研究等業績 - 原著論文 - 羽渕 友則
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A prospective multicenter study of intermittent chemotherapy with docetaxel and prednisolone for castration-resistant prostate cancer.
Shintaro Narita, Takuya Koie, Shigeyuki Yamada, Kazuhiko Orikasa, Shigeki Matsuo, Hiroshi Aoki, Shigeto Ishidoya, Senji Hoshi, Norihiko Tsuchiya, Chikara Ohyama, Yoichi Arai, Tomonori Habuchi
Japanese journal of clinical oncology 46 ( 6 ) 547 - 553 2016年06月
研究論文（学術雑誌）
OBJECTIVE: The optimal schedule of docetaxel chemotherapy for castration-resistant prostate cancer is unknown, although continuous administration is accepted as the standard. We conducted a Phase II trial to evaluate the outcome of intermittent docetaxel and prednisolone therapy in castration-resistant prostate cancer. METHODS: The patients were treated using a 28-day cycle of docetaxel (70 mg/m2 on Day 1) and oral prednisolone (10 mg/day). After three consecutive administrations of docetaxel, a holiday was taken until prostate specific antigen levels returned to the baseline. The therapy was continued intermittently until the disease progressed, drug toxicity occurred, or the patients refused further treatment. The primary endpoint was overall survival. Time to treatment failure, adverse events, the duration of chemotherapy holiday and quality of life were also evaluated. RESULTS: A total of 120 patients were enrolled. The median age and pretreatment prostate specific antigen level were 72 years and 37.5 ng/ml, respectively. Sixty (50.0%) patients resumed chemotherapy after the first holiday, and a maximum of six courses were administered to four patients. The median period of the first, second and third-to-fifth holiday was 18.6, 11.0 and 4.9 weeks, respectively. Toxicity was moderate, except for two fatal adverse events. The median time to treatment failure and overall survival from the initiation of docetaxel and prednisolone therapy in all patients were 17.5 and 35.0 months, respectively. All quality-of-life scores were unchanged statistically from the start of docetaxel and prednisolone therapy to the beginning of the second course. CONCLUSIONS: Intermittent docetaxel and prednisolone therapy might be a feasible treatment option for castration-resistant prostate cancer with comparable outcome and successful chemotherapy holidays.
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Influence of everolimus on the pharmacokinetics of tacrolimus in Japanese renal transplant patients.
Takenori Niioka, Hideaki Kagaya, Mitsuru Saito, Takamitsu Inoue, Kazuyuki Numakura, Ryohei Yamamoto, Yumiko Akamine, Tomonori Habuchi, Shigeru Satoh, Masatomo Miura
International journal of urology : official journal of the Japanese Urological Association 23 ( 6 ) 484 - 90 2016年06月
研究論文（学術雑誌）
OBJECTIVES: To examine whether a trough concentration of everolimus in the therapeutic range of 3-5 ng/mL affects the pharmacokinetics of tacrolimus in renal transplant patients. METHODS: A total of 52 Japanese renal transplant patients receiving tacrolimus were enrolled in this study. In 28 of them, everolimus was co-administered on day 14 after surgery. Changes in the dose-adjusted blood trough concentration of tacrolimus from day 14 to 28 after surgery were investigated. RESULTS: The dose-adjusted blood trough concentration of tacrolimus on day 28 was affected by CYP3A5*3/*3 and hemoglobin level (P < 0.001 and P = 0.007), but not by everolimus (P = 0.171). In addition, there was no change in the dose-adjusted blood trough concentration of tacrolimus in patients before or after everolimus coadministration (P = 0.165). On day 28, there was no correlation between the rate of change in the dose-adjusted blood trough concentration of tacrolimus and the blood trough concentration or area under the plasma concentration-time curve from 0 to 12 h for everolimus after initiation of combination therapy (r = 0.341, P = 0.076 and r = 0.234, P = 0.231). CONCLUSIONS: A pharmacokinetic interaction between tacrolimus and everolimus was not observed clinically in renal transplant patients. Safe and reliable immunosuppressive therapy in renal transplant patients might be achieved using a combination of tacrolimus and everolimus.
