研究等業績 - その他 - 成田　伸太郎

Successful local control of recurrent penile cancer treated with a combination of systemic chemotherapy, irradiation, and mohs' paste: a case report.

Naoki Komine, Shintaro Narita, Teruaki Kigure, Hiroshi Tsuruta, Kazuyuki Numakura, Susumu Akihama, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Shigeru Satoh, Hiroshi Nanjo, Tomonori Habuchi

Case reports in oncology   7 ( 2 ) 522 - 7   2014年05月

Penile squamous cell carcinoma (pSCC) is a rare disease, making it difficult to establish a standard of care, particularly in the advanced stage. We report a case of pSCC with advanced lymph node metastasis treated with multimodal therapy consisting of combination chemotherapy, irradiation, and chemosurgery using Mohs' zinc chloride-containing paste. An 80-year-old male with a past history of local treatment for penile cancer presented with a large painful inguinal mass with an ulcer and exudates. The patient underwent multimodal treatment with combination chemotherapy, irradiation, and Mohs' paste. The combination chemotherapy consisted of cisplatin, 5-fluorouracil, and docetaxel. The patient received 50-Gy external-beam radiation therapy to the left inguinal region along with daily local treatment with Mohs' paste. After the initiation of treatment, the pain and bleeding in the inguinal region considerably ameliorated. The wound became dry and flattened 20 days after the initiation of chemotherapy. A CT scan showed that the tumor had decreased 70% in diameter 1 month after the initiation of chemotherapy. After the first course of chemotherapy, the patient and his family decided not to continue treatment because of socio-economic reasons. The patient underwent no additional treatments; nevertheless, he had no local progression of the inguinal tumors for 8 months. We report a case of successful local control of recurrent inguinal pSCC treated with multimodal therapy. Combination treatment with taxane-based chemotherapy, external-beam radiation therapy, and Mohs' paste is an option for the management of recurrent pSCC.

DOI PubMed

ANALYSIS OF FACTORS ASSOCIATED WITH IMPROVEMENT OF METABOLIC DISORDERS FOLLOWING LAPAROSCOPIC ADRENALECTOMY IN PATIENTS WITH CUSHING'S SYNDROME

Kazuyuki Numakura, Norihiko Tsuchiya, Hiroshi Tsuruta, Susumu Akihama, Mitsuru Saito, Takamitsu Inoue, Shintaro Narita, Mingguo Huang, Shigeru Satoh, Tomonori Habuchi

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  191 ( 4 ) E11 - E11   2014年04月

研究発表要旨（国際会議）  

FUNCTIONAL RECOVERY OF HYPOCOMPLIANT DEFUNCTIONALIZED BLADDER DUE TO LONG-TERM DIALYSIS AFTER KIDNEY TRANSPLANTATION

Takamitsu Inoue, Shigeru Satoh, Takashi Obara, Mingguo Huang, Mitsuru Saito, Kazuyuki Numakura, Shintaro Narita, Norihiko Tsuchiya, Tomonori Habuchi

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  191 ( 4 ) E389 - E389   2014年04月

研究発表要旨（国際会議）  

INVERSE RELATIONSHIP BETWEEN INSULIN RECEPTOR EXPRESSION AND FAVORABLE OUTCOMES IN PATIENTS WHO UNDERWENT RADICAL NEPHRECTOMY FOR RENAL CELL CARCINOMA

Makoto Takahashi, Takamitsu Inoue, Mingguo Huang, Mitsuru Saito, Hiroshi Tsuruta, Kazuyuki Numakura, Susumu Akihama, Shintaro Narita, Norihiko Tsuchiya, Tomonori Habuchi

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  191 ( 4 ) E307 - E307   2014年04月

研究発表要旨（国際会議）  

MEASUREMENT OF PROSTATE CANCER-ASSOCIATED ABERRANT GLYCOSYLATION OF PROSTATE SPECIFIC ANTIGEN CAN IMPROVE DIAGNOSTIC ACCURACY

Tohru Yoneyama, Yuki Tobisawa, Shingo Hatakeyama, Shintaro Narita, Tomonori Habuchi, Takuya Koie, Chikara Ohyama

