Advancements in Urology 2011: A Japanese Urological Association (JUA)/American Urological Association (AUA) Symposium
Article first published online: 25 APR 2011
© 2011 The Japanese Urological Association
International Journal of Urology
Volume 18, Issue 5, pages 388–408, May 2011
How to Cite
Naito, S., Egawa, S. and Nakagawa, M. (2011), Advancements in Urology 2011: A Japanese Urological Association (JUA)/American Urological Association (AUA) Symposium. International Journal of Urology, 18: 388–408. doi: 10.1111/j.1442-2042.2011.02758.x
- Issue published online: 25 APR 2011
- Article first published online: 25 APR 2011
Recent developments in the medical field are astonishing and remarkable. Urologists are expected to be skilled with new knowledge and innovative technology, such as minimally invasive therapy and medical treatment with molecular targeting drugs. Under these circumstances, the Japanese Urological Association (JUA) has been aiming to further develop our society through international exchange activities with the American Urological Association (AUA), European Association of Urology (EAU) and Urological Association of Asia (UAA). We are also focusing on carrying out various development programs for young urologists.
In 2006, we started international exchange programs, such as the AUA Lecture, Resident Program, the Academic Exchange Program and the Reciprocal Exhibit Booth, in cooperation with the AUA. It is very significant that at the Advancements in Urology 2011, we held a JUA/AUA Symposium, which is the first joint educational event held outside the country between both societies.
Primary goals of this joint venture were to further enhance and update physicians' knowledge, and to develop international leadership among young urologists who will take the lead in the future. The programs also aimed to deepen communication between urologists of both societies. With the participation of more than 180 urologists, we think our intended goal has been fully met and our venture will further steam along.
We wish to tender our cordial thanks to the Japan–USA faculties and coordinators, especially Dr Gopal H Badlani (AUA program director), Dr Datta G Wagle (President of the AUA) and Dr Robert C Flanigan (Secretary General of the AUA), with whom we have been fostering close friendships for years.
Seiji Naito M.D., JUA President
Shin Egawa M.D., Chair, JUA International Committee
Masayuki Nakagawa M.D., Chair, JUA Educational Committee
|Thursday 17 February 2011|
|6:00–6:50||Continental Breakfast and Registration|
|6:50–6:55||Welcome and Introductions|
|6:55–7:10||AUA Initiatives – Datta G Wagle M.D.|
|Session 1:||Prostate Cancer|
|Moderators:||AUA – Datta G Wagle M.D.|
|JUA – Seiji Naito M.D. (Kyushu University)|
|7:10–7:40||Keynote Lecture. Robert C Flanigan M.D.|
|7:40–7:55||PSA Velocity Conundrums. Anton J Bueschen M.D.|
|7:55–8:40||Technical Aspects of Radical Prostatectomy|
|7:55–8:10||Open. J Brantley Thrasher M.D.|
|8:10–8:25||Laparoscopic. Shin Egawa M.D. (Jikei University)|
|8:25–8:40||Robotic. Inderbir S Gill M.D.|
|8:40–8:55||Dealing with Surgical Complications that Result from Treatment of Prostate Cancer.|
|Gopal H Badlani M.D.|
|8:55–9:25||CaP Advanced Disease:|
|8:55–9:10– Hormone Ablation. J Brantley Thrasher M.D.|
|9:10–9:25– Beyond Hormonal Therapy. John H Lynch M.D.|
|Session 2:||Panel Discussion for Case Management for Prostate Cancer|
|9:25–10:10||Moderators:||AUA – John H Lynch M.D.|
|JUA – Mikio Namiki M.D. (Kanazawa University)|
|AUA Panelists:||Inderbir S Gill M.D.|
|Peter A Pinto M.D.|
|JUA Panelists:||Shigeo Horie M.D. (Teikyo University)|
|Kazuto Ito M.D. (Gunma University)|
|Session 3:||Renal Cancer|
|Moderators:||AUA – Sushil S Lacy, M.D.|
|JUA – Hirotsugu Uemura M.D. (Kinki University)|
|10:40–11:10||Keynote Lecture. Inderbir S Gill M.D.|
|11:10–11:25||Guidelines: Small Renal Masses. Robert C Flanigan M.D.|
|11:25–11:40||Image Guided Therapy for Small Renal Masses. Peter A Pinto M.D.|
|11:40–11:55||Laparoscopic vs Robotic Partial Nephrectomy. Inderbir S Gill M.D.|
|11:55–12:10||Targeted Therapy for Locally Advanced RCC. Peter A Pinto M.D.|
|Session 4:||Panel Discussion for Case Management for Renal Cell Carcinoma|
|12:10–12:55||Moderators:||AUA – Pramod C Sogani M.D.|
|JUA – Osamu Ogawa M.D. (Kyoto University)|
|AUA Panelists:||Robert C Flanigan M.D.|
|J Brantley Thrasher M.D.|
|JUA Panelists:||Mototsugu Oya M.D. (Keio University)|
|Masatoshi Eto M.D. (Kumamoto University)|
|CME Program Concludes|
|12:55–14:00||Cultivating a Strong Approach for the Treatment of OAB – A non-CME lunch symposia supported by Pfizer|
|(Guidance to the afternoon session by Yoshiyuki Kakehi M.D.)|
|Session 5:||Small Group Discussion – Faculty Development|
|14:00–16:00||Each group involves 10–15 Japanese participants with 1–2 AUA and JUA facilitators. One or two volunteers will present a summary of their discussion on 18 February.|
|SG1 Chemoprevention for Prostate Cancer, Is it Recommended? J Brantley Thrasher M.D.|
|Attendees:||Taro Iguchi (Osaka City University), Yoshiaki Kawano (Kumamoto University), Kentaro Kuroiwa (Kyushu University), Jun Miki (Jikei University), Mai Miyakubo (Gunma University), Masashi Morita (Showa University), Yasutomo Nakai (Osaka University), Shinichi Sakamoto (Chiba University), Sayuri Takahashi (Mitsui Memorial Hospital), Kosuke Takehara (Nagasaki University) and Gaku Tamaki (Asahikawa Medical University)|
|SG2 Role of Neoadjuvant and Adjuvant Therapy in the Era of Molecular Targeting Drug for Renal Cell Carcinoma. Peter A Pinto M.D.|
|Attendees:||Takayuki Goto (Miyazaki University), Yoshihide Higuchi (Hyogo Medical University), Manabu Kato (Mie University), Kazumori Kawakami (Kagoshima University), Sei Naitoh (Yamagata University), Kogenta Nakamura (Aichi Medical University), Takeo Nomura (Oita University), Keisuke Saito (Teikyo University) Noboru Sakamoto (Tokyo Medical University), Koji Shiraishi (Yamaguchi University),|
|Kazumasa Torimoto (Nara Medical University) and Tsuyoshi Yoshizawa (Nippon University)|
|SG3 Role of Neoadjuvant Chemotherapy for Muscle Invasive Bladder Carcinoma. Pramod C Sogani M.D.|
|Attendees:||Ryosuke Ando (Nagoya City University), Tetsutaro Hayashi (Hiroshima University), Takashi Kasahara (Niigata University), Yoshiyuki Matsui (Kyoto University), Akihiro Morii (Toyama University), Shuichi Morizane (Tottori University), Takayuki Sugiyama (Hamamatsu Medical University), Nobuyuki Tanaka (Keio University) and Kazuma Udo (Saga University)|
|SG4 Role of Lymph Node Dissection for Upper Urinary Tract Carcinoma. Inderbir S Gill M.D.|
|Attendees:||Takashige Abe (Hokkaido University), Junya Furukawa (Kobe University), Takamitsu Inoue (Akita University), Takuma Kato (Kagawa University), Ryoji Kimata (Nippon Medical School), Yasunori Kimura (Kyoto Prefectural University of Medicine), Yoshiki Kodama (Wakayama Medical University), Yoshihisa Matsukawa (Nagoya University), Koji Mitsuzuka (Tohoku University) and Kazuaki Yoshikawa (Mutsu General Hospital)|
|SG5 T1a Renal Cell Carcinoma, Partial vs Radical Nephrectomy? Robert C Flanigan M.D.|
|Attendees:||Satoshi Ashimine (Ryukyu University), Tomoya Fukawa (Tokushima University), Akio Hoshi (Tokai University), Yasuaki Kubota (Toyota Memorial Hospital), Yuji Maeda (Kanazawa University), Yosuke Matsuta (Fukui University), Masafumi Nakamura (Yokohama City University), Takehiro Oikawa (Tsukuba University), Toshiaki Tanaka (Sapporo Medical University) and Katsunori Tatsugami (Kyushu University)|
|Friday 18 February 2011|
|6:30–7:00||Continental Breakfast and Registration|
|Session 6:||Urinary Incontinence|
|Moderators:||AUA – Kevin Pranikoff M.D.|
|JUA – Yukio Homma (The University of Tokyo)|
|7:00–7:30||Keynote Lecture. Gopal H Badlani M.D.|
|7:30–7:45||Refractory OAB. Masayuki Takeda M.D. (Yamanashi University)|
|7:45–8:00||Which Sling Is Best? Sandip P Vasavada M.D.|
|8:00–8:15||Prolapse Repair. Gopal H Badlani M.D.|
|8:15–8:30||Male Sling vs AUS. Alexis E Te M.D.|
|Session 7:||Case Based Discussion – Urinary Incontinence|
|8:30–9:15||Moderators:||AUA – Richard A Memo M.D.|
|JUA – Momokazu Gotoh M.D. (Nagoya University)|
|AUA Panelists:||Sandip P Vasavada M.D.|
|Kevin Pranikoff M.D.|
|JUA Panelist:||Satoru Takahashi M.D. (Nippon University)|
|Momokazu Gotoh M.D. (Nagoya University)|
|Session 8:||Management of BPH|
|Moderators:||AUA – John H Lynch M.D.|
|JUA – Yoshihiko Hirao M.D. (Nara Medical University)|
|9:45–10:15||Keynote Lecture. Alexis E Te M.D.|
|10:15–10:30||LUTS and BPH (Metabolic Syndrome/Racial Differences), Taiji Tsukamoto M.D. (Sapporo Medical University)|
|10:30–10:45||Minimally Invasive Techniques – Long-Term Data. Gopal H Badlani M.D.|
|10:45–11:00– Green Light. Alexis E Te M.D.|
|11:00–11:15– Bipolar. Gopal H Badlani M.D.|
|Session 9:||Case Based Discussion – BPH|
|11:15–12:00||Moderators:||AUA – B Thomas Brown M.D.|
|JUA – Yoichi Arai M.D. (Tohoku University)|
|AUA Panelists:||Alexis E Te M.D.|
|John H Lynch M.D.|
|JUA Panelists:||Naoya Masumori M.D. (Sapporo Medical University)|
|Yasuhiko Igawa M.D. (The University of Tokyo)|
|Session 10:||Breakout Session|
|12:00–13:00||Moderators:||Glenn M Preminger M.D and Sandip P Vasavada M.D.|
|Tomohiko Ichikawa M.D. (Chiba University)|
|Part I: Manuscript Writing||AUA – Glenn M Preminger M.D.|
|JUA – Yoshihiko Tomita M.D. (Yamagata University)|
|Part II: Public Speaking||AUA – Sandip P Vasavada M.D.|
|JUA – Nobuo Shinohara (Hokkaido University)|
|13:00–14:00||PVP: GreenLight HPS – Technological Advancement Based on Proven Legacy – A non-CME lunch symposia supported by AMS|
|Session 11:||Group Presentation and Discussion|