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[Recent trend in the development of novel treatments based on the mechanisms of prostate cancer progression].
Takamitsu Inoue, Shintaro Narita, Tomonori Habuchi
Nihon rinsho. Japanese journal of clinical medicine 74 Suppl 3 211 - 20 2016年05月
研究論文（学術雑誌）
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[Treatment strategy for high-risk localized prostate cancer].
Shintaro Narita, Takamitsu Inoue, Tomonori Habuchi
Nihon rinsho. Japanese journal of clinical medicine 74 Suppl 3 693 - 700 2016年05月
研究論文（学術雑誌）
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Influence of 1 year of androgen deprivation therapy on lipid and glucose metabolism and fat accumulation in Japanese patients with prostate cancer
K. Mitsuzuka, A. Kyan, T. Sato, K. Orikasa, M. Miyazato, H. Aoki, N. Kakoi, S. Narita, T. Koie, T. Namima, S. Toyoda, Y. Fukushi, T. Habuchi, C. Ohyama, Y. Arai
Prostate Cancer and Prostatic Diseases 19 ( 1 ) 57 - 62 2016年03月
研究論文（学術雑誌）
We prospectively examined influence of androgen deprivation therapy (ADT) on lipid and glucose metabolisms in Japanese patients with prostate cancer.Methods:Patients with prostate cancer who were hormone-naive and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight, abdominal circumference and blood testing associated with lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat before and after 1 year of ADT. ADT was limited to a luteinizing hormone-releasing hormone (LHRH) agonist with or without bicalutamide.Results:Of 218 patients registered, data were available from 177 patients who completed 1 year of ADT. Of these, CT was performed before and after 1 year of ADT in 88 patients. Median age was 75 years (range, 49-85 years). Median PSA before ADT was 16.7 ng ml-1 (range, 0.3-3316). Clinical stage was B (54.2%), C (23.2%) and D (20.9%). Mean increases in body weight and abdominal circumference after 1 year of ADT were 2.9 and 3.0%, respectively. Mean increases in total, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were 10.6, 14.3, 7.8 and 16.2%, respectively. Mean increases in fasting blood sugar and hemoglobin A1c (HbA1c) were 3.9 and 2.7%, respectively. Lipid alterations were noted in patients without comorbidities, whereas changes in HbA1c were noted in patients with diabetes mellitus at baseline. These lipid and glucose alterations were prominent in the early ADT period. Both visceral and subcutaneous fat, as measured by CT, increased by >20%. The increase in subcutaneous fat was significantly greater than that in visceral fat (P=0.028).Conclusions:One year of ADT significantly changed lipid and glucose metabolism in Japanese patients with prostate cancer. Patient characteristics or comorbidities at baseline may be associated with ADT-induced metabolic changes.