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  191 ( 4 ) E931 - E931   2014年04月

研究発表要旨（国際会議）  

SERUM BAFF LEVELS AND B CELL SUBSETS IN DIFFERENT LYMPHOID ORGANS AFTER RITUXIMAB ADMINISTRATION: ITS ASSOCIATION WITH CLINICAL OUTCOMES

Mitsuru Saito, Shigeru Satoh, Kazuyuki Numakura, Mingguo Huang, Hiroshi Tsuruta, Susumu Akihama, Takamitsu Inoue, Shintaro Narita, Norihiko Tsuchiya, Tomonori Habuchi

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  191 ( 4 ) E824 - E824   2014年04月

研究発表要旨（国際会議）  

Functional mononucleotide repeat polymorphism in the promoter region of HGF is associated with risk and malignant aggressiveness of bladder cancer.

Syuji Chiba, Norihiko Tsuchiya, Yohei Horikawa, Shintaro Narita, Takamitsu Inoue, Susumu Akihama, Mitsuru Saito, Kazuyuki Numakura, Hiroshi Tsuruta, Mingguo Huang, Shigeru Satoh, Tomonori Habuchi

International journal of oncology   44 ( 3 ) 678 - 84   2014年03月

Increased expression of hepatocyte growth factor (HGF) has been shown to be associated with aggressiveness in several types of cancer. Shorter variants of deoxyadenosine tract element (DATE) located in the HGF promoter region have been reported to enhance the expression of HGF. In this study, we investigated the role of HGF DATE variants in bladder cancer risk, HGF expression and clinicopathological features. The frequency of individuals with a short DATE (<28 repeats) in peripheral blood lymphocytes (PBLs) was significantly higher in bladder cancer patients compared to controls (p<0.001). Somatic mutations were observed in 37 of 70 bladder tumor (BT) tissues and the frequency of mutation to long DATE was significantly higher than that to short DATE (p=0.047). The presence of the short DATE in BT tissue was significantly associated with higher tumor grade (p=0.015). HGF mRNA levels were significantly higher in pT2 tumors than pTa or pT1 tumors (p=0.019), and in grade 3 tumors than grade 1 or 2 tumors (p=0.020). Furthermore, BT tissues with the short DATE showed significantly higher levels of HGF mRNA (p<0.001). In patients who underwent radical cystectomy, those with higher HGF expression had a significantly shorter overall survival than those with lower HGF expression (p=0.012). In conclusion, HGF may be associated with the prognosis of patients who undergo radical cystectomy, and the HGF DATE may affect the risk and aggressiveness of bladder cancer by altering HGF expression.

DOI PubMed

Organ-specific and tumor-size-dependent responses to sunitinib in clear cell renal cell carcinoma.

Norihiko Tsuchiya, Takeshi Yuasa, Shinya Maita, Shintaro Narita, Takamitsu Inoue, Kazuyuki Numakura, Mitsuru Saito, Shigeru Satoh, Junji Yonese, Tomonori Habuchi

BMC urology   14   26 - 26   2014年03月

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been used as standard therapy for patients with advanced renal cell carcinoma (RCC). However, information on factors predicting response to treatment with TKIs is lacking. This study aimed to assess the association between initial tumor size, involved organs, pre-treatment C-reactive protein (CRP) levels, and reduction in tumor size in patients with clear cell RCC (CCRCC) treated with sunitinib. METHODS: Patients with advanced CCRCC with target lesions with a maximum diameter ≥ 10 mm treated with sunitinib were evaluated. The tumor diameter representing the best overall response was designated as the post-treatment tumor diameter. RESULTS: A total of 179 lesions in 38 patients were analyzed. Organ-specific analysis demonstrated that pre-treatment diameter of lung metastatic lesions had a moderate inverse association with percent reduction in post-treatment tumor diameter (R = 0.341). Lung lesions showed significantly greater percent reductions in diameter than liver and kidney lesions (P = 0.007 and 0.002, respectively). Furthermore, based on a CRP cut-off level of 2.0 mg/dl, mean tumor size reduction was significantly greater in patients with low CRP levels than in patients with high CRP levels in lesions with diameters < 20 mm (P = 0.002). CRP level had no effect on mean size reduction in lesions with a diameter ≥ 20 mm. CONCLUSIONS: Patients with CCRCC with smaller lung metastatic lesions and lower CRP levels may achieve greater percent reductions in tumor size with sunitinib therapy than patients with extra-pulmonary lesions, large lung lesions, and/or higher CRP levels.

