostomy site. No pain and no elevated serum creatinine were present. As the ureter was easily accessed, we performed a ureterolithotripsy, which would confirm whether a suture caused the calculus. Despite ureteral tortuosity, laser stone fragmentation succeeded. The calculus was completely removed with an antegrade guidewire. Mild postoperative ureteral stenosis resolved with a temporary ureteral stent without balloon dilation. Ureterolithotripsy is effective even in renal transplant recipients with ureteroureterostomy.

DOI： 10.18926/AMO/55445

Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf-3 expressing adenoviral vector for hepatocellular carcinoma Reviewed

Hiroaki Sawahara, Hidenori Shiraha, Daisuke Uchida, Hironari Kato, Ryo Kato, Atsushi Oyama, Teruya Nagahara, Masaya Iwamuro, Shigeru Horiguchi, Koichiro Tsutsumi, Mari Mandai, Tetsushige Mimura, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Masami Watanabe, Masakiyo Sakaguchi, Akinobu Takaki, Kazuhiro Nouso, Takahito Yagi, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Okada

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 32 ( 10 ) 1769 - 1777 2017.10

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Background and Aim: Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC/Dkk-3-expressing adenoviral vector (Ad-REIC) was found to induce cancer-selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re-construct an Ad-REIC vector, termed the Ad-SGE-REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad-SGE-REIC on hepatocellular carcinoma (HCC) was assessed.
Methods: Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK-Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1-6) were used in this study. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined in vitro, and the anti-tumor effects of Ad-SGE-REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti-tumor immunological effects on the immunocompetent mice.
Results: REIC/Dkk-3 expression was decreased in HCC cell lines and HCC tissues. Ad-SGE-REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated in vivo anti-cancer immunostimulatory effects on the HCC cell line (Hepa1-6).
Conclusions: Ad-SGE-REIC treatment not only enhanced cell killing effects in vitro but also elicited significant therapeutic effects, with tumor growth suppression, in vivo. REIC/Dkk-3 gene therapy using Ad-SGE-REIC potentially represents an innovative new therapeutic tool for HCC.

DOI： 10.1111/jgh.13757

Effects of Cold Ischemia on RNA Stability and Quality of Lung Tissues Based on Standard PREanalytical Code Categorization. International journal

Takehiro Matsubara, Shuta Tomida, Junichi Soh, Takahiro Uwabo, Yoshiko Mori, Mizuki Morita, Yasutomo Nasu, Susumu Kanazawa, Shinichi Toyooka

Biopreservation and biobanking 15 ( 5 ) 484 - 486 2017.10

高位精巣摘除術14年後に再発を認めたStageIセミノーマの1例

和田里章悟, 高本篤, 和田耕一郎, 堀川雄平, 丸山雄樹, 西村慎吾, 甲斐誠二, 杉本盛人, 谷本竜太, 小林泰之, 荒木元朗, 渡辺豊彦, 那須保友

西日本泌尿器科 79 ( 増刊 ) 145 - 145 2017.10

Overexpression of REIC/Dkk-3 suppresses the expression of CD147 and inhibits the proliferation of human bladder cancer cells Reviewed

Yuhei Horikawa, Masami Watanabe, Takuya Sadahirai, Yuichi Ariyoshi, Yasuyuki Kobayashi, Motoo Araki, Koichiro Wada, Kazuhiko Ochiai, Shun-Ai Li, Yasutomo Nasu

ONCOLOGY LETTERS 14 ( 3 ) 3223 - 3228 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Our group previously developed an adenoviral vector encoding the REIC/Dkk-3 gene (Ad-REIC), a tumor suppressor, for cancer gene therapy. The Ad-REIC agent induces apoptosis and inhibits invasion in a number of cancer cell lines; however, the molecular mechanisms underlying its effects remain unclear. Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a key molecule that promotes cancer proliferation and invasion. In order to elucidate the therapeutic mechanism of Ad-REIC, its effect on the expression of CD147 in human bladder cancer KK47 cells was investigated. Treatment with Ad-REIC markedly downregulated the expression of CD147 and significantly inhibited cellular proliferation. Since the expression of CD147 is reported to be under the positive control of mitogen-activated protein kinase (MAPK) signaling and the c-Myc protein, the correlations between the expression of CD147 and the activation of MAPKs or the expression of c-Myc were examined. Unexpectedly, no positive correlation was observed between the level of CD147 and the potential regulators that were assessed, indicating that another signaling pathway is responsible for the downregulation of CD147. The results from the present study demonstrate that Ad-REIC treatment can significantly downregulate the expression of CD147 in bladder cancer cells. Downregulation of the cancer-progression factor CD147 may be a novel mechanism that underlies the therapeutic effects of Ad-REIC treatment.

DOI： 10.3892/ol.2017.6548

腎細胞癌に合併し腎摘により改善した腎アミロイドーシスの1例

加納弓月, 北川正史, 山村裕理子, 加藤綾子, 木野村賢, 杉山斉, 小林泰之, 那須保友, 和田淳

日本腎臓学会誌 59 ( 6 ) 749 - 749 2017.9

Robotic Renal Autotransplantation: First Case Outside of North America Reviewed

Motoo Araki, Koichiro Wada, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Takashi Yoshioka, Yuichi Ariyoshi, Kei Fujio, Atsushi Takamoto, Morito Sugimoto, Katsumi Sasaki, Yasuyuki Kobayashi, Shin Ebara, Hideki Taninishi, Hiroyuki Amano, Masashi Inui, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

ACTA MEDICA OKAYAMA 71 ( 4 ) 351 - 355 2017.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

A 38-year-old woman with a 2.7-cm left ureteral stenosis requiring chronic ureteral stent exchange elected to undergo robotic renal autotransplantation. Left ureteropelvic junction obstruction (UPJO) was also suspected. Robotic donor nephrectomy contributed to the fine dissection for desmoplastic changes. The kidney was removed through a Gelport and examined on ice. UPJO was not seen. An end-to-side robotic anastomosis was created between the renal and external iliac vessels. The console time was 507 min, and the warm ischemia time was 4 min 5 sec. She became stent-free. Robotic renal autotransplantation is a new, minimally invasive approach to renal preservation.

DOI： 10.18926/AMO/55313

Antimicrobial susceptibilities of Chlamydia trachomatis isolated from the urethra and pharynx of Japanese males Reviewed

Seiji Kai, Koichiro Wada, Takuya Sadahira, Motoo Araki, Ayano Ishii, Toyohiko Watanabe, Koichi Monden, Satoshi Uno, Tohru Araki, Yasutomo Nasu

JOURNAL OF INFECTION AND CHEMOTHERAPY 23 ( 8 ) 512 - 516 2017.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Objectives: Sexually transmitted infections due to Chlamydia trachomatis (C. trachomatis) are a worldwide public health problem. The aim of this study was to investigate the drug susceptibilities of C. trachomatis strains isolated from the urethra and pharynx of Japanese males.
Methods: Urethral and pharyngeal swabs were collected between 2013 and 2014 from Japanese males with urethritis. Using a McCoy cell line, 18 chlamydial strains were isolated from urethra in 18 patients and 7 from the pharynx in 7 of the 18 patients. The minimum inhibitory concentrations (MICs) of levofloxacin (LVFX) and azithromycin (AZM) were measured using the standard method of the Japanese Society of Chemotherapy.
Results: The MICs of LVFX and AZM against urethral chlamydial strains were 0.125-0.5 mu g/mL and 0.125-0.25 mu g/mL, respectively. In pharyngeal strains, the MICs of LVFX and AZM were 0.125-0.25 mu g/mL and 0.125-0.25 mu g/mL, respectively. In 7 patients with chlamydial strains isolated from both the urethra and pharynx, the MICs of LVFX between these strains were identical in 3 of 6 patients (no growth was observed for one pharyngeal strain), while the MICs of AZM between these strains were identical in all 6 patients (not performed for one patient).
Conclusions: Our data suggest that C. trachomatis strains isolated from the urethra and pharynx of Japanese males are susceptible to LVFX and AZM. Although measuring the MICs of chlamydial strains is labor intensive, it is a significant surveillance tool for treating chlamydial infections and preventing the spread of STIs. (C) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2017.04.005

Robust cancer-specific gene expression by a novel cassette with hTERT and CMV promoter elements Reviewed

Masakiyo Sakaguchi, Takuya Sadahira, Hideo Ueki, Rie Kinoshita, Hitoshi Murata, Ken-Ichi Yamamoto, Junichiro Futami, Yasutomo Nasu, Kazuhiko Ochiai, Hiromi Kumon, Nam-Ho Huh, Masami Watanabe

ONCOLOGY REPORTS 38 ( 2 ) 1108 - 1114 2017.8

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

We developed and validated a novel hTERT/CMV promoter element-driven gene expression cassette that can robustly enhance cancer-specific gene expression. The following gene expressional elements were located in tandem within the plasmid construct: [hTERT core promoter, cytomegalovirus (CMV) minimized promoter, RU5' sequence, an inserted gene, BGH polyA, hTERT enhancer]; this is hereafter referred to as the hT/Cm-R-hT construct. Using various human cancer cell lines and normal cells, the cancer-specific transcription of the green fluorescent protein (GFP) gene was examined by western blotting and fluorescence microscopy. Cancer-specific gene expression was robustly achieved in the hT/Cm-R-hT plasmid in comparison to the other control hT/Cm-driven construct. Notably, the expression level of GFP observed in the hT/Cm-RhT-driven construct was superior to that of the control plasmid with the conventional CMV promoter in HEK293 cells, which are known to possess higher hTERT activity than normal cells. We next examined the availability of hT/Cm-R-hT in detecting the target GFP expressing cancer cells from human peripheral blood mononuclear cells (PBMCs). The hT/Cm-R-hT plasmid successfully induced cancer-specific gene expression; the robust expression of GFP was observed in target HeLa cancer cells, whereas GFP was not visibly expressed in normal PBMCs. The plasmid allowed for the selective visualization of viable HeLa cancer cells in mixed cell cultures containing up to 10000-fold more PBMCs. These findings indicate that the hT/Cm-R-hT expressional system is a valuable tool for detecting viable cancer cells mixed with normal cells. The current system can therefore be applied to the in vitro detection of cancer cells that are disseminated in the blood and other types of body fluid in vivo. Since the current system can also be applied to other types of vectors, including virus vectors, this approach using the hTERT promoter-based construct is expected to become a valuable tool for enhancing cancer specific gene expression.

DOI： 10.3892/or.2017.5710

生体腎移植レシピエントにおける予防的抗菌薬と周術期感染症に関する後ろ向き調査

和田耕一郎, 荒木元朗, 西村慎吾, 山下里美, 河村香澄, 光井洋介, 吉岡貴史, 有吉勇一, 小林泰之, 渡邉豊彦, 北川正史, 田邊克幸, 杉山斉, 和田淳, 那須保友

移植 52 ( 総会臨時 ) 467 - 467 2017.8

岡山大学病院における鏡視下ドナー腎採取術の検討

西村慎吾, 荒木元朗, 小林泰之, 山下里美, 河村香澄, 光井洋介, 吉岡貴史, 有吉勇一, 和田耕一郎, 渡辺豊彦, 那須保友

移植 52 ( 総会臨時 ) 422 - 422 2017.8

Expression of tumor suppressor REIC/Dkk-3 by a newly improved adenovirus vector with insertion of a hTERT promoter at the 3'-side of the transgene Reviewed

Endy Widya Putranto, Rie Kinoshita, Masami Watanabe, Takuya Sadahira, Hitoshi Murata, Ken-Ichi Yamamoto, Junichiro Futami, Ken Kataoka, Yusuke Inoue, I. Made Winarsa Ruma, I. Wayan Sumardika, Chen Youyi, Miyoko Kubo, Yoshihiko Sakaguchi, Kenji Saito, Yasutomo Nasu, Hiromi Kumon, Nam-Ho Huh, Masakiyo Sakaguchi

ONCOLOGY LETTERS 14 ( 1 ) 1041 - 1048 2017.7

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3) overexpression, induced using an adenovirus (Ad)-REIC, has been revealed to have a dramatic therapeutic effect on multiple types of cancer. To achieve an improved therapeutic effect from Ad-REIC on cancer, our group previously developed an enhanced gene expression system, the C-TSC cassette [cytomegalovirus (CMV)-RU5' located upstream (C); another promoter unit composed of triple tandem promoters, human telomerase reverse transcriptase (hTERT), simian virus 40 and CMV, located downstream of the cDNA (TSC); plus a polyadenylation (polyA) signal]. When applied to the conventional Ad-REIC, this novel system induced the development of an enhanced product, Ad-C-TSC-REIC, which exhibited a noticeable anticancer effect. However, there were difficulties in terms of Ad-C-TSC-REIC productivity in HEK293 cells, which are a widely used donor cell line for viral production. Productivity of Ad-C-TSC-REIC was significantly reduced compared with the conventional Ad-REIC, as the Ad-C-TSC-REIC had a significantly higher ability to induce apoptotic cell death of not only various types of cancer cell, but also HEK293 cells. The present study aimed to overcome this problem by modifying the C-TSC structure, resulting in an improved candidate: A C-T cassette (C: CMV-RU5' located upstream; T: another promoter unit composed of a single hTERT promoter, located downstream of the cDNA plus a polyA signal), which demonstrated gene expression comparable to that of the C-TSC system. The improved adenovirus REIC/Dkk-3 product with the C-T cassette, named Ad-C-T-REIC, exhibited a higher expression level of REIC/Dkk3, similar to that of Ad-C-TSC-REIC. Notably, the vector mitigated the cell death of donor HEK293 cells, resulting in a higher rate of production of its adenovirus. These results indicated that Ad-C-T-REIC has the potential to be a useful tool for application in cancer gene therapy.

DOI： 10.3892/ol.2017.6201

Successful microscopic renal autotransplantation for left renal aneurysm associated with segmental arterial mediolysis. International journal

Takashi Yoshioka, Motoo Araki, Yuichi Ariyoshi, Koichiro Wada, Noriyuki Tanaka, Yasutomo Nasu

Journal of vascular surgery 66 ( 1 ) 261 - 264 2017.7

Language：English Publishing type：Research paper (scientific journal)

Segmental arterial mediolysis (SAM) is an uncommon, nonarteriosclerotic vascular disease. SAM is characterized by lysis of arterial media and can lead to aneurysm formation. The renal arteries are the third most common arteries associated with SAM. We report the case of a 32-year-old man with left renal artery aneurysm associated with SAM. We successfully performed left renal autotransplantation using microscopic vascular reconstruction. SAM is characterized by vascular fragility; therefore, microscopic surgery is favorable for treating aneurysms associated with SAM.

DOI： 10.1016/j.jvs.2016.09.039

Tracking and Imaging of Tumor Progression and Immune Function in a Preclinical Mouse Model

Peng Huang, Naijin Xu, Eiji Matsuura, Masami Watanbe, Hiromi Kumon, Yasutomo Nasu, Chunxiao Liu

MOLECULAR THERAPY 25 ( 5 ) 98 - 98 2017.5

The Downregulation of the Expression of CD147 by Tumor Suppressor REIC/Dkk-3, and Its Implication in Human Prostate Cancer Cell Growth Inhibition Reviewed

Akihiro Mori, Masami Watanabe, Takuya Sadahira, Yasuyuki Kobayashi, Yuichi Ariyoshi, Hideo Ueki, Koichiro Wada, Kazuhiko Ochiai, Shun-Ai Li, Yasutomo Nasu

ACTA MEDICA OKAYAMA 71 ( 2 ) 135 - 142 2017.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

DOI： 10.18926/AMO/54982

Clinical pharmacokinetics of oral levofloxacin and sitafloxacin in epididymal tissue Reviewed

Takuya Sadahira, Koichiro Wada, Kazuro Ikawa, Norifumi Morikawa, Hiroaki Kurahashi, Takashi Yoshioka, Yuichi Ariyoshi, Yasuyuki Kobayashi, Motoo Araki, Ayano Ishii, Masami Watanabe, Shinya Uehara, Toyohiko Watanabe, Yasutomo Nasu

JOURNAL OF INFECTION AND CHEMOTHERAPY 23 ( 4 ) 214 - 217 2017.4

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Objectives: This study aimed to investigate the penetration of fluoroquinolones into human epididymal tissue.
Methods: The penetration of levofloxacin (LVFX) 500 mg or sitafloxacin (STFX) 100 mg into epididymal tissue was examined. Patients with prostate cancer who were referred for orchiectomy were included. LVFX 500 mg (n = 9) or STFX 100 mg (n = 9) was administered orally 1 h before orchiectomy, and 0.5 g of epididymal tissue and blood samples were collected simultaneously during surgery. Drug concentrations were measured by high-performance liquid chromatography, and patient characteristics and adverse events were analyzed.
Results: The mean ratio of the epididymal concentration to the serum concentration was 1.48 +/- 0.45 for LVFX and 1.54 +/- 0.81 for STFX. For LVFX, the simulated curves estimated the following: maximum concentrations (Cmax) of 8.84 mu g/ml in serum and 14.1 mu g/g in epididymal tissue and area under the concentration-time curve for 24 h (AUC(24)) of 68.5 mu g h/ml in serum and 108.9 mu g h/g in epididymal tissue. For STFX, the Cmax was 1.22 mu g/ml in serum and 1.66 mu g/g in epididymal tissue, and the AUC24 was 9.58 mu g h/ml in serum and 13.1 mu g h/g in epididymal tissue. Neither treatment-related adverse events nor postoperative urogenital infections were observed.
Conclusions: The results of this study suggest that oral administration of LVFX 500 mg or STFX 100 mg achieves effective epididymal concentrations for treatment of epididymitis. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2016.12.010

A Combination Therapy of Partial Nephrectomy and Cryoablation Achieved Good Cancer Control and Renal Function in Bilateral Synchronous Renal Cell Carcinoma Reviewed

Atsushi Takamoto, Motoo Araki, Koichiro Wada, Morito Sugimoto, Yasuyuki Kobayashi, Katsumi Sasaki, Toyohiko Watanabe, Yasutomo Nasu

ACTA MEDICA OKAYAMA 71 ( 2 ) 187 - 190 2017.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

DOI： 10.18926/AMO/54989

Evaluation of Urinary Stone Composition and Differentiation between Urinary Stones and Phleboliths Using Single-source Dual-energy Computed Tomography.

Nanako Ogawa, Shuhei Sato, Kentaro Ida, Katsuya Kato, Yuichi Ariyoshi, Koichiro Wada, Yasutomo Nasu, Susumu Kanazawa

Acta medica Okayama 71 ( 2 ) 91 - 96 2017.4

Language：English Publishing type：Research paper (bulletin of university, research institution)

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.

DOI： 10.18926/AMO/54976

Impact of Surgeon and Hospital Volume on the Safety of Robot-Assisted Radical Prostatectomy: A Multi-Institutional Study Based on a National Database

Yosuke Hirasawa, Kunihiko Yoshioka, Yasutomo Nasu, Masumi Yamamoto, Shiro Hinotsu, Atsushi Takenaka, Masato Fujisawa, Ryoichi Shiroki, Keiichi Tozawa, Satoshi Fukasawa, Akira Kashiwagi, Katsunori Tatsugami, Masaaki Tachibana, Toshiro Terachi, Momokazu Gotoh

Urologia Internationalis 98 ( 3 ) 334 - 342 2017.4

Publishing type：Research paper (scientific journal)

© 2017 S. Karger AG, Basel. Introduction: We aimed to perform a multi-institutional study using a national database led by the Japanese Society of Endourology to investigate the effect of surgeon or hospital volume on the safety of robot-assisted radical prostatectomy (RARP). Materials and Methods: Clinical data of 3,214 patients who underwent RARP for the treatment of clinically localized prostate cancer between April 2012 and March 2013 in Japan were evaluated. Surgical outcomes and all intra-A nd perioperative complications were collected. Results: The intraoperative complication rate was 0.56%. In a total number of 241 patients, 261 perioperative complications were observed. The following percentages of patients presented the Clavien-graded complications: 7.2%, grades 1-2; 0.84%, grade 3; and 0.093%, grade 4a. No cases of multiple organ dysfunction or death (grades 4b and 5) were found. Multivariable logistic regression analysis showed that the hospital volume (OR 3.6; p = 0.010) for intraoperative complications and surgeon volume (OR 0.19; p < 0.0001) and extended lymph node discectomy (OR 3.9; p < 0.0001) for perioperative complications were significant independent risk factors. Conclusions: Hospital volume for intraoperative complications and surgeon volume and extended lymph node dissection for perioperative complications were significantly associated with increased risk of each complication in RARP.

DOI： 10.1159/000460304

ロボット手術の最前線

荒木元朗, 小林泰之, 和田耕一郎, 渡辺豊彦, 那須保友

IVR: Interventional Radiology 32 ( Suppl. ) 101 - 101 2017.4

岡山大学病院におけるロボット支援腎部分切除術の経験

小林泰之, 荒木元朗, 谷本竜太, 西村慎吾, 高本篤, 堀川雄平, 和田耕一郎, 杉本盛人, 佐々木克己, 渡邊豊彦, 那須保友

日本泌尿器科学会総会 105回 SKH12 - 3 2017.4

BENEFICAL EFFECT OF HYDROGEN SULFIDE ON RENAL ISCHEMIA-REPERFUSION INJURY IN CLAWN MINIATURE SWINE

Yuichi Ariyoshi, Mitsuhiro Sekijima, Takahiro Murokawa, Hisashi Sahara, Motoo Araki, Yasutomo Nasu, Kazuhiko Yamada

JOURNAL OF UROLOGY 197 ( 4 ) E77 - E78 2017.4

Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the growth inhibitor lycorine in a mouse model of renal cell carcinoma Reviewed

Xiezhao Li, Peng Xu, Chongshan Wang, Naijin Xu, Abai Xu, Yawen Xu, Takuya Sadahira, Motoo Araki, Koichiro Wada, Eiji Matsuura, Masami Watanabe, Junxia Zheng, Pinghua Sun, Peng Huang, Yasutomo Nasu, Chunxiao Liu

ONCOTARGET 8 ( 13 ) 21177 - 21186 2017.3

Language：English Publishing type：Research paper (scientific journal) Publisher：IMPACT JOURNALS LLC

Renal cell carcinoma (RCC) management has undergone a major transformation over the past decade; immune checkpoint inhibitors are currently undergoing clinical trials and show promising results. However, the effectiveness of immune checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited. Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is touted as a potential anti-cancer drug because of its demonstrative growth inhibition capacity (induction of cell cycle arrest and inhibition of vasculogenic mimicry formation). Moreover, T cell checkpoint blockade therapy with antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4) has improved outcomes in cancer patients. However, the anti-tumor efficacy of combined lycorine and anti-CTLA-4 therapy remains unknown. Thus, we investigated a combination therapy of lycorine hydrochloride and anti-CTLA-4 using a murine RCC model. As a means of in vitro confirmation, we found that lycorine hydrochloride inhibited the viability of various RCC cell lines. Furthermore, luciferase-expressing Renca cells were implanted in the left kidney and the lung of BALB/c mice to develop a RCC metastatic mouse model. Lycorine hydrochloride and anti-CTLA-4 synergistically decreased tumor weight, lung metastasis, and luciferin-staining in tumor images. Importantly, the observed anti-tumor effects of this combination were dependent on significantly suppressing regulatory T cells while upregulating effector T cells; a decrease in regulatory T cells by 31.43% but an increase in effector T cells by 31.59% were observed in the combination group compared with those in the control group). We suggest that a combination of lycorine hydrochloride and anti-CTLA-4 is a viable therapeutic option for RCC patients.

DOI： 10.18632/oncotarget.15505

Reality of nerve sparing and surgical margins in surgeons’ early experience with robot-assisted radical prostatectomy in Japan

Katsunori Tatsugami, Kunihiko Yoshioka, Ryoichi Shiroki, Masatoshi Eto, Yasushi Yoshino, Keiichi Tozawa, Satoshi Fukasawa, Masato Fujisawa, Atsushi Takenaka, Yasutomo Nasu, Akira Kashiwagi, Momokazu Gotoh, Toshiro Terachi

International Journal of Urology 24 ( 3 ) 191 - 196 2017.3

Language：English Publishing type：Research paper (scientific journal)

© 2017 The Japanese Urological Association Objective: To analyze nerve sparing performance at an early stage of robot-assisted radical prostatectomy, and the correlation between the surgeons’ experience and the risk of a positive surgical margin in patients treated with robot-assisted radical prostatectomy. Methods: Patients’ records from January 2009 to March 2013 were retrospectively reviewed, and 3469 patients with localized prostate cancer were identified at 45 institutions. Individual surgeon's experience with nerve sparing was recorded as the number of nerve sparing cases among total robot-assisted radical prostatectomies beginning with the first case during which nerve sparing was carried out. Patients were selected by propensity score matching for nerve sparing, and predictive factors of positive surgical margins were analyzed in patients with and without positive surgical margins. Results: A total of 152 surgeons were studied, and the median number of robot-assisted radical prostatectomy cases for all surgeons was 21 (range 1–511). In all, 54 surgeons (35.5%) undertook nerve sparing during their first robot-assisted radical prostatectomy case. For 2388 patients selected with (1194) and without (1194) nerve sparing, predictive factors for positive surgical margin were high initial prostate-specific antigen level (P < 0.0001), high biopsy Gleason score (P = 0.0379), presence of neoadjuvant hormone therapy (P = 0.0002) and surgeon's experience with >100 cases (P = 0.0058). Thus, nerve sparing was not associated with positive surgical margins. Conclusion: The surgeon's experience influences the occurrence of positive surgical margins, although a considerable number of surgeons carried out nerve sparing during their early robot-assisted radical prostatectomy cases. Surgeons should consider their own experience and prostate cancer characteristics before carrying out a nerve sparing robot-assisted radical prostatectomy.

DOI： 10.1111/iju.13281

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 Reviewed

Takahiro Waki, Kuniaki Katsui, Toshiharu Mitsuhashi, Takeshi Ogata, Norihisa Katayama, Mitsuhiro Takemoto, Yasutomo Nasu, Hiromi Kumon, Susumu Kanazawa

ACTA MEDICA OKAYAMA 71 ( 1 ) 31 - 39 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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 3.111.3 mm) respectively in an adjusted regression model. SV motion did not differ between the ADT and nonADT 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.

DOI： 10.18926/AMO/54823

Efficacy and safety of 3 day versus 7 day cefditoren pivoxil regimens for acute uncomplicated cystitis: multicentre, randomized, open-label trial Reviewed

Takuya Sadahira, Koichiro Wada, Motoo Araki, Ayano Ishii, Atsushi Takamoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 72 ( 2 ) 529 - 534 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

Background: Fluoroquinolone-non-susceptible Escherichia coli isolated from patients with acute uncomplicated cystitis are a matter of increasing concern. Cefditoren pivoxil is an oral, beta-lactamase-stable, extended-spectrum cephalosporin that is effective against fluoroquinolone-non-susceptible bacteria.
Objectives: To evaluate the clinical and microbiological efficacies of cefditoren pivoxil against acute uncomplicated cystitis and to determine the optimal duration of cefditoren pivoxil treatment.
Methods: We compared 3 and 7 day regimens of cefditoren pivoxil in a multicentre, randomized, open-label study.
Results: A total of 104 female patients with acute uncomplicated cystitis were enrolled and randomized into 3 day (n = 51) or 7 day (n = 53) treatment groups. At first visit, 94 bacterial strains were isolated from the 104 participants of which 81.7% (85/104) were E. coli. Clinical and microbiological efficacies were evaluated 59 days following administration of the final dose of cefditoren pivoxil. The clinical efficacies of the 3 and 7 day groups were 90.9% (40/44) and 93.2% (41/44), respectively (P = 1.000). The microbiological efficacies of the 3 and 7 day groups were 82.5% (33/40) and 90.2% (37/41), respectively (P = 0.349). There were no adverse events due to cefditoren pivoxil treatment, with the exception of a mild allergic reaction in one patient, after which the cefditoren pivoxil was exchanged for another antimicrobial.
Conclusions: Cefditoren pivoxil is safe and effective for uncomplicated cystitis, with no significant differences in clinical and microbiological efficacies between 3 and 7 day regimens.

DOI： 10.1093/jac/dkw424

The Prostate in Female? Clear Cell Adenocarcinoma in a Female Urethral Diverticulum Reviewed

Takuya Sadahira, Yuuki Maruyama, Motoo Araki, Yasuyuki Kobayashi, Toyohiko Watanabe, Yasutomo Nasu

UROLOGY 99 E25 - E26 2017.1

Language：English Publisher：ELSEVIER SCIENCE INC

Urethral diverticular clear cell adenocarcinoma in a female patient is extremely rare. This tumor sometimes displays a characteristic image on magnetic resonance imaging, surrounding the urethra like the prostate does in men. We report a patient with this tumor who underwent cystourethrectomy and ileal conduit diversion. We think that imaging studies could be useful to make the appropriate diagnosis. UROLOGY 99: e25-e26, 2017. (C) 2016 Elsevier Inc.

DOI： 10.1016/j.urology.2016.10.021

Distant Bystander Effect of REIC/DKK3 Gene Therapy Through Immune System Stimulation in Thoracic Malignancies Reviewed

Ken Suzawa, Kazuhiko Shien, Huang Peng, Masakiyo Sakaguchi, Masami Watanabe, Shinsuke Hashida, Yuho Maki, Hiromasa Yamamoto, Shuta Tomida, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Yasutomo Nasu, Hiromi Kumon, Shinichiro Miyoshi, Shinichi Toyooka

ANTICANCER RESEARCH 37 ( 1 ) 301 - 307 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：INT INST ANTICANCER RESEARCH

Background: Reduced expression in immortalized cell (REIC)/Dickkoph-3 (DKK3) is a tumor-suppressor gene, and its overexpression by adenovirus vector (Ad-REIC) exhibits a remarkable therapeutic effect on various human cancer types through a mechanism triggered by endoplasmic reticulum stress. Materials and Methods: We examined the direct anti-tumor effect of Ad-REIC gene therapy on lung cancer and malignant mesothelioma cell lines in vitro, and the distant bystander effect using immunocompetent mouse allograft models with bilateral flank tumors. Results: Ad-REIC treatment showed antitumor effect in many lung cancer and malignant mesothelioma cell lines in vitro. In an in vivo model, Ad-REIC treatment inhibited the growth not only of directly treated tumors but also of distant untreated tumors. By immunohistochemical analysis, infiltration of T-cells and natural killer (NK) cells and expression of the major histocompatibility complex (MHC) class I molecules were observed in bilateral tumors. Conclusion: Ad-REIC treatment not only had a direct antitumor effect but also an indirect bystander effect through stimulation of the immune system.

DOI： 10.21873/anticanres.11321

Value of percutaneous needle biopsy of small renal tumors in patients referred for cryoablation Reviewed

Toshihiro Iguchi, Takao Hiraki, Hideo Gobara, Hiroyasu Fujiwara, Jun Sakurai, Yusuke Matsui, Motoo Araki, Yasutomo Nasu, Susumu Kanazawa

MINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES 26 ( 2 ) 86 - 91 2017

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Purpose: To retrospectively evaluate the safety and diagnostic yield of needle biopsy of small renal tumors, and the clinical consequences of performing needle biopsy in patients referred for percutaneous cryoablation before their treatment.
Material and methods: Biopsy was performed for 120 tumors (mean diameter, 2.2 cm) in 119 patients. All procedures were divided into diagnostic and non-diagnostic biopsies. Various variables were compared between the two groups. All cryoablation procedures were divided into two groups: procedures with or without simultaneous biopsy. The rates of benign or non-diagnostic tumors in each group were compared.
Results: After performing 120 initial and eight repeat biopsies, Grade 1 bleedings occurred in 44 cases. Six tumors were non-diagnostic and 114 were pathologically diagnosed. There were no significant variables between the diagnostic and non-diagnostic biopsies. Unnecessary cryoablation was avoided in nine benign lesions by performing biopsy in advance. Cryoablation performed simultaneously with biopsy included significantly more benign or non-diagnostic tumors than cryoablation performed after biopsy (15.2% vs. 1.4%; p =.01).
Conclusions: Percutaneous biopsy of small renal tumors referred for cryoablation was a safe procedure with high diagnostic yield. The confirmation of pathological diagnosis prior to cryoablation is necessary because patients with benign tumors can avoid unnecessary treatment.

DOI： 10.1080/13645706.2016.1249889

Diagnostic Ureteroscopy for Cases Clinically Suspected of Carcinoma in Situ of the Upper Urinary Tract Reviewed

Katsumi Sasaki, Koichiro Wada, Motoo Araki, Yasuyuki Kobayashi, Morito Sugimoto, Shin Ebara, Toyohiko Watanabe, Yasutomo Nasu

ACTA MEDICA OKAYAMA 71 ( 3 ) 227 - 232 2017

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

DOI： 10.18926/AMO/55205

Development of a Novel “Optical Pu+C2:F23ncture Needle” Using Ultrathin High-Definition Image Guide System for Percutaneous Nephrolithotomy

Tanimoto R, Wada K, Sasaki K, Sadahira T, Takamoto A, Araki M, Kobayashi K, Watanabe T, Nasu Y, Kumon H

Videourology 31 ( 5 ) 2017

Ureterolysis with omental wrap for bilateral hydronephrosis secondary to retroperitoneal fibrosis

Hironori Kojima, Motoo Araki, Kei Fujio, Takashi Yoshioka, Akihiro Mori, Atsushi Takamoto, Yuhei Horikawa, Morito Sugimoto, Koichiro Wada, Katsumi Sasaki, Yasuyuki Kobayashi, Shin Ebara, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Nishinihon Journal of Urology 79 ( 1 ) 12 - 15 2017

Impact of a robotic surgical system on treatment choice for men with clinically organ-confined prostate cancer.

Takashi Kobayashi, Kent Kanao, Motoo Araki, Naoki Terada, Yasuyuki Kobayashi, Atsuro Sawada, Takahiro Inoue, Shin Ebara, Toyohiko Watanabe, Tomomi Kamba, Makoto Sumitomo, Yasutomo Nasu, Osamu Ogawa

International journal of clinical oncology 23 ( 2 ) 1 - 6 2017

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Introducing a new surgical technology may affect behaviors and attitudes of patients and surgeons about clinical practice. Robot-assisted laparoscopic radical prostatectomy (RALP) was approved in 2012 in Japan. We investigated whether the introduction of this system affected the treatment of organ-confined prostate cancer (PCa) and the use of radical prostatectomy (RP). METHODS: We conducted a retrospective multicenter study on 718 patients with clinically determined organ-confined PCa treated at one of three Japanese academic institutions in 2011 (n = 338) or 2013 (n = 380). Two patient groups formed according to the treatment year were compared regarding the clinical characteristics of PCa, whether referred or screened at our hospital, comorbidities and surgical risk, and choice of primary treatment. RESULTS: Distribution of PCa risk was not changed by the introduction of RALP. Use of RP increased by 70% (from 127 to 221 cases, p < 0.0001), whereas the number of those undergoing radiotherapy or androgen deprivation therapy decreased irrespective of the disease risk of PCa. Increased use of RP (from 34 to 100 cases) for intermediate- or high-risk PCa patients with mild perioperative risk (American Society of Anesthesiologists score 2) accounted for 70% of the total RP increase, whereas the number of low- or very low-risk PCa patients with high comorbidity scores (Charlson Index ≥ 4) increased from 8 to 25 cases, accounting for 18%. Use of expectant management (active surveillance, watchful waiting) in very low-risk PCa patients was 15% in 2011 and 12% in 2013 (p = 0.791). CONCLUSIONS: Introduction of a robotic surgical system had little effect on the risk distribution of PCa. Use of RP increased, apparently due to increased indications in patients who are candidates for RP but have mild perioperative risk. Although small, there was an increase in the number of RPs performed on patients with severe comorbidities but with low-risk or very low-risk PCa.

DOI： 10.1007/s10147-017-1203-1

The assessment of renal cortex and parenchymal volume using automated CT volumetry for predicting renal function after donor nephrectomy.

Yosuke Mitsui, Takuya Sadahira, Motoo Araki, Koichiro Wada, Ryuta Tanimoto, Yuichi Ariyoshi, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Clinical and experimental nephrology 22 ( 2 ) 1 - 6 2017

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Contrast-enhanced CT is necessary before donor nephrectomy and is usually combined with a Tc-99m-mercapto-acetyltriglycine (MAG3) scan to check split renal function (SRF). However, all transplant programs do not use MAG3 because of its high cost and exposure to radiation. We examined whether CT volumetry of the kidney can be a new tool for evaluating SRF. METHODS: Sixty-three patients underwent live donor nephrectomy. Patients without a 1.0 mm slice CT or follow-up for <12 months were excluded leaving 34 patients' data being analyzed. SRF was measured by MAG3. Split renal volume (SRV) was calculated automatically using volume analyzer software. The correlation between SRF and SRV was examined. The association between the donor's postoperative estimated glomerular filtration rate (eGFR) and predicted eGFR calculated by MAG3 or CT volumetry was analyzed at 1, 3, and 12 months post nephrectomy. RESULTS: Strong correlations were observed preoperatively in a Bland-Altman plot between SRF measured by MAG3 and either CT cortex or parenchymal volumetry. In addition, eGFR after donation correlated with SRF measured by MAG3 or CT volumetry. The correlation coefficients (R) for eGFR Mag3 split were 0.755, 0.615, and 0.763 at 1, 3 and 12 months, respectively. The corresponding R values for cortex volume split were 0.679, 0.638, and 0.747. Those for parenchymal volume split were 0.806, 0.592, and 0.764. CONCLUSION: Measuring kidney by CT volumetry is a cost-effective alternative to MAG3 for evaluating SRF and predicting postoperative donor renal function. Both cortex and parenchymal volumetry were similarly effective.

