Details of a Researcher - Tanaka, Nobuyuki

Papers - Tanaka, Nobuyuki

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Refraining from Smoking for 15 Years or More Reduced the Risk of Tumor Recurrence in Non-muscle Invasive Bladder Cancer Patients

Ogihara, Koichiro, Kikuchi, Eiji, Yuge, Kazuyuki, Ito, Yujiro, Tanaka, Nobuyuki, Matsumoto, Kazuhiro, Miyajima, Akira, Asakura, Hirotaka, Oya, Mototsugu

ANNALS OF SURGICAL ONCOLOGY 23 ( 5 ) 1752 - 1759 2016.05

Research paper (scientific journal), ISSN 1068-9265

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Relationship Between Increased Expression of the Axl/Gas6 Signal Cascade and Prognosis of Patients with Upper Tract Urothelial Carcinoma

Hattori, Seiya, Kikuchi, Eiji, Kosaka, Takeo, Miyazaki, Yasumasa, Tanaka, Nobuyuki, Miyajima, Akira, Mikami, Shuji, Oya, Mototsugu

ANNALS OF SURGICAL ONCOLOGY 23 ( 2 ) 663 - 670 2016.02

Research paper (scientific journal), ISSN 1068-9265

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Impact of Second-Line Targeted Therapy Dose Intensity on Patients With Metastatic Renal Cell Carcinoma

Shirotake Suguru, Yasumizu Yota, Ito Keiichi, Masunaga Ayako, Ito Yujiro, Miyazaki Yasumasa, Hagiwara Masayuki, Kanao Kent, Mikami Shuji, Nakagawa Ken, Momma Tetsuo, Masuda Takeshi, Asano Tomohiko, Oyama Masafumi, Tanaka Nobuyuki, Mizuno Ryuichi, Oya Mototsugu

Clinical Genitourinary Cancer 2016.01

Research paper (scientific journal), ISSN 1558-7673

Background: Relative dose intensity (RDI) is a simple index for evaluation of the amount of drug administered per unit time. We retrospectively investigated the prognostic impact of RDI for patients with metastatic renal cell carcinoma (mRCC) treated with second-line targeted therapy. Methods: We enrolled 168 patients with mRCC. We assessed RDI at 4 weeks after second-line targeted therapy induction. Results: The median follow-up after second-line targeted therapy was 18.1 months. The median time-to-treatment-failure (TTF) and overall survival (OS) were 4.9 and 25.4 months, respectively. In the Kaplan-Meier analysis, the median OS of patients with second-line RDI <0.7 was significantly shorter than those with RDI ≥ 0.7 (12.1 vs. 31.3 months; P = .030). In the subgroup analysis, second-line RDI was definitely prognostic in the poor-risk group of the International Metastatic Renal Cell Carcinoma Database Consortium criteria, showing second-line RDI was an independent predictor for both TTF (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.6-8.0; P = .002) and OS (HR, 3.1; 95% CI, 1.1-8.4; P = .026). Also, assessing the type of second-line regimen, the multivariate analysis showed that second-line RDI was an independent prognostic indicator of TTF (HR, 1.7; 95% CI, 1.0-2.9; P = .040) and OS (HR, 2.7; 95% CI, 1.3-5.7; P = .009) in patients treated with everolimus. In this group, the median TTF and OS of patients with RDI <0.7 were 2.4 and 11.1 months, and those with RDI ≥ 0.7 were 5.3 and 25.9 months, respectively. Conclusion: The results suggest that second-line RDI may be a prognostic predictor for patients with mRCC treated with second-line targeted therapy, particularly in both the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and everolimus-treated group.

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Are the Formulas Used to Estimate Renal Function Adequate for Patients Treated With Cisplatin-Based Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Carcinoma?