DOI PubMed

Diet-induced macrophage inhibitory cytokine 1 promotes prostate cancer progression.

Mingguo Huang, Shintaro Narita, Takamitsu Inoue, Norihiko Tsuchiya, Shigeru Satoh, Hiroshi Nanjo, Takehiko Sasaki, Tomonori Habuchi

Endocrine-related cancer   21 ( 1 ) 39 - 50   2014年02月

Recent studies have indicated that a high-fat diet (HFD) plays an important role in prostate cancer (PCa) progression. Palmitic acid (PA) is one of the most abundant saturated free fatty acids (FAs) and is associated with carcinogenesis. In this study, we investigated the mechanism underlying the association of dietary fat, including PA, with PCa progression. In four PCa cell lines, in vitro PA administration stimulated the expression of macrophage inhibitory cytokine 1 (MIC1), which is a divergent member of the transforming growth factor-β family. In vivo, LNCaP xenograft tumor growth, serum MIC1 levels, and FA levels in xenograft tumors were significantly higher in mice receiving an HFD containing high amounts of PA than in those receiving a low-fat diet (LFD). In addition, tumor cells with high MIC1 expression invaded to venules and lymph vessels in the LNCaP xenograft. In vitro studies showed that proliferation and invasive capacity were significantly higher in PCa cells cultured with serum from HFD-fed mice than in those cultured with the serum from LFD-fed mice. This effect was attenuated by the addition of neutralizing antibodies against MIC1, but not by isotype control antibodies. Clinically, serum MIC1 levels were significantly higher in PCa patients than in healthy controls, and higher levels were associated with higher pathological grade and obesity. In conclusion, our results indicate that an HFD containing PA may promote growth and invasiveness of PCa cells through the upregulation of MIC1 expression.

DOI PubMed

Pathological and oncological outcomes of elderly men with clinically localized prostate cancer.

Koji Mitsuzuka, Takuya Koie, Shintaro Narita, Yasuhiro Kaiho, Takahiro Yoneyama, Norihiko Tsuchiya, Narihiko Kakoi, Sadafumi Kawamura, Tatsuo Tochigi, Chikara Ohyama, Tomonori Habuchi, Yoichi Arai

Japanese journal of clinical oncology   43 ( 12 ) 1238 - 42   2013年12月

OBJECTIVE: The aim of the study was to characterize pathological and oncological outcomes of elderly men with clinically localized prostate cancer treated with radical prostatectomy. METHODS: Data from 1268 patients undergoing radical prostatectomy between 2000 and 2009 were retrospectively reviewed. Patients were classified according to whether they were of age <70 or ≥70 years at radical prostatectomy. Patient characteristics, pathological and oncological outcomes were compared among the groups. RESULTS: Of the total population, 31.4% (398 of 1268) of patients were ≥70 years of age. The median age in patients <70 and ≥70 years of age was 64 (45-69) and 72 (70-83) years. The proportion of low-risk disease was significantly lower among those ≥70 years of age than in those <70 years, while the proportion of high-risk disease was significantly higher among those ≥70 years of age than in those <70 years (P < 0.001). The proportions of pathological high-risk disease (≥T3b, GS ≥8, positive surgical margin or lymph node invasion) in patients <70 and ≥70 years of age were 42.0 and 50.0%, respectively (P = 0.008). The proportions of organ-confined disease in patients <70 and ≥70 years of age were 69.9 and 65.1%, respectively (P = 0.09). With a median follow-up of 50 months, 5-year biochemical recurrence-free and cancer-specific survival rates were not significantly different among the groups. CONCLUSIONS: Radical prostatectomy was more likely to be performed in those with higher-risk disease among patients ≥70 years of age. About half of the patients ≥70 years of age had pathological, high-risk disease. Radical prostatectomy could be considered for patients with expected long-term life expectancy, even in the setting of advanced age.