DOI： 10.1007/s10157-017-1454-1

ロボット自家腎移植本邦初症例

荒木元朗, 和田耕一郎, 光井洋介, 吉岡貴史, 小林泰之, 渡辺豊彦, 那須保友

日本内視鏡外科学会雑誌 21 ( 7 ) OS194 - 4 2016.12

Adenovirus vector carrying REICIDKK-3 gene: neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy Reviewed

H. Kumon, Y. Ariyoshi, K. Sasaki, T. Sadahira, M. Araki, S. Ebara, H. Yanai, M. Watanabe, Y. Nasu

CANCER GENE THERAPY 23 ( 11 ) 400 - 409 2016.11

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

As the First-In-Human study of in situ gene therapy using an adenovirus vector carrying the human REIC (reduced expression in immortalized cell)/Dkk-3 gene (Ad-REIC), we conducted neoadjuvant intraprostatic injections in patients with high-risk localized prostate cancer undergoing radical prostatectomy (RP). Patients with recurrence probability of 35% or more within 5 years following RP, as calculated by Kaftan's nomogram, were enrolled. Patients received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. After confirming the safety of the therapeutic interventions with initially planned three escalating doses of 1.0 x 10(10), 1.0 x 10(11) and 1.0 x 10(12) viral particles (vp) in 1.0-1.2 ml (n=3, 3 and 6), an additional higher dose of 3.0 x 10(12) vp in 3.6 ml (n=6) Was further studied. All four DLs including the additional dose level-4 (DL-4) were feasible with no adverse events, except for grade 1 or 2 transient fever. Laboratory toxicities were grade 1 or 2 elevated aspartate transaminase/alanine transaminase (n=4). Regarding antitumor activities, cytopathic effects (tumor degeneration With cytolysis and pyknosis) and remarkable tumor-infiltrating lymphocytes in the targeted tumor areas were detected in a clear dose-dependent manner. Consequently, biochemical recurrence-free survival in DL-4 was significantly more favorable than in patient groups DL-1+2+2:

DOI： 10.1038/cgt.2016.53

Dynamin2 GTPase contributes to invadopodia formation in invasive bladder cancer cells Reviewed

Yubai Zhang, Maya Nolan, Hiroshi Yamada, Masami Watanabe, Yasutomo Nasu, Kohji Takei, Tetsuya Takeda

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 480 ( 3 ) 409 - 414 2016.11

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Cancer cell invasion is mediated by actin-based membrane protrusions termed invadopodia. Invadopodia consist of "core" F-actin bundles associated with adhesive and proteolytic machineries promoting cell invasion by degrading extracellular matrix (ECM). Formation of the F-actin core in invadopodia is regulated by various actin-binding proteins including Arp2/3 complex and cortactin. Dynamin GTPase localizes to the invadopodia and is implicated in cancer cell invasion, but its precise role at the invadopodia remained elusive.
In this study, we examined the roles of dynamin at the invadopodia of bladder cancer cells. Although all three dynamin isoforms (dynamin1, 2 and 3) are expressed in human bladder cancer cell line T24, only dynamin2 localizes to the invadopodia. Inhibition of dynamin2 function, using either RNA interference (RNAi) or the dynamin specific inhibitor Dynasore, caused defects in invadopodia formation and suppressed invasive activity of 124 bladder cancer cells. Structure-function analysis using dynamin2 deletion fragments identified the proline/arginine-rich domain (PRD) of dynamin2 as indispensable for invadopodia formation and invasiveness of 124 cells. Thus, dynamin2 contributes to bladder cancer invasion by controlling invadopodia formation in bladder cancer cells and may prove a valuable therapeutic target. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2016.10.063

ロボット自家腎移植本邦初症例

荒木元朗, 和田耕一郎, 光井洋介, 吉岡貴史, 有吉勇一, 佐々木克己, 小林泰之, 江原伸, 渡辺豊彦, 那須保友

Japanese Journal of Endourology 29 ( 3 ) 177 - 177 2016.11

岡山大学病院における生体腎移植レシピエントの術前ワクチン接種の現状

光井洋介, 荒木元朗, 山下里美, 吉岡貴史, 有吉勇一, 西村慎吾, 和田耕一郎, 小林泰之, 渡辺豊彦, 那須保友, 北川正史, 田邊克幸, 杉山斉, 和田淳

移植 51 ( 総会臨時 ) 266 - 266 2016.9

岡山大学病院における腹腔鏡下ドナー腎採取術の検討

西村慎吾, 荒木元朗, 小林泰之, 有森千聖, 山下里美, 光井洋介, 窪田理沙, 吉岡貴史, 有吉勇一, 和田耕一郎, 渡辺豊彦, 北川正史, 田邊克幸, 和田淳, 那須保友

移植 51 ( 総会臨時 ) 331 - 331 2016.9

Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer Reviewed

H. Sawahara, H. Shiraha, D. Uchida, H. Kato, T. Nagahara, M. Iwamuro, J. Kataoka, S. Horiguchi, M. Watanabe, M. Sakaguchi, A. Takaki, K. Nouso, Y. Nasu, H. Kumon, H. Okada

CANCER GENE THERAPY 23 ( 8 ) 278 - 283 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3), a tumor suppressor gene, is downregulated in various cancers. We previously reported the tumor-inhibitory effects of the REIC/Dkk-3 gene, delivered by a conventional adenoviral vector (Ad-CAG-REIC) in pancreatic cancer. Here, we developed an Ad-REIC vector with a novel gene expression system, termed the super gene expression (SGE) system, and assessed its therapeutic effects relative to those of Ad-CAG-REIC in pantreatic cancer cells. Human pancreatic cancer cell lines ASPC1 and MIAPaCa2 were used. REIC/Dkk-3 expression was assessed by western blot analysis. Relative cell viability and apoptotic effects were examined in vitro. The anti-tumor effects of Ad-REIC treatment were assessed in the mouse xenograft model. Compared with Ad-CAG-REIC, Ad-SGE-REIC elicited a significant increase in REIC protein expression in the cells studied, Relative to Ad-CAG-REIC, Ad-SGE-REIC reduced cell viability and induced apoptosis in the ASPC1 and MIAPaCa2 cell lines in vitro, and achieved superior tumor growth inhibition in the mouse xenograft model. Compared with conventional Ad-REIC agents, Ad-SGE-REIC provided enhanced inhibitory effects against tumor growth. Our results indicate that Ad-SGE-REIC is an innovative therapeutic tool for pancreatic cancer.

DOI： 10.1038/cgt.2016.31

A Phase II Clinical Trial Evaluating the Preventive Effectiveness of Lactobacillus Vaginal Suppositories in Patients with Recurrent Cystitis Reviewed

Koichiro Wada, Shinya Uehara, Ayano Ishii, Takuya Sadahira, Masumi Yamamoto, Ritsuko Mitsuhata, Atsushi Takamoto, Motoo Araki, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Hotta, Yasutomo Nasu

ACTA MEDICA OKAYAMA 70 ( 4 ) 299 - 302 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

DOI： 10.18926/AMO/54508

The Efficacy of Rituximab in High-risk Renal Transplant Recipients Reviewed

Motoo Araki, Koichiro Wada, Yosuke Mitsui, Risa Kubota, Takashi Yoshioka, Yuichi Ariyoshi, Yasuyuki Kobayashi, Masashi Kitagawa, Katsuyuki Tanabe, Hiroshi Sugiyama, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Hotta, Yasutomo Nasu

ACTA MEDICA OKAYAMA 70 ( 4 ) 295 - 297 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

DOI： 10.18926/AMO/54507

Multi-institutional retrospective analysis of learning curves on dosimetry and operation time befor and after introduction of intraoperatively built custom-linked seeds in prostate brachytherapy

Ishiyama H, Satoh T, Yorozu A, Saito S, Kataoka M, Hashine K, Nakamura R, Tanji S, Masui K, Okihara K, Ohashi T, Momma T, Aoki M, Miki K, Kato M, Morita M, Katayama N, Nasu Y, Kawanaka T, Fukumori T, Ito F, Shiroki R, Baba Y, Inadome A, Yoshioka Y, Takayama H, Hayakawa K

J Radiat Res 57 ( 1 ) 68 - 74 2016.8

MCAM, as a novel receptor for S100A8/A9, mediates progression of malignant melanoma through prominent activation of NF-kappa B and ROS formation upon ligand binding Reviewed

I. Made Winarsa Ruma, Endy Widya Putranto, Eisaku Kondo, Hitoshi Murata, Masami Watanabe, Peng Huang, Rie Kinoshita, Junichiro Futami, Yusuke Inoue, Akira Yamauchi, I. Wayan Sumardika, Chen Youyi, Ken-Ichi Yamamoto, Yasutomo Nasu, Masahiro Nishibori, Toshihiko Hibino, Masakiyo Sakaguchi

CLINICAL & EXPERIMENTAL METASTASIS 33 ( 6 ) 609 - 627 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

The dynamic interaction between tumor cells and their microenvironment induces a proinflammatory milieu that drives cancer development and progression. The S100A8/A9 complex has been implicated in chronic inflammation, tumor development, and progression. The cancer microenvironment contributes to the up-regulation of this protein complex in many invasive tumors, which is associated with the formation of pre-metastatic niches and poor prognosis. Changing adhesive preference of cancer cells is at the core of the metastatic process that governs the reciprocal interactions of cancer cells with the extracellular matrices and neighboring stromal cells. Cell adhesion molecules (CAMs) have been confirmed to have high-level expression in various highly invasive tumors. The expression and function of CAMs are profoundly influenced by the extracellular milieu. S100A8/A9 mediates its effects by binding to cell surface receptors, such as heparan sulfate, TLR4 and RAGE on immune and tumor cells. RAGE has recently been identified as an adhesion molecule and has considerably high identity and similarity to ALCAM and MCAM, which are frequently over-expressed on metastatic malignant melanoma cells. In this study, we demonstrated that ALCAM and MCAM also function as S100A8/A9 receptors as does RAGE and induce malignant melanoma progression by NF-kappa B activation and ROS formation. Notably, MCAM not only activated NF-kappa B more prominently than ALCAM and RAGE did but also mediated intracellular signaling for the formation of lung metastasis. MCAM is known to be involved in malignant melanoma development and progression through several mechanisms. Therefore, MCAM is a potential effective target in malignant melanoma treatment.

DOI： 10.1007/s10585-016-9801-2

Clinical analysis of bacterial strain profiles isolated from urinary tract infections: A 30-year study. International journal

Koichiro Wada, Shinya Uehara, Masumi Yamamoto, Takuya Sadahira, Ritsuko Mitsuhata, Motoo Araki, Yasuyuki Kobayashi, Ayano Ishii, Reiko Kariyama, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 22 ( 7 ) 478 - 482 2016.7

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: We analyzed bacterial strains isolated from urine samples of patients with urinary tract infections (UTI) at Okayama University Hospital over a 30-year period to characterize trends in species and antimicrobial susceptibilities. METHODS: Clinical isolates were collected from in- and out-patients with pyuria and bacteriuria who were treated between 1984 and 2014 (one episode per patient and plural isolates were counted in polymicrobial infection). We examined these isolates to identify pathogens and tested for antimicrobial susceptibility. RESULTS: Isolates from complicated UTI over a 30-year period revealed Pseudomonas aeruginosa (P. aeruginosa) was the most frequently isolated in the first decade (1984-1994), MRSA in the second decade (1995-2004), and Escherichia coli (E. coli) in the latest decade (2005-2014). In uncomplicated UTI examined over 20 years, E. coli was the most frequently isolated species accounting for 47-94% of isolates. Fluoroquinolone (FQs)-insusceptible E. coli were first isolated in 1994 and increased to about 35% in 2013 in patients with complicated UTI. CONCLUSIONS: Complicated UTI involving P. aeruginosa and MRSA decreased over the last 10 years. Our data suggest that several factors such as shorter hospitalizations, shorter indwelling catheter use, and appropriate antimicrobial use has decreased colonization of P. aeruginosa and MRSA with relative increases in isolation of E. coli including FQs-insusceptible strains. We must continue our surveillance of antimicrobial-resistant bacteria isolated from urine samples and evaluate antibiograms, since their persistence in the urinary tract would be problematic.

DOI： 10.1016/j.jiac.2016.04.004

Comparison of implant quality between intraoperatively built custom-linked seeds and loose seeds in permanent prostate brachytherapy using sector analysis. International journal

Norihisa Katayama, Mitsuhiro Takemoto, Atsushi Takamoto, Hiroki Ihara, Kuniaki Katsui, Shin Ebara, Yasutomo Nasu, Susumu Kanazawa

Journal of radiation research 57 ( 4 ) 393 - 9 2016.7

Language：English Publishing type：Research paper (scientific journal)

We compared the implant quality of intraoperatively built custom-linked (IBCL) seeds with loose seeds in permanent prostate brachytherapy. Between June 2012 and January 2015, 64 consecutive prostate cancer patients underwent brachytherapy with IBCL seeds (n = 32) or loose seeds (n = 32). All the patients were treated with 144 Gy of brachytherapy alone. Brachytherapy was performed using a dynamic dose calculation technique. Computed tomography/magnetic resonance imaging fusion-based dosimetry was performed 1 month after brachytherapy. Post-implant dose-volume histogram (DVH) parameters, prostate sector dosimetry, operation time, seed migration, and toxicities were compared between the IBCL seed group and the loose seed group. A sector analysis tool was used to divide the prostate into six sectors (anterior and posterior sectors at the base, mid-gland, and apex). V100 (95.3% vs 89.7%; P = 0.014) and D90 (169.7 Gy vs 152.6 Gy; P = 0.013) in the anterior base sector were significantly higher in the IBCL seed group than in the loose seed group. The seed migration rate was significantly lower in the IBCL seed group than in the loose seed group (6% vs 66%; P < 0.001). Operation time per seed was significantly longer in the IBCL seed group than in the loose seed group (1.31 min vs 1.13 min; P = 0.003). Other post-implant DVH parameters and toxicities did not differ significantly between the two groups. Our study showed more dose coverage post-operatively in the anterior base prostate sector and less seed migration in IBCL seed implantation compared with loose seed implantation.

DOI： 10.1093/jrr/rrw018

Effectiveness and Safety of Ureteroscopic Holmium Laser Lithotripsy for Upper Urinary Tract Calculi in Elderly Patients Reviewed

Takashi Yoshioka, Hideo Otsuki, Shinya Uehara, Toshihiro Shimizu, Wataru Murao, Koji Fujio, Kei Fujio, Koichiro Wada, Motoo Araki, Yasutomo Nasu

ACTA MEDICA OKAYAMA 70 ( 3 ) 159 - 166 2016.6

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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 '< 65 group' (< 65 years old, n=108), the '65-74 group' (65-74 years old, n=42), and the '>= 75 group' (>= 75 years old, n=39). The patients '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.

DOI： 10.18926/AMO/54414

A Case of Metastatic Urachal Cancer Including a Neuroendocrine Component Treated with Gemcitabine, Cisplatin and Paclitaxel Combination Chemotherapy Reviewed

Shin Ebara, Yasuyuki Kobayashi, Katsumi Sasaki, Motoo Araki, Morito Sugimoto, Koichirou Wada, Kei Fujio, Atsushi Takamoto, Toyohiko Watanabe, Hiroyuki Yanai, Yasutomo Nasu

ACTA MEDICA OKAYAMA 70 ( 3 ) 223 - 227 2016.6

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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/m(2)) on day 1, 8, cisplatin (70mg/m(2)) on day 1, and paclitaxel (80mg/m(2)) on day 1 and 8. After three cycles of chemotherapy, PET-CT showed complete regression of the disease. So the patient underwent total cystoure-threctomy, 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.

DOI： 10.18926/AMO/54423

Synergistic anti-pancreatic cancer immunological effects by treatment with reduced expression in immortalized cells/dickkopf-3 protein and peripheral blood mononuclear cells Reviewed

Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Hiroaki Sawahara, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Masami Watanabe, Akinobu Takaki, Kazuhiro Nouso, Yasutomo Nasu, Hiromi Kumon, Kazuhide Yamamoto

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 31 ( 6 ) 1154 - 1159 2016.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Background and AimReduced expression in immortalized cells/dickkopf-3 (REIC/DKK3) is a reported tumor suppressor gene and has potential to become an innovative therapy for various cancers. We examined the antitumor immunological effects of human REIC/DKK3 protein against pancreatic cancer.
MethodsActivation of extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 by REIC/DKK3 protein was assessed in human peripheral blood mononuclear cells using immunoblotting. Pancreatic cancer cell lines (AsPC-1 and MIA Paca-2) were cocultured with peripheral blood mononuclear cells, and the anticancer effects of REIC/DKK3 protein were assessed using the methyl thiazole tetrazolium, cytotoxicity, and enzyme-linked immunospot assays. The antitumor immunological effects of the combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells were also assessed in a pancreatic cancer model using non-obese diabetic/severe combined immunodeficiency mice.
ResultsThe REIC/DKK3 protein activated extracellular signal-regulated kinases 1 and 2, mammalian target of rapamycin, and signal transducer and activator of transcription 3 in peripheral blood mononuclear cells. REIC/DKK3 protein inhibited in vitro cancer cell viability and enhanced cytotoxicity when incubated with peripheral blood mononuclear cells. REIC/DKK3 protein induced significant production of interferon gamma from lymphocytes incubated with pancreatic cancer cells, indicating that CD8+ T cells were activated in the peripheral blood mononuclear cells when cocultured with AsPC-1 and MIA Paca-2 in the presence of REIC/DKK3 protein. Combined treatment with REIC/DKK3 protein and peripheral blood mononuclear cells produced in vivo anticancer immunostimulatory effects on pancreatic cancer cells.
ConclusionsThe REIC/DKK3 protein and peripheral blood mononuclear cells synergistically enhanced anticancer immunological effects against pancreatic cancer cells. The observed immunomodulatory effect of combined treatment likely occurs in adenovirus-mediated REIC/DKK3 gene therapy and provides important clues to the therapeutic mechanisms involving immune cells.

DOI： 10.1111/jgh.13259

The induction of antigen-specific CTL by in situ Ad-REIC gene therapy Reviewed

Y. Ariyoshi, M. Watanabe, S. Eikawa, C. Yamazaki, T. Sadahira, T. Hirata, M. Araki, S. Ebara, Y. Nasu, H. Udono, H. Kumon

GENE THERAPY 23 ( 5 ) 408 - 414 2016.5

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

An adenovirus vector carrying the human Reduced Expression in Immortalized Cell (REIC)/Dkk-3 gene (Ad-REIC) mediates simultaneous induction of cancer-selective apoptosis and augmentation of anticancer immunity. In our preclinical and clinical studies, in situ Ad-REIC gene therapy showed remarkable direct and indirect antitumor effects to realize therapeutic cancer vaccines. We herein aimed to confirm the induction of tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) by Ad-REIC. Using an ovalbumin (OVA), a tumor-associated antigen, expressing E.G7 tumor-bearing mouse model, we investigated the induction and expansion of OVA-specific CTLs responsible for indirect, systemic effects of Ad-REIC. The intratumoral administration of Ad-REIC mediated clear antitumor effects with the accumulation of OVA-specific CTLs in the tumor tissues and spleen. The CD86-positive dendritic cells (DCs) were upregulated in the tumor draining lymph nodes of Ad-REIC-treated mice. In a dual tumor-bearing mouse model in the left and right back, Ad-REIC injection in one side significantly suppressed the tumor growth on both sides and significant infiltration of OVA-specific CTLs into non-injected tumor was also detected. Consequently, in situ Ad-REIC gene therapy is expected to realize a new-generation cancer vaccine via anticancer immune activation with DC and tumor antigen-specific CTL expansion.

DOI： 10.1038/gt.2016.7

[Gene therapy]. Reviewed

Watanabe M, Sadahira T, Nasu Y

Nihon rinsho. Japanese journal of clinical medicine 74 Suppl 3 221 - 225 2016.5

Promising Therapeutic Efficacy of a Novel REIC/Dkk-3 Expressing Adenoviral Vector for Hepatocellular Carcinoma Reviewed

Sawahara Hiroaki, Hidenori Shiraha, Daisuke Uchida, Masakiyo Sakaguchi, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Okada

GASTROENTEROLOGY 150 ( 4 ) S1153 - S1153 2016.4

Factors Predicting Adhesion between Renal Capsule and Perinephric Adipose Tissue in Partial Nephrectomy Reviewed

Yasuyuki Kobayashi, Hiroaki Kurahashi, Yuko Matsumoto, Koichiro Wada, Katsumi Sasaki, Motoo Araki, Shin Ebara, Toyohiko Watanabe, Yasutomo Nasu

ACTA MEDICA OKAYAMA 70 ( 2 ) 69 - 74 2016.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

In minimally invasive partial nephrectomy (MIPN), it is important to preoperatively predict the degree of difficulty of tumor resection. When severe adhesions occur between the renal capsule and perinephric adipose tissue, detachment can be difficult. Preoperative prediction of adhesion is thought to be useful in the selection of surgical procedure. Subjects were 63 patients of a single surgeon who had received MIPN between April 2008 and August 2013 at Okayama University Hospital. Of these patients, this study followed 47 in whom the presence or absence of adhesions between the renal capsule and perinephric adipose tissue was confirmed using intraoperative videos. Data collected included: sex, BMI, CT finding (presence of fibroids in perinephric adipose tissue), comorbidities and lifestyle. Adhesion was observed in 7 patients (14.9). The mean operative time was 291.6min in the adhesion group, and 226.3min in the group without. The increased time in the adhesions group was significant (p<0.05). Predictive factors were a positive CT finding for fibroid structure and comorbidity of hypertension (p<0.05). In MIPN, difficulty of surgery can be affected by the presence of adhesion of the perinephric adipose tissue. Predicting such adhesion from preoperative CT is thus important.

DOI： 10.18926/AMO/54185

Development of a Novel REIC/DKK-3-Encoding Adenoviral Agent: Its Robust and Promising Therapeutic Effects in Pancreatic Cancer Reviewed

Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Sawahara Hiroaki, Masakiyo Sakaguchi, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Okada

GASTROENTEROLOGY 150 ( 4 ) S294 - S294 2016.4

Comparison of implant quality between intraoperatively built custom-linked seeds and loose seeds in permanent prostate brachytherapy using sector analysis

Katayama N, Takemoto M, Takamoto A, Ihara H, Katsui K, Ebara S, Nasu Y, Kanazawa S

J Radiat Res 57 ( 4 ) 393 - 399 2016.3

The gender specific risk factors for prolonged hospitalization due to acute pyelonephritis in a Japanese tertiary emergency center Reviewed

Risa Muneishi, Ryuta Tanimoto, Koichiro Wada, Philip Hsiao, Jun Eguchi, Motoo Araki, Toyohiko Watanabe, Yasutomo Nasu, Naoki Akebi

JOURNAL OF INFECTION AND CHEMOTHERAPY 22 ( 1-2 ) 108 - 111 2016.1

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Objectives: The aim of this study is to characterize the potential differences between male and female patients with acute pyelonephritis (AP) and to predict the severity of AP based on the length of hospital stay.
Methods: We conducted a retrospective medical chart review of 172 consecutive adult patients who were hospitalized in Tsuyama Central Hospital due to AP from January 2007 through June 2012. We analyzed the length of hospital stay by the proportional hazard model.
Results: A total of 172 patients were identified who were admitted to our hospital with a diagnosis of AP. Of them, 62% (106/172) were female. Except for urological malignancy, there was no significant difference between men and women in underlying disease. Out of 26 variables, univariate analysis in male showed that only urolithiasis (OR 1.75, p = 0.0294) was significantly associated with longer hospital stay, while septic shock (OR 3.18, P = 0.003), urological malignancy (OR 2.94, P = 0.002), age over 65 (OR 1.66, p = 0.018) and neurogenic bladder (OR 1.92, p = 0.014) were all associated with longer hospital stay in female patients.
Conclusions: This is the first report to identify the risk factors for prolonged hospital stay for the patients who were admitted with AP in the Japanese population. The risk factors causing prolonged hospital stay were totally different between males and females. Reviewing the medical history based on sex gender might enable a clinician to predict the severity of acute pyelonephritis during the initial evaluation. (C) 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2015.11.007

An Open-Label, Randomized Phase II Trial of Personalized Peptide Vaccination in Patients with Bladder Cancer that Progressed after Platinum-Based Chemotherapy Reviewed

Masanori Noguchi, Kazumasa Matsumoto, Hirotsugu Uemura, Gaku Arai, Masatoshi Eto, Seiji Naito, Chikara Ohyama, Yasutomo Nasu, Masatoshi Tanaka, Fukuko Moriya, Shigetaka Suekane, Satoko Matsueda, Nobukazu Komatsu, Tetsuro Sasada, Akira Yamada, Tatsuyuki Kakuma, Kyogo Itoh

CLINICAL CANCER RESEARCH 22 ( 1 ) 54 - 60 2016.1

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC CANCER RESEARCH

Purpose: The prognosis of platinum-based chemotherapy-resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity.
Experimental Design: In this randomized, open-label, phase II study, patients ages >= 18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1: 1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary end-points were overall survival (OS), immune response, and toxicity.
Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4-1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34-0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5-12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8-6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions.
Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results. (C) 2015 AACR.

DOI： 10.1158/1078-0432.CCR-15-1265

Tumor suppressor REIC/DKK-3 and co-chaperone SGTA: Their interaction and roles in the androgen sensitivity Reviewed

Kazuhiko Ochiai, Masami Morimatsu, Yuiko Kato, Toshina Ishiguro-Oonuma, Chihiro Udagawa, Oumaporn Rungsuriyawiboon, Daigo Azakami, Masaki Michishita, Yuichi Ariyoshi, Hideo Ueki, Yasutomo Nasu, Hiromi Kumon, Masami Watanabe, Toshinori Omi

ONCOTARGET 7 ( 3 ) 3273 - 3286 2016.1

Language：English Publishing type：Research paper (scientific journal) Publisher：IMPACT JOURNALS LLC

REIC/DKK-3 is a tumor suppressor, however, its intracellular physiological functions and interacting molecules have not been fully clarified. Using yeast two-hybrid screening, we found that small glutamine-rich tetratricopeptide repeat-containing protein a (SGTA), known as a negative modulator of cytoplasmic androgen receptor (AR) signaling, is a novel interacting partner of REIC/DKK-3. Mammalian two-hybrid and pull-down assay results indicated that the SGTA-REIC/DKK-3 interaction involved the N-terminal regions of both REIC/DKK-3 and SGTA and that REIC/DKK-3 interfered with the dimerization of SGTA, which is a component of the AR complex and a suppressor of dynein motor-dependent AR transport and signaling. A reporter assay in human prostate cancer cells that displayed suppressed AR signaling by SGTA showed recovery of AR signaling by REIC/DKK-3 expression. Considering these results and our previous data that REIC/DKK-3 interacts with the dynein light chain TCTEX-1, we propose that the REIC/DKK-3 protein interferes with SGTA dimerization, promotes dynein-dependent AR transport and then upregulates AR signaling.

Multi-institutional retrospective analysis of learning curves on dosimetry and operation time before and after introduction of intraoperatively built custom-linked seeds in prostate brachytherapy. Reviewed International journal

Hiromichi Ishiyama, Takefumi Satoh, Atsunori Yorozu, Shiro Saito, Masaaki Kataoka, Katsuyoshi Hashine, Ryuji Nakamura, Susumu Tanji, Koji Masui, Koji Okihara, Toshio Ohashi, Tetsuo Momma, Manabu Aoki, Kenta Miki, Masako Kato, Masashi Morita, Norihisa Katayama, Yasutomo Nasu, Takashi Kawanaka, Tomoharu Fukumori, Fumitaka Ito, Ryoichi Shiroki, Yuji Baba, Akito Inadome, Yasuo Yoshioka, Hitoshi Takayama, Kazushige Hayakawa

Journal of radiation research 57 ( 1 ) 68 - 74 2016.1

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

This multi-institutional retrospective analysis examined learning curves for dosimetric parameters and operation time after introduction of intraoperatively built custom-linked (IBCL) seeds. Data from consecutive patients treated with seed implantation before and after introduction of IBCL seeds (loose seed, n = 428; IBCL seed, n = 426) were collected from 13 centers. Dose-volume histogram parameters, operation times, and seed migration rates were compared before and after introduction of IBCL seeds. At the 1-month CT analysis, no significant differences were seen in dose to 90% of prostate volume between before and after IBCL seed introduction. No learning curve for dosimetry was seen. Prostate and rectal volume receiving at least 150% of prescription dose (V150 and RV150) were higher in the loose-seed group than in the IBCL-seed group. Operation time was extended by up to 10 min when IBCL seeds were used, although there was a short learning curve of about five patients. The percentage of patients with seed migration in the IBCL-seed group was one-tenth that in the loose-seed group. Our study revealed no dosimetric demerits, no learning curve for dosimetry, and a slightly extended operation time for IBCL seeds. A significant reduction in the rate of seed migration was identified in the IBCL-seed group.

DOI： 10.1093/jrr/rrv065

Percutaneous CT-guided Radiofrequency Ablation for Renal Cell Carcinoma in von Hippel-Lindau Disease: Midterm Results

Hideo Gobara, Takao Hiraki, Toshihiro Iguchi, Hiroyasu Fujiwara, Yasutomo Nasu, Susumu Kanazawa

Interventional Radiology 1 ( 1 ) 1 - 6 2016

Feasibility of Neoadjuvant Ad-REIC Gene Therapy in Patients with High-Risk Localized Prostate Cancer Undergoing Radical Prostatectomy Reviewed

Hiromi Kumon, Katsumi Sasaki, Yuichi Ariyoshi, Takuya Sadahira, Motoo Araki, Shin Ebara, Hiroyuki Yanai, Masami Watanabe, Yasutomo Nasu

CTS-CLINICAL AND TRANSLATIONAL SCIENCE 8 ( 6 ) 837 - 840 2015.12

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

In a phase I/IIa study of in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC), we assessed the inhibitory effects of cancer recurrence after radical prostatectomy (RP), in patients with high risk localized prostate cancer (PCa). After completing the therapeutic interventions with initially planned three escalating doses of 1.0 x 10(10), 1.0 x 10(11), and 1.0 x 10(12) viral particles (VP) in 1.0-1.2 mL (n = 3, 3, and 6), an additional higher dose of 3.0 x 10(12) VP in 3.6 mL (n = 6) was further studied. Patients with recurrence probability of 35% or more within 5 years after RP as calculated by Kattan's nomogram, were enrolled. They received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. Based on the findings of MRI and biopsy mapping, as a rule, one track injection to the most prominent cancer area was given to initial 12 patients and 3 track injections to multiple cancer areas in additional 6 patients. As compared to the former group, biochemical recurrence-free survival of the latter showed a significantly favorable outcome. Neoadjuvant Ad-REIC, mediating simultaneous induction of cancer selective apoptosis and augmentation of antitumor immunity, is a feasible approach in preventing cancer recurrence after RP. (199)

DOI： 10.1111/cts.12362

ロボット自家腎移植 Feasibility study

荒木元朗, 和田耕一郎, 有吉勇一, 吉岡貴史, 平田武志, 小林泰之, 佐々木克己, 江原伸, 渡辺豊彦, 那須保友

日本内視鏡外科学会雑誌 20 ( 7 ) OS45 - 7 2015.12

われわれはこうして技術認定取得者を育てている岡山大学泌尿器科における腹腔鏡教育プログラム手技の言語化に基づいた教育

小林泰之, 那須保友

日本内視鏡外科学会雑誌 20 ( 7 ) PD20 - 2 2015.12

リツキシマブを使用した腎移植症例

有吉勇一, 荒木元朗, 光井洋介, 吉岡貴史, 和田耕一郎, 小林泰之, 渡辺豊彦, 那須保友, 山下里美

今日の移植 28 ( 6 ) 705 - 706 2015.12

超細径HDIGスコープによる直視下管腔穿刺システムの開発と多方面への応用性

和田耕一郎, 荒木元朗, 佐々木克己, 小林泰之, 江原伸, 渡辺豊彦, 谷本竜太, 公文裕巳, 那須保友

日本内視鏡外科学会雑誌 20 ( 7 ) OS168 - 2 2015.12

岡山大学病院における腹腔鏡下膀胱全摘除術の検討

堀川雄平, 佐々木克己, 小林泰之, 杉本盛人, 和田耕一郎, 荒木元朗, 江原伸, 渡辺豊彦, 那須保友, 佃和憲

Japanese Journal of Endourology 28 ( 3 ) 231 - 231 2015.11

ロボット自家腎移植 Feasibility study

荒木元朗, 和田耕一郎, 有吉勇一, 吉岡貴史, 平田武志, 小林泰之, 佐々木克己, 江原伸, 渡辺豊彦, 那須保友

Japanese Journal of Endourology 28 ( 3 ) 168 - 168 2015.11

生体腎移植後に移植尿管結石、一時的尿管狭窄を生じた症例

光井洋介, 荒木元朗, 山下里美, 吉岡貴史, 有吉勇一, 和田耕一郎, 小林泰之, 江原伸, 渡邉豊彦, 那須保友, 北川正史, 田辺克幸, 杉山斉

西日本泌尿器科 77 ( 増刊 ) 127 - 127 2015.10

Distant Bystander Effect of REIC/Dkk-3 Gene Therapy through Immune System Stimulation in a Murine Model of Thoracic Malignancies Reviewed

Suzawa Ken, Shien Kazuhiko, Huang Peng, Sakaguchi Masakiyo, Watanabe Masami, Hashida Shinsuke, Soh Junichi, Yamamoto Hiromasa, Maki Yuho, Asano Hiroaki, Tsukuda Kazunori, Nasu Yasutomo, Kumon Hiromi, Miyoshi Shinichiro, Toyooka Shinichi

JOURNAL OF THORACIC ONCOLOGY 10 ( 9 ) S599 2015.9

当院で施行した先行的腎移植(preemptive renal transplantation:PRT)の検討

光井洋介, 荒木元朗, 山下里美, 吉岡貴史, 有吉勇一, 和田耕一郎, 小林泰之, 江原伸, 渡辺豊彦, 那須保友, 北川正史, 田邊克幸, 杉山斉, 和田淳

移植 50 ( 総会臨時 ) 316 - 316 2015.9

生体腎移植レシピエントにおける周術期感染症に関する検討

和田耕一郎, 荒木元朗, 山下里美, 吉岡貴史, 有吉勇一, 小林泰之, 江原伸, 渡辺豊彦, 山成俊夫, 北川正史, 田邊克幸, 杉山斉, 和田淳, 那須保友

移植 50 ( 総会臨時 ) 299 - 299 2015.9

生体腎移植におけるリツキシマブの効果と有害事象の検討

荒木元朗, 和田耕一郎, 宗石理沙, 吉岡貴史, 有吉勇一, 山下里美, 小林泰之, 江原伸, 渡辺豊彦, 那須保友, 田邊克幸, 北川正史, 杉山斉, 和田淳

移植 50 ( 総会臨時 ) 475 - 475 2015.9

精嚢造影併用の経尿道的内視鏡手術が診断治療に有用であった射精障害の一例

杉本盛人, 石井和史, 光井洋介, 吉岡貴史, 倉橋寛明, 松本裕子, 瀬野祐子, 小林泰之, 渡部昌実, 渡邊豊彦, 那須保友

日本性機能学会雑誌 30 ( 2 ) 198 - 198 2015.8

岡山大学病院における腹腔鏡下膀胱全摘除術の初期期成績の報告

小林泰之, 佐々木克己, 平田武志, 和田耕一郎, 荒木元朗, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳

泌尿器外科 28 ( 臨増 ) 869 - 869 2015.5

A vaccine strategy with multiple prostatic acid phosphatase (PAP)-fused cytokines for prostate cancer treatment. Reviewed

Kei Fujio, Masami Watanabe, Hideo Ueki, Shun-Ai Li, Rie Kinoshita, Kazuhiko Ochiai, Junichiro Futami, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon

Oncology Reports 33 ( 4 ) 1585 - 1592 2015.4

Ad-REIC Gene Therapy: Promising Results in a Patient with Metastatic CRPC Following Chemotherapy. Reviewed International journal

Hiromi Kumon, Katsumi Sasaki, Yuichi Ariyoshi, Takuya Sadahira, Shin Ebara, Takao Hiraki, Susumu Kanazawa, Hiroyuki Yanai, Masami Watanabe, Yasutomo Nasu

Clinical Medicine Insights. Oncology 9 31 - 38 2015.3

Language：English

A 63-year-old man with metastatic castration-resistant prostate cancer (CRPC) was successfully treated for two years with in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC), following chemotherapy. Ad-REIC mediates simultaneous induction of cancer-selective apoptosis and augmentation of antitumor immunity, and a Phase I/IIa clinical study on Ad-REIC has been conducted at Okayama University Hospital since January 2011. At the time of enrollment in December 2012, the patient presented with rapid progression of lymph node (LN) metastases. Two scheduled Ad-REIC injections and 10 additional Ad-REIC injections into metastatic pelvic and para-aortic LNs under CT guidance, with an average four weeks' interval, exhibited the potent direct and indirect effects of Ad-REIC as a therapeutic cancer vaccine. During the next 12 months, three additional injections into para-aortic LNs showing regrowth achieved adequate control of all metastatic LNs with prostate-specific antigen (PSA) decline, without any particular adverse events.

DOI： 10.4137/CMO.S23252

Integrin antagonist augments the therapeutic effect of adenovirus-mediated REIC/Dkk-3 gene therapy for malignant glioma. Reviewed International journal

Y Shimazu, K Kurozumi, T Ichikawa, K Fujii, M Onishi, J Ishida, T Oka, M Watanabe, Y Nasu, H Kumon, I Date

Gene therapy 22 ( 2 ) 146 - 154 2015.2

Language：English Publishing type：Research paper (scientific journal)

Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) was identified as a gene whose expression is reduced in many human cancers. REIC/Dkk-3 expression is also downregulated in malignant glioma and regulates cell growth through caspase-dependent apoptosis. cRGD (EMD121974), an antagonist of integrins, has demonstrated preclinical efficacy against malignant glioma. In this study, we investigated the antiglioma effect of combination therapy using an adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) and cRGD. Quantitative real-time reverse-transcription PCR revealed the reduction of REIC/Dkk-3 mRNA levels in malignant glioma cell lines. The reduction of REIC/Dkk-3 protein expression in malignant glioma cell lines was also confirmed with western blot analysis. After treatment with Ad-REIC and cRGD, the proliferative rate of malignant glioma cells was significantly reduced in a time-dependent manner. In vivo, there was a statistically significant increase in the survival of mice treated with Ad-REIC and cRGD combination therapy compared with Ad-REIC monotherapy. We identified an apoptotic effect following monotherapy with Ad-REIC. Moreover, cRGD augmented the antiglioma efficacy of Ad-REIC. These results may lead to a promising new approach for the treatment of malignant glioma.

DOI： 10.1038/gt.2014.100

当科で施行した生体腎移植レシピエント、ドナーのQOL評価

有吉勇一, 荒木元朗, 宗石理沙, 吉岡貴史, 和田耕一郎, 小林泰之, 佐々木克己, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳, 有森千聖, 北川正史, 田邊克幸, 森永裕士, 菊本陽子, 内田治仁, 喜多村真治, 前島洋平, 杉山斉, 槇野博史

移植 49 ( 4-5 ) 377 - 377 2014.11

岡山大学病院における腹腔鏡下膀胱全摘除術の検討

佐々木克己, 小林泰之, 杉本盛人, 和田耕一郎, 荒木元朗, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳

Japanese Journal of Endourology 27 ( 3 ) 199 - 199 2014.11

Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population

Matsuda K, Takahashi A, Middlebrooks C.D, Obara W, Nasu Y, Inoue K, Tamura K, Yamasaki I, Naya Y, Tanikawa C, Cui R, Figueroa J.D, Silverman D.T, Rothman N, Namiki M, Tomita Y, Nishiyama H, Kohri K, Deguchi T, Nakagawa M, Yokoyama M, Miki T, Kumon H, Fujioka T, Ludmila P.O, Kubo M, Nakamura Y, Shuin T

Human Molecular Genetics 24 ( 4 ) 1177 - 1184 2014.10

リツキシマブを使用した生体腎移植症例の検討

和田耕一郎, 荒木元朗, 宗石理沙, 吉岡貴史, 有吉勇一, 小林泰之, 佐々木克己, 江原伸, 渡辺豊彦, 那須保友, 森永裕士, 北川正史, 公文裕巳

西日本泌尿器科 76 ( 増刊 ) 119 - 119 2014.10

Significant association between the Axin2 rs2240308 single nucleotide polymorphism and the incidence of prostate cancer Reviewed

Chao Ma, Chunxiao Liu, Peng Huang, Haruki Kaku, Jie Chen, Kai Guo, Hideo Ueki, Akiko Sakai, Yasutomo Nasu, Hiromi Kumon, Kenji Shimizu, Masami Watanabe

ONCOLOGY LETTERS 8 ( 2 ) 789 - 794 2014.8

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

The Wnt signaling pathway plays a crucial role in human cancer development, and axis inhibition protein 2 (Axin2) is a master scaffold protein involved in Wnt signaling. Axin2 negatively regulates Wnt signaling and acts as a tumor suppressor protein. The present study evaluated the association between the Axin2 single nucleotide polymorphism (SNP) rs2240308 [guanine (G)/adenine (A)] and the incidence of prostate cancer. In total, 103 patients with prostate cancer and 100 cancer-free control males were included in this case-control study, and were genotyped using the genomic DNA extracted from peripheral blood samples. The results revealed a higher incidence of prostate cancer in the subjects with the homozygous GG genotype and a reduced cancer incidence in the patients with the GA genotype of the rs2240308 SNP (G/A) in the Axin2 gene. T-he adjusted odds ratio for carriers with the GA genotype was 0.377 (95% CI, 0.206-0.688; P=0.001) and that for the AA genotype was 0.830 (95% CI, 0.309-2.232; P=0.712) compared with the GG genotype. Therefore, the GA genotype was found to exhibit a protective effect that decreased the risk of prostate cancer. To the best of our knowledge, this is the first study to demonstrate the significant association between this SNP (rs2240308, G/A) and the risk of prostate cancer. This association indicates the possibility that the variations in the Axin2 gene in this position may play a significant role in promoting the development of cancer in the prostate. We believe that the Axin2 SNP (rs2240308) could be a useful biomarker for the predisposition and early diagnosis of the disease.