|Groups will present and feedback summary of their findings and summaries (previous day discussions, presenters to be selected from the group)|
|14:00–16:00||Moderators:||AUA – Robert C Flanigan M.D.|
|JUA – Yoshiyuki Kakehi M.D. (Kagawa University)|
|SG1 Chemoprevention for Prostate Cancer, Is it Recommended? J Brantley Thrasher M.D.|
|SG2 Role of Neoadjuvant and Adjuvant Therapy in the Era of Molecular Targeting Drug for Renal Cell Carcinoma. Peter A Pinto M.D.|
|SG3 Role of Neoadjuvant Chemotherapy for Muscle Invasive Bladder Carcinoma. Pramod C Sogani M.D.|
|SG4 Role of Lymph Node Dissection for Upper Urinary Tract Carcinoma. Inderbir S Gill M.D.|
|SG5 T1a Renal Cell Carcinoma, Partial vs Radical Nephrectomy? Robert C Flanigan M.D.|
|Saturday 19 February 2011|
|6:30–7:00||Continental Breakfast and Registration|
|Session 12:||Bladder Cancer|
|Moderators:||AUA – Dennis A Pessis|
|JUA – Tomonori Habuchi M.D. (Akita University)|
|7:00–7:30||Keynote Lecture. Peter A Pinto M.D.|
|7:30–7:45||Role of Cytology and Markers. Hideyasu Matsuyama M.D. (Yamaguchi University)|
|7:45–8:00||Endoscopic Advances (NBI, Blue Light). Stephen Y Nakada M.D.|
|8:00–8:30||Cystectomy: Tips & Tricks|
|8:00–8:15– Open. Robert C Flanigan M.D.|
|8:15–8:30– Robotic. Peter A Pinto M.D.|
|8:30–8:45||Choice in Urinary Diversion. Chikara Ohyama M.D. (Hirosaki University)|
|8:45–9:00||Role of Adjuvant and Neoadjuvant Treatment. Peter A Pinto M.D.|
|9:00–9:15||Upper Tract TCC: Endoscopic Management. Glenn M Preminger M.D.|
|Session 13:||Case Based Discussion – Bladder Cancer|
|9:15–10:00||Moderators:||AUA – John C Prince M.D.|
|JUA – Masayuki Nakagawa M.D. (Kagoshima University)|
|AUA Panelists:||J Brantley Thrasher M.D.|
|Peter A Pinto M.D.|
|JUA Panelists:||Tomonori Habuchi M.D. (Akita University)|
|Isao Hara M.D. (Wakayama Medical University)|
|Moderators:||AUA – David F Green M.D.|
|JUA – Atsushi Nagai M.D. (Kawasaki Medical University)|
|10:30–11:00||Keynote Lecture: Dean G Assimos M.D.|
|11:00–11:15||Guidelines for Ureteral Stones. Glenn M Preminger M.D.|
|11:15–11:30||Optimization for ESWL Treatment. Dean G Assimos M.D.|
|11:30–11:45||Flexible Ureteroscopy: Tips and Tricks. Glenn M Preminger, M.D.|
|11:45–12:00||Metabolic Evaluation. Dean G Assimos M.D.|
|12:00–12:30||Difficult Stone Cases. Glenn M Preminger M.D.; Dean G Assimos M.D.; Stephen Y Nakada M.D.|
|12:30||Summary – Seiji Naito M.D.|
Small group discussion
Yoshiyuki Kakehi M.D.
Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan
Robert C Flanigan M.D.
Department of Urology, Loyola University Medical Center, Maywood, IL, USA
Fifty-two young urologists from JUA participated in this program. The aim of this program was to provide young Japanese doctors with an opportunity to learn how to debate on a controversial issue.
Each small group was supported by one senior doctor from AUA (Dr J Brantley Thrasher for SG1, Dr Peter A Pinto for SG2, Dr Pramod C Sogani for SG3, Dr Inderbir S Gill for SG4 and Dr Robert C Flanigan for SG5).
Following were the subjects of each small group:
SG1: Chemoprevention for prostate cancer; Is it recommended?
SG2: Role of neoadjuvant and adjuvant therapy in the era of molecular targeting drug for renal cell carcinoma.
SG3: Role of neoadjuvant chemotherapy for muscle invasive bladder carcinoma.
SG4: Role of lymph node dissection for upper urinary tract carcinoma.
SG5: T1a renal cell carcinoma; Partial vs radical nephrectomy?
On 17 February (the first day) afternoon, each small group had 2 hours' discussion for each subject using a couple of key articles that had been recommended by the facilitators. Discussion was very much stimulated by AUA facilitators in a friendly atmosphere. At the end of discussion, one volunteer doctor for each small group was selected to prepare for the presentation on the second day.
On 18 February (the second day), the volunteer doctors presented a summary of their discussion in approximately 15 minutes in English. Lots of thoughtful advice was given by the moderator, Dr Flanigan, the program director, Dr Badlani, and the other facilitators, including Dr Pinto.
Participants in the program responded to the questionnaire from the organizing committee of JUA after the meeting. The questionnaire consisted of two simple questions, simultaneously accepting free comments. The first question was “What did you expect from the sessions (SG discussion) before attending the meeting?” and the second was “Did the sessions meet your needs?” As to the first question, the most frequent answer was to learn skills of debate (44%), followed by to meet AUA experts (30%) as shown in Figure 1. With respect to the grade of satisfaction with the program (second question), the program seemed to be useful to 83% of participants (Fig. 2).
Judging from the free comments made by the participants, together with the response to the questionnaire, overall assessment of the program was successful and useful. Its aim, however, was not fully understood by the Japanese participants, because this was the first attempt. In addition, many Japanese participants hoped to have a chance to debate with young urologists from AUA in the future attempt. The next opportunity of a similar program, if realized, is certainly expected to be a more fruitful one.
Analyses of novel genes encoding secreted and transmembrane proteins identified by the Escherichia coli ampicillin secretion trap: Expression of CDON is involved in tumor cell growth and invasion
Tetsutaro Hayashi, Shinya Ohara, Jun Teishima, Koichi Shoji, Kazuhiro Sentani, Naohide Oue, Wataru Yasui and Akio Matsubara
Objectives: Genes that are expressed only in cancer tissue and are especially related to proteins located on the cell membrane might be useful molecular markers for diagnosis as well as good therapeutic targets. To identify genes that encode transmembrane proteins present in prostate cancer (PCa), we used a survival-based signal sequence trap method, Escherichia coli ampicillin secretion trap (CAST).
Methods: We generated cDNA libraries from normal prostate and two PCa cell lines, LNCaP and DU145. These CAST libraries were ligated into the pCAST plasmid with a mutant b-lactamase lacking the endogenous signal peptide. The CAST method detects survival on ampicillin only when various cDNA fragments encoding a signal sequence are inserted.
Results: We sequenced 3264 ampicillin-resistant colonies from the CAST library and detected 284 genes, including 144 (51%) genes encoding membrane-spanning proteins and 21 (7%) encoding secreted proteins. To confirm that these candidates were PCa-specific, we compared mRNA levels in nine PCa tissues and 15 kinds of normal tissues with quantitative reverse transcription polymerase chain reaction analyses. Of the 64 candidates, STEAP1 was found to show high specificity for PCa, followed by ADAM9 and CDON. Although CDON is a cell surface receptor of the immunoglobulin/fibronectin type III repeat family, its expression in human cancers, including PCa, has not been investigated. Western blot analysis showed high CDON expression in DU145 cell extracts, which was suppressed by treatment with CDON-specific siRNA. Cell invasion and MTT assays showed that CDON knockdown in DU145 cells inhibited both cell growth and invasion ability.
Conclusions: CAST is a robust and rapid method to identify cell surface and secreted proteins. Using this method, CDON was found to be upregulated in PCa and to participate in cell growth and invasion. These findings suggest that CDON might be a good therapeutic target.
Talin1 is a novel mediator of prostate cancer cell migration, invasion and metastasis via activating integrin mediated pathway and anoikis resistance
Shinichi Sakamoto,1,2 Koji Kawamura,1 Takashi Imamoto,1 Naoki Nihei,1 Natasha Kyprianou2 and Tomohiko Ichikawa1
1Chiba University, 2University of Kentucky College of Medicine
Objectives: Talin1 is an integrin binding protein that regulates integrin activation towards mediating cell signaling interactions with the extracellular matrix (ECM). The role of talin1 in human cancer metastasis has not been yet explored. This study investigated the functional significance of talin1 in prostate cancer cell invasion, tumor microenvironment and metastasis in vitro and in vivo.
Methods: Talin1 expression was determined by immunohistochemical analysis using the TRAMP mouse model of increasing ages (6–28 weeks) and human tissue microarray. Cell apoptosis induction was determined by Annexin-V analysis and caspase cleavage. ShRNA was used to study the consequences of talin1 loss on prostate cancer cells. The in vivo contribution of talin1 to metastasis was assessed by the tail vein injection metastasis assay.
Results: Talin1 overexpression correlated with prostate cancer progression to metastasis in the TRAMP mouse model. Tissue microarray analysis of human prostate cancer specimens showed increased talin1 immunoreactivity in metastatic lesions compared with normal or primary prostate tumors (P < 0.05). Within primary tumors, talin1 expression was significantly higher in poor differentiated tumors (Gleason 8/9) compared with moderately differentiated tumors (Gleason 6/7; P < 0.01). Talin1 overexpression in prostate cancer cells, enhanced cell adhesion and migration, and promoted their invasion potential in vitro, whereas ShRNA-mediated silencing of talin1 inhibited those abilities. ShRNA of Talin1 mediated significant inhibition in metastasis potential in vivo. Dissection of the underlying mechanism shows that talin1 regulates cell survival signals through activation/phosphorylation of focal adhesion kinase (FAK) and AKT. Talin1 overexpression also mediated anoikis resistance through activating the GSK-3b/ILK-1 pathway.