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Diet-induced alteration of fatty acid synthase in prostate cancer progression
M. Huang, A. Koizumi, S. Narita, T. Inoue, N. Tsuchiya, H. Nakanishi, K. Numakura, H. Tsuruta, M. Saito, S. Satoh, H. Nanjo, T. Sasaki, T. Habuchi
Oncogenesis 5 2016年02月
研究論文（学術雑誌）
Fatty acid synthase (FASN) is a cytosolic metabolic enzyme that catalyzes de novo fatty acid synthesis. A high-fat diet (HFD) is attributed to prostate cancer (PCa) progression, but the role FASN on HFD-mediated PCa progression remains unclear. We investigated the role of FASN on PCa progression in LNCaP xenograft mice fed with HFD or low-fat diet (LFD), in PCa cells, and in clinical PCa. The HFD promoted tumour growth and FASN expression in the LNCaP xenograft mice. HFD resulted in AKT and extracellular signal-regulated kinase (ERK) activation and 5' adenosine monophosphate-activated protein kinase (AMPK) inactivation. Serum FASN levels were significantly lower in the HFD group (P=0.026) and correlated inversely with tumour volume (P=0.022). Extracellular FASN release was enhanced in the PCa cells with phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinase (MAPK) inhibition and AMPK signalling activation. FASN inhibition resulted in decrease of PCa cell proliferation through PI3K/MAPK downregulation and AMPK activation. Furthermore, AMPK activation was associated with FASN downregulation and PI3K/MAPK inactivation. Clinically, high FASN expression was significantly associated with high Gleason scores and advanced pathological T stage. Moreover, FASN expression was markedly decreased in the PCa response to androgen deprivation therapy and chemotherapy. HFD modulates FASN expression, which may be an important mechanism in HFD-associated PCa progression. Furthermore, a critical stimulatory loop exists between FASN and the PI3K/MAPK system, whereas AMPK signalling was associated with suppression. These may offer appropriate targets for chemoprevention and cancer therapy in HFD-induced PCa.
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[Current status of castration-resistant prostate cancer translational research].
Atsushi Maeno, Tomonori Habuchi
Nihon rinsho. Japanese journal of clinical medicine 74 ( 1 ) 40 - 4 2016年01月
研究論文（学術雑誌）
Recently, new drugs including abiraterone and enzalutamide have been able to be used for castration resistant prostate cancer(CRPC) patients. However, a subset of these patients who receive the new drugs does not response to the therapies. Furthermore, most patients who initially response to the drugs, progress to secondary resistance eventually. Therefore, it is important to investigate a novel therapeutic target and a novel treatment-selection marker for CRPC. In this review, we focused on AR-V7, TMPRSS2-ERG fusion gene and EP4 antagonist as representative translational researches.
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Development of RNA-FISH Assay for Detection of Oncogenic FGFR3-TACC3 Fusion Genes in FFPE Samples.
Masahiro Kurobe, Takahiro Kojima, Kouichi Nishimura, Shuya Kandori, Takashi Kawahara, Takayuki Yoshino, Satoshi Ueno, Yuichi Iizumi, Koji Mitsuzuka, Yoichi Arai, Hiroshi Tsuruta, Tomonori Habuchi, Takashi Kobayashi, Yoshiyuki Matsui, Osamu Ogawa, Mikio Sugimoto, Yoshiyuki Kakehi, Yoshiyuki Nagumo, Masakazu Tsutsumi, Takehiro Oikawa, Koji Kikuchi, Hiroyuki Nishiyama
PloS one 11 ( 12 ) e0165109 2016年
研究論文（学術雑誌）
INTRODUCTION AND OBJECTIVES: Oncogenic FGFR3-TACC3 fusions and FGFR3 mutations are target candidates for small molecule inhibitors in bladder cancer (BC). Because FGFR3 and TACC3 genes are located very closely on chromosome 4p16.3, detection of the fusion by DNA-FISH (fluorescent in situ hybridization) is not a feasible option. In this study, we developed a novel RNA-FISH assay using branched DNA probe to detect FGFR3-TACC3 fusions in formaldehyde-fixed paraffin-embedded (FFPE) human BC samples. MATERIALS AND METHODS: The RNA-FISH assay was developed and validated using a mouse xenograft model with human BC cell lines. Next, we assessed the consistency of the RNA-FISH assay using 104 human BC samples. In this study, primary BC tissues were stored as frozen and FFPE tissues. FGFR3-TACC3 fusions were independently detected in FFPE sections by the RNA-FISH assay and in frozen tissues by RT-PCR. We also analyzed the presence of FGFR3 mutations by targeted sequencing of genomic DNA extracted from deparaffinized FFPE sections. RESULTS: FGFR3-TACC3 fusion transcripts were identified by RNA-FISH and RT-PCR in mouse xenograft FFPE tissues using the human BC cell lines RT112 and RT4. These cell lines have been reported to be fusion-positive. Signals for FGFR3-TACC3 fusions by RNA-FISH were positive in 2/60 (3%) of non-muscle-invasive BC (NMIBC) and 2/44 (5%) muscle-invasive BC (MIBC) patients. The results of RT-PCR of all 104 patients were identical to those of RNA-FISH. FGFR3 mutations were detected in 27/60 (45%) NMIBC and 8/44 (18%) MIBC patients. Except for one NMIBC patient, FGFR3 mutation and FGFR3-TACC3 fusion were mutually exclusive. CONCLUSIONS: We developed an RNA-FISH assay for detection of the FGFR3-TACC3 fusion in FFPE samples of human BC tissues. Screening for not only FGFR3 mutations, but also for FGFR3-TACC3 fusion transcripts has the potential to identify additional patients that can be treated with FGFR inhibitors.