Niwa Naoya, Kikuchi Eiji, Masashi Matsushima, Tanaka Nobuyuki, Nishiyama Toru, Miyajima Akira, Saito Shiro, Oya Mototsugu

Clinical Genitourinary Cancer 2015.12

Research paper (scientific journal), ISSN 1558-7673

Objective: The relationship between endogenous creatinine clearance (eCrCl) and renal function values obtained using mathematical formulas has not yet been fully elucidated, especially in patients with upper tract urothelial carcinoma that are treated with radical nephroureterectomy followed by cisplatin-based chemotherapy. Methods: Sixty patients who received cisplatin-based chemotherapy for locally advanced or metastatic upper tract urothelial carcinoma after radical nephroureterectomy between 2000 and 2012 were retrospectively identified. eCrCl was measured based on 24-hour urine specimens obtained immediately prior to each cycle of chemotherapy. Renal function was estimated with 4 different formulas: the Cockcroft-Gault, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, and Wright formulas. We evaluated the relationship between eCrCl and the renal function values obtained with each formula using the Pearson correlation coefficient and κ statistics. Results: The median eCrCl was 53.9 mL/min. The Pearson correlation coefficients and κ statistics for the relationships between eCrCl and the renal function values obtained with each of the mathematical formulas ranged from 0.600 to 0.763 and from 0.29 to 0.67, respectively. Among the patients with eCrCl of ≥ 60 mL/min, 70%, 60%, 50%, and 20% were estimated to have the renal function values of <60 mL/min by the Cockcroft-Gault, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, and Wright formulas, respectively. Conclusions: All 4 of the tested formulas underestimated eCrCl. The values obtained with the Wright formula were most closely associated with eCrCl.

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Nicotine induces tumor growth and chemoresistance through activation of the PI3K/Akt/mTOR pathway in bladder cancer

Yuge Kazuyuki, Kikuchi Eiji, Hagiwara Masayuki, Yasumizu Yota, Tanaka Nobuyuki, Kosaka Takeo, Miyajima Akira, Oya Mototsugu

Molecular Cancer Therapeutics 14 ( 9 ) 2112 - 2120 2015.09

Research paper (scientific journal), ISSN 1535-7163

Continued smoking is highly associated with not only a higher incidence but also greater risk of tumor recurrence, progression, and acquired chemoresistance of urothelial carcinoma. We investigated whether nicotine affects urothelial carcinoma, and the detailed mechanism by which nicotine could induce tumor growth and any associated chemoresistance. Cell viability was evaluated in the human bladder cancer cell line T24 exposed to nicotine with or without cisplatin (CDDP) and NVP-BEZ235 as a PI3K/mTOR dual inhibitor by the WST-1 assay. Protein expression of the PI3K/Akt/mTOR pathway was investigated by Western blotting or immunohistochemical analysis. The influence of nicotine on tumor growth was also evaluated with or without CDDP and/or NVP-BEZ235 in a subcutaneous bladder tumor model. The result demonstrated that cell proliferation was increased in T24 cells after exposure to nicotine. Phospho-specific Akt (pAkt) and phospho-specific p70 S6 kinase (pS6) were significantly upregulated by nicotine exposure. Tumor growth in vivo was significantly induced by nicotine exposure in accordance with increased pS6 expression. Nicotine attenuated inhibition of T24 cell growth by CDDP and further upregulated pS6 expression in vitro and in vivo. NVP-BZE235 inhibited T24 cell proliferation and pAkt and pS6 expression induced after exposure to nicotine and/or CDDP. In conclusion, nicotine increases tumor growth and induces acquired chemoresistance through activation of the PI3K/Akt/mTOR pathway in bladder cancer.