Conclusions: These findings identified talin1 as a regulator of prostate tumor cell migration, invasion and intracellular survival signaling. Thus, talin1 emerges as a potential therapeutic target, as well as a marker of prostate cancer progression to metastasis.
Anti-tumor effects of zoledronic acid and somatostatin analogues in murine androgen-independent neuroendocrine carcinomas a hormone refractory prostate cancer model
Kohei Hashimoto, Naoya Masumori, Toshiaki Tanaka, Hiroshi Kitamura and Taiji Tsukamoto
Sapporo Medical University School of Medicine
Objectives: We investigated whether neuroendocrine (NE) carcinoma models (NE-10, NE-CS) were controlled by several agents, including zoledronic acid (ZOL) and the somatostatin analogs, octreotide (SMS) and pasireotide (SOM), having potential antitumor activities.
Methods: Nine-week-old male BALB/c nude mice, which were castrated and inoculated subcutaneously (s.c.) with a 50-mg tissue block of a NE-10 tumor, were treated for 6 weeks with ZOL (3 µg/body/week s.c.), SMS (2 µg/body/day, s.c.), SOM (4 µg/body/day, s.c.), ZOL plus SMS, ZOL plus SOM, or saline (an equal volume of solvent/day, s.c.). The effects of treatment on tumor growth were determined by measuring tumor volume. In vivo and in vitro, tumor cell apoptosis and proliferation were assessed by immunohistochemistry using TdT-mediated dUTP-biotin nick-end labeling and a Ki-67 antibody, respectively. The apoptotic index (AI) and the Ki-67 labeling index (KI) were determined as the ratios of immunohistochemically positive cells per 1000 NE cells.
Results: Growth of NE-10 tumors in mice treated with ZOL, ZOL plus SMS, or ZOL plus SOM was significantly slowed compared with the saline control (P = 0.003, P < 0.001 and P = 0.001, respectively). The AI was significantly increased in tumors from mice treated with ZOL, ZOL plus SMS, or ZOL plus SOM compared with the saline control (means 9.2, 11.6 and 12.7, respectively, vs 2.4, P < 0.001). In contrast, the KI was significantly decreased in tumors from mice treated with ZOL, ZOL plus SMS, or ZOL plus SOM compared with the saline control (means 5.3, 8.3 and 4.2, respectively, vs 15.9, P < 0.05). In vitro, ZOL induced time- and dose-dependent growth inhibition and apoptosis of NE-CS cells involving the Ras/MAPkinase pathway through mevalonate pathway inhibition. Neither SMS nor SOM induced growth inhibition of 50% or greater in NE cells.
Conclusions: ZOL induces growth inhibition and apoptosis of murine androgen-independent NE carcinoma.
Intraductal carcinoma in prostate needle biopsy can predict clinical failure of prostate cancer
Kyosuke Kimura,1 Tsukii Toyonori,2 Osanu Kamihira,1 Naoto Sassa,3 Tomonori Komathu,3 Ryohei Hattori3 and Momokazu Gotoh3
1Komaki Municipal Hospital, 2Nagoya Daini Red Cross Hospital, 3Nagoya University
Objectives: The presence of intraductal carcinoma (IDC) is well known as high risk factor of biochemical failure after prostatectomy. There are, however, few reports showing whether or not the presence of IDC in prostate biopsy can predict the clinical failure of prostate cancer after prostatectomy. We examined the relationships between the presence of IDC and its prognosis.
Methods: A total of 57 cases of postoperative recurrence were selected for the present study among the 155 patients who had undergone radical prostatectomy for high-risk prostate cancer in the authors' institutions between January 2001 and December 2008. The subjects were classified into group A, consisting of 20 patients (35%) who had ductal spreading during diagnosis by prostate needle biopsy, and group B, consisting of 37 patients (65%) who did not have ductal spreading. Prostate-specific antigen (PSA)-free survival and clinical cancer (metastasis)-free survival rates were analyzed by the log–rank test and we calculated these rates by the Cox regression hazard model. PSA failure was defined as the PSA value being 0.2 ng/mL or higher.
Results: The results were as follows: the median age at diagnosis was A/B 66/67 years (P = 0.7); median follow up was A/B 40/56 months (P = 0.007); median PSA at diagnosis was A/B 21/34 ng/mL (P = 0.76); mean biopsy Gleason score was A/B 8.2/7.7 (P = 0.1); organ-confined was A/B 35/54% (P = 0.31); mean biochemical recurrence free duration was A/B 12.4/16.9 months (P = 0.19); and cancer specific survival rates were A/B 30/100% (P = 0.001). On multivariate analysis, ductal spreading (P = 0.03) was an independent prognostic factor in cancer-specific survival.
Conclusions: The present study suggested that the presence of IDC in needle biopsies might influence disease-specific survival in a high-risk group.
Health-related quality of life in patients with localized prostate cancer received high-dose-rate brachytherapy: A time-course analysis
Shinjiro Shimizu, Yoshimasa Jo, Teruhiko Yokoyama, Mikako Kaifu, Ryoei Hara, Tomohiro Fujii, Yoshiyuki Miyaji and Atsushi Nagai
Kawasaki Medical School
Objectives: The purpose of the present study was to make a time-course analysis of health-related quality of life (HRQoL) in patients with localized prostate cancer receiving high-dose-rate brachytherapy (HDR-BT) using general and disease-specific measures.
Methods: Examination of HRQoL has been carried out since 1 May 2004. The 36-item Short-Form Health Survey version 2.0 (SF-36v2) and the University of California Los Angeles Prostate Cancer Index (UCLA-PCI) were used. Patients were required to complete these two questionnaires before (baseline) and 1, 6, 12 and 24 months after treatment, and patients who completed them at all points were eligible for the present study. The average scores of both the SF-36 and the UCLA-PCI were calculated at every point to make clear the time-course change.
Results: The total number of patients was 229. The average scores in all aspects of the SF-36 at 24 months were better than those at the baseline. For the UCLA-PCI, the average scores for urination (UF and UB) and bowel movement (BF and BB) showed a similar transition to the SF-36, but those for sexuality (SF and SB) showed a significant declination.
Conclusions: HRQoL associated with HDR-BT seemed to be favorable, but the effects on sexual function and sexual bother were not so favorable. Therefore, more attention should be paid to sexuality to achieve a better patient HRQoL.
High-dose-rate brachytherapy with external beam radiotherapy for localized prostate cancer: Five-year results in 166 patients
Shunsuke Tsuzuki, Masahito Kido, Toshihiro Yamamoto, Jun Miki, Takahiro Kimura, Kenta Miki, Manabu Aoki and Shin Egawa
Jikei University School of Medicine
Objectives: To present outcome and morbidity of high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) for localized prostate cancer.
Methods: Between May 2005 and December 2009, 166 patients underwent Ir-192 HDR brachytherapy with EBRT and passed after HDR brachytherapy for more than 1 year. The median follow up was 34 months (range 2–66 months). All patients had localized prostate cancer. Median prostate-specific antigen (PSA) was 24 ng/mL (range 3.8–366 ng/mL). Median Gleason score was 8 (range 6–10). In the initial 84 patients, the total prescribed dose was 11 Gy in two fractions of HDR and 45 Gy in 15 fractions of EBRT. In the recent 82 patients, the total prescribed dose was 18 Gy in two fractions of HDR and 40 Gy in 16 fractions of EBRT. All patients were treated with neoadjuvant hormonal therapy over 6 months and with adjuvant hormonal therapy over 24 months.
Results: A total of 13 patients had shown biochemical failure (BCF) by the Phoenix definition. The 5-year BCF free rate was 83.8%. Univariate analysis showed that clinical T stage and pre-HDR PSA level were predictors of BCF. The BCF rate was 92.5% vs 33.9% and 97.3% vs 70.2% in the clinical stage (<T3 vs T3≥) and PSA level (<0.1 vs 0.1≥), respectively. Only one patient had died of prostate cancer. Of the 166 patients, only one patient showed grade 3 late GI toxicity. There were no other acute nor late severe toxicities.
Conclusions: Clinical T stage and pre-HDR PSA level were predictive factors of BCF. HDR brachytherapy for localized prostate cancer resulted in good outcomes and had comparatively minor toxicity.
Combination chemotherapy with docetaxcel, estramustine phosphate and doxifluridiine in hormone refractory prostate cancer patients
Juro Nakanishi, Yoshihiro Wada, Wataru Takahashi, Jiro Honda and Masatoshi Eto
Kumamoto University Hospital
Objectives: To evaluate the efficacy and toxicity of the combination of docetaxcel (DTX), estramustine phosphate (EMP) and doxifluridine in Japanese patients with hormone-refractory prostate cancer (HRPC).
Methods: From April 2003 through to August 2006, a total of 55 patients with HRPC were treated with a chemotherapeutic regimen including DTX, EMP and doxifluridine at our institution.
Results: The patients received a range from 1 to 64 cycles of treatment. During follow up, 37 patients (67.2%) achieved the prostate-specific antigen (PSA) response (a decrease in PSA level of more than 50% from baseline was defined as a PSA response). Major severe toxicities were grade 3 or 4 hematological toxicities in 20 (36.3%) patients, interstitial pneumonia and deep vein thrombosis in two (3.6%) patients, and disseminated intravascular coagulation, ALT elevation and anorexia in only one (1.8%) patient. However, these patients recovered. Finally, no treatment-related deaths were seen during the observation period. Five patients were continuously able to receive this treatment over 2 years without severe toxicities. Subgroup analysis of these patients showed that younger age and lower PSA level before treatment initiation were significant factors regarding survival benefits
Conclusions: Combination chemotherapy with DTX, EMP and doxifluridine was effective and well tolerated in Japanese patients with HRPC.
Clinical application of Japan Cancer of the Prostate Risk Assessment for prostate cancer patients treated with combined androgen blockade
Yasuhide Kitagawa, Kazuyoshi Shigehara, Sotaro Miwa, Toru Miyagi, Yoshifumi Kadono, Hiroyuki Konaka, Atsushi Mizokami and Mikio Namiki
Objectives: The Japan Cancer of the Prostate Risk Assessment (J-CAPRA) was developed for patients undergoing primary androgen deprivation therapy. We carried out a retrospective review of the clinical courses of patients treated with combined androgen blockade, and examined whether the clinical outcomes of these patients could be stratified using the J-CAPRA score.
Methods: A total of 152 patients with prostate cancer treated with a luteinizing hormone-releasing hormone (LHRH) agonist plus anti-androgen agents were included in this analysis. Progression-free survival periods of primary androgen deprivation therapy were compared among patients divided according to their prostate-specific antigen (PSA) level at diagnosis, Gleason score on biopsy specimens, TNM classification and J-CAPRA score.
