Details of a Researcher - Kosaka, Takeo

Papers - Kosaka, Takeo

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Intravesical dual PI3K/mTOR complex 1/2 inhibitor NVP-BEZ235 therapy in an orthotopic bladder cancer model

Matsushima Masashi, Kikuchi Eiji, Matsumoto Kazuhiro, Hattori Seiya, Takeda Toshikazu, Kosaka Takeo, Miyajima Akira, Oya Mototsugu

International Journal of Oncology 47 ( 1 ) 377 - 383 2015.07

ISSN 1019-6439

NVP-BEZ235 is an inhibitor of both phosphati-dylinositol 3-kinase (PI3K) and mammalian target of rapamycin complex 1/2 (mTORCl/2), and its antitumor activity is expected to be higher than that of mTORCl inhibitors because it inhibits the upregulation of pAkt through mTORC2. We examined the efficacy of intravesical NVP-BEZ235 therapy in the treatment of bladder cancer using an orthotopic bladder cancer model. The cytotoxic effects of various concentrations of NVP-BEZ235 in MBT-2 cells were examined using a WST assay. The expression of pAkt, pS6 and p4EBPl was evaluated in MBT-2 cells treated with NVP-BEZ235 using western blotting. Orthotopic models were established by implanting MBT-2 cells into the bladders of female C3H/He mice. We assigned C3H/He mice to 2 groups: a control group treated with vehicle control (n=15), and a group intravesically administered 40 μM (18.78 mg/1) of NVP-BEZ235 (n=15). NVP-BEZ235 inhibited the viability of MBT-2 cells in a dose-dependent manner. Furthermore, the expression of pAkt, pS6, and p4EBPl was inhibited in NVP-BEZ235-treated MBT-2 cells. Bladder weights were significantly lower in the NVP-BEZ235-treated group than in the control group (P<0.05). An analysis of the tumor tissues revealed that the NVP-BEZ235 treatment strongly reduced pAkt, pS6 and p4EBPl levels. An immunohistochemical analysis showed that NVP-BEZ235 significantly inhibited the expression of pS6. Intravesically administered NVP-BEZ235 exerted significant antitumor effects in the orthotopic bladder cancer model by inhibiting the PI3K/Akt/mTOR pathway. The intravesical instillation of a dual PI3K/mTORC1/2 inhibitor may represent a novel therapy for the treatment of bladder cancer.

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Coincident detection of lung metastasis of prostate cancer and primary lung cancer

Muro Yusuke, Kosaka Takeo, Hato Tai, Mikami Shuji, Oya Mototsugu

Canadian Urological Association Journal 9 ( 7-8 ) E524 - E526 2015.07

ISSN 1920-1214

We report an extremely rare case of 79-year-old man, who was discovered with coincidental lung metastasis of prostate cancer and primary lung cancer. The patient presented with low prostatespecific antigen and two lung lesions: one in the right lower lobe, and one in the right upper lobe, 3 years after he was treated with external beam radiotherapy for Gleason score 4+3=7, cT3aN0M0 prostate cancer. A computed tomography-guided needle biopsy of a nodule in the right lower lobe revealed suspicious metastasis of prostate cancer. Thoracoscopic excisions of both lesions were performed, and each lung lesion was diagnosed as being metastatic prostate cancer and primary lung cancer.

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Predictive factors for severe and febrile neutropenia during docetaxel chemotherapy for castration-resistant prostate cancer

Shigeta Keisuke, Kosaka Takeo, Yazawa Satoshi, Yasumizu Yota, Mizuno Ryuichi, Nagata Hirohiko, Shinoda Kazunobu, Morita Shinya, Miyajima Akira, Kikuchi Eiji, Nakagawa Ken, Hasegawa Shintaro, Oya Mototsugu