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Immunosuppressive protocol for the recipients with donor specific antibodies
Mitsuru Saito, Tomonori Habuchi, Shigeru Satoh, Ryohei Yamamoto, Hiroshi Tsuruta, Takamitsu Inoue, Shintaro Narita, Norihiko Tsuchiya
Japanese Journal of Clinical Urology 69 ( 13 ) 1138 - 1143 2015年12月
研究論文（学術雑誌）
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Laparoendoscopic single-site donor nephrectomy : the present status and perspectives
Takamitsu Inoue, Shintaro Narita, Norihiko Tsuchiya, Kazuyuki Numakura, Atsushi Maeno, Mitsuru Saito, Tomonori Habuchi, Shigeru Satoh
Japanese Journal of Clinical Urology 69 ( 13 ) 1102 - 1109 2015年12月
研究論文（学術雑誌）
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Reassessment of the risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer treated using radical prostatectomy.
Shintaro Narita, Koji Mitsuzuka, Norihiko Tsuchiya, Takuya Koie, Sadafumi Kawamura, Chikara Ohyama, Tatsuo Tochigi, Takuhiro Yamaguchi, Yoichi Arai, Tomonori Habuchi
International journal of urology : official journal of the Japanese Urological Association 22 ( 11 ) 1029 - 35 2015年11月
研究論文（学術雑誌）
OBJECTIVES: To assess the risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer patients treated using radical prostatectomy. METHODS: We retrospectively reviewed the medical records of 1268 men with prostate cancer treated using radical prostatectomy without neoadjuvant therapy. The association between various risk factors and biochemical recurrence was then statistically evaluated. The Kaplan-Meier method, log-rank tests and Cox proportional hazards models were used for statistical analysis. RESULTS: In the intermediate-risk group, 96 patients (14.5%) experienced biochemical recurrence during a median follow up of 41 months. In the intermediate-risk group, preoperative prostate-specific antigen level, prostate volume and prostate-specific antigen density were significant preoperative risk factors for biochemical recurrence, whereas other factors including age, primary Gleason 4, clinical stage >T2 and percentage of positive biopsies were not. In multivariate analysis, higher preoperative prostate-specific antigen level and density, and a smaller prostate volume were independent risk factors for biochemical recurrence in the intermediate-risk group. Biochemical recurrence-free survival of patients in the intermediate-risk group with a higher prostate-specific antigen level and density (≥15 ng/mL, ≥0.6 ng/mL/cm(3), respectively), and lower prostate volume (≤10 mL) was comparable with that of high-risk group individuals (P = 0.632, 0.494 and 0.961, respectively). CONCLUSIONS: Preoperative prostate-specific antigen, prostate volume and prostate-specific antigen density are significant risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer patients treated using radical prostatectomy. Using these variables, a subset of the intermediate-risk patients can be identified as having equivalent outcomes to high-risk patients.
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Identification of a subgroup with worse prognosis among patients with poor-risk testicular germ cell tumor.