DOI： 10.3892/ol.2014.2177

腎移植における手術用顕微鏡下血管形成・血管吻合

荒木元朗, 和田耕一郎, 有吉勇一, 吉岡貴史, 宗石理沙, 有森千聖, 上松克利, 小林泰之, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳, 長谷川健二郎

日本移植学会総会プログラム抄録集 50回 412 - 412 2014.8

リツキシマブを使用した生体腎移植症例の検討

和田耕一郎, 荒木元朗, 宗石理沙, 吉岡貴史, 有吉勇一, 有森千聖, 小林泰之, 渡辺豊彦, 那須保友, 公文裕巳, 森永裕士, 北川正史, 杉山斉, 和田淳

日本移植学会総会プログラム抄録集 50回 416 - 416 2014.8

当科で施行した先行的腎移植後の健康関連QOL評価

有吉勇一, 荒木元朗, 宗石理沙, 吉岡貴史, 和田耕一郎, 小林泰之, 有森千聖, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳

日本移植学会総会プログラム抄録集 50回 415 - 415 2014.8

Dramatic Increase in Expression of a Transgene by Insertion of Promoters Downstream of the Cargo Gene Reviewed

Masakiyo Sakaguchi, Masami Watanabe, Rie Kinoshita, Haruki Kaku, Hideo Ueki, Junichiro Futami, Hitoshi Murata, Yusuke Inoue, Shun-Ai Li, Peng Huang, Endy Widya Putranto, I. Made Winarsa Ruma, Yasutomo Nasu, Hiromi Kumon, Nam-ho Huh

MOLECULAR BIOTECHNOLOGY 56 ( 7 ) 621 - 630 2014.7

Language：English Publishing type：Research paper (scientific journal) Publisher：HUMANA PRESS INC

For expression of genes in mammalian cells, various vectors have been developed using promoters including CMV, EF-1 alpha, and CAG promoters and have been widely used. However, such expression vectors sometimes fail to attain sufficient expression levels depending on the nature of cargo genes and/or on host cell types. In the present study, we aimed to develop a potent promoter system that enables high expression levels of cargo genes ubiquitously in many different cell types. We found that insertion of an additional promoter downstream of a cargo gene greatly enhanced the expression levels. Among the constructs we tested, C-TSC cassette (C: CMV-RU5' located upstream; TSC: another promoter unit composed of triple tandem promoters, hTERT, SV40, and CMV, located downstream of the cDNA plus a polyadenylation signal) had the most potent capability, showing far higher efficiency than that of potent conventional vector systems. The results indicate that the new expression system is useful for production of recombinant proteins in mammalian cells and for application as a gene therapeutic measure.

DOI： 10.1007/s12033-014-9738-0

Immunological aspects of REIC/Dkk-3 gene therapy : the mechanism of the robust anti-tumor effects. Reviewed

Masami Watanabe, Peng Huang, Fernando Abarzua, Haruki Kaku, Katsumi Sasaki, Hideo Ueki, Toyohiko Wananabe, Yasutomo Nasu, Hiromi Kumon

JOURNAL OF GENE MEDICINE 16 ( 7-8 ) 226 - 227 2014.7

Retroperitoneal bronchogenic cyst: a rare incidentaloma discovered in a juvenile hypertensive patient. International journal

Tomohiro Terasaka, Fumio Otsuka, Kanako Ogura-Ochi, Tomoko Miyoshi, Kenichi Inagaki, Yasuyuki Kobayashi, Yasutomo Nasu, Hirofumi Makino

Hypertension research : official journal of the Japanese Society of Hypertension 37 ( 6 ) 595 - 7 2014.6

Potential of adenovirus-mediated REIC/Dkk-3 gene therapy for use in the treatment of pancreatic cancer Reviewed

Daisuke Uchida, Hidenori Shiraha, Hironari Kato, Teruya Nagahara, Masaya Iwamuro, Junro Kataoka, Shigeru Horiguchi, Masami Watanabe, Akinobu Takaki, Kazuhiro Nouso, Yasutomo Nasu, Takahito Yagi, Hiromi Kumon, Kazuhide Yamamoto

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 29 ( 5 ) 973 - 983 2014.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Background and AimThe reduced expression in immortalized cells REIC/the dickkopf 3 (Dkk-3) gene, tumor suppressor gene, is downregulated in various malignant tumors. In a prostate cancer study, an adenovirus vector carrying the REIC/Dkk-3 gene (Ad-REIC) induces apoptosis. In the current study, we examined the effects of REIC/Dkk-3 gene therapy in pancreatic cancer.
MethodsREIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry in the pancreatic cancer cell lines (ASPC1, MIAPaCa2, Panc1, BxPC3, SUIT-2, KLM1, and T3M4) and pancreatic cancer tissues. The Ad-REIC agent was used to investigate the apoptotic effect in vitro and antitumor effects in vivo. We also assessed the therapeutic effects of Ad-REIC therapy with gemcitabine.
ResultsThe REIC/Dkk-3 expression was lost in the pancreatic cancer cell lines and decreased in pancreatic cancer tissues. Ad-REIC induced apoptosis and inhibited cell growth in the ASPC1 and MIAPaCa2 lines in vitro, and Ad-REIC inhibited tumor growth in the mouse xenograft model using ASPC1 cells. The antitumor effect was further enhanced in combination with gemcitabine. This synergistic effect may be caused by the suppression of autophagy via the enhancement of mammalian target of rapamycin signaling.
ConclusionsAd-REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/Dkk-3 gene therapy is an attractive therapeutic tool for pancreatic cancer.

DOI： 10.1111/jgh.12501

岡山大学泌尿器科におけるpreemptive腎移植症例の検討

有吉勇一, 荒木元朗, 宗石理沙, 吉岡貴史, 和田耕一郎, 小林泰之, 佐々木克己, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳, 清水千聖, 赤木滋, 森永裕士, 田邊克幸, 北川正史, 杉山斉, 和田淳, 槇野博史

移植 49 ( 1 ) 167 - 167 2014.5

多発転移を伴ったXp11.2転座型腎癌の1例

有吉勇一, 江原伸, 小林泰之, 賀来春紀, 那須保友, 公文裕巳, 田中健大, 柳井広之, 黒田直人

泌尿器外科 27 ( 別冊号 ) 76 - 76 2014.5

Adenovirus-mediated REIC/Dkk-3 gene therapy: Development of an autologous cancer vaccination therapy (Review) Reviewed

Masami Watanabe, Yasutomo Nasu, Hiromi Kumon

ONCOLOGY LETTERS 7 ( 3 ) 595 - 601 2014.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3 is a tumor suppressor and therapeutic gene and has been studied with respect to the application of cancer gene therapy. Our previous studies demonstrated that the intratumoral injection of an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC) suppresses tumor growth in mouse models of prostate, breast and testicular cancer and malignant mesothelioma. The mechanisms underlying these antitumor therapeutic effects have only been clarified recently. It has been demonstrated that Ad-REIC treatment inhibits cancer progression via the upregulation of systemic anticancer immunity. Under experimental conditions, autologous cancer vaccination via cancer-specific apoptosis and anticancer immune activation is a possible therapeutic mechanism. The robust anticancer effects observed in previous preclinical studies support the clinical utility of Ad-REIC. At present, a phase I-IIa study of Ad-REIC gene therapy in prostate cancer patients is ongoing. The current study reviews the observations of previous fundamental studies and summarizes the anticancer mechanisms of intratumoral Ad-REIC treatment in terms of cancer vaccination.

DOI： 10.3892/ol.2013.1777

A novel gene expression system strongly enhances the anticancer effects of a REIC/Dkk-3-encoding adenoviral vector Reviewed

Masami Watanabe, Masakiyo Sakaguchi, Rie Kinoshita, Haruki Kaku, Yuichi Ariyoshi, Hideo Ueki, Ryuta Tanimoto, Shin Ebara, Kazuhiko Ochiai, Junichiro Futami, Shun-Ai Li, Peng Huang, Yasutomo Nasu, Nam-Ho Huh, Hiromi Kumon

ONCOLOGY REPORTS 31 ( 3 ) 1089 - 1095 2014.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Gene expression systems with various promoters, including the cytomegalovirus (CMV) promoter, have been developed to increase the gene expression in a variety of normal and cancer cells. In particular, in the clinical trials of cancer gene therapy, a more efficient and robust gene expression system is required to achieve sufficient therapeutic outcomes. By inserting the triple translational enhancer sequences of human telomerase reverse transcriptase (hTERT), Simian virus 40 (SV40) and CMV downstream of the sequence of the BGH polyA, we were able to develop a novel gene expression system that significantly enhances the expression of the genes of interest. We termed this novel gene expression cassette the super gene expression (SGE) system, and herein verify the utility of the SGE cassette for a replication-deficient adenoviral vector. We newly developed an adenoviral vector expressing the tumor suppressor, reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3), based on the CMV promoter-driven SGE system (Ad-SGE-REIC) and compared the therapeutic utility of Ad-SGE-REIC with that of the conventional adenoviral vectors (Ad-CMV-REIC or Ad-CAG-REIC). The results demonstrated that the CMV promoter-SGE system allows for more potent gene expression, and that the Ad-SGE-REIC is superior to conventional adenoviral systems in terms of the REIC protein expression and therapeutic effects. Since the SGE cassette can be applied for the expression of various therapeutic genes using various vector systems, we believe that this novel system will become an innovative tool in the field of gene expression and gene therapy.

DOI： 10.3892/or.2013.2958

Retroperitoneal bronchogenic cyst: a rare incidentaloma discovered in a juvenile hypertensive patient

Terasaka T, Otsuka F, Ogura-Ochi K, Miyoshi T, Inagaki K, Kobayashi Y, Nasu Y, Makino H

Hypertens Res 37 ( 6 ) 595 - 597 2014.3

A Rare Complication: Misdirection of an Indwelling Urethral Catheter into the Ureter Reviewed

Tsutomu Ishikawa, Motoo Araki, Takeshi Hirata, Masami Watanabe, Shin Ebara, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon

ACTA MEDICA OKAYAMA 68 ( 1 ) 47 - 51 2014.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

DOI： 10.18926/AMO/52144

Anti-Cancer Effects of REIC/Dkk-3-encoding Adenoviral Vector for the Treatment of Non-small Cell Lung Cancer Reviewed

Kazuhiko Shien, Norimitsu Tanaka, Masami Watanabe, Junichi Soh, Masakiyo Sakaguchi, Keitaro Matsuo, Hiromasa Yamamoto, Masashi Furukawa, Hiroaki Asano, Kazunori Tsukuda, Yasutomo Nasu, Nam-Ho Huh, Shinichiro Miyoshi, Hiromi Kumon, Shinichi Toyooka

PLOS ONE 9 ( 2 ) 2014.2

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

Objectives: REIC/Dkk-3 is down-regulated in a broad range of human cancer cells and is considered to function as a tumor suppressor. We previously reported that REIC/Dkk-3-expressing adenovirus vector (Ad-REIC) induced endoplasmic reticulum (ER) stress and cancer-specific apoptosis in human prostate cancer. In this study, we examined the therapeutic impact of Ad-REIC on non-small cell lung cancer (NSCLC).
Materials and Methods: We examined the anti-tumor effect of Ad-REIC on 25 NSCLC cell lines in vitro and A549 cells in vivo. Two of these cell lines were artificially established as EGFR-tyrosine kinase inhibitor (TKI) resistant sublines.
Results: Ad-REIC-treatment inhibited the cell viability by 40% or more in 13 (52%) of the 25 cell lines at multiplicity of infection (MOI) of 20 (20 MOI). These cell lines were regarded as being highly sensitive cells. The cell viability of a nonmalignant immortalized cell line, OUMS-24, was not inhibited at 200 MOI of Ad-REIC. The effects of Ad-REIC on EGFR-TKI resistant sublines were equivalent to those in the parental cell lines. Here, we demonstrated that Ad-REIC treatment activated c-Jun N-terminal kinase (JNK) in NSCLC cell lines, indicating the induction of ER stress with GRP78/BiP (GRP78) up-regulation and resulting in apoptosis. A single intratumoral injection of Ad-REIC significantly inhibited the tumorigenic growth of A549 cells in vivo. As predictive factors of sensitivity for Ad-REIC treatment in NSCLC, we examined the expression status of GRP78 and coxsackievirus and adenovirus receptor (CAR). We found that the combination of the GRP78 and CAR expressional statuses may be used as a predictive factor for Ad-REIC sensitivity in NSCLC cells.
Conclusion: Ad-REIC induced JNK activation and subsequent apoptosis in NSCLC cells. Our study indicated that Ad-REIC has therapeutic potential against NSCLC and that the expression statuses of GRP78 and CAR may predict a potential therapeutic benefit of Ad-REIC.

DOI： 10.1371/journal.pone.0087900

Other Link： http://orcid.org/0000-0003-1761-6314

Robot-Assisted Radical Prostatectomy: Modified Ultradissection Reduces pT2 Positive Surgical Margins on the Bladder Neck Reviewed

Motoo Araki, Wooju Jeong, Sung Yul Park, Young Hoon Lee, Yasutomo Nasu, Hiromi Kumon, Sung Joon Hong, Koon Ho Rha

ACTA MEDICA OKAYAMA 68 ( 1 ) 35 - 41 2014.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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 D'Amico 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.

Testosterone replacement elevates the serum uric acid levels in patients with female to male gender identity disorder Reviewed

Hiroaki Kurahashi, Masami Watanabe, Morito Sugimoto, Yuichi Ariyoshi, Sabina Mahmood, Motoo Araki, Kazushi Ishii, Yasutomo Nasu, Atsushi Nagai, Hiromi Kumon

ENDOCRINE JOURNAL 60 ( 12 ) 1321 - 1327 2013.12

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN ENDOCRINE SOC

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.

DOI： 10.1507/endocrj.EJ13-0203

腹腔鏡下膀胱全摘除術における初期経験に関する報告

佐々木克己, 小林泰之, 倉橋寛明, 和田耕一郎, 杉本盛人, 荒木元朗, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳

Japanese Journal of Endourology 26 ( 3 ) 299 - 299 2013.11

腎盂尿管移行部狭窄症に対するAnderson-Hynes法によるロボット支援腹腔鏡下腎盂形成術

小林泰之, 荒木元朗, 倉橋寛明, 和田耕一郎, 佐々木克己, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳

Japanese Journal of Endourology 26 ( 3 ) 227 - 227 2013.11

限局性前立腺癌における治療法別PSA非再発生存期間の検討、過去10年間での治療成績

高本篤, 谷本竜太, 小林泰之, 江原伸, 那須保友, 公文裕己

日本癌治療学会誌 48 ( 3 ) 1095 - 1095 2013.9

尿路上皮癌に対する術後補助療法としてのGCP療法

小林泰之, 谷本竜太, 江原伸, 那須保友, 公文裕巳

日本癌治療学会誌 48 ( 3 ) 2468 - 2468 2013.9

Predictive factors for acute and late urinary toxicity after permanent interstitial brachytherapy in Japanese patients

KANIMOTO Ryuta, BEKKU Kensuke, KATAYAMA Norihisa, KOBAYASHI Yasuyuki, EBARA Shin, ARAKI Motoo, TAKEMOTO Mitsuhiro, YANAI Hiroyuki, NASU Yasutomo, KUMON Hiromi

20 ( 8 ) 812 - 817 2013.8

岡山大学泌尿器科における腎移植症例の検討

宗石理沙, 荒木元朗, 和田耕一郎, 有吉勇一, 吉岡貴史, 上松克利, 小林泰之, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳, 清水千聖

移植 48 ( 総会臨時 ) 357 - 357 2013.8

拡張型心筋症を合併した生体腎移植の1例

有吉勇一, 荒木元朗, 宗石理沙, 吉岡貴史, 清水千聖, 和田耕一郎, 佐々木克己, 小林泰之, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳

移植 48 ( 総会臨時 ) 396 - 396 2013.8

Clinical significance of CD24 as a predictor of bladder cancer recurrence. Reviewed

Chunxiao Liu, Shaobo Zheng, Haiyan Shen, Kai Xu, Jie Chen, Hulin Li, Yawen Xu, Abai Xu, Binshen Chen, Haruki Kaku, Yasutomo Nasu, Hiromi Kumon, Peng Huang, Masami Watanabe

Oncology Letters 96 - 100 2013.7

多発転移を伴ったXp11.2転座型腎癌の1例

有吉勇一, 江原伸, 小林泰之, 賀来春紀, 那須保友, 公文裕巳, 田中健大, 柳井広之, 黒田直人

腎癌研究会会報 ( 43 ) 49 - 49 2013.7

Laparoscopic radical cystectomy: A report of our initial four cases

Yasuyuki Kobayashi, Hiroaki Kurahashi, Kensuke Bekku, Kouichiro Wada, Ryuta Tanimoto, Katsumi Sasaki, Motoo Araki, Shin Ebara, Toyohiko Watanabe, Hiromi Kumon, Yasutomo Nasu

Nishinihon Journal of Urology 75 ( 7 ) 352 - 358 2013.7

Language：Japanese Publishing type：Research paper (scientific journal)

Although previously, laparoscopic radical cystectomy (LRC) has been performed as advanced medicine only within limited institutions, it can now be performed using national health insurance according to the medical treatment fee revision of 2012. We began preparing for LRC from 2011 in our institution and we performed LRC for the first timein July 2012. To date, we have performed LRC in four cases. First case : we performed LRC and left retroperitoneal nephroureterectomy for left renal pelvic cancer. Operative time was 450 minutes (LRC, 190 minutes) and estimated blood loss was 700 ml. Second case : we performed LRC for bladder cancer (BCG failure). Operative time was 390 minutes and estimated blood loss was 1000 ml. Third case : we performed LRC and lymphadenectomy for bladder cancer (cT2N0M0). Operative time was 510 minutes and estimated blood loss was 500 ml. Fourth case: we performed LRC and lymphadenectomy for bladder cancer (cT2N0M0). Operative time was 550 minutes and estimated blood loss was 335 ml. As regards problems at the time of introduction of LRC, indication, lymphadenectomy, and urinary tract diversion, etc. are discussed.

岡山大学病院泌尿器科における初期腎移植症例の検討

和田耕一郎, 荒木元朗, 吉岡貴史, 有吉勇一, 小林泰之, 渡辺豊彦, 那須保友, 清水千聖, 赤木滋, 杉山斉, 槇野博史, 上松克利, 公文裕巳

日本透析医学会雑誌 46 ( Suppl.1 ) 627 - 627 2013.5

Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder

NAKAMURA Aya, WATANABE Masami, SUGIMOTO Morito, SAKO Tomoko, MAHMOOD Sabina, KAKU Haruki, NASU Yasutomo, ISHII Kazushi, NAGAI Atsushi, KUMON Hiromi

Endocrinologia Japonica 60 ( 3 ) 275 - 281 2013.3

Language：English Publishing type：Research paper (scientific journal) Publisher：The Japan Endocrine Society

Gender identity disorder (GID) is a conflict between a person's actual physical gender and the one they identify him or herself with. Testosterone is the key agent in the medical treatment of female to male GID patients. We conducted a dose-response analysis of testosterone replacement therapy (TRT) in 138 patients to determine the onset of the therapeutic effects. The TRT consisted of intramuscular injection of testosterone enanthate and patients were divided into three groups; 250 mg every two weeks, 250 mg every three weeks and 125 mg every two weeks. The onset of deepening of voice, increase in facial hair and cessation of menses was evaluated in each group. At one month after the start of TRT, the onset of these physical changes was more prevalent in the group receiving the higher dose of testosterone, and there were dose-dependent effects observed between the three treatment groups. On the other hand, at six months after the start of TRT, most of the patients had achieved treatment responses and there were no dose-dependent effects with regard to the percentage of patients with therapeutic effects. No significant side effects were observed in any of the treatment groups. We demonstrated that the early onset of the treatment effects of TRT is dose-dependent, but within six months of starting TRT, all three doses were highly effective. Current study provides useful information to determine the initial dose of TRT and to suggest possible changes that should be made in the continuous dosage for long term TRT.

DOI： 10.1507/endocrj.EJ12-0319

Other Link： http://search.jamas.or.jp/link/ui/2014114876

当科における上部尿路BCG灌流療法の治療成績

別宮謙介, 江原伸, 平田武志, 谷本竜太, 小林泰之, 賀来春紀, 那須保友, 公文裕巳

泌尿器外科 26 ( 3 ) 334 - 335 2013.3

腹腔鏡下膀胱全摘除術における初期経験に関する報告

小林泰之, 佐々木克己, 別宮謙介, 和田耕一郎, 荒木元朗, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 104 ( 2 ) 303 - 303 2013.3

Could salvage surgery after chemotherapy have clinical impact on cancer survival of patients with metastatic urothelial carcinoma? Reviewed

Kensuke Bekku, Takashi Saika, Yasuyuki Kobayashi, Ryo Kioshimoto, Taiki Kanbara, Yasutomo Nasu, Hiromi Kumon

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 18 ( 1 ) 110 - 115 2013.2

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

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.

DOI： 10.1007/s10147-011-0350-z

Cancer stem cell-like characteristics of a CD133+ subpopulation in the J82 human bladder cancer cell line. Reviewed

Peng Huang, Masami Watanabe, Haruki Kaku, Hideo Ueki, Hirofumi Noguchi, Morito Sugimoto, Takeshi Hirata, Hiroshi Yamada, Kohji Takei, Shaobo Zheng, Kai Xu, Yasutomo Nasu, Yasuyuki Fujii, Chunxiao Liu, Hiromi Kumon

Molecular and Clinical Oncology 180 - 184 2013.1

岡山大学泌尿器科における腎移植症例の検討

有吉勇一, 荒木元朗, 吉岡貴史, 和田耕一郎, 小林泰之, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳, 清水千聖, 赤木滋, 杉山斉, 槇野博史, 齋藤和英, 高橋公太

移植 47 ( 6 ) 489 - 489 2012.12

DIRECT THERAPEUTIC EFFECT OF REIC/DKK-3-ENCODING ADENOVIRAL VECTOR FOR NON-SMALL CELL LUNG CANCER Reviewed

Yamamoto Hiromasa, Tanaka Norimitsu, Toyooka Shinichi, Watanabe Masami, Sakaguchi Masakiyo, Soh Junichi, Shien Kazuhiko, Furukawa Masashi, Asano Hiroaki, Tsukuda Kazunori, Nasu Yasutomo, Huh Nam-ho, Kumon Hiromi, Miyoshi Shinichirou

JOURNAL OF THORACIC ONCOLOGY 7 ( 11 ) S463 2012.11

Preclinical biodistribution and safety study of reduced expression in immortalized cells/Dickkopf-3-encoding adenoviral vector for prostate cancer gene therapy Reviewed

Morito Sugimoto, Masami Watanabe, Haruki Kaku, Shun-Ai Li, Hirofumi Noguchi, Hideo Ueki, Masakiyo Sakaguchi, Nam-Ho Huh, Yasutomo Nasu, Hiromi Kumon

ONCOLOGY REPORTS 28 ( 5 ) 1645 - 1652 2012.11

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

The biodistribution and safety of adenoviral vectors encoding the human REIC/Dkk-3 tumor suppressor gene (Ad-REIC) were examined in this preclinical study for in situ prostate cancer gene therapy. First, the in vitro apoptotic effects of Ad-REIC in normal and cancer cells derived from the prostate and liver were examined. Significant apoptotic effects were observed at 100 MOI (multiplicity of infection) in prostate cancer cells (LNCaP, PC3) and hepatoma cells (HEP3B and HEPG2); however, no effects were seen in normal cells. To analyze the safety of intraprostatic Ad-REIC administration, the biodistribution and histology after Ad-REIC injection were evaluated in various organs of normal male C57BL6 mice. In a supporting study, vector dissemination following intravenous injection of Ad-REIC into tail veins was determined. To evaluate whether Ad-REIC was present in the collected tissue specimens, human REIC gene detection was performed using DNA-PCR. Intraprostatic treatment administered at lower doses showed vector biodistribution into the colon, urinary bladder and prostate. At higher doses, vector dissemination was observed in tissues more distant from the prostate, including the lung, thymus, heart, liver and adrenal gland. After intravenous injection a: Ad-REIC, dissemination was observed in the liver and spleen. These results indicate that the biodistribution of Ad-REIC is determined by the dose and route of administration. Although acute inflammatory effects were observed in the prostate after intraprostatic administration at higher doses, no abnormal histological findings were noted in the other tissues, including those of intravenously treated mice. Regarding the safety of Ad-REIC administration, no deaths and no signs of toxicity or unusual behavior were observed in the mice in any treatment group. Based on these preclinical experiments, adenovirus-mediated in situ REIC/Dkk-3 gene therapy is considered to be safe for use as a treatment for human prostate cancer.

DOI： 10.3892/or.2012.2001

尿管ステント留置症例の臨床的検討

和田耕一郎, 谷本竜太, 小林泰之, 佐々木克己, 荒木元朗, 江原伸, 上原慎也, 渡辺豊彦, 那須保友, 公文裕巳

Japanese Journal of Endourology 25 ( 3 ) 280 - 280 2012.11

岡山大学病院におけるロボット補助下前立腺全摘術の初期経験

平田武志, 小林泰之, 荒木元朗, 江原伸, 上原慎也, 渡邊豊彦, 雑賀隆史, 那須保友, 公文裕巳

Japanese Journal of Endourology 25 ( 3 ) 242 - 242 2012.11

Laparoscopic management of complicated urachal remnants in adults Reviewed

Motoo Araki, Takashi Saika, Daiji Araki, Yasuyuki Kobayashi, Shinya Uehara, Toyohiko Watanabe, Kiyoshi Yamada, Yasutomo Nasu, Hiromi Kumon

WORLD JOURNAL OF UROLOGY 30 ( 5 ) 647 - 650 2012.10

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Objectives The traditional surgical approach for removing a urachal remnant is via a large transverse or midline infraumbilical incision. We review our experience with laparoscopic urachal cyst excision and report the efficacy and outcomes of this approach as a less morbid, minimally invasive alternative.
Methods Between August 2005 and March 2009, eight patients with a mean age of 26 years who had symptomatic urachal cysts underwent laparoscopic radical excision of the urachal remnant. Using three ports, the urachal remnant was dissected from the umbilicus to the bladder dome and then removed intact via the umbilicus. Umbilicoplasty was performed by a plastic surgeon. We retrospectively reviewed the perioperative records to assess morbidity and outcomes.
Results All eight operations were completed successfully. No intraoperative or postoperative complications were reported at a mean follow-up of 3.2 years. Mean operative time was 147.5 min including umbilicoplasty. Pathological evaluation confirmed a benign urachal remnant in each case. There have been no recurrences of symptoms nor postoperative complications during follow-up. Mean time to full recovery, defined as return to normal life without pain, was 16 days. The patients with bladder cuff resection had a delayed full convalescence (25 vs. 13 days) due to a minimum degree of dysuria.
Conclusion A laparoscopic approach with the removal of urachal remnants via the umbilicus appears to be a safe and effective alternative with better cosmesis when compared to an open approach.

DOI： 10.1007/s00345-012-0829-x

救済化学療法後にhCG plateauとなった精巣腫瘍の3例の検討

小林泰之, 別宮謙介, 谷本竜太, 江原伸, 那須保友, 公文裕巳

西日本泌尿器科 74 ( 増刊 ) 137 - 137 2012.10

虫垂炎術前CTにて偶発的に発見されたXp11.2転座型腎癌、多発転移の1例

高村剛輔, 小林泰之, 弓狩一晃, 神原太樹, 和田耕一郎, 杉本盛人, 江原伸, 那須保友, 公文裕巳, 柳井広之

西日本泌尿器科 74 ( 増刊 ) 167 - 167 2012.10

生体腎移植後に血中アスペルギルス抗原陽性となった2症例

有吉勇一, 荒木元朗, 吉岡貴史, 清水千聖, 和田耕一郎, 小林泰之, 江原伸, 渡辺豊彦, 那須保友, 公文裕巳

移植 47 ( 総会臨時 ) 346 - 346 2012.9

岡山大学泌尿器科における腎移植症例の検討

吉岡貴史, 荒木元朗, 和田耕一郎, 有吉勇一, 清水千聖, 小林泰之, 佐々木克己, 江原伸, 渡邉豊彦, 那須保友, 公文裕巳

移植 47 ( 総会臨時 ) 328 - 328 2012.9

REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer Reviewed

Takeshi Hirata, Masami Watanabe, Haruki Kaku, Yasuyuki Kobayashi, Hiroshi Yamada, Masakiyo Sakaguchi, Kohji Takei, Nam-Ho Huh, Yasutomo Nasu, Hiromi Kumon

INTERNATIONAL JOURNAL OF ONCOLOGY 41 ( 2 ) 559 - 564 2012.8

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Bladder cancer is one of the most common urogenital malignancies. The intravesical instillation of anticancer agents is an attractive strategy to treat a superficial lesion or floating/disseminated cancer cells after transurethral operation. An adenovirus carrying REIC/Dkk-3, a tumor suppressor gene (Ad-REIC), exhibits cancer-specific apoptotic effects in various types of cancer cells. The aim of the present study was to examine the potential of Ad-REIC as a therapeutic agent for bladder cancer. KK47 and RT4 human bladder cancer cells were sensitive to the Ad-REIC treatment for apoptosis induction, but some human bladder cancer cell lines (T24, J82 and TccSup) were resistant. Significant cell growth inhibition was observed when these resistant cancer cell lines were treated with Ad-REIC in a condition of floating cells, which is clinically observed after transurethral operation and becomes a cause of intravesical cancer dissemination. The therapeutic potential of Ad-REIC for the treatment of multidrug-resistant bladder cancer was investigated. The adriamycin-resistant KK47 bladder cancer cells (KK47/ADM), which also present multidrug resistance, showed induction of significant apoptosis following Ad-REIC treatment. The Ad-REIC treatment induced downregulation of P-glycoprotein in KK47/ADM cells and restored the sensitivity to doxorubicin (adriamycin). Ad-REIC suppressed P-glycoprotein expression in a c-Jun-NH2-kinase (JNK)-dependent manner. Therefore, the current study indicated two therapeutic aspects of the Ad-REIC agent against human bladder cancer cells, as an apoptosis inducer/cell growth inhibitor and as a sensitizer of chemotherapeutic agents in multidrug-resistant cancer cells. The intravesical instillation of Ad-REIC could be an attractive therapeutic method in human bladder cancer where the treatment of superficial lesions and floating/disseminated or multidrug-resistant cancer cells is necessary.

DOI： 10.3892/ijo.2012.1503

Clear cell sarcoma of the kidney with inferior vena cava tumor thrombus in a child: A case report

Akihiro Mori, Kensuke Bekku, Katsumi Sasaki, Ryo Kishimoto, Kazushi Ishii, Shinya Uehara, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon, Yoshiko Miyamura, Hiroyuki Yanai

Nishinihon Journal of Urology 74 ( 8 ) 449 - 453 2012.8

Language：Japanese Publishing type：Research paper (scientific journal)

Clear cell carcinoma of the kidney is a rare renal tumor accounting for about 4% of childhood malignant renal neoplasms, and inferior vena cava thrombus is extremely rare. In this report, we present a case of clear cell sarcoma of the kidney with inferior vena cava tumor thrombus in a child, this being the second report of clear cell carcinoma of the kidney with tumor thrombus in Japan. The patient was a 16-month-old girl, who was admitted to our hospital for investigation of a right renal tumor with inferior vena cava thrombus. At first, we performed tumor needle biopsy and made a diagnosis of clear cell sarcoma of the kidney. According to the protocol issued by National Wilms Tumor Study-5, chemotherapy comprising vincristine, doxorubicin, cyclophosphamide and etoposide was started. After 2 cycles of the chemotherapy, radical nephrectomy, thrombectomy and segmental hepatectomy were performed and complete resection was possible. Following radiotherapy to the renal bed and adjuvant chemotherapy with ifosfamide, carboplatin, and etoposide, no clinical evidence of recurrence or metastasis has been noted during the subsequent period of about 1 year.

A novel gene expression system for detecting viable bladder cancer cells Reviewed

Hideo Ueki, Masami Watanabe, Haruki Kaku, Peng Huang, Shun-Ai Li, Kazuhiko Ochiai, Takeshi Hirata, Hirofumi Noguchi, Hiroshi Yamada, Kohji Takei, Yasutomo Nasu, Yuji Kashiwakura, Hiromi Kumon

INTERNATIONAL JOURNAL OF ONCOLOGY 41 ( 1 ) 135 - 140 2012.7

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

A novel transcriptional system was developed that can robustly enhance cancer-specific gene expression. In the system, hTERT promoter-driven gene expression was enhanced by an advanced two-step transcriptional amplification (TSTA). This construct was used to develop a novel system for detection of bladder cancer cells. The current study evaluated the advanced TSTA system by examining the cancer-specific gene transcription in various bladder cancer cell lines. The system significantly enhanced cancer-specific luciferase gene expression in the bladder cancer cell lines in comparison to the previous expression system of one-step or conventional TSTA. The fold gain of the enhancement was significantly correlated to the telomerase activity of the cell lines. A green fluorescent protein (GFP) gene encoding plasmid vector was constructed where hTERT promoter-driving transcription is enhanced by the advanced TSTA to utilize the system for the imaging and detection of viable bladder cancer cells. The advanced TSTA-hTERT-GFP plasmid successfully induced cancer-specific gene expression, showing robust GFP expression in human bladder cancer cell lines, but no visible GFP expression in normal bladder urothelial cells. The control GFP plasm id with a CMV promoter yielded GFP expression in both normal bladder cells and cancer cells. The advanced TSTA-hTERT-GFP plasmid allowed selective visualization of viable human bladder cancer cells in mixed cell culture containing 10- and 100-fold more normal bladder urothelial cells. These findings indicate that the advanced TSTA-hTERT expressional system is a valuable tool for detecting viable bladder cancer cells. The current system can be applied for in vitro detection of bladder cancer cells in urine and other types of cancer cells disseminated in vivo.

DOI： 10.3892/ijo.2012.1417

Implications of transcriptional factor, OCT-4, in human bladder malignancy and tumor recurrence Reviewed

Peng Huang, Jie Chen, Lei Wang, Yanqun Na, Haruki Kaku, Hideo Ueki, Katsumi Sasaki, Ken Yamaguchi, Kai Zhang, Takashi Saika, Yasutomo Nasu, Masami Watanabe, Hiromi Kumon

MEDICAL ONCOLOGY 29 ( 2 ) 829 - 834 2012.6

Language：English Publishing type：Research paper (scientific journal) Publisher：HUMANA PRESS INC

OCT-4, which is also known as POU5f1, is a key regulator of self-renewal in embryonic stem cells. The new cancer stem cell concept proposes that the expression of such genes is potentially correlated with tumorigenesis and can affect some aspects of the cancer behavior, such as recurrence or metastasis. This study investigated the association between OCT-4 expression in cancer tissues obtained by transurethral surgery and the clinical data to clarify the involvement of OCT-4 in human bladder malignancy. Immunohistochemical analysis demonstrated that a positive rate of OCT-4 expression was significantly associated with the higher-grade cancer (G2 and G3) in comparison with that of the lower grade (G1). In addition, positive OCT-4 expression was significantly associated with the intra-bladder tumor recurrence after the operation. The staining intensity of OCT-4 expression was also correlated with tumor recurrence. These data indicate that positive OCT-4 expression may be involved in the development of high-grade bladder cancer and with the bladder cancer recurrence. This is the first study showing a correlation between the expression of OCT-4 and bladder cancer recurrence. OCT-4 may be a valuable clinical marker for the progression of bladder cancer and may be an attractive therapeutic target for the development of new medicines for the treatment of malignancy.

DOI： 10.1007/s12032-011-9962-4

Ureteroscopic Management of Chronic Unilateral Hematuria: A Single-Center Experience over 22 Years Reviewed

Motoo Araki, Shinya Uehara, Katsumi Sasaki, Koichi Monden, Masaya Tsugawa, Toyohiko Watanabe, Manoji Monga, Yasutomo Nasu, Hiromi Kumon

PLOS ONE 7 ( 6 ) e36729 2012.6

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

Objective: To analyze the short and long term safety and efficacy of ureteroscopic evaluation and management of chronic unilateral hematuria.
Methods: We retrospectively reviewed patients with chronic unilateral hematuria from 1987 to 2008. The distal to middle ureter was evaluated with a semi-rigid ureteroscope without a guidewire. Subsequently, the flexible ureteroscope was advanced into the upper ureter to the renal pelvis using a low-pressure automated irrigant system (Uromat (TM)). Lesions identified ureteroscopically were treated with diathermy fulguration.
Results: One hundred and four (56 male, 48 female) patients were identified, with a median age of 37 (14-80) years and median follow-up of 139 (34-277) months. The median preoperative duration of gross hematuria was 5 (1-144) months. Endoscopic findings included 61 (56%) minute venous rupture (MVR; a venous bleeding without clear abnormalities), 21 (20%) hemangioma (vascular tumor-like structure), 3 (3%) varix (tortuous vein), 1 (1%) calculus and 18 (17%) no lesions. The incidence of "no lesions" was less in the recent 12 years (9%) than the first 10 years (27%), while the incidence of MVR increased from 40 to 66% (p<0.05). All patients were treated endoscopically. Immediate success rate was 96% (100% in the recent 12 years). Long-term recurrent gross hematuria rate was 7%. Six resolved spontaneously and only 1 required ureteroscopy, revealing a different bleeding site.
Conclusion: Ureteroscopy and diathermy fulguration is highly useful for evaluation and treatment of chronic unilateral hematuria. Sophisticated technique and improved instrumentation contributes to a better outcome.

DOI： 10.1371/journal.pone.0036729

The clinical impact of pathological review on selection the treatment modality for localized prostate cancer in candidates for brachytherapy monotherapy Reviewed

Ryo Kishimoto, Takashi Saika, Kensuke Bekku, Hiroyuki Nose, Fernando Abarzua, Yasuyuki Kobayashi, Motoo Araki, Hiroyuki Yanai, Yasutomo Nasu, Hiromi Kumon

WORLD JOURNAL OF UROLOGY 30 ( 3 ) 375 - 378 2012.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

To evaluate the impact of pathological review by pathologist with genitourinary expertise (PGU) on treatment modality of localized prostate cancer, we analyzed Gleason grade (GG) migration and the final treatment decision in a cohort of patients designated for permanent prostate brachytherapy (PPB).
From February 2005 to July 2010, a total of 247 patients with localized prostate cancer diagnosed by local community hospitals were referred to our hospital for PPB monotheray. All pathologic slides of prostate biopsies were reviewed by a single PGU. Patients ultimately selected their treatment modality from our recommendations based on the review. Indication for PPB monotherapy was the NCCN classification of patients as good or intermediate risk. In addition, patient with Primary GG 4 was regarded as unadapted case.
Six cases were reinterpreted as no cancer (2.4%). GG change occurred in 94 cases (38.1%) of which 77 (81.9%) were upgraded and 17 (18.1%) downgraded. Of the total 247 patients, 86 (34.8%) changed therapies and 30 (12.1%) did so based on the pathologic slide review.
Pathological review of biopsy specimens is mandatory for the determination of treatment modality especially in candidates for monotherapy of permanent prostate brachytherapy.

