Papers

• Comparative study of lymph node dissection, and oncological outcomes of laparoscopic and open radical nephroureterectomy for patients with urothelial carcinoma of the upper urinary tract undergoing regional lymph node dissection.
  Takashige Abe, Tsunenori Kondo, Toru Harabayashi, Norikata Takada, Ryuji Matsumoto, Takahiro Osawa, Keita Minami, Satoshi Nagamori, Satoru Maruyama, Sachiyo Murai, Kazunari Tanabe, Nobuo Shinohara
  Japanese journal of clinical oncology, 48, 11, 1001, 1011, 01 Nov. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Objective: To assess the number of lymph nodes removed as a surrogate marker of the extent of lymph node dissection, and compare survival outcomes between laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) in patients undergoing standardized lymph node dissection. Methods: We retrospectively analyzed the data of 214 cTanyN0M0 patients undergoing radical NU with regional lymph node dissection according to the tumor location. The Kaplan-Meier method and Cox hazards model were utilized for survival analyses, including recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Results: A total of 114 patients underwent LRNU and 100 underwent ORNU. There was no significant difference in the pT stage, pN stage, or tumor grade, but distal ureteral tumors were more frequent in the LRNU group. The number of lymph nodes removed did not differ between the two groups [LRNU: 12 (median), ORNU: 11.5, P = 0.3852]. Lymph node metastasis was pathologically identified in 19 patients (8.9%). The 5-year RFS (ORNU: 71.7%, LRNU: 74%, P = 0.7829), CSS (77.8 and, 80%, P = 0.8441) and OS (72.8, and 75.9%, P = 0.3456) did not differ between the two groups. In the sub-analysis of pT3/4 patients (n = 83), there were no significant differences in RFS, CSS, or OS between the two groups, although Kaplan-Meier survival curves were slightly better for those receiving ORNU. In the multivariate model, LRNU was not significantly correlated with a poorer RFS, CSS or OS. Conclusion: Our data support the feasibility of lymph node dissection with a laparoscopic approach and the equivalent oncological outcome of LRNU compared with ORNU when regional lymph node dissection is performed. However, LRNU should be performed after careful patient selection for advanced disease.
• Outcome and prognostic factors in metastatic urothelial carcinoma patients receiving second-line chemotherapy: an analysis of real-world clinical practice data in Japan.
  Ryuji Matsumoto, Takashige Abe, Junji Ishizaki, Hiroshi Kikuchi, Toru Harabayashi, Keita Minami, Ataru Sazawa, Tango Mochizuki, Tomoshige Akino, Masashi Murakumo, Takahiro Osawa, Satoru Maruyama, Sachiyo Murai, Nobuo Shinohara
  Japanese journal of clinical oncology, 48, 8, 771, 776, 01 Aug. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Objectives: The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Methods: Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan-Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. Results: The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. Conclusions: The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.
• Validation of the nomogram for predicting 90-day mortality after radical cystectomy in a Japanese cohort.
  Osawa T, Abe T, Takada N, Ito YM, Murai S, Shinohara N
  International journal of urology : official journal of the Japanese Urological Association, 25, 7, 699, 700, Jul. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Characteristics of Medical Adverse Events/Near Misses Associated With Laparoscopic/Thoracoscopic Surgery: A Retrospective Study Based on the Japanese National Database of Medical Adverse Events.
  Abe T, Murai S, Nasuhara Y, Shinohara N
  Journal of patient safety, 15, 4, 343, 351, Sep. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal, OBJECTIVES: The aim of this study was to clarify the characteristics of adverse events/near misses during laparoscopic/thoracoscopic surgery. METHODS: Using relevant key words for minimally invasive surgeries, 540 records were identified in the database of the Japan Council for Quality Health Care. After data review and the classification of adverse events, 746 events associated with laparoscopic (laparo group) and/or thoracoscopic (thoraco group) surgery were identified. We calculated the frequency of each event, compared the frequency regarding recurrent events, and evaluated the types of event that had resulted in deaths between the 2 groups. RESULTS: There were 582 events in the laparo group, 159 in the thoraco group, and 5 in those undergoing combined surgery. Overall, injury of other organs (11.4%, 85/746), retention of a foreign body (9.1%, 68/746), breakage/failure of medical equipment or devices (6.2%, 46/746), massive bleeding (5.9%, 44/746), misperception of anatomy (5.6%, 42/746), and vascular injury (4.8%, 36/746) were frequently reported. There were marked differences in the frequency of injury of other organs (laparo group: 13.4%, 78/582; thoraco group: 4.4%, 7/159), massive bleeding (laparo group: 3.4%, 20/582; thoraco group: 14.5%, 23/159), and vascular injury (laparo group: 2.6%, 15/582; thoraco group: 12.6%, 20/159) between the 2 groups. Among the 56 patient-death reports, 132 adverse events were identified. In the thoraco group, bleeding events were frequently observed, whereas in the laparo group, various categories of events were noted. CONCLUSIONS: We observed recurrent incidents and differences in the frequency between the 2 groups. Surgeons should keep in mind these characteristics. Retention of a foreign body and the breakage/malfunctioning of instruments might be reduced by the introduction of specialized checklists.