DOI PubMed

Is pelvic lymph node dissection required at radical prostatectomy for low-risk prostate cancer?

Koji Mitsuzuka, Takuya Koie, Shintaro Narita, Yasuhiro Kaiho, Takahiro Yoneyama, Sadafumi Kawamura, Tatsuo Tochigi, Chikara Ohyama, Tomonori Habuchi, Yoichi Arai

International journal of urology : official journal of the Japanese Urological Association   20 ( 11 ) 1092 - 6   2013年11月

OBJECTIVES: To determine the necessity of pelvic lymph node dissection for low-risk prostate cancer, we analyzed the incidence of lymph node invasion and the therapeutic value of pelvic lymph node dissection in low-risk prostate cancer patients. METHODS: Medical records for 1268 patients undergoing open radical prostatectomy between January 2000 and December 2009 who had not undergone neoadjuvant therapy were retrospectively reviewed. Patients with low-risk disease (n = 222; prostate-specific antigen <10 ng/mL, biopsy Gleason score ≤6, clinical T1c or T2a) were classified according to whether they underwent pelvic lymph node dissection (pelvic lymph node dissection group, n = 147) or did not (no pelvic lymph node dissection group, n = 75). Pelvic lymph node dissection was carried out in a limited style, which included the external iliac vein and the obturator fossa. The incidence of lymph node invasion was determined and referred to the preoperative nomogram developed for Japanese patients (Japanese nomogram), Partin and Kattan nomograms. The 5-year biochemical recurrence-free survivals in both groups were analyzed. RESULTS: Lymph node invasion in low-, intermediate- and high-risk disease was 0.7% (1/147), 1.2% (7/595) and 6.1% (23/374). The 5-year biochemical recurrence-free survival rates for patients with low-risk disease were 87.6% in the pelvic lymph node dissection group and 87.1% in the no pelvic lymph node dissection group (P = 0.65, log-rank). No patients in the pelvic lymph node dissection group exceeded 2% of lymph node invasion risk with Japanese and Partin nomograms. With the Kattan nomogram, 22.4% (33/147) of the pelvic lymph node dissection group exceeded 2% of lymph node invasion risk, and one patient had documented lymph node invasion, but none exceeded 2.5%. CONCLUSIONS: Pelvic lymph node dissection can be spared at radical prostatectomy for low-risk disease, as its diagnostic and therapeutic value is poor.

DOI PubMed

高脂肪食摂取下の前立腺癌進展におけるFatty acid synthase(FASN)の役割(Role of fatty acid synthase(FASN) on HFD induced prostate cancer progression)

黄 明国, 成田 伸太郎, 土谷 順彦, 井上 高光, 佐藤 滋, 佐々木 雄彦, 羽渕 友則

日本癌学会総会記事 ( 日本癌学会 )  72回   509 - 509   2013年10月

シスプラチン腎障害により維持透析に至った2例

山本 竜平, 井上 高光, 五十嵐 龍馬, 小泉 淳, 沼倉 一幸, 秋濱 晋, 齋藤 満, 成田 伸太郎, 堀川 洋平, 土谷 順彦, 佐藤 滋, 羽渕 友則

秋田腎不全研究会誌 ( 秋田腎不全研究会 )  16   159 - 162   2013年10月

進行性腎細胞癌患者におけるsunitinibの血中濃度と治療アウトカムの検討

土谷 順彦, 藤山 信弘, 成田 伸太郎, 井上 高光, 斎藤 満, 沼倉 一幸, 秋濱 晋, 鶴田 大, 佐藤 滋, 三浦 昌朋, 羽渕 友則

日本癌治療学会誌 ( (一社)日本癌治療学会 )  48 ( 3 ) 1614 - 1614   2013年09月

Changes in indications and oncological outcomes of radical prostatectomy after 2000--data from 1268 Japanese patients treated with radical prostatectomy between 2000 and 2009.