DOI： 10.1007/s00345-011-0738-4

DNA methylation status of REIC/Dkk-3 gene in human malignancies Reviewed

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

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 138 ( 5 ) 799 - 809 2012.5

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

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.

DOI： 10.1007/s00432-012-1158-6

Preoperative positive urine cytology is a risk factor for subsequent development of bladder cancer after nephroureterectomy in patients with upper urinary tract urothelial carcinoma Reviewed

Yasuyuki Kobayashi, Takashi Saika, Yoshiyuki Miyaji, Michinao Saegusa, Ryoji Arata, Naoki Akebi, Tadasu Takenaka, Daisuke Manabe, Yasutomo Nasu, Hiromi Kumon

WORLD JOURNAL OF UROLOGY 30 ( 2 ) 271 - 275 2012.4

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

To determine the independent risk factors of bladder recurrence in patients with upper urinary tract urothelial carcinoma (UUT-UC).
A total of 364 patients underwent nephroureterectomy (NUx) for UUT-UC between January 2005 and April 2009 in Okayama University and 17 affiliated hospitals. Patients with concomitant bladder cancer were excluded from the analysis. The clinicopathologic data for the remaining 288 patients with UUT-UC were retrospectively reviewed. Median follow-up after NUx was 20.2 months. The following variables were evaluated for any association with bladder recurrence: sex, age, tumor stage, tumor grade, venous invasion, lymphatic invasion, tumor location, multifocality, surgical modalities, time of ligation of the ureter, and preoperative urine cytology. The significance of each variable was tested univariately using the log-rank test. The simultaneous effects of multiple risk factors were estimated by multiple regression analysis using the Cox proportional hazards model.
Bladder recurrence occurred in 103 patients (35.8%). Median time to first bladder recurrence was 6.9 months. Significant risk factors for bladder recurrences on univariate analysis were tumor location (P = 0.046) and preoperative positive urine cytology (P < 0.001). Multivariate analysis revealed that preoperative urine cytology positive was significant for bladder recurrence (HR: 1.977; 95% CI: 1.310-2.983, P = 0.001).
Risk factor for subsequent development of bladder cancer after NUx was preoperative positive urine cytology.

DOI： 10.1007/s00345-011-0731-y

Gene therapy for prostate cancer - Research and development of a new immuno-gene therapy

Katsumi Sasaki, Ryuta Tanimoto, Shin Ebara, Hiromi Kumon, Yasutomo Nasu, Masami Watanabe, Haruki Kaku, Hiroyuki Yanai

Nishinihon Journal of Urology 74 ( 4 ) 197 - 202 2012.4

Language：Japanese Publishing type：Research paper (international conference proceedings)

We have performed three clinical studies for prostate cancer at Okayama University Hospital. In the first study (Suicide gene therapy using adenovirus vector (ADV) expressing herpes simplex virus-thymidine kinase gene and Ganciclovir), 9 castration-resistant prostate cancer (CRPC) patients without metastasis were treated from 2001 to 2005, demonstrating the safety profile and some clinical responses. In the second study (Immunogene therapy using ADV expressing the Interleukin-12 gene), 10 CRPC patients with or without metastasis were treated from 2008, demonstrating the safety profile and some immuno-clinical responses. The latest study (Gene therapy creating cancer vaccine using ADV expressing reduced expression in immortalized cells
REIC/Dkk-3 gene, which mediates simultaneous induction of cancer-selective apoptosis and augmentation of anti-tumor immunity), was initiated in Jan., 2011. The study category includes 2 groups: A, CRPC
and B, newly diagnosed high-risk localized cancer with indication for surgical resection (Neo-adjuvant). Four CRPC patients and 9 neo-adjuvant patients have been entered into the study with an excellent safety profile. Patients treated with the intermediate vector dose demonstrated modest clinical and/or immunological effects, and an increased vector dose showed remarkable immuno-pathological effects. Ad/REIODkk-3, a revolutionary gene-based medicine creating a cancer vaccine, could be a promising treatment option for prostate cancer.

Partial sensitization of human bladder cancer cells to a gene-therapeutic adenovirus carrying REIC/Dkk-3 by downregulation of BRPK/PINK1 Reviewed

Yu Jin, Hitoshi Murata, Masakiyo Sakaguchi, Ken Kataoka, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Nam-Ho Huh

ONCOLOGY REPORTS 27 ( 3 ) 695 - 699 2012.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

REIC/Dkk-3 is a tumor suppressor gene that was first identified as a gene downregulated in association with immortalization of normal human fibroblasts. We have demonstrated that an adenovirus carrying REIC/Dkk-3 (Ad-REIC) showed a tumor-specific killing effect on a wide range of cancers. However, some human cancers, bladder cancers in particular, are resistant to Ad-REIC. In this study, we investigated the combination effect of downregulation of BRPK/PINK1 (PINK1) and Ad-REIC on bladder cancer cells. Five bladder cancer cell lines among six cell lines examined were resistant to Ad-REIC. Among the cell lines, the resistance of two cell lines was probably due to low infection efficiency of the adenovirus. PINK1-specific siRNA remarkably downregulated Bcl-x(L) and TRAP1 proteins and upregulated BAX protein expression. Finally, downregulation of PINK1 partially sensitized the other three cell lines that were resistant to Ad-REIC. This sensitization was associated with increasing production of reactive oxygen species (ROS). These results indicate that PINK1 is one of the key molecules for the mitochondrial protection system and that PINK1 can be a new target molecule to sensitize bladder cancer cells that are resistant to Ad-REIC.

DOI： 10.3892/or.2011.1543

転移性尿路上皮癌に対する全身化学療法後救済手術療法の有用性についての検討

別宮謙介, 神原太樹, 平田武志, 岸本涼, 谷本竜太, 小林泰之, 江原伸, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 103 ( 2 ) 501 - 501 2012.3

尿路上皮癌に対する術後補助療法としてのGemcitabine-Cisplatin-Paclitaxel(GCP)療法の治療成績

小林泰之, 別宮謙介, 江原伸, 上原慎也, 渡辺豊彦, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 103 ( 2 ) 432 - 432 2012.3

腎細胞癌に対する根治的腎摘除術と腎部分切除術の生存率及び心血管系イベントに関する検討

神原太樹, 小林泰之, 別宮謙介, 岸本涼, 平田武志, 谷本竜太, 江原伸, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 103 ( 2 ) 448 - 448 2012.3

Preclinical Safety and Efficacy of in Situ REIC/Dkk-3 Gene Therapy for Prostate Cancer Reviewed

Keiichiro Kawauchi, Masami Watanabe, Haruki Kaku, Peng Huang, Kasumi Sasaki, Masakiyo Sakaguchi, Kazuhiko Ochiai, Nam-ho Huh, Yasutomo Nasu, Hiromi Kumon

ACTA MEDICA OKAYAMA 66 ( 1 ) 7 - 16 2012.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

DOI： 10.18926/AMO/48076

Primary Gleason grade 4 impact on biochemical recurrence after permanent interstitial brachytherapy in Japanese patients with low- or intermediate-risk prostate cancer. Reviewed International journal

Uesugi T, Saika T, Edamura K, Nose H, Kobuke M, Ebara S, Abarzua F, Katayama N, Yanai H, Nasu Y, Kumon H

International journal of radiation oncology, biology, physics 82 ( 2 ) e219 - 23 2012.2

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To reveal a predictive factor for biochemical recurrence (BCR) after permanent prostate brachytherapy (PPB) using iodine-125 seed implantation in patients with localized prostate cancer classified as low or intermediate risk based on National Comprehensive Cancer Network (NCCN) guidelines. METHODS AND MATERIALS: From January 2004 to December 2009, 414 consecutive Japanese patients with clinically localized prostate cancer classified as low or intermediate risk based on the NCCN guidelines were treated with PPB. The clinical factors including pathological data reviewed by a central pathologist and follow-up data were prospectively collected. Kaplan-Meier and Cox regression analyses were used to assess the factors associated with BCR. RESULTS: Median follow-up was 36.5 months. The 2-, 3-, 4-, and 5-year BCR-free rates using the Phoenix definition were 98.3%, 96.0%, 91.6%, and 87.0%, respectively. On univariate analysis, the Gleason score, especially primary Gleason grade 4 in biopsy specimens, was a strong predicting factor (p < 0.0001), while age, initial prostate-specific antigen (PSA) level, T stage, and minimal dose delivered to 90% of the prostate volume (D90) were insignificant. Multivariate analysis indicated that a primary Gleason grade 4 was the most powerful prognostic factor associated with BCR (hazard ratio = 6.576, 95% confidence interval, 2.597-16.468, p < 0.0001). CONCLUSIONS: A primary Gleason grade 4 carried a worse BCR prognosis than the primary grade 3 in patients treated with PPB. Therefore, the indication for PPB in patients with a Gleason sum of 4 + 3 deserves careful and thoughtful consideration.

DOI： 10.1016/j.ijrobp.2011.04.018

URETEROSCOPIC MANAGEMENT FOR UPPER TRACT UROTHELIAL CARCINOMA: LONG-TERM SINGLE INSTITUTION EXPERIENCE Reviewed

Araki Motoo, Uehara Shinya, Watanabe Toyohiko, Koichi Monden, Masaya Tsugawa, Yasuyuki Kobayashi, Shin Ebara, Saika Takashi, Yasutomo Nasu, Hiromi Kumon

JOURNAL OF ENDOUROLOGY 25 A177 - A177 2011.11

Advanced two-step transcriptional amplification as a novel method for cancer-specific gene expression and imaging Reviewed

Masami Watanabe, Hideo Ueki, Kazuhiko Ochiai, Peng Huang, Yasuyuki Kobayashi, Yasutomo Nasu, Katsumi Sasaki, Haruki Kaku, Yuji Kashiwakura, Hiromi Kumon

ONCOLOGY REPORTS 26 ( 4 ) 769 - 775 2011.10

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

The two-step transcriptional amplification (TSTA) system was previously reported to enhance the tissue-specific gene expression driven by weak promoters, but the enhancement of the gene expression is limited to use in in vitro and in vivo experimental situations. To achieve robust tissue-specific gene expression using the TSTA system, we developed an advanced TSTA system which includes polyglutamines and rat glucocorticoid receptor sequences between the GAL4 and VP16 sequences in the region of the first step of transcription. We evaluated the advanced TSTA system as a method to enhance the human telomerase reverse transcriptase (hTERT) promoter-driving cancer-specific transcription in various cancer cell lines. As a result, the advanced TSTA enhanced cancer-specific luciferase gene expression in all of the examined cancer cell lines, when compared with both the one-step and conventional TSTA systems (an similar to 6- and similar to 17-fold enhancement, respectively). Notably, the enhancement of the hTERT driven expression by the conventional TSTA system was modest and even inferior to the one-step system in several cancer cell lines. We then constructed a luciferase gene encoding the adeno-associated virus vector in which the hTERT promoter-mediated expression was driven by the advanced TSTA or control systems. In an orthotopic liver tumor model, mice were treated with the vector via tail vein injection. An optical imaging device was used to visualize the in vivo luciferase expression in the orthotopic tumor. The advanced TSTA system significantly enhanced the luciferase expression compared with the one-step and conventional TSTA systems (18.0+/-1.0- and 15.9+/-0.85-fold gain, respectively). Therefore, the advanced TSTA system significantly improves hTERT-dependent cancer-specific gene expression both in vitro and in vivo when compared with the previous systems. Since the advanced TSTA method can also be applied to other site-specific gene expression systems using tissue-specific promoters, this approach is expected to become a valuable tool enabling in vivo site-specific targeting in the field of gene therapy and molecular imaging.

DOI： 10.3892/or.2011.1371

Single Nucleotide Polymorphism WRN Leu1074Phe Is Associated with Prostate Cancer Susceptibility in Chinese Subjects Reviewed

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

ACTA MEDICA OKAYAMA 65 ( 5 ) 315 - 323 2011.10

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

T2^*-weighted Image/T2-weighted Image Fusion in Postimplant Dosimetry of Prostate Brachytherapy

KATAYAMA Norihisa, TAKEMOTO Mitsuhiro, YOSHIO Kotaro, KATSUI Kuniaki, UESUGI Tatsuya, NASU Yasutomo, MATSUSHITA Toshi, KAJI Mitsumasa, KUMON Hiromi, KANAZAWA Susumu

Journal of Radiation Research 52 ( 5 ) 680 - 684 2011.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Radiation Research Editorial Committee

Computed tomography (CT)/magnetic resonance imaging (MRI) fusion is considered to be the best method for postimplant dosimetry of permanent prostate brachytherapy; however, it is inconvenient and costly. In T2*-weighted image (T2*-WI), seeds can be easily detected without the use of an intravenous contrast material. We present a novel method for postimplant dosimetry using T2*-WI/T2-weighted image (T2-WI) fusion. We compared the outcomes of T2*-WI/T2-WI fusion-based and CT/T2-WI fusion-based postimplant dosimetry. Between April 2008 and July 2009, 50 consecutive prostate cancer patients underwent brachytherapy. All the patients were treated with 144 Gy of brachytherapy alone. Dose-volume histogram (DVH) parameters (prostate D90, prostate V100, prostate V150, urethral D10, and rectal D2cc) were prospectively compared between T2*-WI/T2-WI fusion-based and CT/T2-WI fusion-based dosimetry. All the DVH parameters estimated by T2*-WI/T2-WI fusion-based dosimetry strongly correlated to those estimated by CT/T2-WI fusion-based dosimetry (0.77 ≤ R ≤ 0.91). No significant difference was observed in these parameters between the two methods, except for prostate V150 (p = 0.04). These results show that T2*-WI/T2-WI fusion-based dosimetry is comparable or superior to MRI-based dosimetry as previously reported, because no intravenous contrast material is required. For some patients, rather large differences were observed in the value between the 2 methods. We thought these large differences were a result of seed miscounts in T2*-WI and shifts in fusion. Improving the image quality of T2*-WI and the image acquisition speed of T2*-WI and T2-WI may decrease seed miscounts and fusion shifts. Therefore, in the future, T2*-WI/T2-WI fusion may be more useful for postimplant dosimetry of prostate brachytherapy.

DOI： 10.1269/jrr.11011

Other Link： https://jlc.jst.go.jp/DN/JALC/00377998290?from=CiNii

転移性尿路上皮癌に対する全身化学療法後救済手術療法の有用性についての検討

別宮謙介, 雑賀隆史, 小林泰之, 神原太樹, 岸本涼, 江原伸, 那須保友, 公文裕巳

日本癌治療学会誌 46 ( 2 ) 982 - 982 2011.9

尿路上皮癌に対する術後補助療法としてのGem-CDDP-Pac(GCP)療法の治療成績

小林泰之, 別宮謙介, 江原伸, 上原慎也, 渡辺豊彦, 那須保友, 公文裕巳

日本癌治療学会誌 46 ( 2 ) 979 - 979 2011.9

Tumor suppressor REIC/Dkk-3 interacts with the dynein light chain, Tctex-1 Reviewed

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

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 412 ( 2 ) 391 - 395 2011.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

REIC/Dkk-3 is a member of the Dickkopf family proteins known as Wnt-antagonists, and REIC/Dkk-3 expression is downregulated in a broad range of cancer types. REIC/Dkk-3 acts as a tumor suppressor in multiple cancer cell lines by inducing apoptosis through endoplasmic reticulum (ER) stress signaling. However, the intracellular interaction partners of REIC/Dkk-3 have not been fully elucidated. By employing yeast two-hybrid screening, we identified the human dynein light chain, Tctex-1, as a novel interaction partner of REIC/Dkk-3. We further disclosed that the interaction involves the 136-157 amino acid region of REIC/Dkk-3 by using the mammalian two-hybrid system. Interestingly, this binding region of REIC/Dkk-3 with Tctex-1 contains an amino acid sequence motif [-(E) under bar -X-(G) under bar-(R) under bar-(R) under bar -X-(H) under bar-] which was previously reported as the Tctex-1 binding domain of dynein intermediate chain (DIC). Immunocytochemistry demonstrated that both REIC/Dkk-3 and Tctex-1 were localized around the ER of human fibroblasts, and the similar distribution pattern of the proteins suggests that their interaction occurs around the ER. This is the first study showing the interaction of a Dickkopf family protein with a dynein motor complex protein. The link between REIC/Dkk-3 and Tctex-1 may be of significance for understanding the molecular functions of the proteins in ER stress signaling and intracellular dynein motor dynamics, respectively. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2011.07.109

Epigenetic Silencing of MicroRNA-34b/c Plays an Important Role in the Pathogenesis of Malignant Pleural Mesothelioma Reviewed

Takafumi Kubo, Shinichi Toyooka, Kazunori Tsukuda, Masakiyo Sakaguchi, Takuya Fukazawa, Junichi Soh, Hiroaki Asano, Tsuyoshi Ueno, Takayuki Muraoka, Hiromasa Yamamoto, Yasutomo Nasu, Takumi Kishimoto, Harvey I. Pass, Hideki Matsui, Nam-ho Huh, Shinichiro Miyoshi

CLINICAL CANCER RESEARCH 17 ( 15 ) 4965 - 4974 2011.8

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC CANCER RESEARCH

Purpose: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal prognosis. Unlike other malignancies, TP53 mutations are rare in MPM. Recent studies have showed that altered expression of microRNA (miRNA) is observed in human malignant tumors. In this study, we investigated the alterations of miR-34s, a direct transcriptional target of TP53, and the role of miR-34s on the pathogenesis of MPM.
Experimental Design: Aberrant methylation and expression of miR-34s were examined in MPM cell lines and tumors. miR-34b/c was transfected to MPM cells to estimate the protein expression, cell proliferation, invasion, and cell cycle.
Results: Aberrant methylation was present in 2 (33.3%) of 6 MPM cell lines and 13 (27.7%) of 47 tumors in miR-34a and in all 6 MPM cell lines (100%) and 40 (85.1%) of 47 tumors in miR-34b/c. Expression of miR-34a and 34b/c in all methylated cell lines was reduced and restored with 5-aza-2'-deoxycytidine treatment. Because epigenetic silencing was the major event in miR-34b/c, we investigated the functional role of miR-34b/c in MPM. miR-34b/c-transfected MPM cells with physiologic miR-34b/c expression exhibited antiproliferation with G(1) cell cycle arrest and suppression of migration, invasion, and motility. The forced overexpression of miR-34b/c, but not p53, showed a significant antitumor effect with the induction of apoptosis in MPM cells.
Conclusions: We show that the epigenetic silencing of miR-34b/c by methylation is a crucial alteration and plays an important role in the tumorigenesis of MPM, suggesting potential therapeutic options for MPM. Clin Cancer Res; 17(15); 4965-74. (C)2011 AACR.

DOI： 10.1158/1078-0432.CCR-10-3040

Nerve growth factor level in the prostatic fluid of patients with chronic prostatitis/chronic pelvic pain syndrome is correlated with symptom severity and response to treatment Reviewed

Toyohiko Watanabe, Miayabi Inoue, Katsumi Sasaki, Motoo Araki, Shinya Uehara, Koichi Monden, Takashi Saika, Yasutomo Nasu, Hiromi Kumon, Michael B. Chancellor

BJU INTERNATIONAL 108 ( 2 ) 248 - 251 2011.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

OBJECTIVE
To explore whether levels of nerve growth factor (NGF) in expressed prostatic secretions (EPS) are correlated with symptom severity in chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS).
PATIENTS AND METHODS
All patients with CP/CPPS underwent a complete history and physical examination, and were scored according to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI).
Expressed prostatic secretion samples from 20 patients with CP/CPPS and from four asymptomatic control patients were collected and frozen, and NGF levels in EPS were measured by enzyme-linked immunosorbent assay.
Patients were asked to complete NIH-CPSI questionnaires at baseline and 8 weeks after treatment and patients with at least a 25% decrease in total NIH-CPSI score from the baseline values were classified as responders to treatment.
RESULTS
The mean (+/-SD) NGF levels in EPS of patients with CP/CPPS and asymptomatic control patients were 7409 (+/-3788) pg/mL and 4174 (+/-1349) pg/mL, respectively. The NGF level in patients with CP/CPPS correlated directly with pain severity (P = 0.014, r = 0.541).
There were no significant differences between NGF levels in EPS before and after treatment. However, successful treatment significantly decreased NGF levels in responders (P = 0.001).
CONCLUSION
Nerve growth factor might contribute to the pathophysiology of CP/CPPS as changes in NGF level in EPS occurred in proportion to pain severity. Therefore, these results suggest that NGF could be used as a new biomarker to evaluate the symptoms of CP/CPPS and the effects of treatment.

DOI： 10.1111/j.1464-410X.2010.09716.x

Maintenance therapy with bacillus Calmette-Guerin Connaught strain clearly prolongs recurrence-free survival following transurethral resection of bladder tumour for non-muscle-invasive bladder cancer

Shiro Hinotsu, Hideyuki Akaza, Seiji Naito, Seiichiro Ozono, Yoshiteru Sumiyoshi, Sumio Noguchi, Akito Yamaguchi, Satoshi Nagamori, Akito Terai, Yasutomo Nasu, Haruki Kume, Yoshihiko Tomita, Yoshinori Tanaka, Shoji Samma, Hirotsugu Uemura, Hirofumi Koga, Tomoyasu Tsushima

BJU INTERNATIONAL 108 ( 2 ) 187 - 195 2011.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

OBJECTIVETo confirm the recurrence-preventing efficacy and safety of 18-month bacillus Calmette-Guerin (BCG) maintenance therapy for non-muscle-invasive bladder cancer.PATIENTS AND METHODSThe enrolled patients had been diagnosed with recurrent or multiple non-muscle-invasive bladder cancer (stage Ta or T1) after complete transurethral resection of bladder tumours (TURBT).The patients were randomized into three treatment groups: a maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks as induction therapy, followed by three once-weekly instillations at 3, 6, 12 and 18 months after initiation of the induction therapy), a non-maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks) and an epirubicin group (epirubicin, 40 mg, intravesically instilled nine times). The primary endpoint was recurrence-free survival (RFS).RESULTSEfficacy analysis was performed for 115 of the full-analysis-set population of 116 eligible patients, including 41 maintenance group patients, 42 non-maintenance group patients and 32 epirubicin group patients.At the 2-year median point of the overall actual follow-up period, the final cumulative RFS rates in the maintenance, non-maintenance and epirubicin groups were 84.6%, 65.4% and 27.7%, respectively.The RFS following TURBT was significantly prolonged in the maintenance group compared with the non-maintenance group (generalized Wilcoxon test, P = 0.0190).CONCLUSIONBCG maintenance therapy significantly prolonged the post-TURBT RFS compared with BCG induction therapy alone or epirubicin intravesical therapy.

DOI： 10.1111/j.1464-410X.2010.09891.x

Nerve growth factor level in the prostatic fluid of patients with chronic prostatitis/chronic pelvic pain syndrome is correlated with symptom severity and response to treatment

Watanabe T, Inoue M, Sasaki K, Araki M, Uehara S, Monden K, Saika T, Nasu Y, Kumon H, Chancellor MB

JU 185 ( 4 ) 1301 - 1302 2011.7

[REIC/Dkk-3 gene therapy]. Reviewed

Masami Watanabe, Haruki Kaku, Peng Huang, Hiromi Kumon, Yasutomo Nasu

Nihon rinsho. Japanese journal of clinical medicine 69 Suppl 5 559 - 63 2011.6

Unexpected occurrence of adrenal Cushing's syndrome in a patient with systemic lupus erythematosus Reviewed

Akihiro Katayama, Fumio Otsuka, Katsuyuki Tanabe, Naoko Tsukamoto, Ryutaro Yamanaka, Yoshinori Matsumoto, Yasutomo Nasu, Hirofumi Makino

HYPERTENSION RESEARCH 34 ( 5 ) 662 - 663 2011.5

Intraperitoneal administration of an adenovirus vector carrying REIC/Dkk-3 suppresses peritoneal dissemination of scirrhous gastric carcinoma Reviewed

Swe Swe Than, Ken Kataoka, Masakiyo Sakaguchi, Hitoshi Murata, Fernando Abarzua, Chika Taketa, Gang Du, Masakazu Yashiro, Kazuyoshi Yanagihara, Yasutomo Nasu, Hiromi Kumon, Nam-Ho Huh

ONCOLOGY REPORTS 25 ( 4 ) 989 - 995 2011.4

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Expression levels of the novel tumor suppressor gene REIC/Dkk-3 are reduced in many human cancers. We have previously showed that an adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) induced apoptosis of cancer cells selectively and exerted bystander antitumor effects via ER stress. We examined possible effects of Ad-REIC in a peritoneal dissemination model of scirrhous gastric carcinoma (SGC). Among various types of gastric cancer, SGC continues to be associated with the worst prognosis due to a high incidence of metastases in the peritoneal cavity. We found that a single intraperitoneal injection of Ad-REIC suppressed tumor dissemination and disease progression. Immunomodulation by Ad-REIC led to recruitment of natural killer cells inside tumor nodules. We conclude that Ad-REIC gene therapy may be a potential tool in combinatorial approaches to achieve curative effects in SGC.

DOI： 10.3892/or.2011.1149

CHANGES IN CLITORIAL BLOOD FLOW FOLLOWING SURGERY WITH TENSION-FREE VAGINAL MESH FOR PELVIC ORGAN PROLAPSE Reviewed

Toyohiko Watanabe, Miyabi Inoue, Ayano Ishii, Toyoko Yamato, Motoo Araki, Shinya Uehara, Takashi Saika, Yasutomo Nasu, Hiromi Kumon

JOURNAL OF UROLOGY 185 ( 4 ) E685 - E685 2011.4

PRIMARY GLEASON GRADE 4 IMPACTS ON BIOCHEMICAL RECURRENCE AFTER PERMANENT INTERSTITIAL BRACHYTHERAPY IN JAPANESE PATIENTS WITH LOW- OR INTERMEDIATE-RISK PROSTATE CANCER Reviewed

Takashi Saika, Tatsuya Uesugi, Kohei Edamura, Hiroyuki Nose, Makoto Kobuke, Shin Ebara, Norihisa Katayama, Hiroyuki Yanai, Yasutomo Nasu, Hiromi Kumon

JOURNAL OF UROLOGY 185 ( 4 ) E523 - E523 2011.4

Prognostic Factors Influencing Survival after Nephroureterectomy for Transitional Cell Carcinoma of the Upper Urinary Tract Reviewed

Yasuyuki Kobayashi, Takashi Saika, Daisuke Manabe, Yasutomo Nasu, Hiromi Kumon

ACTA MEDICA OKAYAMA 65 ( 2 ) A27 - A31 2011.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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 disease-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 (p < 0.0001), tumor grade (p = 0.0324), and venous invasion (p < 0.0001). Multivariate analysis revealed that only venous invasion was significant for disease-specific survival rate (p = 0.0205). Venous invasion was the only independent prognostic factor in pathologically localized UUT-UC.

URETEROSCOPIC EVALUATION AND TREATMENT OF CHRONIC UNILATERAL HEMATURIA: A 24-YEAR EXPERIENCE Reviewed

Motoo Araki, Shinya Uehara, Koichi Monden, Toyohiko Watanabe, Takashi Saika, Yasutomo Nasu, Hiromi Kumon

JOURNAL OF UROLOGY 185 ( 4 ) E556 - E557 2011.4

PP-762 当院におけるeverolimusの使用経験(発表・討論,一般演題ポスター,第99回日本泌尿器科学会総会)

神原太樹, 雑賀隆史, 岸本涼, 別宮謙介, 能勢宏幸, 佐々木克己, 小林泰之, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 102 ( 2 ) 531 - 531 2011

めざせ1 座長のメッセージ(泌尿器科医のアフター5充実した余暇も多忙な日常診療へのギアチェンジ,めざせ!泌尿器科の星1,第99回日本泌尿器科学会総会)

白木良一, 篠原克人, 市川智彦, 那須保友

日本泌尿器科学会雑誌 102 ( 2 ) 269 - 269 2011

OP-048 進行胚細胞癌に対する化学療法後後腹膜リンパ節郭清術の検討 : 腫瘍学的、射精機能温存のアウトカム(精巣腫瘍,一般演題口演,第99回日本泌尿器科学会総会)

雑賀隆史, 神原太樹, 別宮謙介, 岸本涼, 小林泰之, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 102 ( 2 ) 348 - 348 2011

PP-780 転移性尿路上皮癌に対する全身化学療法後救済手術療法の有用性についての検討(発表・討論,一般演題ポスター,第99回日本泌尿器科学会総会)

別宮謙介, 雑賀隆史, 小林泰之, 岸本涼, 神原太樹, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 102 ( 2 ) 534 - 534 2011

Expression pattern of REIC/Dkk-3 in various cell types and the implications of the soluble form in prostatic acinar development

Kai Zhang, Masami Watanabe, Yuji Kashiwakura, Shun-Al Li, Kohei Edamura, Peng Huang, Ken Yamaguchi, Yasutomo Nasu, Yasuyuki Kobayashi, Masakiyo Sakaguchi, Kazuhiko Ochiai, Hiroshi Yamada, Kohji Takei, Hideo Ueki, Nam-Ho Huh, Ming Li, Haruki Kaku, Yanqun Na, Hiromi Kumon

INTERNATIONAL JOURNAL OF ONCOLOGY 37 ( 6 ) 1495 - 1501 2010.12

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

The tumor suppressor REIC/Dkk-3 is a secretory protein which was originally identified to be downregulated in human immortalized cells In the present study, we investigated the expression pattern of REIC/Dkk-3 in various cell types to characterize its physiological functions We first examined the expression level of REIC/Dkk-3 in a broad range of cancer cell types and confirmed that it was significantly downregulated in all of the cell types We also examined the tissue distribution pattern in a variety of normal mouse organs Ubiquitous REIC/Dkk-3 protein expression was observed in the organs The expression was abundant in the liver, heart and brain tissue, but was absent in the spleen and peripheral blood mononuclear cells The immunohistochemical analyses revealed that the subcellular localization of REIC/Dkk-3 had a punctate pattern around the nucleus, indicating its association with secretory vesicles In cancer cells stably transfected with REIC/Dkk-3 the protein was predominantly localized to the endoplasmic reticulum (ER) under observation with confocal microscopy Because REIC/ Dkk-3 was found to be abundantly expressed in the acinar epithelial cells of the mouse prostate, we analyzed the effects of recombinant REIC/Dkk-3 protein on the acinar morphogenesis of RWPE-1 cells, which are derived from human normal prostate epithelium Statistically significant acinar growth was observed in the culture condition with 10 mu g/m1 REIC/Dkk-3 protein, implicating the soluble form m prostatic acinar development Current results suggest that REIC/Dkk-3 may play a role in regulating the morphological process of normal tissue architecture through an autocrine and/or paracrine manner

DOI： 10.3892/ijo_00000802

Indications for Ureteropyeloscopy Based on Radiographic Findings and Urine Cytology in Detection of Upper Urinary Tract Carcinoma Reviewed

Akira Takao, Takashi Saika, Shinya Uehara, Koichi Monden, Fernando Abarzua, Yasutomo Nasu, Hiromi Kumon

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 40 ( 11 ) 1087 - 1091 2010.11

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

To verify the indication of diagnostic ureteropyeloscopy based on clinical features for upper urinary tract urothelial cancer with over 100 patients and over a 10-year series.
From January 1997 to December 2008, consecutive 129 units in 124 patients underwent ureteropyeloscopy to obtain a definitive diagnosis of upper urinary tract cancer or to rule out a malignancy. Patients were divided into four subgroups based on voided urine cytology and preoperative radiographic findings: group A (n = 8), positive urine cytology and positive radiographic findings; group B (n = 4), positive cytology and negative radiographic findings; group C (n = 55), negative cytology and positive radiographic findings and group D (n = 62), gross hematuria originating from the upper urinary tract with negative cytology and negative radiographic findings. Ureteropyeloscopic findings were compared with radiographic and cytological results. Adverse effects were also investigated.
In group A, all patients had confirmed cancer. In group B, one revealed small cancer and the remaining three confirmed carcinoma in situ by biopsy with ureteropyeloscopy. In groups C and D, 33 patients (60%) and four (6.5%) revealed cancer. Seventy-eight patients out of 80 (97.5%) in groups C and D were confirmed to have benign disease. No patient was found with malignancy during follow up after negative finding of ureteropyeloscopy.
Ureteropyeloscopy can help in detecting upper urinary tract cancer or to rule out malignancy for patients with negative voiding cytology. However, ureteropyeloscopy is redundant for patients with positive radiographic findings and positive voiding cytology.

DOI： 10.1093/jjco/hyq096

術前6週間の免疫抑制とリツキサンを用いて成功した免疫学的ハイリスク生体腎移植症例の1例

河内啓一郎, 荒木元朗, 小武家誠, 上松克利, 小林泰之, 雑賀隆史, 那須保友, 公文裕巳, 齋藤和英, 高橋公太

移植 45 ( 5 ) 535 - 536 2010.10

次世代の外科治療腎がんに対するCTガイド下経皮的ラジオ波焼灼療法(RFA)の現状と将来

那須保友, 小林泰之, 雑賀隆史, 公文裕巳, 郷原英夫, 金澤右

西日本泌尿器科 72 ( 増刊 ) 81 - 81 2010.10

Bladder cancer working group report

Kakehi Y, Hirao Y, Kim W-J, Ozono S, Masumori N, Miyanaga N, Nasu Y, Yokomizo A

Jpn J Clin Oncol 40 ( Suppl1 ) 57 - 64 2010.9

Hepatocyte growth factor activator inhibitors(HAI-1 and HAI-2) are potential targets in uterine leiomyosarcoma

Nakamura K, Abarzua F, Hongo A, Kodama J, Nasu Y, Kumon H, Hiramatsu Y

Int J Oncol 37 ( 3 ) 605 - 614 2010.9

早期前立腺がんの治療戦略前立腺癌に対する根治療法前立腺全摘除術or密封小線源療法単一施設における検討

枝村康平, 雑賀隆史, 上杉達也, 能勢宏幸, 小林泰之, 真鍋大輔, 小武家誠, 江原伸, 那須保友, 公文裕巳

日本癌治療学会誌 45 ( 2 ) 492 - 492 2010.9

岡山大学における低、中リスク限局性前立腺癌に対するI-125永久密封小線源療法の成績

岸本涼, 枝村康平, 能勢宏幸, 上杉達也, 小武家誠, 小林泰之, 賀来春紀, 雑賀隆史, 那須保友, 公文裕巳

日本癌治療学会誌 45 ( 2 ) 677 - 677 2010.9

進行尿路上皮癌に対する化学療法奏功例におけるSalvage Surgeryの臨床的意義

雑賀隆史, 別宮謙介, 岸本涼, 枝村康平, 小林泰之, 賀来春紀, 那須保友, 公文裕巳

日本癌治療学会誌 45 ( 2 ) 1045 - 1045 2010.9

Two instillations of epirubicin as prophylaxis for recurrence after transurethral resection of Ta and T1 transitional cell bladder cancer: a prospective, randomized controlled study Reviewed

Takashi Saika, Tomoyasu Tsushima, Yasutomo Nasu, Yoshiyuki Miyaji, Michihisa Saegusa, Katsuji Takeda, Hiromi Kumon

WORLD JOURNAL OF UROLOGY 28 ( 4 ) 413 - 418 2010.8

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Although transurethral resection (TUR) is the standard treatment for non-muscle-invasive bladder tumors, 40-80% of tumors recur in spite of complete resection.
To evaluate the efficacy, dose effectiveness and safety of early short-duration intravesical instillation therapy using epirubicin (EPI) administered immediately after TUR and on the next day following TUR.
Between 1995 and 2001, 303 patients with Ta and T1 non-muscle-invasive bladder carcinoma were enrolled in this study. Patients were randomized into three groups. Group A patients were treated with two intravesical infusions of EPI 20 mg/40 ml saline immediately after TUR and within 24 h. Group B patients were treated with EPI 50 mg/100 ml on the same schedule as group A. Group C patients were treated by TUR alone as a control group. The primary endpoint was a duration to the first recurrence.
Of the 303 patients, 79 in Group A, 84 in Group B, and 77 in Group C could be evaluated for recurrence. Median follow-up was 44 months. Median recurrence-free survival durations for Groups A, B, and C were 24, 38, and 13 months, respectively. The difference between Groups B and C was statistically significant (p = 0.04). Adverse reactions related to instillation were observed in about 30% of the patients. These reactions included micturition pain and frequency. These toxicities were mild and transient.
Intravesical instillation of EPI 50 mg twice within 24 h after TUR was effective as prophylactic therapy for non-muscle-invasive bladder cancer with tolerable toxicity problems.

DOI： 10.1007/s00345-009-0502-1

5alphaDH-DOC (5alpha-dihydro-deoxycorticosterone) activates androgen receptor in castration-resistant prostate cancer. International journal

Motohide Uemura, Seijiro Honma, Suyoun Chung, Ryo Takata, Mutsuo Furihata, Kazuo Nishimura, Norio Nonomura, Yasutomo Nasu, Tsuneharu Miki, Taro Shuin, Tomoaki Fujioka, Akihiko Okuyama, Yusuke Nakamura, Hidewaki Nakagawa

Cancer science 101 ( 8 ) 1897 - 1904 2010.8

Language：English Publishing type：Research paper (scientific journal)

Prostate cancer often relapses during androgen-depletion therapy, even under the castration condition in which circulating androgens are drastically reduced. High expressions of androgen receptor (AR) and genes involved in androgen metabolism indicate a continued role for AR in castration-resistant prostate cancers (CRPCs). There is increasing evidence that some amounts of 5alpha-dihydrotestosterone (DHT) and other androgens are present sufficiently to activate AR within CRPC tissues, and enzymes involved in the androgen and steroid metabolism, such as 5alpha-steroid reductases, are activated in CRPCs. In this report, we screened eight natural 5alphaDH-steroids to search for novel products of 5alpha-steroid reductases, and identified 11-deoxycorticosterone (DOC) as a novel substrate for 5alpha-steroid reductases in CRPCs. 11-Deoxycorticosterone (DOC) and 5alpha-dihydro-deoxycorticosterone (5alphaDH-DOC) could promote prostate cancer cell proliferation through AR activation, and type 1 5alpha-steroid reductase (SRD5A1) could convert from DOC to 5alphaDH-DOC. Sensitive liquid chromatography-tandem mass spectrometric analysis detected 5alphaDH-DOC in some clinical CRPC tissues. These findings implicated that under an extremely low level of DHT, 5alphaDH-DOC and other products of 5alpha-steroid reductases within CRPC tissues might activate the AR pathway for prostate cancer cell proliferation and survival under castration.

DOI： 10.1111/j.1349-7006.2010.01620.x

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 Reviewed

P. Huang, H. Kaku, J. Chen, Y. Kashiwakura, T. Saika, Y. Nasu, Y. Urata, T. Fujiwara, M. Watanabe, H. Kumon

CANCER GENE THERAPY 17 ( 7 ) 484 - 491 2010.7

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

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. Cancer Gene Therapy (2010) 17, 484-491; doi:10.1038/cgt.2010.5; published online 19 February 2010

DOI： 10.1038/cgt.2010.5

A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer

Masanori Noguchi, Tatsuyuki Kakuma, Hirotsugu Uemura, Yasutomo Nasu, Hiromi Kumon, Yasuhiko Hirao, Fukuko Moriya, Shigetaka Suekane, Kei Matsuoka, Nobukazu Komatsu, Shigeki Shichijo, Akira Yamada, Kyogo Itoh

CANCER IMMUNOLOGY IMMUNOTHERAPY 59 ( 7 ) 1001 - 1009 2010.7

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.