Takahiro Kojima, Koji Kawai, Kunihiko Tsuchiya, Takashige Abe, Nobuo Shinohara, Toshiaki Tanaka, Naoya Masumori, Shigeyuki Yamada, Yoichi Arai, Shintaro Narita, Norihiko Tsuchiya, Tomonori Habuchi, Hiroyuki Nishiyama
International journal of urology : official journal of the Japanese Urological Association 22 ( 10 ) 923 - 7 2015年10月
研究論文（学術雑誌）
OBJECTIVES: To clarify the significance of the International Germ Cell Cancer Collaborative Group classification in the 2000s, especially in intermediate- and poor-prognosis testicular germ cell tumor in Japan. METHODS: We retrospectively analyzed 117 patients with intermediate- and poor-prognosis testicular non-seminomatous germ cell tumor treated at five university hospitals in Japan between 2000 and 2010. Data collected included age, levels of tumor markers, spread to non-pulmonary visceral metastases, treatment details and survival. RESULTS: The median follow-up period of all patients was 57 months. A total of 50 patients (43%) were classified as having intermediate prognosis, and 67 patients (57%) as poor prognosis according to the International Germ Cell Cancer Collaborative Group classification. As first-line chemotherapy, 92 patients (79%) received bleomycin, etoposide and cisplatin. Of all patients, 74 patients (63%) received second-line chemotherapy. The most commonly used second-line chemotherapy regimens were a combination of taxanes, ifosfamide and platinum in 49 cases (66%). Overall, 33 patients (28%) received third-line chemotherapy. A total of 88 patients (75%) underwent post-chemotherapy surgery. The 5-year overall survival for intermediate (n = 50) and poor prognosis (n = 67) was 89% and 83% (P = 0.21), respectively. In poor prognosis patients, patients with two or more risk factors (any of high lactic dehydrogenase, alpha-fetoprotein and human chorionic gonadotropin levels, and presence of non-pulmonary visceral metastases) had significantly worse survival than those with only one risk factor (71% and 91%, respectively, P = 0.01). CONCLUSIONS: The 5-year overall survivals of poor-prognosis testicular non-seminomatous germ cell tumor patients reached 83%. Further stratification of poor-prognosis patients based on a number of risk factors has the potential to further identify those with poorer prognosis.
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Lymph node dissection
Norihiko Tsuchiya, Hiroshi Tsuruta, Mitsuru Saito, Takamitsu Inoue, Shintaro Narita, Tomonori Habuchi
Japanese Journal of Clinical Urology 69 ( 11 ) 918 - 923 2015年10月
研究論文（学術雑誌）
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Neoadjuvant luteinizing-hormone-releasing hormone agonist plus low-dose estramustine phosphate improves prostate-specific antigen-free survival in high-risk prostate cancer patients: a propensity score-matched analysis.
Takuya Koie, Koji Mitsuzuka, Takahiro Yoneyama, Shintaro Narita, Sadafumi Kawamura, Yasuhiro Kaiho, Norihiko Tsuchiya, Tatsuo Tochigi, Tomonori Habuchi, Yoichi Arai, Chikara Ohyama, Tohru Yoneyama, Yuki Tobisawa
International journal of clinical oncology 20 ( 5 ) 1018 - 25 2015年10月
研究論文（学術雑誌）
BACKGROUND: The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with a neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). In the present study, we used a retrospective design via propensity score matching to elucidate the clinical benefit of neoadjuvant LHRH+EMP for high-risk Pca. METHODS: The Michinoku Urological Cancer Study Group database contained data for 1,268 consecutive Pca patients treated with RP alone at 4 institutions between April 2000 and March 2011 (RP alone group). In the RP alone group, we identified 386 high-risk Pca patients. The neoadjuvant LHRH+EMP group included 274 patients with high-risk Pca treated between September 2005 and November 2013 at Hirosaki University. Neoadjuvant LHRH+EMP therapy included LHRH and EMP administration at a dose of 280 mg/day for 6 months before RP. The outcome measures were overall survival (OS) and BRFS. RESULTS: The propensity score-matched analysis indicated 210 matched pairs from both groups. The 5-year BRFS rates were 90.4 and 65.8 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P < 0.0001). The 5-year OS rates were 100 and 96.1 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P = 0.110). CONCLUSIONS: Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP appeared to reduce the risk of biochemical recurrence. A prospective randomized study is warranted to determine the clinical implications of the neoadjuvant therapy described here.