International Journal of Clinical Oncology 20 ( 3 ) 605 - 612 2015.06

ISSN 1341-9625

Background: The aim of this study is to identify factors that increase the occurrence of severe neutropenia (SN) and febrile neutropenia (FN) during docetaxel treatment for castration-resistant prostate cancer (CRPC). Methods: We retrospectively reviewed 258 courses during the first three cycles among 95 patients. Docetaxel at a dose of 75 mg/m2 was administered every 3 or 4 weeks. Patient background, laboratory data, and bone scan results were collected to assess predictive factors for SN and FN. We defined SN as an absolute neutrophil count (ANC) of <500/mm3 and defined FN as an ANC of <1000/mm3 with a body temperature of >38.3 °C. Results: The mean age of the patients was 72.6 ± 6.4 years and the mean prostate-specific antigen was 135.4 ± 290.9 ng/ml. During the first three courses of treatment, SN occurred in 72.6 % of patients and FN occurred in 9.5 % of patients. Univariate analysis demonstrated that age ≥75 years (p = 0.002), number of comorbidities ≥1.2 (p = 0.008 and p = 0.006) and previous external beam radiation therapy (EBRT) (p = 0.001) were predictive factors for the development of SN or FN. In multivariate analysis, significant predictors of SN or FN were age ≥75 years (hazard ratio [HR] 5.77; p = 0.004) and previous EBRT (HR 14.5; p = 0.012). According to the subgroup analysis dividing SN and FN separately, multivariate analysis also revealed that age ≥75 years and previous EBRT were also significant predictors for developing SN (HR 5.09; p = 0.023, HR 12.7; p = 0.020, respectively) and for developing FN (HR 5.45; p = 0.042, HR 7.72; p = 0.015, respectively). Conclusions: Patients aged ≥75 years and with a history of localized radiation therapy are at higher risk for significant neutropenic events and require closer surveillance.

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Efficacy of treatment with a GnRH antagonist in prostate cancer patients previously treated with a GnRH agonist

Ezaki Taisuke, Kosaka Takeo, Mizuno Ryuichi, Shinojima Toshiaki, Kikuchi Eiji, Miyajima Akira, Oya Mototsugu

Cancer Chemotherapy and Pharmacology 76 ( 2 ) 301 - 306 2015.06

ISSN 0344-5704

Purpose: The efficacy of switching from a GnRH agonist to a GnRH antagonist for prostate cancer patients resistant to treatment with the GnRH agonist has not been fully characterized yet. We aimed to evaluate the efficacy of the switch to a GnRH antagonist in patients with PSA failure after hormonal therapy with a GnRH agonist. Methods: We retrospectively examined 18 patients with prostate cancer who received androgen-deprivation therapy and who were treated with a GnRH antagonist (degarelix) after they showed an elevated PSA while on GnRH agonist therapy. We evaluated the characteristics of the patients and analyzed some clinical factors for their potential association with the patient response to the switch. Results: The median PSA at the switch was 7.9 (0.37-1709) ng/ml, and the median testosterone level was 0.17 (<0.08-0.81) ng/ml. Three months after the switch, the median PSA level was 11.3 (0.22-2636) ng/ml, and the median testosterone level was 0.14 (<0.08-0.23) ng/ml. The PSA decreased in six patients (33.3 %) 1 month after the switch, and in three of them it decreased by more than 50 % by 3 months after the switch. Univariate analyses revealed that the lower number of prior treatment lines for prostate cancer before the switch was associated with a favorable decrease in PSA. Conclusions: Switching from GnRH agonist to GnRH antagonist therapy was effective for some prostate cancer patients with PSA failure. The small number of prior treatment lines for prostate cancer before the switch was significantly associated with a good PSA response.

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Evaluation of histopathological findings at the injection site following degarelix administration

Maeda Takahiro, Kosaka Takeo, Honda Aki, Okata Utako, Hayakawa Nozomi, Ito Yujiro, Nagata Hirohiko, Chen Ko Ron, Nakamura So, Oya Mototsugu

Supportive Care in Cancer 23 ( 5 ) 1377 - 1381 2015.05

ISSN 0941-4355

Purpose: The aims of the present study were to investigate the incidence of injection site reactions (ISRs) following administration of 240 mg degarelix and identify the risk factors for ISRs. Methods: This study was conducted in 50 consecutive men treated with degarelix for the first time. ISRs after an initial degarelix dose of 240 mg (administered subcutaneously as two 3 ml subcutaneous injection) were evaluated using the five categories of the Common Terminology Criteria for Adverse Events Version 4 of the National Cancer Institute. We also assessed the differences in patient background between patients with and without an ISR. Results: The mean age of patients and prostate-specific antigen (PSA) level just before degarelix administration were 75.6 and 198.4 ng/ml, respectively. Hormonal therapy with degarelix was administered for the first time to 33 patients; 11 of the 50 patients were receiving an oral steroid, 6 for prostate cancer, 1 for hematological disease, and 4 for allergic conditions. ISRs were observed in 25 patients, and all of the ISRs were categorized as grade 1 or 2; however, 2 patients discontinued this procedure due to the ISR. Significant differences in the first experience with subcutaneous therapy (p = 0.007) and rate of combination with a steroid (p = 0.017) were observed between patients with and without ISRs. Conclusion: The incidences of ISRs in patients receiving subcutaneous therapy for the first time and in patients also receiving an oral steroid were 64 and 18 %, respectively. Patients should be provided with information concerning the possible occurrence of ISR due to degarelix prior to the administration, particularly patients who are not receiving steroids and patients who have no experience with subcutaneous injections.