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Comparison of outcomes between ultrasonography and cystoscopy in the surveillance of patients with initially diagnosed TaG1-2 bladder cancers: A matched-pair analysis

Niwa, Naoya, Matsumoto, Kazuhiro, Hayakawa, Nozomi, Ito, Yujiro, Maeda, Takahiro, Akatsuka, Seiya, Masuda, Takeshi, Nakamura, So, Tanaka, Nobuyuki

UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS 33 ( 9 ) E13 - E13 2015.09

Research paper (scientific journal), ISSN 1078-1439

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Impact of Combined Use of Blood-based Inflammatory Markers on Patients with Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy

Tanaka Nobuyuki, Kikuchi Eiji, Kanao Kent, Matsumoto Kazuhiro, Shirotake Suguru, Miyazaki Yasumasa, Kobayashi Hiroaki, Kaneko Gou, Hagiwara Masayuki, Ide Hiroki, Obata Jun, Hoshino Katsura, Hayakawa Nozomi, Kosaka Takeo, Hara Satoshi, Nakagawa Ken, Jinzaki Masahiro, Oya Mototsugu

European Urology Focus 1 ( 1 ) 54 - 63 2015.08

Research paper (scientific journal)

Background: Previous studies showed the prognostic impact of preoperative levels of neutrophil-to-lymphocyte ratio (NLR), plasma fibrinogen, and serum C-reactive protein (CRP) in surgically treated upper tract urothelial carcinoma; however, few papers have discussed the proper use of these indices. Objective: To investigate whether combinations of these three markers, as a cumulative marker score (CMS), improve the accuracy of prognostic models following radical nephroureterectomy (RNU). Design, setting, and participants: A total of 394 patients from multiple institutions were included. Median follow-up was 30 mo. Intervention: All patients underwent RNU without neoadjuvant chemotherapy. Outcome measurements and statistical analysis: Associated outcomes were assessed using multivariate analysis. The CMS was defined as the number of elevated levels of preoperative NLR, plasma fibrinogen, and serum CRP. Results and limitations: Multivariate analyses revealed that an increasing CMS was independently associated with high rates of disease recurrence, cancer-specific mortality, and all-cause mortality following RNU. Addition of the CMS to a model that included standard clinicopathologic predictors significantly improved predictive accuracy by 2.7% for disease recurrence, 3.9% for cancer-specific mortality, and 4.0% for all-cause mortality, which were the highest among other prognostic models using each marker alone or combinations of two. The study is limited by its retrospective nature. Conclusions: Although the use of each inflammatory marker alone may be as predictive as clinicopathologic indices for prognosis, combinations like CMS can provide more accurate prognostic models following RNU. Patient summary: Elevation of blood-based inflammatory markers may be useful for predicting prognosis because of their low cost and accessibility. Among blood-based indices, we examined the efficacy of preoperative neutrophil-to-lymphocyte ratio, plasma fibrinogen, and serum C-reactive protein levels. Although use of each marker alone provides additional prognostic information, the combination of all three markers would be more predictive than any single marker or combinations of two.

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Impact of an Adjuvant Chemotherapeutic Regimen on the Clinical Outcome in High Risk Patients with Upper Tract Urothelial Carcinoma: A Japanese Multi-Institution Experience

Shirotake, Suguru, Kikuchi, Eiji, Tanaka, Nobuyuki, Matsumoto, Kazuhiro, Miyazaki, Yasumasa, Kobayashi, Hiroaki, Ide, Hiroki, Obata, Jun, Hoshino, Katsura, Kaneko, Gou, Hagiwara, Masayuki, Kosaka, Takeo, Kanao, Kent, Kodaira, Kiichiro, Hara, Satoshi, Oyama, Masafumi, Momma, Tetsuo, Miyajima, Akira, Nakagawa, Ken, Hasegawa, Shintaro, Nakajima, Yosuke, Oya, Mototsugu

JOURNAL OF UROLOGY 193 ( 4 ) 1122 - 1128 2015.04

Research paper (scientific journal), ISSN 0022-5347

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Down-regulation of NF kappa B activation is an effective therapeutic modality in acquired platinum-resistant bladder cancer

Ito, Yujiro, Kikuchi, Eiji, Tanaka, Nobuyuki, Kosaka, Takeo, Suzuki, Eriko, Mizuno, Ryuichi, Shinojima, Toshiaki, Miyajima, Akira, Umezawa, Kazuo, Oya, Mototsugu