DOI： 10.1007/s00262-010-0822-4

Down-regulation of BiP/GRP78 sensitizes resistant prostate cancer cells to gene-therapeutic overexpression of REIC/Dkk-3 Reviewed

Ryuta Tanimoto, Masakiyo Sakaguchi, Fernando Abarzua, Ken Kataoka, Kaoru Kurose, Hitoshi Murata, Yasutomo Nasu, Hiromi Kumon, Nam-Ho Huh

INTERNATIONAL JOURNAL OF CANCER 126 ( 7 ) 1562 - 1569 2010.4

Language：English Publishing type：Research paper (scientific journal) Publisher：JOHN WILEY & SONS INC

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.

DOI： 10.1002/ijc.24764

Frequent silencing of tumor suppressive MicroRNA-34b/c by aberrant methylation in malignant mesothelioma Reviewed

Takafumi Kubo, Shinichi Toyooka, Kazunori Tsukuda, Hiroaki Asano, Masakiyo Sakaguchi, Junichi Soh, Tsuyoshi Ueno, Hiromasa Yamamoto, Masaomi Yamane, Takahiro Oto, Yasutomo Nasu, Hideki Matsui, Nam Ho Huh, Shinichro Miyoshi

CANCER RESEARCH 70 2010.4

CLITORIAL BLOOD FLOW CHANGES AFTER SURGERY WITH TENSION-FREE VAGINAL MESH FOR PELVIC ORGAN PROLAPSE Reviewed

Watanabe Toyohiko, Inoue Miyabi, Ishii Ayano, Yamato Toyoko, Nose Hiroyuki, Uematsu Katsutoshi, Sasaki Katsumi, Araki Motoo, Uehara Shinya, Saika Takashi, Nasu Yasutomo, Kumon Hiromi

JOURNAL OF UROLOGY 183 ( 4 ) E583 2010.4

Prognostic Factors Influencing Survival after Nephroureterectomy for Transitional Cell Carcinoma of the Upper Urinary Tract Reviewed

Yasuyuki Kobayashi, Takashi Saika, Daisuke Manabe, Yasutomo Nasu, Hiromi Kumon

ACTA MEDICA OKAYAMA 64 ( 1 ) 27 - 31 2010.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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 wits 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 (p < 0.0001), tumor grade (p = 0.0324), and venous invasion (p < 0.0001). Multivariate analysis revealed that only venous invasion was significant for disease-specific survival rate (p = 0.0205). Venous invasion wits the only independent prognostic factor in pathologrically localized UUT-UC.

PP-416 新しい遠隔操作装置を用いた超音波ドプラ排尿動態検査(発表・討論,第98回日本泌尿器科学会総会)

上松克利, 渡辺豊彦, 鬼武万由子, 太田尚子, 宗宮昌子, 佐々木克己, 能勢宏幸, 小澤秀夫, 矢吹孝之, 谷本圭司, 山内博明, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 101 ( 2 ) 472 - 472 2010

REIC/Dkk-3 stable transfection reduces the malignant phenotype of mouse prostate cancer RM9 cells

Jie Chen, Masami Watanabe, Peng Huang, Masakiyo Sakaguchi, Kazuhiko Ochiai, Yasutomo Nasu, Mamoru Ouchida, Nam-Ho Huh, Kenji Shimizu, Yuji Kashiwakura, Haruki Kaku, Hiromi Kumon

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 24 ( 6 ) 789 - 794 2009.12

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

The reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3. a member of the Dkk gene family, is a tumor suppressor in a broad range of cancers. REIC/Dkk-3 transfected stable clones of mouse prostate cancer RM9 cells (RM9-REIC) and the empty vector-transfected control clone cells (RM9-EV) were established. Clones were used to evaluate the anti-cancer effects and a proteomics analysis of REIC/Dkk-3 continuous expression was performed. The RM9-REIC cells show a feeble appearance and the cell membrane shows irregular buds known as blebs. In vitro cell proliferation was significantly suppressed in RM9-REIC clones in comparison to the control. The apoptosis assay was done under standard culture conditions and RM9-REIC showed a higher incidence of apoptosis. The RM9-EV and RM9-REIC cells were orthotopically implanted into a C57BL/6 mouse prostate. After 2 weeks, the tumor growth was significantly inhibited in RM9-REIC cells in comparison to the control. Two-dimensional gel electrophoresis was used to examine the modification of protein expression by the gene transfection. The analysis with mass spectrometry disclosed that expression of peroxiredoxin-l, GST-P1. transgelin-2, MRP-L12, ARD, GRP78 and Sorcin were increased and eEF1A-1 and cyclophilin-40 protein were decreased in RM9-REIC cells. Therefore, REIC/Dkk-3 stable transfectants show a reduction of malignancy in mouse prostate cancer RM9 cells in vitro and in vivo. The result of the proteomics analysis might provide important clues to clarify the anti-cancer molecular mechanism of REIC/Dkk-3 gene transfer.

DOI： 10.3892/ijmm_00000293

Dynasore, a dynamin inhibitor, suppresses lamellipodia formation and cancer cell invasion by destabilizing actin filaments Reviewed

Hiroshi Yamada, Tadashi Abe, Shun-Ai Li, Yuki Masuoka, Mihoko Isoda, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Akira Asai, Kohji Takei

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 390 ( 4 ) 1142 - 1148 2009.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Dynamic remodeling of actin filaments are bases for a variety of cellular events including cell motility and cancer invasion, and the regulation of actin dynamics implies dynamin, well characterized endocytotic protein. Here we report that dynasore, a inhibitor of dynamin GTPase, potently destabilizes F-actin in vitro, and it severely inhibits the formation of pseudopodia and cancer cell invasion, both of which are supported by active F-actin formation. Dynasore rapidly disrupted F-actin formed in brain cytosol in vitro, and the dynasore's effect on F-actin was indirect. Dynasore significantly suppressed serum-induced lamellipodia formation in U2OS cell. Dynasore also destabilized F-actin in resting cells, which caused the retraction of the plasma membrane. A certain amount of dynamin 2 in U2OS cells localized along F-actin, and co-localized with cortactin, a physiological binding partner of dynamin and F-actin. However. these associations of dynamin were partially disrupted by dynasore treatment. Furthermore, invasion activity of H1080 cell, a lung cancer cell line, was suppressed by approximately 40% with dynasore treatment. These results strongly suggest that dynasore potently destabilizes F-actin, and the effect implies dynamin. Dynasore or its derivative would be suitable candidates as potent anti-cancer drugs. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2009.10.105

腹腔鏡下尿膜管遺残摘出術の4例

荒木元朗, 雑賀隆史, 上原慎一, 那須保友, 小林泰之, 渡邊豊彦, 公文裕巳

日本内視鏡外科学会雑誌 14 ( 7 ) 344 - 344 2009.12

A comparison of proteomic profiles changes during 17beta-estradiol treatment in human prostate cancer PC-3 cell line. Reviewed

Chen J,Huang P, Kaku H, Zhang K, Watanabe M, Saika T, Nasu Y, Kumon H

Cancer Genomics Proteomics 2009.11

Overexpression of the potential kinase serine/threonine/tyrosine kinase 1 (STYK 1) in castration-resistant prostate cancer

CHUNG Suyoun, TAMURA Kenji, FURIHATA Mutsuo, UEMURA Motohide, DAIGO Yataro, NASU Yasutomo, MIKI Tsuneharu, SHUIN Taro, FUJIOKA Tomoaki, NAKAMURA Yusuke, NAKAGAWA Hidewaki

100 ( 11 ) 2109 - 2114 2009.11

CTガイド下RFAが困難であったVHL随伴腎癌に対する腹腔鏡補助下RFAの経験

上松克利, 雑賀隆史, 郷原秀夫, 三村秀文, 荒木元朗, 石井亜矢乃, 小林泰之, 那須保友, 金澤右, 公文裕巳

Japanese Journal of Endourology and ESWL 22 ( 3 ) 165 - 165 2009.11

陰茎原発epithelioid sarcomaに対し陰茎全摘除術後に尿道陰茎再建術行った1例

西村慎吾, 枝村康平, 小林泰之, アバラズア・フェルナンド, 石井和史, 雑賀隆史, 那須保友, 公文裕巳

西日本泌尿器科 71 ( 増刊 ) 132 - 132 2009.10

右心房・右心室への進展をみとめる血栓患者に対する根治的腎摘出術(Radical Nephrectomy for a patient with a thrombus extending into the right atrium and ventricle)

Fernando Abarzua, 小林泰之, 西村慎吾, 雑賀隆史, 那須保友, 公文裕巳

西日本泌尿器科 71 ( 増刊 ) 168 - 168 2009.10

前立腺癌に対するHybrid radical prostatectomyのOncological outcomes

雑賀隆史, 小林泰之, 上原慎也, 荒木元朗, 高尾彰, 上杉達也, 那須保友, 公文裕巳

日本癌治療学会誌 44 ( 2 ) 428 - 428 2009.9

進行性尿路上皮癌に対するGCP療法の検討

枝村康平, 雑賀隆史, 谷本竜太, 高尾彰, 小林泰之, 上杉達也, 賀来春紀, 那須保友, 公文裕巳

日本癌治療学会誌 44 ( 2 ) 593 - 593 2009.9

上部尿路疾患に対する腎盂尿管鏡の有用性に関する検討

高尾彰, 雑賀隆史, 枝村康平, 小林泰之, 小武家誠, 上杉達也, 上原慎也, 賀来春紀, 門田晃一, 那須保友, 公文裕巳

日本癌治療学会誌 44 ( 2 ) 763 - 763 2009.9

The role of hepatocyte growth factor activator inhibitor-1(HAI-1)as a prognostic indicator in cervical cancer

Nakamura K, Abarzua F, Hongo A, Kodama J, Nasu Y, Kumon H, Hiramatsu Y

Int J Oncol 35 ( 2 ) 239 - 248 2009.8

Overexpressing PKIB in prostate cancer promotes its aggressiveness by linking between PKA and Akt pathways

Chung S, Furihata M, Tamura K, Uemura M, Daigo Y, Nasu Y, Miki T, Shuin T, Fujioka T, Nakamura Y, Nakagawa H

Oncogene 28 ( 32 ) 2849 - 2859 2009.8

Prospective Longitudinal Comparative Study of Health-Related Quality of Life in Patients Treated with Radical Prostatectomy or Permanent Brachytherapy for Prostate Cancer Reviewed

Makoto Kobuke, Takashi Saika, Yoshiko Nakanishi, Shin Ebara, Daisuke Manabe, Tatsuya Uesugi, Hiroyuki Nose, Ryoji Arata, Tomoyasu Tsushima, Yasutomo Nasu, Hiromi Kumon

ACTA MEDICA OKAYAMA 63 ( 3 ) 129 - 135 2009.6

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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 I 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 I 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.

Overexpression of REIC/Dkk-3 in Normal Fibroblasts Suppresses Tumor Growth via Induction of Interleukin-7

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

JOURNAL OF BIOLOGICAL CHEMISTRY 284 ( 21 ) 14236 - 14244 2009.5

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

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.

DOI： 10.1074/jbc.M808002200

Expression of Matriptase and Clinical Outcome of Human Endometrial Cancer Reviewed

Keiichiro Nakamura, Atsushi Hongo, Junichi Kodama, Fernando Abarzua, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

ANTICANCER RESEARCH 29 ( 5 ) 1685 - 1690 2009.5

Language：English Publishing type：Research paper (scientific journal) Publisher：INT INST ANTICANCER RESEARCH

Background: Matriptase, a type II transmembrane serine protease is involved in angiogenesis, degradation of extracellular matrix and in progression of some epithelial cancers. The purpose of the present study was to examine matriptase expression and evaluate its clinicopathological significance in endometrial cancer. Patients and Methods: Matriptase expression was examined in normal endometrium (n=20), endometrial hyperplasia (n=11) and endometrial cancer (n=65) samples. The distribution of cases that scored positive for each of the biological parameters examined was correlated with matriptase expression status obtained by immunohistochemistry. Results: Matriptase was found to be significantly overexpressed in endometrial cancer as compared with normal endometrium and endometrial hyperplasia. Interestingly, matriptase expression is associated with stage (p=0.010), grade (p=0.021), depth of myometrial invasion (p=0.004), cervical involvement (p=0.021), lymph node metastasis (p=0.009), LVS involvement (p=0.041) and peritoneal cytology (p=0.045). The high matriptase expression was a significant predictor for poor prognosis when compared with low matriptase expression (Disease-free survival rate; p=0.032, Overall survival rate; p=0.011). Conclusion: High matriptase expression in endometrial cancer may be associated with poor prognosis.

Stanniocalcin 2 overexpression in castration-resistant prostate cancer and aggressive prostate cancer

Tamura K, Furihata M, Chung S.Y, Uemura M, Yoshioka H, Iiyama T, Ashida S, Nasu Y, Fujioka T, Shuin T, Nakamura Y, Nakagawa H

Cancer Sci 100 ( 5 ) 914 - 919 2009.5

Prostate-specific antigen 'bounce' after permanent 125I -implant brachytherapy in Japanese men:a multi-institutional pooled analysis

Satoh T, Ishiyama H, Matsumoto K, Tsumura H, Kitano M, Hayakawa K, Ebara S, Nasu Y, Kumon H, Kanazawa S, Miki K, Egawa S, Aoki M, Toya K, Yorozu A, Nagata H, Saito S, Baba S

BJU International 103 ( 8 ) 1064 - 1068 2009.4

Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression

Masami Watanabe, Yuji Kashiwakura, Peng Huang, Kazuhiko Ochiai, Junichiro Futami, Shun-Ai Li, Munenori Takaoka, Yasutomo Nasu, Masakiyo Sakaguchi, Nam-Ho Huh, Hiromi Kumon

INTERNATIONAL JOURNAL OF ONCOLOGY 34 ( 3 ) 657 - 663 2009.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

The REIC/Dkk-3 gene has been reported to be a tumor suppressor and the expression is significantly down-regulated in a broad range of cancer cell types. The protein is secretory, but the physiological function remains unclear. This study demonstrated that recombinant REIC/Dkk-3 protein induced the differentiation of human CD14(+) monocytes into a novel cell type ((REIC/Dkx-3)Mo). (REIC/Dkk-3)Mo resembles immature dendritic cells generated with IL-4 and GM-CSF. Both these cell populations exhibit similar proportions of CD11c(+), CD40(+), CD86(+) and HLA-DR(+) cells and endocytic capacity, but (REIC/Dkk-3)Mo is negative for CD1a antigen. An analysis of the signal transducers and activators of transcription (STAT) pathways revealed that REIC/Dkk-3 induces phosphorylation of STAT 1 and STAT 3. Furthermore, intratumoral administration of REIC/Dkk-3 protein significantly suppressed tumor growth with CD11c(+) and CD8(+) (dendritic and killer T cell marker, respectively) cell accumulation and enhanced anticancer cytolytic activity of splenocytes. These data indicated a cytokine-like role of REIC/Dkk-3 protein in monocyte differentiation that might be exploited therapeutically.

DOI： 10.3892/ijo_00000191

Expression of hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) in ovarian cancer

Nakamura K, Abarzua F, Kodama J, Hongo A, Nasu Y, Kumon H, Hiramatsu Y

Int J Oncol 34 ( 2 ) 345 - 353 2009.2

エンドユロロジー・腹腔鏡領域腎癌に対するCTガイド下経皮的ラジオ波焼灼療法

小林泰之, 郷原英夫, 枝村康平, 小武家誠, 上杉達也, 雑賀隆史, 那須保友, 金澤右, 公文裕巳

日本泌尿器科学会雑誌 100 ( 2 ) 77 - 77 2009.2

Hepatocyte growth factor activator inhibitor-2(HAI-2)is a favorable prognosis marker and inhibits cell growth through the apoptotic pathway in cervical cancer

Nakamura K, Abarzua F, Hongo A, Kodama J, Nasu Y, Kumon H, Hiramatsu Y

Annals of Oncology 20 ( 1 ) 63 - 70 2009.1

OP-209 限局性前立腺癌に対する高密度焦点式超音波(HIFU)による治療成績(前立腺腫瘍/HIFU,一般演題口演,第97回日本泌尿器科学会総会)

津川昌也, 中村あや, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 100 ( 2 ) 241 - 241 2009

OP-303 岡山大学病院におけるI125前立腺癌永久密封小線源療法の治療成績(前立腺腫瘍/放射線治療3,一般演題口演,第97回日本泌尿器科学会総会)

上杉達也, 小武家誠, 藤尾圭, 谷本竜太, 小林泰之, 賀来春紀, 雑賀隆史, 那須保友, 公文裕巳, 小林知子, 江原伸

日本泌尿器科学会雑誌 100 ( 2 ) 264 - 264 2009

APP-031-PM 上部尿路上皮癌に対する腎尿管全摘除術術後の膀胱内再発に関する検討 : 早期尿管結紮は膀胱内再発のリスクを軽減するか?(総会賞応募ポスター,第97回日本泌尿器科学会総会)

小林泰之, 雑賀隆史, 江原伸, 宮地禎幸, 倉繁拓志, 津島知靖, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 100 ( 2 ) 140 - 140 2009

A comparison of proteomic profiles changes during 17β-estradiol treatment in human prostate cancer PC-3 cell line Reviewed

Jie Chen, Peng Huang, Haruki Kaku, Kai Zhang, Masami Watanabe, Takashi Saika, Yasutomo Nasu, Hiromi Kumon

Cancer Genomics and Proteomics 6 ( 6 ) 331 - 335 2009

Language：English Publishing type：Research paper (scientific journal) Publisher：International Institute of Anticancer Research

Human telomerase reverse transcriptase (hTERT) is overexpressed in prostate cancer. Estrogen plays a central role in the development of prostate cancer. hTERT activity has been shown to be increased after estrogen treatment. Although significant efforts have been made to understand the role of estrogen, the telomerase connection with estrogen is poorly understood. In this report, we describe a proteomics approach for investigating the global changes in protein expression in estrogen-treated human prostate cancer PC-3 cells. PC-3 cells were seeded in medium and then treated with estrogen
the protein extract from these cells was used for two-dimensional (2D) gel electrophoresis. The protein spots were subjected to comparative analysis by liquid chromatography/mass spectrometry (LC/MS). We observed that the expression of 17 proteins, including stress-induced phosphoprotein 1 and lamin-A/C was down-regulated, and that the expression of proteins such as subunit a of T-complex protein 1, tubulin alpha-1B, and other 13 proteins was up-regulated. These proteins may have been closely associated with estrogen-induced hTERT activity. The expression level of these proteins could be a useful parameter for evaluating the estrogen-induced hTERT activity in clinical specimens of human prostate cancer.

Initial report of hybrid radical prostatectomy for prostate cancer: reduced bleeding, clear vision, and secure surgical margins. Reviewed

Saika T, Kobayashi Y, Watanabe T, Manabe D, Ebara S, Uehara S, Nasu Y, Kumon H

Acta medica Okayama 62 ( 6 ) 379 - 384 2008.12

Language：English Publishing type：Research paper (scientific journal)

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 220 min, median blood loss was 550 ml, 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.

DOI： 10.18926/AMO/30950

Mechanistic analysis of resistance to REIC/Dkk-3-induced apoptosis in human bladder cancer cells. Reviewed

Kobayashi T, Sakaguchi M, Tanimoto R, Abarzua F, Takaishi M, Kaku H, Kataoka K, Saika T, Nasu Y, Miyazaki M, Kumon H, Huh NH

Acta medica Okayama 62 ( 6 ) 393 - 401 2008.12

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.18926/AMO/30945

An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces apoptosis

Fernando Abarzua, Yuji Kashiwakura, Munenori Takaoka, Masami Watanabe, Kazuhiko Ochiai, Masakiyo Sakaguchi, Takao Iwawaki, Ryuta Tanimoto, Yasutomo Nasu, Nam-ho Huh, Hiromi Kumon

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 375 ( 4 ) 614 - 618 2008.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Overexpression of REIC/Dkk-3 (a tumor suppressor gene) induces cancer cell apoptosis through endoplasmic reticulum (ER) stress. Therefore, the identification of the portion of REIC/Dkk-3 that causes ER stress may be essential for the development of cancer treatment based on REIC/Dkk-3. Here, we made several truncated forms of REIC/Dkk-3 and investigated their therapeutic potentials against prostate cancer. Among three truncated forms, a variant comprising the N-terminal 78 amino acid region of REIC/Dkk-3 ((1-78) REIC/Dkk-3) most strongly induced ER stress and apoptosis in human prostate cancer cells (PC3). For in vivo gene expression, we coupled a biodegradable polymer with naked DNA, which attained robust trans-gene expression in PC3-derived subcutaneous tumor. In therapeutic experiments, we demonstrated that multiple direct injections of polymer-conjugated (1-78)REIC/Dkk-3 plasmid provoke ER stress and significantly reduced the subcutaneous tumor volume compared with the control group. We suggest this non-viral strategy may be an effective alternative to viral gene therapy. (C) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2008.08.079

Down-regulation of Inhibition of Differentiation-1 via Activation of Activating Transcription Factor 3 and Smad Regulates REIC/Dickkopf-3-Induced Apoptosis

Yuji Kashiwakura, Kazuhiko Ochiai, Masami Watanabe, Fernando Abarzua, Masakiyo Sakaguchi, Munenori Takaoka, Ryuta Tanimoto, Yasutomo Nasu, Nam-ho Hub, Hiromi Kumon

CANCER RESEARCH 68 ( 20 ) 8333 - 8341 2008.10

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC CANCER RESEARCH

REIC/Dickkopf-3 (Dkk-3), a tumor suppressor gene, has been investigated in gene therapy studies. Our previous study suggested that REIC/Dkk-3-induced apoptosis mainly resulted from phosphorylation of c-Jun-NH2 kinase (JNK) in prostate cancer cells. However, the precise mechanisms, especially the molecular mechanisms regulating JNK phosphorylation, remain unclear. In this study, we investigated the mechanisms participating in JNK phosphorylation in the context of a refractory cancer disease, malignant mesothelioma (MM). Adenovirus-mediated overexpression of REIC/Dkk-3 induced apoptosis mainly through JNK activation in immortalized MM cells (211H cells). Interestingly, transcriptional down-regulation of inhibition of differentiation-1 (Id-1) was detected in REIC/Dkk-3-overexpressed 211H cells. Moreover, restoration of Id-1 expression antagonized REIC/Dkk-3-induced JNK phosphorylation and apoptosis. Mutagenesis experiments with the 2.1-kb human Id-1 promoter revealed that activating transcription factor 3 (ATF3) and Smad interaction, with their respective binding motifs, was essential for REIC/Dkk-3-mediated suppression of Id-1 promoter activity. ATF3 activation was probably induced by endoplasmic reticulum stress. Finally, we showed strong antitumor effects from REIC/Dkk-3 gene transfer into the pleural cavity in an orthotopic MM mouse model. Relative to control tumor tissue, REIC/Dkk-3-treated tumor tissue showed down-regulated expression of Id-1 mRNA, enhanced expression of phosphorylated JNK, and an increased number of apoptotic cells. In summary, we first showed that both ATF3 and Smad were crucially and synergistically involved in down-regulation of Id-1, which regulated JNK phosphorylation in REIC/Dkk-3-induced apoptosis. Thus, gene therapy with REIC/Dkk-3 may be a promising therapeutic tool for MM. [Cancer Res 2008;68(20):8333-41]

DOI： 10.1158/0008-5472.CAN-08-0080

難治性尿路上皮癌および精巣腫瘍に対する化学療法難治性精巣腫瘍にたいする3rd line化学療法としてのGemcitabine(GEM)、Cisplatinum(CDDP)、Paclitaxel(PTX)併用療法の経験

雑賀隆史, 小武家誠, 上杉達也, 小林泰之, 谷本竜太, 枝村康平, 賀来春紀, 那須保友, 公文裕巳

西日本泌尿器科 70 ( 増刊 ) 112 - 112 2008.10

切除不能・再発尿路上皮癌に対するGemcitabine(GEM)、Cisplatin(CDDP)、Paclitaxel(PAC)-GCP療法-の検討

谷本竜太, 枝村康平, 雑賀隆史, 和田耕一郎, 小林泰之, 小武家誠, 大和豊子, 賀来春紀, 那須保友, 公文裕巳

日本癌治療学会誌 43 ( 2 ) 486 - 486 2008.10

岡山大学病院におけるI125前立腺癌永久密封小線源療法の治療成績

上杉達也, 小武家誠, 藤尾圭, 谷本竜太, 小泉文人, 小林泰之, 雑賀隆史, 那須保友, 公文裕巳, 小林知子, 江原伸

日本癌治療学会誌 43 ( 2 ) 711 - 711 2008.10

後腹膜鏡下膀胱部分切除術を行った膀胱頂部炎症性筋線維芽細胞腫の1例

和田耕一郎, 雑賀隆史, 佐古真一, 小林泰之, 上原慎也, 渡邊豊彦, 門田晃一, 那須保友, 公文裕巳

西日本泌尿器科 70 ( 増刊 ) 203 - 203 2008.10

The benefits of clamping the renal artery in laparoscopic partial nephrectomy Reviewed

Yasuyuki Kobayashi, Takashi Saika, Daisuke Manabe, Yasutomo Nasu, Hiromi Kumon

ACTA MEDICA OKAYAMA 62 ( 4 ) 269 - 273 2008.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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 (99m)Technetium-mercaptoacetyltriglycine (Tc-99m-MAG3). Intraoperative blood loss was significantly higher in the group without clamping than in the group with clamping (p = 0.04). In the group with clamping, the median warm ischemic time was 35 min (range 25-40 min). 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.

進行性尿路上皮癌に対するGemcitabine(GEM)、Cisplatin(CDDP)、Paclitaxel(PAC)-GCP療法-の検討

谷本竜太, 雑賀隆史, 和田耕一郎, 小林知子, 小林泰之, 小武家誠, 大和豊子, 賀来春紀, 那須保友, 公文裕巳

日本化学療法学会雑誌 56 ( Suppl.A ) 178 - 178 2008.5

Adenovirus-mediated REIC/DKK-3 gene transfer prevented mesothelioma tumor progressions in orthotopic mice model Reviewed

Kashiwakura Yuji, Watanabe Masami, Abarzua Fernando, Sakaguchi Masakiyo, Takaoka Munenori, Tanimoto Ryuta, Nasu Yasutomo, Huh Nam-ho, Kumon Hiromi

JOURNAL OF GENE MEDICINE 10 ( 4 ) 469 - 470 2008.4

REIC/DKK-3 as a potential gene therapeutic agent against human testicular cancer Reviewed

Tanimoto Ryuta, Abarzua Fernando, Sakaguchi Masakiyo, Nasu Yasutomo, Kumon Hiromi, Huh Nam-Ho

JOURNAL OF GENE MEDICINE 10 ( 4 ) 454 2008.4

A comparative study of the oncological long-term outcome of laparoscopic nephroureterectomy and standard nephroureterectomy for upper urinary tract transitional cell carcinoma Reviewed

Kobayashi Yasuyuki, Manabe Daisuke, Uehara Shinya, Watanabe Toyohiko, Saika Takashi, Nasu Yasutomo, Kumon Hiromi

JOURNAL OF UROLOGY 179 ( 4 ) 291 2008.4

Renal oncocytoma with synchronous contralateral renal cell carcinoma: A report of two cases

Takeshi Hirata, Koichi Monden, Hiromu Tsuboi, Ayano Ishii, Kazushi Ishii, Shinya Uehara, Takashi Saika, Yasutomo Nasu, Hiromi Kumon

Nishinihon Journal of Urology 70 ( 3 ) 162 - 166 2008.3

Language：Japanese Publishing type：Research paper (scientific journal)

We report two cases of renal oncocytoma with contralateral renal cell carcinoma. [Case 1] A 72-year-old man was admitted with a 17 mm right renal mass incidentally found by computed tomography. Under the diagnosis of right renal cell carcinoma, we performed radical right nephrectomy. Pathological diagnosis was renal cell carcinoma, four months later, another renal mass was found in the left kidney by computed tomography, and this mass had a diameter of 13 mm. We could not rule out the possibility of contralateral renal cell carcinoma. We performed left partial nephrectomy. Pathological diagnosis was oncocytoma. [Case 2] The patient was 61-year-old woman, who had been on hemodyalysis for 27 years. CT revealed bilateral renal masses, which had a diameter of 30 mm (right kidney), and 20 mm (left kidney). We diagnosed the case as bilateral renal cell carcinoma. Firstly, we performed laparoscopic left nephrectomy. Then, laparoscopic right nephrectomy was performed two months later. Pathological diagnosis was left papillary renal cell carcinoma and right oncocytoma. To our knowledge, these are the fourth and fifth cases of renal oncocytoma with synchronous contralateral renal cell carcinoma to be reported in Japan.

A rare tumor in the adrenal region: Neuron-specific enolase (NSE)-producing leiomyosarcoma in an elderly hypertensive patient Reviewed

Junko Goto, Fumio Otsuka, Ryo Kodera, Tomoko Miyoshi, Masaru Kinomura, Hiroyuki Otani, Yukari Mimura, Toshio Ogura, Hiroyuki Yanai, Yasutomo Nasu, Hirofumi Makino

ENDOCRINE JOURNAL 55 ( 1 ) 175 - 181 2008.2

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN ENDOCRINE SOC

A 73-year-old Japanese woman was referred for examination of right flank pain and progressive hypertension. Abdominal CT incidentally detected a right adrenal mass 8 cm in size. The tumor exhibited isodensity by CT and contained high-intense lesion by T2-weighted MRI. Scintigraphy with I-131-metaiodobenzylguanidine and I-131-adosterol showed no abnormal uptake by whole body scan. Positron emission tomography scan with F-18-2-fluoro-D-deoxyglucose demonstrated an exclusive uptake in the right adrenal mass. Adrenocortical hormone levels and catecholamine secretion were within normal range; however, the level of serum neuron-specific enolase (NSE) was found to be markedly high. After controlling systemic blood pressure with an alpha 1-blocker, the right adrenal tumor was surgically removed, along with the right kidney and inferior vena cava which adhered to it. The tumor was pathologically proven to be leiomyosarcoma, which was immunohistochemically positive with a-smooth muscle actin and negative with CD57, S-100 and c-kit proteins. Notably, NSE protein was massively expressed in the resected tumor. After surgery blood pressure was controlled with regular medication and serum NSE levels have since normalized. The possibility of leiomyosarcoma should be kept in mind in adrenal incidentalomas with rapid growth and atypical radiological images. Our findings suggest that circulating NSE levels may be clinically useful for early detection of recurrence.

DOI： 10.1507/endocrj.K07E-020

Iodine-125 seed implantation (permanent brachytherapy) for clinically localized prostate cancer Reviewed

Shin Ebara, Yoshihisa Katayama, Ryuta Tanimoto, Kohei Edamura, Hiroyuki Nose, Daisuke Manabe, Tomoko Kobayashi, Yasuyuki Kobayashi, Makoto Kobuke, Mitsuhiro Takemoto, Takashi Saika, Yasutomo Nasu, Susumu Kanazawa, Hiromi Kumon

ACTA MEDICA OKAYAMA 62 ( 1 ) 9 - 13 2008.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

From January 2004 to March 2007, 308 patients with clinically localized prostate cancer were treated using iodine-125 (I-125) seed implantation (permanent brachytherapy) at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. We evaluated the treatiment's efficacy and morbidity in 300 prostate cancer patients who were followed up for more than I 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 classified 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 difficulty in urination, pollakisuria/urgency, miction pain, and/or urinary incontinence, all of which might be associated with radiation prostatitis during the first month after brachytherapy, these symptoms gradually improved. I-125 seed implantation brachytherapy is safe and effective for localized prostate cancer within short-term follow up.

Expression of the serine protease hepsin and clinical outcome of human endometrial cancer

Matsuo T, Nakamura K, Takamoto N, Kodama J, Hongo A, Abrzua F, Nasu Y, Kumon H, Hiramatsu Y

Anticancer Research 28 159 - 164 2008

New highly potent and specific E6 and E7 siRNAs for treatment of HPV 16 positive cervical cancer

YAMATO K

Cancer Gene Ther 15 140 - 153 2008

Secretory leukoprotease inhibitor inhibits cell growth through apoptotic pathway on ovarian cancer

Keiichiro Nakamura, Norio Takamoto, Atsushi Hongo, Junichi Kodama, Fernando Abrzua, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

ONCOLOGY REPORTS 19 ( 5 ) 1085 - 1091 2008

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

In light of the poor prognosis for ovarian cancer, research continues for innovative and efficacious treatment modalities. It is now widely accepted that new approaches for the treatment of ovarian cancers are pivotal in further improving prognosis of this disease. Secretory leukoprotease inhibitor (SLPI) is an 11.7-kDa non-glycosylated, serine protease inhibitor that has a broad inhibitory spectrum against serine protease. SLPI showed potential therapeutic inhibitory effects mediated by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), TNF-alpha, death receptor (DR)-4, DR-5 and TNF receptor (TNFR)-I expression which lead to an activation of apoptosis pathway through Caspase-2, Caspase-8 and Caspase-9. We examined whether levels of SLPI protein expression correlated with clinicopathological characteristics in 58 ovarian cancer samples, and investigated the role of SLPI and its biological functions. SLPI expression showed a significant correlation between low expression of SLPI and amount of ascites (p=0.021), lymph node metastasis (p=0.011). We propose that SLPI could be considered a therapeutic target for the treatment of ovarian cancer.

Hepsin inhibits the cell growth of endometrial cancer

Keiichiro Nakamura, Norio Takamoto, Fernando Abarzua, Atsushi Hongo, Junichi Kodama, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 22 ( 3 ) 389 - 397 2008

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Currently, several therapeutic approaches including surgery, chemotherapy, and radiation therapy are available for the treatment of endometrial cancer. However, endometrial cancer cells may survive, resulting in relapse of the disease, and ultimately causing demise of the patient. Hepsin is a cell surface-expressed chymotrypsin-like serine protease and a member of the, family of type II transmembrane serine proteases. To date, little is known about its precise mechanisms of action. We investigated the biological functions and effects in vitro and in vivo of Hepsin, using endometrial cancer cell lines transfected with Hepsin. In stably transfected Ishikawa/Hepsin cell lines (Hepsin-10 and -12), we observed a significant inhibitory effect on cell growth in a monolayer culture system and in anchorage-independent cell growth in soft agar in vitro. Furthermore, in a xenograft model, growth inhibitory effects were observed when compared with the effects of mock-transfected cells used as a control. Overall, Hepsin showed potential inhibitory effects mediated by the induction of 14-3-3 sigma expression which leads to both cell cycle arrest at the G(2)/M phase through cyclin B and cyclin A and the p53-dependent pathway activated by increasing the level of Bak and reducing the level of Bcl-2 and Bcl-xL.

DOI： 10.3892/ijmm_00000035

REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer

K. Kawasaki, M. Watanabe, M. Watanabe, M. Sakaguchi, Y. Ogasawara, K. Ochiai, Y. Nasu, H. Doihara, H. Doihara, Y. Kashiwakura, N. H. Huh, H. Kumon, H. Kumon, H. Date

Cancer Gene Therapy 16 ( 1 ) 65 - 72 2008

The overexpression of reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3), a tumor suppressor gene, induced apoptosis in human prostatic and testicular cancer cells. The aim of this study is to examine the potential of REIC/Dkk-3 as a therapeutic target against breast cancer. First, the in vitro apoptotic effect of Ad-REIC treatment was investigated in breast cancer cell lines and the adenovirus-mediated overexpression of REIC/Dkk-3 was thus found to lead to apoptotic cell death in a c-Jun-NH2-kinase (JNK) phosphorylaion-dependent manner. Moreover, an in vivo apoptotic effect and MCF/Wt tumor growth inhibition were observed in the mouse model after intratumoral Ad-REIC injection. As multidrug resistance (MDR) is a major problem in the chemotherapy of progressive breast cancer, the in vitro effects of Ad-REIC treatment were investigated in terms of the sensitivity of multidrug-resistant MCF7/ADR cells to doxorubicin and of the P-glycoprotein expression. Ad-REIC treatment in MCF7/ADR cells also downregulated P-glycoprotein expresssion through JNK activation, and sensitized its drug resistance against doxorubicin. Therefore, not only apoptosis induction but also the reversal of anticancer drug resistance was achieved using Ad-REIC. We suggest that REIC/Dkk-3 is a novel target for breast cancer treatment and that Ad-REIC might be an attractive agent against drug-resistant cancer in combination with conventional antineoplastic agents. © 2009 Nature Publishing Group All rights reserved.

DOI： 10.1038/cgt.2008.58

WS1-2-3 A Comparative Study of the Oncological Long-term Outcomeof Laparoscopic Nephroureterectomy and Standard Nephroureterectomy For Upper Urinary Tract Trasitionalcell Carcinoma(Urothelial Cell Cancer)

Kobayashi Yasuyuki, Saika Takashi, Watanabe Toyohiko, Uehara Shinya, Nasu Yasutomo, Kumon Hiromi

The Japanese Journal of Urology 99 ( 2 ) 146 - 146 2008

Routine transurethral biopsy of the bladder is not necessary to evaluate the response to bacillus Calmette-Guerin therapy Reviewed

Takanori Murakami, Shin Ebara, Takashi Saika, Shin Irie, Katsuji Takeda, Yoshio Maki, Sadayuki Miyaji, Daisuke Manabe, Haruki Kaku, Yasutomo Nasu, Tomoyasu Tsushima, Hiromi Kumon

ACTA MEDICA OKAYAMA 61 ( 6 ) 341 - 344 2007.12

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

The efficacy of neoadjuvant androgen deprivation therapy as a prostate volume reduction before brachytherapy for clinically localized prostate cancer Reviewed

Shin Ebara, Daisuke Manabe, Yasuyuki Kobayashi, Ryuta Tanimoto, Takashi Saika, Yasutomo Nasu, Shirou Saito, Takefumi Satoh, Kenta Miki, Katsuyoshi Hashine, Hiromi Kumon

ACTA MEDICA OKAYAMA 61 ( 6 ) 335 - 340 2007.12

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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) agonis, 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 NUB. 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.

Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model Reviewed

K. Edamura, Y. Nasu, M. Takaishi, T. Kobayashi, F. Abarzua, M. Sakaguchi, Y. Kashiwakura, S. Ebara, T. Saika, M. Watanabe, N-H Huh, H. Kumon

CANCER GENE THERAPY 14 ( 9 ) 765 - 772 2007.9

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

We had previously reported that REIC/Dkk-3, a member of the Dickkopf ( Dkk) gene family, works as a tumor suppressor. In this study, we evaluated the therapeutic effects of an intratumoral injection with adenoviral vector encoding REIC/Dkk-3 gene ( Ad-REIC) using an orthotopic mouse prostate cancer model of RM-9 cells. We also investigated the in vivo anti-metastatic effect and in vitro anti-invasion effect of Ad-REIC gene delivery. We demonstrated that the Ad-REIC treatment inhibited prostate cancer growth and lymph node metastasis, and prolonged mice survival in the model. These therapeutic responses were consistent with the intratumoral apoptosis induction and in vitro suppression of cell invasion/migration with reduced matrix metalloprotease-2 activity. We thus concluded that in situ Ad-REIC/Dkk-3 gene transfer may be a promising therapeutic intervention modality for the treatment of prostate cancer.