• Perioperative morbidity and mortality of octogenarians treated by radical cystectomy-a multi-institutional retrospective study in Japan.
  Takashige Abe, Norikata Takada, Hiroshi Kikuchi, Ryuji Matsumoto, Takahiro Osawa, Sachiyo Murai, Naoto Miyajima, Satoru Maruyama, Nobuo Shinohara
  Japanese journal of clinical oncology, 47, 8, 755, 761, 01 Aug. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Objective: To determine the characteristics of 90-day morbidity and mortality after radical cystectomy in Japanese octogenarians. Methods: A retrospective multi-institutional study. We reviewed the records of 834 patients treated by open radical cystectomy between 1997 and 2010. All complications within 90 days after surgery were sorted into the 11 categories proposed by the Memorial Sloan-Kettering Cancer Center and graded according to the modified Clavien-Dindo system. We compared the characteristics of complications between ≥80-year (n = 86) and <80-year (n = 748) groups. Multivariate regression models were used to determine the predictors of complications. Results: American Society of Anesthesiologists score III-IV was more frequent (14% vs. 6%, respectively, P < 0.0001), and ureterocutaneostomy was more frequently performed (30% vs. 21%, respectively, P = 0.0148) in the ≥80-year group compared with <80-year group. There were no significant differences in the rates of any complication, major (Grade 3-5) complication, or 90-day mortality between the two groups (≥80-year group: 70%, 21%, 3.5%, respectively, <80-year group: 68%, 22%, 2%, respectively). The ≥80-year group had fewer genitourinary complications (7% vs. 16%, respectively, P = 0.0131). Multivariate regression analyses revealed that bowel-using urinary diversion (P = 0.0031) and the operative time (P = 0.0269) were significant predictors of any grade of complications, and a male sex (P = 0.0167), annual cystectomy volume (P = 0.0284) and prior cardiovascular comorbidity (P = 0.0034) were significant predictors of major complications. Conclusions: In our experience, radical cystectomy in Japanese octogenarians caused similar perioperative comorbidities. Old age as a single criterion should not be used to abandon radical cystectomy; careful preoperative assessment is mandatory.
• Outcome of metastatic urothelial carcinoma treated by systemic chemotherapy: Prognostic factors based on real-world clinical practice in Japan.
  Takashige Abe, Junji Ishizaki, Hiroshi Kikuchi, Keita Minami, Ryuji Matsumoto, Toru Harabayashi, Ataru Sazawa, Tango Mochizuki, Satoshi Chiba, Tomoshige Akino, Masashi Murakumo, Naoto Miyajima, Kunihiko Tsuchiya, Satoru Maruyama, Sachiyo Murai, Nobuo Shinohara
  Urologic oncology, 35, 2, 38.e1-38.e8, 38.e8, Feb. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIM: To clarify prognostic factors of metatstatic urothelial carcinoma treated by systemic chemotherapy in real-world clinical practice in the Japanese population. MATERIALS AND METHODS: A total of 228 patients with metastatic urothelial carcinoma undergoing systemic chemotherapy between 2000 and 2013 were included in the present multi-institutional study. The gemcitabine plus cisplatin regimen was administered as first-line chemotherapy to 131 patients, whereas methotrexate, vinblastine, doxorubicin, and cisplatin or its modified regimen was given to 71 patients. Of the 228 patients, 119 received at least 2 different regimens and 22 underwent resection of metastases (metastasectomy). Multivariate survival analysis was performed using the Cox proportional hazards model. The characteristics included were age, sex, Eastern Cooperative Oncology Group performance status (PS), primary site, pathology of primary site, hemoglobin levels, lactate dehydrogenase levels, C-reactive protein levels, corrected calcium levels, estimated glomerular filtration rate levels, history of prior chemotherapy, metastatic sites, resection of primary site, number of metastatic organs, and metastasectomy. RESULTS: The median overall survival (OS) time was 17 months. On multivariate analysis, female sex, good Eastern Cooperative Oncology Group PS at presentation, hemoglobin level≥10g/dl, and single organ metastasis were significant independent predictors of prolonged OS. For the survival effect of metastasectomy, the median OS time of the 22 patients with metastasectomy was 53 months, which was significantly longer when compared with patients not undergoing metastasectomy (15mo). After adjustment for the 4 aforementioned prognostic factors, metastasectomy still remained significant (hazard ratio: 0.364, P = 0.0008). CONCLUSIONS: Female sex, more favorable PS at presentation, hemoglobin level>10g/dl, and single organ metastasis were favorable prognostic factors. In addition, metastasectomy was associated with long-term disease control.