BMC CANCER 15 2112 - 2120 2015.04

Research paper (scientific journal), ISSN 1471-2407

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Prognostic Impact of Renin–Angiotensin System Blockade on Renal Cell Carcinoma After Surgery

Miyajima Akira, Yazawa Satoshi, Kosaka Takeo, Tanaka Nobuyuki, Shirotake Suguru, Mizuno Ryuichi, Kikuchi Eiji, Oya Mototsugu

Annals of Surgical Oncology 22 ( 11 ) 3751 - 3759 2015.02

Research paper (scientific journal), ISSN 1068-9265

Background: Angiotensin 2 is a key biologic peptide in the renin–angiotensin system (RAS) that regulates blood pressure and renal hemodynamics. The potential role of the RAS in the promotion of tumor growth, angiogenesis, and metastasis also has been shown in the past few decades. This study investigated the prognostic impact of RAS blockade on patients with renal cell carcinoma (RCC) after surgery. Methods: The study identified 557 patients with pathologically diagnosed RCC (pT1-4 N0M0) and evaluated the prognostic factors after surgery for patients administered or not administered angiotensin-converting enzyme inhibitors (ACEs) or angiotensin 2 receptor blockers (ARBs). Results: The median follow-up period was 5.1 years. Radical nephrectomy was performed for 349 patients (62.7 %), whereas the remaining 208 patients (37.3 %) underwent partial nephrectomy. A total of 104 patients (18.7 %) were administered RAS inhibitors: ACEs (n = 22) or ARBs (n = 82). Multivariate analysis showed that administration of RAS inhibitors (P = 0.044; HR 2.69), longer tumor length (P < 0.001; HR 1.02), high-grade tumor (P < 0.001; HR 3.55), and positive microvascular invasion (P < 0.003; HR 3.13) were not independent risk factors for a decrease in subsequent disease-specific survival after surgery for RCC. The 5-year disease-specific survival rate was 96.8 % among the patients administered RAS inhibitors and 89.8 % among their counterparts (P = 0.019). Conclusions: The authors propose renin–angiotensin blockade as a possible potent choice for effective treatment after surgical treatment of RCC.

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A Multi-Institutional Validation of the Prognostic Value of the Neutrophil-to-Lymphocyte Ratio for Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy

Tanaka, Nobuyuki, Kikuchi, Eiji, Kanao, Kent, Matsumoto, Kazuhiro, Shirotake, Suguru, Miyazaki, Yasumasa, Kobayashi, Hiroaki, Kaneko, Gou, Hagiwara, Masayuki, Ide, Hiroki, Obata, Jun, Hoshino, Katsura, Hayakawa, Nozomi, Kosaka, Takeo, Hara, Satoshi, Oyama, Masafumi, Momma, Tetsuo, Nakajima, Yosuke, Jinzaki, Masahiro, Oya, Mototsugu

ANNALS OF SURGICAL ONCOLOGY 21 ( 12 ) 4041 - 4048 2014.11

Research paper (scientific journal), ISSN 1068-9265

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Ductal Adenocarcinoma of the Prostate Forming a Mass in the Retrovesical Space

Niwa, Naoya, Tanaka, Nobuyuki, Horinaga, Minoru, Hayashi, Yuichiro, Hisazumi, Hiromi, Masuda, Takeshi

UROLOGY 84 ( 4 ) E9 - E10 2014.10

Research paper (scientific journal), ISSN 0090-4295

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Independent Predictors for Bladder Outcomes after Treatment of Intravesical Recurrence following Radical Nephroureterectomy in Patients with Primary Upper Tract Urothelial Carcinoma

Tanaka, Nobuyuki, Kikuchi, Eiji, Kanao, Kent, Matsumoto, Kazuhiro, Shirotake, Suguru, Kobayashi, Hiroaki, Miyazaki, Yasumasa, Ide, Hiroki, Obata, Jun, Hoshino, Katsura, Hayakawa, Nozomi, Hagiwara, Masayuki, Kosaka, Takeo, Oyama, Masafumi, Miyajima, Akira, Momma, Tetsuo, Nakagawa, Ken, Jinzaki, Masahiro, Hasegawa, Shintaro, Nakajima, Yosuke, Oya, Mototsugu