DOI： 10.1038/sj.cgt.7701071

体腔鏡下腎尿管全摘除術の上部尿路上皮癌に対する治療成績

小武家誠, 雑賀隆史, 小林泰之, 上原慎也, 那須保友, 公文裕巳, 真鍋大輔, 入江伸, 津島知靖, 山田大介

日本癌治療学会誌 42 ( 2 ) 552 - 552 2007.9

Health-related quality of life after radical cystectomy for bladder cancer in elderly patients with an ileal conduit, ureterocutaneostomy, or orthotopic urinary reservoir: A comparative questionnaire survey Reviewed

Takashi Saika, Ryoji Arata, Tomoyasu Tsushima, Yasutomo Nasu, Bunzo Suyama, Katsuji Takeda, Shin Ebara, Daisuke Manabe, Tomoko Kobayashi, Ryuta Tanimoto, Hiromi Kumon

ACTA MEDICA OKAYAMA 61 ( 4 ) 199 - 203 2007.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

To compare the health-related quality of life of elderly patients after radical cystectomy for bladder cancer in urinary diversion groups: ileal conduit, ureterocutaneostomy, or orthotopic urinary reservoir. The 109 participating elderly patients aged 75 or older completed self-reporting questionnaires: the QNQ-C30, and on satisfaction with urinary diversion methods. Fifty-six patients had undergone constructions for ileal conduit diversion, 31 for ureterocutaneostomy, and 22 for orthotopic urinary reservoir (OUR). The median follow-up period for each group was 4.0 years (range 0.3-11.2), 4.5 years (range 0.3-18.0), and 3.3 years (range 0.3-6.7), respectively. Regardless of the type of urinary diversion, the majority of patients reported having good overall quality of life, although with some problem of pain. No significant differences among urinary diversion subgroups were found in any quality of life area in the QLQ-C30 questionnaire. More patients in the OUR sub-group felt disappointment than those in the ileal conduit or cutaneostomy sub-groups. However, a questionnaire which asked which diversion method would be preferable showed a trend that more patients in the OUR subgroup would have chosen the same one. Health-related quality of life appeared relatively good in these 3 groups. Patient demands and expectations may be so different from the results that the details of each urinary diversion method should be explained thoroughly. OUR construction could be a candidate even for elderly patients.

Orthotopic ileal neobladder versus sigmoidal neobladder: A "Quality of life" (QOL) survey Reviewed

Ryoji Arata, Takashi Saika, Tomoyasu Tsushima, Fernando Abarzua, Yasutomo Nasu, Hiromi Kumon

ACTA MEDICA OKAYAMA 61 ( 4 ) 229 - 234 2007.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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 differences between the 2 groups. Concerning the voiding condition, bladder emptying, frequency, and urgency, scores in the sigmoidal OUR group were significantly 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.

Natural course of lower urinary tract symptoms following discontinuation of alpha-1-adrenergic blockers in patients with benign prostatic hyperplasia Reviewed

Teruhiko Yokoyama, Toyohiko Watanabe, Takashi Saika, Yasutomo Nasu, Hiromi Kumon, Yoshiyuki Miyaji, Atsushi Nagai

INTERNATIONAL JOURNAL OF UROLOGY 14 ( 7 ) 598 - 601 2007.7

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL PUBLISHING

Objectives: 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.

DOI： 10.1111/j.1442-2042.2007.01784.x

Heat shock proteins play a crucial role in tumor-specific apoptosis by REIC/Dkk-3 Reviewed

Fernando Abarzua, Masakiyo Sakaguchi, Ryuta Tanimoto, Hiroyuki Sonegawa, Dai-Wei L, Kohei Edamura, Tomoko Kobayashi, Masami Watanabe, Yuji Kashiwakura, Haruki Kaku, Takashi Saika, Keiichiro Nakamura, Yasutomo Nasu, Hiromi Kumon, Nam-Ho Huh

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 20 ( 1 ) 37 - 43 2007.7

Language：English Publishing type：Research paper (scientific journal) Publisher：PROFESSOR D A SPANDIDOS

We recently showed that overexpression of REIC/Dickkopf-3 (Dkk-3), a tumor suppressor gene, induced apoptosis in a tumor cell-specific manner. The aim of the present study was to determine the mechanisms underlying the selective induction of apoptosis. At first, we found a mouse renal carcinoma cell line, RENCA, to be extremely sensitive to an adenovirus carrying REIC/Dkk-3 (Ad-REIC), and we showed that activation of c-Jun N-terminal kinase (JNK) was a critical step in cell death, i.e. a process similar to that in human prostate and testicular cancer observed in our previous studies. Among the proteins interfering with the activation of JNK, heat shock protein (Hsp)70/72 was reduced in expression in RENCA cells compared with that in NIH3T3 cells. An Hsp70/72 inducer protected RENCA cells from Ad-REIC-induced apoptosis, while an Hsp70/72 inhibitor sensitized NIH3T3 cells for apoptosis induction. These results indicate that functionally active Hsp70/72 is a key factor in tumor cell-specific induction of apoptotic cell death and that analyses of the expression levels of Hsp70/72 may be essential in determining the significance of Ad-REIC-based gene therapy against human cancer.

Molecular features of hormone-refractory prostate cancer cells by genome-wide gene expression profiles Reviewed

Kenji Tamura, Mutsuo Furihata, Tatsuhiko Tsunoda, Shingo Ashida, Ryo Takata, Wataru Mara, Hiroki Yoshioka, Yataro Daigo, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Konaka, Mikio Namiki, Keiichi Tozawa, Kenjiro Kohri, Nozomu Tanji, Masayoshi Yokoyama, Toru Shimazui, Hideyuki Akaza, Yoichi Mizutani, Tsuneharu Miki, Tomoaki Fujioka, Taro Shuin, Yusuke Nakamura, Hidewaki Nakagawa

CANCER RESEARCH 67 ( 11 ) 5117 - 5125 2007.6

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC CANCER RESEARCH

One of the most critical issues in prostate cancer clinic is emerging hormone-refractory prostate cancers (HRPCs) and their management. Prostate cancer is usually androgen dependent and responds well to androgen ablation therapy. However, at a certain stage, they eventually acquire androgen-independent and more aggressive phenotype and show poor response to any anticancer therapies. To characterize the molecular features of clinical HRPCs, we analyzed gene expression profiles of 25 clinical HRPCs and 10 hormone-sensitive prostate cancers (HSPCs) by genome-wide cDNA microarrays combining with laser microbeam microdissection. An unsupervised hierarchical clustering analysis clearly distinguished expression patterns of HRPC cells from those of HSPC cells. In addition, primary and metastatic HRPCs from three patients were closely clustered regardless of metastatic organs. A supervised analysis and permutation test identified 36 up-regulated genes and 70 down-regulated genes in HRPCs compared with HSPCs (average fold difference > 1.5; P < 0.0001). We observed overexpression of AR, ANLN, and SNWPE and down-regulation of NR4A1, CYP27A1, and HLA-A antigen in HRPC progression. AR overexpression is likely to play a central role of hormone-refractory phenotype, and other genes we identified were considered to be related to more aggressive phenotype of clinical HRPCs, and in fact, knockdown of these overexpressing genes by small interfering RNA resulted in drastic attenuation of prostate cancer cell viability. Our microarray analysis of HRPC cells should provide useful information to understand the molecular mechanism of HRPC progression and to identify molecular targets for development of HRPC treatment.

DOI： 10.1158/0008-5472.CAN-06-4040

Suicide gene therapy with adenoviral delivery of HSV-tK gene for patients with local recurrence of prostate cancer after hormonal therapy Reviewed International journal

Nasu Yasutomo, Saika Takashi, Ebara Shin, Kusaka Nobuyuki, Kaku Haruki, Abarzua Fernando, Manabe Daisuke, Thompson Timothy C, Kumon Hiromi

MOLECULAR THERAPY 15 ( 4 ) 834 - 840 2007.4

Language：English Publishing type：Research paper (scientific journal)

We conducted a Phase I study of in situ herpes simplex virus thymidine kinase (HSV-tk) plus ganciclovir (GCV) gene therapy, which was approved by the Japanese government as the first prostate cancer gene therapy trial. Major inclusion criteria were local recurrence of prostate cancer after hormonal therapy and no metastasis. Adv.HSV-tk was injected directly into the prostate in escalating doses from 10(9) to 10(10) infection units, followed by intravenous administration of GCV for 14 days. Eight patients received nine courses of this gene therapy. The detection of vector DNA in blood/urine was only transient and no remarkable adverse events were observed in any patient. With regard to clinical response, significant prolongation of the median serum prostate-specific antigen (PSA) doubling time from 2.9 to 6.2 months (P = 0.041) was detected. In five patients (six injections), a clear decrease of PSA values was observed. One patient showed repeated clinical response after repeated injections. Serum cytokine analysis showed no notable changes after treatment. Fluorescence-activated cell sorting analysis also showed no influence on phenotypic distribution in peripheral blood samples, except for an increasing trend of CD8(+)/HLA-DR(+) after therapy. This study confirmed the safety profile and possibility of clinical response at the surrogate marker level in a clinical trial of HSV-tk gene therapy for hormone-refractory prostate cancer.

DOI： 10.1038/mt.sj.6300096

Comparative study of oncologic outcome of laparoscopic nephroureterectomy and standard nephroureterectomy for upper urinary tract transitional cell carcinoma Reviewed

Daisuke Manabe, Takashi Saika, Shin Ebara, Shinya Uehara, Atsushi Nagai, Ryuji Fujita, Shin Irie, Daisuke Yamada, Tomoyasu Tsushima, Yasutomo Nasu, Hiromi Kumon

UROLOGY 69 ( 3 ) 457 - 461 2007.3

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

OBJECTIVES To determine the oncologic safety of laparoscopic nephroureterectomy (LNU), we compared the long-term oncologic outcome of LNU versus open nephroureterectomy (ONU) in patients with upper tract transitional cell carcinoma.
METHODS A total of 367 nephroureterectomy procedures were performed at our institutes for upper tract transitional cell carcinoma without distant metastases. Of 224 patients without concomitant or previous bladder cancer, 58 underwent LNU with open intact specimen retrieval plus open distal ureter and bladder cuff removal and 166 underwent ONU. Their data were reviewed and analyzed retrospectively. The mean follow-up was 13.6 months (range 14 to 34) for the LNU group and 28.0 months (range 14 to 36) for the ONU group.
RESULTS Bladder recurrence was recognized in 19 patients (32.8%) after LNU at a median follow-up of 5.6 months compared with 63 patients (38.0%) after ONU. Local recurrence only developed in 2 patients (1.1%) after ONU. One port site metastasis occurred in a patient who had undergone LNU. Distant metastases developed in 10 patients (17.2%) after LNU and 33 patients (19.9%) after ONU. The frequency of bladder recurrence, local recurrence, and distant metastases did not differ significantly between the two groups. The actual disease-free 2-year survival rates were similar (75.6% versus 81.7%). In all patients, the risk of metastases and death increased with advanced tumor stage and grade, but not by surgical procedure.
CONCLUSIONS In the surgical management of upper tract transitional cell carcinoma, LNU does not negatively affect long-term oncologic control and can be considered an alternative modality. Tumor stage and grade are, however, important prognostic factors in the incidence of metastases and cancer-specific mortality.

DOI： 10.1016/j.urology.2006.11.005

REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer Reviewed

Ryuta Tanimoto, Fernando Abarzua, Masakiyo Sakaguchi, Mikiro Takaishi, Yasutomo Nasu, Hiromi Kumon, Nam-Ho Huh

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 19 ( 3 ) 363 - 368 2007.3

Language：English Publishing type：Research paper (scientific journal) Publisher：PROFESSOR D A SPANDIDOS

Human testicular cancer is very sensitive to chemotherapy and radiation therapy and is regarded as a curable cancer. The cancer prevails in the young reproductive generation and testicular dysfunction is often observed as a side effect, remaining a serious challenge. In the present study, we examined the potential utility of REIC/Dkk-3-based gene therapy against human testicular cancer. Expression of REIC/Dkk-3 was reduced in all of the human seminoma and non-seminomatous germ cell tumor tissues. Overexpression of REIC/Dkk-3 using an adenovirus vector (Ad-REIC) induced apoptosis in a testicular germ cell cancer cell line NCCIT but not in normal human fibroblasts. c-Jun terminal kinase (JNK) was activated by Ad-REIC and the induction of apoptosis was abrogated by a JNK inhibitor. A single intratumoral injection of Ad-REIC markedly inhibited the tumorigenic growth of NCCIT cells in nude mice. These results indicate that Ad-REIC may lead to developing less insulting and non-genotoxic therapeutic measures against human testicular cancer.

Primary aldosteronism caused by a unilateral adrenal adenoma accompanied by autonomous cortisol secretion

Suzuki J, Otsuka F, Inagaki K, Otani H, Miyoshi T, Terasaka T, Ogura T, Omori M, Nasu Y, Makino H

Hypertens Res 30 ( 4 ) 367 - 373 2007

Implication of Amphiphysin 1 and Dynamin 2 in Tubulobulbar Complex Formation and Spermatid Release

Kusumi Norihiro, Watanabe Masami, Yamada Hiroshi, Li Shun-Ai, Kashiwakura Yuji, Matsukawa Takashi, Nagai Atsushi, Nasu Yasutomo, Kumon Hiromi, Takei Kohji

Cell Struct. Funct. 32 ( 2 ) 101 - 113 2007

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Society for Cell Biology

Tubulobulbar complexes (TBCs) are composed of several tubular invaginations formed at the plasma membrane of testicular Sertoli cells. TBCs are transiently formed at the contact region with spermatids at spermatogenic stage VII in rat and mouse, and such TBC formation is prerequisite for spermatid release. Since the characteristic structure of TBCs suggests that the molecules implicated in endocytosis could be involved in TBC formation, we here investigated the localization and physiological roles of endocytic proteins, amphiphysin 1 and dynamin 2, at TBCs. We demonstrated by immunofluorescence that the endocytic proteins were concentrated at TBCs, where they colocalized with cytoskeletal proteins, such as actin and vinculin. Immunoelectron microscopy disclosed that both amphiphysin 1 and dynamin 2 were localized on TBC membrane. Next, we histologically examined the testis from amphiphysin 1 deficient {Amph^–/–} mice. Morphometric analysis revealed that the number of TBCs was significantly reduced in Amph^–/–. The ratio of stage VIII seminiferous tubules was increased, and the ratio of stage IX was conversely decreased in Amph^–/–. Moreover, unreleased spermatids in stage VIII seminiferous tubules were increased in Amph^–/–, indicating that spermatid release and the following transition from stage VIII to IX was prolonged in Amph^–/– mice. These results suggest that amphiphysin 1 and dynamin 2 are involved in TBC formation and spermatid release at Sertoli cells.<br>

DOI： 10.1247/csf.07024

PP-352 部分珊瑚状結石に対し、尿管アクセスシース (AquaGuide URETERAL ACCESS SHEATH) を用いて施行したTULの2例(第95回日本泌尿器科学会総会)

上原慎也, 門田晃一, 渡辺豊彦, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 98 ( 2 ) 484 - 484 2007

OP-045 無阻血と阻血による体腔鏡下腎部分切除術の周術期成績の比較検討(第95回日本泌尿器科学会総会)

小林泰之, 真鍋大輔, 江原伸, 雑賀隆史, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 98 ( 2 ) 302 - 302 2007

WS2-6 ヨウ素125永久挿入密封小線源治療後のQOLに関する研究(限局性前立腺癌に対する非観血的治療-各治療の有害事象とQOLへの影響を中心に, 第95回日本泌尿器科学会総会)

江原伸, 雑賀隆史, 真鍋大輔, 谷本竜太, 小林泰之, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 98 ( 2 ) 190 - 190 2007

PP-686 体腔鏡下腎尿管全摘除術の上部尿路癌に対する治療成績 (第2報)(第95回日本泌尿器科学会総会)

真鍋大輔, 雑賀隆史, 江原伸, 上原慎也, 小林泰之, 那須保友, 公文裕巳, 伊藤誠一, 入江伸, 山田大介, 津島知靖

日本泌尿器科学会雑誌 98 ( 2 ) 568 - 568 2007

Nerve growth factor in prostatic fluid as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome

Toyohiko Watanabe, Shinya Uehara, Daishi Araki, Miyabi Inoue, Koichi Monden, Takashi Saika, Yasutomo Nasu, Hiromi Kumon, Teruhiko Yokoyama

Nishinihon Journal of Urology 69 ( 10 ) 578 - 583 2007

Language：Japanese Publishing type：Research paper (scientific journal)

Nerve growth factor (NGF) plays a key role as the peripheral mediator of several types of painful inflammatory conditions. In search of new biomarkers with which to more clearly define chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), we investigated whether or not NGF in expressed prostatic secretions (EPS) is correlated with symptom severity in CP/CPPS. All CP/CPPS patients underwent a complete history and physical examination, including the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). EPS samples from 16 patients and 3 asymptomatic controls were collected and frozen. The levels of NGF in EPS were measured by enzyme-linked immunosorbent assay. Patients were asked to complete the questionnaires of NIH-CPSI at baseline and at 8 weeks after treatment. Responders for treatment were defined as a 25% decrease in total NIH-CPSI score from the baseline values. Mean NGF in EPS of CP/CPPS patients and asymptomatic controls were 7,555 ± 3,990 pg/ml and 4,374 ± 825 pg/ml, respectively. The levels of NGF in CP/CPPS patients were correlated directly with pain severity (P = 0.042, r = 0.521), but were not correlated with urinary symptoms or the quality of life. There were no significant differences between pre-treatment and post-treatment levels of NGF in EPS. However, in responders, NGF levels were significantly decreased after successful treatment (P = 0.0165). NGF might contribute to the pathophysiology of CP/CPPS. The NGF level in EPS can change according to pain severity. Therefore, these results suggest that nerve growth factor could be used as a new biomarker to evaluate the symptoms of CP/CPPS and the effects of treatment.

Phase study of adenoviral vector delivery of HSV-tk gene and the intravenous administration of ganciclovir in men with local recurrence of prostate cancer after hormonal therapy Reviewed

Nasu Yasutomo, Kaku Haruki, Ebara Shin, Saika Takashi, Thompson Timothy C, Kumon Hiromi

JOURNAL OF GENE MEDICINE 8 ( 12 ) 1443 2006.12

Telomerase-specific replication-selective virotherapy for prostate cancer Reviewed

Kaku Haruki, Nasu Yasutomo, Huang Peng, Saika Takashi, Kagawa Shunsuke, Fujiwara Toshiyoshi, Kumon Hiromi, Urata Yasuo

JOURNAL OF GENE MEDICINE 8 ( 12 ) 1454 2006.12

無阻血と阻血による体腔鏡下腎部分切除術の周術期成績の比較検討

小林泰之, 真鍋大輔, 江原伸, 雑賀隆史, 那須保友, 公文裕巳

日本内視鏡外科学会雑誌 11 ( 7 ) 424 - 424 2006.12

尿路性器癌におけるHybrid Surgery 良い視野、少ない出血、確実なcancer control

雑賀隆史, 小林泰之, 真鍋大輔, 江原伸, 上原慎也, 那須保友, 公文裕巳

Japanese Journal of Endourology and ESWL 19 ( 3 ) 249 - 249 2006.10

前立腺癌におけるHybrid radical prostatectomy 良い視野、少ない出血、確実なcancer control

雑賀隆史, 小林泰之, 真鍋大輔, 江原伸, 上原慎也, 渡邊豊彦, 那須保友, 公文裕巳

西日本泌尿器科 68 ( 増刊 ) 124 - 124 2006.10

ゾレドロン酸使用と関連したCRP上昇

甲斐誠二, 雑賀隆史, 上原慎也, 松本裕子, 平田武志, 小林泰之, 石井亜矢乃, 石井和史, 江原伸, 那須保友, 公文裕巳

西日本泌尿器科 68 ( 増刊 ) 197 - 197 2006.10

密封小線源療法を施行された前立腺癌患者のQOLに関する研究恥骨後式根治的前立腺摘除術とのProspectiveな比較において

雑賀隆史, 中西代志子, 江原伸, 真鍋大輔, 谷本竜太, 枝村康平, 小林知子, 賀来春紀, 津島知靖, 那須保友, 公文裕巳

日本癌治療学会誌 41 ( 2 ) 581 - 581 2006.9

進行性尿路上皮癌に対するGemcitabine(GEM)、Cisplatin(CDDP)、Paclitaxel(PAC)-GCP療法-の検討

谷本竜太, 眞鍋大輔, 和田耕一郎, 枝村康平, 小林知子, 江原伸, 賀来春紀, 雑賀隆史, 那須保友, 公文裕巳

日本癌治療学会誌 41 ( 2 ) 596 - 596 2006.9

腎癌術後に発症した単発性骨転移に対し椎体置換術を施行した3例

枝村康平, 雑賀隆史, 田中雅人, 谷本竜太, 小林知子, 真鍋大輔, 江原伸, 賀来春紀, 那須保友, 津島知靖, 尾崎敏文, 公文裕巳

腎癌研究会会報 ( 31 ) 11 - 12 2006.9

125Iシード線源による前立腺癌永久挿入密封小線源治療

江原伸, 真鍋大輔, 枝村康平, 谷本竜太, 小林知子, 雑賀隆史, 那須保友, 公文裕巳

日本癌治療学会誌 41 ( 2 ) 574 - 574 2006.9

Phase I/II Study of Adenoviral Vector Delivery of HSV-tk Gene and the Intravenous Administration of Ganciclovir in Men with Local Recurrence of Prostate Cancer after Hormonal Therapy Reviewed

Nasu Yasutomo, Kaku Haruki, Ebara Shin, Saika Takashi, Kumon Hiromi, Thompson Timothy C

MOLECULAR THERAPY 13 S19 - S20 2006.5

Effects of radiofrequency ablation on individual renal function: Assessment by technetium-99m mercaptoacetyltriglycine renal scintigraphy Reviewed

T Mukai, S Sato, T Iguchi, H Mimura, K Yasui, H Gobara, T Saika, Y Nasu, H Kumon, S Kanazawa

ACTA MEDICA OKAYAMA 60 ( 2 ) 85 - 91 2006.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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 I 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.

Time course of serum testosterone and luteinizing hormone levels after cessation of long-term luteinizing hormone-releasing hormone agonist treatment in patients with prostate cancer Reviewed

H Kaku, T Saika, T Tsushima, S Ebara, T Senoh, T Yamato, Y Nasu, H Kumon

PROSTATE 66 ( 4 ) 439 - 444 2006.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-LISS

INTRODUCTION. In order to elucidate the influence of hormone-releasing hormone (LHRH) agonist therapy cessation on pituitary/testicular function and its clinical implications, we investigated prospectively hormonal (luteinizing hormone: LH; testosterone: T) responses in patients with prostate cancer who received long-term LH-RH 10 agonist therapy.
PATIENTS AND METHODS. A consecutive 32 patients who had received LH-RH agonist therapy over 24 months were enrolled. As a baseline, T and LH were measured at the time of LHRH agonist therapy cessation, monthly for 3 months, and subsequently, every 3 months.
RESULTS. The median duration of LH-RH agonist therapy was 30 months (24-87 months) with median follow-up duration of 24 months following cessation. All patients had castrated T levels and suppressed LH levels at baseline. Median duration of castrated T levels following cessation was 6 months. Median time to normalization of T levels was 24 months. LH levels returned to normal within 3 months in all cases. Patients who received androgen deprivation therapy for 30 months or longer required a longer time for recovery of T levels. Patients over 65 years of age showed a statistically significant longer time for recovery of T levels (P = 0.0167).
CONCLUSIONS. Long-term LH-RH agonist therapy has remarkable effects on serum T level that last for a significant time after cessation, a fact that should be applied to the interpretation of both PSA and serum T levels after cessation of androgen deprivation therapy.

DOI： 10.1002/pros.20341

Combination chemotherapy with estramustine phosphate, ifosfamide and cisplatin for hormone-refractory prostate cancer Reviewed

H Kaku, T Saika, T Tsushima, A Nagai, T Yokoyama, F Abarzua, S Ebara, D Manabe, Y Nasu, H Kumon

ACTA MEDICA OKAYAMA 60 ( 1 ) 43 - 49 2006.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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/m(2) IFM on days 1 to 5 and 70 mg/m(2) 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.

Retroperitoneal neurogenic tumors mimicking lymph node metastasis of malignant disease: A report of two cases

Shinsuke Gohara, Tomoko Kobayashi, Kyouhei Kurose, Shin-Ya Uehara, Haruki Kaku, Takashi Saika, Yasutomo Nasu, Tomoyasu Tsushima, Hiromi Kumon

Nishinihon Journal of Urology 68 ( 2 ) 55 - 59 2006.2

Language：Japanese Publishing type：Research paper (scientific journal)

We experienced two cases of neurogenic tumor arising from the retroperitoneal space during the clinical course of malignant disease (Case 1: testicular cancer, Case 2: kidney cancer) These retroperitoneal tumors mimicked lymph node metastasis from each of the malignant diseases and a definitive preoperative diagnosis was not made. Tumors were removed under the diagnosis of lymph node metastasis. Postoperative histological analysis revealed neurogenic tumor (Case 1: ganglioneuroma, Case 2: paraganglioma). The postoperative clinical course was uneventful without any additional treatments. Retroperitoneal neurogenic tumor found during the clinical course of active malignant disease can not be differentiated from its metastatic lesion. Preoperative needle biopsy is still controversial. Further development of functional imaging analysis may solve this clinical problem.

Comparison of 25 and 75 mg/day naftopidil for lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective, randomized controlled study.

Yokoyama T, Kumon H, Nasu Y, Takamoto H, Watanabe T

Int J Urol 13 ( 7 ) 932 - 938 2006

The Jounal of gene medicine Japanese society of gene therapy young investigator award 2006

Nasu Y

The Journal of Gene Medicine 8 1363 - 1364 2006

Hepsin shows inhibitory effects through apoptotic pathway on ovarian cancer cell lines

Nakamura K, Nasu Y, Hongo A, Matsuo T, Kodama J, Ebara S, Nagai A, Abrzua F, Kumon H, Hiramatsu Y

International Journal of Oncology 28 393 - 398 2006

Induction of cell death in human papillomavirus 18-positive cervical cancer cells by E6 siRNA

Yamato K, Fen J, Kobuchi H, Nasu Y, Yamada T, Nishihara T, Ikeda Y, Kizaki M, Yoshinouchi M

Cancer Gene Therapy 13 234 - 241 2006

OP-114 性状未確定のリンパ節病変に対する鏡視下リンパ節摘除の有用性(一般演題口演,第94回日本泌尿器科学会総会)

村田匡, 雑賀隆史, 上原慎也, 江原伸, 真鍋大輔, 永井敦, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 97 ( 2 ) 309 - 309 2006

MP-650 体腔鏡下腎尿管全摘除術が施行された上部尿路癌の長期成績について : 開放手術との比較において(一般演題ポスター,第94回日本泌尿器科学会総会)

真鍋大輔, 雑賀隆史, 江原伸, 上原慎也, 谷本竜太, 賀来春紀, 藤田竜二, 入江伸, 野崎邦浩, 津島知靖, 永井敦, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 97 ( 2 ) 529 - 529 2006

MP-453 1251シード線源による前立腺癌永久挿入密封小線源治療(一般演題ポスター,第94回日本泌尿器科学会総会)

江原伸, 真鍋大輔, 枝村康平, 谷本竜太, 小林知子, 雑賀隆史, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 97 ( 2 ) 480 - 480 2006

S11-6 密封小線源療法を施行された前立腺癌患者のQOLに関する研究 : 恥骨後式根治的前立腺摘除術とのProspectiveな比較において(シンポジウム11「限局性前立腺癌の治療成績とQOL」,第94回日本泌尿器科学会総会)

雑賀隆史, 江原伸, 真鍋大輔, 能勢宏幸, 枝村康平, 谷本竜太, 小林知子, 津島知靖, 那須保友, 中西代志子, 公文裕巳

日本泌尿器科学会雑誌 97 ( 2 ) 165 - 165 2006

Intracavernous injection of prostaglandin E-1 is effective in patients with erectile dysfunction not responding to phosphodiesterase 5 inhibitors Reviewed

A Nagai, N Kusumi, H Tsuboi, K Ishii, T Saika, Y Nasu, H Kumon

ACTA MEDICA OKAYAMA 59 ( 6 ) 279 - 280 2005.12

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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(1), was performed in this non-responder group. An ICI of 20 or 40 mcg of PGE(1) in 1 ml saline was performed and the responses evaluated. Forty-nine out of 64 (77%) cases responded to 20 mcg of PGE(1). Forty mcg of PGE(1) was injected into the 15 non-responding cases, and 9 patients responded favorably. The overall effective rate was 58/64 (91 %). No major adverse effects were observed.

Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of c-Jun-NH2-kinase Reviewed

F Abarzua, M Sakaguchi, M Takaishi, Y Nasu, K Kurose, S Ebara, M Miyazaki, M Namba, H Kumon, N Huh

CANCER RESEARCH 65 ( 21 ) 9617 - 9622 2005.11

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC CANCER RESEARCH

Alteration in genes which takes place during malignant conversion and progression could be potential targets for gene therapy. We previously identified REIC/Dkk-3 as a gene whose expression is reduced in many human cancers. Here, we showed that expression of REIC/Dkk-3 was consistently reduced in human prostate cancer tissues in a stage-dependent manner. Forced expression of REIC/Dkk-3 induced apoptosis in human prostate cancer cell lines lacking endogenous REIC/Dkk-3 expression but not in REIC/Dkk3-proficient normal prostate epithelial and stromal cells. The apoptosis involved c-jun-NH2-kinase activation, mitochondrial translocation of Bax, and reduction of Bcl-2. A single injection of an adenovirus vector carrying REIC/Dkk-3 showed a dramatic antitumor effect on a xenotransplanted human prostate cancer. Thus, REIC/Dkk-3 could be a novel target for gene-based therapy of prostate cancer.

DOI： 10.1158/0008-5472.CAN-05-0829

Long-term clinical outcomes of 420 consecutive prostate cancer patients in a single institute Reviewed

K Edamura, T Saika, T Senoh, F Koizumi, D Manabe, S Ebara, H Kaku, T Yokoyama, F Abarzua, A Nagai, Y Nasu, T Tsushima, H Kumon

ACTA MEDICA OKAYAMA 59 ( 5 ) 195 - 199 2005.10

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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% for all treatment modalities, including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml showed an 81% 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% and 100% cause-specific survival rates, respectively, and those treated by hormonal therapy alone showed a 79% 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.

当院における膀胱全摘除術の臨床統計

谷本竜太, 雑賀隆史, 枝村康平, 小林知子, 眞鍋大輔, 江原伸, 賀来春紀, 那須保友, 公文裕巳

西日本泌尿器科 67 ( 増刊 ) 148 - 148 2005.10

腎癌に対するCTガイド下経皮的ラジオ波治療(Radiofrequency Ablation) 15例の臨床的検討

小林知子, 眞鍋大輔, 江原伸, 生口俊浩, 郷原英夫, 賀来春紀, 雑賀隆史, 那須保友, 公文裕巳

日本癌治療学会誌 40 ( 2 ) 621 - 621 2005.9

125Iシード線源による前立腺癌永久挿入密封小線源治療

江原伸, 真鍋大輔, 谷本竜太, 枝村康平, 雑賀隆史, 那須保友, 公文裕巳

日本癌治療学会誌 40 ( 2 ) 736 - 736 2005.9

ホルモン抵抗性前立腺癌に対するドセタキセル,エストラムスチン,デキサメサゾン併用療法の臨床経験

真鍋大輔, 江原伸, 雑賀隆史, 小林知子, 枝村康平, 谷本竜太, 賀来春紀, 那須保友, 津島知靖, 公文裕巳

日本癌治療学会誌 40 ( 2 ) 739 - 739 2005.9

Adrenal myelolipoma treated by laparoscopic adrenalectomy: A report of two cases

Hiromu Tsuboi, Masami Watanabe, Osamu Fujita, Nobuyuki Kusaka, Takashi Senoh, Takashi Saika, Atsushi Nagai, Yasutomo Nasu, Hiromi Kumon

Nishinihon Journal of Urology 67 ( 9 ) 562 - 567 2005.9

Language：Japanese Publishing type：Research paper (scientific journal)

We herein report 2 cases of adrenal myelolipoma which were treated with laparoscopic adrenalectomy. In Case 1, a 46-year-old woman presented with right flank pain. A right adrenal mass was detected by abdominal ultrasonography. In Case 2, a 56-year-old woman presented with a cough. A right adrenal mass was incidentally detected by chest CT. In both cases, endocrine study of the adrenal cortex and medulla demonstrated normal results. According to ultrasonography, CT and MRI, each of the adrenal masses seemed most likely to be an adrenal myelolipoma. Adrenalectomy was performed by laparoscopic procedure. The tumor size was 6.5 × 6.0 × 6.0 cm and 4.5 × 3.5 × 3.0 cm in Cases 1 and 2, respectively. Histology showed a complex of hematopoietic and adipose tissues, corresponding to adrenal myelolipoma. In each case, the courses has been uneventful both during and after surgery. Laparoscopic adrenalectomy is recommended for the treatment of myelolipoma since earlier postoperative recovery can be expected compared with open surgery.

Clinical results of one-stage urethroplasty with parameatal foreskin flap for hypospadias Reviewed

A Nagai, Y Nasu, M Watanabe, N Kusumi, H Tsuboi, H Kumon

ACTA MEDICA OKAYAMA 59 ( 2 ) 45 - 48 2005.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

Predicting postoperative renal insufficiency in patients undergoing nephrectomy for renal malignancy: Assessment by renal scintigraphy using (99m)Technetium-mercaptoacetyltriglycine Reviewed

Y Shirasaki, T Saika, T Tsushima, Y Nasu, R Arata, H Kumon

JOURNAL OF UROLOGY 173 ( 2 ) 388 - 390 2005.2

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Purpose: We performed 99(m)Tc-mercaptoacetyltriglycine (MAG3) renal scintigraphy in patients with renal malignancy to evaluate the function of each renal unit before and after nephrectomy to see if postoperative functional deterioration could be predicted based on scintigraphy results and creatinine clearance.
Materials and Methods: A total of 22 men and 13 women with renal malignancy, including 32 with renal cell carcinoma and 3 with urothelial cancer, were prospectively enrolled in this study. Average patient age was 64.3 years (median 65, range 43 to 88). All patients underwent MAG3 renal scintigraphy before and after unilateral nephrectomy. At the same time serum creatinine and endogenous creatinine clearance were determined.
Results: Mean serum creatinine was 0.93 mg/dl before and 1.31 after nephrectomy (p <0.0001). Preoperative endogenous creatinine clearance was 70.8 ml per minute per 1.73 m(2), which decreased to 49.0 ml per minute per 1.73 m(2) after nephrectomy (p <0.0001). Mean MAG3 clearance of the remaining kidney increased 35.1% above baseline from 156.5 to 211.5 ml per minute per 1.73 m(2) following nephrectomy. Spearman rank core analysis revealed that preoperative MAG3 clearance of the remaining kidney significantly correlated with postoperative creatinine clearance (r = 0.596, p = 0.0005). Preoperative MAG3 clearance of the remaining kidney more than 130 ml per minute per 1.73 M-2 coincided with postoperative creatinine clearance above 40 ml per minute per 1.73 m(2).
Conclusions: MAG3 renal scintigraphy may be useful for predicting renal insufficiency after nephrectomy. The findings in this study suggest that preoperative MAG3 clearance of the remaining kidney less than 130 ml per minute per 1.73 m(2) is a risk factor for postoperative renal insufficiency.

DOI： 10.1097/01.ju.0000149980.61593.5f

Varicocele rupture due to sexual intercourse

Nishiyama Y, Nagai A, Nasu Y, Watanabe M, Kusumi N, Monden K, Kumon H

Int J Urol 12 585 - 587 2005

Sex reassignment surgery for male to female transsexuals: initial experience in Okayama university hospital.

Atsushi Nagai, Eijirou Tokuyama, Yuzaburo Nanba, Tetsuya Tsutsui, Yoshihiro Kimata, Mikiya Nakatsuka, Isao Koshima, Takashi Saika, Yasutomo Nasu, Hiromi Kumon

Acta medica Okayama 59 ( 5 ) 231 - 233 2005

Language：English Publishing type：Research paper (scientific journal)

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.

Adeno-associated virus-mediated human IL-10 gene transfer suppresses the development of experimental autoimmune orchitis

Watanabe M, Kashiwakura Y, Kusumi N, Tamayose K, Nasu Y, Nagai A, Shimada T, Daida H, Kumon H

Gene Therapy 12 1126 - 1132 2005

Minimal invasiveness and effectivity of subinguinal microscopic varicocelectomy:A comparative study with retroperitoneal high and laparoscopic approaches

Watanabe M, Nagai A, Kusumi N, Tsuboi H, Nasu Y, Kumon H

Int J Urol 12 892 - 898 2005

Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study.

Toyoaki Uchida, Shiro Baba, Akira Irie, Shigehiro Soh, Naoya Masumori, Taiji Tsukamoto, Hiroomi Nakatsu, Hiroyuki Fujimoto, Tadao Kakizoe, Takeshi Ueda, Tomohiko Ichikawa, Nobutaka Ohta, Tadaichi Kitamura, Makoto Sumitomo, Masamichi Hayakawa, Teiichiro Aoyagi, Masaaki Tachibana, Ryusuke Ikeda, Kohji Suzuki, Nobuo Tsuru, Kazuo Suzuki, Seiichiro Ozono, Kiyohide Fujimoto, Yoshihiko Hirao, Kohichi Monden, Yasutomo Nasu, Hiromi Kumon, Kazuhiko Nishi, Shoichi Ueda, Hirofumi Koga, Seiji Naitoh

Hinyokika kiyo. Acta urologica Japonica 51 ( 10 ) 651 - 658 2005

Language：English Publishing type：Research paper (scientific journal)

We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.

Analysis of human ejaculation using color doppler ultrasonography:A comparison between antegrade and retrograde ejaculation

Nagai A, Watanabe M, Nasu Y, Iguchi H, Kusumi N, Kumon H

Urology 65 ( 2 ) 365 - 368 2005

Adeno-associated virus 2-mediated intratumoral prostate cancer gene therapy: long-term maspin expression efficiently suppresses tumor growth. International journal

Masami Watanabe, Yasutomo Nasu, Yuji Kashiwakura, Norihiro Kusumi, Kenji Tamayose, Atsushi Nagai, Tetsuo Sasano, Takashi Shimada, Hiroyuki Daida, Hiromi Kumon

Human gene therapy 16 ( 6 ) 699 - 710 2005

Language：English Publishing type：Research paper (scientific journal)

Maspin is a member of the serine protease inhibitors and the maspin gene, a tumor suppressor gene, is down-regulated in a large fraction of prostate cancers. We evaluated the use of adeno-associated virus (AAV, serotype 2) vector encoding maspin as a means for in vivo gene therapy for human prostate cancer. TUNEL assay of subcutaneously formed LNCaP or DU145 tumors in nude mice showed that intratumoral AAV-mediated maspin expression significantly upregulated the number of apoptotic cells compared with AAV-LacZ treatment. Immunofluorescence double staining for maspin protein and apoptosis in LNCaP tumors showed that the percentage of apoptotic cells in AAV-maspin-mediated maspin-expressing cells was significantly high compared with that in AAV-GFP-mediated GFP-expressing cells. Moreover, significantly fewer CD31-positive microvessels were observed in AAV-maspin-treated tumors compared with the control tumors. These therapeutic responses were highly correlated to persistent maspin expression in tumors, confirmed by Western blot analysis until at least day 56 after treatment. Finally, intratumoral delivery of AAV-maspin significantly suppressed growth of LNCaP and DU145 tumors and improved survival of mice. We conclude that AAV-mediated prolonged maspin expression efficiently suppresses human prostate tumor growth in vivo by apoptosis induction and inhibition of angiogenesis.