• A Multi-Center International Study Assessing the Impact of Differences in Baseline Characteristics and Perioperative Care Following Radical Cystectomy.
  Osawa T, Lee CT, Abe T, Takada N, Hafez KS, Montgomery JS, Weizer AZ, Hollenbeck BK, Skolarus TA, Murai S, Shinohara N, Morgan TM
  Bladder cancer (Amsterdam, Netherlands), 2, 2, 251, 261, Apr. 2016, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Background: To identify potential avenues for quality improvement, we compared the variations in clinical practice and their association with perioperative morbidity and mortality following radical cystectomy (RC) for bladder cancer in the United States (US) and Japan. Methods: We reviewed our retrospectively collected database of 2240 patients who underwent RC for bladder cancer at the University of Michigan (n = 1427) and in 21 Japanese institutions (n = 813) between 1997 and 2014. We performed a systematic comparison of clinical and perioperative factors and assessed predictors of perioperative morbidity and mortality. Death within 90 days of surgery was the primary outcome. Results: There were apparent differences between the two study populations. Notably, US patients had a significantly greater BMI and higher ASA score. In Japanese institutions, median postoperative hospital stay was significantly higher (40 days vs. 7 days, p <  0.001) and 90-day readmission rates were significantly lower (0.6% vs. 26.8% , p <  0.001). There was a total of 1372/2240 (61.2%) patients with complications within 90 days and 66/2240 (2.9%) patient deaths. Significant predictors of 90-day mortality were older age (OR 1.04, CI 1.01-1.07), higher body mass index (OR 1.07, CI 1.02-1.12), node-positive disease (OR 3.14, CI 1.78-5.47), increased blood loss (OR 1.02, CI 1.01-1.03), and major (Clavien-grade 3 or greater) complication (OR 3.29, CI 1.88-5.71). Conclusion: Despite major differences in baseline characteristics and care of cystectomy patients between the two study populations, peri-operative mortality rates proved to be comparable. This data supports an exploration of non-traditional factors that may influence mortality after cystectomy.
• Five-point Likert scaling on MRI predicts clinically significant prostate carcinoma.
  Taisuke Harada, Takashige Abe, Fumi Kato, Ryuji Matsumoto, Hiromi Fujita, Sachiyo Murai, Naoto Miyajima, Kunihiko Tsuchiya, Satoru Maruyama, Kohsuke Kudo, Nobuo Shinohara
  BMC urology, 15, 91, 91, 04 Sep. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: To clarify the relationship between the probability of prostate cancer scaled using a 5-point Likert system and the biological characteristics of corresponding tumor foci. METHODS: The present study involved 44 patients undergoing 3.0-Tesla multiparametric MRI before laparoscopic radical prostatectomy. Tracing based on pathological and MRI findings was performed. The relationship between the probability of cancer scaled using the 5-point Likert system and the biological characteristics of corresponding tumor foci was evaluated. RESULTS: A total of 102 tumor foci were identified histologically from the 44 specimens. Of the 102 tumors, 55 were assigned a score based on MRI findings (score 1: n = 3; score 2: n = 3; score 3: n = 16; score 4: n = 11 score 5: n = 22), while 47 were not pointed out on MRI. The tracing study revealed that the proportion of >0.5 cm(3) tumors increased according to the upgrade of Likert scores (score 1 or 2: 33%; score 3: 68.8%; score 4 or 5: 90.9%, χ(2) test, p < 0.0001). The proportion with a Gleason score >7 also increased from scale 2 to scale 5 (scale 2: 0%; scale 3: 56.3%; scale 4: 72.7%; 5: 90.9%, χ(2) test, p = 0.0001). On using score 3 or higher as the threshold of cancer detection on MRI, the detection rate markedly improved if the tumor volume exceeded 0.5 cm(3) (<0.2 cm(3): 10.3%; 0.2-0.5 cm(3): 25%; 0.5-1.0 cm(3): 66.7%; 1.0 < cm(3): 92.1%). CONCLUSIONS: Each Likert scale favobably reflected the corresponding tumor's volume and Gleason score. Our observations show that "score 3 or higher" could be a useful threshold to predict clinically significant carcinoma when considering treatment options.