Results: The median age of the patients was 75 years. Median PSA at diagnosis was 49.0 ng/mL, and median Gleason score on biopsy was 7. A total of 44 patients (28.9%) had distant metastasis at diagnosis. Clinical stage was higher in patients aged 75 years or less than in those aged 76 years or more. Median follow up was 34 months, and 47 patients (30.9%) showed clinical progression, mainly biological PSA recurrence. PSA at diagnosis, Gleason score on biopsy and clinical TNM stage were significant risk factors for clinical progression. There was a significant difference in progression-free survival rate among patients stratified according to J-CAPRA score (Fig. 1). The probabilities of progression-free survival at 2 years were 100%, 91.3% and 31.6% in patients with J-CAPRA scores of 0–2, 3–7 and 8–12, respectively.
Conclusions: The progression-free survival rate of patients treated with combined androgen blockade could be stratified by J-CAPRA, even for a relatively short-term follow-up period. J-CAPRA is thought to be a useful risk assessment tool for prostate cancer patients treated with combined androgen blockade.
Transperineal ultrasound-guided multiple core biopsy using template for patients with one or more previous negative biopsies: Comparison with systematic 10-core biopsy
Takuma Kato, Toshifumi Yano, Hiromi Hirama, Hiotsugu Uetsuki, Hiroyuki Tsunemori, Masashi Inui, Mikio Sugimoto and Yoshiyuki Kakehi
Objectives: To compare cancer detection rates, pathological accordance rates with compatibility in radical prostatectomy specimens and morbidity rates between systematic 10-core biopsy (group A) and the transperineal ultrasound-guided template biopsy (group B) for patients with one or more previous negative biopsies.
Methods: From April 2006 to April 2010, a total of 66 patients underwent biopsy of the prostate for patients with one or more previous negative biopsies. Group A had 37 patients and group B had 29 patients. Additional cores were obtained from suspicious lesions on rectal examination or ultrasound in group A. The number of biopsy cores was dependent on prostate volume in group B. The average number of cores were 10.1 (median 10) and 50.9 (49) in group A and group B, respectively. There were no significant differences in age, prostate volume or prostate-specific antigen between group A and group B. The number of previous biopsies for group A was more than group B (P = 0.038).
Results: Cancer detection rates were 24% in group A and 51% in group B (P = 0.041), respectively. Radical prostatectomy was carried out in five group A patients and 10 group B patients. The accordance rate of Gleason scores (GS) between biopsy and prostatectomy specimens was 60% in group A and 70% in group B (P = 0.52). GS was upgraded to one out of five in group A and two out of 10 in group B. Two out of five in group A and one out of 10 in group B were upstaged. Two patients suffered from transient subcutaneous hemorrhage in perineal lesions in group B.
Conclusions: Although the present study was not a randomized controlled study, the cancer detection rates in the template biopsy group were higher than the 10-core biopsy. However, the template biopsy is not superior to the systematic 10-core biopsy from the viewpoint of pathological accordance with prostatectomy.
Effectiveness of three-weekly docetaxel treatment on patients with hormone refractory prostate cancer
Keisuke Ichimatsu, Hiroaki Iida, Akihiro Morii, Kenji Yasuda, Akihiko Watanabe, Tetsuo Nozaki, Akira Komiya and Hideki Fuse
University of Toyama
Objectives: To evaluate the efficacy and safety of three-weekly docetaxel therapy for hormone refractory prostate cancer patients.
Methods: A total of 22 Japanese patients with CRPC treated between October 2008 and September 2010 were included in the present study. Docetaxel was given at a dose of 60 mg/m2 on day 2, and 280 mg of estramustine was given twice daily on days 1–5. Zoledronic acid was given to the patients with bone metastasis. One cycle was for 3 weeks. Patients were evaluated for prostate-specific antigen (PSA) response and toxicity.
Results: The median age of the patients was 74 years (range 59–95). Median follow-up time was 10.5 months (range 1–23). Median number of cycles of this regimen was seven (range 2–32). Of 22 patients, 17 (77.2%) had a PSA decline, and eight (36.4%) had a PSA decline of 50% or more. Median overall survival was 15 months. One patient died of pneumocystis pneumonia. Grade 3 or 4 neutropenia was recognized in eight patients (36.4%).
Conclusions: Three-weekly docetaxel therapy is considered to be effective and well tolerated in Japanese CRPC patients.
Clinical value of diffusion weighted magnetic resonance imaging for the detection of prostate cancer
Objectives: The objective of the present study was to compare T2-weighted magnetic resonance imaging (T2WI), diffusion weighted imaging (DWI) and combined T2WI and DWI in the identification of the site of prostate cancer.
Methods: A total of 83 patients with elevated serum levels (≥4.0 ng/mL) of prostate-specific antigen (PSA) were evaluated by T2WI and DWI at 1.5T using body phased array coil before needle biopsy. The obtained data from T2WI and DWI were examined retrospectively for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).
Results: The sensitivity, specificity, PPV and NPV for the detection of prostate cancer were 55%, 90%, 91% and 47%, respectively, for T2WI alone, 53%, 67%, 74% and 44%, respectively, for DWI alone, 36%, 93%, 90% and 45%, respectively, for combined T2WI and DWI, and 72%, 63%, 78% and 56%, respectively, for T2WI or DWI.
Conclusions: DWI is inferior to T2WI in the sensitivity and specificity, but information of DWI improves specificity and NPV for the detection of prostate cancer. This means DWI has the potential to improve an accuracy to detect prostate cancer and to prevent an unnecessary needle biopsy.
Novel anti-androgen ARD1 downregulates androgen receptor levels and activity and suppresses prostate cancer LNCaP cell growth in vitro and in vivo
Hidetoshi Kuruma,1 Kilian Gust,1 Hiroaki Matsumoto,1 Amina Zoubeidi,1 Ladan Fazli,1 Sarah Loddick,2 Nigel Brooks2 and Martin Gleave1
1The Vancouver Prostate Centre, 2AstraZeneca Pharmaceuticals
Objectives: Androgen receptor (AR) plays a critical role in the development and progression of prostate cancer (CaP). Even in castration-resistant prostate cancer (CRPC), AR activity is active and drives progression. Downregulation of AR is a promising strategy for next generation anti-AR agents. In the present study, we evaluated the efficacy of a novel anti-AR agent (ARD1) under androgen-stimulated and androgen-deprived conditions in AR-positive and AR-negative CaP cell lines.
Methods: AR-positive LNCaP and C4-2 cells, and AR-negative PC3 and DU145 cells, were used for in vitro study. Cell growth rates, as well as protein/gene expression, were analyzed using crystal violet assay, flow cytometry, western blotting and reverse transcription polymerase chain reaction, respectively. AR transcriptional activity was measured by PSA-luciferase reporter assay, whereas AR translocation was assessed by immunofluorescence. The effects of ARD1 on castration-resistant LNCaP tumor growth was compared with bicalutamide in castrated male athymic mice.
Results: ARD1 potently suppressed LNCaP and C4-2 cell growth rates in a dose-dependent manner compared with PC-3 and DU-145 cells. Compared with bicalutamide, ARD1 more potently suppressed LNCaP and C4-2 cell growth rates (by up to 50%) under both androgen-stimulated and androgen-depleted conditions. In vitro, ARD1 inhibited AR nuclear translocation and AR transcriptional activity more potently than bicalutamide. ARD1 decreased AR levels both in vitro and in vivo. LNCaP tumor volume and serum PSA levels were significantly lower after treatment by castration plus ARD1 (−54% and −93%, respectively) compared with castration plus bicalutamide (108% and −17%, respectively) or castration plus vehicle (531% and 147%, respectively). In castration-resistant LNCaP tumors, ARD1 treatment induced PSA responses and delayed castration-resistant tumor progression superior to bicalutamide. At 6 weeks post-treatment, compared with vehicle- and bicalutamide-treated groups, serum PSA in ARD1-treated groups decreased by 81% and 65%, respectively, whereas LNCaP tumor volume was 68% and 43%, respectively.
Conclusions: ARD1 strongly downregulated AR levels and activity, and suppressed castration-resistant LNCaP cell growth in vitro and in vivo, providing preclinical proof-of-principle as a promising next generation anti-AR agent.
Source of funding: The fund of AstraZeneca Pharmaceuticals.
Prospective evaluation of 3T magnetic resonance imaging performed prior to an initial transrectal ultrasound-guided biopsy in the detection of prostate cancer
Han Y Choi, Jong W Park, Seo Y Park, Hyun M Lee, Seong S Jeon, Seong I Seo and Byung K Park
Objectives: It is still unclear whether 3T magnetic resonance imaging (MRI) carried out before transrectal ultrasound (TRUS)-guided biopsy is useful for the detection of prostate cancer. The present study prospectively evaluated whether 3T MRI carried out before an initial TRUS-guided biopsy can contribute to detection of prostate cancer.
Methods: Men with an abnormal digital rectal examination or increased prostate-specific antigen (PSA) were enrolled in this prospective randomized study. Participants were randomly allocated into two groups; the MRI group underwent MRI before biopsy and the non-MRI group did not. TRUS-guided biopsy was carried out with or without knowing information on the cancer location. All participants underwent a systematic 10 or 12 core biopsy with or without a target biopsy. The cancer detection rate and positive core rate were obtained to compare MRI and non-MRI groups.
Results: The MRI and non-MRI groups enrolled 44 and 39 participants, respectively. Both groups were not significantly different regarding age, PSA and prostate volume. The MRI group (29.5% [13/44]) had a higher cancer detection rate than the non-MRI group (10.3% [4/39]), but there was no significant difference (P = 0.054). The MRI group (9.9% [52/527]) had a higher positive core rate than the non-MRI group (2.5% [11/432]), with a significant difference (P = 0.000).
Conclusions: Because 3T MRI can offer information on cancer location, TRUS-guided biopsy with preceding MRI has a greater potential to sample cancer tissue than TRUS-guided biopsy without preceding MRI. Subsequently, MRI that is carried out before TRUS-guided biopsy might contribute to the detection of prostate cancer.
Acknowledgment: The present study was supported by the Samsung Medical Center (Clinical Research Development Program grant, #CRS 108-13-1).
Chronic hypoxia enhances androgen-independent growth and the malignant potential of prostate cancer cells via overexpression of Vav3
Kenichi Hirai, Takeo Nomura, Mutsushi Yamasaki, Takanori Matsubara, Fuminori Sato and Hiromitsu Mimata
Objectives: Hypoxia is a major feature of solid tumor, which increases treatment resistance and favors tumor progression. Our previous studies showed that chronic hypoxia (1% oxygen for over 6 months) promoted androgen-independent growth and malignant cell behavior in a human prostate cancer cell line. In the present study, we analyzed gene expression profiles and specifically focused on the biological functions of the Vav3 gene in vitro.