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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 ( 1 ) 2015.04

Background: No previous study has addressed the efficacy of NF-κ B blockade when bladder tumors develop acquired resistance toward CDDP-treatments. We investigated the changes in NF-κ B activation and therapeutic impact of NF-κ B blockade by the novel NF-κ B inhibitor dehydroxymethyl derivative of epoxyquinomicin (DHMEQ) in CDDP-resistant bladder cancer cells. Methods: Two human invasive bladder cancer cell lines, T24 and T24PR, were used. The T24PR cell line was newly established as an acquired platinum-resistant subline by culturing in CDDP-containing medium for 6 months. Expression of intranuclear p65 protein in the fractionated two cell lines was determined by Western blotting analysis. DNA-binding activity of NF-κ B was detected by electrophoretic mobility shift assay. The cytotoxic effects and induction of apoptosis were analyzed in vivo and in vitro. Results: Intranuclear expression and DNA-binding activity of p65 were strongly enhanced in T24PR cells compared with those of T24 cells, and both were significantly suppressed by DHMEQ. Lowered cell viability and strong induction of apoptosis were observed by treatment with DHMEQ alone in these chemo-resistant cells compared with parent cells. As T24PR cells did not show dramatic cross-resistance to paclitaxel in the in vitro study, we next examined whether the combination of DHMEQ with paclitaxel could enhance the therapeutic effect of the paclitaxel treatment in T24PR tumors. Using mouse xenograft models, the mean volume of tumors treated with the combination of DHMEQ (2 mg/kg) and paclitaxel (10 mg/kg) was significantly smaller than those treated with paclitaxel alone (p < 0.05), and the reduction of tumor volume in mice treated with DHMEQ in combination with paclitaxel and paclitaxel alone as compared to vehicle control was 66.9% and 17.0%, respectively. Conclusion: There was a distinct change in the activation level of NF-κ B between T24 and T24PR cells, suggesting strong nuclear localization of NF-κ B could be a promising target after developing acquired platinum-resistance in bladder cancer.

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The efficacy of enzalutamide in castration resistant prostate cancer

Kosaka Takeo, Oya Mototsugu

Japanese Journal of Clinical Urology 69 ( 5 ) 386 - 392 2015.04

ISSN 0385-2393

Expression of TNF-α and CD44 is implicated in poor prognosis, cancer cell invasion, metastasis and resistance to the sunitinib treatment in clear cell renal cell carcinomas

Mikami Shuji, Mizuno Ryuichi, Kosaka Takeo, Saya Hideyuki, Oya Mototsugu, Okada Yasunori

International Journal of Cancer 136 ( 7 ) 1504 - 1514 2015.04

ISSN 0020-7136

Tumor necrosis factor-α (TNF-α) is involved in epithelial-mesenchymal transition (EMT) and expression of CD44, a cancer stem cell marker, in several cancers. This study was performed to clarify the significance of TNF-α and CD44 in clear cell renal cell carcinomas (ccRCCs). Expression of TNF-α and CD44 was examined by immunohistochemistry in 120 ccRCCs. Involvement of TNF-α in EMT and induction of CD44 was analyzed by monitoring expression of EMT-related genes and CD44, and invasion in cultured ccRCC cell lines. TNF-α and CD44 were immunolocalized mainly to carcinoma cells of high-grade ccRCCs with positive correlations with primary tumor stage. A positive correlation was also obtained between TNF-α and CD44 expression, and co-upregulation of TNF-α and CD44 was associated with primary tumor stage, distant metastasis, and poor prognosis. TNF-αenhanced migration and invasion of ccRCC cells together with down-regulation of E-cadherin expression and up-regulation of matrix metalloproteinase 9 and CD44 expression. TNF-α also up-regulated the expression of TNF-α itself in ccRCC cells. Among the 25 ccRCC patients treated with sunitinib for metastatic disease, high CD44 expression was associated with poor treatment outcome. Importantly, residual carcinoma cells in the sunitinib-treated metastatic ccRCCs were strongly positive for CD44, and the CD44 expression was significantly higher in the tumors from the sunitinib-treated patients than in those from untreated ones. Our data show that TNF-α plays an important role in progression of ccRCCs by inducing EMT and CD44 expression, and suggest that CD44 induced by TNF-α may be involved in the resistance to the sunitinib treatment.