• Prospective mapping of lymph node metastasis in Japanese patients undergoing radical cystectomy for bladder cancer: characteristics of micrometastasis.
  Ryuji Matsumoto, Norikata Takada, Takashige Abe, Keita Minami, Toru Harabayashi, Satoshi Nagamori, Kanako C Hatanaka, Naoto Miyajima, Kunihiko Tsuchiya, Satoru Maruyama, Sachiyo Murai, Nobuo Shinohara
  Japanese journal of clinical oncology, 45, 9, 874, 80, Sep. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal, OBJECTIVE: To investigate node-disease prevalence including micrometastases and its survival impact on bladder cancer patients. METHODS: A total of 60 patients participated in this study, in which extended lymph node dissection was carried out according to the prospective rule (below aortic bifurcation). Radical cystectomy and extended lymph node dissection were performed by open surgery (n = 23) or laparoscopically (n = 37). Perioperative, pathological and follow-up data were collected. Micrometastasis in lymph nodes was investigated by pan-cytokeratin immunohistochemistry. Recurrence-free survival was estimated with the Kaplan-Meier method. RESULTS: The median number of lymph nodes removed was 29 (range: 10-103) and there was no significant difference between the two groups (open group: median 30, laparoscopic group: median 29). Routine pathological examination revealed that 10 patients had lymph node metastases. Immunohistochemistry revealed micrometastases in four additional patients (pNmicro+), who had been diagnosed with pN0 on routine pathological examination. After excluding the three patients with pure nonurothelial carcinoma on the final pathology (small cell carcinoma: n = 2, adenocarcinoma: n = 1), 10 out of the 57 urothelial carcinoma patients (17.5%) had node metastasis, and an additional 4 out of the 47 pN0 patients (4/47, 8.5%) had micrometastasis. The 2-year recurrence-free survival rates divided by pN stage were 82.4% for pN0, 66.7% for pNmicro+ and 12.5% for pN+ (three-sample log-rank test, P < 0.0001). Three out of the four patients with pNmicro+ were disease free at the last follow-up. CONCLUSIONS: We confirmed under extended lymph node dissection that a substantial proportion of the patients had node metastasis (pN+: n = 10 and pNmicro+: n = 4), and the pN stage influenced patient survival. Our observations of micrometastasis yielded additional evidence for the potential survival benefit of extended lymphadenectomy by eliminating microdisease.
• Diagnostic outcome of ureteroscopy in urothelial carcinoma of the upper urinary tract: Incidence of later cancer detection and its risk factors after the first examination
  Norihiro Murahashi, Takashige Abe, Nobuo Shinohara, Sachiyo Murai, Toru Harabayashi, Ataru Sazawa, Satoru Maruyama, Kunihiko Tsuchiya, Naoto Miyajima, Kanako Hatanaka, Katsuya Nonomura
  BMC UROLOGY, 15, 92, Sep. 2015, [Peer-reviewed]
  English, Scientific journal
• Prognosis of Japanese patients with previously untreated metastatic renal cell carcinoma in the era of molecular-targeted therapy.
  Nobuo Shinohara, Wataru Obara, Katsunori Tatsugami, Sei Naito, Tomomi Kamba, Masayuki Takahashi, Sachiyo Murai, Takashige Abe, Koji Oba, Seiji Naito
  Cancer science, 106, 5, 618, 26, May 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal, A multicenter cooperative study was conducted to clarify the prognosis of Japanese patients with metastatic renal cell carcinoma in the era of molecular-targeted therapy and the clinical usefulness of the Japanese metastatic renal cancer (JMRC) prognostic classification. Of 389 consecutive patients for whom treatment was started between 2008 and 2010 at 23 hospitals in Japan, 357 patients who received vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) or cytokine as initial systemic therapy were the subject of the present study. Patients were classified into three prognostic groups according to the JMRC prognostic classification. The endpoints were progression-free survival (PFS) and overall survival (OS) after the start of the initial treatment. The median PFS and OS for the entire cohort of 357 patients were 9.1 and 27.2 months, respectively. VEGFR-TKI were selected for patients with multiple organ metastases, those with liver metastasis, and those with bone metastasis. The median PFS and OS were 11.0 and 23.2 months and 5.4 and 38.2 months in the VEGFR-TKI group and the cytokines group, respectively. The JMRC prognostic classification was useful as a prognostic model for PFS and OS (c-indexes: 0.613 and 0.630 in patients who initially received VEGFR-TKI and 0.647 and 0.642 in patients who received cytokines, respectively). The present study showed for the first time the prognosis of Japanese patients with metastatic renal cell carcinoma in the era of molecular-targeted therapy. The JMRC prognostic classification may be clinically useful as a prognostic model.