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[PRIMARY MEDIASTINAL GERM CELL TUMOR ARISING IN A PATIENT WITH NEUROFIBROMATOSIS TYPE 1].
Soki Kashima, Mitsuru Saito, Norihiko Tsuchiya, Hajime Saito, Hiroshi Nanjo, Kazuyuki Numakura, Hiroshi Tsuruta, Susumu Akihama, Takamitsu Inoue, Shintaro Narita, Yoshihiro Minamiya, Shigeru Satoh, Tomonori Habuchi
Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 106 ( 3 ) 178 - 84 2015年07月
研究論文（学術雑誌）
Neurofibromatosis type 1 (NF1) is a distinct genetic disorder due to the NF1 gene mutation which induces the aberrant activation of the RAS-signaling. Because RAS-related proteins function as oncogenic factors, NF1 patients frequently develop malignant tumors, especially of neural crest origin, such as peripheral nerve sheath. In addition, malignant tumors of the pancreas, colorectum, and lung have been reported to frequently arise in NF1 patients. However, the association between germ cell tumor and NF1 has not been clarified yet. A 29-year-old male with dyspnea was referred to our hospital because of the large mass in the anterior mediastinum and cervical lymph node swelling. The diagnosis was extragonadal germ cell tumor with cervical lymph node metastasis, and complete remission was obtained by multidisciplinary treatment consisted of combination chemotherapy and surgical resection. To our acknowledgement, this is the first case of extragonadal germ cell tumor in NF1 patients. We discuss the relevance between activation of the RAS-signaling and the development of germ cell tumor.
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INPP4B Is a PtdIns(3,4,5)P3 Phosphatase That Can Act as a Tumor Suppressor.
Satoshi Kofuji, Hirotaka Kimura, Hiroki Nakanishi, Hiroshi Nanjo, Shunsuke Takasuga, Hui Liu, Satoshi Eguchi, Ryotaro Nakamura, Reietsu Itoh, Noriko Ueno, Ken Asanuma, Mingguo Huang, Atsushi Koizumi, Tomonori Habuchi, Masakazu Yamazaki, Akira Suzuki, Junko Sasaki, Takehiko Sasaki
Cancer discovery 5 ( 7 ) 730 - 9 2015年07月
研究論文（学術雑誌）
UNLABELLED: Inositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumor suppressor mutated in human breast, ovary, and prostate cancers. The molecular mechanism underlying INPP4B's tumor-suppressive role is currently unknown. Here, we demonstrate that INPP4B restrains tumor development by dephosphorylating the PtdIns(3,4,5)P3 that accumulates in situations of PTEN deficiency. In vitro, INPP4B directly dephosphorylates PtdIns(3,4,5)P3. In vivo, neither inactivation of Inpp4b (Inpp4b(Δ/Δ)) nor heterozygous deletion of Pten (Pten(+/-)) in mice causes thyroid abnormalities, but a combination of these mutations induces malignant thyroid cancers with lung metastases. At the molecular level, simultaneous deletion of Inpp4b and Pten synergistically increases PtdIns(3,4,5)P3 levels and activates AKT downstream signaling proteins in thyroid cells. We propose that the PtdIns(3,4,5)P3 phosphatase activity of INPP4B can function as a "back-up" mechanism when PTEN is deficient, making INPP4B a potential novel therapeutic target for PTEN-deficient or PIK3CA-activated cancers. SIGNIFICANCE: Although INPP4B expression is reduced in several types of human cancers, our work on Inpp4B-deficient mice provides the first evidence that INPP4B is a bona fide tumor suppressor whose function is particularly important in situations of PTEN deficiency. Our biochemical data demonstrate that INPP4B directly dephosphorylates PtdIns(3,4,5)P3.