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Impact of an adjuvant chemotherapeutic regimen on the clinical outcome in high risk patients with upper tract urothelial carcinoma

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

ISSN 0022-5347

Purpose Current guidelines do not yet provide any recommendations for adjuvant chemotherapy in patients with upper tract urothelial carcinoma managed with radical nephroureterectomy. We evaluated whether an adjuvant chemotherapeutic regimen would affect the clinical outcome in patients with high risk upper tract urothelial carcinoma. Materials and Methods We identified 873 patients who had undergone radical nephrouretectomy for localized upper tract urothelial carcinoma at 14 Japanese institutions between 1993 and 2011. We assessed whether the type of regimen, such as methotrexate, vinblastine, doxorubicin and cisplatin, and gemcitabine and cisplatin, in an adjuvant setting, could affect the subsequent clinical outcome of patients with upper tract urothelial carcinoma. Results On multivariate analysis pathological T stage, tumor grade, lymphovascular invasion and lymph node involvement were prognostic factors for recurrence-free survival and cancer specific survival. We defined 229 patients with 3 or more of these factors as the high risk group. In an analysis according to adjuvant regimen, Kaplan-Meier curves showed that the 1 and 2-year recurrence-free survival rates in the methotrexate, vinblastine, doxorubicin and cisplatin treated group were 71.4% and 47.9%, which were significantly higher than in the gemcitabine and cisplatin treated group (48.2% and not reached, p=0.022) or those not treated with adjuvant chemotherapy (53.4% and 39.6%, p=0.039). Similar results were observed in terms of cancer specific survival. Conclusions Our study showed that pT3-4, tumor grade 3, positive lymphovascular invasion and lymph node involvement were independent risk factors for disease mortality in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. In the high risk group methotrexate, vinblastine, doxorubicin and cisplatin adjuvant chemotherapy contributed to improve subsequent mortality compared to gemcitabine and cisplatin or no adjuvant chemotherapy.

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Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer

Nozawa Masahiro, Mukai Hirofumi, Takahashi Shunji, Uemura Hiroji, Kosaka Takeo, Onozawa Yusuke, Miyazaki Jun, Suzuki Kazuhiro, Okihara Koji, Arai Yoichi, Kamba Tomomi, Kato Masashi, Nakai Yasutomo, Furuse Hiroshi, Kume Haruki, Ide Hisamitsu, Kitamura Hiroshi, Yokomizo Akira, Kimura Takahiro, Tomita Yoshihiko, Ohno Keiji, Kakehi Yoshiyuki

International Journal of Clinical Oncology 20 ( 5 ) 1026 - 1034 2015.03

ISSN 1341-9625

Background: We previously reported the pharmacokinetic profile and preliminary tolerability of cabazitaxel in a phase I study in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Here we report the final safety profile and anti-tumor activity of cabazitaxel in a larger population, including all patients enrolled in the expansion cohort of the study. Methods: Japanese patients with mCRPC previously treated with docetaxel received cabazitaxel intravenously every 3 weeks plus daily prednisolone. In patients treated with the maximum tolerated dose of 25 mg/m² we evaluated adverse events including treatment-related neutropenia, prostate-specific antigen (PSA) response and objective response. Results: In total, 44 patients were treated with the maximum tolerated dose. The most frequent adverse events (any grade) were neutropenia (100 %), febrile neutropenia (54.5 %), fatigue (54.5 %), nausea (52.3 %) and diarrhea (50.0 %). There were no deaths due to treatment-related adverse events. Neutropenia with prior docetaxel did not appear to influence the probability of febrile neutropenia with cabazitaxel. Most patients received therapeutic granulocyte colony-stimulating factor (G-CSF; cycle 1: 86.4 %; cycle 2 or later: 81.8 %). In the efficacy population, two of 12 patients with measurable disease had partial response (objective response rate: 16.7 %), while 10 had stable disease. PSA response rate was 29.3 % (12/41 patients). Median time to PSA progression was 3.68 months (95 % confidence interval 1.35–4.63). Conclusions: In this heavily pretreated Japanese population, the occurrence of neutropenia and febrile neutropenia was high, suggesting G-CSF prophylaxis may be required as part of toxicity management. However, the efficacy of cabazitaxel was consistent with global studies. ClinicalTrials.gov identifier: NCT01324583.