Methods: We used LNCaP cells under normoxic, acute hypoxic (1% oxygen for 48 hours) and chronic hypoxic conditions for comprehensive mRNA profiling by an Agilent 44 K array platform and Ingenuity Pathways Analysis. We validated the expression by quantitative reverse transcription polymerase chain reaction and western blot analyses. To analyze the function of Vav3, knockdown by siRNA was carried out. Next, we transfected LNCaP with the Vav3 cDNA expression vector (control cells were transfected with the neo expression vector) and isolated stable clones with high or low expression. The growth of cancer cells was evaluated in vitro. Also, we examined cell invasiveness and migration using the Matrigel invasion assay. For cell cycle analysis, flow cytometric analysis of propidium iodide-stained nuclei was carried out.
Results: Among about 200 genes elevated in only a chronic hypoxic condition, Vav3 was associated with cell growth, migration, invasiveness and androgen dependence. Overexpression of both Vav3 mRNA and protein was observed under chronic hypoxia, respectively. And LNCaP cells under chronic hypoxia showed less malignant potential and the apoptosis by interrupting Vav3 expression using Vav3 siRNA. Furthermore, Vav3 expression positively correlated with the growth, invasiveness and motility of LNCaP cells.
Conclusions: The present results showed that chronic hypoxia promoted androgen-independent growth and the malignant potential of prostate cancer cells through overexpression of Vav3.
Everolimus-based treatment for Japanese patients with metastatic renal cell carcinoma after tyrosine kinase inhibitor therapy
Yasuyuki Seno, Masao Kato and Koji Mita
Hiroshima City Asa Hospital
Objectives: To evaluate the tolerability of everolimus (an mTOR inhibitor) in Japanese patients with metastatic renal cell carcinoma.
Methods: Nine patients with metastatic renal cell carcinoma were treated with everolimus (10 mg/day) daily during the period from April 16 to August 31 2010 to investigate the tolerability of treatment and adverse events.
Results: All of the patients were men and their mean age was 64.7 years (range 52–78 years). The median follow-up period was 52 days (12–126 days). The sites of metastasis were the lung (n = 8), liver (n = 4), bone (n = 2), lymph nodes (n = 1) and brain (n = 1). The number of metastases was one in three patients, two in five patients, and three in one patient. All of the patients had progressive disease (PD) after treatment with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (TKI) (sunitinib following interferon in three, sorafenib following interferon in one, both of these TKI following interferon in two and sunitinib alone in three patients). Typical adverse events were stomatitis (n = *) and renal dysfunction (n =). Four patients discontinued treatment with everolimus, with discontinuation being as a result of PD in three patients and stomatitis (grade 3) in 1 patient.
Conclusions: Only one of the nine patients discontinued treatment as a result of intolerance of everolimus. The incidence of serious adverse events was relatively low during everolimus therapy, and treatment could generally be continued. Everolimus is a possible option for second-line therapy after failure of treatment with a VEGF receptor TKI.
Anti-b2-microglobulin antibody is a novel therapeutic agent for human renal cell carcinoma
Takeo Nomura,1 Wen-Chin Huang,2 Leland WK Chung2 and Hiromitsu Mimata1
1Oita University, 2Samuel Oschin Comprehensive Cancer Institute
Objectives: We previously reported that the biological functions of b2-microglobulin (b2M) include antigen presentation and oncogenic activity. The present study investigated b2M regulation of human renal cell carcinoma (RCC) growth, survival and apoptosis, and its antagonism by anti-b2M neutralizing antibody, a promising new therapeutic antibody for human RCC.
Methods: We examined the effects of recombinant b2M protein and anti-b2M antibody on RCC cell growth and apoptosis in vitro. To understand the molecular mechanisms of b2M and anti-b2M antibody, we analyzed alterations in the growth and survival signaling components of phosphatidylinositol 3-kinase (PI3K)/Akt-, extracellular signal-regulated kinase (ERK)-, Bcl-2 and c-jun N-terminal kinase (JNK)-mediated pathways and cell death signaling mediated by Bad using corresponding kinase inhibitors or phosphorylation site-specific antibodies in SN12C cells.
Results: Recombinant b2M protein increased the growth of three human RCC cell lines, SN12C, Caki-1 and ACHN, in a dose- and time-dependent manner. Treatment of SN12C, Caki-1 and ACHN cells with an anti-b2M polyclonal antibody strongly suppressed the growth of these cells in vitro, also in a dose- and time-dependent manner. Additions of recombinant b2M protein or anti-b2M antibody increased or decreased anchorage-independent growth of SN12C cells, respectively. Recombinant b2M protein accelerated cell growth through activating PI3K/Akt and ERK, and inducing phosphorylation of Bad. Treatment with anti-b2M antibody induced cell death by inhibiting the phosphorylation of Akt and ERK, and activating JNK, resulting in the induction of phosphorylation of Bcl-2 and decreased phosphorylation of Bad, leading to apoptosis.
Conclusions: Our results showed that b2M has an important role in regulating the growth and survival of RCC cells, and anti-b2M antibody offers a potential novel therapy for the treatment of human RCC.
Long-term administration of sunitinib for metastatic renal cell carcinoma
Masaya Murakami, Jun Miki, Takahiro Kimura, Takashi Hatano and Shin Egawa
Objectives: The purpose of the present study was to examine the clinical outcome and adverse events (AE) associated with long-term sunitinib treatment.
Methods: We retrospectively reviewed clinicopathological features in seven patients receiving sunitinib for more than 12 months. We evaluated AE using NCI-CTCAE and RECIST guidelines.
Results: The median age was 60 years. All patients received previous treatment with radical nephrectomy. Five patients had a clear cell histological component, and the others had papillary and unclassified renal cell carcinoma. The object response rate resulted in five patients with partial response and two patients with stable disease. The common AE were decreased platelet count, hypothyroidism and stomatitis with two patients each. The severe AE was a case of rectal perforation. Now, four patients continue to be treated with sunitinib, one patient discontinued this treatment and two patients died as a result of tumor progression.
Conclusions: Patients who are treated with sunitinib might acquire maximum response rate with 3–6 months, but most AE appear within 7 weeks. However, kidney dysfunction, gastrointestinal bleeding and perforation might appear with long-term administration. We should predict and manage AE according to the duration of treatment.
Prognostic factors for survival in patients with T1 renal cell carcinoma: A multi-institutional study in the Hokuriku district, Japan
Yosuke Matsuta, Hironobu Akino, Mikio Namiki, Hideki Fuse, Kouji Suzuki and Osamu Yokoyama
Hokuriku Renal Cancer Research Group
University of Fukui
Objectives: We investigated the survival and the prognostic factors of T1 renal cell carcinoma (RCC) cases in the Hokuriku district of Japan.
Methods: We reviewed the records of 796 patients who had undergone nephrectomy and had been diagnosed as T1 RCC. Patient records from January 1997 to December 2004 were collected from plural institutions in the Hokuriku district, and used in our research. We identified the factors associated with prognosis using the Cox proportional-hazards model. We examined the following items: age, sex, mode of tumor discovery, presence of inflammatory reaction, histological subtype, T classification, N classification, presence of distant metastasis, histological grade, mode of infiltration, venous invasion, usage of interferon-α or interleukin-2 and surgical procedure.
Results: The average age of the subjects was 62.4 years (range 13–96 years). The average follow-up period was 54.3 months (range 0–79 months). The multivariate analysis showed that lymph node metastasis, distant metastasis, T1b cases and non-clear cell carcinoma type were independent prognostic factors in T1 RCC cases. Furthermore, distant metastasis and lymph node metastasis for T1a cases, and histological grade 3 component, distant metastasis, and non-clear cell carcinoma type for those of T1b cases were independent prognostic factors. In respect to the cases without metastasis (cases expecting curative resection), histological grade 3 component and T1b cases were independent prognostic factors. As for the T1a cases, surgical procedure (partial nephrectomy vs radical nephrectomy) did not show a significant difference in survival.
Conclusions: The presence of metastasis affects prognosis strongly. Because there is no significant difference in survival despite procedure, it seems to be rational for T1a RCC patients to be offered nephron-sparing surgery. However, careful follow up should be carried out with cases having a histological grade 3 component.
Primary vesicouretheral reflux in our hospital from 1977 to September 2010
Chie Onizuka, Toshio Kamimura, Masafumi Nagano, Takanori Yamaguchi and Toshiyuki Kamoto
University of Miyazaki
Objectives: To analyze primary vesicoureteral reflux (VUR) in patients who were treated in our hospital during the past 34 years. We examined whether we could predict spontaneous resolution of reflux and also determined the effectiveness of antimicrobial prophylaxis.
Methods: We studied 283 patients with primary VUR who were ≤15 years-of-age and presented between 1977 and September 2010. We defined grades IV and V as high-grade VUR (96 cases). We examined clinical outcomes, dimercaptosuccinic acid (DMSA) renal scans and antimicrobial prophylaxis in the 96 cases.
Results: There were 54 (22.9%) cases with spontaneous resolution of reflux in a total of 236 cases, except for the yet uncertain or unknown cases. Spontaneous resolution occurred in 24 cases (45.3%) within 1 year of diagnosis, and 18 cases (34.0%) were within 2 years of diagnosis. Clinical outcomes of the high-grade VUR cases included corrective surgery (70), spontaneous resolution (7), still uncertain (12) and unknown (7). A total of 65 high-grade VUR cases had DMSA scans at the time of diagnosis and 38 (58.5%) cases already had renal scars. A total of 73 cases had antimicrobial prophylaxis. Breakthrough infections (BTI) were found in 19 cases (26.0%). None of the cases had DMSA scans before BTI occurred.
Conclusions: We attempted to evaluate the significance of antimicrobial prophylaxis in high-grade VUR patients by examining DMSA scans before and after BTI. However, no DMSA scans were carried out before BTI occurred. There were a few cases of spontaneous resolution in high-grade VUR cases. There were also a few cases of end-stage renal failure with hemodialysis for reflux nephropathy. It is important for high-grade VUR patients, especially those in their pre-adolescent years, to undergo corrective surgery considering the factors of age at diagnosis, period of time from diagnosis, renal scars in DMSA scans and BTI.
How do we manage preoperative quantified bacteriuria by antimicrobial administration?
Jiro Hashimoto, Satoshi Takahashi, Teruhisa Uehara, Yuichiro Kurimura and Taiji Tsukamoto
Sapporo Medical University
Objectives: Bacteriuria is common in patients with complicated urinary tract conditions. If such patients undergo an operation without any preoperative antimicrobial chemotherapy, postsurgical infection can occur as a result of dissemination of bacteria. We retrospectively examined the association between preoperative bacteriuria and postsurgical infection in patients with urological surgery.