ANNALS OF SURGICAL ONCOLOGY 21 ( 9 ) 3151 - 3158 2014.09

Research paper (scientific journal), ISSN 1068-9265

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Optimal timing of hormonal therapy for prostate-specific antigen recurrence after radical prostatectomy

Matsumoto, Kazuhiro, Mizuno, Ryuichi, Tanaka, Nobuyuki, Ide, Hiroki, Hasegawa, Masanori, Ishida, Masaru, Hayakawa, Nozomi, Yasumizu, Yota, Hagiwara, Masayuki, Hara, Satoshi, Kikuchi, Eiji, Miyajima, Akira, Nakagawa, Ken, Nakajima, Yosuke, Nakamura, So, Nakashima, Jun, Oya, Mototsugu

MEDICAL ONCOLOGY 31 ( 7 ) 2019 - 2020 2014.07

Research paper (scientific journal), ISSN 1357-0560

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Survival following primary androgen deprivation therapy for localized intermediate- or high-risk prostate cancer: comparison with the life expectancy of the age-matched normal population

Matsumoto, Kazuhiro, Hagiwara, Masayuki, Tanaka, Nobuyuki, Hayakawa, Nozomi, Ishida, Masaru, Ninomiya, Akiharu, Nakajima, Yosuke, Nakamura, So

MEDICAL ONCOLOGY 31 ( 6 ) 3645 - 3649 2014.06

Research paper (scientific journal), ISSN 1357-0560

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Metastatic Behavior of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: Association with Primary Tumor Location

Tanaka, Nobuyuki, Kikuchi, Eiji, Kanao, Kent, Matsumoto, Kazuhiro, Kobayashi, Hiroaki, Ide, Hiroki, Miyazaki, Yasumasa, Obata, Jun, Hoshino, Katsura, Shirotake, Suguru, Akita, Hirotaka, Kosaka, Takeo, Miyajima, Akira, Momma, Tetsuo, Nakagawa, Ken, Hasegawa, Shintaro, Nakajima, Yosuke, Jinzaki, Masahiro, Oya, Mototsugu

ANNALS OF SURGICAL ONCOLOGY 21 ( 3 ) 1038 - 1045 2014.03

Research paper (scientific journal), ISSN 1068-9265

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Long term follow-up in patients with initially diagnosed low grade Ta non-muscle invasive bladder tumors

Kobayashi Hiroaki, Kikuchi Eiji, Mikami Shuji, Maeda Takahiro, Tanaka Nobuyuki, Miyajima Akira, Nakagawa Ken, Oya Mototsugu

BMC Urology 14 ( 1 ) 2014.01

Research paper (scientific journal)

Background: We evaluated the clinical outcome of low grade Ta bladder cancer followed-up for a long period using the 2004 WHO grading system. Methods. We retrospectively reviewed 190 patients with primary, low grade Ta bladder cancer. We defined worsening progression (WP) as confirmed high grade Ta, all T1 or Tis/concomitant CIS of bladder recurrence, upper urinary tract recurrence (UTR), or progression to equal to or more than T2. The associations between clinicopathological factors and tumor recurrence as well as WP pattern were analyzed. We also evaluated the late recurrence of 76 patients who were tumor-free for more than 5 years. Results: Tumor recurrence and WP occurred in 82 (43.2%) and 21 (11.1%) patients during follow-up (median follow-up: 101.5 months), respectively. WP to high grade Ta, all T1 or Tis/concomitant CIS was seen in 17 patients, and UTR and progression to equal to or more than T2 were seen in 2 and 2 patients, respectively. Multivariate analyses demonstrated that multiple tumor (p < 0.001, HR: 2.97) and absence of intravesical instillation (IVI) (p < 0.001, HR: 2.88) were significant risk factors for tumor recurrence while multiple tumor was the only risk factor for WP (p = 0.001, HR: 5.26). After a 5-year tumor-free period, 9 patients experienced late recurrence in years 5 and 10 and were diagnosed at a follow-up cystoscopy, however, only 2 patients recurred beyond 10 years and were found by gross hematuria. There were no significant risk factors of late recurrence. Conclusions: Multiple tumor was a risk factor for both tumor recurrence and WP while IVI did not affect the occurrence of WP. Our results suggest that routine follow-up of patients with low grade Ta bladder cancer is needed up to 10 years from the initial diagnosis.