• Comparison of 90-day complications between ileal conduit and neobladder reconstruction after radical cystectomy: a retrospective multi-institutional study in Japan.
  Takashige Abe, Norikata Takada, Nobuo Shinohara, Ryuji Matsumoto, Sachiyo Murai, Ataru Sazawa, Satoru Maruyama, Kunihiko Tsuchiya, Shino Kanzaki, Katsuya Nonomura
  International journal of urology : official journal of the Japanese Urological Association, 21, 6, 554, 9, Jun. 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal, OBJECTIVE: To determine the differences in the type, incidence, and severity of 90-day morbidity after radical cystectomy between two different methods of urinary diversion, ileal conduit and neobladder. METHODS: We carried out a retrospective multi-institutional study by reviewing the records of 668 patients treated with open radical cystectomy, and ileal conduit (n = 493) or neobladder substitution (n = 175) between 1997 and 2010. All complications within 90 days after surgery were divided into 11 specific categories as reported by the Memorial-Sloan Kettering Cancer Center, and graded according to the modified Clavien system. Type, incidence and severity of the 90-day morbidity between the two different types of urinary diversions were compared. RESULTS: There was no significant difference in the overall complication rates between the two groups (ileal conduit: 72% [353/493], neobladder: 74% [129/175], P = 0.5909), whereas the neobladder group had fewer major (grade 3 or more) complications (13 vs 20%, respectively, P = 0.0271). The neobladder group had more infectious complications (43 vs 31%, respectively, P = 0.0037), mainly as a result of urinary tract infection, whereas the ileal conduit group had more wound-related complications (24 vs 14%, respectively, P = 0.0068), mainly as a result of surgical site infection. The 90-day mortality rates were 1.1% (2/175) in the neobladder group and 1.6% (8/493) in the ileal conduit group (P = 0.6441). CONCLUSIONS: There was no significant difference in the overall complication rates between the two methods, and patients with neobladder had fewer major complications. The neobladder group had more infectious complications, whereas the ileal conduit group had more wound-related complications.
• RENAL nephrometry score is a predictive factor for the annual growth rate of renal mass.
  Ryuji Matsumoto, Takashige Abe, Nobuo Shinohara, Sachiyo Murai, Satoru Maruyama, Kunihiko Tsuchiya, Katsuya Nonomura
  International journal of urology : official journal of the Japanese Urological Association, 21, 6, 549, 52, Jun. 2014, [Peer-reviewed], [International Magazine]
  English, Scientific journal, OBJECTIVE: To evaluate the association between the RENAL nephrometry score and annual growth rates of renal masses presumed to be renal cell carcinoma. METHODS: The current study included 47 renal tumors followed up for at least 12 months, of which 26 tumors were found to be pathologically proven renal cell carcinomas. Annual tumor growth rates were calculated from changes in the maximal diameter on computed tomography, and RENAL nephrometry scores were recorded on initial imaging by two senior urologists. The associations between clinical characteristics including the RENAL nephrometry score and annual growth rates were analyzed using a linear regression model. RESULTS: The median tumor size at diagnosis was 1.7 cm (range 0.6-5.8). The median nephrometry score at diagnosis was 7 (range 4-10). Overall, the median tumor growth rate was 0.34 cm per year (range -0.19-2.0). Linear regression analysis showed that the annual tumor growth rate was associated with the RENAL nephrometry score (P < 0.0001), but it was independent of the age at diagnosis, sex and initial tumor size. In addition, the correlation between the RENAL nephrometry score and annual growth rate remained significant in the 26 pathologically proven renal cell carcinomas. CONCLUSIONS: The RENAL nephrometry score is associated with the annual growth rate of renal masses. Our findings further support the association between the RENAL nephrometry score and tumor biology.
• Outcome of Metastasectomy for Urothelial Carcinoma: A Multi-Institutional Retrospective Study in Japan
  Takashige Abe, Hiroshi Kitamura, Wataru Obara, Nagahide Matsumura, Taiji Tsukamoto, Tomoaki Fujioka, Isao Hara, Sachiyo Murai, Nobuo Shinohara, Katsuya Nonomura
  JOURNAL OF UROLOGY, 191, 4, 932, 936, Apr. 2014, [Peer-reviewed]
  English, Scientific journal