Koji Mitsuzuka, Takuya Koie, Shintaro Narita, Yasuhiro Kaiho, Takahiro Yoneyama, Norihiko Tsuchiya, Narihiko Kakoi, Sadafumi Kawamura, Tatsuo Tochigi, Chikara Ohyama, Tomonori Habuchi, Takuhiro Yamaguchi, Yoichi Arai

Japanese journal of clinical oncology   43 ( 8 ) 821 - 6   2013年08月

OBJECTIVE: The aim of the study was to characterize trends in indications for and oncological outcomes of radical prostatectomy after 2000. METHODS: Data from 1268 patients undergoing radical prostatectomy without neoadjuvant therapy between 2000 and 2009 at four urological centers in Japan were retrospectively reviewed. Changes in age at radical prostatectomy, prostate-specific antigen level, biopsy Gleason score, clinical T stage, D'Amico risk classification, organ-confined disease and tumor volume in surgical specimens were analyzed over time. RESULTS: The median age at radical prostatectomy decreased from 68 years in 2000-2 to 65 years in 2009 (P < 0.001). Approximately 63.3% of patients were ≥65 years old, and 31.4% of patients were ≥70 years old during the whole study period. The median prostate-specific antigen level decreased from 8.61 ng/ml in 2000-2 to 6.90 ng/ml in 2009 (P < 0.001). The rate of organ-confined disease increased from 52.8% in 2000-2 to 72.5% in 2009 (P = 0.004). The median tumor volume decreased from 1.70 cc in 2000-2 to 1.28 cc in 2009 (P = 0.017). The proportion of biopsy Gleason score 7 increased from 40.6% in 2000-2 to 60.1% in 2009 (P < 0.001), and the proportion of the intermediate-risk group increased from 39.5% in 2000-2 to 59.5% in 2009 (P < 0.001). CONCLUSIONS: Age at radical prostatectomy for men with localized prostate cancer was higher in Japan than in the USA or Europe. Prostate-specific antigen, non-organ-confined disease and tumor volume decreased during the study period, whereas Gleason score 7 and intermediate-risk disease increased during the study period. This information enables comparison of outcomes between various treatments, between various geographic regions and between various time periods.

DOI PubMed

グラセプタのトラフ値はプログラフと同等か? 移植1年まで

佐藤 滋, 新岡 丈典, 加賀谷 英彰, 沼倉 一幸, 井上 高光, 斎藤 満, 小峰 直樹, 秋濱 晋, 成田 伸太郎, 土谷 順彦, 羽渕 友則, 三浦 昌朋

日本臨床腎移植学会雑誌 ( (一社)日本臨床腎移植学会 )  1 ( 1 ) 78 - 81   2013年07月

タクロリムス(Tac)には1日2回服用のプログラフ(Tac-BID)と1日1回のグラセプタ(Tac-QD)があり、Tac-BIDからTac-QDへ切替えた初期報告(Allowayらの報告)では、「1日同量服用で同等の薬物動態が得られた」と報告されている。一方、同量服用ではTac-QDのトラフ値(Cmin)や24時間血中濃度時間曲線下面積(AUC0-24)が低値になるとの報告が多くなされている。また、Tacはチトクローム(CYP)3A5の基質薬剤であり、CYP3A5イントロン3のA6986Gには多型が存在し、CYP3A5 expresserはCYP3A5*1アレルを有し、non-expresserはCYP3A5*3/*3 genotypeを表す。そこで今回、CYP3A5のアレル頻度を同一にしたTac-BID群とTac-QD群の各24例を対象とし、服用直後と移植後1ヵ月および1年時の薬物動態について比較検討した。その結果、CYP3A5 non-expresserにおいてはTac-QDの目標CminがTac-BIDより低値でもTac-BIDと同等のAUC0-24を得られる可能性が示唆された。

Pathological and biochemical outcomes after radical prostatectomy in men with low-risk prostate cancer meeting the Prostate Cancer International: Active Surveillance criteria.