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The Predictive Value of C-reactive Protein for Prognosis in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy: A Multi-institutional Study

Tanaka, Nobuyuki, Kikuchi, Eiji, Shirotake, Suguru, Kanao, Kent, Matsumoto, Kazuhiro, Kobayashi, Hiroaki, Miyazaki, Yasumasa, Ide, Hiroki, Obata, Jun, Hoshino, Katsura, Hayakawa, Nozomi, Ito, Yujiro, Kosaka, Takeo, Kodaira, Kiichiro, Oyama, Masafumi, Miyajima, Akira, Momma, Tetsuo, Nakagawa, Ken, Ueno, Munehisa, Oya, Mototsugu

EUROPEAN UROLOGY 65 ( 1 ) 227 - 234 2014.01

Research paper (scientific journal), ISSN 0302-2838

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The predictive value of positive urine cytology for outcomes following radical nephroureterectomy in patients with primary upper tract urothelial carcinoma: A multi-institutional study

Tanaka, Nobuyuki, Kikuchi, Eiji, Kanao, Kent, Matsumoto, Kazuhiro, Shirotake, Suguru, Kobayashi, Hiroaki, Miyazaki, Yasumasa, Ide, Hiroki, Obata, Jun, Hoshino, Katsura, Hayakawa, Nozomi, Kosaka, Takeo, Oyama, Masafumi, Miyajima, Akira, Momma, Tetsuo, Nakagawa, Ken, Jinzaki, Masahiro, Nakajima, Yosuke, Oya, Mototsugu

UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS 32 ( 1 ) E229 - E230 2014.01

Research paper (scientific journal), ISSN 1078-1439

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Survival following primary androgen deprivation therapy for localized intermediate- Or high-risk prostate cancer

Matsumoto Kazuhiro, Hagiwara Masayuki, Tanaka Nobuyuki, Hayakawa Nozomi, Ishida Masaru, Ninomiya Akiharu, Nakajima Yosuke, Nakamura So

Medical Oncology 31 ( 6 ) 2014

Research paper (scientific journal), ISSN 1357-0560

The representative guidelines do not recommend androgen deprivation therapy (ADT) as a primary treatment for localized prostate cancer. However, in clinical practice, the use of primary ADT for localized prostate cancer has been widespread, especially among older patients. We performed a retrospective review of the efficacy of primary ADT for localized prostate cancer and compared their outcomes with the life expectancy of the normal population. The study cohort consisted of 410 men diagnosed with localized intermediate- or high-risk prostate cancer over the period 1992-2012 at five institutions. All patients underwent ADT as a primary cancer therapy, and mean follow-up was 6.0 years. Their progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) rates were calculated. Patients' expected survival rates were estimated by the Hakulinen method. Multivariate analysis demonstrated that Gleason score ≥8 and cT3a were independent risk factors for all of PFS, CSS, and OS. In patients who have none or one of these risk factors, minimum OS rates were not inferior to the expected survival curves of the normal population. Meanwhile, in patients with both risk factors, the OS curve fell below the expected survival rates, especially after 6 years of follow-up. We conclude that primary ADT might be one of the therapeutic options for localized intermediate- and high-risk prostate cancer. However, for high-risk cases with Gleason score ≥8 and cT3a, the choice of primary ADT should be deliberated carefully because the OS of these cases was inferior to the expected survival, especially at a late time point.

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