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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

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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Effect and adverse event of enzalutamide and abiraterone in prostate cancer

Kosaka Takeo, Oya Mototsugu

Nihon rinsho. Japanese journal of clinical medicine 73 308 - 312 2015.02

ISSN 0047-1852

[Molecular targeting drug of kinase inhibitors for castration resistant prostate cancer]

Kosaka Takeo, Oya Mototsugu

Nihon rinsho. Japanese journal of clinical medicine 72 ( 12 ) 2186 - 2192 2014.12

ISSN 0047-1852

Prostate cancer (PCa) is the most common cancer type in men. One of the most troublesome aspects of PCa is that androgen-dependent PCa inevitably progresses to highly aggressive and life-threatening castration resistant prostate cancer (CRPC). Kinases are key regulators of critical cancer processes such as cancer cell proliferation, invasion, differentiation or angiogenesis. Recent advances have shed light on molecular targeting inhibitors of kinases in CRPC. Aberrant expression of certain kinases has been implicated in the development and progression of PCa. Among them, some kinase inhibitors have emerged as promising drug targets for CRPC. In this review, we provide an overview of new therapeutic agents which arrived in an advanced stage of clinical testing, especially focusing on the targets of HGF/c-Met and PI3K/AKT/mTOR signaling pathways.

Complete response to ethnylestradiol prolonged for almost two years in patients with castration-resistant prostate cancer

Hongo Hiroshi, Kosaka Takeo, Oya Mototsugu

Journal of the Canadian Urological Association 8 ( 11-12 DECEMBER ) e921 - e923 2014.12

ISSN 1911-6470

An 80-year-old man with an elevated prostate-specific antigen (PSA) level of 120 ng/mL) presented to the hospital in February 2011. A prostate needle biopsy was performed, and pathological examination revealed prostatic adenocarcinoma. The Gleason score was 4+5=9. Computed tomography revealed metastases of the pelvic lymph nodes. Combined androgen blockade was started. The PSA concentration decreased to 1.68 ng/mL, but started increasing again in August 2012 to 6.08 ng/mL. Although bicalutamide was discontinued due to antiandrogen withdrawal syndrome, the PSA concentration increased even more. The PSA concentration reached 21.62 ng/mL in September 2012, at which time ethnylestradiol was started. The PSA concentration decreased again and has remained below the limit of sensitivity for almost 2 years. To our knowledge, this is first case report describing a complete response to ethnylestradiol that lasted for almost 2 years in a patient with castration-resistant prostate cancer.

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Limited in vitro efficacy of CYP17A1 inhibition on human castration resistant prostate cancer

Kosaka, Takeo, Miyajima, Akira, Yasumizu, Yota, Miyazaki, Yasumasa, Kikuchi, Eiji, Oya, Mototsugu

STEROIDS 92 39 - 44 2014.12

Research paper (scientific journal), ISSN 0039-128X

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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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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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Prognostic value of preoperative multiparametric magnetic resonance imaging (MRI) for predicting biochemical recurrence after radical prostatectomy

Hattori, Seiya, Kosaka, Takeo, Mizuno, Ryuichi, Kanao, Kent, Miyajima, Akira, Yasumizu, Yota, Yazawa, Satoshi, Nagata, Hirohiko, Kikuchi, Eiji, Mikami, Shuji, Jinzaki, Masahiro, Nakagawa, Ken, Tanimoto, Akihiro, Oya, Mototsugu

BJU INTERNATIONAL 113 ( 5 ) 741 - 747 2014.05

Research paper (scientific journal), ISSN 1464-4096

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Metastatic behavior of upper tract urothelial carcinoma after radical nephroureterectomy

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

ISSN 1068-9265

Purpose: To investigate the site-specific pattern of disease recurrence and/or metastasis and the associated patient outcomes after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). Methods: A total of 733 patients with UTUC from a retrospective multi-institutional cohort were included, with a median follow-up of 34 months. Associated patient outcomes were analyzed by multivariate analysis. To evaluate the influence of primary tumor location, we divided it into four areas: renal pelvis, and upper, middle, and lower ureter. Results: A total of 218 patients experienced disease recurrence, with the majority of relapses occurring within the first 3 years. Cumulative incidence rates of first disease recurrence at 1 and 3 years were 18.9 and 29.8 %, respectively. Of these patients, 38.5 % developed distant recurrence; 17.4 % experienced both local and distant recurrences; and 44.0 % developed isolated local recurrence. The predominant sites of distant metastasis were lung, liver, and bone. Multivariate analysis revealed that the prevalence of local recurrence and lung metastasis was significantly associated, with primary tumor location being independent of other clinicopathological variables. Lower/middle ureter tumors had a higher rate of local recurrence in the pelvic cavity, and renal pelvic tumors had a higher prevalence of distant relapse in the lungs. Similar results were obtained when rerunning the data set by excluding patients who received adjuvant chemotherapy (n = 131). Conclusions: This multi-institutional study provided a detailed picture of metastatic behavior after RNU, and primary tumor locations were associated with unique patterns of metastatic spread in UTUC patients.

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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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