Koji Mitsuzuka, Shintaro Narita, Takuya Koie, Yasuhiro Kaiho, Norihiko Tsuchiya, Takahiro Yoneyama, Narihiko Kakoi, Sadafumi Kawamura, Tatsuo Tochigi, Tomonori Habuchi, Chikara Ohyama, Yoichi Arai

BJU international   111 ( 6 ) 914 - 20   2013年05月

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Active surveillance has been widely accepted as a treatment tool for low-risk prostate cancer, and use of the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria can select smaller and less aggressive tumours in low-risk disease. The study shows the pathological outcomes of radical prostatectomy for patients with low-risk disease who met the PRIAS criteria. It found that ~20% had unfavourable pathological features and only 30% satisfied insignificant cancer criteria with pT2 stage, a Gleason score ≤6 and tumour volume <2.5 mL. It concludes that close follow-up including repeat biopsy or MRI is necessary to minimize unexpected progression of disease. OBJECTIVE: To assess the effectiveness of the Prostate Cancer Research International Active Surveillance (PRIAS) criteria in identifying indolent cancer. PATIENTS AND METHODS: Data from 1268 patients undergoing radical prostatectomy without neoadjuvant therapy were retrospectively reviewed. Within this cohort, patients with low-risk disease (n = 211) were classified according to whether they met (Group A, n = 87) or did not meet (Group B, n = 124) the PRIAS criteria. Pathological upstaging, upgrading, tumour volume and 5-year prostate-specific antigen (PSA) recurrence-free survival were compared between the two groups, and factors that predicted upstaging, upgrading and PSA recurrence were analysed by univariate and multivariate methods. RESULTS: Pathological T3 stage was present in 10.3% of patients in Group A and in 18.5% of patients in Group B (P = 0.08). Gleason score upgrading to 4+3 or greater was seen in 19.5% of Group A and in 29.9% of Group B (P = 0.01). The mean (range) tumour volume was 0.81 (0.03-5.09) mL in Group A and 1.40 (0.04-8.21) mL in Group B (P < 0.01). The rates of insignificant cancer with total tumour volume <2.5 mL, Gleason score ≤6 and stage pT2 were 30.6% in Group A and 15.4% in Group B (P = 0.07). With a median follow-up of 44 months, the 5-year PSA recurrence-free survival rates were 91.2% in Group A and 86.4% in Group B (P = 0.47). In multivariate analysis, PSA density and the PRIAS criteria were independent factors that predicted upstaging. CONCLUSIONS: Although use of the PRIAS criteria could select more favourable tumours even in low-risk prostate cancer, about one in five men had unfavourable pathological outcomes and only three in ten had insignificant cancer. Close and careful follow-up is necessary to avoid misclassification or progression of disease, especially during the first few years of active surveillance.

DOI PubMed

進行性腎細胞癌患者におけるsunitinibの薬物動態とその臨床的意義

土谷 順彦, 藤山 信弘, 成田 伸太郎, 井上 高光, 沼倉 一幸, 秋濱 晋, 佐藤 滋, 三浦 昌朋, 羽渕 友則

泌尿器外科 ( 医学図書出版(株) )  26 ( 臨増 ) 712 - 712   2013年05月

CAN BIOPSY GLEASON SCORE 3+4 BE INDICATED FOR ACTIVE SURVEILLANCE CRITERIA?

Koji Mitsuzuka, Shintaro Narita, Takuya Koie, Narihiko Kakoi, Yasuhiro Kaiho, Norihiko Tsuchiya, Takahiro Yoneyama, Sadafumi Kawamura, Tatsuo Tochigi, Tomonori Habuchi, Chikara Ohyama, Yoichi Arai

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  189 ( 4 ) E273 - E273   2013年04月

研究発表要旨（国際会議）  

LACK OF CLINICAL FACTORS INCREASING QUANTITATIVE INTERSTITIAL FIBROSIS AFTER RENAL TRANSPLANTATION UNDER A LOWER TARGET TROUGH STRATEGY OF TACROLIMUS

Naoki Komine, Shigeru Satoh, Kazuyuki Numakura, Mitsuru Saito, Takamitsu Inoue, Shintaro Narita, Yoshiko Miura, Norihiko Tsuchiya, Hideaki Kagaya, Masatomo Miura, Tomonori Habuchi

JOURNAL OF UROLOGY ( ELSEVIER SCIENCE INC )  189 ( 4 ) E868 - E868   2013年04月

研究発表要旨（国際会議）