Methods: Medical charts were reviewed from April 2007 to December 2009, and 413 patients who underwent urological clean-contaminated surgery and were followed for at least 1 month were enrolled in the present study. The protocol for surgical antimicrobial prophylaxis in our department is as follows: a single antimicrobial agent is given just before the start of transurethral surgery, and from just before surgery up to 48 h after open surgery. The decision for preoperative antimicrobial administration for patients with bacteriuria depends on the results of culture and antimicrobial sensitivity tests.
Results: Of 413 patients, transurethral surgery was carried out in 211 patients, and open and laparoscopic surgeries in 204 patients. A total of 38 of the 413 patients developed infections within 1 month after surgery. There was no significant difference in the frequency of postoperative infectious disease between patients with preoperative bacteriuria of ≥10∧4 colony-forming units (CFU)/mL and those without preoperative bacteriuria (P = 0.924). In the patients with preoperative bacteriuria of ≤10∧3 CFU/mL, there was no significant difference in the frequency of postsurgical infection whether or not there was preoperative antimicrobial chemotherapy (P = 0.563).
Conclusions: In the present study, the frequency of postoperative infectious disease was almost the same in the antimicrobial-treated patients with significant preoperative bacteriuria (≥10∧4 CFU/mL) and those without preoperative bacteriuria. If the patients with significant preoperative bacteriuria undergo a clean-contaminated operation, preoperative antimicrobial chemotherapy contributes to controlling postsurgical infection. When the patients with preoperative urine ≤10∧3 CFU/mL undergo operation, preoperative antimicrobial chemotherapy is not necessary for prevention of postsurgical infection.
Health-related quality of life for patients treated for benign prostatic hyperplasia with Holmium laser enucleation of the prostate
Kazuhiko Fukumoto, Teruhiko Yokoyama, Mikako Kaifu, Ryoei Hara, Tomohiro Fujii, Yoshimasa Jo, Yoshiyuki Miyaji and Atsushi Nagai
Kawasaki Medical School
Objectives: Holmium laser enucleation of the prostate (HoLEP) for patients with benign prostatic hyperplasia (BPH) is expected to improve urinary symptoms. We investigated the efficacy of HoLEP and health-related quality of life (QOL) after HoLEP using the SF-36 questionnaire.
Methods: A total of 190 patients, aged 50–91 years were treated with HoLEP. The effects were evaluated before and 3, 6, and 12 months after treatment by international prostate symptom score (IPSS), QOL index and uroflowmetry. The SF-36 questionnaire was obtained before treatment and 3, 6, and 12 months subsequently.
Results: The mean prostate specimen weight was 33.8 g, with a range of 3–116 g. The mean IPSS score improved from 20.6 to 7.7 at 3 months (P < 0.001), to 6.7 at 6 months (P < 0.001), to 6.4 at 12 months (P < 0.001). The mean QOL index improved from 5.3 to 2.0 at 3 months (P < 0.001), to 1.9 at 6 months (P < 0.001), to 1.9 at 12 months (P < 0.001). The mean Qmax improved from 6.5 mL/s to 16.5 mL/s at 3 months (P < 0.001), to 15.9 mL/s at 6 months (P < 0.001), to 15.0 mL/s at 12 months (P < 0.001). Regarding SF-36, every eight question items were lower than 50 (below average national health condition) before treatment. Four items out of eight, general health perceptions (GH), social functioning (SF), bodily pain (BP) and mental health (MH) were significantly improved after treatment. However, other items, role physical (RP), vitality (VT), mental health (MH) and role emotional (RE), showed no change after treatment.
Conclusions: HoLEP for BPH patients improved some mental and physical conditions, as well as urinary conditions.
Overactive bladder can induce hypertension
Kazumasa Torimoto,1 Takeshi Takami,2 Akihide Hirayama,1 Masaomi Kuwada,1 Yoriaki Kagebayashi,3 Shoji Samma,3 Kiyohide Fujimoto1 and Yoshihiko Hirao1
1Nara Medical University, 2Clinic Jingumae, 3Nara Prefectural Nara Hospital
Objectives: It is reported that hypertension is related to overactive bladder (OAB). Detrusor overactivity (DO) in OAB patients is induced through bladder afferent C fibers. The C fiber-induced DO also occurs in patients with spinal cord injury higher than the T6 level, which causes severe hypertension by autonomic dysreflexia. We hypothesized that OAB is not only the result of hypertension, but also one of the causes of hypertension. The aim of the present study was to show whether DO induces hypertension.
Methods: Study 1: Blood pressure (BP) was continuously monitored during a urodynamic study in 10 male outpatients. Study 2: A frequency volume chart and BP were recorded for 24 h in five male inpatients. BP was measured by ambulatory blood pressure monitoring.
Results: Study 1: DO occurred in seven out of 10 patients. The systolic pressure (sBP) significantly increased together with DO (D29.4 ± 4.0 mmHg). Overactive bladder symptom score (OABSS) in patients with and without DO was 7.7 ± 0.9 and 6.0 ± 2.9, respectively. Study 2: sBP together with urgency or urge was significantly higher than that in filling phase in both patient groups with OAB (n = 2, OABSS 11.5 ± 1.5; 170.5 ± 9.6 vs 129.4 ± 3.0 mmHg, P < 0.0001) and those without OAB (n = 3, OABSS 2.3 ± 0.3; sBP: 122.7 ± 2.8 vs 116.5 ± 1.9 mmHg, P = 0.045). The difference was greater in patients with OAB.
Conclusions: It is suggested that OAB with DO causes hypertension.
Effects of solifenacin in patients with overactive bladder on symptoms and health-related quality of life
Yoshiyuki Ishiura, Hiroshi Yaegashi and Kiyoshi Koshida
NHO Kanazawa Medical Center
Objectives: The present study compared the overactive bladder symptom score (OABSS) with the overactive bladder questionnaire (OAB-q) and examined the responsiveness of solifenacin.
Methods: OAB patients were treated with solifenacin for 4–12 weeks in our outpatient clinic. The OABSS and the OAB-q were collected at pre- and post-treatment. The relationship between the OABSS and the OAB-q, and responsiveness of solifenacin were analyzed.
Results: A total of 34 patients enrolled (mean age 73.1 years, 47.1% male, 73.5% OAB wet). The average point of sum score of the OABSS, daytime frequency, night-time frequency, urgency and urgency incontinence before therapy was 8.5, 0.8, 2.1, 3.3 and 2.2, respectively. In a point of OAB-q subscale before therapy, the average of symptom bother, coping, concern, sleep, social interaction and health-related quality of life (HRQL) total was 29.1, 71.4, 75.5, 71.9, 84.7 and 75.3, respectively. Before therapy, the sum score of the OABSS was significantly correlated with all OAB-q subscales except for social interaction. Correlation with OAB-q at pretreatment was examined, which was greatest for the sum score of the OABSS, followed by urgency, night-time frequency, urgency incontinence and daytime frequency. A significant correlation was seen between age and the OABSS, but not seen between age and the OAB-q. The sum score of the OABSS was significantly decreased (6.0) after therapy. Daytime frequency (0.6), night-time frequency (1.7), urgency (2.2) and incontinence (1.4) were also significantly decreased. After treatment, significant improvements occurred in all OAB-q subscales. The average of symptom bother, coping, concern, sleep, social interaction and HRQL total was 23.5, 77.1, 83.1, 76.4, 88.8 and 82.0, respectively.
Conclusions: OAB symptoms are correlated with OAB-related HRQL and symptom bother. Both symptoms and HRQL were improved by solifenacin. The OABSS appears to be a useful outcome measure with OAB patients, as well as the OAB-q.
Our experience of botulinum toxin type A for the treatment of interstitial cystitis in the Japanese population
Yoshiko Maeda1 and Yuki Sekiguchi2
1Tokyo Women's Medical University Aoyama Hospital, 2Yokohama Motomachi Women's Clinic LUNA
Objectives: No specific medicine is available for interstitial cystitis, which is therefore now being treated with hydrodistension plus medication. However, most cases are refractory to this treatment and recur after the treatment. In the field of urology, botulinum toxin type A has been reported to be effective for the treatment of interstitial cystitis, but is not generally medicated because of its disapproval for health care services provided by health insurance. We report herein our experience with injections of this agent into the urinary bladder wall for the treatment of intractable interstitial cystitis.
Methods: We injected 100 units of botulinum toxin type A (Botox) into the bladder wall, sparing the trigone, of five women with a diagnosis of interstitial cystitis. We evaluated its efficacy by collecting questionnaires before and after the treatment: ICI Questionnaire-Short Form, Overactive Bladder Symptom Score, Interstitial Cystitis Symptom Index, Interstitial Cystitis Problem Index and International Prostate Symptom Score.
Results: Every score was reduced after the treatment as compared with before the treatment, but the difference was not statistically significant. Although quality of life related to incontinence and symptoms of urinary retention was improved, no pain was relieved. It has bee recommended in recent studies that Botox be injected into the trigone of the bladder for interstitial cystitis therapy. We did not inject the agent into the trigone, which might partially account for our failure to alleviate pain.
Conclusions: We injected Botox into the bladder wall for the treatment of interstitial cystitis, which was improved in symptoms of urinary retention, but not in pain.
Case report of interstitial cystitis successfully managed by acupuncture treatment
Takahiro Shitamura, Katumi Inoue, Kiyotaka Nose and Toshiyuki Kamoto
University of Miyazaki
Objectives: Acupuncture is one of the standard neuromodulatory therapies available in Japan. However, acupuncture treatment is not general used for interstitial cystitis. It reports to here because it experienced effective in dramatic form by the acupuncture treatment of interstitial cystitis.
Methods: A 60-year-old female was diagnosed with interstitial cystitis and treated by hydroexpantion of the bladder several times but there were no effect. Furthermore, she used to frequently have failed in hyperbalic oxygenation treatment. We decided to try acupuncture treatment in consultation with a specialist. Stainless steel was used. It is needling in the sacral hiatus in six spaces. It energized 3Hz once for 20 minutes once every 2 weeks.
Results: After 10 weeks, the lower abdominal pain and urinary frequency had improved dramatically and the bladder capacity had increased from 200 mL to 400 mL. Additionally, findings of a cystoscopy and the intravesical pressure had normalized in 1 year.
Conclusions: Acupuncture is one of the standard neuromodulatory therapies available in Japan. Acupuncture treatment might be a possible treatment option for intractable interstitial cystitis patients.
Most common diagnostic and therapeutic approaches of 458 patients with interstitial cystitis in Japan
Hiroshi Hayami,1 Hideki Enokida,1 Masayuki Nakagawa,2 Seiji Naito,3 Tetsuro Matsumoto,4 Jiro Uozumi,5 Hiromitsu Mimata6 and MineoTakei6
1Kagoshima University, 2Kyushu University, 3University of Occupational and Environmental Health, 4Saga University, 5Oita University, 6Hara Sanshin General Hospital
Objectives: Interstitial cystitis (IC) is a chronic disease of unknown etiology. A delay in diagnosis and treatment of IC can cause severe deterioration of the quality of life of the patients. The aim of the present study was to ascertain the most common diagnostic and therapeutic approaches of IC patients.