XAGE-1 rnRNA expression in prostate cancer and antibody response in patients Reviewed

F Koizumi, Y Noguchi, T Saika, K Nakagawa, S Sato, AMA Eldib, Y Nasu, H Kumon, E Nakayama

MICROBIOLOGY AND IMMUNOLOGY 49 ( 5 ) 471 - 476 2005

Language：English Publishing type：Research paper (scientific journal) Publisher：CENTER ACADEMIC PUBL JAPAN

To evaluate the feasibility of cancer vaccine targeting XAGE-1, we investigated the expression of 4 XAGE-1 transcript variants and the humoral immune response to XAGE-1 in prostate cancer patients. XAGE-1a, b, c, d mRNA expression was analyzed in 54 prostate cancer specimens and 8 specimens of benign prostate hypertrophy (BPH) by reverse transcription-polymerase chain reaction (RT-PCR). The Immoral response to XAGE-1 was investigated in sera obtained from 278 patients with prostate cancer and 40 healthy volunteers by enzyme-linked immunosorbent assay (ELISA) using recombinant protein. XAGE-1b mRNA expression was observed in 14 of 54 (26%) prostate cancer specimens, while XAGE-1a, c, and d mRNA expressions were observed in 1, 1, and 3, respectively. None of the 4 XAGE-1 transcript variants was observed in the 8 BPH specimens. Antibody against XAGE-1 was detected in sera from 2 of 129 stage D2 patients, whereas none of sera from 149 patients with localized prostate cancer or lymph node metastasis had detectable XAGE-1 antibody. No reactivity to XAGE-1 was found in sera from the 40 healthy individuals.

前立腺癌発生率におけるテストステロンの影響に関する疫学的検討 : 元ハンセン病患者を検診対象として(第93回日本泌尿器科学会総会)

大和豊子, 雑賀隆史, 黒瀬恭平, 那須保友, 津島知靖, 公文裕巳

日本泌尿器科学会雑誌 96 ( 2 ) 165 - 165 2005

精巣腫瘍に対する後腹膜リンパ節郭清術の検討(第93回日本泌尿器科学会総会)

津島知靖, 雑賀隆史, 枝村康平, 村上貴典, 小泉文人, 小林知子, 真鍋大輔, 江原伸, 賀来春紀, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 96 ( 2 ) 270 - 270 2005

^<125>Iシード線源による前立腺癌永久刺入密封小線源治療(第93回日本泌尿器科学会総会)

江原伸, 真鍋大輔, 能勢宏幸, 枝村康平, 雑賀隆史, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 96 ( 2 ) 426 - 426 2005

Long-term consequence of renal function following nephrectomy for renal cell cancer Reviewed

Y Shirasaki, T Tsushima, Y Nasu, H Kumon

INTERNATIONAL JOURNAL OF UROLOGY 11 ( 9 ) 704 - 708 2004.9

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL PUBLISHING ASIA

Aim: A retrospective analysis was performed involving patients who had undergone radical nephrectomy for renal cell cancer to determine the long-term outcome of this surgery on renal status.
Materials and Methods Between 1977 and 2001, 172 patients having undergone radical nephrectomy for renal cell cancer were followed for a period of more than one year at the Department of Urology Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. The preoperative and postoperative serum creatinine values of these individuals were reviewed. Long-term effects of radical nephrectomy on renal function and factors influencing postoperative renal dysfunction were analyzed.
Results: Six (3.5%) of the 172 individuals progressed to hemodialysis. Eleven (6.4%) patients displayed serum creatinine values of greater than or equal to1.6 mg/dL. The remaining 155 patients (90.1%) demonstrated postoperative serum creatinine values of <1.6 mg/dL. The present study suggests that aging, a high degree of proteinuria, hypertension and diabetes mellitus were the predominant risk factors for renal deterioration following nephrectomy.
Conclusions: We have primarily selected radical nephrectomy for cases exhibiting smaller renal tumors with a normal contralateral kidney. We encourage nephron-sparing surgery where possible in patients displaying risk factors, including a high degree of proteinuria, hypertension, or diabetes mellitus.

腎癌に対するCTガイド下経皮的ラジオ波治療(Radiofrequency Ablation) 12例の臨床的検討

小林知子, 眞鍋大輔, 江原伸, 雑賀隆史, 那須保友, 公文裕巳, 生口俊浩, 金澤右, 日下信行, 津島知靖

日本癌治療学会誌 39 ( 2 ) 929 - 929 2004.9

Positive correlation between allelic loss at chromosome 14q24-31 and poor prognosis of patients with renal cell carcinoma Reviewed

H Kaku, S Ito, S Ebara, M Ouchida, Y Nasu, T Tsushima, H Kumon, K Shimizu

UROLOGY 64 ( 1 ) 176 - 181 2004.7

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Objectives. To report our development of a new application of the inter-AN long polymerase chain reaction (PCR) for genomic scanning to screen for tumor-specific alterations in tumor DNA. Using this method, we detected a rearranged chromosomal region in renal cell carcinomas (RCCs). We then examined tumor-specific allelic loss in this region using microsatellite markers and determined whether a relationship was present between this allelic loss and the clinicopathologic features of the patients.
Methods. The inter-Alu long PCR genomic scan method was performed using RCC DNA samples and primers specific for a minor subset of the human repeat sequence Alu. We analyzed DNA samples from 42 pairs of matched normal and nonpapillary RCC tissues with seven microsatellite markers.
Results. The inter-Alu long PCR genomic scan method revealed an altered DNA region on chromosome 14q24-31, which is the location of several putative tumor suppressor genes. At least one of seven microsatellite markers on chromosome 14q24-31 showed loss of heterozygosity in 23 (54.8%) of 42 informative cases of RCC. The prevalent loss region was confined to a 2-Mb region around D14S67. We found a positive correlation between the presence of the loss of heterozygosity on 14q24-31 and tumor stage (P < 0.05). We also found that cases with allelic loss at 14q24-31 had a poor prognosis (P = 0.045).
Conclusions. Our inter-Alu long PCR genomic scan method is a powerful method for the screening of DNA alterations, and our data suggest that the chromosome 14q24-31 region contains likely tumor suppressor genes associated with the progression of RCC. (C) 2004 Elsevier Inc.

DOI： 10.1016/j.urology.2004.03.015

Effects of conadotropin-releasing hormone agonists on bone metabolism markers and bone mineral density in patients with prostate cancer Reviewed

Y Miyaji, T Saika, Y Yamamoto, N Kusaka, R Arata, S Ebara, Y Nasu, T Tsushima, H Kumon

UROLOGY 64 ( 1 ) 128 - 131 2004.7

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Objectives. To better understand bone metabolism and predict bone loss in treatment using gonadotropin-releasing hormone agonist for patients with prostate cancer.
Methods. The changes in bone mineral density and blood levels of bone metabolism markers and the level of pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen, a specific marker of bone resorption, and carboxy-terminal pro-peptide of human type I procollagen, a specific marker of bone formation, were examined in 27 consecutive patients with prostate cancer without bone metastasis.
Results. After 2 years of gonadotropin-releasing hormone treatment, the bone mineral density was significantly lower (median 0.937 g/cm(2)) than before treatment. Pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen began to increase significantly 6 months after the start of treatment (3.0 to 8.3 ng/mL, median 4.6, at baseline versus 3.4 to 8.2 ng/mL, median 5.2, after 6 months). Carboxy-terminal pro-peptide of human type I procollagen began to show a significant rise I year after the start of treatment (from 72.8 to 221.5 ng/mL, median 102.0, at baseline to 82.7 to 293.4 ng/mL, median 132.0, at I year).
Conclusions. Functional coupling between bone resorption and formation was noted, and a decrease in bone mass, even in men, owing to androgen deficiency, was biochemically demonstrated. Fluctuations in these two bone metabolism markers preceded the decrease of bone mineral density. Therefore, these markers might be a predictor of bone loss. (C) 2004 Elsevier Inc.

DOI： 10.1016/j.urology.2004.03.012

Kidney function after nephrectomy for renal cell carcinoma Reviewed

Y Shirasaki, T Tsushima, T Saika, Y Nasu, H Kumon

UROLOGY 64 ( 1 ) 43 - 47 2004.7

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Objectives. To evaluate the function of the remaining kidney after nephrectomy for renal cell cancer by technetium-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) renal scintigraphy.
Methods. We evaluated 30 consecutive patients who were undergoing unilateral radical nephrectomy by Tc-99m-MAG3 scintigraphy. All patients underwent three consecutive 99mTc-MAG3 scintigraphy studies. The first study was performed before nephrectomy, the second 1 month after surgery, and the third 1 year after surgery. At these times, the serum creatinine levels were also evaluated.
Results. The mean preoperative MAG3 clearance of the remaining kidney of the 30 patients was 155.4 mL/min/1.73 m(2). The mean MAG3 clearance of the remaining kidney had increased to 209.2 mL/min/1.73 m(2) by I month after nephrectomy, and the average percentage increase was 39.5%. After 1 year, it had increased to 211.3 mL/min/1.73 m(2), with a 40.5% average percentage increase. The preoperative MAG3 clearance of the remaining kidney was inversely correlated with the percentage of increase in MAG3 clearance of the remaining kidney. Abnormal serum creatinine levels (greater than 1.3 mg/dL) were more common after nephrectomy, occurring in 6 patients at 1 month and in 5 patients at 1 year postoperatively. In all 6 patients with elevated creatinine levels, the preoperative MAG3 clearance of the remaining kidney was less than 150 mL/min/1.73 m(2).
Conclusions. Adaptive hyperfunction occurs soon after nephrectomy that is not associated with age or sex and continues for at least 1 year. A greater compensatory response is produced in patients with more severe renal deterioration. Using (99)mTc-MAG3 scintigraphy, we may be able to predict postoperative renal function. (C) 2004 Elsevier Inc.

DOI： 10.1016/j.urology.2004.02.039

Comparative study of ureteral stripping versus open ureterectomy for nephroureterectomy in patients with transitional carcinoma of the renal pelvis Reviewed

T Saika, J Nishiguchi, T Tsushima, Y Nasu, A Nagai, Y Miyaji, Y Maki, T Akaeda, M Saegusa, H Kumon

UROLOGY 63 ( 5 ) 848 - 852 2004.5

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Objectives. To evaluate the clinical outcome of nephroureterectomy with endoscopically assisted transurethral ureteral stripping for transitional cell carcinoma of the renal pelvis in a comparative study.
Methods. Sixty patients with localized renal pelvic cancer were enrolled in a prospective comparative nonrandomized study. Of these, 28 patients underwent nephroureterectomy with endoscopically assisted transurethral ureteral stripping and 32 underwent conventional nephroureterectomy with a bladder cuff. Both short-term and long-term results were analyzed in this series.
Results. The operating time for patients with ureteral stripping was significantly shorter than for those with a standard two-incision nephroureterectomy (median 183 versus 250 minutes, P = 0.0231), and the amount of blood loss was significantly less (median 150 versus 390 mL, P = 0.0002). Intravesical recurrence was detected in 10 (35.7%) of the 28 patients with ureteral stripping, and the 1-year and 3-year recurrence-free rate was 68.0% and 57.7%, respectively. Seven patients treated by the standard two-incision nephroureterectomy (21.9%) experienced intravesical recurrence, with a 1-year and 3-year recurrence-free rate of 96.8% and 75.0%, respectively. The recurrence rate was significantly greater in the group with ureteral stripping (P = 0.0287).
Conclusions. Compared with conventional nephroureterectomy with a bladder cuff, nephroureterectomy with transurethral stripping is a minimally invasive procedure with a shorter operating time and less blood loss, but a statistically significantly greater intravesical recurrence rate. Greater consideration should be taken before selecting this procedure. (C) 2004 Elsevier Inc.

DOI： 10.1016/j.urology.2003.12.003

Analysis of retrograde ejaculation using color Doppler ultrasonography before and after transurethral collagen injection

NAGAI A

Int J Impot Res 16 456 - 458 2004

Ureteroscopy using a detachable access sheath.

Abarzua Fernando, Monden Koichi, Nagai Atsushi, Nasu Yasutomo, Kumon Hiromi

Acta Medica Okayama 58 ( 4 ) 215 - 216 2004

Decreased Expression of REIC/Dkk-3 in Human Renal Clear Cell Carcinoma

KYOUHEI KUROSE, MASAKIYO SAKAGUCHI, YASUTOMO NASU, SHIN EBARA, HARUKI KAKU, REIKO KARIYAMA, YUJIROU ARAO, MASAHIRO MIYAZAKI, TOMOYASU TSUSHIMA, MASAYOSHI NAMBA, HIROMI KUMON, NAM-ho HUH

Journal of Urology 171 ( 3 ) 1314 - 1318 2004

Dynamin-2 regulates oxidized low-density lipoprotein-induced apoptosis of vascular smooth muscle cell.

Kashiwakura Y, Watanabe M, Kusumi N, Sumiyoshi K, Nasu Y, Yamada H, Sawamura T, Kumon H, Takei K, Daida H

Circulation 110 ( 21 ) 3329 - 3334 2004

OP4-085 99mTc-MAG3腎シンチグラフィーによる腎摘後腎機能障害の予測(一般演題(口演))

白崎義範, 那須保友, 津島知靖, 公文裕巳

日本泌尿器科学会雑誌 95 ( 2 ) 427 - 427 2004

PP3-058 岡山大学において最近18年間に経験した上部尿路腫瘍105例の臨床的検討(一般演題(ポスター))

賀来春紀, 小林知子, 黒瀬恭平, 日下信行, 江原伸, 妹尾孝司, 雑賀隆史, 那須保友, 津島知靖, 公文裕巳

日本泌尿器科学会雑誌 95 ( 2 ) 488 - 488 2004

The quality of life in patients with bladder cancer after cystectomy

Ryoji Arata, Tomoyasu Tsushima, Takashi Saika, Yasutomo Nasu, Hiromi Kumon, Tadashi Oeda, Yoshiyuki Miyaji, Ayano Ishii, Hitoshi Takamoto

Nishinihon Journal of Urology 66 ( 4 ) 279 - 290 2004

Language：Japanese Publishing type：Research paper (international conference proceedings)

A survey carried out by means of questionnaires was conducted to assess the impact of different forms of urinary diversion on the quality of life (QOL) in patients with bladder cancer. First, a QOL survey using self-administered questionnaires was carried out on 330 patients who were followed up for more than 3 months after cystectomy at the Okayama University Hospital and its affiliated hospitals. QOL assessment was performed using EORTC QLQ-C30, supplemented with detailed questionnaires about sexual function, voiding function, continence and patient's satisfaction. Among these 330 patients, 80 had an orthotopic urinary reservoir (OUR), 27 had a continent urinary reservoir (CUR) and 223 had a urostomy. Based on the answes to these questionnaires, there was little difference in the QOL score among the three groups. However, as regards satisfaction with the methods of urinary diversion, patients in the OUR group expressed better satisfaction than those in the other two groups. Second, a survey based on the same questionnaires was performed to assess the changes in the QOL of 57 patients observed prospectively from pre-surgery to one year post-surgery. Two kinds of urinary diversion were compared: 26 patients received OUR and 31 patients received urostomy. In most areas, the QOL returned to the prior level within six months after surgery. However, patients were restricted as regards their sexual function. Concerning voiding condition and continence in the OUR group, the score did not return to the prior level within one year. After one year post-surgery, no difference was recognized with regard to any of the items between the two groups.

Anterior urethral recurrence of superficial bladder cancer: Its clinical significance Reviewed

T Saika, T Tsushima, Y Nasu, R Arata, H Kaku, N Akebi, N Kusaka, H Kumon

ACTA MEDICA OKAYAMA 57 ( 6 ) 293 - 297 2003.12

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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.

NY-ESO-1 mRNA expression and immunogenicity in advanced prostate cancer Reviewed

Tetsuya Nakada, Yuji Noguchi, Shuichiro Satoh, Toshiro Ono, Takashi Saika, Takushi Kurashige, Sacha Gnjatic, Gerd Ritter, Yao-Tseng Chen, Elisabeth Stockert, Yasutomo Nasu, Tomoyasu Tsushima, Hiromi Kumon, Lloyd J. Old, Eiichi Nakayama

Cancer Immunity 3 1 - 12 2003.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Academy of Cancer Immunology

NY-ESO-1 mRNA expression was investigated in advanced prostate cancer by conventional and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). NY-ESO-1 mRNA was detected in 20 of 53 (38%) tumor specimens. Four of 15 (27%) stage C, 1 of 3 stage D1 (33%) and 15 of 35 (43%) stage D2 prostate cancers were positive. The presence of NY-ESO-1 antibodies was evaluated in sera from a panel of 218 patients with prostate cancer, including the 53 patients whose tumors were examined for NY-ESO-1 mRNA expression. NY-ESO-1 antibodies were detected in 1 of 30 (3.3%) stage D1 and 9 of 110 (8.2%) stage D2 patients, whereas none of the 78 patients with localized prostate cancer (stages A, B and C) had detectable NY-ESO-1 antibodies. Of the 53 patients whose tumors were examined for NY-ESO-1 mRNA expression, 2 of 20 patients with NY-ESO-1 mRNA-positive tumors had NY-ESO-1 antibodies. No antibody was found in the sera of 32 patients with NY-ESO-1 mRNA-negative tumors, with the exception of one patient with regional lymph node metastasis (stage D1). CD8 T cell responses specific to NY-ESO-1 were detected in two of three patients with NY-ESO-1 antibodies.

Laparoscopic removal of mullerian structures and orchiopexy for persistent mullerian duct syndrom

Shirasaki Y, Nagai A, Nasu Y, Iguchi H, Kumon H

Urology 62 ( 6 ) 1121 2003

前立腺癌に対する自殺遺伝子治療臨床研究の経過報告

江原伸, 那須保友, 津島知靖, 公文裕, Thompson Timothy

日本泌尿器科学会雑誌 94 ( 2 ) 387 - 387 2003

腎細胞癌の臨床的検討

白崎義範, 那須保友, 津島知靖, 公文裕巳

日本泌尿器科学会雑誌 94 ( 2 ) 305 - 305 2003

前立腺癌と良性疾患の鑑別に最も有効な前立腺関連マーカーの組み合わせに関する研究

津島知靖, 那須保友, 雑賀隆史, 新良治, 石戸則孝, 高本均, 山田大介, 陶山文三, 原雅弘, 赤澤信幸, 小武家誠, 宮地禎幸, 公文裕巳

日本泌尿器科学会雑誌 94 ( 2 ) 318 - 318 2003

Clinical study of G3 superficial bladder cancer without concomitant CIS treated with conservative therapy Reviewed

T Saika, T Tsushima, Y Nasu, R Arata, H Kaku, N Kusaka, H Kumon

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 32 ( 11 ) 461 - 465 2002.11

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

Objective: The treatment for superficial G3 transitional cell carcinoma (TCC) of the urinary bladder remains controversial. It is important to reveal the clinical features of superficial G3 bladder cancer that can be treated conservatively.
Patients and Methods: A total of 39 patients with primary superficial bladder cancer (Ta, T1) with G3 components but without concomitant carcinoma in situ (CIS), who had been treated initially with transurethral resection (TUR), were retrospectively analyzed for factors related to tumor recurrence, progression and survival. The patients were 34 males and five females who,se age ranged from 49 to 85 years (average, 68 years). Initial tumor stages were Ta in one patient and T1 in 38. Initial treatments were TUR alone in 18 patients and TUR with adjuvant therapy (intravesical chemotherapy or BCG therapy) in 21. Factors examined included age, gender, morphology, size and number of tumors and adjuvant therapies.
Results: Follow-up periods were 3-138 months (median, 37 months). Tumor recurrence, progression and cancer death were observed in 23, seven and four cases, respectively. The 5-year progression-free rate (75%) and survival rate (83%) in 39 patients with G3 did not show a statistically significant difference from those of the 109 patients with G1 or the 187 patients with G2-superficial bladder cancer who were treated with TUR initially. Only the rate of recurrence of patients with G3 was significantly higher than that of patients with G2 or G1. Adjuvant therapies reduced the recurrence rate of the patients with G3. Only tumor morphology, papillary or non-papillary, affected both the progression-free rate and the survival rate of patients with G3. There were no statistically significant differences associated with other factors.
Conclusion: The results suggest that superficial G3 bladder cancer could be treated with TUR initially, especially for papillary tumors.

前立腺全摘術後のPSA failureの定義とその妥当性について-超高感度測定法にて3ポイント連続上昇と定義した場合

妹尾孝司, 雑賀隆史, 那須保友, 津島知靖, 公文裕巳, 三宅知子, 宮地禎幸, 石戸則孝, 高本均, 小林泰之, 武田克治, 枝村康平, 林俊秀

西日本泌尿器科 64 ( 増刊 ) 179 - 179 2002.11

転移巣切除を行った腎細胞癌骨転移の2例

中田哲也, 倉繁拓志, 日下信行, 白崎義範, 賀来春紀, 新良治, 那須保友, 津島知靖, 公文裕巳, 中田英二, 上野孝展, 杉原進介, 原田良昭, 井上一

骨転移: 病態・診断・治療 17 ( 1 ) 23 - 30 2002.9

Language：Japanese Publisher：岡山骨転移カンファレンス事務局

症例1:67歳男.背部痛を主訴とした.右腎腫瘍の診断で,根治的右腎摘出術及び下大静脈人工血管置換術施行の既往があった.背部痛と両下半身の痺れが徐々に増悪し,第9腰椎に対しCTガイド下骨生検を施行した結果,腎細胞癌の胸椎転移と診断した.放射線療法施行後に第9胸椎全摘椎体置換術,第6-12胸椎後方固定術を行い,症状の改善をみた.症例2:49歳男.右大腿部痛,食欲不振を主訴とした.CT及びMRIより腎細胞癌の骨,肺転移巣と診断し,左腎摘術を施行した.肺転移巣は腎摘後,IFN-α投与開始早期に消失した.右大腿骨頭転移巣に対し放射線治療と右大腿骨腫瘍広範切除術を施行し,第6肋骨転移巣に対しては肋骨切除術を施行した.いずれも癌細胞を認めなかった.以上より,腎細胞癌骨転移症例における転移巣への治療法は姑息的治療が中心となっているが,症例を選択すれば転移巣切除術も有効な治療法となり得ると考えられた

Prostate specific antigen complexed to alpha-1-antichymotrypsin in patients with intermediate prostate specific antigen levels Reviewed

T Saika, T Tsushima, Y Nasu, N Kusaka, Y Miyaji, H Takamoto, K Takeda, S Uno, H Kumon

CANCER 94 ( 6 ) 1685 - 1691 2002.3

Language：English Publishing type：Research paper (scientific journal) Publisher：JOHN WILEY & SONS INC

BACKGROUND. The authors attempted to evaluate prospectively the usefulness of serum prostate specific antigen (PSA) complexed to alpha-1-antichymotrypsin (PSA-ACT) in the early detection of prostate carcinoma and its ability to discriminate between prostate carcinoma and benign prostatic hyperplasia (BPH), especially among patients with intermediate PSA levels.
METHODS. Between December 1999 and August 2000, systematic sextant biopsies were performed on 281 prospective patients with prostate carcinoma who had serum PSA levels between 4.1 ng/mL and 20.0 ng/mL. The serum samples were assayed by using kits that were designed specifically for measuring serum PSA, PSA-ACT, and free PSA levels. The clinical values of PSA, PSA-ACT, the free PSA to total PSA ratio (F/T ratio), the free PSA to PSA-ACT ratio, PSA density (PSAD), and PSA-ACT density (ACTD) were compared by using receiver operating characteristic (ROC) curve analysis.
RESULTS. Biopsy yielded no evidence of malignancy in 198 patients, and prostate carcinoma was confirmed in 83 patients. ROC analysis demonstrated that the area under the curve (AUC) for PSA-ACT was greater than that for total PSA and was equivalent to that for the F/T ratio in both groups of patients (PSA ranges of 4.1-20.0 ng/mL and 4.1-10.0 ng/mL, respectively). The AUC for the ACTD was greater than the AUC for the PSAD and had the highest value of all parameters.
CONCLUSIONS. The measurement of PSA-ACT represents an alternative to the use of total and free PSA. The ACTD value is the most useful for discriminating between BPH and prostate carcinoma. (C) 2002 American Cancer Society

DOI： 10.1002/cncr.10377

Laparoscopic radical prostatectomy: initial cases at Okayama University Hospital.

Nagai Atsushi, Nasu Yasutomo, Shirasaki Yoshinori, Iguchi Hiroki, Arata Ryouji, Tsugawa Masaya, Tsushima Tomoyasu, Kumon Hiromi

Acta Medica Okayama 56 ( 1 ) 51 - 52 2002

Validation of transrectal ultrasonographic volumetry for orthotopic prostate tumours in mice

Kraaji R, van Weerden W.M, de Ridder C.M, Gussenhoven E.J, Honkoop J, Nasu Y, Bangma C.H

Lab Anim 36 ( 2 ) 165 - 172 2002

Gene therapy for prostate cancer: toxicological profile of four HSV-tk transducing adenoviral vectors regulated by different promoters Reviewed

S Ebara, S Shimura, Y Nasu, H Kaku, H Kumon, G Yang, J Wang, TL Timme, E Aguilar-Cordova, TC Thompson

PROSTATE CANCER AND PROSTATIC DISEASES 5 ( 4 ) 316 - 325 2002

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Adenoviral vector delivery of the Herpes simplex virus thymidine kinase (HSV-tk) gene in combination with the prodrug ganciclovir (GCV) has been tested in phase I clinical trials for prostate cancer and found to exhibit a satisfactory toxicity profile. We have developed additional adenoviral vectors with differing promoters to optimize the expression profile and in the present study evaluate the potential systemic toxicity of these vectors. Four recombinant adenoviral vectors that express the HSV-tk gene were generated using three different promoters: CMV (leftward orientation); RSV (both rightward and leftward orientation); and the mouse caveolin-1 (cav-1) promoter (leftward orientation). Efficacy was determined in vitro by cytotoxicity assays in a mouse prostate cancer cell line, RM-9, and in vivo by treating orthotopic tumors. Potential toxicity was evaluated from liver histology and apoptotic cell counts and enzyme levels in the serum following intravenous adenoviral vector injection. Although there were differences in HSV-tk expression at the protein level among the four vectors there were no significant differences in in-vitro cytotoxicity studies with GCV or in vivo in tumor growth suppression of an orthotopic mouse prostate cancer model in GCV treated mice. Intravenous delivery of high doses of all adenoviral vectors lead to abnormalities in liver function as measured by specific serum markers and histological evaluation of liver tissue and increased levels of apoptosis in the liver. These abnormalities were most prevalent with the vector containing the CMV promoter and the rightward oriented RSV promoter. They were least prevalent in the vector regulated by the cav-1 promoter. Upregulation of specific chemokines, MIP-2 and MIP-1beta was correlated with apoptotic counts. Our results demonstrate that comprehensive toxicological analysis of adenoviral vectors provides internally consistent information that can differentiate vectors with comparable efficacy based on toxicity. In these studies vectors with the cav-1 promoter-driven and leftward RSV-driven HSV-tk gene demonstrated minimal toxicities with cytotoxic effectiveness comparable to more toxic vectors. Our studies further suggest that promoter selection can influence the toxic effects of an adenoviral gene therapy vector.

DOI： 10.1038/sj.pcan.4500610

表在性膀胱癌に対するエピルビシン(EPI)術後補助膀注療法

津島知靖, 雑賀隆史, 新良治, 賀来春紀, 那須保友, 公文裕巳, 朝日俊彦, 武田克治, 荒巻謙二, 三枝道尚, 大和豊子, 宮地禎幸, 小武家誠

日本泌尿器科学会雑誌 93 ( 2 ) 177 - 177 2002

進行性前立腺癌におけるNY-ESO-1の発現と免疫原性の検討

中田哲也, 倉繁拓志, 雑賀隆史, 野口雄司, 小野俊朗, 那須保友, 津島知靖, 中山容一, 公文裕巳, 宮地禎幸, 村上貴典, 牧佳男

日本泌尿器科学会雑誌 93 ( 2 ) 331 - 331 2002

前立腺癌に対する自殺遺伝子治療臨床研究について

那須保友, 公文裕巳, Thompson Timothy C.

日本泌尿器科学会雑誌 93 ( 2 ) 99 - 99 2002

腎細胞癌における新しい癌抑制遺伝子(REIC gene)の発現について

黒瀬恭平, 江原伸, 賀来春紀, 狩山玲子, 荒尾雄二郎, 那須保友, 津島知靖, 公文裕巳

日本泌尿器科学会雑誌 93 ( 2 ) 261 - 261 2002

膀胱全摘除術後患者の経時的QOL変化

新良治, 津島知靖, 小武家誠, 宮地禎幸, 高松正武, 大枝忠史, 石井和史, 大和豊子, 石井亜矢乃, 国富公人, 高本均, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 93 ( 2 ) 307 - 307 2002

Orthotopic neobladder reconstruction in elderly bladder cancer patients Reviewed

T Saika, B Suyama, T Murata, D Manabe, T Kurashige, Y Nasu, T Tsushima, H Kumon

INTERNATIONAL JOURNAL OF UROLOGY 8 ( 10 ) 533 - 538 2001.10

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL SCIENCE ASIA

Background: We compared the clinical results of orthotopic neobladder reconstruction in elderly patients and those in younger patients retrospectively in order to verify whether age is a critical factor in selecting a method of urinary diversion.
Methods: Following radical cystectomy for bladder cancer, 12 patients aged 75 or older and 17 patients under 75 who underwent orthotopic neobladder reconstruction between January 1992 and May 1999 were investigated in this study. The authors TS and BS were among the surgeons who performed operations for all cases. Of the 12 elderly patients, orthotopic neobladders were constructed according to Hautmann's method in nine cases, Studer's method in one case and Reddy's method in two cases. Of the 17 younger patients, these methods were employed in 12, one and four cases, respectively. Operative procedure, early and late complications, prognosis, continence and voiding pattern were investigated in these patients.
Results: The follow-up periods for elderly and younger groups ranged from 21.3 to 82.7 months and from 8.8 to 94.2 months, respectively. No difference in operation time, amount of bleeding or postoperative length of hospitalization was observed between elderly and younger patients. The rates of early complications in elderly and younger patients were 41.7% and 35.3%, respectively. Late complication rates were 33.3% and 47.1%, respectively The difference in these complication rates was not statistically significant. One of the elderly and two of the younger patients had local recurrence and metastasis postoperatively. Those three patients had died of their bladder cancer. No statistically significant difference between groups was recognized in either cause-specific survival or overall survival, nor was there such a difference in relation to micturition/continence.
Conclusion: Based on these results, we believe that because age is not a critical factor in the selection of urinary diversion method, neobladder reconstruction following cystectomy for bladder cancer is indicated in elderly patients. As stoma management is difficult for the patients, we consider orthotopic neobladder reconstruction to be the method of choice if the patients' general physical condition allows.

Retro peritoneoscopic pyelotomy combined with the transposition of crossing vessels for ureteropelvic junction obstruction

NAGAI A

J Urol 165 23 - 26 2001

Optimal starting time for flutamide to prevent disease flare in prostate cancer patients treated with a gonadotropin-releasing hormone agonist Reviewed

T Tsushima, Y Nasu, T Saika, Y Maki, M Noda, B Suyama, T Yamato, H Kumon

UROLOGIA INTERNATIONALIS 66 ( 3 ) 135 - 139 2001

Language：English Publishing type：Research paper (scientific journal) Publisher：KARGER

Objective: Flare-up phenomena, such as an increase in prostate-specific antigen (PSA) and/or deterioration of symptoms, are observed in some patients undergoing gonadotropin-releasing hormone (GnRH) agonist therapy. This study was carried out to determine the optimal time for starting the administration of flutamide to prevent flare-up phenomena. Patients and Methods: Twenty-six patients with prostate cancer and elevated serum levels of PSA were randomly assigned to 5 groups. Group A patients (n = 6) were treated with a subcutaneous injection of 3.75 mg leuprorelin acetate depot alone. Group B, C, D and E patients (5 patients in each group) were treated with 375 mg/day of orally administered flutamide combined with leuprorelin. Flutamide was initiated on the day of leuprorelin injection in group B, and at 1, 2 and 4 weeks before leuprorelin injection in groups C, D and E, respectively. Serum PSA and testosterone levels were measured in each patient. Results: Pretreatment with flutamide increased the serum testosterone level, but the testosterone surge after leuprorelin administration was almost the same in all 5 treatment groups. In patients who had been treated with flutamide in combination with leuprorelin, the mean PSA level did not exceed the pretreatment levels after leuprorelin administration. The rate of decrease in PSA in the group receiving simultaneous administration of flutamide with leuprorelin showed a decline comparable to that during the period before leuprorelin administration in the flutamide pretreatment groups. Conclusion: Simultaneous administration of flutamide with a GnRH agonist is sufficient to prevent flare-up phenomena. Copyright (C) 2001 S. Karger AG, Basel.

Treatment of androgen-independent prostate cancer with dexamethasone: A prospective study in stage D2 patients Reviewed

T Saika, N Kusaka, T Tsushima, T Yamato, T Ohashi, B Suyama, R Arata, Y Nasu, H Kumon

INTERNATIONAL JOURNAL OF UROLOGY 8 ( 6 ) 290 - 294 2001

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL SCIENCE ASIA

Purpose: In order to evaluate the efficacy of dexamethasone in the treatment of Japanese men with androgen-independent prostate cancer, a prospective study was conducted using prostate-specific antigen (PSA) as a primary end-point.
Methods: Nineteen Japanese men with stage D2 androgen-independent prostate cancer were registered and treatment was started. After ruling out anti-androgen withdrawal syndrome, they were treated with dexamethasone (1.5 mg daily). Patients were monitored for PSA, symptoms, radiologic response, survival rate, time to disease progression, time to treatment failure and complications.
Results: Prostate-specific antigen levels decreased in nine patients (50.0%); five (27.8%) showed a 50% or greater decrease and two (11.1%) showed an 80% or greater decrease. For the nine patients, the mean duration of PSA response was 7.3 months and the median duration was 2.1 months (range, 1.2-27.5+). Bone pain, which was noted in 13 patients at study entry, improved in seven patients (53.8%). Of nine patients who had serial radiographic examinations with bone scan, three (33%) showed partial response, two (22%) were stable and four (44%) showed disease progression. Treatment was well tolerated, except for one patient who suffered a severe pulmonary infection.
Conclusion: Dexamethasone decreased PSA levels and produced subjective symptomatic improvement in the patients with stage D2 androgen-independent prostate cancer.

Total PSA 4.0〜20.0ng/ml症例におけるPSA α1-antichymotrypsin complex(PSA-ACT)の有用性

津島知靖, 那須保友, 永井敦, 門田晃一, 雑賀隆史, 新良治, 賀来春紀, 白崎義範, 公文裕巳, 宮地禎幸, 高本均, 武田克治, 宇埜智

日本泌尿器科学会雑誌 92 ( 2 ) 275 - 275 2001

移行上皮癌におけるCancer/Testis抗原NY-ESO-1の発現と免疫応答

倉繁拓志, 雑賀隆史, 中田哲也, 野口雄司, 小野俊朗, 日下信行, 白崎義範, 賀来春紀, 新良治, 那須保友, 津島知靖, 中山睿一, 公文裕巳

日本泌尿器科学会雑誌 92 ( 2 ) 347 - 347 2001

腎細胞癌に対する腎部分切除術の検討

白崎義範, 新良治, 那須保友, 津島知靖, 公文裕巳, 市川孝治, 光畑直喜, 西光雄, 林俊秀

日本泌尿器科学会雑誌 92 ( 2 ) 248 - 248 2001

経尿道的手術直後に膀胱内注入されたピラルビシン(THP)の血漿および血球への移行

津島知靖, 那須保友, 雑賀隆史, 新良治, 白崎義範, 日下信行, 公文裕巳, 橋本英昭, 森永修, 石井和史, 大和豊子, 上原偵也, 赤枝輝明

日本泌尿器科学会雑誌 92 ( 2 ) 258 - 258 2001

前立腺癌に対するIn Situ Gene Therapy : マウス前立腺癌転移モデルを用いた併用療法とその投与時期の検討

江原伸, 雑賀隆史, 佐藤威文, 那須保友, 津島知靖, TERRY TIMME L., GUANG YANG, TIMOTHY THOMPSON C., 公文裕巳

日本泌尿器科学会雑誌 92 ( 2 ) 266 - 266 2001

内分泌療法抵抗性再燃前立腺癌に対するbicalutamideの効果

中田哲也, 倉繁拓志, 村田匡, 白崎義範, 賀来春紀, 新良治, 那須保友, 津島知靖, 公文裕巳, 渡辺雄一, 宮地禎幸, 牧佳男, 高本均

日本泌尿器科学会雑誌 92 ( 2 ) 284 - 284 2001

LH-RH agonist投与中止後におけるテストステロン値の推移について

賀来春紀, 中田哲也, 倉繁拓志, 日下信行, 新良治, 那須保友, 津島知靖, 公文裕巳

日本泌尿器科学会雑誌 92 ( 2 ) 391 - 391 2001

Efficacy of ultrasound contrast agent in the diagnosis and treatment of prostate diseases

Masaya Tsugawa, Katsumi Sasaki, Takashi Senoo, Ryoji Arata, Yasutomo Nasu, Hiromi Kumon

Nishinihon Journal of Urology 62 ( 4 ) 176 - 181 2000.4

Language：Japanese Publishing type：Research paper (scientific journal)

The efficacy of an ultrasound contrast agent (Levovist(TM)) for ultrasonography during prostatic biopsy and transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia (BPH) was examined. Between March and September, 1999, 25 patients who were suspected of having prostate cancer according to PSA, MRI or transrectal ultrasonography (TRUS), underwent transrectal prostatic biopsy. The ultrasound contrast agent was administered intravenously at a concentration of 300 mg/ml and at a rate of 1.0 ml/min. Similarly, between January and September, 1999, for 3 patients with symptomatic BPH, changes in blood flow signals in the prostate gland during TUMT were observed using transrectal color Doppler ultrasound using the ultrasound contrast agent. The ultrasound contrast agent was administered intravenously at a concentration of 300 mg/ml and at a rate of 0.5 ml/min. Prostatic cancer was detected in 17 (68.0%) of the 25 patients. Evaluating all the samples obtained, the sensitivity and specificity were 70.6% and 84.3% for TRUS, 64.7% and 86.1% for color Doppler ultrasound, and 64.7% and 87.0% for enhanced color Doppler ultrasound, respectively. Although this is only a preliminary report, we were able to conclude that the use of an ultrasound contrast agent during prostatic biopsy can enable the lesion to be depicted clearly, however there is little impact on the improvement of sensitivity and specificity in the diagnosis of prostate cancer. The signals of blood flow in the prostate gland increased just after the initiation of TUMT in all patients. Avascular areas in the prostate appeared about 10 minutes after TUMT treatment and expanded time dependently in all patients. These avascular areas were correlated with the coagulative necrosis areas detected by MRI 2 weeks after treatment. The real-time observation of avascular areas using an ultrasound contrast agent during TUMT for BPH has become possible, and this will be helpful in establishing the treatment conditions for each patient.

Ureteropyeloscopy for upper urinary tract lesions - Its techniques and applications

Masaya Tsugawa, Yasutomo Nasu, Hiromi Kumon

Nishinihon Journal of Urology 62 ( 4 ) 147 - 152 2000.4

Language：Japanese Publishing type：Research paper (scientific journal)

Since 1987, we have employed ureteropyeloscopic diagnosis and treatment for the patients with unilateral renal bleeding of uncertain etiology and upper urinary tract transitional cell carcinoma. The techniques and procedures have improved dramatically with the advancement of endoscopes and other related instruments. In this article, we introduce our recent procedures for ureteropyeloscopy with special reference to technical pitfalls. In addition, our clinical results are also reported. Between July, 1987 and September, 1999, 59 patients with essential hematuria were examined and treated endoscopically. The duration of gross hematuria was 1 to 144 months (average 29.5 months). The right side was affected in 21 patients, the left in 37, and both in 1 patient. The localized bleeding point was detected in 41 out of 59 patients. All these lesions were treated endoscopically. Among the 41 patients with localized bleeding, transitional cell carcinoma was found in 2, hemangioma in 14, minute venous rupture in 20, varices in 3 and calculus in 2. Between July, 1987 and September, 1999, we carried out endoscopic treatment for 16 patients with upper urinary tract transitional cell carcinoma. There were 3 patients who died of renal pelvic carcinoma, but there were no patients who died of ureteral carcinoma. However, the prognosis of patients with bilateral lesions, diffuse non-papillary carcinoma or preoperative positive urine cytology was particularly poor. In conclusion, ureteropyeloscopy is useful for the patients with unilateral renal bleeding of uncertain etiology. In cases of transitional cell carcinoma of the upper urinary tract with diffuse non-papillary carcinoma and/or preoperative positive urine cytology, total nephroureterectomy should be considered.