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Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.
Ali Amin Al Olama, Sara Benlloch, Antonis C Antoniou, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, Jenny L Donovan, Kenneth Muir, Johanna Schleutker, Brian E Henderson, Christopher A Haiman, Fredrick R Schumacher, Nora Pashayan, Paul D P Pharoah, Elaine A Ostrander, Janet L Stanford, Jyotsna Batra, Judith A Clements, Suzanne K Chambers, Maren Weischer, Børge G Nordestgaard, Sue A Ingles, Karina D Sorensen, Torben F Orntoft, Jong Y Park, Cezary Cybulski, Christiane Maier, Thilo Doerk, Joanne L Dickinson, Lisa Cannon-Albright, Hermann Brenner, Timothy R Rebbeck, Charnita Zeigler-Johnson, Tomonori Habuchi, Stephen N Thibodeau, Kathleen A Cooney, Pierre O Chappuis, Pierre Hutter, Radka P Kaneva, William D Foulkes, Maurice P Zeegers, Yong-Jie Lu, Hong-Wei Zhang, Robert Stephenson, Angela Cox, Melissa C Southey, Amanda B Spurdle, Liesel FitzGerald, Daniel Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Michelle Guy, Tokhir Dadaev, Sarah J Little, Koveela Govindasami, Emma Sawyer, Rosemary Wilkinson, Kathleen Herkommer, John L Hopper, Aritaya Lophatonanon, Antje E Rinckleb, Zsofia Kote-Jarai, Rosalind A Eeles, Douglas F Easton
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 24 ( 7 ) 1121 - 9 2015年07月
研究論文（学術雑誌）
BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. RESULTS: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). CONCLUSIONS: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. IMPACT: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.
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[Pazopanib for three patients with recurrence of retroperitoneal liposarcoma : initial clinical experience].
Atsushi Koizumi, Takamitsu Inoue, Koichiro Takayama, Makoto Takahashi, Kazuyuki Numakura, Hiroshi Tsuruta, Susumu Akihama, Mitsuru Saito, Shintaro Narita, Norihiko Tsuchiya, Shigeru Satoh, Tomonori Habuchi
Hinyokika kiyo. Acta urologica Japonica 61 ( 4 ) 153 - 8 2015年04月
研究論文（学術雑誌）
Pazopanib, a novel tyrosine kinase inhibitor, is an effective therapeutic agent for patients with advanced soft tissue sarcoma. Here we report three patients with recurrent retroperitoneal liposarcoma who were treated with pazopanib. Case 1: A 54-year-old male received three courses of combined chemotherapy consisting of doxorubicin and ifosfamide for recurrent left retroperitoneal dedifferentiated liposarcoma and liver metastasis following tumor excision. Because of the lack of response to chemotherapy, 400 mg/day of pazopanib was subsequently administered for two weeks. The patient died 3 weeks after the initiation of pazopznib therapy. Case 2: A 78-year-old male with right retroperitoneal dedifferentiated liposarcoma underwent irradiation for a recurrent tumor 16 months after the initial tumor excision. Pazopanib (600 mg/day) was partially effective for 2 months. Pazopanib was administered for 7 months, but the patient died 8 months after the initiation of pazopanib therapy. Case 3 : An 80-year-old male with locally recurrent right retroperitoneal myxoid liposacroma was treated with 600 mg/day of pazopanib from 5 months after tumor excision. He remains alive and has had stable disease for 17 months to date. In conclusion, pazopanib may be effective in a subset of patients with recurrent retroperitoneal liposarcoma.
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A solitary positive prostate cancer biopsy does not predict a unilateral lesion in radical prostatectomy specimens.