Methods: We retrospectively evaluated 458 IC patients who had fulfilled the Japanese Clinical Guideline for IC at 11 university hospitals in Japan between 2002 and 2006. Patients were interviewed about their sex, age, medical history and predominant symptoms. Regarding laboratory findings, we evaluated voided volume and cystoscopic findings at hydrodistension. Clinical parameters and laboratory findings were statistically analyzed to evaluate the therapeutic efficacy on the basis of the Global Response Assessment.
Results: Our cohort consisted of 354 female and 104 male patients, with a median age of 62 years. The interval between symptom onset and first medical encounter was 33.7 months on average (range 1–456 months). The frequent symptoms were urinary frequency (69.4%), bladder pain and urinary urgency in order. The voided volume was 142 mL on average (24–460 mL). The most common diagnostic approach of IC was cystoscopy at the time of hydrodistension. Cystoscopic findings showed “glomerulation” and “Hunner's ulcer” in 371 cases (81.0%) and 55 cases (12.0%), respectively. Those patients were treated with hydrodistension (399 cases, 87.1%), oral administration (305 cases, 66.5%) and intravesical instillation (89 cases, 26.2%) in order, and 163 patients had a combined treatment of hydrodistension and oral administration. Overall, these treatments were effective for symptom improvement in 76% of the patients. Multivariate analysis showed that hydrodistension was the most effective treatment for IC patients (P = 0.0196).
Conclusions: The present study suggests that hydrodistension followed by cystoscopy is the most effective among the treatment modalities and is a useful diagnostic tool at the same time for patients with IC.
Comparison of different α1-adrenoceptor antagonists, tamsulosin hydrochloride and silodosin for treatment of male lower urinary tract symptoms: A prospective randomized crossover study
Teruhiko Yokoyama, Kazuhiko Fukumoto, Ryoei Hara, Tomohiro Fujii, Yoshimasa Jo, Yoshiyuki Miyaji and Atsushi Nagai
Kawasaki Medical School
Objectives: We assess the efficacy and safety of two α1-adrenoceptor antagonists, tamsulosin hydrochloride and silodosin, for the treatment of male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia.
Methods: Men who were 50 years-of-age or older who had a total international prostate symptom score (IPSS) of 8 or higher and quality-of-life (QOL) index of 3 or higher were enrolled in the present study. A total of 46 patients (mean age 69.5 years, range 56–83) were randomized into two groups. A total of 23 patients were initially prescribed tamsulosin hydrochloride 0.2 mg once daily for 3 months, followed by silodosin 8 mg twice daily for 3 months (group T); another 23 patients were initially prescribed silodosin for 3 months, followed by tamsulosin hydrochloride for 3 months (group S). Patients changed to the alternative treatment after a 1-month clearance period in between groups. Evaluations included clinical determination of IPSS, QOL index, maximum flow rate (Qmax) and postvoid residual urine volume (PVR) before and after treatment.
Results: A total of 46 men, including 23 in group T and 23 in group S, were treated, and 41 (89.1%) completed the treatment. IPSS, QOL index, Qmax and PVR were significantly improved in group T and S after treatment. There was no significant difference between the two groups. The total IPSS of group S after 1-month clearance was significantly lower than that of group T. A total of 18 patients preferred silodosin, 11 patients preferred tamsulosin and the others felt the same effects after treatment. Six patients during silodosin treatment experienced adverse events. Four patients complained of ejaculatory dysfunction and three patients stopped medication. Two patients complained of nasal congestion or a dry mouth.
Conclusions: Two types of α-blockers in the same individuals provided similar efficacy. Subjective improvement might be sustained even after cessation of silodosin. Although adverse events were higher, more patients preferred silodosin treatment.
Oxidative stress agent, 8-hydroxydeoxyguanosine closely relates with male storage symptoms: A community-based study
Noritaka Kamimura, Naoki Fujita, Noriko Tokui, Teppei Okamoto, Kengo Imanishi, Naoki Sugiyama, Atsushi Imai and Chikara Ohyama
Objectives: We investigated serum markers that closely relate to lower urinary tract symptom (LUTS) in healthy male subjects. In particular, we were interested in an oxidative stress agent, 8-hydroxydeoxyguanosine (8-OHdG), as an indication for storage symptoms. Male LUTS are believed to be caused by ischemia-reperfusion injury of the detrusor smooth muscle.
Methods: The subjects were 345 healthy males with an average age of 56 years (range 26–83 years) who participated in the Iwaki Health Promotion Project in 2006. They were residents of the Iwaki district, Hirosaki City, in northern Japan. We used the International Prostate Symptom Score (IPSS) surveys at the site of examination. We measured the serum level of glucohemoglobin (HbA1c), high-sensitivity CRP (hs-CRP), cholinesterase (ChE), high sensitivity prostate-specific antigen (hs-PSA) and 8-OHdG of all subjects.
Results: Seventy five participants (21.7%) scored 8 points over on the total I-PSS survey. Multi-logistic regression analysis revealed a) hs-CRP (P = 0.002) and hs-PSA (P = 0.005) are the independently significant indicators of LUTS based on total I-PSS, b) 8-OHdG (P = 0.012) and hs-PSA (P = 0.015) are the independently indicators of LUTS on storage symptom score, c) only hs-PSA (P = 0.041) is the independently significant indicators of LUTS on voiding symptom score.
Conclusions: Hs-PSA is an indicator of LUTS on total IPSS, storage symptom score and voiding symptom score. Hs-CRP is an indicator of LUTS on total IPSS, and 8-OHdG is an indicator of LUTS on storage symptom score.
Identification of tumor suppressive microRNA (miR-1 and miR-133a) and their target genes based on genome-wide screening in bladder cancer
Hirofumi Yoshino,1 Takeshi Chiyomaru,1 Hideki Enokida,1 Kazumori Kawakami,1 Shuichi Tatarano,1 Kenryu Nishiyama,1 Naohiko Seki2 and Masayuki Nakagawa1
1Kagoshima University, 2Chiba University
Objectives: MicroRNA (miRNA) play a role in targeting messages of protein-coding genes involved in the development of various cancers. The aim of the present study was to identify novel tumor suppressive miRNA in bladder cancer (BC) and to identify the target genes.
Methods: To identify the miRNA signature specific to BC, we analyzed the expression profiles of miRNA in BC by using a platform of miRNA microarray, which contains 665 miRNA. We examined the expression levels of the top five miRNA and carried out gain-of-function studies using the miRNA. Oligo microarray analyses of the candidate miRNA transfectants were carried out to identify target genes. The luciferase reporter assay was used to confirm the actual binding sites between the miRNA and the target mRNA. We examined the expression levels of the target gene and carried out loss-of-function studies using small interfering RNA. Immunohistochemistry was carried out on the tissue microarray.
Results: MiRNA microarray analysis showed the top five downregulated miRNA. Reverse transcription polymerase chain reaction showed that these miRNA expressions were significantly lower in BC specimens and BC cell lines. MiR-1 and miR-133a showed the potential role of tumor suppressors by functional analyses of BC cells, such as cell proliferation, apoptosis, migration and invasion assays. Molecular target searches of these miRNA showed that TAGLN2 was directly regulated by both miR-1 and miR-133a. The expression levels of TAGLN2 mRNA were significantly higher in BC cell lines. TAGLN2 mRNA and protein expression were markedly repressed in miR-1 and miR-133a transfectants. Silencing of the TAGLN2 study showed significant inhibitions of cell proliferation and an increase of apoptosis in BC cell lines. Immunohistochemistry showed there were significant correlations between the expression of TAGLN2 scores and tumor grade/metastasis.
Conclusions: Our data suggest that miR-1 and miR-133a might function as a tumor suppressor through repression of oncogenic TAGLN2 expression in BC. These pathways might have a critical role in BC oncogenesis.
Tumor suppressive function of miR-218: located on chromosome 4p15.31 in frequent genomic loss region in bladder cancer
Shuichi Tatarano,1 Takeshi Chiyomaru,1 Kazumori Kawakami,1 Hideki Enokida,1 Hirofumi Yoshino,1 Kenryu Nishiyama,1 Naohiko Seki2 and Masayuki Nakagawa1
1Kagoshima University, 2Chiba University
Objectives: MicroRNA (miRNA) are an abundant class of small non-coding RNA, and show aberrant expression patterns and functional abnormalities in human diseases, including cancers. Although some miRNA function as tumor suppressors and are downregulated in cancer cells, other miRNA act as oncogenes. However, genetic or epigenetic regulations of these miRNA in bladder cancer (BC) are not fully elucidated at this time. We hypothesize that chromosomal loss region harbors downregulated miRNA that have a tumor suppressive function in BC.
Methods: On the basis of our previous comparative genomic hybridization (CGH) array data in BC cell lines, we focused on chromosome 4, because it was the frequent genomic loss region, and 23 miRNA were coded there. The expression levels of miRNA were evaluated by a real-time polymerase chain reaction in four BC cell lines and 22 clinical samples. The miRNA's transfected BC cell lines were subjected to cell viability assays by cell growth, wound healing and matrigel invasion assay; and apoptosis assay by flow cytometory. To find which genes were differentially regulated by the miRNA, the gene expression profile of the miRNA's transfectants was carried out.
Results: Among the miRNA on chromosome 4, miR-218 located on chromosome 4p15.31 was actually downregulated in BC cell lines and clinical BC samples in comparison with normal bladder epitheliums (P = 0.0004). Significant cell viability inhibitions of cell growth, invasion and migration were observed in miR-218 transfectants (each, P < 0.005). The flow cytometory showed that the apoptotic fraction was significantly greater in the miR-218 transfectants (each, P < 0.005). Oligomicroarray analyses identified that 337 downregulated genes and 162 upregulated genes were differently expressed in the transfectants.
Conclusions: Our data suggest that miR-218 might be a tumor suppressive miRNA and that its expression was generally downregulated in BC as a result of the chromosomal loss region where the miRNA harbors.
Operative outcomes of retroperitoneal total cystectomy for patients with invasive bladder cancer
Takehiko Segawa,1 Takeshi Takahashi,2 Keiyu Matsumoto,1 Takayuki Sumiyoshi,1 Noriaki Utsunomiya,1 Koei Muguruma1 and Mutsushi Kawakita1
1Kobe City Medical Center General Hospital, 2Hyogo Prefectural Tsukaguchi Hospital
Objectives: The peritoneal cavity is usually opened at a very early stage of the operation in a conventional total cystectomy. Theoretically, if the peritoneal cavity is preserved until urinary diversion with the retroperitoneal approach, the time of bowel exposure to the air can be minimized. However, some arguments exist concerning the quality of the lymph node dissections with the retroperitoneal approach. The present study aimed to discuss whether the retroperitoneal procedure has advantages or disadvantages in terms of operative quality, bowel recovery and postoperative complications.