Primary malignant lymphoma of the adrenal gland diagnosed by percutaneous needle biopsy: A report of two cases

Daisuke Manabe, Atsushi Nagai, Tomoyasu Tsushima, Kazushi Manabe, Koichi Monden, Yasutomo Nasu, Hiromi Kumon

Nishinihon Journal of Urology 62 ( 3 ) 136 - 139 2000.3

Language：Japanese Publishing type：Research paper (scientific journal)

Two cases of adrenal malignant lymphoma were treated at our hospital. Case 1 was a 68-year-old man whose chief complaint was right flank pain. He was referred to us for treatment of bilateral adrenal tumors which had been detected at another hospital. A diagnosis of non Hodgkin's lymphoma (diffuse large cell type) was confirmed by US-guided needle biopsy. The patient did not respond to cisplatin-based combination chemotherapy and died within a week. Case 2 was a 72-year-old woman who visited our hospital complaining of left flank pain. CT scan revealed bilateral bulky masses confined to the adrenal gland. As in Case 1, US-guided needle biopsy revealed non-Hodgkin's lymphoma (diffuse large cell type). Despite partial response following CHOP chemotherapy, thrombocytopenia progressed and the patient died after four courses of chemotherapy.

Prognosis of patients with stage T1 and T2 renal cell carcinoma according to tumor size

Tomoyasu Tsushima, Yasutomo Nasu, Nobuyuki Kusaka, Ryoji Arata, Haruki Kaku, Yasuo Yamamoto, Yoshiyuki Miyaji, Mikio Kishi, Hiromi Kumon

Nishinihon Journal of Urology 62 ( 2 ) 55 - 58 2000.2

Language：Japanese Publishing type：Research paper (scientific journal)

In an attempt to define the relationship between tumor size and survival, the records of 307 patients with renal cell carcinoma were analyzed. Larger tumors were associated with a worse survival in T1-2 patients. When T1-2 patients were divided according to a tumor size of 70 mm, there was a statistically significant difference between the two groups (p = 0.01). There was no statistically significant difference between T1 and T2 patients divided according to a tumor size of 25 mm (p = 0.15). It would thus seem to be more appropriate to divide T1 and T2 patients into two groups according to a tumor size of 70 mm rather than 25 mm.

Noninvasive urodynamic evaluation of bladder outlet obstruction using Doppler ultrasonography

OZAWA H.

Urology 56 ( 3 ) 408 - 412 2000

Reliability of color doppler ultrasound urodynamics in the evaluation of bladder outlet obstruction

Yew Yoong Ding, Ozawa H, Yokoyama T, Nasu Y, Chancellor M.B, Kumon H

Urology 56 ( 6 ) 967 - 971 2000

The clinical value of contrast-enhanced color doppler ultrasound : is it really useful in the diagnosis of prostate cancer?

Nasu Y, Saika T, Arata R, Tsugawa M, Tsushima T, Kumon H, Seno T

J Urol 163 ( 4 ) 280 2000

前立腺癌遺伝子治療の基礎研究と臨床研究について

那須保友

日本泌尿器科学会雑誌 91 ( 3 ) 138 - 138 2000

腎細胞癌に対する腎摘除術後の対側腎機能の検討

白崎義範, 那須保友, 津島知靖, 公文裕巳, 明比直樹

日本泌尿器科学会雑誌 91 ( 3 ) 269 - 269 2000

ヒト腎細胞癌におけるシクロオキシゲナーゼ2の発現

山本康雄, 津島知康, 那須保友, 雑賀隆史, 新良治, 賀来春紀, 日下信行, 倉繁拓志, 公文裕巳

日本泌尿器科学会雑誌 91 ( 3 ) 186 - 186 2000

マウス前立腺同所移植モデルを用いた前立腺癌に対する治療評価系の構築 : 超音波細経プローブを用いたモニタリング法の確立

日下信行, 那須保友, 新良治, 雑賀隆史, 津島知靖, 公文裕巳

日本泌尿器科学会雑誌 91 ( 3 ) 260 - 260 2000

尿路変向の違いによる膀胱全摘術後患者のQOL

新良治, 日下信行, 雑賀隆史, 那須保友, 津島知靖, 公文裕巳, 武田克治, 光畑直喜, 西光雄, 陶山文三

日本泌尿器科学会雑誌 91 ( 3 ) 342 - 342 2000

Retroperitoneoscopic pyelotomy combined with transposition of crossing vessels for ureteropelvic junction obstruction

Atsushi Nagai, Hideaki Hashimoto, Masaya Tsugawa, Yasutomo Nasu, Hiromi Kumon

Nishinihon Journal of Urology 61 ( 4 ) 308 - 312 1999.4

Language：Japanese Publishing type：Research paper (international conference proceedings)

We have developed a new approach comprising retroperitoneoscopic pyelotomy combined with transposition of crossing vessels for ureteropelvic junction obstruction. From February 1997 to March 1998, we identified 6 cases of ureteropelvic junction obstruction due to crossing vessels by helical computed tomography. 'Ureterovascular hydronephrosis' characterized by malrotated renal pelvis with anterior crossing vessels was observed in 4, while ureteropelvic junction obstruction with posterior crossing vessels was observed in 2. Two female and 4 male patients, ranging from 9 to 60 years of age underwent retroperitoneoscopic surgery. After insertion of an endoureterotomy stent cystoscopically, retroperitoneoscopic surgery was carried out in the standard kidney position. Crossing vessels were found after removal of the periureteral adipose tissue and were freed from the ureter. After complete detachment, the vessels were transposed to a higher position in the renal pelvis and fixed with absorbable clips using peripelvic tissue. The resulting ureteropelvic junction was incised longitudinally for about 1.5 cm with a potassium titanyl phosphate (KTP) laser in 4 cases, although this incision was omitted in 2 cases where ureteropelvic junction obstruction appeared perfectly normal. The postoperative course was uneventful in all cases and the stent was removed 4-8 weeks postoperatively. Postoperative excretory urography (IVP) showed significant resolution of the hydronephrosis in 5 patients, but no significant resolution in 1 patient, who had not received the pyelotomy. This procedure is a simple but reliable method for ureterovascular hydronephrosis and related conditions as a minimally invasive alternative to conventional antegrade or retrograde endopyelotomy.

Primary non-Hodgkin lymphoma of the ureter Reviewed

H Hashimoto, M Tsugawa, Y Nasu, T Tsushima, H Kumon

BJU INTERNATIONAL 83 ( 1 ) 148 - 149 1999.1

Effective steroid therapy for retrovesical inflammatory pseudotumor in children: A case report

Shunko Kaku, Tomoyasu Tsushima, Masaya Tsugawa, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Ohmori

Nishinihon Journal of Urology 60 ( 9 ) 669 - 672 1998.9

Language：Japanese Publishing type：Research paper (scientific journal)

A 10-year-old boy complained of fever and frequent miction pain. CT scan revealed right hydronephrosis and a retrovesical mass. Based on the histological diagnosis of a specimen obtained by transrectal needle biopsy, the mass was determined to be an inflammatory pseudotumor. Steroid therapy was selected, resulting in the complete disappearance of the mass. Although surgery is the preferred treatment, steroid therapy should be considered in cases with this rare condition.

Partial cystectomy in the treatment of invasive bladder cancer

Tomoyasu Tsushima, Takanori Murakami, Shin Ebara, Nobuyuki Kusaka, Shunko Kaku, Yoshiyuki Miyaji, Yasuo Yamamoto, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Ohmori

Nishinihon Journal of Urology 60 ( 5 ) 397 - 401 1998.5

Language：Japanese Publishing type：Research paper (international conference proceedings)

Forty-eight patients with localized muscle-invasive bladder cancer underwent partial cystectomy. Their median age was 70 years. Of these patients, 67% had G3 tumors, and 40% had stage pT3b or pT4 tumors. Nine patients received neoadjuvant therapy. Thirty-one patients received adjuvant chemotherapy and 21 received postoperative radiotherapy, among whom 19 received adjuvant chemo-radiotherapy. The median follow-up was 38 months for all patients, and 68 months for the surviving patients. The cause-specific 5- year survival rate was 63%, while the non-recurrence 5-year survival rate was 58%. Univariate analysis of prognostic factors was carried out with regard to cause-specific survival. Prognosis was statistically better in patients with tumors less than 2cm in diameter, in those with stages pT2 and 3a disease, and in those without hydronephrosis. Partial cystectomy can be recommended in certain clearly selected patients with localized muscle-invasive bladder cancer.

Clinical Evaluation of Serum Prostate-Specific Antigen-Alpha^1-Antichymotrypsin Complex Values in Diagnosis of Prostate Cancer: A Cooperative Study

KURIYAMA Manabu, UENO Kazuya, UNO Hiromi, KAWADA Yukimichi, AKIMOTO Susumu, NODA Masatoshi, NASU Yasutomo, TSUSHIMA Tomoyasu, OHMORI Hiroyuki, SAKAI Hideki, SAITO Yasushi, MEGURO Norio, USAMI Michiyuki, KOTAKE Toshihiko, SUZUKI Yuji, ARAI Yoichi, SHIMAZAKI Jun

Int. J. Urol. 5 ( 1 ) 48 - 54 1998

Gene therapy for prostate cancer

Bangma C.H, Thompson T.C, Timme T.L, Scardino P.T, Yang G, Wang J, Nasu Y, Park S.H, Hull J.W

Prostate Cancer and Prostatic Diseases 1 ( S-1 ) 33 1998

Prospective Randomized Comparative Study of Antibiotic Prophylaxis in Urethrocystoscopy and Urethrocystography

TSUGAWA Masaya, MONDEN Kohichi, NASU Yoshitsugu, KUMON Hiromi, OHMORI Hiroyuki

Int J Urol 5 ( 5 ) 441 - 443 1998

Absorption of epirubicin instilled intravesically immediately after transurethral resection of superficial bladder cancer Reviewed

T Tsushima, Y Miyaji, M Noda, Y Nasu, H Kumon, H Ohmori

UROLOGIA INTERNATIONALIS 60 ( 3 ) 161 - 164 1998

Language：English Publishing type：Research paper (scientific journal) Publisher：KARGER

As postoperative adjuvant therapy for superficial bladder cancer, intravesical instillation therapy is commonly conducted. In this case, from the view point of prevention of intraoperative dissemination, commencement of instillation therapy at an early postoperative period is preferred. However, increased drug permeability is suspected because of damage to the bladder mucosa during operation. Therefore, this study was conducted to investigate the plasma level of epirubicin (EPI) instilled immediately after transurethral operation. EPI (20 mg/40 ml or 50 mg/100 ml) was instilled immediately after a transurethral operation, and retained in the bladder for 1 h. Blood samples were obtained before instillation, as well as 30, 60, 120 and 240 min after instillation, and EPI levels were assayed. The mean EPI concentrations (ng/ml) among the 20-mg/40 ml group (n = 5) were <2.5 and <2.0 at 30 and 60 min, respectively, after which they were undetectable. The 50-mg/100 ml group (n = 5) recorded 5.0, 4.4 and <3.0 after 30, 60 and 120 min, respectively, and after 240 min it was undetectable. Intravesical instillation of EPI immediately after a transurethral operation causes a small increase in the plasma level and it is thought to cause small systemic side effects.

Statistical analysis of factors affecting progression of superficial bladder cancer

Naoki Akebi, Tomoyasu Tsushima, Kenji Kobashi, Yasutomo Nasu, Yoshiyuki Miyaji, Takanori Murakami, Hiroyuki Ohmori, Hiromi Kumon

Nishinihon Journal of Urology 60 ( 10 ) 692 - 697 1998

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Kyushu University

Three hundred and three consecutive patients with superficial bladder cancer, stages Ta and T1, who were initially treated at the Department of Urology, Okayama University Medical School between 1965 and 1990, were retrospectively reviewed regarding tumor progression. One hundred and fifty (49.5%) patients had disease recurrence, while 24 (7.0%) patients subsequently developed deep muscle invasion or distant metastasis. The interval between initial treatment and progression ranged from 8 to 122 months, with a median of 45.5 months. Of these 24 patients, 7 (29.2%) were initially diagnosed as stage Ta and 17 (70.8%) as stage T1, whilst 3 (12.5%) were diagnosed as histological grade 1, 17 (70.8%) as grade 2 and 4 (16.7%) as grade 3. Twelve factors including age, sex, clinical symptoms, number of tumors, tumor size, tumor shape, tumor involvement of the bladder neck, stage, grade, interval to first recurrence, urine cytology, and urethral recurrence were selected as variables of tumor progression and analyzed statistically. From univariate analysis of variables obtained from the initial diagnosis of 303 cases, nonpapillary tumor shape, stage T1, positive urine cytology and interval to first recurrence within 12 months were found to be significantly correlated with tumor progression. However, multivariate analysis using Cox's proportional hazards model revealed that only tumor shape and interval to first recurrence were of significant prognostic value. In 150 cases with recurrent tumors, the most unfavorable factor with regard to tumor progression as determined from the clinical records of each case was also analyzed statistically. Univariate analysis showed that urethral recurrence, grade 3, stage T1 and nonpapillary tumor shape were all significant predictors for progression. Further multivariate analysis using logistic model indicated that urethral recurrence was the most important factor followed by the histological grade.

INHIBITION OF A PRIMARY MOUSE PROSTATE TUMOR WITH ADENOVIRAL MEDIATED HERPES SIMPLEX VIRUS THYMIDINE KINASE GENE TRANSDUCTION ＆ GANCICLOVIR THERAPY

Hall S.J, Yang G, Mutchnik S.E, Adier H.L, Nasu Y, Timme T.L, Woo S.L.C, Thompson T.C

The Journal of Urology 157 ( S-4 ) 368 1997

THE EFFECT OF A GONADOTROPIN-RELEASING HORMONE AGONIST ON BONE MINERAL DENSITY OF PROSTATIC CANCER PATIENTS

Noda M, Tsushima T, Nasu Y, Ohmori H

The Journal of Urology 157 ( S-4 ) 232 1997

Study of the Nephrotoxicity of Iron Oxide Fumes Released by Welding in an Experimental Model

Noda M, Tsushima T, Nasu Y, Kumon H, Ohmori H, Okada S

Pathophysiology 4 221 - 226 1997

尿路上皮癌における細胞表面糖鎖とDNA量の同時解析に関する基礎的・臨床的研究

宮地禎幸, 郭春鋼, 那須保友, 津島知靖, 大森弘之

日本泌尿器科学会雑誌 88 ( 2 ) 275 - 275 1997

Clinical Studies on Advantages and Safety of Visual Laser Ablation for Patients with Benign Prostatic Hyperplasia

Nasu Y, Watanabe T, Kumon H, Ohmori H

Int J Urol 3 ( S-1 ) S53 - S54 1996

New Technological Methods of Managing BPH －Visual Laser Ablation of Prostate(VLAP):Non-contact－

Nasu Y, Kumon H, Ohmori H

Japanese Journal of Endourology and ESWL 9 ( 2 ) 137 - 139 1996

Relationship of intracellular concentration and duration of contamination of pirarubicin and adriamycin in human bladder cancer cell lines and human bladder normal mucosa cell line Reviewed

T. Saika, T. Tsushima, Y. Nasu, N. Akebi, H. Ohmori

Japanese Journal of Cancer and Chemotherapy 23 ( 7 ) 905 - 909 1996

Language：Japanese Publishing type：Research paper (scientific journal)

To establish a method for reasonable clinical use of adriamycin (ADM) and pirarubicin (THP) in the intravesical chemotherapy for superficial bladder cancer, intracellular concentrations of these drugs were examined in culture cell lines (T-24, T-24/ADM and FHS736b1) with variable durations of contamination. The intracellular concentration of THP showed a plateau at 15- 30 min. contamination in T-24, and in T-24/ADM, and showed the time dependence of contamination in FHS736b1, human normal bladder mucosa cell line. The intracellular concentration of ADM showed the time dependence of contamination in T-24, T-24/ADM and FHS736b1. And these concentrations of THP were 20 times higher than those of ADM. In conclusion, it seems better that THP was retained for 5-15 min. in the bladder in the intravesical chemotherapy, from the point of view of drug efficacy and preventing side effects. And it seems good that ADM was retained for more than 30 min. in the case with drug sensitive tumors.

膀胱癌培養細胞におけるアポトーシス関連物質の検討

郭春鋼, 那須保友, 津島知靖, 大森弘之

日本泌尿器科学会雑誌 87 ( 2 ) 402 - 402 1996

膀胱癌におけるFlSH法による染色体数的異常の検討

井上高明, 那須保友, 津島知靖, 大森弘之

日本泌尿器科学会雑誌 87 ( 2 ) 519 - 519 1996

尿路癌における細胞表面糖鎖とDNA量の同時解析に関する基礎的・臨床的研究

宮地禎幸, 那須保友, 津島知靖, 大森弘之

日本泌尿器科学会雑誌 87 ( 2 ) 518 - 518 1996

上部尿路疾患におけるヘリカルCTによる三次元画像診断

橋本英昭, 那須保友, 公文裕巳, 大森弘之, 清哲朗, 安井光太郎, 平木祥夫

日本泌尿器科学会雑誌 87 ( 2 ) 322 - 322 1996

前立腺癌の診断におけるsystematic biopsyの検討

村上貴典, 野田雅俊, 那須保友, 津島知靖, 大森弘之

日本泌尿器科学会雑誌 87 ( 2 ) 315 - 315 1996

前立腺癌診断におけるfree PSA/total PSA(TOSOH)の有用性

野田雅俊, 津島知靖, 那須保友, 大森弘之

日本泌尿器科学会雑誌 87 ( 2 ) 251 - 251 1996

Prostatic cancer presenting as palpable lymph-node metastases: A case report

Ryuji Fujita, Atsushi Nagai, Masaya Tsugawa, Yasutomo Nasu, Tomoyasu Tsushima, Hiroyuki Ohmori

Nishinihon Journal of Urology 58 ( 1 ) 41 - 43 1996

Language：Japanese Publishing type：Research paper (scientific journal)

A 48-year-old man visited our hospital complaining of nodules in the left neck. Physical examination revealed firm, smooth and movable masses of 1 to 2 cm in diameter in the bilateral neck, and in the left supraclavicular, bilateral axillar anti bilateral inguinal regions. On digital rectal examination, a hen's egg sized, smooth and elastic firm prostate was observed. The serum prostatic acid phosphatase and prostate-specific antigen levels were elevated. Needle biopsy of the prostate showed poorly differentiated adenocarcinoma. Treatment with LH-RH agonist, diethylstilbestrol diphosphate, ifosfamide and cisplatinum was effective and the patient has responded well. The enlarged lymph nodes have since shrunk markedly, and the serum prostatic acid phosphatase and prostate-specific antigen levels have also fallen to normal levels. This case indicated the presence of an unusual prostatic cancer in which non-regional superficial lymph-node metastases occurred.

Endoscopic removal of a spontaneously disrupted double J ureteral stent : A case report

Koichi Monden, Seiichi Itou, Ryuji Fujita, Masaya Tsugawa, Yasutomo Nasu, Hiromi Kumon, Hiroyuki Ohmori

Nishinihon Journal of Urology 58 ( 12 ) 1230 - 1232 1996

Language：Japanese Publishing type：Research paper (scientific journal)

We report a case, showing spontaneous disruption of a double J ureteral stent where the patient was subjected to endoscopic surgery. A 69-year-old woman had right hydronephrosis probably due to UPJ and UVJ stenosis. A double J ureteral stent (6Fr. 28cm, COOK) had been inserted at another institution. One month after the insertion, the ureteral stent spontaneously broke into 2 pieces. The stent then broke into 4 pieces 3 months later. She was admitted to our hospital for removal of the broken stent. We retrieved the stent through a semi-rigid ureteroscope (10.9Fr. OLYMPUS) using a 2-pronged grasper (5Fr. STORZ).

PSAにおけるsubtypeの研究 : その存在と各種PSA抗体に対する親和性の違いについて

野田雅俊, 津島知靖, 那須保友, 宮地禎幸, 大森弘之

日本泌尿器科学会雑誌 86 ( 3 ) 432 - 432 1995

尿路癌におけるアポトーシスについて : 臨床例におけるアポトーシスの発現

郭春鋼, 那須保友, 津島知靖, 大森弘之

日本泌尿器科学会雑誌 86 ( 3 ) 648 - 648 1995

フローサイトメトリーを用いた尿路移行上皮癌における細胞表面糖鎖抗原の定量化について

高松正武, 那須保友, 津島知靖, 大森弘之

日本泌尿器科学会雑誌 86 ( 1 ) 201 - 201 1995

前立腺肥大症に対するVLAPの臨床的検討 : 長期成績と合併症について

那須保友, 渡辺豊彦, 公文裕巳, 大森弘之, 入江伸, 西村元一, 金重哲三

日本泌尿器科学会雑誌 86 ( 1 ) 239 - 239 1995

前立腺癌における神経内分泌細胞(Neuroendocrine cell)の意義 : Chromogranin Aおよびneuron specific enolaseの発現と治療の反応性について

郭春鋼, 那須保友, 津島知靖, 大森弘之

日本泌尿器科学会雑誌 86 ( 1 ) 169 - 170 1995

尿路癌におけるアポトーシスについて : In vitroにおけるアポトーシスの誘導

那須保友, 郭春鋼, 津島知靖, 大森弘之

日本泌尿器科学会雑誌 86 ( 3 ) 648 - 648 1995

膀胱癌におけるフローサイトメトリーを用いた細胞表面糖鎖抗原の定量化について : レクチンサイトメトリー法の基礎的・臨床的検討

宮地禎幸, 高松正武, 那須保友, 津島知靖, 大森弘之

日本泌尿器科学会雑誌 86 ( 3 ) 644 - 644 1995

FISH法を用いた膀胱癌組織の染色体数的異常の検出

井上高明, 那須保友, 津島知靖, 大森弘之

日本泌尿器科学会雑誌 86 ( 3 ) 805 - 805 1995

腹腔鏡下精索静脈瘤手術の臨床的検討

永井敦, 大枝忠史, 秋山博伸, 小澤秀夫, 市川孝治, 那須保友, 公文裕巳, 大森弘之

日本泌尿器科学会雑誌 86 ( 3 ) 818 - 818 1995

THERAPEUTIC OUTCOME OF G-CSF THERAPY ON ADVANCED TESTICULAR TUMORS Reviewed

T TSUSHIMA, M TAKAMATSU, T SAIKA, Y MAKI, N AKEBI, Y NASU, H OHMORI

PROCEEDINGS OF THE XVI INTERNATIONAL CANCER CONGRESS - FREE PAPERS AND POSTERS, TOMES 1-4 2225 - 2229 1994

EPIDERMAL GROWTH FACTOR AS A MARKER FOR RECURRENCE OF THE BLADDER CANCER Reviewed

T SAIKA, T TSUSHIMA, Y NASU, M NODA, Y MORIYA, H OHMORI

PROCEEDINGS OF THE XVI INTERNATIONAL CANCER CONGRESS - FREE PAPERS AND POSTERS, TOMES 1-4 2145 - 2149 1994

OVER‐EXPRESSION OF METALLOTHIONEIN AND DRUG‐RESISTANCE IN BLADDER CANCER Reviewed

Takashi Saika, Tomoyasu Tsushima, Jyunzo Och, Naoki Akebi, Yasutomo Nasu, Yosuke Matsumura, Hiroyuki Ohmori

International Journal of Urology 1 ( 2 ) 135 - 139 1994

Language：English Publishing type：Research paper (scientific journal)

Metallothionein (MT) in tumor cells has been implicated as one of the factors involved in mechanisms of resistance to anti‐cancer drugs, including cis‐diaminedichroloplatinum (CDDP) and adriamycin (ADM). The relationship between the expression of MT and chemotherapy with anti‐cancer drugs was studied in CDDP‐ and ADM‐resistant human bladder cancer cell lines and tissue samples from clinical cases. In drug‐resistant cell lines (T‐24/ADM, CI‐7/CDDP) established in our laboratory, MT expression was studied by immunohistochemistry using the avidin‐biotin peroxidase complex (ABC) method and radioimmunoassay (RIA), using anti‐MT antibody. In addition, other potentfal mechanisms of drug resistance, such as P‐glycoprotein expression were examined and the levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and glutathione‐S‐transferase (GST) determined in these cell lines. The results of these investigations demonstrate that the expression of MT in resistant cell lines increased 2.1‐ and 2.5‐fold when compared with parent cell lines (CI‐7, T‐24). GSH, GSSG and GST levels were unchanged and P‐glycoprotein was not over‐expressed. A total of 120 tissue samples from 35 clinical cases of bladder cancer, before and after chemotherapy, were stained for MT which was detected in 10 of the 35 cases before chemotherapy. The incidence of MT expression was significantly higher (p less than 0.05) in cases with lower pathological tumor grades. By analyzing the MT staining after chemotherapy in the cases whose MT staining was negative before chemotherapy, it was found that cases receiving continuous administration (intravesical chemotherapy or peroral chemotherapy) showed a higher incidence (9/13) of positive staining for MT, than patients receiving intermittent administration (intravenous chemotherapy) (1/8), (p less than 0.05). These results demonstrate that: 1) a correlation exists between MT expression and tumor differentiation and 2) repetitive and continuous administration of anti‐cancer drugs results in increased MT expression in bladder cancer cells. MT expression may therefore be one of the mechanisms by which urothelial tumors acquire resistance to anti‐cancer drugs. Copyright © 1994, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1442-2042.1994.tb00022.x

Clinical study of urethral recurrence of superficial bladder cancer : its clinical significance as a prognostic implication

Nasu Y, Tsushima T, Akebi N, Maki Y, Takamatsu M, Inoue T, Ohmori H

J Urol 151 ( 5 ) 232A 1994

Therapeutic outcome of G-CSF therapy for the treatment of advanced testicular tumors

M. Takamatsu, T. Tsushima, Y. Nasu, M. Noda, T. Saika, S. Kaku, H. Ohmori

Nishinihon Journal of Urology 56 ( 12 ) 1508 - 1512 1994

Language：Japanese Publishing type：Research paper (scientific journal)

In the present study, we assessed the effect of granulocyte colony-stimulating factor (G-CSF) on patients with advanced testicular tumors. The subjects were 24 patients with stage II B or higher, advanced testicular tumors treated in the Department of Urology, Okayama University Hospital during the 12-year period from 1980 to 1991 (5, stage II B and 19, stage III: 19 primary cases and 5 recurrent cases). We compared the intensity of the CDDP dose against prognosis in 24 patients, 12 of whom were treated prior to 1986 when G-CSF had not been available, the other 12 patients being treated after 1987 using G-CSF. The CDDP dose intensity was increased significantly from 16.9-32.2 mg/m2/wk (20.6 ± 6.2 mg/m2/wk, mean ± SD) to 20.9-37.0 mg/m2/wk (29.6 ± 5.2 mg/m2/wk) after the introduction of G-CSF (t-test, p &lt
0.001). The 5-year survival rate was 40% in those patients treated without G-CSF as opposed to 90% after the introduction of G-CSF, and this result was statistically significant (logrank test, p = 0.04). Before the introduction of G-CSF, adverse reactions such as leukocytopenia forced us to reduce the doses and to change the schedules. Chemotherapy could be performed at full doses and on schedule due to the concomitant use of G-CSF, with the result that the therapeutic outcome was much improved.

Hyperthermotherapy Added to the Multidisciplinary Therpay for Penile Cancer

Kuroda M, Tsushima T, Nasu Y, Asaumi J, Nishikawa K, Gao X.S, Joja I, Takeda Y, Togami I, Makihata E, Kawasaki S, Ohmor H, Hiraki Y

Acta Med. Okayama 47 ( 3 ) 169 - 174 1993

Endopyeloplasty for ureteropelvic junction obstruction with a new, multifunction surgical endoscope in children

KUMON H.

Jpn J Endourol ESWL 6 ( 1 ) 35 - 38 1993

Tissue concentration of intravesically instilled (2″R)-4′-0-tetrahydropyranyl-adriamycin or adriamycin in superficial bladder cancer Reviewed

Takashi Saika, Tomoyasu Tsushima, Yasutomo Nasu, Masatoshi Noda, Naoki Akebi, Syunko Kaku, Masatake Takamatsu, Hiroyuki Ohmori, Satoru Uno, Taiichiro Johsen

Japanese Journal of Urology 84 ( 7 ) 1206 - 1210 1993

Language：English Publishing type：Research paper (scientific journal)

Twenty-one patients with superficial bladder cancer entered an analysis of single dose (2′R)-4′-0-tetrahydropyranyladriamycin (THP) or adriamycin (ADM) administration. The patients in each group that have been or not have been treated previously with anti-cancer drugs were randomized into two groups, one was given THP and the other ADM. Thirty-mg of THP or ADM dissolved in 30 ml of physiologic saline was instilled into the bladder, and retained for 1 hour. After 1 hour retention of the drugs, tumor tissues and normal mucosas were removed by punch biopsy forceps transurethrally. The tissue concentrations of THP and ADM were estimated by high performance liquid chromatography. The tissue concentrations of THP and ADM in the tumors were significantly greater (p&lt
0.05) than those in the normal bladder mucosas. The tissue concentration of THP in the tumors were greater than that of ADM. The tissue concentrations of THP and ADM in the tumor of patients who have been treated with anti-cancer drugs priviously were less than those of patients who have not. This results demonstrated that prior therapy with anti-cancer drug may cause a resistance for intravesical instillation chemotherapy. However in patients with prior therapy, the tissue concentration of THP in the tumors were greater than that of ADM. Based on these findings, THP has been shown to be were effective as an intravesical instillating agent expecially, in cases with prior chemotherapy. © 1993, THE JAPANESE UROLOGICAL ASSOCIATION. All rights reserved.

DOI： 10.5980/jpnjurol1989.84.1206

膀胱腫瘍におけるMalignant potentialの指標としてのABH-isoantigen-PCNA, c-erb B-2との関連について : 第80回日本泌尿器科学会総会

郭春鋼, 那須保友, 津島知靖, 明比直樹, 野田雅俊, 高松正武, 大森弘之

日本泌尿器科学会雑誌 84 ( 1 ) 178 - 178 1993

腎細胞癌患者と職業歴の関連性に関する検討 : 溶接歴と腎細胞癌発生について : 第80回日本泌尿器科学会総会

野田雅俊, 津島知晴, 那須保友, 明比直樹, 郭春鋼, 高松正武, 大森弘之, 岡田茂, 松村陽右

日本泌尿器科学会雑誌 84 ( 1 ) 211 - 211 1993

腹腔鏡下精索静脈瘤手術の経験 : 第80回日本泌尿器科学会総会

大枝忠史, 山根享, 志田原浩二, 小澤秀夫, 那須保友, 公文裕巳, 大森弘之

日本泌尿器科学会雑誌 84 ( 1 ) 224 - 224 1993

Mucinous adenocarcinoma of the prostate: A case report

T. Watanabe, K. Hata, Y. Nasu, H. Ohmori

Nishinihon Journal of Urology 55 ( 11 ) 1654 - 1657 1993

Hyperthermotherapy for penile cancer

Kuroda, M., Makihata, E., Asaumi, J., Nishikawa, K., Gao, X.S., Nakagawa, T., Kimoto, S., Hiraki, Y., Tsushima, T., Nasu, Y., Ohmori, H., Kawasaki, S.

Japanese Journal of Clinical Radiology 38 ( 4 ) 1993

Intra-arterial infusion chemotherapy for superficial bladder cancer

T. Saika, S. Kaku, T. Tsushima, Y. Nasu, M. Takamatsu, M. Noda, Y. Matsumura, H. Ohmori

Nishinihon Journal of Urology 55 ( 3 ) 360 - 364 1993

Renal cyst with cholesterol crystals: A case report

T. Watanabe, Y. Nasu, H. Kumon, H. Ohmori

Nishinihon Journal of Urology 55 ( 11 ) 1658 - 1661 1993

Squamous cell carcinoma of the bladder: Two case reports

S. Kaku, T. Tsushima, Y. Nasu, M. Noda, T. Saika, M. Takamatsu, H. Ohmori

Nishinihon Journal of Urology 55 ( 7 ) 1134 - 1137 1993

Combination chemotherapy with cis-platinum and ifosfamide for advanced prostate cancer: Preliminary report

T. Saika, T. Tsushima, Y. Nasu, M. Noda, M. Takamatsu, S. Kaku, H. Ohmori, Y. Matsumura

Nishinihon Journal of Urology 55 ( 6 ) 829 - 832 1993

PROPHYLACTIC INTRAVESICAL INSTILLATION THERAPY IN PATIENTS WITH SUPERFICIAL BLADDER CANCER:Results of a Randomized Prospective Study

Tsushima Tomoyasu, Nasu Yasutomo, Abeki Naoki, Noda Masatoshi, Saika Takashi, Ohmori Hiroyuki, Kobashi Kenji, Ozaki Yujiro, Matsumura Yosuke, Tanahashi Toyoko, Namba Katsuichi, Shiraga Tsuyoshi, Takamoto Hitoshi, Araki Tohru, Takeda Katsuji, Asahi Toshihiko, Akaeda Teruaki

The Japanese Journal of Urology 83 ( 8 ) 1314 - 1321 1992

Publisher：The Japanese Urological Association

A randomized prospective study was conducted for the purpose of investigating the efficacy of intravesical chemoprophylaxis of superficial bladder cancers. Eligible patients were randomized into three groups: 1) adriamycin (ADM) group; intravesical instillation with 50mg of ADM dissolved in 100ml physiological saline, 2) mitomycin C (MMC) group; intravesical instillation with 30mg of MMC dissolved in 100ml of physiological saline, 3) control group; transurethral resection or transurethral coagulation only.<br>The characteristic features of our protocol consisted of frequent (six times) instillations of the drugs within two weeks after transurethral resection, followed by instillations on two consecutive days at four-week intervals for two years. Furthermore, large quantities (100ml) of instillation fluid containing relatively low concentrations of the drugs (500μg/ml for ADM or 300μg/ml for MMC) were employed.<br>One hundred and forty-four patients have been submitted to the study; 110 patients were fully evaluable for recurrence and 34 patients were eliminated as non-evaluable patients. The cumulative five-year non-recurrence rates of the patients with multiple tumors were 32% in the MMC group, 25% in the ADM group and 7% in the control group. The cumulative non-recurrence rates of the ADM and MMC groups were significantly higher than that of the control group.<br>It is considered that this instillation therapy with ADM and MMC is useful for preventing the recurrence of superficial bladder cancers.

DOI： 10.5980/jpnjurol1989.83.1314

Other Link： http://search.jamas.or.jp/link/ui/1993101168

HISTOPATHOLOGICAL STUDY OF METALLOTHIONEIN IN BLADDER CANCER AND RENAL CELL CARCINOMA

Saika Takashi, Tsushima Tomoyasu, Nasu Yasutomo, Akebi Naoki, Noda Masatoshi, Kobashi Kenji, Matsumura Yousuke, Ohmori Hiroyuki

The Japanese Journal of Urology 83 ( 5 ) 636 - 642 1992

Publisher：The Japanese Urological Association

Metallothionein (MT) is a low molecularmetal binding protein with multiple biological functions. Recently, MT has been implicated as a factor involved in resistance to anticancer drugs, which presumably inactivates anticancer drugs, including cisplatin, and doxorubicin. In this report, we investigated the relationship of MT expression with the clinical features in bladder cancer and renal cell carcinoma.<br>In 35 cases of bladder cancer, 10 cases of renal cell carcinoma and 3 cases of normal mucosa of bladder, the expression of MT was immunohistologically examined by avidinebiotin-peroxidase (ABC) staining of paraffin-embedded tissue specimens with anti-MT antibody.<br>Intense MT expression was noted in all cases of normal mucosa of bladder. MT was detected in 10 of 35 cases of bladder cancer, with the incidence of MT expression being significantly higher increases with lower pathological tumor grade. MT was detected in 8 of 10 cases of renal cell carcinoma, and all of the their normal renal tubules showed more intense staining.<br>A number of hypotheses can be proposed from these observations. First, our observation of decreased MT expression in poorly differentiated carcinomas, which are the more proliferating tumors, this suggests correlation of MT expression with proliferative status of cancer. Second, the higher incidence of MT expression in renal cell carcinoma than in bladder cancer may suggest that it is a factorresponsible for the lower efficacy of chemo-therapy in renal cell carcinoma than in bladder cancer.

DOI： 10.5980/jpnjurol1989.83.636

Other Link： http://search.jamas.or.jp/link/ui/1992251205

Phase 2 study of 5'-DFUR for bladder and prostatic cancer Reviewed

H. Ohmori, Y. Matsumura, J. Ochi, K. Kobashi, N. Akebi, T. Saika, K. Nanba, T. Tanahashi, T. Josen, Y. Nasu, M. Saegusa, Y. Ozaki, M. Hara, T. Asahi, N. Ike, T. Tsushima, N. Mitsuhata, T. Akagi, T. Kaeda

Japanese Journal of Cancer and Chemotherapy 18 ( 13 ) 2307 - 2314 1991

Language：Japanese Publishing type：Research paper (scientific journal)

Phase 2 study of 5'-DFUR in bladder and prostatic cancer was conducted at 15 collaborative institutions including Okayama University. 5'-DFUR was orally administered to patients at a daily dose of 800-1200 mg for more than 4 weeks. Forty-one patients with bladder cancer and 12 patients with prostatic cancer were evaluated. The response rate for bladder cancer was 31.7% (CFR, 1 case: PR, 12 cases), against no response with prostatic cancer. Moreover, the concentration of 5-FU in bladder tumors was confirmed to be high. Adverse reactions such as diarrhea, anorexia, and nausea were observed. Thus, 5'-DFUR seems to be useful for the treatment of bladder cancer.

ISOANTIGENS ABH IN BLADDER TUMORS AS AN INDICATOR OF MALIGNANT POTENTIAL The Staining Pattern by PAP Method and its Correlation with Prognosis

Saegusa Michihisa, Nasu Yasutomo, Kumon Hiromi, Matsumura Yosuke, Ohmori Hiroyuki

The Japanese Journal of Urology 81 ( 2 ) 196 - 203 1990

Publisher：The Japanese Urological Association

Blood group antigens (BGA) were stained by PAP methods and the relation between staining pattern (classified into five types: I, II, IIIa, IIIb and IV) and tumor prognosis was examined in 54 patients with primary superficial bladder tumor. The recurrence rate was significantly higher in BGA negative (Type IIIb or IV) or Type IIIa cases than in antigen positive (Type I or II) cases. Stage-up was observed only in BGA negative cases. Although staining pattern of recurrent tumor differed from that of primary tumor in some cases, it is believed that prediction of malignant potential should be performed at the primary development, when tumor has not been influenced by treatments. With regard to the relation between staining pattern and tumor prognosis, no significant difference was found between the cases of A, B and AB blood groups and those of O group.

DOI： 10.5980/jpnjurol1989.81.196

Other Link： http://search.jamas.or.jp/link/ui/1990217480

A COMBINED LIGHT AND SCANNING ELECTRON-MICROSCOPY ON HUMAN URINARY CYTOLOGY Reviewed

H KUMON, Y NASU, Y MATSUMURA, H OHMORI, T TANAKA

JOURNAL OF ELECTRON MICROSCOPY 32 ( 1 ) 27 - 32 1983

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