Takuya Koie, Koji Mitsuzuka, Shintaro Narita, Takahiro Yoneyama, Sadafumi Kawamura, Yasuhiro Kaiho, Norihiko Tsuchiya, Tatsuo Tochigi, Tomonori Habuchi, Yoichi Arai, Chikara Ohyama
Scandinavian journal of urology 49 ( 2 ) 103 - 7 2015年04月
研究論文（学術雑誌）
OBJECTIVE: Prostate cancer (PCa) may be a multifocal and bilateral disease. Patients with low-risk PCa and a low number of positive biopsy cores may choose to undergo active surveillance or focal therapy. The aim of this study was to determine the correlation between a solitary positive prostate biopsy core and the pathological outcome after radical prostatectomy (RP). MATERIAL AND METHODS: The Michinoku Japan Urological Cancer Study Group database contains data, including preoperative and postoperative information, on 1268 consecutive patients with PCa treated with RP alone at four institutions. This study focused on 151 patients with a single positive biopsy core, preoperative prostate-specific antigen (PSA) level less than 10 ng/ml, biopsy Gleason score less than 8, and clinical stage T1c/T2a/T2b disease. Potential preoperative predictors of unilateral PCa were age, preoperative PSA level, biopsy Gleason score and clinical T stage. RESULTS: The median age and preoperative PSA level were 65 years (range 47-76 years) and 6.00 ng/ml (range 0.50-9.80 ng/ml), respectively. Unilateral PCa was identified in 41% of the patients. Extraprostatic extension or seminal vesicle invasion was observed in 26% of all patients. CONCLUSION: Serum PSA levels were significantly higher in the bilateral PCa group than in the unilateral PCa group in the current study. For patients with PCa having a solitary positive prostate biopsy core, definitive therapy such as RP should be considered.
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Successful introduction of laparoendoscopic single-site donor nephrectomy after experience with laparoscopic single-site plus-one trocar donor nephrectomy.
Takamitsu Inoue, Norihiko Tsuchiya, Shintaro Narita, Hiroshi Tsuruta, Susumu Akihama, Mitsuru Saito, Shigeru Satoh, Tomonori Habuchi
Journal of endourology 29 ( 4 ) 435 - 42 2015年04月
研究論文（学術雑誌）
PURPOSE: To assess the feasibility, safety, and efficacy of the laparoendoscopic single-site (LESS) donor nephrectomy (LESSDN) procedure after experience with the LESS-plus-one-trocar donor nephrectomy (LEPODN) procedure. PATIENTS AND METHODS: From 2009 to 2014, 126 left laparoscopic donor nephrectomies (LDNs) were performed, including 59 Standard (Std)-LDN, 30 LEPODN, and 37 LESSDN. In the LEPODN procedure, a 5-mm trocar was added as a right-hand working trocar to the LESSDN procedure. A GelPOINT(®) platform was applied on a pararectal single incision in both LEPODN and LESSDN procedures. After performing the LEPODN procedure several times, each surgeon performed the LESSDN procedure. RESULTS: Std-LDN, LEPODN, and LESSDN procedures were performed by 10, 10, and 7 surgeons, respectively. The mean operative time, estimated blood loss, warm ischemia time, time to ambulation, and length of postoperative hospital stay were the shortest for the LESSDN procedure (P<0.012, P=0.007, P<0.001, P=0.027, and P=0.001, respectively). No significant difference in the complication rate, delayed graft function rate, and mean 7-day post-transplant serum creatinine levels was observed among the three procedures. Individual results of the operative time and estimated blood loss for the LESSDN procedure were not significantly inferior to those of Std-LDN and LEPODN procedures for each surgeon. CONCLUSIONS: The LESSDN procedure can be introduced safely and effectively without compromising the operative time, complication rate, and graft function after experience with the LEPODN procedure among multiple surgeons. The LEPODN procedure may be an effective bridge from standard multiport LDN to LESSDN.