Methods: A total of 25 patients, 13 with the retroperitoneal approach and 12 with conventional peritoneal approach, underwent total cystectomy in Kobe City Medical Center General Hospital from 2008 to 2010. The protocol consisted of preoperative, intraoperative and postoperative measures for these patients. The clinical parameters assessed were the time to the return of bowel movements, the occurrence of postoperative ileus and other bowel-related complications. For the measurement of quality of total cystectomy, the number of dissected lymph nodes was compared.
Results: The time to bowel recovery was shorter in retroperitoneal cystectomy compared with conventional peritoneal cystectomy (flatus 2.0 vs 3.4 days, stool 2.9 vs 4.4 days, fluid intake 2.8 vs 3.8 days, diet 4.8 vs 5.7 days). Three patients with conventional peritoneal cystectomy suffered from postoperative ileus. The number of dissected lymph nodes was comparable in the retroperitoneal approach with the peritoneal approach, 17.0 vs 14.1.
Conclusions: With retroperitoneal cystectomy, the short time to the resumption of normal intestinal function and a low incidence of postoperative ileus was observed. The quality of the operation in terms of lymph node dissections was not negatively affected by this procedure.
Evaluation of the role of second transurethral resection for transurethral resection of bladder tumor in one piece
Hiroshi Ikeda,1 Masayoshi Nomura,2 Takehiko Shou,1 Kaori Ishikawa,1 Eiji Kashiwagi,1 Takashi Dejima,1 Hayato Sanefuji1 and Kouji Okumura3
1Kitakyushu General Hospital, 2Kameda Medical Center, 3Nippon Steel Yawata Memorial Hospital
Objectives: Since transurethral resection of bladder tumor in one piece (TURBO) was reported in the Journal of Urology in 2000 by Ukai, some urologists have carried out TURBO. We analyzed treatment results of TURBO in our hospital and examined the value of this procedure, especially for the pathological findings, recurrence and necessity of second TUR for TURBO.
Methods: A total of 14 patients with bladder tumors had TURBO carried out under spinal anesthesia, in some cases blocking the obturator nerve, from April 2006 to June 2009 in our hospital. All cases were followed for over 1 year. The procedure is (i) point marking; (ii) circular incision; (iii) level incision; and (4) specimen retrieval using a needle electrode in accordance with Ukai's method. We investigated pathological findings (margin situation), operation time, complications and recurrence.
Results: It is possible to diagnose the precise pathological findings by TURBO. We judged the width and depth ew in sequential sections. There were no complications during and after the operation. Operation time of TURBO (35–170 min) was longer than TUR-BT. The urethral catheter holding period and hospitalization period after TURBO was the same as TUR-BT. TURBO is a relatively safe procedure, even for beginners. Five cases had a recurrence in 13 months. Two cases had a recurrence in less than 1 year, but the locations were other places. One case had a same place recurrence after 13 months. There were no cases of same place recurrence in less than 1 year among margin-negative cases. Therefore, we judged that ew-negative cases had no residual cancers.
Conclusions: TURBO is a safe and useful procedure that provides precise pathological findings with minimal complications. Second TUR is not necessary for TURBO. TURBO has the possibility of being the gold standard of treatment for non-muscle invasive bladder cancer.
Experience of laparoscopic radical cystectomy after radiation therapy for prostate cancer
Takafumi Yanagisawa, Jun Miki, Gen Ishii, Shigehiro Bando, Kenta Miki and Shin Egawa
Objectives: We experienced two cases of laparoscopic radical cystectomy for invasive bladder cancer after limited part radiation therapy for localized prostate cancer.
Methods: Case 1: The patient was a 77-year-old man. The transrectal prostate needle biopsy showed adenocarcinoma, a Gleason score of 4 + 3, cT1cN0M0, with prostate-specific antigen (PSA) of 7.4 ng/mL in December 2004. The patient received external beam radiation therapy (EBRT) at a total dose of 60 Gy. In January 2010, gross hematuria appeared, multiple non-papillary bladder tumors were seen by cystoscopy, and it became a diagnosis of UC, G3 and pT2 by TUR-BT. Laparoscopic radical cystectomy and ureterostomy were carried out in June 2010. Case 2: The patient was a 69-year-old man. The transrectal prostate needle biopsy showed adenocarcinoma, a Gleason score of 3 + 3, cT1cN0M0, with PSA of 7.2 ng/mL in July 2004. The patient received brachytherapy (I125) in July 2005. In June 2010, gross hematuria appeared, a papillary bladder tumor at the bladder neck, and the prostate urethra was seen by cystoscopy, and it became a diagnosis of UC, G3 and pT4a by TUR-BT. Laparoscopic radical cystectomy and removal of the urethra and the ileal conduit diversions were carried out in October 2010.
Results and Conclusions: In both cases, the adhesion of prostate surroundings was advanced, and was more difficult than usually identification and the peeling off an anatomy layer. In particular, in case 2 after brachytherapy treatment, although the prostate apex and the rectum adhered strongly, the layer of peeling was able to be confirmed under looking straight by using the laparoscope, and the operation was able to be completed safely. Though, the operation after the radiation therapy in the pelvis was assumed that the risk such as the rectum injury was high so far, enough stripped layer was able to be observed in the operation using the laparoscope, and utility was suggested as one of the treatment choices.
Frequency of tumor recurrence is a strong predictor of stage progression in initially diagnosed non-muscle invasive bladder cancers
Nobuyuki Tanaka, Eiji Kikuchi, Kazuhiro Matsumoto, Akira Miyajima, Ken Nakagawa and Mototsugu Oya
Objectives: Although patients with non-muscle invasive bladder cancer (NMIBC) usually experience multiple instances of tumor recurrence until stage progression occurs, few papers have estimated accurately the prognostic impact of the timing and/or pattern of tumor recurrence. Using our long-term follow-up data, we examined whether the frequency of tumor recurrence (FTR) provides additional predictive information concerning stage progression.
Methods: A total of 484 patients with initially diagnosed NMIBC were identified at our institution. Median follow up was 7.2 years. FTR was analyzed to determine if it affected subsequent stage progression.
Results: Of these patients, 40 (8.3%) experienced stage progression during follow up. Kaplan–Meier analysis according to various recurrence rates in each cut-off period after initial TUR-BT showed that patients with a recurrence rate >1/year during the first 2 years could be most strongly predicted to have subsequent stage progression (P < 0.001), whereas similar results were observed during the first 1 and 3 years. Using the defined parameter of recurrence rate >1/year during the first 2 years, multivariate analysis showed that the appearance of tumor grade 3 (P = 0.027, risk ratio 2.36), carcinoma in situ (P = 0.045, risk ratio 2.44) and a recurrence rate >1/year during the first 2 years (P < 0.001, risk ratio 7.40) were independent risk factors for subsequent stage progression. The 10-year progression-free survival rate was 58.0% in patients with a recurrence rate of 1 or more per year during the first 2 years and 93.3% in their counterparts (P < 0.001).
Conclusions: FTR is a strong predictor of subsequent stage progression in patients initially diagnosed with NMIBC. More appropriate follow up and aggressive treatment as a result of a higher malignant potential for stage progression might be recommended in patients with a recurrence rate of >1/year during the first 2 years.
TUR-BT of T1G3 bladder cancer
Gen Ishii, Jun Miki, Ryuji Tabata, Takahiro Kimura and Shin Egawa
Objectives: To evaluate the pathological outcome of second transurethral resection (TUR) in primitive T1G3 bladder cancer.
Methods: From October 2007 to December 2010, 15 patients had second TUR in 4–10 weeks after being diagnosed with T1G3 urothelial carcinoma in an initial TUR. All patients believed complete resection at first resection were selected.
Results: Of the 15 patients, 7 (47%) had residual tumor and especially 5 (33.3%) was presented T1G3 at second TUR. 8 patients finding no residual tumor was treated by intravescial BCG, and now no evidence of recurrence. Four patients with residual tumor was underwent early radical cystectm following second TUR, and pathological finding was upstaging in 3 (75%), and one patient (25%) had lymphnode metastasis.
Conclusions: Second TUR is the standard option for high-grade superficial bladder cancer. Upstaging is found in 75% of early radical cystectomies of T1G3 carried out in our hospital, therefore early cystectomy should be considered in the high-risk group of T1G3 bladder cancer.
Development and external validation of a nomogram for predicting the stone-free rate after SWL for single stone performed with Dornier HM-3
Koji Kawamura, Shinichi Sakamoto, Takanobu Utsumi, Takashi Imamoto, Naoki Nihei and Tomohiko Ichikawa
Objectives: Although SWL is established as a standard therapy for urinary stones, there are few studies of predictive models, such as nomograms predicting the treatment results. In the present study, we developed and externally validated the novel nomogram predicting the stone-free rate after SWL for single stone carried out with Dornier HM-3.
Methods: We developed the nomogram using the dataset of 1982 patients operated on with Dornier HM-3 at the Funabashi Clinic. Age, stone size and location were independent predictors of stone-free rate and used for this nomogram. For study validation, 20% of these data were randomly reserved. Logistic regression analysis estimated relative risk, 95% confidence intervals and P-values. In addition, this predictive model was externally validated in two different cohorts from the Funabashi clinic (n = 239) in which SWL was carried out with Phillips LDM and Aoba Hospital (n = 208) in which SWL was carried out with Siemens Lithostar Multiline. Furthermore, the predictive accuracy quantified with, based on the receiver–operator characteristic (ROC) curve-derived area under the curve (AUC), was compared directly.
Results: The AUC was significantly higher for the model (0.7228) than for each variable alone (location 0.6300, size 0.6600, age 0.5939). According to external validation, our nomogram could achieve excellent predictive accuracy for the Dornier HM-3 cohort (0.7733). However, inadequate accuracies were achieved for the patients treated with Phillips LDM and Siemens Lithostar Multiline (0.6687, 0.6113). The calibration plot gave an ideal plotting in the Dornier HM-3 cohort. On the contrary, the calibration gave an overestimation as compared with actual probability in Phillips LDM and Siemens Lithostar Multiline cohort.
Conclusions: This nomogram could predict a more precise stone-free rate for individual patients than each single variable, and achieved excellent predictive accuracy for patients treated with Dornier HM-3. However the predictive accuracy was inadequate with the other kind of machine. These results suggest that a SWL nomogram might be needed for each kind of SWL machine.